Multiparametric mapping of Covid-19 immune responses in Kidney transplant recipients

AbstractAs of May 2020, over five million confirmed cases of COVID-19 have been reported globally with over 400,000associated deaths. Around 5-20% of patients develop critical illness, which predominantly manifests as acuterespiratory distress syndrome. When this develops, the estimated mortality is around 40%, and as high as 80%in ventilated patients. Several early reports describe the development of an excessive inflammatory response,the so-called `cytokine storm', which is strongly associated with rapid deterioration in clinical condition andmortality.Early reports of kidney transplant recipients, who are at high risk due to chronic immunosuppression andadditional comorbid diseases, portray a concerning picture. In one series of 36 patients, 39% requiredmechanical ventilation, 21% required renal replacement therapy, and 28% died. Of the 11 patients that wereintubated, 64% died. However, there is still an unmet need of understanding disease natural course, specificrisk factors, identifying biomarkers, as well as potential impact of COVID-19 on graft/patient survival invulnerable KTRs. To fill this information gap, we propose a comprehensive observational analysis of epidemiological factors and immunological assay results in COVID19-infected KTRs at 2 medical centers atthe epicenter of COVID19 infection in NYC (Mount Sinai Hospital in Manhattan and Montefiore Hospital in theBronx). We hypothesize that specific recipient clinical characteristics affect COVID-19 clinical courseand that recipient immunosuppression in KTRs alters the ability of COVID-19 KTRs to developprotective anti-COVID-19 humoral and cell-mediated immunity that contributes to the morbidity andmortality of these individuals.We will test this hypothesis by 1) examining risk factors of COVID-19 severity in a large dataset of KTRs andindividuals from the general population with COVID-19 (aim 1); 2) by characterizing the COVID-19 reactivehumoral and cellular immune response in serially collected samples from COVID-19 KTRs (aim 2); and 3) bycomprehensive assessment of DNA and serial serum, RNA, and PBMC from COVID-19 KTRs to identifydisease mechanisms and potentially informative biomarkers for outcomes (aim 3).The proposed work is significant because of the high incidence of the disease, rate of community transmission,high mortality, and absence of clearly effective therapeutic options. Our studies will be amongst the first todefine risk factors, predictors, and pathogenic mechanisms of COVID-19 in Kidney transplantation and mayapply to recipients of other transplanted organs, as well as to individuals on chronic immunosuppression due toautoimmune diseases.