Sandbox: GDS

COVID-19 Infection in Transplant Patients

Risk of COVID-19 in renal transplant patients is higher because of immunosuppression, underlying chronic kidney disease, and other co morbidities such as diabetes and hypertension, which are presently perceived as noteworthy components impacting the results in patients with COVID-19 .It is realized that any transplant recipient presented to the infection would result in a high level of cases; however the risk of donor to recipient transmission is unknown. The chances of a donor to recipient infection might be affected by exposure of the donor, infectivity of the the donor during the incubation period and the degree of viremia as well as the viability of virus in specific organ system.In this manner, in spite of the conceivable negative outcomes, temporary interruption of kidney transplantation might be fundamental in regions where the rate of infection is high..

General Considerations for Renal transplant Patients

• Maintain adequate hygiene. Wash your hands frequently with soap and water for at least 20s, or with an alcohol-based hand sanitizer (at least 60% alcohol), especially: after using the bathroom, before eating, after blowing, coughing or sneezing and after direct contact with sick people or their surroundings. Avoid touching your eyes, nose and mouth before washing your hands.
• Cleaning of house surfaces should be done regularly. Clean and disinfect frequently touched objects and surfaces.
• Avoid contact or maintain a distance of at least two meters with people with respiratory infection symptoms (fever, cough, generalized sore muscle, sore throat or respiratory difficulty) and do not share personal belongings.
• During the lockdown situation you must remain at home except for the stipulated exceptions, according to the rules established by the political and health authorities. Phone the kidney transplant clinic at your referral center or the phone numbers authorized by the health authorities.
• Try to follow a correct diet. Avoid smoking and alcohol. In addition to being harmful to health, these substances weaken the immune system, making the body more vulnerable to infectious diseases.
• Avoid sharing food and utensils (cutlery, glasses, napkins, handkerchiefs, etc.) and other objects without cleaning them properly.
• The Centers for Disease Control and Prevention and (CDC): does not recommend to the general population that people who are well to wear a face mask to protect himself from respiratory diseases, including COVID-19. Today, the kidney transplant population must comply with the recommended measures of protection in the general population, especially if they are asymptomatic at home. However, the responsible physicians will recommend the use of a mask on an individual basis, mainly in cases where the patient goes to a health center or other place with agglomeration. People who show symptoms of being infected with SARS-CoV-2 should wear masks to prevent the spread of the disease to others.
• It would be advisable to authorize a sick leave in patients whose profession entails a high risk for infection.
• It is recomended to monitor kidney transplant patients through teleconsultation in order to reduce the time spent in health centers and minimize the risk of infection

Specific recommendations for kidney transplant patients suspected of SARS-CoV-2 infection

All kidney transplant patients with symptoms compatible with COVID-19 are recommended to contact their transplant specialist or primary care physician (preferably by telephone), indicating clearly their chronic diseases and the type of treatment they take regularly. Depending on the symptoms presented, it is recommended:

• Mild symptoms (without dyspnea/tachypnea) and temperature <38°C in a kidney receptor with adequate functional reserves: the patient will be asked to contact by phone with phone number that has been designed by the Health Authorities in each Autonomic Community to have the diagnostic test performed and remain at home monitoring symptoms and alarm signs with telephone monitoring by the transplant team every 24–48h.
• Moderate/severe symptoms, temperature >38°C or fragile receptor: the patient will be instructed to go to the Hospital Emergency Department to be clinically evaluated.

Pathophysiology

Acute Kidney Injury has been described with COVID-19 infections in up to 15% patients, and occurrence of proteinuria or hematuria has been reported. In a case observation that 4 of 7 patients had AKI (57%) may be an early signal that transplant patients are at higher risk of AKI with COVID-19 infection, compared with 29% AKI in critically ill patients of general population in Wuhan, China. Angiotensin-converting enzyme 2 and dipeptidyl peptidase, which are expressed in proximal tubule cells. have been identified as receptors for SARS-CoV and MERS-CoV. Uptake of SARS-CoV-2 virus into the proximal tubular epithelium is a possible explanation for AKI.

Lab Findings

Presenting symptoms are similar to those of non-renal transplant patients.

• Respiratory symptons
  • Cough
  • Chest Pain
  • Dysnea
• Fever
• Hypoxia
• Lymphopenia
• High C-Reactive Protein

Valuable prognostic blood tests that can be done are

• Lymphocyte count
  • As many patients on immunosuppression are likely to have baseline lymphopenia, a further drop in lymphocyte count is likely to be of prognostic value.
• D-dimer
• Ferritin
• Troponin
  • Marked increase (in particular D dimer) later during the course of her illness can signify microvascular thrombosis or disseminated intravascular coagulation with possible gut ischemia. D dimer, ferritin, and troponin should be measured in all patients with severe COVID-19 infection on admission and subsequently in those who are not showing clinical improvement.

Immuno-suppression Status in Transplant patients

Kidney transplant patients, due to immunosuppression, the immune response have been altered and particularly the T-cell immune response. There is little evidence regarding the minimization or management pattern of immunosuppression, especially in the kidney transplant population infected by COVID-19. There has been a very short period of time since the appearance of COVID-19 with very limited accumulated experience and the insufficient published scientific evidence. To date, only one case of a patient with COVID-19 pneumonia in a kidney transplant recipient has been published, whose clinical manifestations were similar to those of the population not carrying a kidney transplant

Managing immunosuppression in these patients is challenging and should take into account age, severity of COVID-19 infection, associated comorbidities, and time post-transplant. In transplant patients with mild to moderate infections, the usual practice is to continue or make reductions in the dose of immunosuppressive drugs, but this approach might favor high mortality in patients admitted to hospital with COVID-19 infection.It is suggested that antiproliferative agents (MMF and azathioprine) should be stopped at the time of admission to hospital, dose of prednisolone should be either unchanged or increased, and tacrolimus dose should be reduced. In severe infections (requiring intubation and ventilation),calcineurin inhibitors should be stopped completely while maintaining corticosteroid therapy. The role of cytokine storm and inflammation due to antiviral immune response as a driver of severe respiratory disease and acute respiratory distress syndrome has been discussed since the outbreak of this disease in December 2019, prompting trials of anti-interleukin 6 monoclonal antibody tocilizumab and case for continuing steroids in infected patients. Low dose of Tacrolimus can be continued but more evidence is needed before drawing firm conclusions. There is a risk of rejection with reduction in immunosuppression but given the high mortality rate of COVID-19 infection in hospitalized patients, clinicians should focus on keeping their patients alive with a careful case-by-case assessment of risks versus benefits of continuing immunosuppression.

Low-dose systemic corticosteroids have several beneficial effect due to their immunomodulatory, anti-inflammatory and vascular properties, which confer immunological protection of the renal allograft; Corticoids produce inhibition of proinflammatory cytokines, reduction of white blood cell traffic and maintenance of integrity and permeability of the endothelium, thus maintaining homeostasis and controlling dysregulation of the immune system.

Treatment

With regard to specific antiviral therapies, although a recent trial showed no benefit of lopinavir-ritonavir in hospitalized patients with severe COVID-19, it remains possible that treatment with these drugs as well as hydroxychloroquine will be considered in patients with COVID-19 pneumonia. The choice of calcineurin inhibitor may also have a role to play. Thus, for instance, cyclosporin A has been shown to have an inhibitory effect on proliferation of corona viruses and hepatitis C virus in vitro, while this is not the case for tacrolimus. Cyclosporin A is thought to inhibit the replication of a diverse array of coronaviruses through its impact on cyclophilin A and B.