SARS-CoV-2 lineage-dependent temporal phylogenetic distribution and viral load in immunocompromised and immunocompetent individuals.

OBJECTIVES

Mutational dynamics of SARS-CoV-2 in immunocompromised hosts, although well documented, remain a relatively unexplored mechanism. This study aims to compare the viral replication load and genetic diversity of SARS-CoV-2 in immunocompromised patients and non-immunocompromised individuals (NICs) from two major hospitals in Paris from January 2021 to May 2023.

METHODS

Cycle threshold (CT) values were measured by TaqPath COVID-19 RT-PCR (Thermo Fisher Scientific). The SARS-CoV-2 whole-genomes from 683 immunocompromised patients and 296 NICs was sequenced using Oxford Nanopore Technologies and used to determine lineage and mutational profile.

RESULTS

All immunocompromised patients, but not oncology patients, had lower SARS-CoV-2 viral loads than NICs. The genetic distribution of SARS-CoV-2 was homogeneous between immunocompromised individuals and NICs, with more mutations in immunocompromised patients (IRR = 1,013). Indeed, extensive genomic analysis revealed several mutations specifically associated with immunosuppression status, such as S: T95I, S:N764K, M:Q19E and ORF10:L37F. Conversely, the S: R346K and NSP13:T127N mutations were more common in NICs.

CONCLUSION

Immunocompromised patients have lower viral loads, probably due to their later diagnosis compared to NICs and oncology patients, who have better access to on-site SARS-CoV-2 testing and follow-up. In addition, mutational profiles differ between the two groups, with immunocompromised hosts accumulating more mutations compared to NICs.