Kidney Transplant Patient Immunological Hyporesponsiveness to SARS-CoV-2 Vaccination

Background: Multiple studies have shown an association between immune status and SARS CoV-2 disease severity, however data on specific immunosuppressive medications is not fully described. Immunocompromised individuals are at increased risk of mortality and morbidity therefore, vaccination against COVID-19 is essential. Research also suggests that elevated IgG levels post-vaccination correlate with host viral neutralization. We present data indicating that induction and maintenance immunosuppression therapy affects responsiveness to SARS CoV-2 vaccination among kidney transplant recipients. Method(s): 48 kidney transplant patients at our institution were retrospectively analyzed after receiving two doses of the SARS CoV-2 mRNA type vaccine between January and March 2021. Kidney transplantation occurred between 1983 and 2020. SARS-CoV-2 spike antigen-specific IgG levels were measured after 30-days to evaluate immunological responsiveness to the vaccine. Result(s): 35% of study subjects showed detectable peak COVID IgG serum levels 30 days after the second vaccine dose while 65% showed no response. Of the nonresponders, (62%) were predominantly heavily immunocompromised;on either high dose Mycophenolate (at least 720 mg twice daily) in addition to standard Calcineurin inhibitor/Sirolimus +\- Prednisone), or had received high dose Thymoglobulin (6 mg/kg or more) within a year of vaccination. This contrasts to published reports of over 95% immunological responsiveness or viral neutralization after the second vaccination dose among immunocompetent patients. Conclusion(s): Induction therapy with Anti-Thymocyte globulin and maintenance immunosuppression with Mycophenolate serve as the cornerstone of transplantation management. However, their utilization impacts B cell proliferation which is hypothesized to reduce antibody production and the effectiveness of the SARS-CoV-2 vaccine in transplant patients. This finding supports the need for a third or possibly fourth booster dose to achieve a sustained and effective response in combination with ongoing immunological surveillance post-vaccination among transplant patients.

Transplant Graft TMA Injury Post COVID-19 Vaccination

Vaccination against SARS-CoV-2 is essential. Complicating this effort are reports of a suboptimal response to the SARS-CoV-2 spike protein in patients on immunosuppressive medications and possible thrombotic microangiopathy (TMA) in renal transplant patients. 48-year-old male who received a living unrelated transplant in 2015. Pre-operative creatinine was 10.42 mg/dL and decreased to 2.48 mg/dL within a week. Patient received Basiliximab induction and maintained on tacrolimus and mycophenolate (MMF). One month post-transplant patient was diagnosed with TMA. Tacrolimus was stopped and patient was switched to Sirolimus and continued on MMF. Patient was followed closely by transplant nephrology for the next 5 years with a baseline creatinine of 1.9 mg/dL, protein to creatinine ratio below 0.5 mg/mg and well controlled diabetes. No DSA Class I or II detected on regular testing. Patient was compliant with all prescribed medications. On January 25 2021 patient received Pfizer Vaccine. Second Pfizer vaccine administered on February 18 2021. A week later creatinine was noted to be 3.44 mg/dL. Repeat creatinine of 4.27 mg/dL. Biopsy revealed diffuse lymphocytic interstitial inflammation, peritubular capillaritis, and C4D negative. Findings consistent with chronic TMA. DSA testing revealed Class II DSA:DQ2 (SI- 5933), Allosure 1.2 %. BK < 500 and CMV undetected. Patient received therapeutic plasma exchange, IV Ig infusion and steroids while on MMF and sirolimus. His creatinine decreased to 2.9 mg/dL on discharge. Over the next 6 months graft function deteriorated. He is now CKD stage 5 and under evaluation for a second transplant. There are case reports of COVID-19 vaccine administration and transplant graft dysfunction. A possible mechanism involves the mRNA lipid nanoparticle-encapsulated platform producing such a robust CD4 and CD8 T-cell response that pro-inflammatory cytokines are activated or that immune complex associated glomerular disease occurs resulting in the development of TMA in susceptible patients. A possible link between SARS CoV-2 vaccination and kidney transplant TMA warrants the implementation of close surveillance of vaccinated transplant patients, particularly susceptible individuals. More research is needed to determine if this link exists.

Pericardial Effusion: A Potential Late Complication of COVID-19 Infection

COVID-19 infection involves entry of SARS-CoV-2 virus into cells via interaction between its spike protein and angiotensin converting enzyme resulting in an NF-kB mediated inflammatory response. Cardiac manifestations without pulmonary symptoms is uncommon but has been described in the literature during an acute infection. We report a rare case of a potential late cardiac complication months after an acute COVID-19 infection. 62-year-old male with hypertension and end stage renal disease on hemodialysis three times a week. Patient presented with fever, arthralgia and myalgia. He denied chest pain or respiratory symptoms. Patient tested positive for COVID-19 and received only treatment of symptoms. Over the next nine months he reported persistent fatigue and new onset of shortness of breath. He continued dialysis without interruption. His symptoms progressed resulting in hospital admission. All laboratory investigations, including BUN (27mg/dL), were within normal limits. Chest Xray revealed cardiomegaly. Echocardiogram showed a large pericardial effusion without tamponade. Pericardiocentesis was accomplished with removal of 1700 ml of bloody fluid. Cell count, LDH, protein and glucose was normal. Fungal, viral, aerobic and anaerobic cultures of the pericardial fluid was negative. No malignant cells detected. Serial echocardiograms at 1, 3 and 5 months revealed a persistent small pericardial effusion. Cardiac manifestations of SARS-CoV-2 includes myocarditis, pericarditis and pericardial effusions. In case reports, the presence of the cardiac inflammatory state occurred simultaneously with an acute COVID-19 infection. In our case the COVID-19 infection occurred over nine months earlier yet remains a plausible explanation for his hemorrhagic pericardial effusion due to the absence of other identified causes. Further, COVID-19 molecular PCR testing of pericardial testing remains low yield due to its specific development for nasopharyngeal swab sampling. Cardiac manifestations of SARS-CoV-2 infection typically occur at the time of diagnosis. A late cardiac complication of COVID-19 may include pericardial inflammation with effusion. Further data and testing needs to be developed to confirm the diagnosis and guide therapy.

Criteria and practice patterns for accepting living donors with prior COVID-19: A national survey

Purpose: A critical question facing transplant programs is if, when and how to safely accept living kidney donors (LKD) who have a history and recovered from COVID-19 Infection. The purpose of the study is to understand current practices related to accepting living donors for donation who have recovered from COVID-19. Methods: We surveyed US transplant programs from September 3, 2020 through November 3, 2020 by e-mail and postings to professional society list-serves. Center level as well individual opinion based responses were analyzed. Results: A total of 174 US respondents from 115 unique centers responded, representing 59% of US Living Donor Programs and 72.4% of 2019 and 71.9% of 2020 LKD volume (as of October 31, 2020). Respondent Roles included Nephrologist (53.4%);Surgeon (19.5%);Infectious Disease (11.5%);Coordinator (9.8%). Overall during the survey period, 48.6% of responding centers had received inquiries from such LKDs, while 44.3% were currently evaluating such donors. A total of 98 donors were reported to be in the evaluation phase, while 27.8% centers had approved a total of 42 such donors to proceed with donation. Conclusions: Selection practices and criteria for LKD who have recovered from COVID-19 are variable. Ongoing research and consensus building are needed to guide optimal practices to ensure the safety of accepting such donors.

Epidemiology, risk, myths, pharmacotherapeutic management and socio-economic burden due to novel covid-19: A recent update

The novel human coronavirus disease (COVID-19) is the major pandemic throughout the globe and its occurrence is due to the presence of severe acute respiratory syndrome coronavirus (SARS-CoV2). That began from Wuhan, Hubei province of China in late 2019 and afterward drastically spread worldwide. It effects around 213 countries and territories around the globe and have reported a total of 8,128,490 confirmed cases of COVID-19. As an unprecedented global pandemic it sweeps the planet and affects each and every human being either physically, mentally or economically. The most common symptoms of COVID-19 are pyrexia, tiredness, and dry cough but in some cases it is asymptomatic. It can be diagnosed by a health care provider based on symptoms and confirmed through laboratory tests. Till date there is not even a single drug or vaccine that can be used for the effective treatment for this disease. The international community is to introduce a global synchronized strength to prevent the outbreak that needs a strong public health response, high level political commitment and sufficient funding. The aim of this review article is to summarise the recent state of awareness, epidemiology and social impact on surrounding due to outbreak of COVID-19 pandemic.