**2. Methods**

#### *2.1. Study Design*

This was a single-center retrospective cohort study that included all adult LTRs at the Henry Ford Transplant Institute, who were symptomatic and tested positive for SARS-CoV-2 with a real-time polymerase chain reaction (RT-PCR) test via a nasopharyngeal swab from March 2020 to March 2022. This study was approved by the Henry Ford Health System Institutional Review Board (#14948) and consent was waived.

## *2.2. Data Collection and Definitions*

Patient information was obtained by review of the electronic health records (EHR). Demographics, clinical characteristics, comorbidities, date and indication of transplantation, date of COVID-19 diagnosis, disease severity, and management were evaluated. COVID-19 vaccination data were obtained from the EHR and the Michigan Care Improvement Registry (MCIR), which reports COVID-19 vaccine administration. All patients were followed until 31 March 2022.

"COVID-19 severity" was defined as per the National Institutes of Health (NIH) COVID-19 guidelines [23]. "Vaccine-breakthrough infection" was defined as having COVID-19 diagnosed at least 14 days after the administration of a COVID-19 vaccine, i.e., a minimum of 2 doses of an mRNA vaccine [21]. The periods of activity in the United States of America (USA) of the various SARS-CoV-2 variants were based on the Center for Disease Control and Prevention (CDC) timeline [23]. The approximate periods of activity for the variants were: wild-type (March 2020–December 2021); Alpha (January 2021–April 2021); Delta (May 2021–December 2021); and Omicron (January 2022 onwards).
