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.