Virol J
. 2025 Apr 25;22(1):118.
doi: 10.1186/s12985-025-02711-z. SARS-CoV-2 lineage-dependent temporal phylogenetic distribution and viral load in immunocompromised and immunocompetent individuals
Karen Zafilaza 1 , Antoine Fauchois 2 , Valentin Leducq 2 , Romain Coppée 3 4 , Romane Guilbaud 3 , Anna-Maria Franco Yusti 3 , Eve Todesco 2 , Antoine Bridier-Nahmias 3 , Quentin Le Hingrat 3 , Sylvain Choquet 5 , Patrice Cacoub 6 , Zahir Amoura 7 , Benoit Barrou 8 , Valérie Pourcher 9 , Jean-Philippe Spano 10 , Martine Louet 11 , Laura Kramer 12 , Tiphaine Goulenok 13 , Mathilde Salpin 14 , Eric Daugas 15 , Richard Dorent 16 , Sébastien Ottaviani 17 , Gérard Zalcman 18 , Jade Ghosn 3 19 , Charlotte Charpentier 3 , Diane Descamps 3 , Anne-Geneviève Marcelin 2 , Vincent Calvez 2 , Valentine Marie Ferre 3 , Stéphane Marot # 2 , Cathia Soulie # 2
Affiliations
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.
Keywords: Immunocompromised host; SARS-CoV-2; Single mutation analysis; Viral load; Whole-Genome sequencing.
. 2025 Apr 25;22(1):118.
doi: 10.1186/s12985-025-02711-z. SARS-CoV-2 lineage-dependent temporal phylogenetic distribution and viral load in immunocompromised and immunocompetent individuals
Karen Zafilaza 1 , Antoine Fauchois 2 , Valentin Leducq 2 , Romain Coppée 3 4 , Romane Guilbaud 3 , Anna-Maria Franco Yusti 3 , Eve Todesco 2 , Antoine Bridier-Nahmias 3 , Quentin Le Hingrat 3 , Sylvain Choquet 5 , Patrice Cacoub 6 , Zahir Amoura 7 , Benoit Barrou 8 , Valérie Pourcher 9 , Jean-Philippe Spano 10 , Martine Louet 11 , Laura Kramer 12 , Tiphaine Goulenok 13 , Mathilde Salpin 14 , Eric Daugas 15 , Richard Dorent 16 , Sébastien Ottaviani 17 , Gérard Zalcman 18 , Jade Ghosn 3 19 , Charlotte Charpentier 3 , Diane Descamps 3 , Anne-Geneviève Marcelin 2 , Vincent Calvez 2 , Valentine Marie Ferre 3 , Stéphane Marot # 2 , Cathia Soulie # 2
Affiliations
- PMID: 40281619
- PMCID: PMC12023422
- DOI: 10.1186/s12985-025-02711-z
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.
Keywords: Immunocompromised host; SARS-CoV-2; Single mutation analysis; Viral load; Whole-Genome sequencing.