SARS-CoV-2 evolution among patients with immunosuppression in a nosocomial cluster of a Japanese medical center during the Delta (AY.29 sublineage) surge

BACKGROUND: Previous studies have shown that patients with immunosuppression tend to have longer-lasting SARS-CoV-2 infections and a number of mutations were observed during the infection period. However, these studies were, in general, conducted longitudinally. Mutation evolution among groups of patients with immunosuppression have not been well studied, especially among Asian populations. METHODS: Our study targeted a nosocomial cluster of SARS-CoV-2 infection in a Japanese medical center during Delta surge (AY.29 sublineage), involving ward nurses and inpatients. Whole-genome sequencing analyses were performed to examine mutation changes. Haplotype and minor variant analyses were furtherly performed to detect the mutations on the viral genomes in detail. In addition, sequences of the first wild-type strain hCoV-19/Wuhan/WIV04/2019 and AY.29 wild-type strain hCoV-19/Japan/TKYK15779/2021 were used as references to assess the phylogenetical development of this cluster. RESULTS: A total of 6 nurses and 14 inpatients were identified as a nosocomial cluster from September 14 through 28, 2021. All were Delta variant (AY.29 sublineage) positive. 92.9% of infected patients (13 out of 14) were either cancer patients and/or receiving immunosuppressive or steroid treatments. Compared to AY.29 wild type, a total of 12 mutations were found in the 20 cases. Haplotype analysis found one index group of eight cases with F274F (N) mutation and 10 other haplotypes with one to three additional mutations. Furthermore, we found that cases with more than three minor variants were all cancer patients under immunosuppressive treatments. The phylogenetical tree analysis, including 20 nosocomial cluster-associated viral genomes, the first wild-type strain and the AY.29 wild-type strain as references, indicated the mutation development of the AY.29 virus in this cluster. CONCLUSION: Our study of a nosocomial SARS-CoV-2 cluster highlights mutation acquisition during transmission. More importantly, it provided new evidence emphasizing the need to further improve infection control measures to prevent nosocomial infection among immunosuppressed patients.