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

Abstract

Clinical outcomes in solid organ transplant (SOT) recipients with breakthrough COVID (BTCo) after two doses of mRNA vaccination compared to the non-immunocompromised/immunosuppressed (ISC) general population, are not well described. In a cohort of adult patients testing positive for COVID-19 between December 10, 2020 and April 4, 2022, we compared the cumulative incidence of BTCo in a non-ISC population to SOT recipients (overall and by organ type) using the National COVID Cohort Collaborative (N3C) including data from 36 sites across the United States. We assessed the risk of complications post-BTCo in vaccinated SOT recipients versus SOT with unconfirmed vaccination status (UVS) using multivariable Cox proportional hazards and logistic regression. BTCo occurred in 4776 vaccinated SOT recipients over a median of 149 days (IQR 99-233), with the highest cumulative incidence in heart recipients. The relative risk of BTCo was greatest in SOT recipients (relative to non-ISC) during the pre-Delta period (HR 2.35, 95% CI 1.80-3.08). The greatest relative benefit with vaccination for both non-ISC and SOT cohorts was in BTCo mortality (HR 0.37, 95% CI 0.36-0.39 for non-ISC; HR 0.67, 95% 0.57-0.78 for SOT relative to UVS). While the relative benefit of vaccine was less in SOT than non-ISC, SOT patients still exhibited significant benefit with vaccination.

Keywords: COVID-19; MACE; MARCE; SARS-CoV-2; allograft type; breakthrough; cardiac; heart; infection; kidney; liver; lung; mortality; outcome; solid organ transplantation; vaccination.

FIGURE 1

The cumulative incidence of COVID-19 breakthrough infection in the 6 months postVAX2 in the non-ISC population and in the SOT cohort by organ type. ISC, immunosuppressed/immunocompromised.

FIGURE 2

The proportion of non-immunosuppressed, all solid organ transplant, and organ specific transplant (kidney, liver, lung, heart) patients who experienced adverse outcomes in the 90 days after COVID-19 infection in those with two doses of mRNA or one dose of Johnson & Johnson (VAX2). ISC, immunosuppressed/immunocompromised; SOT, solid organ transplant; MARCE, major adverse renal or cardiac event; MACE, major adverse cardiac event; AKI, acute kidney injury; ECMO, extracorporeal membrane oxygenation.

FIGURE 3

The adjusted relative hazard ratios for adverse outcomes after COVID-19 infection in VAX2 non-ISC patients and SOT recipients relative to those with unconfirmed vaccination status. ISC, immunosuppressed/immunocompromised; SOT, solid organ transplant; MARCE, major adverse renal or cardiac event; MACE, major adverse cardiac event; AKI, acute kidney injury; ECMO, extracorporeal membrane oxygenation; HR, hazard ratio; OR, odds ratio.