Sex and organ-specific risk of major adverse renal or cardiac events in solid organ transplant recipients with COVID-19

Abstract

While older males are at the highest risk for poor coronavirus disease 2019 (COVID‐19) outcomes, it is not known if this applies to the immunosuppressed recipient of a solid organ transplant (SOT), nor how the type of allograft transplanted may impact outcomes. In a cohort study of adult (>18 years) patients testing positive for COVID‐19 (January 1, 2020‐June 21, 2021) from 56 sites across the United States identified using the National COVID Cohort Collaborative (N3C) Enclave, we used multivariable Cox proportional hazards models to assess time to MARCE after COVID‐19 diagnosis in those with and without SOT. We examined the exposure of age‐stratified recipient sex overall and separately in kidney, liver, lung, and heart transplant recipients. 3996 (36.4%) SOT and 91 646 (4.8%) non‐SOT patients developed MARCE. Risk of post‐COVID outcomes differed by transplant allograft type with heart and kidney recipients at highest risk. Males with SOT were at increased risk of MARCE, but to a lesser degree than the non‐SOT cohort (HR 0.89, 95% CI 0.81–0.98 for SOT and HR 0.61, 95% CI 0.60–0.62 for non‐SOT [females vs. males]). This represents the largest COVID‐19 SOT cohort to date and the first‐time sex‐age–stratified and allograft‐specific COVID‐19 outcomes have been explored in those with SOT.

The risk and consequences of breakthrough SARS-CoV-2 infection in solid organ transplant recipients relative to non-immunosuppressed controls

“…We have previously shown that in the pre‐vaccine era, the outcomes after COVID‐19 infection vary by SOT type, with heart and kidney recipients at the greatest risk for most complications. 8 A later study examined the differential antibody response to a second dose of the mRNA vaccine in SOT recipients by organ type, and demonstrated the lowest seroconversion rate in heart (18.8%), followed by kidney (45.5%), and liver (69.4%) recipients. However, the total SOT included in the study was only 226, and lung transplant recipients were not included, with no assessment of clinical outcomes following vaccination.…”

“…Outcomes after BTCo included MARCE defined as a composite of acute kidney injury (AKI) with or without dialysis, acute myocardial infarction, angina, stent occlusion/thrombosis, stroke, transient ischemic attack, congestive heart failure or death from any cause, 8 major adverse cardiac events (MACE) in isolation, renal failure requiring dialysis or AKI not requiring dialysis, death from any cause, hospitalization, and severe COVID‐19 (including need for ventilation, extra corporeal membrane oxygenation [ECMO], or death) in the 90 days following COVID‐19 diagnosis. In the SOT population, we also examined the outcomes of acute rejection and graft loss.…”

“… 7 The risk of post‐COVID outcomes differs by organ type, with heart and kidney recipients at the highest risk of MARCE, and lung and heart recipients at the highest risk of organ rejection. 8 , 9 …”

“…7 The risk of post-COVID outcomes differs by organ type, with heart and kidney recipients at the highest risk of MARCE, and lung and heart recipients at the highest risk of organ rejection. 8,9 COVID-19 vaccines, which developed rapidly over the first year of the pandemic, have proved remarkably effective in the general population, including the elderly and those with comborbidities [10][11][12] ; however, the benefit of vaccination in immunosuppressed SOT has been questioned. Although SOT recipients appear to mount an adequate humoral response to natural SARS-CoV-2 infection, poor anti-spike antibody responses to mRNA vaccination in SOT recipients have been reported (e.g., 46%-97.4% non-response after the second dose).…”

Immune Response to SARS-CoV-2 Vaccine among Heart Transplant Recipients: A Systematic Review

“…Heart transplant (HTX) recipients constitute a high-risk population of patients in the setting of COVID-19. 7 - 9 In addition to harboring higher number of comorbidities, 10 HTX patients have a suppressed immune state, which has been a controversial risk factor for the development of more severe COVID-19 or poor clinical outcomes. 7 , 8 , 11 …”