Reinfection of SARS-CoV-2 Variants in Immunocompromised Patients with Prolonged or Relapsed Viral Shedding

Immunocompromised patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection often have prolonged viral shedding, and some are clinically suspected of reinfection with different SARS-CoV-2 variants. However, data on this issue are limited. This study investigated the SARS-CoV-2 variants in serially collected respiratory samples from immunocompromised patients with prolonged viral shedding for over 12 weeks or relapsed viral shedding after at least 2 weeks of viral clearance.

From February 2022 to September 2023, we prospectively enrolled immunocompromised patients with coronavirus disease 2019 who had hematologic malignancies or had undergone transplantation and were admitted to a tertiary hospital. Weekly saliva or nasopharyngeal swabs were collected from enrolled patients for at least 12 weeks after diagnosis. Genomic RNA polymerase chain reaction (PCR) was performed on samples, and those testing positive underwent viral culture to isolate the live virus. Spike gene full sequencing via Sanger sequencing and real-time reverse transcription-PCR for detecting mutation genes were conducted to identify SARS-CoV-2 variants.

Among 116 enrolled patients, 20 with prolonged or relapsed viral shedding were screened to identify the variants. Of these 20 patients, 7 (35%) exhibited evidence of re-infection; one of 8 patients with prolonged viral shedding and 6 of 12 with relapsed viral shedding were reinfected with SARS-CoV-2.

Our data suggest that approximately one-third of immunocompromised patients with persistent or relapsed viral shedding had reinfection with different variants of SARS-CoV-2.