|Year : 2020 | Volume
| Issue : 1 | Page : 1-4
Corona, COVID and kidney transplantation
Manisha Sahay1, Vivek Kute2, Narayan Prasad3
1 Department of Nephrology, Osmania Medical College and General Hospital, Hyderabad, Telangana, India
2 Department of Nephrology, Institute of Kidney Disease and Research Centre, Ahmedabad, Gujarat, India
3 Department of Nephrology, Sanjay Gandhi Post Graduate Institute, Lucknow, Uttar Pradesh, India
|Date of Submission||25-Mar-2020|
|Date of Acceptance||25-Mar-2020|
|Date of Web Publication||31-Mar-2020|
Prof. Manisha Sahay
Department of Nephrology, Osmania Medical College and General Hospital, Hyderabad - 500 012, Telangana
Source of Support: None, Conflict of Interest: None
Severe acute respiratory syndrome corona virus 2 (SARS CoV2) is responsible for corona virus disease (COVID-19). Many organizations have given guidelines for the prevention of COVID-19. Other societies have given updates regarding living and deceased donor transplantation during the pandemic. This article reviews the literature available on corona virus and its impact on living and deceased donor transplantation.
Keywords: Corona virus, COVID-19, pandemic, transplntation
|How to cite this article:|
Sahay M, Kute V, Prasad N. Corona, COVID and kidney transplantation. Indian J Transplant 2020;14:1-4
| Introduction|| |
Corona virus disease (COVID-19) is caused by single-stranded RNA virus called severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The first human case was reported in Wuhan, Hubei province of China in December 2019. It spread all over the world and has been declared a global pandemic on March 11, 2020. The first case of COVID was reported in India on January 30, 2020. More than 372,757 confirmed cases have been reported to the WHO till date, and more than 16,231 people have lost their lives.,,,
The World Health organization,, the Centers for Disease Control and Prevention (CDC),, and the Ministry of Health MoHFW, Government of India (MoHFW),,, have given guidelines about the prevention of COVID-19. The American Society of Transplantation (AST), and the transplantation society, have given guidelines about transplant recipients and about organ transplantation. These are regularly getting updated and should be referred. This article provides a short summary about COVID in transplantation.
| Clinical Presentation|| |
The incubation period may range from 2 to 14 days. It spreads through aerosol and by contact spread as droplets may deposit on fomites and can be carried by hands to a person's nose or mouth. Spread through stool or urine is unlikely. Newborn COVID has been reported, but whether it is vertical transmission or postnatal infection is not clear. The inoculum to infect a transplant recipient may be lower.
Symptoms and signs are mild (80%) and include fever, cough (which may be productive), sore throat, hemoptysis, headache, myalgia or fatigue, and shortness of breath. Some have diarrhea and nausea. Some patients may be asymptomatic and may have subclinical infection. There may be clinical deterioration during the 2nd week of illness with a development of dyspnea. Severe disease is seen in about 15% of patients and is characterized by hypoxemia (paO2 <93%, RR >30/min, and >50% lung involvement in 24–48 h). Critical disease seen in 5% of patients is characterized by respiratory failure, acute respiratory distress syndrome (ARDS), cardiac injury, arrhythmia, septic shock, liver dysfunction, acute kidney injury (AKI), and multiorgan failure. Pregnancy-related complications are reported. A description of disease in transplant recipients is still not available. The disease is uncommon and less severe in children.
Renal involvement may be characterized by hematuria, proteinuria, elevated creatinine, and urea. AKI may occur due to sepsis. Kidneys show low echogenicity on ultrasound, indicating inflammation and edema. The kidney involvement may be due to cytokine storm or due to direct involvement of renal tubular cells which have angiotensin-converting enzyme and DPP4 (dipeptidyl peptidase) receptors which can bind corona virus.
| Risk Factors|| |
Risk factors for severe illness include old age; chronic medical conditions such as lung disease, cancer, heart failure, cerebrovascular disease, renal dysfunction, liver disease, diabetes, immunocompromising conditions, and untreated hypertension; those with critical illness; and pregnancy. Lymphopenia may predispose to severe disease. Transplant recipients are immunosuppressed and may have medication-induced lymphopenia and may be at higher risk.
| Stages of Transmission|| |
- Stage 1 (imported) is virus imported from travel to affected countries
- Stage 2 (local transmission) is by direct contact of those coming from international exposure
- Stage 3 (community transmission) is unknown origin of infection, i.e. no contact with the above two categories
- Stage 4 (epidemic) spreads to massive number of people.
| Mortality|| |
Patients who have no underlying medical conditions have an overall case–fatality rate of 0.9%. Mortality appears to be age dependent, with the highest rates among older adults (age 50–59 years: 1.3%, 60–69 years: 3.6%, 70–79 years: 8%, and 80 years and above: 14.8%). Case–fatality rate is 5%–10% in patients with comorbidities and may be 50% in patients who develop respiratory failure, septic shock, or multiorgan dysfunction.
| Lab Diagnosis|| |
The most common laboratory abnormalities include leukopenia, lymphopenia, thrombocytopenia, and elevated alanine aminotransferase and aspartate aminotransferase levels. Leukocytosis is uncommon. Most patients have normal serum procalcitonin. Elevated C-reactive protein, lactate dehydrogenase, and ferritin may be seen. Chest X-ray and chest computed tomography may show bilateral involvement with multiple areas of consolidation and ground-glass opacities or may be normal. However, imaging is not required routinely for diagnosis due to high risk of infection transmission.
Antibody tests are not useful for diagnosis. Reverse transcriptase polymerase chain reaction (PCR) is used to detect SARS-CoV-2 RNA from nasopharynx, oropharynx, and lower respiratory tract specimens, i.e. bronchoalveolar lavage (BAL) fluid. Sputum should not be induced and BAL should not be routinely used except in patients on ventilator. Prolonged detection of SARS-CoV RNA has been reported in respiratory and stool specimens up to 30 days after illness onset. Transplant recipients may have high viral loads and may shed the virus longer.,
| Who Should Be Tested?|| |
- All individuals who have undertaken international travel in the last 14 days should be tested only if they become symptomatic
- All symptomatic contacts of laboratory confirmed cases
- All symptomatic health-care workers
- All hospitalized patients with severe acute respiratory illness (fever AND cough and/or shortness of breath)
- Asymptomatic direct and high-risk contacts of a confirmed case should be tested once between day 5 and day 14 of coming in his/her contact.
| Management for Transplant Recipients|| |
There may be four types of scenarios regarding transplant recipients:
- Recipients without any exposure or symptoms should preferably stay at home. Patients should avoid elective clinic visits. Telephonic consultations or telemedicine should be encouraged. Elective procedures, i.e. protocol biopsies, should be avoided. For all recipients, prompt implementation of recommended infection prevention and control measures
- Masks: Those recipients who are healthy need not to wear masks. Medical masks should be worn by those who have cough and cold. If clinic visit is necessary, the patients should wear masks during that time. Masks, when indicated, should be worn properly, i.e. should cover nose and mouth and should be tightly fitting. Should not be worn for more than 6 h and should be disposed properly in a closed bin. When removing the mask, care should be taken to avoid touching the outer surface. If masks are not used properly, they may become the source of infection
- Hand hygiene: Hands should be sanitized with sanitizer (70% isopropyl alcohol). If visibly soiled, they should be washed with soap and water. Hand-washing should be for 20 s and steps of hand-washing should be followed. Frequent touching of face should be avoided
- Respiratory hygiene: When coughing, mouth should be covered with tissue paper which should be promptly disposed in a closed bin. If tissue paper is not available, cough into flexed elbow. Hand hygiene should be done after this
- Social distancing: Avoid visiting crowded places, avoid using public transport, and maintain distance from others of >1 m even at home
- 70% alcohol or bleach (1 part of household bleach of 5% sodium hypochlorite mixed with 9 parts of water equal to 5000 ppm) should be used at home for mopping and cleaning surfaces, toilets, etc., Garbage should be disposed in appropriate bins.
- Patients with a history of international travel or those exposed to confirmed or suspected case within 14 days but are asymptomatic should be quarantined at home. Required laboratory testing of such patients during the 14 days should be done in such a way as to avoid potential exposure of other patients. Local guidelines should be followed
- Asymptomatic COVID positive or those with mild symptoms may be monitored at home or may be hospitalized for monitoring as per clinical situation
- All patients with severe symptoms need to be hospitalized. Transplant units should be prepared to receive transplant patients who need hospitalization. All infection control measures should be followed. Patients should be housed in single rooms with an attached bathroom, and all staff attending to them should be in full Personal Protective Equipment (PPE), until infection with COVID-19 is ruled out. PPE includes medical mask, goggles, long-sleeved nonsterile gown, and gloves/face shields. During aerosol-generating procedures, N95 mask and also waterproof apron over disposable gown should be used. Close coordination is needed with other departments (e.g. radiology) and other laboratory services. Schedules may be readjusted to permit separation of patients. However, the 2-week incubation period, asymptomatic shedding, and negative PCRs early in the course of the disease make “ruling out“ very difficult. Clinical management of symptomatic patients includes
- Severely ill patients need supportive management, i.e. oxygen. They should be treated for coinfections. Fluids should be used conservatively
- Critical ill patients, i.e. those with ARDS, need intensive respiratory support. High-flow oxygen therapy and noninvasive ventilation should be avoided. Endotracheal intubation and mechanical ventilation with high PEEP and low tidal volume are preferred. Some patients need extracorporeal membrane oxygenation. The surviving sepsis guidelines should be followed for the management of patients with sepsis and multiorgan dysfunction
- Transplant patients needing dialysis: Any suspected patient should be dialyzed in an isolation unit not in dialysis centers
- Drugs: There are currently no antiviral drugs licensed by the U. S. Food and Drug Administration to treat patients with COVID-19. Remdesivir is an investigational antiviral drug and is undergoing trials and is approved for compassionate use. Lopinavir/ritonavir and inhalation interferon has been tried. Tocilizumab which is monoclonal antibody to IL6 may have some role
- Drug–drug interactions with immunosuppressant medications need to be managed, especially with the lopinavir/ritonavir which leads to marked elevations in the levels of calcineurin inhibitors and mTOR inhibitors due to profound CYP34A-mediated inhibition of their metabolism by ritonavir (AST). Interferon may increase the risk of rejection. There is a suggestion that continued ARB and ACE inhibitor therapy may be detrimental, but data are limited and there is no firm recommendation for the discontinuation of these. The impact of immunosuppression on COVID-19 is not known, but decreasing immunosuppression should only be considered for infected recipients (ie stop MMF and reduce CNI by 50%), if there are no recent rejection episodes.
| Prophylaxis|| |
HCQ is recommended by the ICMR at a dose of 400 mg twice a day on day 1, followed by 400 mg once weekly for next 3 weeks for asymptomatic household contacts of laboratory-confirmed cases and for 7 weeks for asymptomatic health-care workers involved in the care of suspected or confirmed cases of COVID-19 to be taken with meals.
In the United States, the National Institutes of Health and in Israel, collaborators are working on the development of candidate vaccines.
| Transplant-Specific Recommendations for Donor and Recipients Posted for Transplants|| |
Deceased donor transplants
The true risk of donor to patient transmission is not known. However, viral RNAemia has been seen in 15% of patients. Guiding principles for deceased donor transplants state that:
- Organ retrieval should be avoided from deceased donors at this time who have (i) active COVID-19 infection, (ii) test positive for COVID-19 as part of the evaluation, and (iii) classified as at risk (epidemiological history of travel or contact with COVID positive in the last 14 days and symptomatic ie fever >100.3°F, cough, malaise, and breathlessness on screening and SARS-CoV-2 testing not available
- Deceased donors should be tested for COVID-19. Organs from donors who have no risk factors or/and are negative for COVID may be used as per local policy. The decision-making should include the candidates or their proxy and explaining lack of currently approved therapies. Transplant programs accepting organs from these donors should consider placing recipients in contact and airborne isolation. Organ retrieval centers should maintain blood specimens for serologic or NAT testing on all deceased donors that can be made available for retrospective testing
- Organs from deceased donors who have recovered from COVID-19 and have resolution of symptoms greater than 28 days prior to procurement and repeated negative testing are likely safe to use as per AST.
- In countries where only sporadic cases of COVID-19 cases are occurring, there is no evidence to suspend all deceased donor transplants. A tiered suspension may be considered (i.e., deferral of more elective transplants, i.e., kidney, pancreas, and heart transplantation). If there is evidence of widespread community transmission in a country, the deceased donor program should be temporarily suspended. Local guidelines should be followed.
Living-related donor transplants
Guidelines for living donor transplants given by AST, are as follows:
- We do not recommend using organs from a living donor with active COVID-19 at this time
- Living donors who are classified as high risk should have donation postponed until they are at least 28 days beyond symptom resolution and have a negative SARS-CoV-2 PCR test
In India, temporary suspension of elective living donor transplantation has to be considered to protect the potential donor as well as the recipient,
- If transplantation is required as a life-saving procedure, it can be conducted with appropriate assessment of infection in donor and recipient (RT-PCR) and with appropriate informed consent.
Staff who have returned from international travel 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.
Regular updates be taken from the CDC, WHO, MoHFW, and ICMR. The Indian Society of Organ Transplantation has come out with detailed Indian guidelines.
| Conclusion|| |
COVID19 has emerged as a global pandemic of 2020. Patients present with predominant respiratory symptoms. Mode of spread is through droplet and fomites. Prevention is important by social distancing and hand and respiratory hygiene. Treatment is supportive. New drugs and vaccines are under trials. In countries with community spread, deceased and live donor transplantation should be suspended unless it is an emergency. As this is an emerging infection, for decision-making, careful attention to reports from local health authorities as well as review of updated data is essential.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |