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

• Maintenance of general hygiene. Washing your hands as often as possible with cleanser and water, or with a alcohol based hand sanitizer (60% alc), particularly: after utilizing the restroom, before eating, in the wake of blowing, coughing or sneezing and after direct contact with patient or their surroundings. Abstain from touching your eyes, nose and mouth before washing your hands.
• Regular cleaning of home with disinfection of objects and surfaces.
• Keep a distance of at least two metres from people with general symptoms such as fever, cough, malaise, sore throat or dyspnea). Abstain from sharing personal belongings.
• During the lockdown circumstance you should stay at home aside from the specified exemptions, as indicated by the standards built up by the political and wellbeing specialists. Telephone the kidney transplant facility at your referral community or the telephone numbers approved by the wellbeing specialists.
• Attempt to follow a right eating routine. Abstain from smoking and liquor. These substances weaken the immune system, and increase the risk of infectious diseases.
• Abstain from sharing food, utensils (cutlery, glasses, napkins, tissues etc) and different articles without cleaning them appropriately.
• 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 is prudent to approve a sick leave in patients whose profession involves a high hazard for disease.
• It is recommended to screen kidney transplant patients through teleconsultation so as to decrease the time spent in healthcare centers and decrease the risk of infection

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

All kidney transplant patients with suspected symptoms of COVID-19 are advised to contact their healthcare provider (ideally by phone), to discuss the full course of their treatment and other chronic conditions that they are having. Depending upon the symptoms :-

• Mild symptoms ie
  • without Dyspnea or Tachypnea
  • Temperature <38°C
  • Kidney receptor with adequate functional reserves
    • The patient can be asked to remain in contact via teleconsultation to have the diagnostic tests performed, monitor the symptoms and communicate alarming to the transplant team every 24–48h.
• Moderate/Severe symptoms
  • Temperature >38°C
  • Presence of Dyspnea
  • Presence of Tachypnea
  • Fragile Kidney receptor
    • Patient can be asked to report to Emergency Department for clinical evaluation.

Pathophysiology

Acute Kidney Injury has been reported in patients with COVID-19 infection and presence of proteinuria, hematuria has also been reported. In a case observation, 4 out of 7 patients had AKI which may indicate that renal transplant patients are at higher risk AKI on being infected with COVID-19 whereas only 29% AKI was seen in critically ill patients of general population..

• Uptake of SARS-Cov-2 virus into proximal tubule cells is possible explanation for the AKI seen in COVID patients. Angiotensin-converting enzyme 2 and Dipeptidyl peptidase have been implicated in the uptake of SARS-Cov and MERS-CoV. These receptors are found in the proximal tubules of kidney..ACE2: ACE ratio is higher in the kidneys compared to the respiratory system. (1:1 in the kidneys VS 1:20 in the respiratory system)

Lab Findings

Presenting symptoms in renal transplant patients 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
  • Renal transplant patients generally have a low lymphocyte count due to immunosuppression, hence finding a further drop in the lymphocyte count can be of prognostic value.
• D-dimer
• Ferritin
• Troponin
  • Microvascular thrombosis and disseminated intravascular coagulation( with gut ischemia) can occur later in the course of illness. They are characterized by marked increase in the levels of D-dimer particularly. D dimer, ferritin, and troponin should be measured in all patients with severe COVID-19 infection on admission and in those who fail to show any 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.