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1.
Am J Transplant ; 20(11): 3149-3161, 2020 11.
Article in English | MEDLINE | ID: covidwho-835285

ABSTRACT

Whether kidney transplant recipients are capable of mounting an effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adaptive immune response despite chronic immunosuppression is unknown and has important implications for therapy. Herein, we analyzed peripheral blood cell surface and intracellular cytokine phenotyping by flow cytometry along with serum antibody testing in 18 kidney transplant recipients with active coronavirus disease 2019 (COVID-19) infection and 36 matched, transplanted controls without COVID-19. We observed significantly fewer total lymphocytes and fewer circulating memory CD4+ and CD8+ T cells in the COVID-19 subjects. We also showed fewer anergic and senescent CD8+ T cells in COVID-19 individuals, but no differences in exhausted CD8+ T cells, nor in any of these CD4+ T cell subsets between groups. We also observed greater frequencies of activated B cells in the COVID-19 patients. Sixteen of 18 COVID-19 subjects tested for anti-SARS-CoV-2 serum antibodies showed positive immunoglobulin M or immunoglobulin G titers. Additional analyses showed no significant correlation among immune phenotypes and degrees of COVID-19 disease severity. Our findings indicate that immunosuppressed kidney transplant recipients admitted to the hospital with acute COVID-19 infection can mount SARS-CoV-2-reactive adaptive immune responses. The findings raise the possibility that empiric reductions in immunosuppressive therapy for all kidney transplant recipients with active COVID-19 may not be required.


Subject(s)
COVID-19/epidemiology , Immunity, Humoral , Immunocompromised Host , Kidney Transplantation/adverse effects , Pandemics , Renal Insufficiency/epidemiology , Transplant Recipients , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Comorbidity , Female , Humans , Male , Middle Aged , Renal Insufficiency/surgery , Retrospective Studies , SARS-CoV-2 , United States/epidemiology
2.
Am J Transplant ; 20(11): 3140-3148, 2020 11.
Article in English | MEDLINE | ID: covidwho-638753

ABSTRACT

Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID-19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID-19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID-19 during the 9-week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow-up period of 52 days (IQR: 16-66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin-6 levels. In sum, hospitalized kidney transplant recipients with COVID-19 have higher rates of acute kidney injury and mortality.


Subject(s)
COVID-19/epidemiology , Graft Rejection/prevention & control , Immunosuppression Therapy/methods , Kidney Transplantation/statistics & numerical data , Pandemics , SARS-CoV-2 , Transplant Recipients , Aged , Comorbidity , Europe/epidemiology , Female , Follow-Up Studies , Graft Rejection/epidemiology , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , North America/epidemiology , Retrospective Studies
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