| Additional evaluation may be required when considering kidney or lung transplantation from donors with previous COVID-19. |
| Self-quarantining, when feasible, especially for donors travelling by air. Maintaining social distancing. |
| 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. |
| There is currently no evidence to suggest transplant patients are at greater risk of acquiring infection, thus immunosuppression should be continued unless otherwise indicated to discontinue or reduce doses. |
| 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. |
| We recommend deferring routine surveillance biopsies if clinically feasible in patients with stable allograft function and a low risk of rejection, until local resources and capacity allow. Such patients may include those that are > 3 months from transplant, have no recent history of rejection, and those that are not sensitized or with a positive cross match. For patients < 3 months post-transplant or with a history of recent rejection or at high risk for rejection, performing surveillance biopsies should be weighed against the risk of exposure to the patient and health care personnel. Local resources and capacity should also be considered. |
| 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. |
| For asymptomatic patients we recommend home quarantine for 2 weeks and testing for SARS-CoV-2 by PCR-based test only if symptoms occur unless local or national public health guidelines recommend testing of asymptomatic individuals for contact tracing. |
| 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. |
| Donor or candidate with a known exposure to a confirmed/ probable case of COVID19 within past 14 days should be avoided as patients may be in an incubation phase even if asymptomatic. |
| 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. |
| The minimum number of personnel should be involved in the procurement team and related travel to reduce the risk of exposure and infection. |
| Standard surgical masks are considered sufficient for heart retrieval and transplantation, along with suggested face shield if no lung retrieval is being performed in the same donor. Where available, negative pressure operating room should be used for lung surgical procedures. Bronchoscopy in cases of suspected COVID-19 or in areas where community transmission is occurring should be done using airborne isolation precautions. |
| 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 with former COVID-19 following complete clinical recovery, at least 28 days from symptom onset, and two negative PCR tests 24-48 hours apart may carefully be assessed for donation and ultimately be considered eligible for donation if no permanent end-organ damage resulted from COVID-19 and appropriate donor organ function is confirmed. |
| 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). |
| 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. |
| « 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. |
| Maintain frequent hand hygiene habit, avoid unnecessary physical contact. The use of a mask in social/hospital settings has no clear indication. |
| If clinical suspicion, postpone for 28 days. |
| Does not specify DD or LD. Test all potential recipient with epidemiological and/or clinical suspicion. |
| 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.
If testing is not available for deceased donors (intermediate risk), we recommend NOT transplanting lungs or intestines. The decision to transplant other organs should be made with caution after careful consideration of the risks and benefits.
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.
Consider notifying patients that the COVID-19 pandemic may impact their waiting time on the transplant list; Notify patients that family and visitor access to them during their hospital stay may be limited or prohibited.
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.
Recommend screening and self-isolation after travel as per local practice and protocols.
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.
Recommend screening and self-isolation after travel as per local practice and protocols.
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.
1) Postponing routine surveillance heart biopsies and bronchoscopies in patients that are more than 3-6 months from transplantation. 2) Increased importance of home as opposed to hospital based spirometry. 3) for heart recipients, suggest considering the use of non-invasive methods for rejection surveillance, as available such as gene expression profiling.
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.
Recommend a combination of tele-practice, pre-visit screening calls and limiting visits further if patient has COVID-19 consistent symptoms ISHLT.
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.
Regardless of donor screening, the centre should have a discussion of risk-benefit with the recipient.
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. |
Defer regardless of symptoms.
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. |
Program was suspended but the decision now is to start the program in phases (nephrologists have been given guides to slowly start again).
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.
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.
Recommend continued life-saving transplantation on case-by-case basis.
Consider transplantation from COVID-19 + donors on case by case basis, continue donation as usual if COVID-19 negative.
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.
Decision must be made on case by case basis considering local resources and transmission risk.
Recommend continued life-saving transplantation on case-by-case basis.
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.
As a general guideline, transplantation that are not lifesaving in the short term should be delayed until the end of the COVID epidemic. Liver, heart, and lung transplantation programs continue. As a general guideline, priority should be given to hyper-urgent and urgent 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.
We do not recommend a general cessation of all transplant or VAD activity due to the COVID-19 pandemic solely to liberate resources for treating COVID-19 patients.
As a general guideline, transplantation that are not lifesaving in the short term should be delayed until the end of the COVID epidemic. At that stage, liver, heart, and lung transplantation programs continue. As a general guideline, priority should be given to hyper-urgent and urgent transplants.
Recommend continued life-saving transplantation on case-by-case basis.
Consider suspending living donor liver transplant programs during the pandemic, except for pediatric patients with acute liver failure.
All centres are open with DBD nearing normal numbers and DCD increasing.
Consider transplantation from COVID-19 + donors on case by case basis, continue donation as usual if COVID-19 negative.
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.
All living-donor kidney transplantations and deceased donor transplantations in patients that are stable on dialysis are put on hold until the end of the COVID-19 epidemic.
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.
Recommend continued life-saving transplantation on case-by-case basis.
| It is recommended that patients are transplanted at the earliest opportunity with a deceased or living kidney donor derived organ. 5 of the 8 pancreas centres open to accept offers and transplants. |
| At this time, the joint transplant centers have decided to postpone almost all renal transplant operations. This therefore applies to both kidney transplants with a kidney from a living and a deceased donor and pancreatic / islet transplants. |
Consider transplantation from COVID-19 + donors on case by case basis, continue donation as usual if COVID-19 negative. COVID-19 screening results of donor must be available prior to organ recovery.
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.
All deceased donor transplantation in patients that are stable on dialysis are put on hold until the end of the COVID-19 epidemic. Centres can perform kidney transplantation in patients with Eurotransplant high urgency HU) status. Renal transplantation in highly immunized patients with long waiting times can be envisioned in case a well-matched donor kidney against which the patient has no preformed donor-specific antibodies becomes available and the transplant centre considers that the risk-benefit ratio is beneficial and that the necessary resources for successful transplantation are available. Pediatric renal transplantation can therefore be performed in case treating physicians consider the benefit outweighs the potential risks related to COVID-19 infection under high dose immunosuppression. The decision should be taken after discussion with the patient’s caregivers and eventually the patient her- or himself. Kidney-pancreas transplantation is to be suspended except for high urgency transplants or in highly immunized patients according the definition given above for renal transplantation.
Islet transplantation is suspended.
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.
All transplant programs should consider suspending deceased kidney transplants, except for highly sensitized recipients (PRA>=99%) or because of an urgent medical need due to a lack of access to dialysis.
Should report all post-transplant patients with suspected or confirmed COVID-19 to local infection control. Contact ODO and/or UNOS if suspected transmission through donated organ.
Separated systems will keep the infected from the uninfected.
Cohort patients with COVID from non-infected inpatients.
Prudent to limit visitors.
Severe limitations recommended such as only for hospice patients or at time of discharge instructions.
RIVM advises the vulnerable group to stay at home, to receive as little visitors as possible, to keep 1.5 meters away, to wash hands often and to allow contact with others to take place by telephone as much as possible.
| Consider suspending non-essential clinic visits. |
Limit all non-essential contact and recommend increased use of distance consultation. Ensure at least 90 day supply of medications.
Recommend distance consultation as much as possible. Limit lab or radiology that requires transfers within or between hospitals. Patients should be given 90 day medication supplies.
Recommend against coming to hospital if symptomatic unless advised by transplant team, encourage phone or video conference visits.
Transplant patients with fever and/or respiratory symptoms should be instructed to call the transplant centre and avoid presenting to the clinic without notifying the centre in advance to avoid inadvertent exposures.
Mention possible increased risk to shed and transmit virus among immunocompromised patients that have COVID-19.
Transplant units advised to consider ways to limit hospital attendance for patients such as (rescheduling on urgent out patient appts, virtual or tele-medicine or telephonic appts, home delivery of immmunosuppression if feasible). Patients with stable graft function and adequate drug supply can avoid routine follow-up visits to transplant hospitals.
Determine approaches to minimize exposure to the healthcare setting.
Contact transplant program if develop fever and/or respiratory symptoms, GI symptoms and other COVID related symptoms.
Recommend all symptomatic patients contact transplant teams and avoid general hospital areas.
When should I contact my medical specialist in the hospital?
• If you have a fever above 38 degrees
• If you feel feverish and have a cold like coughing, sore throat or cough
Increased risk of infection and severity among immunocompromised likely though unproven.
Fever, cough, difficulty breathing; immediately call respective transplant centre.
Implement procedures to screen patients coming to clinic for fever and respiratory symptoms.
| Mask or face covering if out in public. |
Recently transplanted patients should follow respiratory principle and wear a mask when available.
Prudent to limit visitors.
Severe limitations recommended such as only for hospice patients or at time of discharge instructions.
RIVM advises the vulnerable group to stay at home, to receive as little visitors as possible, to keep 1.5 meters away, to wash hands often and to allow contact with others to take place by telephone as much as possible.
Current risk is unknown but that severe disease have been reported.
One should assume that it is likely to acquire COVID-19 disease from a blood entry pathway.
State that evidence from SARS and MERS does not suggest increased mortality for post-transplant patients. Immunosuppression may decrease severity of disease but likely increases viral shedding.
Transplants are probably just as likely to get the COVID-19 virus as people without a transplant. It is much more important to properly follow the guidelines of the RIVM. This will reduce your chance of getting a Corona virus infection.
Mention possible increased risk to shed and transmit virus among immunocompromised patients that have COVID-19.
We recommend strict application of protective measures in transplant patients and in case of even mild clinical signs suggestive of COVID-19, a lower threshold for screening since they represent a higher risk population for infection and contagion.
| Self-quarantining, when feasible, especially for donors travelling by air. Frequent hand washing. Maintaining social distancing. Mask or face covering if out in public. |
Recommend strict adherence to social distancing recommendations.
Limit travel and respect social distancing recommendations (including advocating for patients to work from home).
Follow the advice of RIVM. RIVM advises the vulnerable group to stay at home, to receive as little visitors as possible, to keep 1.5 meters away, to wash hands often and to allow contact with others to take place by telephone as much as possible.
Strictly follow travel advisories and take extra precautions.
Adhere to travel advisories issued by their respective health authorities/govt bodies. This may necessitate postponing travel to countries with >10 infected patients. Recipients should avoid travel to all locations where COVID is currently circulating. Transplant recipients should avoid all cruise ship travel.
Take respiratory precautions and wash hands frequently and thoroughly.
Masks or face covering when in public.
Mask any patient with suspected COVID-19.
Patients with suspected COVID-19 or who require testing to rule out COVID-19 should wear a surgical mask, be placed in isolation and have evaluation and testing coordinated with infection control or Transplant ID team, consistent with local policies.
We recommend strict application of protective measures in transplant patients.
Wear mask.
Any symptomatic transplant recipient should wear mask during any hospital or clinic visit, be placed in isolation, and have ID consult for management consistent with local policies.
| Self-quarantining, when feasible, especially for donors travelling by air. |
Follow national recommendations.
Teams should follow local health department guidelines for isolating, quarantining, testing, and monitoring returned travellers from endemic areas.
14 days after international travel
| 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. |
14 days
We recommend against the use of lopinavir/ritonavir for first line therapy given early data that it lacks efficacy and the potential for severe drug-drug interactions.
Consider remdesivir for the treatment of hospitalized patients with severe COVID-19 under the FDA’s EUA; recommends against lopinavir-ritonavir…Hydroxychloroquine with or without azithromycin is not routinely recommended.
| Use should be considered in conjunction with local practice or as part of clinical trial. Early thrombophylaxis strongly recommended, unless contraindicated. |
Specifically told not to change therapy unless advised by physician.
Consider reducing high dose steroids (careful to avoid aderenal insufficiency). Consider reducing calcineurin inhibitor dosage and azathioprine or mycophenolate dosages in the setting of lymphopenia.
Stop antiproliferative agents (MMF/azathioprine), review total burden of immunosuppression, high does steroid can be counterproductive, minimise calcineurin inhibitors in early disease.
Consider holding mycophenolate mofetil or azathioprine while admitted with moderate/ severe illness (with close monitoring for rejection).
Drug-drug interactions with immunosuppressant medications need to be evaluated and managed.
There is overall agreement of stopping antimetabolite drugs and decrease calcineurin inhibitors by 50%. Steroid should be continued on same doses (based on Mass General recommendations).
Decreasing immunosuppression should be considered for infected recipients, if no recent rejection episodes.
Not for asymptomatic patients.
It is very important that patients do not stop taking immunosuppressive medicines.
There is a paucity of data, however, for safety we recommend limited use of induction therapy during this COVID-19 surge. Lymphocyte depletion should be used with great caution.
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.
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.
Also to the Vigilance and Surveillance Expert Advisory Committee (VSEAC) of the Organ and Tissue Authority (OTA) in addition to any immediate state and territory reporting requirements.
Test as soon as patient arrives at hospital, especially if they show symptoms.
Lung transplant specifically for COVID-19 related lung disease should be considered with grave caution in carefully selected cases following two negative PCR based tests as noted above. Recent data indicate that myocarditis may occur at this stage, and thorough cardiac evaluation is warranted.
Await full symptom resolution and then have at least 2 negative screens (PCR).
Recipients with active COVID-19 or recovering from an acute COVID-19 infection should not undergo transplantation.
RT-PCR testing.
| Documentation of negative PCR testing at least 24 hours apart is recommended before a candidate should be cleared for transplant unless the need for transplant is urgent. |
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.
Recommend waiting 14 days if candidate travelled through endemic area. Clinical prudence paramount.
WRT to general COVID diagnosis, not recommended. Should only be used to diagnose pneumonia in certain populations.
CT thorax to screen for typical COVID-associated lung lesions is also recommended at admission to the hospital for transplantation.
14 days.
Does not specify if recommendations are only for DD recipients.