New Trainee Co-Lead: Daniela Massierer The CDTRP Education and Training Platform is pleased to announce its newest co-lead and trainee representative, Daniela Massierer. Daniela Massierer graduated in Physiotherapy at Methodist University Center, Brazil (2007), followed by a Master’s degree (2010) and PhD (2016) in Health Sciences at Federal University of Rio Grande do Sul, [...]
CAN-RESTORE symposium: Building Resilience for the Transplant Journey – The Role of Pre-habilitation CAN-RESTORE is happy to invite the community to their second Annual Virtual Symposium on Tuesday, May 27, 2021 from 3pm to 6pm ET. They invite submissions of scientific abstracts or case studies for e-poster or oral presentations from multi-disciplinary perspectives on the topics of pre-habilitation for [...]
Freshly funded: Congratulations to Dr. Seema Mital and Dr. Marcelo Cypel The CDTRP wishes to congratulate Dr. Seema Mital and Dr. Marcelo Cypel and their teams at UHN for their success in the CIHR Fall 2020 competitions. Dr. Seema Mital's Project: A Role for novel regulatory variants in childhoood cardiomyopathy (link here) Abstract: Cardiomyopathy [...]
CDTRP 2021 Webinar Series: Diversifying Your Research The CDTRP is pleased to announce its 2021 Webinar Series: Diversifying Your Research. The topics below were voted on by CDTRP Trainees. The Webinar Series is public and will be open to the community. The Series will count on 7 speakers from Canada, United States and [...]
Freshly funded: Congratulations to the CINERGY Team The CDTRP wishes to congratulate the CINERGY team, led by Fréderick D'Aragon and Maureen Meade, on their funding received from CIHR 2020 Fall Competition. We asked them a few questions about the process: How was the CDTRP contributed to this work? The CDTRP has supported the CINERGY [...]
DePPaRT Webinar: Insights and Implications On Tuesday, March 30 at 3pm EST, Canadian Blood Services' Donation Physician Network and Donor Coordinator Network will host a joint webinar on theDePPaRT study, led by Dr. Sonny Dhanani followed by a panel discussion. Click here to join the meeting or find a local number to call in [...]
Surveillance of Organ Transplant Recipients Affected by COVID-19: Data posted The emergence of COVID-19 has had far-reaching implications for the public’s health and has been particularly impactful in vulnerable populations such as transplant recipients. Through a collaboration between Dr. Deepali Kumar and Tina Marinelli (transplant infectious disease specialist, UHN), the Canadian Society of Transplantation (CST), [...]
First International Workshop of the Canadian NASH Network (CanNASH) Joint with Single Topic Conference of the Canadian Association for the Study of the Liver (CASL) Due to the obesity and co-epidemic of type 2 diabetes, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in our country, affecting one in fourth [...]
CDTRP New Research Manager: Katie Bain The CDTRP is pleased to announce that Katie Bain has accepted the role of Research Manager for Themes 3, 4 and 5. We welcome her expertise in the field of research and are excited to work with her on the team! Katie's bio Katie Bain lives, works [...]
CDTRP Support for Research Proposals and Spring 2021 CIHR Project Grants CDTRP offers a wide variety of research support that can be integrated into CIHR Project Grant proposals (or any other funding applications). For example, we offer cash contributions toward economic, legal, ethics, or social analysis, funding to support the integration of patient, family [...]
| Should include evaluating availability of intensive care beds, ventilators, blood products, dialysis supplies, and hospital staffing. |
| The CDC recommends all people wear masks or face coverings when in public. Transplant candidates, recipients, and potential living donors should be educated about the importance of performing frequent hand hygiene, avoidance of crowds, and applying social distancing. |
| “At this point in time, given negative data on the use of chloroquine and hydroxychloroquine, we do not recommend the use of these drugs, in accordance with National Institutes of Health (NIH) and IDSA guidelines.” |
| “Decreasing immunosuppression should be considered for infected recipients who have not had recent rejection episodes, but the decision to reduce immunosuppression should be based on severity of COVID-19 disease in comparison with rejection risk.” |
| “A candidate have complete symptom resolution and have a negative SARS-CoV-2 PCR from the upper respiratory tract prior to transplantation.” |
| “Temporary suspension of elective living donor transplantation or non-urgent deceased donor transplants may be considered in areas with high rates of COVID-19.” |
| Document says that clinical data critical to maintaining spot on waitlist can be carried forward in place of acquiring new data, to avoid COVID risk. |
| Yes, but only in some moderate cases and in severe cases. Otherwise, do not change. |
Recommend informing all parties of risks.
| Recipients should be cared for in single rooms where available or prioritised for access to single rooms. If single rooms are not available, multi-occupancy bays with recipients should ideally admit only SARS-CoV-2 negative patients, and have an enhanced cleaning regime for shared bathroom facilities and common touch points, e.g. doors, switches. |
| There is a lack of evidence to recommend for or against routine screening of asymptomatic patients on the waiting list for a transplant. It is recommended that local hospital policy on screening of asymptomatic patients should be followed. |
| Currently there is no evidence for or against routine surveillance testing for SARSCoV-2 RNA in asymptomatic patients on the waiting list. |
| Strictly enforce the active version of national/local guidance on visitor policy. |
| It is advised that transplant centres undertake a risk assessment to determine which patients would benefit from transplantation despite an increased risk of infection. |
| If hospital infra-structure allows, and the required multi-disciplinary team input can be safely and sustainably delivered, transplantation should be performed in a ‘Green’ or ‘Cold’ (absence of non-elective patient admissions) hospital site. |
| If an organ transplant recipient tests positive for SARS-CoV-2 RNA within two weeks of donation, OTDT Clinical Governance must be informed via the incident reporting site. |
| Those with proven COVID-19 should be suspended for an appropriate period according to the clinical context. Those who recover and are symptom-free for more than 28 days can be considered for re-activation on the list. |
| Local policies on SARS-CoV-2 RNA testing must be in line with national guidance5
Where swab results are positive pre-transplant, transplantation would not usually |
| Potential transplant recipients must be carefully questioned for symptoms consistent with COVID-19 and for contact with persons with confirmed or suspected COVID-19. A comprehensive social history is required, with details of the patient’s social distancing practices and of those within their household, in order to build a picture to inform a risk assessment. Ideally, this would happen before the patient is admitted to hospital. Examination must include a careful chest assessment with measurement of peripheral arterial oxygen saturations. Patients with a significant contact history, or where clinical suspicion of COVID-19 is present, must be discussed with a consultant in virology or infectious diseases. Some units have used chest CT to screen potential transplant recipients for asymptomatic COVID-19 at admission for transplantation. The use of chest CT as a COVID-19 screening test has largely been supplanted by rapid turnaround time SARS-CoV-2 nose and throat swabs primarily due to concerns about false positive and false negative results |
| All professionals likely to have contact with the SOT recipient must have access to and adhere to national/local PPE use, hand hygiene and social distancing guidance. |
|
| Donation will be deferred until the donor is considered cured (more than 14 days since the initiation of symptoms, more than 72 hours with no symptomatology, and negative result for SARS-CoV-2 by RT-PCR in a sample of the respiratory tract), always performing an individualized risk/benefit assessment. |
| Universal screening for SARS-CoV-2 is indicated in all potential donors prior to surgery. |
| Donation will not proceed in the following circumstances: 1. Cases with high clinical suspicion of COVID-19, regardless of microbiological results. 2. Cases with a positive or inconclusive result in the screening for SARS-CoV-2 by RT-PCR. 3. Confirmed cases of COVID-19. |
|
|
| The general principles, indications and contraindications for lung transplantation must be met. This also means that the estimate must be met that there is an 80% chance of survival of at least five years after lung transplantation (ISHLT consensus document). |
| Donation is only allowed if the PCR test, preferably on sputum or deep respiratory material, for SARS-CoV-2 is negative and the test is no older than approximately 24 hours. A (hetero) history is made of each donor from 14 days before admission to the time of the donor evaluation. If the donor previously had an infection / contamination with COVID-19, the donor must be > 14 days symptom-free and have a negative PCR test result twice with at least 24 hours in between. |
| For members of an organ transplant team without complaints, a face mask (type IIR) should be worn in the Netherlands and for foreign countries it may be required to wear an FFP2 mask instead of type IIR. |
| A foreign team may come to the Netherlands if the team members have no complaints. A type IIR or FFP-2 mouth mask should always be worn. Due to limited transportation measures for incoming thoracic teams, only 4 team members can be transported to the donor hospital. |
| In the event of a suspected or confirmed case of donor derived COVID-19 in a recipient a notification should also be made to the Vigilance and Surveillance Expert Advisory Committee (VSEAC) of the Organ and Tissue Authority (OTA). |
Nose and throat swab (PCR); blood for retrospective serology testing.
Nose and throat swab (PCR) test – blood for restrospective serology testing.
Nose and throat swab (PCR) test.
Name: Navneet Singh
Email: n72singh@uwaterloo.ca
Supervisor: Istvan Mucsi
Theme: 1
Authors: Navneet Singh (1), Aghna Wasim (1), Gaauree Chawla (1), Faisal Jamil (1), Marzan Hamid (1), Rabail Siddiqui (1), Eric Lui (1), Noor El-Dassouki (1), Marta Novak (1,2), Istvan Mucsi (1)
Affiliations: University Health Network, Multi-Organ Transplant Program and Division of Nephrology, Toronto, Canada (1); Centre for Mental Health, University Health Network, Toronto, Canada (2)
Background
Compared to Whites, Asian Canadians with end stage kidney disease (ESKD) are less likely to receive living donor kidney transplant (LDKT). We explored the importance of pros and cons in the kidney transplant (KT) decision making for Asian Canadians with ESKD.
Methods
Cross-sectional convenience sample of adults with ESKD in Toronto completed the Transplant Decisional Balance Survey. Ethnicity (White, Asian [South and East], other) was self-identified. Patients rated importance of positive and negative outcomes to their decision about KT on a scale from 1-5 (“not important” – “extremely important”). LDKT and deceased donor KT (DDKT) pro/con scores were calculated by summing individual item scores. Items were then dichotomized (not/slightly/moderately vs very/extremely important) and their association with ethnicity was analyzed in multivariable logistic regression models.
Results
Among the 539 participants (mean[SD] age 57[13] years, 62% male), 23% were Asian, and 45% were White. The LDKT pro, LDKT con, and DDKT pro scores were similar between the groups. However, Asian patients rated DDKT con significantly higher (median [IQR]: 9[5,13] vs 12[8,16]; p=0.002). LDKT and DDKT pro items were not significantly associated with ethnicity. In univariable analysis, compared to White patients, Asians were more likely to indicate that pain from surgery (OR, 2.27 [95% CI: 1.32, 3.90]), taking many medications post-transplant (OR, 2.08 [95% CI: 1.32, 3.27]), and “if transplant failed it would be a lot of work/pain for nothing” (OR, 3.07 [95% CI: 1.66, 5.70) were very/extremely important to their transplant decision. These associations remained significant after adjusting for sociodemographic variables, comorbidity, and transplant knowledge, (OR, 1.97 [95% CI: 1.10, 3.54]), (OR, 1.90 [95% CI: 1.14, 3.17]), (OR, 3.38 [95% CI: 1.65, 6.90], respectively).
Conclusion
Anticipated pain, concerns about post-transplant medications and potential unsuccessful transplant weighs into KT decisions among Asian Canadians with ESKD more than for Whites.
Living donor kidney transplantation (LDKT) is the optimal treatment for many patients with advanced kidney disease. Compared to Caucasians, Asian Canadians are less likely to undergo LDKT. In Ontario, Asian Canadians are also less likely to register for deceased organ donation compared to the general public. We explored the importance of pros and cons in the kidney transplant (KT) decision making for Asian Canadians with ESKD. A sample of adults with ESKD in Toronto completed the Transplant Decisional Balance Survey, in which they rated the importance of positive and negative outcomes to their decision about KT on a scale from 1 to 5 (“not important” to “extremely important”). When making transplant decisions, compared to Caucasian patients, Asian patients with ESKD were more concerned about the anticipated pain from transplant surgery, concerns about post-transplant medication, and potential unsuccessful transplants. Further qualitative research is needed to better understand the reasons for these ethnicity-specific differences in decision making. This will allow us to create more tailored support so that Asian patients with ESKD will have equitable access to transplant.
Name: Navneet Singh
Email: n72singh@uwaterloo.ca
Supervisor: Istvan Mucsi
Theme: 1
Authors: Navneet Singh (1), Aghna Wasim (1), Ward Hajjar (1), Karthik Mohan (1), Nasab El-Dassouki (1), Hiba Habbal (1), Lydia Angarso (1), Adrian Dychiao (1), Sara Macanovic (1), Istvan Mucsi (1)
Affiliations: University Health Network, Multi-Organ Transplant Program and Division of Nephrology, Toronto, Canada (1)
Background
Compared to Whites, African, Caribbean and Black (ACB) Canadians with end stage kidney disease (ESKD) are less likely to receive a living donor kidney transplant (LDKT). We explored the importance of pros and cons for kidney transplant (KT) decisions for ACB patients with ESKD.
Methods
Cross-sectional convenience sample of adults with ESKD in Toronto completed the Transplant Decisional Balance Survey. Ethnicity was self-identified. Patients rated importance of positive and negative outcomes to KT decision from 1-5 (“not important” – “extremely important”). Individual items were scored to yield LDKT and deceased donor KT (DDKT) pro/con scores. Items were dichotomized (not/slightly/moderately vs very/extremely important) and their association with ethnicity was analyzed in multivariable logistic regression.
Results
Among the 539 patients (mean[SD] age 57[13] years, 62% male), 27% were ACB, and 45% were White. ACB patients were more likely to live in areas with material deprivation (20% vs 72%, p<0.001). The LDKT scores and DDKT pro score were similar between the groups. However, ACB patients rated DDKT con (9[5,13] vs 12[5.5,16]; p=0.002) higher than Whites. In univariable analysis, ACB patients were more likely to indicate that “taking many medications posttransplant” (OR, 2.79 [95% CI: 1.76, 4.44]), “pain from surgery” (OR, 1.88 [95% CI: 1.15, 3.05]), “health problems due to transplant” (OR, 1.72 [95% CI: 1.12, 2.63), and “trouble paying for medications” (OR, 2.98 [95% CI: 1.81, 4.90), were important to transplant decision. These associations remained significant for “taking many medications” (OR, 2.15 [95% CI: 1.30, 3.56) and “trouble paying for medications” (OR, 1.71 [95% CI: 1.03, 2.83) after adjusting for sociodemographic variables, comorbidity, and transplant knowledge.
Conclusion
Concerns about post-transplant medications and anticipated financial strain weighs into KT decisions among ACB Canadians with ESKD more than for Whites.
Living donor kidney transplantation (LDKT) is the optimal treatment for many patients with advanced kidney disease. Compared to Caucasians, African, Caribbean and Black (ACB) Canadians are less likely to undergo LDKT. Lack of transplant related knowledge, lack of awareness about the benefits of KT, concerns about the safety of the donor or culturally determined negative attitudes contribute to barriers for ACB Canadians to pursue LDKT. We explored the importance of pros and cons in the kidney transplant (KT) decision making for ACB Canadians with ESKD. A sample of adults with ESKD in Toronto completed the Transplant Decisional Balance Survey, in which they rated the importance of positive and negative outcomes to their decision about KT on a scale from 1 to 5 (“not important” to “extremely important”). When making transplant decisions, compared to Caucasian patients, ACB patients with ESKD were more concerned about the post-transplant medications, and the anticipated financial strain from the medication. Further qualitative research is needed to better understand the reasons for these ethnicity-specific differences in decision making. This will allow us to create more tailored support so that ACB patients with ESKD will have equitable access to transplant.
Name: Kevin Rey
Email: peru.rey@gmail.com
Supervisor: Jonathan Choy
Theme: 4
Authors: Rey (1), W. Enns (1), T. Van Rossum (2), F.S.L. Brinkman (1), J.C. Choy (1)
Affiliations: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada (1); European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, BW, Germany (2)
Background
The gut microbiota influences immune development and function, in part through the production of short chain fatty acids that result from the fermentation of dietary resistant starches and metabolism of host intestinal mucins. Importantly, dysbiosis of this microbial community early in life is associated with immune disorders in adulthood. Our study examines the effect of antibiotic-mediated disruption of the gut microbiota early in life on immune-mediated vascular rejection of organ transplants.
Methods
The gut microbiota of C57BL/6 mice was disrupted by administration of an antibiotic cocktail (ampicillin, vancomycin, metronidazole, neomycin sulfate) for only the first 3 weeks of life. Some antibiotic treated mice were cohoused with untreated mice starting at 3 weeks old to normalize their microbiota. The composition of the bacterial microbiome was determined by 16S and whole genome shotgun sequencing of fecal samples. Vascular rejection was then examined by interposition grafting of allogeneic aortic segments from Balb/c donors into recipients that were 8 – 12 weeks old.
Results
Treatment of graft recipients with antibiotics early in life increased the accumulation of neutrophils and associated medial injury in allograft arteries, effects that were more apparent in female mice than male counterparts. Analysis of 16S sequencing indicated that antibiotic treatment resulted in persistent changes in the microbiota of adult mice that included alteration in the relative abundance of several bacterial classes. Inference of metabolic gene content from 16S sequences suggested that antibiotic treatment caused a decrease in several enzymatic processes that contribute to the metabolism of mucin, which may affect short chain fatty acid production. Analysis of whole genome shotgun sequencing showed several bacterial species were eliminated by antibiotic treatment, including Akkermansia muciniphila which degrades mucin and produces the short chain fatty acid acetate. Reduction of A. muciniphila was associated with a decrease in the mucin degrading enzyme acetyl-N-hexosaminidase. Cohousing mice normalized the levels of A. muciniphila and acetyl-N-hexosaminidase as well as prevented the exacerbation of neutrophil accumulation caused by antibiotic treatment early in life.
Conclusion
The composition of the gut microbiota influences the development of acute vascular rejection, potentially by regulating neutrophil responses via A. muciniphila metabolism of mucin and resultant production of acetate.
Background
The community of microbes in the digestive tract, the gut microbiota, influences virtually all aspects of human health. Importantly, the gut microbiota ensure that the immune system develops properly; harmful alteration of the gut microbiota early in life increases the likelihood of developing immune disorders and asthma. This influence is exerted in part by the molecules that the gut microbiota produce as they break down indigestible starches and the mucus that lines the gut. Our study focuses on the damage that immune cells cause to blood vessels during transplant rejection and how that is linked to the gut microbiota.
Methods
To model the rejection that occurs in humans, we use mice and transplant a section of the aorta. The genetic differences between the donor and recipient means that the host immune system rejects the aorta similar to how this occurs in humans. In order to modify the gut microbiota, we use a cocktail of antibiotics to deplete them early in life and then allow them to recover. To restore the microbiota of antibiotic treated mice to normal, we place them in the same cage as untreated mice since they will naturally transfer bacteria. We sequenced the DNA in stool samples to determine which bacteria and genes are present.
Results
When mice have their microbiota disrupted by antibiotics early in life, it exacerbates the rejection of their aortic transplant; we see many more white blood cells called neutrophils accumulate in the blood vessel wall. In those same mice, their microbiota in adulthood is significantly different than untreated mice and has decreased copies of genes that break down mucus. When we looked for specific species of bacteria, we saw that antibiotic treatment eliminated Akkermansia muciniphila, which degrades mucus and produces acetate which inhibit neutrophils. Cohousing the mice restored their gut microbiota to normal as well as reduced the neutrophils in their transplants. This suggests that the composition of the gut microbiota modifies the severity of immune damage to blood vessels in transplant rejection.
Conclusion
Our studies show that the gut microbiota modifies the severity of transplant rejection in blood vessels, possibly by controlling the behaviour of neutrophils via A. muciniphila and its production of acetate.
Name: Nicholas Murphy
Email: nmurphy9@uwo.ca
Supervisor: Charles Weijer
Theme: 2
Authors: Nicholas Murphy (1), Charles Weijer (2), Maxwell Smith (3), Jennifer Chandler (4), Erika Chamberlain (5), Teneille Gofton (6), Marat Slessarev (7)
Affiliations: Department of Philosophy, Western University, London, Canada (1); Departments of Philosophy and Medicine, Western University (2); Faculty of Health Sciences, Western University (3); Faculty of Law, University of Ottawa, Ottawa, Canada (4); Faculty of Law, Western University (5); Department of Clinical Neurological Sciences, Western University (6); Department of Medicine, Western University (7)
Background
Controlled donation after circulatory determination of death (cDCDD) is an important strategy for increasing the pool of eligible organ donors. Despite widespread adoption of cDCDD in jurisdictions worldwide, disagreement regarding the ethical propriety of aspects of the practice remains evident among bioethicists and health care practitioners. Our scoping review offers a neutral resource which maps the contours of this ethical terrain and signals to those working in this area the prominent locations where further nuance and discussion can be found. We identify key themes, concerns, concepts and arguments and provide an overview of prominent debates.
Method
We used scoping review methodology to obtain a panoramic view of the ethics of cDCDD. Publications were retrieved from PubMed, Embase and SCOPUS. A manual search of bibliographies from selected articles was conducted to identify articles that did not appear in the databases. Articles were included if they addressed ethical concerns related to cDCDD and were published in English. 167 publications bearing on the ethics of cDCDD were included for analysis.
Results
Our review identifies 6 major themes in the cDCDD ethics literature: (1) Interpretations of irreversibility. Debate here concerns how to understand the term ‘irreversible.’ (2) Death determination. Disagreement in this area focuses on suitable criteria for determinations of death in the context of cDCDD. (3) The dead donor rule. We discuss a worry from some quarters that cDCDD practice could violate this ethical imperative. (4) Potential harms versus benefits to donors. Discussion on this theme encompasses the permissibility of certain ante- and post-mortem interventions. (5) Conflicts of interest. Given the tension between the duty to provide care and the need to retrieve viable organs, some scholars are concerned that conflicts of interest may arise in practice. (6) Public trust. Some authors worry that public trust in organ donation schemes could erode if the public were aware of cDCDD protocol or the apparent uncertainty over its ethical permissibility.
Discussion
We conclude that the plurality of viewpoints found in this literature is a natural result of not only empirical uncertainties, but also complex debates concerning the metaphysics of death and value-laden judgements concerning the legitimate scope of medical practice. Together with public engagement, continued collaboration between scientists, medical practitioners and ethicists is required as cDCDD continues to develop and advance.
Background
Controlled donation after circulatory determination of death (cDCDD) is an important strategy for increasing the pool of eligible organ donors. Despite widespread adoption of cDCDD in jurisdictions worldwide, disagreement regarding the ethical propriety of aspects of the practice remains evident among bioethicists and health care practitioners. Our scoping review offers a neutral resource which maps the contours of this ethical terrain and signals to those working in this area the prominent locations where further nuance and discussion can be found. We identify key themes, concerns, concepts and arguments and provide an overview of prominent debates.
Method
We used scoping review methodology to obtain a panoramic view of the ethics of cDCDD. Publications were retrieved from PubMed, Embase and SCOPUS. A manual search of bibliographies from selected articles was conducted to identify articles that did not appear in the databases. Articles were included if they addressed ethical concerns related to cDCDD and were published in English. 167 publications bearing on the ethics of cDCDD were included for analysis.
Results
Our review identifies 6 major themes in the cDCDD ethics literature: (1) Interpretations of irreversibility. Debate here concerns how to understand the term ‘irreversible.’ (2) Death determination. Disagreement in this area focuses on suitable criteria for determinations of death in the context of cDCDD. (3) The dead donor rule. We discuss a worry from some quarters that cDCDD practice could violate this ethical imperative. (4) Potential harms versus benefits to donors. Discussion on this theme encompasses the permissibility of certain ante- and post-mortem interventions. (5) Conflicts of interest. Given the tension between the duty to provide care and the need to retrieve viable organs, some scholars are concerned that conflicts of interest may arise in practice. (6) Public trust. Some authors worry that public trust in organ donation schemes could erode if the public were aware of cDCDD protocol or the apparent uncertainty over its ethical permissibility.
Discussion
We conclude that the plurality of viewpoints found in this literature is a natural result of not only empirical uncertainties, but also complex debates concerning the metaphysics of death and value-laden judgements concerning the legitimate scope of medical practice. Together with public engagement, continued collaboration between scientists, medical practitioners and ethicists is required as cDCDD continues to develop and advance.
Name: Eric Mauti
Email: eric.mauti@mail.utoronto.ca
Supervisor: Istvan Mucsi
Theme: 5
Authors: Eric Mauti (1,2), Karthik Mohan (1), Jasleen Gill (1), Rabail Siddiqui (1), Setareh Aghamohammadi (1), Junayd Hussain (1), Mohammed Saqib (1), Evan Tang (1), Marta Novak (1), Nazia Selzner (1), Istvan Mucsi (1)
Affiliations: University Health Network, Multi-Organ Transplant Program and Division of Nephrology, Toronto, Canada (1); Faculty of Medicine, University of Toronto, Toronto, Canada (2)
BACKGROUND
About 1 in 5 Canadians were born outside of Canada, therefore they are considered immigrants. Immigrant status may be associated with higher anxiety and depression compared to non-immigrants due to the psychological, financial, and social stressors associated with immigration. Chronic liver disease is frequent among immigrants, due to higher prevalence of hepatitis B and C infection. Liver transplant (LT) is the only definitive treatment for liver failure. Immigrant LT recipients (LTRs) may have greater anxiety and depression than non-immigrant LTRs. The objective was to assess if immigrant status is associated with self-reported anxiety and depression among LTRs.
METHODS
A cross-sectional cohort of adult LTRs completed the PROMIS CAT Anxiety and Depression item banks. Information about immigration status, sociodemographics, and clinical variables were also collected. Independent samples t-test was used to compare anxiety and depression scores between immigrants and non-immigrants. Multivariable linear regression was used to adjust for age, sex, income, ethnicity, and education. Information about age at immigration, years in Canada, and immigration method were also assessed.
RESULTS
145 participants were included: mean(SD) age 56(15) years, 70% male, 67% White, 28% immigrant. Mean(SD) anxiety score was 51(9), and mean(SD) depression score was 50(9). Immigrants, compared to non-immigrants, had lower depression and similar anxiety scores. Upon adjustment for potential confounders, anxiety and depression scores were similar between groups (b[95% CI] 1.0[-2.6–4.6], p=0.583, and -2.5[–6.0–1.0, p=0.160). Mean(SD) time since immigration was 38(17) years, and mean(SD) age at immigration was 21(15) years. Most immigrants (90%) were landed immigrants. When adjusted for age and sex, older age at immigration was associated with a lower depression score (-0.3[-0.5–-0.1], p=0.005).
CONCLUSION
Anxiety and depression among LTRs were similar between immigrants and non-immigrants. Immigrants who immigrated at an older age had lower depression scores.
BACKGROUND
About 1 in 5 Canadians were born outside of Canada, therefore they are considered immigrants. Immigrant status may be associated with higher anxiety and depression compared to non-immigrants due to the psychological, financial, and social stressors associated with immigration. Chronic liver disease is frequent among immigrants, due to higher prevalence of hepatitis B and C infection. Liver transplant (LT) is the only definitive treatment for liver failure. Immigrant LT recipients (LTRs) may have greater anxiety and depression than non-immigrant LTRs. The objective was to assess if immigrant status is associated with self-reported anxiety and depression among LTRs.
METHODS
A cross-sectional cohort of adult LTRs completed the PROMIS CAT Anxiety and Depression item banks. Information about immigration status, sociodemographics, and clinical variables were also collected. Anxiety and depression scores were compared between immigrants and non-immigrants, and were adjusted for age, sex, income, ethnicity, and education. Information about age at immigration, years in Canada, and immigration method were also assessed.
DISCUSSION AND CONCLUSION
Anxiety and depression among LTRs were similar between immigrants and non-immigrants. Immigrants who immigrated at an older age had lower depression scores. Individuals in this group may have greater personal and economic stability at the time of immigration. This may result in fewer immigration stressors, potentially leading to lower self-reported depression scores. As well, selective immigration policies, which are preferential to healthier and more educated immigrants, may also influence this relationship. Additionally, immigrants who immigrate at an older age may maintain greater cultural ties as a result of decreased assimilation. This could reflect the observed lower depression scores.
Name: Katherine MacDonald
Email: kmacdonald2@bcchr.ca
Supervisor: Megan Levings
Theme: 4
Authors: Katherine N. MacDonald (1,2,3,#), Sabine Ivison (2,4,#), Jason Acker (5,6), Tracey Turner (5), Romy E. Hoeppli (2,4,#), I. Esme Dijke (6,7,#), Lori J. West (7,8,9,#), James M. Piret (3,10,#), Megan K. Levings (1,2,4,#)
Affiliations: School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada (1); BC Children’s Hospital Research Institute, Vancouver, BC, Canada (2); Michael Smith Laboratories, Vancouver, BC, Canada (3); Department of Surgery, University of British Columbia, Vancouver, BC, Canada (4); Centre for Innovation, Canadian Blood Services, Edmonton, Alberta, Canada (5); Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada (6); Alberta Transplant Institute, University of Alberta, Edmonton, AB, Canada (7); Department of Pediatrics, University of Alberta, Edmonton, AB, Canada (8); Department of Surgery, University of Alberta, Edmonton, AB, Canada (9); Department of Chemical and Biological Engineering, University of British Columbia, Vancouver, BC, Canada (10) #Canadian Donation and Transplantation Research Program Investigator
Introduction
Animal and early clinical studies have shown that regulatory T cell (Treg) therapy can prevent graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. However, manufacturing a homogeneous and consistent product, especially one that includes cryopreservation, has been challenging. We previously found that the thymus, routinely removed during pediatric cardiac surgery, is a plentiful source of Tregs with advantages including cell quantity, homogeneity and stability. We have since developed methods to isolate, expand and cryopreserve thymus-derived Tregs using GMP-compatible methods and reagents. To use thymus-derived Tregs as a cell therapy in humans, we are scaling-up our methods for isolation, expansion and cryopreservation.
Methods
CD4+CD8-CD25+ thymic Tregs were isolated from pediatric thymuses using GMP-compatible magnetic bead-based separation. Tregs were expanded using anti-CD3/CD28 conjugated beads in the presence of IL-2 and rapamycin. For large-scale expansion, we compared expanding Tregs using a rocking motion bioreactor, gas-permeable culture flask, gas-permeable culture bags, and tissue culture flasks. Expanded Tregs were cryopreserved using CryoStor CS10 using an isopropanol-free freezing container in a -80°C freezer, a liquid nitrogen-based controlled rate freezer, and a liquid nitrogen-free controlled rate freezer.
Results
The recovery, viability and purity of isolated thymic Tregs were similar between isolations performed at the small- and large-scales. In comparing large-scale expansion systems, the highest expansion was obtained using the gas-permeable culture flask; however, the viability and purity of expanded Tregs was highest using gas-permeable culture bags. The recovery, viability and purity were similar between Tregs cryopreserved with the different rate-controlled freezers upon thaw.
Conclusion
We have established protocols to manufacture and cryopreserve thymic Tregs at using larger-scale isolation, expansion and cryopreservation platforms. Our process yields a product with high expression of FOXP3, the master transcription factor of Tregs, and suppressive capacity. We are working on translating these protocols to the Alberta Cell Manufacturing Facility for further process development. These protocols will allow allogeneic thymic Tregs to be used as an “off-the-shelf” therapy to treat GVHD.
Introduction
Blood and bone marrow transplants can be used to treat blood cancers such as leukemia. The transplant can provide a cure when the donor immune cells attack and kill leukemia cells. Unfortunately, the donor cells often also attack the patient’s own tissue, causing serious short- and long-term consequences. To prevent these negative immune responses without inhibiting the anti-cancer effect of the transplant, our strategy is to also give patients a dose of the type of immune cell that suppress the negative immune responses. These are called regulatory T cells, or Tregs. Initial studies with Tregs have been promising, but there are many challenges to using Tregs as a therapy. One major issue is that Tregs are very rare – less than 1% of white blood cells – so to obtain enough cells to use in a patient, we must develop methods to isolate and grow Tregs, then store them until they are needed. Rather than obtaining Tregs from the blood, we are isolating them from the thymus, an immune organ located above the heart that is routinely removed during pediatric cardiac surgery. The thymus is a plentiful source of Tregs that are more uniform in their characteristics than Tregs from the blood. We have developed methods to isolate these cells and grow them in the lab, using materials that will be compatible with clinical standards. We are now scaling up these methods, so we can produce enough cells to treat a patient.
We have developed a method to isolate Tregs from the thymus that results in a pure cell product at the large-scale. We compared different devices for growing Tregs and found that of the devices tested, the highest quality Tregs were obtained using specialized bags that allow for gases to be exchanged through the sides. After we increase numbers of Tregs, they will be frozen to allow for storage until needed to treat a patient. We compared different devices for freezing cells and found that the number and quality of cells that could be obtained were similar for all devices after the cells were thawed.
These methods will allow Tregs to be produced for use as a cell-based therapy to improve outcomes after blood and bone marrow transplantation. We are now working with a clinical cell manufacturing facility to finalize these protocols so that they can be used to apply for a clinical trial.
Name: Haoyue (Helena) Lan
Email: helena.lan@mail.utoronto.ca
Supervisor: Istvan Mucsi
Theme: 5
Authors: Haoyue Helena Lan (1,2), Faisal Jamil (1), Noor Al Kaabi (1), Renad Aser (1), Karma Gyatso (1), Hiba Habbal (1), Sara Macanovic (1), Sumaya Dano (1), Marta Novak (1), Istvan Mucsi (1)
Affiliations: University Health Network, Toronto, Canada (1); Faculty of Medicine, University of Toronto, Canada (2)
BACKGROUND
Patients with end-stage kidney disease treated with renal replacement therapy (RRT, dialysis or kidney transplant) often experience anxiety symptoms. Currently, however, these symptoms frequently remain un-detected. Systematic screening for anxiety may help identify patients with moderate/severe symptoms, who may benefit from multidimensional assessment and support.
OBJECTIVE
To explore the screening performance and efficiency of a hypothetical 2-step screening approach, where an ultra-brief screening tool (Edmonton Symptom Assessment Survey-revised– Anxiety item (ESASr-A) or Generalized Anxiety Disorder-2 (GAD-2)) is followed by a more precise tool (Patient Reported Outcomes Measurement Information System Anxiety Computer Adaptive Test (PROMIS-A-CAT)), for identifying anxiety symptoms in patients treated with RRT.
METHODS
In a multicenter cross-sectional study, we administered multiple symptom screening questionnaires to patients on RRT. Using the dataset of patients who completed ESASr-A, GAD-7 and PROMIS-A-CAT between September 2017 and January 2020, we compared screening performance and efficiency between the scenario in which patients completed PROMIS-A-CAT and hypothetical scenarios where only patients above the pre-screening cut-off would have completed PROMIS-A-CAT. Screening performance was evaluated by sensitivity and specificity. Efficiency was characterized by the average number of questions completed by subjects in the different scenarios.
RESULTS
Our sample included 210 subjects, including 79 patients on dialysis and 131 kidney transplant recipients. Most patients who completed 10-12 PROMIS-A-CAT items had low scores, suggesting the 2-step approach can be helpful to reduce questionnaire burden among patients with mild symptoms. For the 2-step method, using a cut-off of ≥1 and ≥2 for ESASr-A and GAD-2, respectively, produced the best combination of sensitivity and specificity (ESASr-A sensitivity 0.70, specificity 0.95; GAD-2 sensitivity 0.81, specificity 0.95). Compared to administering only PROMIS-A-CAT to all patients, the 2-step screening reduced the average number of questions patients had to complete by 54% and 50%, for ESASr-A and GAD-2, respectively. This reduction was most pronounced among patients with low anxiety scores.
CONCLUSION
A 2-step screening method using either ESASr-A or GAD-2 followed by PROMIS-A-CAT has acceptable specificity and sensitivity, and can help improve the efficiency of identifying patients with anxiety symptoms. Screened in patients will need clinical assessment to establish diagnosis and decide on appropriate psychosocial support.
BACKGROUND
Patients with end-stage kidney disease treated with renal replacement therapy (RRT, dialysis or kidney transplant) often experience anxiety symptoms. Currently, however, these symptoms frequently remain un-detected. Systematic screening for anxiety may help identify patients with moderate/severe symptoms, who may benefit from multidimensional assessment and support.
OBJECTIVE
To explore the screening performance and efficiency of a hypothetical 2-step screening approach, where an ultra-brief screening tool (Edmonton Symptom Assessment Survey-revised– Anxiety item (ESASr-A) or Generalized Anxiety Disorder-2 (GAD-2)) is followed by a more precise tool (Patient Reported Outcomes Measurement Information System Anxiety Computer Adaptive Test (PROMIS-A-CAT)), for identifying anxiety symptoms in patients treated with RRT.
METHODS
In a multicenter cross-sectional study, we administered multiple symptom screening questionnaires to patients on RRT. Using the dataset of patients who completed ESASr-A, GAD-7 and PROMIS-A-CAT between September 2017 and January 2020, we compared screening performance and efficiency between the scenario in which patients completed PROMIS-A-CAT and hypothetical scenarios where only patients above the pre-screening cut-off would have completed PROMIS-A-CAT. Screening performance was evaluated by sensitivity and specificity. Efficiency was characterized by the average number of questions completed by subjects in the different scenarios.
RESULTS
Our sample included 210 subjects, including 79 patients on dialysis and 131 kidney transplant recipients. Most patients who completed 10-12 PROMIS-A-CAT items had low scores, suggesting the 2-step approach can be helpful to reduce questionnaire burden among patients with mild symptoms. For the 2-step method, using a cut-off of ≥1 and ≥2 for ESASr-A and GAD-2, respectively, produced the best combination of sensitivity and specificity (ESASr-A sensitivity 0.70, specificity 0.95; GAD-2 sensitivity 0.81, specificity 0.95). Compared to administering only PROMIS-A-CAT to all patients, the 2-step screening reduced the average number of questions patients had to complete by 54% and 50%, for ESASr-A and GAD-2, respectively. This reduction was most pronounced among patients with low anxiety scores.
CONCLUSION
A 2-step screening method using either ESASr-A or GAD-2 followed by PROMIS-A-CAT has acceptable specificity and sensitivity, and can help improve the efficiency of identifying patients with anxiety symptoms. Screened in patients will need clinical assessment to establish diagnosis and decide on appropriate psychosocial support.
Name: Elena Kum
Email: elenakum@rogers.com
Supervisor: Warren Fingrut
Theme: 1
Authors: Elena Kum (1,2), Adriyan Hrycyshyn (1,3), Gabriele Jagelaviciute (1,3), Angela C. Chen (1,4), Iman Baharmand (1,5), Samer Rihani (1,6), Gabriella Rumball (1,7), Div Patel (1,7), Rana Kandel (1,8), Sylvia Okonofua (1,9), Edward Wei Li (1,10), Sze Wah Samuel Chan (1,10), Shamini Vijaya Kumar (1,10), Kenneth Williams (1,10), Daniel Tarade (1,10), Lillie Prokosch (1,11), Warren Fingrut (1,5,12)
Affiliations: Stem Cell Club (1); Faculty of Health Sciences, McMaster University, Hamilton, ON (2); Faculty of Medicine, Queen’s University, Kingston, ON (3); Faculty of Science, University of Waterloo, Waterloo, ON (4); Faculty of Medicine, University of British Columbia, Vancouver, BC (5); Faculty of Science, Simon Fraser University, Burnaby, BC (6); Faculty of Science, Laurentian University, Sudbury, ON (7); Faculty of Medicine, University of Ottawa, Ottawa, ON (8); Faculty of Science, University of Regina, Regina, SK (9); Faculty of Medicine, University of Toronto, Toronto ON (10); Faculty of Science, Wilfrid Laurier University, Waterloo, ON (11); Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York NY (12)
Background
A community of practice (COP) is a group of people who share a passion for something, and learn how to perform better as they interact regularly. We report the development and evaluation of a COP in stem cell donor recruitment in Canada.
Methods
In 09/2017, we invited stakeholders in donor recruitment to participate in e-meetings and a Facebook group. E-meeting topics included recruiting the most-needed donors, redirecting non-optimal donors, reviewing drive outcomes, using patient stories, reducing donor attrition, and levering social media for online donor recruitment. The Facebook group facilitated discussion and sharing of resources between e-meetings. We invited COP participants to join subcommittees to achieve specific objectives. A survey was sent to COP participants in 01/2020 to evaluate the impact of the COP on donor recruitment practice. Recruitment outcomes by the Canadian donor recruitment organization Stem Cell Club were compared before and after the launch of the COP.
Results
As of 10/2020, the COP Facebook group included 353 stakeholders in donor recruitment (331 donor recruiters, 16 patients/donors, 6 donor registry staff). 120 unique attendees participated in 8 e-meetings. Participants set goals for the COP: to foster collaboration; improve knowledge and practice in donor recruitment; improve recruitment of the most-needed donors; and improve the ability to run quality stem cell drives. 141 posts were published to the Facebook group on recruitment resources (64%), stem cell drive outcomes (15%), recruitment updates (14%), and questions posed by COP participants (5%). 44 COP participants completed the evaluation survey. The majority felt that the Facebook group (86%) and e-meetings (59%) supported the development of a community. 64-84% felt that participating in the COP fostered collaboration; improved their knowledge and practice in donor recruitment; and improved their ability to run quality drives and recruit most-needed donors. Stem Cell Club’s recruitment outcomes improved following the launch of the COP: in 2016-2017, Stem Cell Club recruited 2918 donors (46% male; 55.9% non-Caucasian) compared to 4531 donors in 2018-2019 (52.9% male; 62.7% non-Caucasian). The COP generated outputs, including a whiteboard video series and a stem cell donation story library. COP participants ran national donor recruitment campaigns, securing media coverage across Canada and recruiting thousands of donors.
Conclusion
We describe the first COP in stem cell donor recruitment to our knowledge. The COP was valued by participants and supported efforts to improve donor recruitment. The COP model may be adapted by worldwide donor recruitment organizations to improve outcomes.
Background
A community of practice (COP) is a group of people who share a passion for something, and learn how to perform better as they interact regularly. We report the development and evaluation of a COP in stem cell donor recruitment in Canada.
In 09/2017, we invited individuals in donor recruitment to participate in e-meetings and a Facebook group. E-meeting topics included recruiting the most-needed donors, redirecting non-optimal donors, reviewing drive outcomes, using patient stories, improving donor retention, and levering social media for online donor recruitment. The Facebook group allowed for discussion and sharing of resources between e-meetings. We invited COP participants to join subcommittees to achieve specific objectives. A survey was sent to COP participants in 01/2020 to evaluate the impact of the COP on their ability to recruit donors. Donor recruitment outcomes by the Canadian donor recruitment organization Stem Cell Club were compared before and after the launch of the COP.
Results
As of 10/2020, the COP Facebook group included 331 donor recruiters, 16 patients/donors, 6 donor registry staff. 120 unique attendees participated in 8 e-meetings. Participants set goals for the COP: to collaborate; improve knowledge and practice in donor recruitment; improve recruitment of the most-needed donors; and improve the ability to run quality stem cell drives. 141 posts were published to the Facebook group on donor recruitment resources (64%), stem cell drive outcomes (15%), updates (14%), and questions posed by COP participants (5%). 44 COP participants completed the evaluation survey. The majority felt that the Facebook group (86%) and e-meetings (59%) supported the development of a community. 64-84% felt that participating in the COP allowed for collaboration; improved their knowledge and practice in donor recruitment; and improved their ability to run quality drives and recruit most-needed donors. Stem Cell Club’s recruitment outcomes improved following the launch of the COP: in 2016-2017, Stem Cell Club recruited 2918 donors (46% male; 55.9% non-Caucasian) compared to 4531 donors in 2018-2019 (52.9% male; 62.7% non-Caucasian). The COP generated resources to support donor recruitment, including a whiteboard video series and a stem cell donation story library. COP participants ran national donor recruitment campaigns, securing media coverage across Canada and recruiting thousands of donors.
Conclusion
We describe the first COP in stem cell donor recruitment that may be similarly adopted by donor recruitment organizations worldwide. The COP was valued by participants and supported efforts to improve donor recruitment.
Name: Hyunyun Kim
Email: khy215@gmail.com
Supervisor: Marie-Josée Hébert
Theme: 3
Authors: Hyunyun Kim (1,2,3), Francis Migneault (2,3), Annie Karakeussian Rimbaud (2,3), Mélanie Dieudé (2,3), Marie-Josée Hébert (1,2,3)
Affiliations: Programme de biologie moléculaire, Faculté de médecine, Université de Montréal, Montréal, QC, Canada (1); Research Centre, Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, QC, Canada (2); Canadian Donation and Transplantation Research Program (CDTRP) (3)
Background
Ischemia-reperfusion injury (IRI) is an integral component of kidney damage in renal transplant recipients and common cause of acute kidney injury (AKI). Harsh microenvironment induced by AKI leads to programmed cell death of endothelial cells (ECs) in peritubular capillaries favoring microvascular rarefaction. We previously show that apoptotic endothelial cells secrete, in addition to classical apoptotic bodies, exosome-like vesicles (ApoExo) that regulate endothelial function. However, the precise role of ApoExo on vascular response to injury remains unclear. Here, we investigate the impact of ApoExo on angiogenesis following vascular injury.
Method
ApoExos were isolated by sequential ultracentrifugation from medium conditioned by apoptotic human ECs or murine ECs. Unilateral hind limb ischemia, a model of persistent vascular injury, was surgically induced by femoral arteriectomy. Mice were injected intravenously (caudal vein) with ApoExo every second day up to eight injections. Blood flow recovery monitored by laser Doppler, ischemic damage, ambulatory impairment and weight were measured at 0, 3, 7, 14 and 21 days post-surgery. Mice were sacrificed at 21 days and capillary density was evaluated on the ischemic hindlimb. We also used in vitro assays with human ECs exposed to ApoExo to assess levels of apoptosis (measured by fluorescence microscopy), wound closure (scratch assay) and angiogenic activity (tube formation assay).
Results
ApoExo-injected mice exhibited enhanced blood flow recovery and reduced ischemic damage from day 7 to 21. Capillary density was increased in the ApoExo injected group, suggesting that ApoExo improves angiogenesis and restore from ischemic damage. In vitro, ApoExo inhibited apoptosis of ECs and promoted endothelial wound closure and tube formation.
Conclusion
Collectively, these results suggest that ApoExo can help restore the microvasculature following severe vascular injury by increasing the resistance of EC to apoptosis and by upregulating their migration and angiogenic activity. The release of ApoExo by damaged ECs likely represents a feedback loop aimed at favoring repair after vascular injury.
Acute kidney injury (AKI) is sudden loss of kidney function caused by reduced blood flow to the kidneys. AKI can lead to chronic kidney disease (CKD), which is a slow, progressive and irreversible deterioration of kidney function. Kidney damage due to lack of nutrients and oxygen is a common cause of AKI, which leads to programmed cell death of microscopic blood vessels. We have previously shown that this process is under the control of caspase-3 and triggers microscopic alarm signals sent in the form of vesicles (ApoExo) detachable from blood vessel cells. However, the precise role of these vesicles on the regeneration of blood vessels remains unclear. Here, we investigate the impact of ApoExo on vascular repair following severe injury. We revealed that these ApoExo can increase the regeneration of small blood vessels following severe vascular injury by protecting the cells from dying and increasing their ability to form new vessels.
Name: Gabriele Jagelaviciute
Email: 15gj5@queensu.ca
Supervisor: Warren Fingrut
Theme: 1
Authors: Gabriele Jagelaviciute (1,2), Elena Kum (1,3), Kenneth Williams (1,4), Edward W. Li (1,4), Rana Kandel (1,5), Aaron Rosenfeld (1,5), Natalie DeGurse (1,6), Sylvia Okonofua (1,7), Alexander Sharp (1,8), Santhosh Thyagu (4,9), Warren Fingrut (1,10, 11)
Affiliations: Stem Cell Club, Canada (www.stemcellclub.ca) (1); Faculty of Medicine, Queen’s University, Kingston, Ontario, Canada (2); Faculty of Health Science, McMaster University, Hamilton, Ontario, Canada (3); Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada (4); Faculty of Medicine, University of Ottawa (5); Faculty of Science, Western University, London, Ontario, Canada (6); Faculty of Science, University of Regina (7); Faculty of Medicine, University of Manitoba (8); Princess Margaret Cancer Centre, Toronto, Ontario, Canada (9); Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada (10); Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY (11)
INTRODUCTION
Most patients in need of allogeneic stem cell transplantation lack a matched family donor and require an unrelated donor. Needs assessment surveys with stakeholders in stem cell donation in Canada identified the need for a library of stories in stem cell donation to support the recruitment of unrelated donors. Here, we describe the development and evaluation of this resource.
METHODS
Why We Swab reports stories about Canadian stem cell donors and recipients, patients searching for a match, and family members. The stories are directed at an audience of potential donors, told in a first-person narrative, and published alongside the storyteller’s photo or video. Stories are published across social media (Facebook, Instagram, Twitter; @WhyWeSwab). Following launch in 09/2019, we evaluated stakeholder perspective on Why We Swab as well as its impact across media, on donor recruitment outcomes, and on eligible donors’ attitudes towards donation.
RESULTS
As of 11/2020, 17 story arcs (84 social media posts) were published online, featuring 27 storytellers from a range of ethnicities (13 patients/recipients; 8 donors; 6 family members). Story segments published to the Why We Swab Facebook page reached an audience of 195,931 people and secured 33,239 engagements (i.e., likes, comments, and shares). Stories reported by Why We Swab were re-published by ten Canadian media outlets. In the first 5 months following launch, the total number of donors recruited by Stem Cell Club increased to 2810 (50% males, 68% non-Caucasian) from 2445 (52% males, 61% non-Caucasian) during the same period the year prior.
51 stakeholders (40 recruiters; 3 recipients; 4 donors; 4 registry staff) completed the post-launch survey to share their perspective. The majority (80-96%) felt Why We Swab helps raise awareness about stem cell donation and supports the education and recruitment of the most-needed donors.
33 eligible stem cell donors (100% male; from 9 different non-Caucasian ethnic groups) completed surveys evaluating the impact of Why We Swab stories on their attitudes towards donation. After being shown a series of Why We Swab story posts, mean scores on the Simmons Ambivalence Scale significantly decreased from 3.85 to 2.70 (p=0.0003). The majority (76-85%) felt the stories positively impacted on their decision to register and would help them talk about donation with friends/family.
CONCLUSIONS
Why We Swab is a library of stories in stem cell donation which supports the recruitment of committed unrelated stem cell donors. Our work is relevant to donor registries worldwide.
INTRODUCTION
Most patients in need of a stem cell transplant lack a matching donor in their family and need an unrelated donor. We surveyed stem cell recipients, donors, and donor recruiters who told us that a library of stories in stem cell donation was needed to support donor registration. Here, we explain the development and evaluation of this resource.
METHODS
Why We Swab shares stories about Canadian stem cell donors and recipients, patients searching for a match, and family members. The stories are directed to potential donors, told in a first-person perspective, and published alongside the storyteller’s photo or video. Stories are published across social media (Facebook, Instagram, Twitter; @WhyWeSwab). After launch in 09/2019, we evaluated perspectives on Why We Swab as well as its impact across media, on donor registration, and on eligible donors’ attitudes towards donation.
RESULTS
As of 11/2020, 17 story arcs (84 social media posts) were published online, featuring 27 storytellers from a range of ethnicities (13 patients/recipients; 8 donors; 6 family members). Story segments published to the Why We Swab Facebook page reached an audience of 195,931 people and secured 33,239 engagements (i.e., likes, comments, and shares). Stories shared by Why We Swab were re-published by ten Canadian media outlets. In the first 5 months following launch, the total number of donors signed up by Stem Cell Club increased to 2810 (50% males, 68% non-Caucasian) from 2445 (52% males, 61% non-Caucasian) during the same period the year prior.
51 individuals (40 recruiters; 3 recipients; 4 donors; 4 registry staff) completed the post-launch survey to share their perspective. The majority (80-96%) felt Why We Swab helps raise awareness about stem cell donation and supports the education and recruitment of the most-needed donors (17-35 years old, male, and ethnically diverse).
33 eligible stem cell donors (100% male; from 9 different non-Caucasian ethnic groups) completed surveys evaluating the impact of Why We Swab stories on their attitudes towards donation. After being shown a series of Why We Swab story posts, average scores on an ambivalence scale significantly decreased. The majority (76-85%) felt the stories positively impacted on their decision to register and would help them talk about donation with friends/family.
CONCLUSIONS
Why We Swab is a library of stories in stem cell donation which supports the recruitment of committed unrelated stem cell donors. Our work is relevant to organizations worldwide that seek to recruit donors.
Name: Anna Horton
Email: anna.horton@mail.mcgill.ca
Supervisor: Shaifali Sandal
Theme: 1
Authors: Anna Horton, Marie-Chantal Fortin, Antonia Maioni, Peter Nugus, David Landsberg, Prosanto Chaudhury, Michel Paquet, Marcelo Cantarovich, Shaifali Sandal
Affiliations: McGill University Health Centre, Montréal, QC
Living Donor Kidney Transplantation (LDKT) has significant advantages for both patients and health care systems, in coping with the burden of end-stage renal disease. Despite these advantages, Canada has struggled overall to effectively implement LDKT. There are large interprovincial variations in LDKT rates in Canada, the reasons for which are not well understood.
We consider the need for a cultural approach to understanding the whole-system functioning of LDKT, towards increasing rates in provinces with lower numbers. Using frameworks from sociological and anthropological paradigms to understand the dynamic and interdependent systems that produce LDKT, we can promote learning at every level in the pursuit of increasing LDKT. Recognizing the dynamic properties of a system and targeting patterns of relationships and flows of behaviour, rather than describing static properties, provides opportunities to understand how a system learns.
Drawing on our ongoing study that aims to learn and compare health systems for LDKT in BC, ON and QC, we explore the conceptual and methodological tools that enable us to understand the ‘culture’ of an LDKT health system. Underpinning our approach is a recognition of complexity, patterns and interrelationships among the elements of a system, which moves beyond a simple focus on cause and effect. Using document analysis, field work and interviews, we aim to trace the organization of LDKT across macro, meso and micro levels. We also focus on emergent and less formal processes that function in ‘real life’ situations.
Our work suggests that understanding practices of LDKT through a cultural lens has an important role in developing strategies to increase rates of LDKT. Approaching health systems in this way enables fostering transferrable competencies that are firmly rooted in the lived realities of the patients and healthcare professionals involved in LDKT. As such, we argue that a cultural approach to understanding the whole-system functioning of LDKT will yield valuable insights and tools for increasing LDKT in provinces with variable rates.
Living Donor Kidney Transplantation (LDKT) is a very good treatment for patients with kidney failure. It also saves money for health care services. Even though we know this, LDKT rates are not as good as they could be in Canada. Some provinces have higher rates of LDKT, whilst other provinces have low rates. We don’t really know why this is.
We think that it would be useful to study health systems in different provinces ‘culturally’, in order to help increase LDKT rates in provinces that don’t do it as much. This means that we will use tools from the disciplines of anthropology and sociology to study how different provincial systems make LDKT happen. These disciplines tend to look at what people think and do in real life. Using tools from these disciplines will help us to understand the different parts of the system, like clinics, healthcare workers and patients, and how they behave and communicate to make LDKT happen. When we understand this, we can make suggestions to help increase LDKT.
We have started doing this work in a study that aims to learn and compare the health systems for LDKT in BC, ON and QC. We are trying to understand the ‘culture’ of these different systems and compare them. These systems are complicated. We think that our research should recognise that complexity and not try to simplify it. To help understand each system, we are looking at documents, interviewing people and observing communication between people. These different tools will help us understand how LDKT works in real life.
Our work so far suggests that this ‘cultural’ approach to understanding how LDKT works might be useful to help increase rates. By looking directly at what people do, what they think and how they communicate, we can make suggestions for improvements that are mindful of what works and what doesn’t work in real life. Because of this, we argue that a ‘cultural’ approach to understanding how systems make LDKT happen will help us make useful suggestions for how to increase LDKT in provinces with lower rates.
Name: Natalie DeGurse
Email: ndegurs@uwo.ca
Supervisor: Warren Fingrut
Theme: 1
Authors: Daniel Tarade (1, 2), Natalie DeGurse (1, 3), Kenneth Williams (1, 2), Shamini Vijaya Kumar (1, 2), Sze Wah Samuel Chan (1, 2), Brendon Lam (1, 2), Kaveh Farrokhi (1, 3), Adriyan Hrycyshyn (1, 4), Dylan Coupal (1, 5), Sylvia Okonofua (1, 5), Hayley Wroot (1, 6), Kyla Pires (1, 6) and Warren Fingrut, MD (1, 6, 7)
Affiliations: Stem Cell Club, ON, Canada (1); University of Toronto, Toronto, ON, Canada (2); Western University, London, ON, Canada (3); Queen’s University, Kingston, ON, Canada (4); University of Regina, Regina, SK, Canada (5); University of British Columbia, Vancouver, BC, Canada (6); Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY (7)
Introduction
Since 2009, gay, bisexual, and other men who have sex with men (MSM) have been eligible to register as stem cell donors for a patient in need. However, many MSM are unaware of their donor eligibility. Targeted recruitment of MSM could promote recruitment of the most needed stem cell donors (young and ethnically-diverse males) and support an inclusive donor registry. We describe a strategy for targeted recruitment of MSM as stem cell donors and outcomes of a pilot campaign spearheaded by the Canadian donor recruitment organization Stem Cell Club (stemcellclub.ca).
Methods
Experienced donor recruiters from Stem Cell Club were invited to run stem cell drives at Pride events. Before these drives, recruiters completed a workshop on blood and stem cell donation for MSM in Canada. The workshop coached recruiters to answer common questions about donation policies regarding MSM, including Canadian blood donation policy for MSM, stem cell donor eligibility of HIV positive registrants, and answering Trans* or gender non-binary questions about the registrant form. Recruiters were taught to share the story of William, a gay man who donated stem cells to an unrelated patient, Susan (CBC News, 2019). An online survey was employed to evaluate recruiter learning outcomes. At Pride stem cell drives, recruiters guided eligible and interested registrants to sign up as potential donors with the Canadian Blood Services Stem Cell Registry.
Results
Since 2018, recruiters from Stem Cell Club ran 7 drives at 5 Pride festivals in 4 cities. 14 club leaders completed the training workshop, with 8 completing the post-workshop survey. Survey participants unanimously agreed or strongly agreed that the workshop improved their knowledge, preparation, and skills to run drives targeting MSM recruitment. Overall, these drives recruited 354 stem cell donors (40% male, 42% non-Caucasian). Recruiters from all drives shared that engaging MSM as stem cell donors was well-received by the community. Multiple LGBTQ people consented to the publication of their photos online to engage the community as donors. Resources such as short videos and TikToks were shared to support virtual recruitment of MSM
Conclusion
We outline a strategy to engage MSM as potential stem cell donors. Our work is relevant to donor recruitment organizations and registries seeking to recruit this unique donor population. Based on these strong outcomes, Stem Cell Club will spearhead a national campaign in partnership with Pride societies across Canada to engage MSM as stem cell donors.
Introduction
Patients with blood diseases may need a stem cell transplant as part of their treatment. Many of these patients do not have a matched donor in their family and require an unrelated donor. Stem Cell Club aims to improve the quality and quantity of Canada’s Stem Cell Registry by recruiting the most-needed stem cell donors (young, ethnically diverse males). Gay, bisexual, and other men who have sex with men (MSM) are eligible to register as stem cell donors in Canada and donate to a patient in need. Recruitment of MSM as stem cell donors could increase registration of the most-needed stem cell donors, but many MSM are unaware of their eligibility. We outline outcomes of a pilot campaign organized by Stem Cell Club targeting MSM recruitment, and describe a strategy for targeted recruitment of MSM as stem cell donors.
Methods
Experienced donor recruiters from Stem Cell Club were invited to run stem cell drives at Pride events. Before these drives, participating donor recruiters attended a training session that focused on answering common questions about blood and stem cell donation policy regarding MSM. Recruiters were taught to share the story of William, a gay man who donated stem cells to an unrelated patient, Susan (CBC News, 2019). An online survey was employed to evaluate recruiter learning outcomes. At Pride events, stem cell drive volunteers recruited eligible and interested participants to register as a stem cell donor to the Canadian Blood Services Stem Cell Registry.
Results
Since 2018, recruiters from Stem Cell Club ran 7 drives at 5 Pride festivals in 4 cities, recruiting a total of 354 stem cell donors (40% male, 42% non-Caucasian). Of the 14 club leaders that attended the training workshop, 8 completed the online post-workshop survey, which found that club leaders felt the training workshop improved their ability to recruit MSM at Pride stem cell drives. At all Pride drives, stem cell volunteers shared that the community welcomed recruitment efforts. Multiple LGBTQ people provided consent for their photos to be published online to engage the community as donors. Resources such as short videos and TikToks were shared to support virtual recruitment of MSM.
Conclusion
We outline a strategy to recruit MSM as stem cell donors. Stem Cell Club will initiate a national campaign in partnership with Pride societies across Canada to engage MSM as stem cell donors.
Name: Mackenzie Cullip
Email: cullipm@mcmaster.ca
Supervisor: Matthew Weiss
Theme: 1
Authors: Mackenzie Cullip (1,2), Matthew J Weiss (1,3), Maureen Meade (1,4)
Affiliations: Canadian Donation and Transplantation Research Program (1); Integrated Biomedical Engineering and Health Sciences, McMaster University(2); Faculté de Médicine, Département de Pédiatrie, Université Laval (3); Hamilton Health Sciences, McMaster University (4)
Background
Death investigators (DIs) such as coroners, medical examiners, and forensic pathologists play important and evolving roles in deceased organ donation, as they have jurisdiction over the deceased and their organs during sudden or unexpected deaths. DIs communicate with organ donation organizations (ODOs) to gather case-specific information, release or restrict organs depending on the need to retain evidence, and ultimately determine the cause and manner of death. This scoping review aims to identify the breadth of roles and decision-making processes that allow or prevent deceased donation in DI cases.
Methods
Investigators interviewed DIs and ODO professionals to identify common and contrasting practices, informing a scoping review. Interviews were initially unscripted but evolved with successive participants to include predetermined questions. Interview topics included DI roles in death investigation and organ donation, education standards and practice protocol, and donation-specific legislation. These informed the inclusion criteria and screening checklist for a scoping review. The primary investigator searched five databases in November 2019: PubMed, OVID, Web of Science, TRIP, and CINAHL.
Results
Investigators interviewed 6 DIs and 4 ODO professionals from 4 countries. Thirty eligible papers described 8 common themes with country-specific nuances. These include: 1) shared (ODO-DI) protocols for early communication around each case; 2) shared (ODO-DI) standards and education for donation and death investigation practices; 3) DI support staff or teams established to facilitate organ donation; 4) donation-specific legislation enacted to enhance DI and/or ODO operations; 5) DI authority to order additional testing and imaging before organ recovery; 6) authority of legally trained DIs to veto donation decisions; 7) DI attendance at organ recovery; and 8) surgeon responsibility to record evidence during organ recovery.
Conclusion
These findings have many cultural and resource-allocation implications and expose gaps in the international literature describing practices at the intersection of deceased organ donation and death investigation. A better understanding of the rationale and execution for varied systems for DI and ODO cooperation may serve to advance both organ donation and death investigation efficacy.
Background
Death investigators (DIs) such as coroners, medical examiners, and forensic pathologists play important and evolving roles in deceased organ donation, as they have jurisdiction over the deceased and their organs during sudden or unexpected deaths. DIs communicate with organ donation organizations (ODOs) to gather case-specific information, release or restrict organs depending on the need to retain evidence, and ultimately determine the cause and manner of death. This scoping review aims to identify the breadth of roles and decision-making processes that allow or prevent deceased donation in DI cases.
Methods
Investigators interviewed DIs and ODO professionals to identify common and contrasting practices, informing a scoping review. Interviews were initially unscripted but evolved with successive participants to include predetermined questions. Interview topics included DI roles in death investigation and organ donation, education standards and practice protocol, and donation-specific legislation. These informed the inclusion criteria and screening checklist for a scoping review. The primary investigator searched five databases in November 2019: PubMed, OVID, Web of Science, TRIP, and CINAHL.
Results
Investigators interviewed 6 DIs and 4 ODO professionals from 4 countries. Thirty eligible papers described 8 common themes with country-specific nuances. These include: 1) shared (ODO-DI) protocols for early communication around each case; 2) shared (ODO-DI) standards and education for donation and death investigation practices; 3) DI support staff or teams established to facilitate organ donation; 4) donation-specific legislation enacted to enhance DI and/or ODO operations; 5) DI authority to order additional testing and imaging before organ recovery; 6) authority of legally trained DIs to veto donation decisions; 7) DI attendance at organ recovery; and 8) surgeon responsibility to record evidence during organ recovery.
Conclusion
These findings have many cultural and resource-allocation implications and expose gaps in the international literature describing practices at the intersection of deceased organ donation and death investigation. A better understanding of the rationale and execution for varied systems for DI and ODO cooperation may serve to advance both organ donation and death investigation efficacy.
Name: Angela Chen
Email: acchen@uwaterloo.ca
Supervisor: Warren Fingrut
Authors: Angela C. Chen (1,2), Meagan Green (3), Jason T. Weiss (3), Dena Mercer (3), Heidi Elmoazzen (3), David Allan (3,6), Warren Fingrut (1,7)
Affiliations: (1) Stem Cell Club; (2) Faculty of Health, University of Waterloo; (3) Canadian Blood Service; (4) Faculty of Medicine, University of Ottawa; (5) Ottawa Hospital Research Institute; (6) Department of Medicine, The Ottawa Hospital; (7) Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center
Introduction
Unrelated stem cell donors are recruited at virtual or in-person recruitment events, at which recruiters guide registrants to provide informed consent and a tissue sample for typing. Checklists are memory recall tools used across healthcare to improve outcomes. Here, we describe the development and evaluation of a checklist to support stem cell donor recruitment.
Methods
A series of checklists was designed with the objectives to 1) improve best practice adherence; 2) reduce errors; and 3) support standardization at stem cell drives. Relevant World Marrow Donor Association guidelines were incorporated. Topics included: donor eligibility screening; informed consent; good documentation practices; and technical aspects of registration and tissue sample collection. Checklists were iteratively revised with input from stakeholders in stem cell donation, including modifications to support virtual drives during the COVID-19 pandemic.
We examined the checklists’ impact on recruitment outcomes and error rates (registrants who were not listed/untraceable due to registration errors) of the Canadian donor recruitment organization Stem Cell Club (SCC) (data obtained from Canadian Blood Services Stem Cell National System Solution). Quantitative and qualitative methods were employed to analyze the recruiters’ perspectives on the checklists and identify common themes.
Results
8 checklists were developed: Stem Cell Drive Setup; Prescreening; Redirect Donors to Help in Other Ways; Informed Consent; Registration; Tissue Sample Collection; Reconciliation; and Post-event (Fig. 1). These checklists were implemented by Stem Cell Club in 09/2015.
From 11/2011 – 09/2016 (prior to implementation), 4,573 registrants were recruited, of which 3,575 were listed as donors (60% male; 58% non-Caucasian; error rate: 15.2%) and 1 registrant went on to donate their stem cells. From 09/2016 – 11/2019 (post-implementation), 10,621 registrants were recruited, of which 10,420 were listed as donors (51% male; 55% non-Caucasian; error rate: 1.9%) and 8 registrants went on to donate their stem cells (Fig. 2).
6 months post-implementation, 52 SCC recruiters completed an online survey about the checklists. The majority (70-96%) felt that checklists were used, valued, and facilitated the completion of tasks at donor recruitment drives. Further, 4 years post-implementation, 10 experienced recruiters participated in focus groups to share their perspectives on the checklists. Qualitative analysis generated rich evidence that the checklists’ objectives were realized from the recruiter perspective (Fig. 3).
Conclusions
We developed checklists to support donor recruitment and showed that their implementation was valued by recruiters and associated with both reduced errors and improved donor recruitment outcomes. The checklists are relevant to donor recruitment organizations worldwide.
Introduction
Stem cell donors are recruited at virtual or in-person recruitment events called stem cell drives, in which recruiters guide registrants to provide informed consent and a DNA sample to determine whether they are a match with a patient in need. Checklists are memory recall tools used across healthcare to improve outcomes. Here, we describe the development and evaluation of checklists to support stem cell donor recruitment.
Methods
Several checklists were designed with the objectives to 1) help guide recruiters and donors through the registration process; 2) reduce errors; and 3) standardize the registration procedure across stem cell drives. The checklists covered all the tasks that recruiters need to complete to register potential donors. The checklists were reviewed by those with experience in stem cell donation. Their feedback was then used to revise the checklists.
We examined the checklists’ impact on recruiting donors and reducing error rates for the Canadian donor recruitment organization Stem Cell Club (SCC). SCC recruiters across Canada shared their perspective about the use and effects of these checklists at stem cell drives.
Results
8 checklists were developed: Stem Cell Drive Setup; Prescreening; Redirect Donors to Help in Other Ways; Informed Consent; Registration; Tissue Sample Collection; Reconciliation; and Post-event (Fig. 1). SCC began using the checklists in 09/2015.
A comparison of the SCC donor recruitment outcomes before and after implementation of the checklists showed an increase in donors recruited (4,573 registrants recruited from 11/2011 – 09/2016 versus 10,420 registrants recruited from 09/2016 – 11/2019) and a decrease in error rate (15.2% from 11/2011 – 09/2016 to 1.9% from 09/2016 – 11/2019).
6 months post-implementation, 52 SCC recruiters completed an online survey about the checklists. The majority (70-96%) felt that checklists were used, valued, and facilitated the completion of tasks at donor recruitment drives. Further, 4 years post-implementation, 10 experienced recruiters participated in focus groups to share their perspectives on the checklists. The participants agreed that the checklists accomplished the objectives we had set out for them to achieve (Fig. 3).
Conclusions
We developed checklists to support stem cell donor recruitment and showed that their implementation was valued by recruiters and associated with both reduced errors and improved donor recruitment outcomes. The checklists are relevant to donor recruitment organizations worldwide.
Name: Alexandre Brodeur
Email: alexandre.brodeur.1@umontreal.ca
Supervisor: Marie-Josée Hébert
Authors: Alexandre Brodeur (1,2), Francis Migneault (1,2), Nicolas Thibodeau (1), Déborah Beillevaire (1), Mélanie Dieudé (1,2), Marie-Josée Hébert (1,2)
Affilitations: Université de Montréal, Canadian Donation and Transplantation Research Program (CDTRP)
Ischemia-reperfusion injury (IRI) induces endothelial apoptosis, which contributes to the maladaptive repair of vascular network. During this process, apoptotic exosome-like vesicles (ApoExo) are released in the bloodstream and are uptaken by endothelial cells (EC). We previously showed that ApoExo modulate gene expression, functions, and morphology of endothelial cells towards endothelial dysfunction. However, the mechanism by which EC internalize ApoExo remains unclear.ApoExo were isolated by ultracentrifugation from serum-free media conditioned by fluorescently labeled EC. Serum-starved primary human EC were then exposed to purified ApoExo in vitro. Confocal microscopy and flow cytometry were used to assess the uptake of ApoExo. Pharmacological inhibitors and gene silencing were used to probe uptake mechanisms. EC morphology was assessed by electronic microscopy (EM).
Efficient uptake of ApoExo by EC was observed in a time- and concentration-dependent manner. ApoExo uptake was significantly decreased by concomitant exposure with unlabeled ApoExo or with Triton X-100-treated ApoExo, confirming a specific response. ApoExo uptake was abolished at 4oC suggesting an energy-dependent mechanism. Blocking the actin polymerization using cytochalasin D decreased the uptake of ApoExo. Inhibition of classical endocytosis pathways, such as clatherin-mediated and caveolae-dependent endocytosis failed to reduce ApoExo uptake, suggesting ApoExo are internalized by non-classical endocytosis. Disruption of membrane integrity by MβCD failed to block the internalization of ApoExo when used on cells. However, the use of MβCD on ApoExo significantly inhibited their uptake by EC. Annexin V, a phosphatidylserine (PS)-binding protein, decreased ApoExo uptake when used on vesicles, but not on cells. Ultrastructural analysis of serum-starved EC revealed lamellipodia-like structures, a hallmark of macropinocytosis. Exposure to ApoExo increased the number of lamellipodia on EC. EIPA, a macropinocytosis inhibitor, significantly reduced ApoExo uptake by EC.
These results demonstrate that EC actively uptake ApoExo through PS-mediated macropinocytosis. Also, ApoExo can further increase this response through a positive feedback loop on lamellipodia formation. These results open new avenues for preventing ApoExo internalisation and preventing the development of endothelial dysfunction.
Ischemia-reperfusion injury (IRI) causes blood vessel cell death via a tightly regulated process called apoptosis, which contributes to the maladaptive repair of the vascular network. During this process, apoptotic exosome-like vesicles (ApoExo) are released in the bloodstream and are uptaken by endothelial cells (EC). We previously showed that ApoExo modulate gene expression, functions, and shape of endothelial cells towards endothelial dysfunction. However, the mechanism by which EC internalize ApoExo remains unclear.
ApoExo were isolated by ultracentrifugation from serum-free media conditioned by fluorescently labeled EC. Fresh, unlabeled serum-starved primary human EC were then exposed to isolated ApoExo in vitro. Confocal microscopy and flow cytometry were used to assess the uptake of ApoExo. Pharmacological inhibitors and gene silencing were used to probe uptake mechanisms. EC morphology was assessed by electron microscopy (EM).
Endothelial cells continuously uptake ApoExo through time. Increased concentration of ApoExo also showed higher uptake levels, suggesting linear dynamics. To verify the specificity of uptake, competition assay involving unlabeled ApoExo shows reduced fluorescence, confirming that the fluorescent dye does not leak into EC. When Triton X-100-treated ApoExo, confirming a specific response. ApoExo uptake was abolished at 4oC suggesting an energy-dependent mechanism. Blocking the actin polymerization, a structure protein often involved in internalization pathway, using cytochalasin D decreased the uptake of ApoExo. Inhibition of classical endocytosis pathways, such as clatherin-mediated and caveolae-dependent endocytosis failed to reduce ApoExo uptake, suggesting ApoExo are internalized by non-classical endocytosis. Disruption of membrane integrity by MβCD failed to block the internalization of ApoExo when used on cells. However, the use of the same inhibitor on ApoExo significantly inhibited their uptake by EC highlighting the importance of ApoExo membrane intergrity. Annexin V, a phosphatidylserine (PS)-binding protein, decreased ApoExo uptake when used on vesicles, but not on cells, again showcasing ApoExo membrane’s implication in their uptake. Ultrastructural analysis of serum-starved EC revealed lamellipodia-like structures, a hallmark of macropinocytosis. Exposure to ApoExo increased the number of lamellipodia on EC. EIPA, a macropinocytosis inhibitor, significantly reduced ApoExo uptake by EC.
These results demonstrate that EC actively uptake ApoExo through PS-mediated macropinocytosis. Also, ApoExo can further increase this response through a positive feedback loop on lamellipodia formation. These results open new avenues for preventing ApoExo internalisation and preventing the development of endothelial dysfunction.
Name: Bushra Anjum
Email: bushara@ualberta.ca
Supervisor: Lori West
Theme: 4
Authors: Bushra Anjum, Ibrahim Adam, Jean Pearcey, Kesheng Tao, Bruce Motyka and Lori J. West
Affiliations: Pediatrics, Alberta Transplant Institute, Canadian Donation and Transplantation Research Program, University of Alberta
Background
ABO histo-blood group incompatibility is a barrier in solid organ transplant due to ‘natural’ preformed ABO antibodies. The ABH glycan microarray, developed in the West lab, determines the isotype (IgM/IgG) and ABH subtype specificity (subtypes I-VI) of natural ABO antibodies in a mouse model. We previously found that BALB/c (BALB) mice produce antibodies specific to subtypes III/IV A-antigens whereas specificity to subtype II A-antigens were low/absent. Females, compared to males, had significantly higher levels of anti-A antibodies and showed a distinct shift in anti-A antibody production from IgM to IgG isotype at about sexual maturity (6-9 weeks of age). Natural ABO antibodies may develop due to cross-reactivity with components of the gut microbiome. To test this hypothesis, we examined serum ABO antibody levels in germ-free and conventionally-housed male and female mice of different ages.
Methods
Germ-free mice and conventionally-housed mice included the inbred strains C57BL/6 (B6) (females/males, n=10 /10) and BALB (females/males, n=10/10), and the outbred strain Swiss Webster (SW) (females/males, n=4/6). Plasma obtained from tail bleeds at different ages was assessed by ABH glycan microarray for ABO antibody subtype specificity and isotype.
Results
Anti-A and anti-B antibodies were present in germ-free B6, BALB and SW mice at levels similar to that of conventionally-housed mice. At 4-weeks of age, IgG (but not IgM) anti-A antibodies were detected in both sexes at levels similar to that of older (12-week) female mice. Anti-A antibodies were present in males >8-weeks of age, however these were at low levels vs females and remained mostly IgM. In females, anti-A antibodies were mostly IgG isotype at 4-weeks of age, predominately IgM isotype at 8-weeks of age, and then shifted to mostly IgG isotype by 12-weeks of age. Anti-B antibodies were detected in both sexes by 8-weeks of age, remained mostly IgM, and were present at lower levels vs anti-A antibodies. Most natural anti-A antibodies, in germ-free or conventionally-housed mice, were specific to subtypes III/IV whereas antibodies specific to subtype II antigens were low/absent.
Conclusion
The distinct IgM to IgG anti-A antibodies class-switching in female mice at about sexual maturity (age 8-weeks) may provide early immunity to pups through passive transfer of IgG anti-A antibodies during pregnancy. Detection of natural anti-A antibodies in germ-free mice combined with higher levels of natural anti-A antibodies in females vs males suggests a unique sex-dependent, alternative mechanism of natural ABO antibody production than cross-reactivity with gut microbiome antigens.
ABH-antigens are sugars on red blood cells and organs. The sugars we have determine our blood group: either A (A-sugars), B (B-sugars), AB (A- and B-sugars), or O (H-sugars). These sugars also come in six different flavours or ‘subtypes’. Different cells can express different flavours of these sugars.
We make antibodies to ABH-sugars that we don’t have. For instance, blood group O people make antibodies to A- and B-sugars. ABO-antibodies can recognize different flavours (subtypes) of sugars. ABO-antibodies themselves can also be different flavours (‘isotypes’), for example, ‘IgM’ and ‘IgG’.
For blood transfusions and transplants, the presence of these antibodies means we normally need to match the ABO-blood group. Mismatched transplantation can lead to rapid organ rejection. However, as ABO-antibodies are not made until about 6 months of age, infants can safely receive an ABO-mismatched heart transplant. Safe ABO-mismatched transplantation allows for increased life-saving transplants and decreased wait times.
It has been suggested that ABO-antibodies are made from similar ABH-sugars found on bacteria in the gut. To test this and to study ABO-antibody development as a function of both sex and age we used mice. Similar to humans, mice produce ABO-antibodies with age. Using a special test we developed in our lab (‘glycan microarray’) we measured different types of ABO-antibodies that react to different kinds of ABH sugars in germ-free (raised in a germ-free environment) versus conventional male and female mice of different ages.
We found that antibodies specific to ABH-sugars were present in germ-free mice, similar to that in conventionally-housed mice. Very young mice (4 weeks and under) had ABO-antibodies that were likely transferred to them from their mothers (mostly IgG ABO-antibodies). With age, these IgG ABO-antibodies decreased and were replaced with ‘self-made’ IgM antibodies. Males and females had different patterns of ABO-antibody development over time with females producing much more antibody to A-sugars and with a shift of antibody isotype from IgM to IgG. Future studies will explore how these ABO-antibodies develop in the absence of bacteria in the gut as well as why females develop ABO-antibodies differently than males. With a better understanding of how ABO-antibodies develop, it may be possible to extend ABO-mismatched heart transplantation to older age groups and increase the number of transplants being performed.
Name: Alshaima Alhinai
Email: al.alhinai@mail.mcgill.ca
Supervisor: Giada Sebastiani
Authors: Alshaima Alhinai, Afsheen Qayyum Khan, Xun Zhang, Patrick Samaha, Marc Deschenes, Philip Wong, Tianyan Chen, Giada Sebastiani
Affilitations: McGill University Health Centre, Montreal, QC, Canada.
Background
Non-alcoholic steatohepatitis (NASH), the progressive counterpart of Non-alcoholic fatty liver disease (NAFLD), is a major health concern in Canada. Previous studies have shown that NAFLD and NASH are common after liver transplant, however most of these studies were retrospective. We aimed to prospectively determine the incidence and predictors of NAFLD and NASH in liver transplant recipients using Fibroscan with CAP (Controlled Attenuation Parameter) and CK-18 (cytokeratin-18), and to evaluate the diagnostic performance of these tests compared to liver histology.
Methods
We performed a prospective study involving consecutive adult patients who received liver transplants between 2015 to 2018. Patients who received liver transplantation due to chronic hepatitis C, genotype 3; and/or failed Fibroscan with CAP assessment were excluded. Post-transplant, patients were followed for a total of 5 study visits over a period of 18 months. Serial measurements of Fibroscan/CAP and CK-18 were recorded. NAFLD and NASH were diagnosed non-invasively by CAP ≥270 dB/m, and by the combination of CAP ≥270 dB/m with CK-18 >130.5 IU/l, respectively. Multivariable Cox regression models were constructed to assess predictors of NAFLD and NASH. The performance of the non-invasive tests to diagnose NAFLD and NASH was compared to liver histology performed on the same patients using sensitivity, specificity, PPV, NPV, accuracy, and LR+ and LR-.
Results
Overall, 40 patients (mean age 57.3±8.5, 70% male, 80% Caucasian, and 30% transplanted due to NASH) were included. During a median follow-up of 16.8 months (IQR 15.6-18), 63% patients developed NAFLD (incidence rate: 71 per 100 PY, 95% CI 45-78) and 48.5% patients developed NASH (incidence rate: 48.6 per 100 PY, 95% CI 31.4-66). On multivariate Cox regression analysis, BMI was an independent predictor of both NAFLD (adjusted HR 1.1, 95% 1.0-1.2) and NASH (adjusted HR 1.1, 95% CI 1.0-1.3). With the CAP cutoff of 270 dB/m, the diagnostic performance for NAFLD compared to liver histology was as follows: sensitivity 58%, specificity 86%, PPV 70%, NPV 79%, accuracy 76%, LR + 4.28, LR – 0.48. The diagnostic performance of a combination of CAP>270 dB/m and CK-18 >130.5 to diagnose NASH was as follows: sensitivity 75%, specificity 83%, PPV 37% and NPV 96%, accuracy 82%, LR + 4.50, LR- 0.3.
Conclusion
NAFLD and NASH are frequent occurrences in liver transplant recipients mainly driven by high BMI. CAP and CK-18 are useful tools for monitoring however the analysis must be replicated in a larger sample for further knowledge on their accuracy.
Background
Non-alcoholic steatohepatitis (NASH), the progressive counterpart of Non-alcoholic fatty liver disease (NAFLD), is a major health concern in Canada. Previous studies have shown that NAFLD and NASH are common after liver transplant, however most of these studies were retrospective. We aimed to prospectively determine the incidence and predictors of NAFLD and NASH in liver transplant recipients using Fibroscan with CAP (Controlled Attenuation Parameter) and CK-18 (cytokeratin-18), and to evaluate the diagnostic performance of these tests compared to liver histology.
Methods
We performed a prospective study involving consecutive adult patients who received liver transplants between 2015 to 2018. Patients who received liver transplantation due to chronic hepatitis C, genotype 3; and/or failed Fibroscan with CAP assessment were excluded. Post-transplant, patients were followed for a total of 5 study visits over a period of 18 months. Serial measurements of Fibroscan/CAP and CK-18 were recorded. NAFLD and NASH were diagnosed non-invasively by CAP ≥270 dB/m, and by the combination of CAP ≥270 dB/m with CK-18 >130.5 IU/l, respectively. Multivariable Cox regression models were constructed to assess predictors of NAFLD and NASH. The performance of the non-invasive tests to diagnose NAFLD and NASH was compared to liver histology performed on the same patients using sensitivity, specificity, PPV, NPV, accuracy, and LR+ and LR-.
| All prior disease-specific therapy or immunosuppression should be continued unless otherwise instructed. |
| Mandatory use of masks. |
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Recommends to avoid all travels.
| Does not specify DD or LD. It will depend on whether the candidate for transplantation is at home or hospitalized. |
| They recommend some considerations to follow, but mention in the end “data regarding the safety of organ donation from donors with previous COVID-19 are extremely limited at this time.” |
| For thoracic organ donors, they recommend testing upper and lower respiratory tract (e.g. tracheal aspirate, bronchial wash, or bronchoalveolar lavage) when feasible. |
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| Recommend some considerations to follow, but mention in the end “data regarding the safety of organ donation from donors with previous COVID-19 are extremely limited at this time.” |
| The surgery team only goes to a hospital where patients with coronavirus are isolated. |
| Pre-transplant testing in candidate: We also recommend PCR based test in the asymptomatic waitlisted candidate prior to transplant surgery and recommend deferring transplant on PCR+ waitlisted candidates. |
| Minimizing social interactions in the community: • For patients with work or other activities that necessitate interactions with many people, we recommend working from home, if possible. For some patients, medical leave or temporary reassignment to non-public facing work in order to minimize possible exposure may be necessary • Basic precautions for patients and their caregivers include staying at home and reducing contact with other people as much as possible. • Stringent hand hygiene with soap and water or hand sanitizer should be reinforced. • Avoid non-essential travel. • Physical distancing of > 1m, routine face mask use, and eye protection independently reduce the risk of developing viral respiratory infections. (10) We recommend mask use when physical distancing is not feasible, such as attending indoor areas, public transportation, and crowded outdoor spaces for all patients to reduce the risk of developing COVID-19. |
| All patients: • Seeing only essential patients in clinic and reducing clinic volume by deferring outpatient visits for patients that are clinically well. • Implementation of telemedicine approaches based on telephone, video or web contact, as locally available, to assess patients’ clinical stability and to screen for symptoms consistent with COVID-19. The remote contact should be noted formally and be part of the patient’s medical record. • For patients who will be attending appointments in the clinic or hospital, consider pre-visit phone calls or screening questionnaires to ensure patients do not have current symptoms of COVID-19, to rule out contacts, and to remind them to alert the program before presenting to the medical facility with active symptoms so they may be appropriately triaged. |
| In particular, mortality on the waitlist compared to the early post-transplant period with COVID-19 needs to be examined to assess benefit of transplant prioritization. |
| Regardless of donor screening, the center should have a discussion of risk-benefit with the recipient regarding transplantation during the ongoing pandemic. |
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| Heart/ Lung Transplant : While actively infected with SARS-CoV-2, we recommend foregoing transplantation and making the patient inactive on the waitlist. • For patients with end stage heart or lung disease who contract COVID-19 while waitlisted and recover from illness, we recommend waiting at least 14 days after initial diagnosis AND two successive negative PCR-based tests at least 48 hours apart PRIOR to transplantation if possible as viral shedding has been demonstrated to occur following resolution of clinical symptoms; prolonged shedding up to 5 weeks in a minority of patients has been described.(31, 32) This timeframe is based on the higher acuity of heart and lung waitlisted patients and lesser opportunities for organ availability. • Lung transplant specifically for COVID-19 related lung disease should be considered with caution in carefully selected cases following two negative PCR based tests as noted above, and after a sufficient observation period for natural recovery of lung function as is often seen after other viral causes of ARDS. • Induction therapy: current experience does not suggest a change in induction protocols with ongoing use of lymphocyte depleting agents if indicated, but it should be noted that COVID-19 is frequently associated with lymphopenia. • When considering appropriate resource allocation in such settings, the expected need for prolonged postoperative care after a transplant in such patients should be weighed against the opportunity of liberating ICU capacity by performing the transplant. |
| Heart/ Lung Transplant : While actively infected with SARS-CoV-2, we recommend foregoing transplantation and making the patient inactive on the waitlist. • For patients with end stage heart or lung disease who contract COVID-19 while waitlisted and recover from illness, we recommend waiting at least 14 days after initial diagnosis AND two successive negative PCR-based tests at least 48 hours apart PRIOR to transplantation if possible as viral shedding has been demonstrated to occur following resolution of clinical symptoms; prolonged shedding up to 5 weeks in a minority of patients has been described.(31, 32) This timeframe is based on the higher acuity of heart and lung waitlisted patients and lesser opportunities for organ availability. • Lung transplant specifically for COVID-19 related lung disease should be considered with caution in carefully selected cases following two negative PCR based tests as noted above, and after a sufficient observation period for natural recovery of lung function as is often seen after other viral causes of ARDS. • Induction therapy: current experience does not suggest a change in induction protocols with ongoing use of lymphocyte depleting agents if indicated, but it should be noted that COVID-19 is frequently associated with lymphopenia. • When considering appropriate resource allocation in such settings, the expected need for prolonged postoperative care after a transplant in such patients should be weighed against the opportunity of liberating ICU capacity by performing the transplant. |
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| Additional evaluation may be required when considering kidney or lung transplantation from donors with previous COVID-19. |
| For donors who were previously known to have had COVID-19, we would recommend only accepting organs from donors who test negative on NAT-based assays. |
| CT scan of the chest should not be relied upon as part of a work up to exclude SARS-CoV-2 infection in potential deceased or living donors. |
| Donors should be screened epidemiologically, and by clinical history for suspected COVID-19 infection. |
Mask.
| Consider endemic levels on an on-going basis to determine whether should adapt program. |
| “SARS-CoV-2-positive transplant candidates may be considered for transplantation at least 14-21 days after symptom resolution and 1 or 2 negative SARS-CoV-2 diagnostic tests.” |
| Only the recipients with symptoms of an upper or lower respiratory tract infection, a nasopharyngeal swab diagnosis for COVID-19 recommended. |
| Ideally, patients should be tested 10-14 days after symptom onset and only once symptoms have resolved. Patients should have 2 negative PCR tests done at least 24 hours apart. |
| Like all persons, transplant recipients should adhere to travel advisories issued by their respective health authorities/government bodies. This may necessitate postponing travel to a country with >10 cases of COVID-19. Transplant recipients should avoid all cruise ship travel. |
| One approach that has been adopted is to have both donor and recipient practise strict social distancing. This may include a 2-week “stay home” period prior to the transplant, with a PCR test for both at the end of the period, prior to transplant. The reason for the swab at the end of the “stay home” period is the asymptomatic shedder – persons who remain asymptomatic throughout the period of viral shedding. |
| here available, testing of upper and lower airway specimens by PCR/NAT of donors with concern for COVID-19 should be considered. Some national guidelines recommend routine testing of donors for SARS-CoV-2. Combining epidemiological data and PCR testing is one approach that has been used. |
| As local community spread can now occur nearly in any country, centers should consult with local health authorities to identify specific rates in your area. |
| Persons who have been exposed to a patient with confirmed or suspected COVID-19 within 14 days should not be accepted as a donor. Likewise donors with unexplained respiratory failure leading to death should be excluded. Donors with positive PCR testing for COVID-19 should not be utilized. |
| Initially limited to Wuhan, infection with COVID-19 is now a pandemic. Hot zones of increasing infections are constantly changing. Currently, rates of COVID-19 are increasing most in South and Central America, Africa and the Indian Subcontinent. As countries re-open their economies, pockets of new cases may emerge regionally. As local community spread can now occur nearly in any country, centers should consult with local health authorities to identify specific rates in your area. |
| In a country with widespread community transmission, temporary suspension of the deceased donor program should be considered, especially when resources at the transplant center may be constrained. |
| Appropriate PPE should be available for the procurement team on site, either provided by the local organ procurement organization, the donor hospital, or carried by the procurement team according to their institutional guidelines. This should be negotiated in advance of commencing travel. |
| When possible, it is strongly recommended that organs should be procured by a local recovery team in order to reduce travel-related risk. |
| When considering appropriate resource allocation in such settings, the expected need for prolonged postoperative care after a transplant in such patients should be weighed against the opportunity of liberating ICU capacity by performing the transplant. |
| We recommend mask use when physical distancing is not feasible, such as attending indoor areas, public transportation, and crowded outdoor spaces for all patients to reduce the risk of developing COVID-19. |
| Basic precautions for patients and their caregivers include staying at home and reducing contact with other people as much as possible. |
| For patients with work or other activities that necessitate interactions with many people, we recommend working from home, if possible.
For some patients, medical leave or temporary reassignment to non-public facing work in order to minimize possible exposure may be necessary. Basic precautions for patients and their caregivers include staying at home and reducing contact with other people as much as possible. Stringent hand hygiene with soap and water or hand sanitizer should be reinforced. Avoid non-essential travel. Physical distancing of > 1m, routine face mask use, and eye protection independently reduce the risk of developing viral respiratory infections. (10) We recommend mask use when physical distancing is not feasible, such as attending indoor areas, public transportation, and crowded outdoor spaces for all patients to reduce the risk of developing COVID-19. |
| For patients who will be attending appointments in the clinic or hospital, consider pre-visit phone calls or screening questionnaires to ensure patients do not have current symptoms of COVID-19, to rule out contacts, and to remind them to alert the program before presenting to the medical facility with active symptoms so they may be appropriately triaged. |
| We recommend mask use when physical distancing is not feasible, such as attending indoor areas, public transportation, and crowded outdoor spaces for all patients to reduce the risk of developing COVID-19. |
| At this time there is no evidence to guide decisions regarding the use of COVID-19 treatment strategies specifically in patients with thoracic transplant, VADs, or pulmonary vascular disease though careful extrapolation from published data may be done with caution. |
| There are multiple ongoing clinical trials evaluating a variety of agents for treatment or prophylaxis of COVID-19. We strongly encourage investigators to facilitate inclusion of patients with chronic lung/heart disease and transplant, mechanical circulatory support and pulmonary vascular disease in clinical trials directed at COVID-19 so that data are available to guide future treatment recommendations. Table outlining therapies and possible drug interactions is also included. |
| A thoracic CT scan may show signs of COVID-19 pneumonia even before development of symptoms or positive PCR and thus should be considered for donor and candidate assessment. |
| The minimum number of personnel should be involved in the procurement team and related travel to reduce the risk of exposure and infection. |
| HCWs are at increased risk of infection with SARS-COV2 and thus specific precautions are recommended. |
| Its use can be more challenging in the acute phase: preliminary data indicate IgM seroconversion can be seen as early as 4 days after symptom onset, thus repeat serological testing may be also informative in the acute setting, especially in patients who continue to follow a COVID-19-like disease course despite negative PCR results. Currently, serology is not suggested as the primary diagnostic test for acute SARS-CoV-2 infection. It is unclear currently if presence of SARs-CoV-2 specific antibodies are indicative of a protective or anamnestic immune response. |
| Donor or candidate currently suffering from a clinical syndrome compatible with COVID-19, regardless of known exposure within the past 14 days and negative PCR test results, should be avoided (unless alternative diagnosis is made). |
| “If local testing strategy and rapid turn-around of PCR-based testing allow, we recommend testing for SARS-CoV-2 by nasopharyngeal/ oropharyngeal swab, sputum/ tracheal aspirate, or bronchoalveolar lavage less than 72 hours before organ donation”. |
| Pre and early post transplant patients to be cared for in single rooms in COVID-19 free wards, when possible. Trusts are advised to avoid placing patients with respiratory symptoms in similar clinical areas to transplant recipients. |
| Patients must be reminded not to stop their immunosuppression in the event of infection, unless recommended to do so by a transplant professional. Levels of immunosuppression should be reviewed but generalised immunosuppression reduction that may jeopardise organ function is not recommended. |
| “The utility of CT chest screening in this setting is unknown but could provide added information especially for lung transplantation” “There is limited data on sensitivity and specificity in the setting of donor screening. CT chest has good sensitivity in patients with symptoms, but has lower sensitivity in asymptomatic individuals. The sensitivity and specificity in deceased donors is not known”. |
| “All organ offers from programs, such as in the United States, where testing of donors may not have reliably occurred, should be considered on a case-by-case basis.” |
| Donor with SARS without defined etiology and laboratory test not available. |
| Recommend 28 days past evidence of symptoms and negative testing prior to consideration for use. |
| All potential donors should be screened. |
| During the community transmission period, consider suspending all transplants with elective live donors to protect both the recipient and the donor. |
| During the community transmission period, consider suspending all transplants with elective live donors to protect both the recipient and the donor. |
| Decrease flow of people in the hospital environment; suspend all non-essential scientific meetings and events. |
| Strictly follow respiratory precautions and contact, and hand hygiene. |
|
| RT-PCR- Depending on test availability. |
| Donors should be screened epidemiologically, and by clinical history for suspected COVID-19 infection. |
| This study plans to learn more about the effects of a medicine called ruxolitinib on the progression of COVID-19 (coronavirus disease of 2019), the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Ruxolitinib is FDA-approved for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. This study intends to define the impact of ruxolitinib on the severity and progression of COVID-19. This drug might to lower the hyperinflammation caused by the virus, which would prevent damage to the lungs and possibly other organs. The study will recruit patients who have been diagnosed with COVID-19. The goal is to recruit 80 patients. |
| It has been suggested that ibuprofen might be associated with more severe cases of coronavirus infections, based on the observation that severe COVID cases had been exposed to ibuprofen, resulting in a warning by the French authorities. This was attributed to: 1. a suggestion that ibuprofen might upregulate ACE-2 thereby increasing the entrance of COVID-19 into the cells, 2. an analogy with bacterial soft-tissue infections where more severe infections on NSAIDs are attributed to an immune-depressive action of NSAIDs, or to belated treatment because of initial symptom suppression, 3. fever is a natural response to viral infection, and reduces virus activity: antipyretic activity might reduce natural defenses against viruses. However fever reduction in critically ill patients had no effect on survival. However, these assertions are unclear: upregulation of ACEII would increase the risk of infection, not necessarily its severity, and would only apply to the use of NSAIDs before the infection, i.e. chronic exposure. It would be irrelevant to the infection once the patients are infected, i.e., to symptomatic treatment of COVID-19 infection. Anti-inflammatory effect masking the early symptoms of bacterial infections resulting in later antibiotic or other treatment is not applicable: there is no treatment of the virus that might be affected by masking symptoms. Antipyretic effect increasing the risk or the severity of infection would apply equally to all antipyretic agents including paracetamol, which share the same mechanism of action for fever reduction. EMA remains prudent about this assertion In addition, excess reliance on paracetamol while discouraging the use of ibuprofen might increase the risk of hepatic injury from paracetamol overdose. Paracetamol is the prime drug associated with liver injury and transplantation, in voluntary and inadvertent overdose or even at normal doses. This might be increased by COVID-related liver function alterations. It is therefore proposed to conduct a case-control study in a cohort of patients admitted to hospital in France with COVID-19 infection. |
| SARS-CoV-2 belong to beta-coronavirus family and its transmission route and symptoms follow those of all community-acquired coronaviruses. The main difference of the novel Coronavirus is the higher mortality rate, that is around 3%. Death rate is over 1% only for patients over 50 years old, whereas until 40 years old is under 0,4%. No fatalities are declared among children under 10 years old to date. Death rate is almost double for male rather than female. This distribution of mortality rate according to age of infected patients could be only partially ascribed to other comorbidities in addition to great age. In fact, patients with no pre-existing conditions have however a case fatality rate of 0,9%. The almost null rate of severe illness in children and generally in patients younger than 40 years old is quite un-explicable. Infant, children and young people could be infected but infection is rapidly self-limited or without symptoms. Older patients undergo severe lung injury as consequence of an immune response that is late in coming. Possible explanation of these phenomena could be something, which assure ability to prompt response to SARS-CoV-2 in younger people independently from the novelty of the virus itself. It would seem to be that younger people are already sensitized to the antigens of the virus without a previous contact. This immunity is not really specific, but “partially specific” for many antigens of the virus, however able to limit the infection in the organism. Something stimulated the immune system and it scattered immunity against more and more antigens present. Children are the age group mostly exposed to all community-circulating viruses. This immunity is not persistent but progressively fade out. It protects from the age of two, when the hypothetical stimulation occurs, to the fifth decade because of its slow decrease. The only external stimulation, which healthy people receive are vaccines. All vaccinations and especially tetanic, diphtheria toxoids and inactivated bacteria as pertussis could stimulate immune system. They develop the specific immunity but generate also a sprouting immunity against antigens in transit, as coronaviruses and other community-circulating viruses. The developed immunity gives some protection against multiple viral infection for years until the natural fade out. After the fifth decade, that immunity is slower to be recall and reactivated. Additionally, transplant recipients and HIV infected patients, which have an immune system inhibited, unexpectedly, do not seem to suffer the worst complications of SARS-CoV-2 infection. An immune system imbalance could be play a pivotal role during the reaction to the virus, limiting destructive consequences of excessive inflammation. According to the medical hypothesis on which the protocol is based on, young people could benefit from a functional adaptation of innate immune cells induced through epigenetic reprogramming and, especially, a pre-existing “partially specific” immunity to the community viruses caused by “bystander effect” of preceding vaccinations. In this study, we will explore the main differences existing among patients infected by SARS-CoV-2 who experience the illness at different degree of severity. We suppose to recognize different populations of patients, each one with a specific immunological pattern. It could differ in terms of cytokines, soluble factors serum level and immune cells activity both of the innate compartment and of the acquired one. The proof of a role of these immunological phenomena in the pathogenesis of Covid-19 are bases for implementation of therapeutic immunomodulatory treatments. In addition, the definition of an immunological risk profile could tailor established therapies to each kind of patient. |
| The emergence and rapid spread of the coronavirus disease 2019 (COVID-19) since December 2019 across 187 countries globally has become a major public health crisis. COVID-19 was declared a pandemic by the World Health Organisation (WHO) on the 11th March 2020. To date, more than 4,500,000 cases and 300,000 deaths have been reported. COVID-19 is an acute respiratory disease caused by the novel SARS-CoV-2 virus from the Betacoronavirus genus, just like SARS-CoV and MERS-CoV. SARS-CoV-2 is primarily transmitted person-to-person through respiratory droplets or close contact. Fomite transmission has also been implicated as a transmission route. Common respiratory symptoms such as fever, sore throat, cough and shortness of breath, may appear 2 – 14 days after exposure. About 20% of infected cases progress to severe disease resulting in an estimated 2 – 5% mortality reported. With the unrelenting increase in cases being reported worldwide, there is thus an urgent need for therapeutics to be developed and used to disrupt the ongoing pandemic. To date, there is no specific proven antiviral treatment for COVID-19. Supportive care is recommended for symptom relief and for severe cases, organ support is critical for optimal outcome. Numerous vaccine candidates against SARS-CoV-2 are under development and a couple have entered Phase 1 clinical trials. Remdesivir, a nucleotide analog, developed by Gilead Sciences as a treatment for Ebola virus disease is currently being repurposed and undergoing multiple clinical trials to evaluate safety and efficacy in COVID-19 patients. In a preliminary study, convalescent plasma containing neutralizing antibodies against SARS-CoV-2 has also been experimentally administered in critically ill COVID-19 patients with promising results. Donor plasma used was rich in virus specific IgG and IgM antibodies as determined by ELISA. Within days of convalescent plasma treatment, patients showed decrease in viral load (via qRT-PCR), as well as improved clinical status being observed. Tychan’s TY027 will be the first biologics in the world, specifically targeting SARS-CoV-2, to enter human clinical trials. It is anticipated that a SARS-COV-2 specific monoclonal antibody therapeutic administered to acutely infected patients could reduce disease severity as well as prevent transmission by reducing viral load and viral shedding. It could also be used as prophylaxis against COVID-19 amongst high risk contacts. |
| The COVID-19 pandemic, commonly referred to as “coronavirus”, first began in the city of Wuhan, China in December 2019. This virus has since spread globally, with infections reported in nearly every country. COVID-19 targets the body’s respiratory system, where infections can be found in the nose, throat and lungs. The effect of COVID-19 infection is very variable, where many people might not know that they have been infected and have recovered from COVID-19. However, COVID-19 infection can cause people to have difficulty breathing. This can be severe enough to require hospitalisation and potentially intensive care treatment. While they are being treated in hospital, COVID-19 infected patients can be found to have inflamed tissue in their lungs (referred to medically as “pneumonitis”). This inflammation is thought to be caused by their body’s immune systems overacting to the infection rather than the COVID-19 virus itself. By potentially dampening down this overreaction of their immune system, it is hoped that COVID-19 patients with inflamed lungs have better and quicker chance to survive. Mesenchymal stromal cells (MSCs) have been shown to have anti-inflammatory and healing properties on injured tissue. MSCs have been trialled in various diseases but have not yet been tested on patients with COVID-19. In this study, the investigators will obtain bone marrow from healthy volunteers to develop a cell-based treatment for COVID-19-related pneumonitis. The investigators will also determine whether it is feasible to recruit bone marrow donors in a clinically useful timeframe to treat COVID-19 patients. A future trial, COMET20, will use the bone marrow-derived MSCs (BM-MSCs) manufactured in COMET20d to treat COVID-19 patients suffering with pneumonitis, to determine whether the BMMSCs can reduce the likelihood for mechanical ventilation and reduce hospitalisation. |
| Objectives: Evaluate the efficacy and safety of Human Menstrual Blood-derived Stem Cells（Mensc） and artificial liver in the treatment of Acute lung Injury (Pneumonia) caused by novel coronavirus pneumonia (NCP), and explore the standard treatment in the treatment of novel coronavirus pneumonia (NCP), establish the effectiveness and safety evaluation system, and create new and effective methods for the novel coronavirus pneumonia (NCP) prevention and treatment, improve the treatment efficiency and patient survival rate, reduce mortality. Inclusion criteria: 1. Diagnosed as novel coronavirus pneumonia (NCP) Patient: 1) Basis of diagnostic criteria: “Notice on Printing and Distributing Pneumonia Diagnosis and Treatment Plan for New Coronavirus Infection (Trial Implementation Fourth Edition)” (National Health Office Medical Letter C2020377) 2019-nCoV diagnosis of pneumonia: (1) Epidemiological history: A. Travel history or residence history in Wuhan area or other areas with continuous local case transmission within 14 days before onset; B. Contact history within 14 days before onset Patients with fever or respiratory symptoms from Wuhan City or other areas where local case transmission is ongoing; C. Aggregative onset or epidemiological association with new coronavirus infection. (2) Clinical manifestations: A. fever; B. imaging characteristics of pneumonia: multiple small patchy shadows and interstitial changes in the early stage, which are obvious in the extrapulmonary zone, and then develop into multiple ground glass infiltrates and infiltrates, which are severe Patients may have pulmonary consolidation, and pleural effusion is rare; C. The total number of white blood cells is normal or reduced in the early stage of onset, or the lymphocyte count is reduced. (3) Any one of the epidemiological history meets any two of the clinical manifestations as suspected cases, and those who have one of the following pathogenic evidence are confirmed cases: A. A new type of real-time fluorescence RT-PCR test for respiratory specimens or blood specimen Coronavirus-positive nucleic acid; B. Sequencing of viral genes in respiratory specimens or blood specimens, highly homologous to known new coronaviruses. (4) It is severe if it meets any of the following: A. Respiratory distress, RR > 30 beats / min; B. In resting state, means oxygen saturation < 93%; C. Arterial partial pressure of oxygen (PaO2) / oxygen Concentration (FiO2) <= 300mmHg (lmmHg = 0.133kPa). (5) It is critical if it meets any of the following: 1) respiratory failure occurs and requires mechanical ventilation; 2) shock occurs; 3) combined organ failure requires ICU monitoring and treatment 2. The patient or legal donor agrees to participate in the study and signs an informed consent form. |
| Infections with Corona-Viruses have shown to be a menace for patients with comorbidities such as hypertension, diabetes, cardiovascular disease or immunosuppression. Those are features almost every nephrological patient brings along, especially those on maintenance dialysis and those with renal transplant. Since the emergence of the novel coronavirus SARS-CoV-2 in November 2019 in Mainland China the fear for pandemic infections has increased. But not only is the course of infection itself important, the prevention of transmission to and by attending medical personnel should be put into perspective. Thus there is a lack of sufficient data of occult immunization or persistent state on immunization. In our study up to 400 health care personnel will be screened serologically for IgM, IgA and IgG against the SARS-CoV-2 virus. Blood and urine samples throughout 12 months will be sampled and analyzed. The aim of the study is to identify the rate of occult immunization and at the same time to gather data about the persistence of immune response to an infection with SARS-CoV-02. The results will help provide sufficient safety measures for health care providers and renal patients undergoing unavoidable clinical treatment. |
| OBJECTIVES: Objective: To undertake a pilot, feasibility RCT of umbilical cord blood derived cell therapy for treatment of adult patients infected with SARS-CoV-2 virus related moderate-to-severe pneumonia to prevent progression to severe ARDS. HYPOTHESIS: Expanded cord blood derived cell therapy will be feasible, well tolerated and show potential efficacy in the treatment of acute COVID-19 related moderate to severe pneumonia in adult patients because of their powerful anti-inflammatory and immunomodulatory properties. TRIAL DESIGN: Pilot, parallel design randomised controlled trial. PARTICIPANTS: The trial will recruit 24 hospitalised patients with confirmed SARS-CoV-2 infection and pneumonia from July to December 2020 at Monash Medical Centre in Melbourne, Australia. INTERVENTION AND COMPARATOR: Intervention: Intravenous injection of expanded umbilical cord blood cells at a dose of 5 million cells/kg (maximum dose – 500 million cells). Cell infusion will occur over 30-60 minutes through a peripheral intravenous cannula. Standard supportive care will continue as needed. Comparator: Standard supportive care. MAIN OUTCOMES: Safety and tolerability of cell administration within first 24 hours of administration; clinical improvement on a seven-category clinical improvement ordinal scale. RANDOMISATION: Randomisation will be done using computer generated allocation to intervention/ control groups in a 1:1 ratio (in blocks of 6) using sealed opaque envelopes. BLINDING (MASKING): This will be an unblinded study, given that it is the first study using expanded cord blood cells in COVID-19 patients. There will be no placebo infusion. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Twelve participants in each group. Total n=24. TRIAL STATUS: CBC-19 protocol v2, dated 23rd April 2020. Recruitment has not started yet. Estimated recruitment timeline is between 1st July – 31st December 2020. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12620000478910, registered 16th April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. |
| Acute Respiratory Distress Syndrome (ARDS) is the main cause of death from COVID-19. One of the main mechanisms for ARDS is the violent storm of cytokines and chemokines, which cause uncontrolled fatal systemic inflammation by the immune system on the body, with additional multiple organ failure. Mortality in cases of severe ARDS caused by COVID 19 varies significantly between 50 and 90%, basically depending on the age of the patient and the presence of comorbidities. The plasticity of Mesenchymal Stem Cells (MSC) regulates inflammation and immunity. MSC can promote and inhibit an immune response, depending on the dynamics of inflammation and depending on the activation force of the immune system, the types of inflammatory cytokines present, and the effects of immunosuppressants. Essentially, the state of inflammation determines the immunoregulatory fate of MSC. Thus, IV application of AMSCa has been shown to control the inflammatory response in various diseases, such as the graft-versus-host reaction and the ARDS caused by H5NI. The objective of this study is to describe the clinical changes secondary to IV administration of MSC allogenic, in patients with bilateral COVID-19 pneumonia complicated by severe ARDS, with the evaluation of the PaO2 / FiO2 ratio, heart and respiratory rates, and the fever curve. Five patients, of either sex, over 18 years of age, with bilateral pneumonia caused by COVID-19 and severe SIRA that has not improved with the standard management measures used at that time in the care center, will be included in the study. This treatment will be administered after discussing it with the relatives that it is a procedure considered as rescue and will be carried out with informed consent. 1×10(6) xKg will be applied IV. The follow-up of the patient will be for three weeks. PaO2 / FiO2 data, fever, inflammatory markers and immunity will be evaluated. The results will be compared with the historical controls attended at INCMNSZ. |
| Background After the emergence of Covid-19 in China, Hubei Province, the epidemic quickly spread to Europe. France was quickly hit and the Croix-Rousse hospital at the Hospices Civils de Lyon was one of the first French university hospital to receive patients infected with Sars-COV2. The predicted massive influx of patients motivated the cancellation of all elective surgical procedures planned to free hospitalization beds and to free intensive care beds. Nevertheless, patients who had to be canceled had to be properly selected to avoid a life threatening. The retained surgical indications were surgical emergencies, oncologic surgery and organ transplantation. The objective was to describe the organization of the Croix-Rousse hospital to allow the continuation of these surgical activities while limiting the exposure of patients to the Sars Cov2. |
| This study aims to use the regenerative and repair abilities of stem cells to fight against the harmful effects of the novel coronavirus Covid-19 and therefore develop a treatment strategy. It is known that fatalities from this virus is largely caused by its damage to lungs and other organs. As the disease progresses, these organs fail and lead to mortality. Our hope is that the stem cell transplantation from healthy donors will repair the damage caused by the virus and result in a healthy recovery. |
| In December 2019, an unknown pneumonia rapidly spread in Wuhan, China, a new coronavirus, 2019 novel coronavirus (2019-nCoV), aroused the attention of the entire world. On January 31, 2020, World Health Organization (WHO) announced the outbreak of Coronavirus Disease 2019 (COVID-19) in China as a Public Health Emergency of International Concern. The number of volunteer non-remunerated blood donors decreased because of quarantine, caring for relatives, and fear of exposure to COVID-19. Due to the blood shortage, patient blood management and cessation of elective surgery are contributing to decreased demand, but sepsis may increase requirements and significant reductions will not be possible in areas such as trauma, cancer patients, hereditary haemolytic anaemias and childbirth. Therefore, recruiting enough blood donors during the epidemic is vital for public health in China, and also worldwide. In order to assess the effects of a questionnaire on blood donor recruitment, the investigators designed two kinds of self-administered, standardized and structured questionnaires. In addition of the basic socio-demographic characteristics, one questionnaire includes the information of precautions of blood donation during epidemic, and the other dose not. The questionnaires were randomly sent to ever blood donors, and the same number of ever blood donors are coded as control. |
| The new SARS-CoV-2 coronavirus is an emerging virus originating in Wuhan, China that has spread rapidly throughout the world. As of March 24, 2020, China had reported 81,767 cases with 3,281 deaths, and the World Health Organization (WHO) declared coronavirus 19 (COVID-19) a pandemic. COVID-19 disease is currently a pandemic without specific therapeutic agents and substantial mortality. So it is of utmost importance to find new treatments. Various therapies, such as Remdesivir and Favipiravir, are being investigated but the antiviral efficacy of these drugs is not yet known. The use of convalescent plasma was used as an empirical treatment during the Ebola virus outbreaks in 2014 and in 2015 a protocol was established for the treatment of the Middle East respiratory syndrome coronavirus (MERS) with convalescent plasma. This approach with other viral infections such as SARS-CoV, H5N1 avian influenza and H1N1 influenza suggesting that plasma transfusion from convalescent donors was effective. For this study, plasma from convalescent donors will be collected from those donors who have recovered from SARS-CoV-2 and are between 10 and 14 days after illness. Immunoassays will be carried out to detect total IgM and IgG antibodies against SARS-CoV-2. Patients will receive 1 to 3 convalescent plasma transfusions, depending on the response to treatment. The expected results are: normal body temperature, decrease in viral load or negative between 10-12 days after transfusion of convalescent plasma, which does not progress to ARDS, extubation of mechanical ventilation within two weeks of treatment, recovery of patient. |
| OBJECTIVES: The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below. TRIAL DESIGN: REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial. PARTICIPANTS: The study will be conducted in Intensive Care Units in hospitals across the United Kingdom. Patients with moderate to severe ARDS as defined by the Berlin definition, receiving invasive mechanical ventilation and with a diagnosis of COVID-19 based on clinical diagnosis or PCR test will be eligible. Patients will be excluded for the following reasons: more than 72 hours from the onset of ARDS; age < 16 years; patient known to be pregnant; major trauma in previous 5 days; presence of any active malignancy (other than non-melanoma skin cancer); WHO Class III or IV pulmonary hypertension; venous thromboembolism currently receiving anti-coagulation or within the past 3 months; patient receiving extracorporeal life support; severe chronic liver disease (Child-Pugh > 12); Do Not Attempt Resuscitation order in place; treatment withdrawal imminent within 24 hours; prisoners; declined consent; non-English speaking patients or those who do not adequately understand verbal or written information unless an interpreter is available; previously enrolled in the REALIST trial. INTERVENTION AND COMPARATOR: Intervention: Allogeneic donor CD362 enriched human umbilical cord derived mesenchymal stromal cells (REALIST ORBCEL-C) supplied as sterile, single-use cryopreserved cell suspension of a fixed dose of 400 x10(6) cells in 40ml volume, to be diluted in Plasma-Lyte 148 to a total volume of 200mls for administration. Comparator (placebo): Plasma-Lyte 148 Solution for Infusion (200mls). The cellular product (REALIST ORBCEL-C) was developed and patented by Orbsen Therapeutics. MAIN OUTCOMES: The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is Oxygenation Index (OI) at day 7. Secondary outcomes include: OI at days 4 and 14; respiratory compliance, driving pressure and PaO(2)/FiO(2) ratio (PF ratio) at days 4, 7 and 14; Sequential Organ Failure Assessment (SOFA) score at days 4, 7 and 14; extubation and reintubation; ventilation free days at day 28; duration of mechanical ventilation; length of ICU and hospital stay; 28-day and 90-day mortality. RANDOMISATION: After obtaining informed consent, patients will be randomised via a centralised automated 24-hour telephone or web-based randomisation system (CHaRT, Centre for Healthcare Randomised Trials, University of Aberdeen). Randomisation will be stratified by recruitment centre and by vasopressor use and patients will be allocated to REALIST ORBCEL-C or placebo control in a 1:1 ratio. BLINDING (MASKING): The investigator, treating physician, other members of the site research team and participants will be blinded. The cell therapy facility and clinical trials pharmacist will be unblinded to facilitate intervention and placebo preparation. The unblinded individuals will keep the treatment information confidential. The infusion bag will be masked at the time of preparation and will be administered via a masked infusion set. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A sample size of 60 patients with 30 patients randomised to the intervention and 30 to the control group. If possible, recruitment will continue beyond 60 patients to provide more accurate and definitive trial results. The total number of patients recruited will depend on the pandemic and be guided by the data monitoring and ethics committee (DMEC). TRIAL STATUS: REALIST Phase 1 completed in January 2020 prior to the COVID-19 pandemic. This was an open label dose escalation study of REALIST ORBCEL-C in patients with ARDS. The COVID-19 pandemic emerged as REALIST Phase 2 was planned to commence and the investigator team decided to repurpose the Phase 2 trial as OVID-19 specific trial. This decision was discussed and approved by the Trial Steering Committee (TSC) and DMEC. Submissions were made to the Research Ethics Committee (REC) and MHRA to amend the protocol to a COVID-19 specific patient population and the protocol amendment was accepted by the REC on 27(th) March 2020 and MHRA on 30(th) March 2020 respectively. Other protocol changes in this amendment included an increase in the time of onset of ARDS from 48 to 72 hours, inclusion of clinical outcomes as secondary outcomes, the provision of an option for telephone consent, an indicative sample size and provision to continue recruitment beyond this indicative sample size. The current protocol in use is version 4.0 23.03.2020 (Additional file 1). Urgent Public Health status was awarded by the NIHR on 2 April 2020 and the trial opened to recruitment and recruited the first participant the same day. At the time of publication the trial was open to recruitment at 5 sites across the UK (Belfast Health and Social Care Trust, King’s College London, Guys and St Thomas’ Hospital London, Birmingham Heartlands Hospital and the Queen Elizabeth Hospital Birmingham) and 12 patients have been recruited across these sites. Additional sites are planned to open and appropriate approvals for these are being obtained. It is estimated recruitment will continue for 6 months. TRIAL REGISTRATION: ClinicalTrials.gov NCT03042143 (Registered 3 Feb 2017). EudraCT 2017-000585-33 (Registered 28 Nov 2017). FULL PROTOCOL: The full protocol (version 4.0 23.03.2020) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). |
| OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection. TRIAL DESIGN: This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor. PARTICIPANTS: Eligible participants include adults (= 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) = 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation [ECMO]) for = 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion. *Use of remdesivir as treatment for COVID-19 is permitted. The study will be undertaken at Columbia University Irving Medical Center in New York, USA. INTERVENTION AND COMPARATOR: The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T. cruzi, ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 – 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 – 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis. MAIN OUTCOMES: The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first. 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation 6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both 7. Death This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma. The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period. RANDOMIZATION: Study participants will be randomized in :1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability. BLINDING (MASKING): The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5. TRIAL STATUS: Protocol AAAS9924, Version 17APR2020, 4/17/2020 Start of recruitment: April 20, 2020 Recruitment is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04359810 Date of trial registration: April 24, 2020 Retrospectively registered FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. |
| Scientists and medical workers all around the world were running out of time to manage COVID-19. Several studies have been done to understand the disease and ultimately to find possible treatment. Based on those studies, one of the potential treatment was antibody transfer from recovered COVID-19 patients. Passive antibody transfer was a fast and easy choice. The rational use of antibody from the patient’s plasma is a natural neutralizing protein to the cell-infected virus and could possibly slow the active infection down. Investigators initiate an intervention study with purposes to produce quality convalescent plasma from the recovered patients, define the safety of plasma for human use and as an alternative treatment to improve the clinical outcomes of severe COVID-19 patients. The study hypothesis is convalescent plasma is safe and could possibly improve outcome of severe (non-critical) COVID-19 patients. This research will conduct the plaque reduction neutralizing test (PRNT) of recipient blood in vitro. The plasma will be collected in the blood transfusion unit (BTU) in Gatot Soebroto hospital. The storage, testing, transfer, and transfusion of eligible convalescent plasma are the authority of Gatot Soebroto BTU. PRNT and plasma antibody titer measurement from donor plasma will be conducted at Eijkman Institute of Molecular Biology. Investigators enroll approximately 10 patients consecutively, who will be admitted at Gatot Soebroto hospital. Baseline demographic characteristics of samples are recorded. Clinical dan laboratory data will be measured before and after plasma transfusion periodically. The measured variables are pharmacological therapy (antivirus, antibiotics, steroids), invasive oxygen therapy, oxygen index, sequential organ failure assessment (SOFA) score, and laboratory parameters such as leukocyte count, blood chemical panel include liver and renal function, C-reactive protein, procalcitonin, IL-6 and immunoglobulin titer of the recipient and also chest X-ray evaluation. The potential expected risk of plasma transfusions is transfusion reaction (immunological or non-immune related) and transferred foreign pathogen. Investigator will report and treat all adverse events after plasma transfusion has been done. A severe adverse event (SAE) will also report in a special form to sponsor and data safety monitoring board (DSMB). There is theoretically antibody-dependent enhancement (ADE) mechanism from COVID-19 whom will receive plasma transfusion to progress to severe immune response. This preliminary study is supposed to provide supporting data and experience of plasma processing to a larger study in the near future. |
| Study aim Evaluation of convalescent plasma therapy in the treatment of patients with COVID-19 disease Design In this intervention study, 60 patients who have the criteria to enter the study are divided into two groups of 30 people by block randomization method. Patients are explained about treatment methods and their benefits and complications, and informed consent is obtained. Settings and conduct 1. Convalescent plasma will be received from those recovering from COVID-19 disease previously hospitalized at Emam Khomeini, Emam Reza and Sabalan Hospitals 2- Convalescent Plasma received from volunteers will be infused to the patients with confirmed infection of COVID-19. Inclusion criteria 1. Blood oxygenation saturation <90% 2. Abnormal lung CT scan 3. Significant shortness of breath 4. Fever 5. Not improving in the next 48 hours 6. There is no possibility of discharge of patient in the next 48 hours 7. Intervention group: The recipient plasma group will receive 500 ml in 4 hours. Control group: The control group receives only routine treatment. Main outcome variables Reduction in all causes mortality; reduction of hospital stay |
| COVID-19 is a global major public health emergency that disproportionately affects patients with risk factors such as advanced age, heart and lung disease, diabetes, hypertension, as well as compromised immunity. Despite the recent worldwide emergence of this disease and its rapid progression to a pandemic, very little is known about the risks facing solid organ recipients. The study aims to elucidate the prevalence of symptomatic, subclinical, and asymptomatic infection in the transplanted population by assessing their immunological response to SARS-CoV-2 infection. This will be studied seroepidemiologically in the whole cohort and retrospectively in transplanted patients admitted to hospital for COVID-19. Primary objective: to elucidate the cumulative prevalence of SARS-CoV-2 infection in the transplanted population related to symptoms and hospitalizations; to assess the magnitude of immunological response and seroconversion kinetics for COVID-19. Secondary objectives: To examine the influence of medical parameters on COVID-19 infection and immune response such as: age, comorbidities current and recent pharmacological treatment, organ transplanted, and blood type, HLA genotype. Study design: Part 1: Longitudinal cohort study for seroepidemiology and disease burden. Part 2: Retrospective case-series for seroconversion kinetics and clinical course assessment. Study population: All solid organ transplanted patients in the Transplant Institute, Sahlgrenska University hospital, catchment area. |
| Patients with comorbid condition are known to be at high risk of severe forms of Covid-19. It is highly probable that immunocompromised patients like solid organ transplant (SOT) recipients are also at risk of severe forms of Covid-19. For this purpose, The investigators conducted a nationwide multicentric and multiorgan Registry to collect data about all French SOT recipients who develop a SARS-CoV-2 infection. The aim is to describe the clinical, biological and virological characteristics of these patients and to give information about evolution and prognosis of these particular population |
| To provide optimal care to patients and to maintain long-term institutional viability, Transplant Centres (TC) must have an awareness of their patients’ health status, their health care needs and priorities, as well as their access to information and health care. For example, it is critical that TCs understand whether their patients are medically suitable for transplant, whether transplantation remains a priority for their patients, how best to communicate with their patients, and whether their patients have sufficient access to medications and health care to undergo transplant safely. The COVID-19 pandemic has had a tremendous impact on people and institutions around the country in a short period of time. At this time, little is known regarding its impact on the transplant community specifically. For example, it has been reported that around 8 million French applied for partial unemployment benefit over the past month, but it is not known if this has affected transplant patients. It has been reported that people with significant chronic medical conditions and those with compromised immune systems may be at increased risk of dying from the COVID-19, but it is not known if this has affected patients’ interest in receiving transplants at this time. The “Societe Francophone de Transplantation (SFT)” published recommendations at the beginning of the pandemic in order to limit the rate of infection in these high-risk population. The purpose of this study is to better understand the impact of COVID-19 on patients on the waiting list and transplant patients. Further, a better understand on how patients have received information about this pandemic and how best to communicate with them. |
| Collect informations on the health status of transplanted patients (kidney, kidney / pancreas, pancreas or pancreatic islet) during the COVID-19 pandemic. All informations will be collected by short questionnaire via phone. |
| End-stage organ failure is estimated to affect more than 4 to 6 million persons worldwide. In 2018, transplant systems across the globe enabled around 150,000 patients to benefit from a kidney, heart, lung, liver, or other solid organ, a number that was far less than the demand. According to data from the World Health Organization, more than 1,500,000 persons live with a transplanted organ worldwide. In the US, approximately 40,000 patients receive an organ transplant every year, but 120,000 still remain waitlisted for transplantation today, with 7,600 dying annually while waiting for an organ transplant. A similar lack of organs and high death rates on the waiting list affect patients in Europe and many other countries. As nations adjust to new realities driven by the coronavirus (COVID-19) outbreak, many health care providers, institutions and patients are concerned about the potential impact that COVID-19 will have on organ donation and transplantation. One concern is that transplant recipients may have a greater susceptibility to infection and greater viral burden. A second concern is that hospitals will lack the resources in terms of staff and equipment to care for recipients after transplantation, who often require intensive care and multispecialty management. Because of the overwhelming healthcare system burden, a dramatic negative effect on worldwide organ donation and transplantation is anticipated, but has not been measured. Our objective was to quantify the worldwide impact of COVID-19 pandemic on organ donation and transplantation and consequences for waitlisted patients. |
| This study aims primarily 1. to assess the frequency, nature and outcome of liver disease caused or associated with COVD-19 Furthermore, the study also aims 2. to assess the impact of COVID-19 on patients with chronic liver disease or after liver transplantation (frequency of infections, course of disease, outcome) 3. to assess, whether quarantine measures impact on the rate of decompensation of liver cirrhosis 4. to assess whether the intake of antiviral drugs protects against SARS-CoV-2 infection or COVID disease. |
| This is a prospective study analyzing the development of humoral immune response against SARS-Cov-2 in patients with previous Covid19: the aim is to compare the incidence, titration and evolution of IgG an IgM in a prospective cohort of liver transplant patients surviving to the first wave of Covid19, in comparison to not inmmunossupressed patients. |
| CORIA is an observational cohort study of immunosuppressed populations who test positive for COVID-19. This includes people living with HIV, cancer, acquired immunodeficiency associated with other immunosuppressive therapy, primary immunodeficiency and recipients of a solid organ transplant. Participants will have routine clinical data collected with optional baseline collection and storage of a blood sample for storage . The study will be conducted in up to 30 sites within Australia. |
| Prospective observational study aimed at analyzing the incidence, clinical characteristics and outcomes of COVID-19 in LT in Spain. |
| The overall purpose of this project is to better understand the incidence, risk factors, etiology, clinical manifestations and outcome of tCOVID19 in solid organ transplant recipients. The results obtained will allow us to gain insight on the need of antiviral treatment, on the strategy for complications surveillance, on how to adjust the immunosuppressant therapy and on the level of care in which each patient should be treated. In order to attain the objectives previously described we will develop a multicenter prospective study of consecutive cases of COVID-19 among solid organ transplant recipients. |
| Background COVID-19 has brought into questioning the equitable distribution of resources. Solid Organ Transplants (SOT) are life-saving procedures. Rapid changes in the management of patients are occurring, with potential for inequity. Drawing on professionals across transplant specialities, we investigated resource distribution specifically for SOT to guide healthcare policies. A multidisciplinary team developed a survey. The survey included demographic questions to contextualise respondents, questions on resource allocation for SOT. Multiple strategies were used to distribute the survey internationally. Descriptive, uni-multivariate ordinal regressions analysis were performed. Open comments were analysed using qualitative methods. |
| SARS-CoV-2 induces over-production of inflammatory cytokines, and especially interleukin-6 (IL-6). The apparently strong association between blood levels of inflammaory cytokines and SARS-CoV-2 disease severity has led clinicians to evaluate the administration of steroids or anti-IL-6 antagonists in severely ill patients. As of this day, biomarkers capable of predicting clinical disease progression in Covid-19 patients with mild-to-moderate symptoms have not yet been formally identified. Identifying such markers and evaluating their predictive value may be exploited to guide patient care management, and as such forms the core objective of this proposal. Because of strong inter-individual variations in the ability of innate immune cells to produce cytokines, the hypothesis formulate and intend to test is that innate IL-6 responsiveness varies between recently infected Covid-19 patients and could predict disease outcome. To test this hypothesis, the investigator propose to follow recently infected kidney transplant patients with moderate Covid-19 symptoms. These patients stand a higher risk to progress to severe disease. The staff plan to collect a blood sample in these patients using a system whereby ex vivo cytokine production is initiated in the very same blood collection tube without prior separation and centrifugation, thus reducing labour and operator bias. After incubation with or without known innate immune stimuli, the cell-free phase from each collection-culture tube will be assayed for IL-6 content. Associations between IL-6 content and disease outcome (encephalopathy, transfer to acute care or death) will be determined in 115 Covid-19 kidney transplant patients with moderate symptoms followed in 9 centers. |
| The utilization of AlloSure to help guide immunosuppression management in solid organ transplant recipients diagnosed with COVID-19 |
| Background and study aims COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe. In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus. Groups who are at a higher risk from infection with the virus, and therefore of developing COVID -19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant . People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus. Currently, there are no drugs proven to treat or delay the progression of COVID-19 and no vaccine is yet available. Efforts are underway to repurpose established drugs with well-understood drug interactions and safety profiles. A number of clinical trials have been established at great speed following the onset of the pandemic, but none of these is enrolling participants with significantly reduced kidney function and/or receiving certain kinds of immunosuppressive medicines such as solid organ transplant recipients. Patients receiving in-centre dialysis are at extremely high risk from COVID-19, particularly as they are unable to self-isolate. The PROTECT trial aims to enrol patients at particularly high risk of COVID-19 and its complications (such as kidney dialysis patients, vasculitis, and transplant patients), seeking to test treatments that either might prevent the disease from occurring or may reduce the number of cases where the disease becomes serious or life-threatening. Inclusion criteria: 1.1. Dialysis patients receiving in-centre haemodialysis, or1.2. Diagnosis of vasculitis (according to Chapel Hill Consensus Conference 2012 definitions) and have received immunosuppression (including prednisolone = 5mg daily and/or an immunosuppressive agent (cyclophosphamide (oral or IV), rituximab, azathioprine, MMF, methotrexate, tociluzumab, alemtuzumab, abatacept, leflunomide) in the last 3 years, or1.3. Transplant patients that have a functional kidney transplant (updated 15/05/2020, previously: Transplant patients)2. Aged at least 18 years3. No previous confirmed COVID-19 diagnosis4. No symptoms highly suggestive of COVID-19 infection at screening or since 1st March 2020 Primary outcome: Time to confirmed COVID-19 diagnosis via online questionnaires at 6 weekly intervals Intervention: Patients will be randomised to receive either 1: 1 oral Hydroxychloroquine (HCQ) or standard care (no HCQ). Randomisation will be carried out using a validated bespoke automated randomisation system. Randomisation will be stratified by PROTECT sub-group, age and centre.Haemodialysis subgroupDosing: 600mg per week given as 200mg three times per week after each haemodialysis session for 6 monthsVasculitis and transplant subgroupsDosing: 800mg for first 2 days followed by 400mg once a week for 6 monthsDuration of follow up (all subgroups): Until the end of the trial, on average 6 months. |
| This will be a randomized trial of maintenance versus reduction in immunosuppression in adult patients (age >18 years old) with functioning renal transplants admitted to hospital with confirmed COVID-19 disease. |
| Wearing mask is mandatory if you go to public place or take public transport (such as bus and metro). |
| COVID-19 test is mandatory for every patients. You can use alternative test method if needed. |
| Self-isolation for 14 days is mandatory. |
| Donors with international travel or contact with confirmed case of COVID-19 should wait until 14 days and must take COVID-19 test. If negative, you can consider transplantation. |
| It is mandatory for all donors. |
| It is mandatory for all donors. |
| COVID-19 test is mandatory for all donors and recipients. |
| Donors with international travel or contact with confirmed case of COVID-19 should wait until 14 days and must take COVID-19 test. If negative, you can consider transplantation. |
| To avoid covid-19 asymptomatic patients, COVID-19 test is mandatory. |
| Donors with international travel or contact with confirmed case of COVID-19 should wait until 14 days and must take COVID-19 test. If negative, you can consider transplantation. In addition, COVID-19 test is mandatory for all donors and recipients. |
| Donors with international travel or contact with confirmed case of COVID-19 should wait until 14 days and must take COVID-19 test. If negative, you can consider transplantation. In addition, COVID-19 test is mandatory for all donors and recipients. |
| Droplet & contact precaution. |
| Including suspected cases and their family. |
| PPE usage by ODT professionals is mandatory in government’s guideline. |
| PPE usage by ODT professionals is mandatory in government’s guideline. |
| Donors with international travel or contact with confirmed case of COVID-19 should wait until 14 days and must take COVID-19 test. If negative, you can consider transplantation. |
| Donors with international travel or contact with confirmed case of COVID-19 should wait until 14 days and must take COVID-19 test. If negative, you can consider transplantation. |
Mandatory for all potential donors.
All patients in regions where SARS-CoV-2 is circulating should be tested for virus prior to transplantation, even if asymptomatic.
Candidates should be educated about preventive strategies such as social distancing, masking when in proximity to non-household contacts and frequent hand washing.
Temporary suspension of elective living donor transplantation may need to be considered.
They recommend use of face masks, eye protection and and N95 masks (for professionals who enter the room of a patient with known or suspected COVID-19 or as specified by institutional policies) and while they remain available.
Must be thoroughly screened; more manageable with living donor.
As with the live donor, a negative COVID-19 PCR, self-isolation for 7-14 days followed by a pre-procedure negative PCR, CXR, and normal exam will provide support that the transplant procedure is performed on an uninfected individual.
We would propose that a medically suitable, COVID-19 PCR- donor with no history of cough or exposures go into self-isolation for a minimum of 7 days, but preferably 7-14 days. Two days prior to proposed donation, another COVID-PCR should be negative, and on the day of surgery a rapid COVID-19 PCR, temperature check, and CXR should be normal.
Acknowledges that significant false negative rate, so must use all information at disposal when making a decision.
Regardless of test outcome, serisously consider not accepting from donor with “recent history of suspicious febrile or respiratory illness and/or chest CT with ground glass infiltrates”.
Other countries not mentioned. However, strongly encouraged local retrieval and shipment to recipient team. Highly recommend against travel.
Must consider recent symptoms and environment.
PCR test on BAL is preference, though must consider risk of aerosols.
Second best to BAL.
SARS-CoV-2-positive transplant candidates may be considered for transplantation at least 14-21 days after symptom resolution and 1 or 2 negative SARS-CoV-2 diagnostic tests.
Document does not delineate b/w deceased and living donors, but certainly recommends screening all potential donors for COVID symptoms, as the test can provide false negatives.
Recommend limiting face-to-face interactions as much as possible, including on patient rounds post-transplant; only include trainees and fellows when adequate PPE available.
The American Gastroenterological Association recommend healthcare workers involved with endoscopy wear a full set of PPE, including N95 masks and double gloves.
| Ideally, organs will be retrieved night to minimize impact on daily theatre activity. Transport times will likely be compromised due to lack of scheduled flights, organ ischaemic times must be considered accordingly. |
| Patients on the active transplant list may be advised to undergo enhanced social distancing (shielding) as per national guidelines. |
Duration of enhanced social distancing pre- and post-donation must be in line with national guidance.
Both recipient and live donor are tested at time of assessment and prior to surgery via swab (must test negative 48-72 hours before planned procedure).
Increased number of vehicles for transport to increase distance between staff. Masks to be worn when social distancing impossible. Anticipate absenteeism for various reasons. Encourage telemedicine, home delivery of immunosuppression, and rescheduling of non-urgent appointments.
Only if not recovered; if recovered, carefully assessed after 28 days or be subject to clinical assessment and multidisciplinary discussion.
Some units have used chest CT to screen potential transplant recipients, but have been largely replaced by nose and throat swabs due to false negative and false positive results concerns.
Unfortunately, no more than one visitor at a time may come to the hospital per patient.
Patients will be tested for COVID-19 just before the transplant. They must take medicines immediately after a transplant to prevent their body from rejecting the new organ. The immune system is therefore much less, and they can become seriously ill from the coronavirus.
The operation team only goes to a hospital where patients with corona are in isolation.
Liver donation programs have been maintained since the beginning of COVID-19.
Use of organs from COVID-19+ donors to be considered on case by case basis and depends on organ.
All potential donors tested by PCR. Paediatric transplantation continue without restriction.
A country with widespread community transmission, temporary suspension of the deceased donor program should be considered, especially when resources at the transplant centre may be constrained.
Consider reduced frequencies of clinic visits and laboratory testing.
Have a plan for physician and staff absences or furloughs due exposure to patients with or team member illness with COVID-19.
Should not be performed on either a donor or recipient who has returned from countries with >10 infected patients or who have been exposed to a patient with confirmed or suspected COVID-19 within 14 days.
Serology assays (IgG and IgM) are becoming available. They have higher sensitivity later in
the course of disease. Their potential utility in donor screening has not been evaluated.
All potential donors must be tested for COVID-19.
We decided this because the recipient of a kidney receives a higher dose of immunosuppressive medicines around the operation. These patients may be extra vulnerable to (and side) infections. The safety of our patients is a priority. That is why we do not want to take extra risk, as long as the exact impact is still unclear at this time.
Recommend avoiding grouping of patients for education or clinical activities.
Ensure that all wait-listed or transplanted patients can adhere to social distance protocols in clinics or hospital.
Recommend temperature screening of all patients seen in clinic.
Recently transplanted patients should follow respiratory principle and wear a mask when available.
Recommend developing guidance for candidates and recipients about risk mitigation, including but not limiting exposure to large crowds, hand hygiene and avoidance of sick exposures.
Consider postponement of routine visits and surveillance.
Postpone all non-essential surveillance of wait-listed patients.
Recommend only seeing critical patients and defer routine surveillance visits.
Develop messaging for candidates and recipients abut how and when to contact the transplant centre in case of illness.
Encourage working from home (and supporting medical justification if needed), eliminate non-essential travel, hand hygiene, general social distancing.
Consider postponement of routine visits and surveillance.
Limit all non-essential contact and recommend increased use of distance consultation.
Detailed recommendations on how to favour remote evaluation (telephone or videoconferencing).
Follow-up with various means like mobile and email.
Potential and actual transplant recipients are by definition an at-risk population.
Acknowledge that exact risk is unknown but very likely increased compared to general population.
At risk of developing severe COVID-19; counsel recipient and family as high-risk.
Consider airborne precautions for recipient if donor had negative testing but epidemiological risk factors.
Should be housed in single rooms with an attached bathroom and all staff attending to them should be in full PPE until infection with COVID-19 is ruled out.
Suspended need for post-transplant follow-up reporting back dated to March 13 declaration of emergency. Also have created new data fields for COVID-19 related refusals of organs.
Recommend confirmation of blood product supply, ventilators and PPE prior to acceptance.
In geographically confined outbreaks, transplant authorities may consider putting transplant candidates on the waiting list at alternative centres for transplantation.
Centre should not be earmarked for the treatment of COVID-19 patients and needs to have protocols for patient movement around the hospital to prevent nosocomial acquisition of COVID.
Apply restrictions in travel for procurement and shipment of organs according to the policies decided by public authorities in the different ET member countries during the epidemic.
Whenever possible, recover organs locally and ship them. For those centres that cannot recover organs locally, the decision to send a surgical team can be assessed on case-by-case basis, relative to recipient urgency.
Screen and test.
Procurement activity has to be planned depending on the locally available resources and ideally by identifying at least one recipient for the organs to be procured ahead of the procedure. Programs should avoid procurement procedures for which subsequently no recipient is found.
All programs assess program specific risk/benefit analyses in devising their own unique additions for the benefit of their staff and patients.
With all this, the benefit of transplantation as compared to the risk of severe COVID infection is therefore difficult to assess and likely to evolve to the detriment of transplantation in the course of a worsening epidemic.
Must consider all resources for entirety of transplant pathway.
The transplant team must evaluate each organ offer for the specific potential recipient in light of resource availability and total course, prior to deciding whether to proceed with transplant. Specific mention of likely shortage of blood and blood products.
Consideration for all donors that have – COVID-19 screening test. ICU capacity to maintain donor or treat recipient is at discretion of ICU consultant (most responsible physician).
State that all transplantation should be done on a case by case balancing ICU resources, risk to patient and risk of immunosuppression.
Recommendations must balance the incidence trends in provinces and territories, the risk posed to potential recipients who will become immunocompromised, and the risks of suspending or delaying transplantation.
If donor had inconclusive or unavailable testing results, informed consent with potential recipient on unknown risk of transmission and lack of currently approved therapies.
Recommend informing all parties of risks during “uncertain times”.
| Separate consent recommendations: https://bts.org.uk/information-resources/covid-19-information/ |
If living donation from a COVID-19 + donor deemed medically necessary, explicit informed consent required for both donor and recipient. Deceased donation: If a graft from a donor with unknown COVID-19 status used, must have explicit informed consent from recipient.
For emergency lifesaving transplantation: appropriate counselling of both the donor and recipient as well as their families should be done, and a high-risk informed consent taken before proceeding with the transplant.
If transplantation is required as a life-saving procedure, it can be conducted with appropriate assessment of infection in door and recipient and with appropriate informed consent.
Recipients of solid organ transplants should be fully informed at time of organ offer of the potential risk of severe complications should they contract the virus at the time of transplant, during the hospital stay, or once discharged from the hospital while being immunosuppressed. This informed consent should be clearly documented in the hospital chart.
| We recommend strict application of protective measures in transplant patients. |
To the extent feasible off-site, remote working and social distancing is prudent.
Recommend limiting face-to-face interactions as much as possible, including on patient rounds post-transplant.
Encourage videoconferencing even within the same building and alterations in catering practices.
Staff involved in care of transplant patients may not be involved in case of other patients.
Determine who can work remotely and ensure they have the resources to do so.
If surgical recovery teams travel, the teams should be as small as possible. Every effort should also be made to minimize the team’s potential exposure to COVID-19. For example, upon arrival in locality, teams should go directly to the OR, they should avoid the emergency department whenever possible, and they should return directly to the plane as soon as they are able.
Respiratory caution for all of us and respiratory barrier protection for healthcare workers should be incorporated into ALL transplant program protocols.
Recommend continuing with hospital procedures for OR PPE use for COVID-19 negative patients (all donors screened).
N95 masks should be required for all ICU and OR staff, when deemed appropriate by
hospital safety protocols (e.g., procedures that may lead to aerosolization of the virus such
as intubation, bronchoscopy, surgical cautery, bone saw).
Surgical mask.
We suggest all health care professionals deploy routine universal precautions (surgical masks, gloves) during the care of COVID-negative donors and recipients.” “acknowledged that there is regional and institutional variability with respect to: i) COVID-specific PPE ii) Universal precautions iii) No routine precautions.
Strict isolation precautions should be followed for anyone with suspected SARS-CoV2.
It is important to follow local protocols for suspected patient infections.
Staff who have returned from countries with >10 infected patients or have been exposed to a confirmed or suspected case of COVID-19 within the last 14 days should follow hospital policies, but should likely not care for transplant patients.
Use airborne and contact precautions with face shield when entering the patient room with suspected + case.
Strong recommendation to follow national guidance adapted to local conditions.
Adhere to local protocols.
During the donation process medical staff should apply appropriate and hygiene and use personal protective
equipment in accordance with national public health guidelines [61,62]. Personal protective measures in the
donation area of a SoHO establishment which is not located in a hospital environment should not be as
stringent as in settings where staff take care of infected or potentially infected patients. Infection control
practices and measures should be in line with the national public health recommendations for COVID-19
[63].
Unless COVID-19 is suspected on epidemiological or clinical grounds, additional precautions to those usually employed for acquiring respiratory samples in standard, non-COVID-19 ICU patients is NOT required. Specifically, there is no need for patient isolation or the use of non-standard ICU PPE in ongoing care of these patients.
…”has to be adequate availability of PPE for care of these patients”
“Full PPE” as per local protocol when in contact with confirmed or suspected COVID-19 + patient.
General hygiene ( frequent hand washing, disinfect surfaces, avoid hand-face contact), avoidance, N95 and eye protection when in close contact.
Suspension of all living donation.
| The October 2020 matching run for the UK Living Kidney Sharing Scheme will proceed on 28th October 2020 according to the previously agreed timetable. |
All living-donor kidney transplantation and deceased donor transplantation in patients that are stable on dialysis are put on hold until the end of the COVID-19 epidemic.
Minimum of 6 weeks (effective Mar 16).
Advised to practice social distancing and not travel 14 days prior to surgery.
Recommend 28 days past resolution of symptoms and negative testing prior to consideration for use.
Two negative tests before being considered for donation and another negative test at the time of donation.
| At least 1 sample from the upper respiratory tract by NAT for SARS-CoV-2 as close to donation as possible, but no longer than 3 days prior to surgery. |
Same as for deceased donors. PCR diagnostics must have been carried out on all living donors prior to organ removal to exclude the possibility of COVID-19 infection. If the PCR test on the living donor is positive, the organ removal must not be carried out.
Testing no longer than 7 days before donation.
Exclude if testing positive.
| Some national guidelines recommend routine testing of donors for SARS-CoV-2. |
Testing occurring as close as possible prior to donation (within 24–48 hours). Current data suggests the optimal test type in this ambulatory setting is a nasopharyngeal swab.
Delay for 14 days.
21 days from travel to endemic area or contact with confirmed case.
At least 14 days after contact with COVID-19 positive or travel to region with sustained community transmission.
Exclusion if international travel in last 14 days or contact in last 14 days with confirmed case of COVID-19.
| Living donation should not be performed on either a donor or recipient who has been exposed to a patient with confirmed or suspected COVID-19 within 14 days. |
If donor has been within an endemic area, wait at least 14 days (presumed incubation period) for symptom development.
The living donor transplant programme may be temporarily suspended…all elective live living kidney and liver transplant should be postponed.
14 days after international travel.
| “Donors should be screened epidemiologically, and by clinical history for suspected COVID-19infection.” |
| Donors who are at risk of COVID-19 or are self- isolating are not to be considered for organ donation. |
| Universal screening for SARS-CoV-2 is indicated in all potential donors prior to surgery. |
Question all potential donors for potential febrile respiratory symptoms or contact with COVID-19 suspected persons in 28 days prior to donation.
Donors should not be utilized if they have fever and/or respiratory symptoms unless SARS-CoV-2 is excluded.
Exclude if history of fever or acute respiratory infection (eg. Shortness of breath, cough, sore throat) with or without fever.
Donors should not be utilized if they have fever and/or respiratory symptoms unless SARS-COV-2 is excluded.
All potential living donors should undergo a symptom screen prior to donation. Any donor with compatible symptoms should be deferred but should also be tested to allow for future planning.
During periods of local transmission, temporary suspension of elective living donor Tx may need to be considered to protect the potential donor as well as the recipient.
Except for medical emergencies (e.g. pediatric acute liver failure).
| “Consider resuming living donor liver transplant programs that were suspended because of the pandemic.” |
In countries with widespread community transmission, temporary suspension of the living-donor kidney and liver transplant programs should be considered when donation can safely be deferred to a later date.
In countries with widespread community transmission, temporary suspension of the living-donor kidney and liver transplant programs should be considered when donation can safely be deferred to a later date.
“Liver donor liver transplantation caries greater urgency…should continue on a case-by-case basis, taking into account recipient medical need and hospital resource utilization depending on the severity of the pandemic in the local jurisdiction.”
During periods of local transmission, temporary suspension of elective living donor Tx may need to be considered to protect the potential donor as well as the recipient.
Recommend suspension until COVID-19 epidemiology better understood in US.
| It is recommended that patients are transplanted at the earliest opportunity with a deceased or living kidney donor derived organ. As capacity allows commence assessment of new referrals for LDKT. As capacity allows, consider inclusion of more complex cases such as ABOi/HLAi transplants. |
| Donation programs will be kept in a pre-pandemic situation. |
Normal, careful activity for COVID-19 negative donors and recipients. Caution kidney transplant resumption.
In countries with widespread community transmission, temporary suspension of the living-donor kidney and liver transplant programs should be considered when donation can safely be deferred to a later date.
All living-donor kidney transplantation and deceased donor transplantation in patients that are stable on dialysis are put on hold until the end of the COVID-19 epidemic.
The living donor transplant programme may be temporarily suspended…all elective live living kidney and liver transplant should be postponed.
In countries with widespread community transmission, temporary suspension of the living-donor kidney and liver transplant programs should be considered when donation can safely be deferred to a later date.
“All living donor kidney transplant programs in Canada should consider postponing living
donor transplants on a case-by-case basis and/or until this issue has resolved.”
Recommend continued life-saving transplantation on case-by-case basis.
All pulmonary centres are open, though some patients are concerned and have “self suspended”.
The hospitals that transplant hearts and lungs strive to carry out heart and lung transplants.
In a country with widespread community transmission, temporary suspension of the deceased donor program should be considered, especially when resources at the transplant centre may be constrained. There is no clear reason to suspend deceased donor transplants in countries only experiencing sporadic cases of COVID-19 cases.
Liver, heart, and lung transplantation programs continue. As a general guideline, priority should be given to hyper-urgent and urgent transplants.
No transplantation of lungs from COVID-19 + donors.
Recommend continued life-saving transplantation on case-by-case basis.
All heart centres are open and operating similarly to pre-COVID-19 numbers.
