{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Marques AD"],"funding":["HHS | National Institutes of Health","Penn Center for Global Genomics","NIAID NIH HHS","NHLBI NIH HHS","HHS | Centers for Disease Control and Prevention","Penn Center for Research on Coronaviruses and Other Emerging Pathogens"],"pagination":["e0011024"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10936176"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(3)"],"pubmed_abstract":["Prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients provides an opportunity for viral evolution, potentially leading to the generation of new pathogenic variants. To investigate the pathways of viral evolution, we carried out a study on five patients experiencing prolonged SARS-CoV-2 infection (quantitative polymerase chain reaction-positive for 79-203 days) who were immunocompromised due to treatment for lymphoma or solid organ transplantation. For each timepoint analyzed, we generated at least two independent viral genome sequences to assess the heterogeneity and control for sequencing error. Four of the five patients likely had prolonged infection; the fifth apparently experienced a reinfection. The rates of accumulation of substitutions in the viral genome per day were higher in hospitalized patients with prolonged infection than those estimated for the community background. The <i>spike</i> coding region accumulated a significantly greater number of unique mutations than other viral coding regions, and the mutation density was higher. Two patients were treated with monoclonal antibodies (bebtelovimab and sotrovimab); by the next sampled timepoint, each virus population showed substitutions associated with monoclonal antibody resistance as the dominant forms (<i>spike</i> K444N and <i>spike</i> E340D). All patients received remdesivir, but remdesivir-resistant substitutions were not detected. These data thus help elucidate the trends of emergence, evolution, and selection of mutational variants within long-term infected immunocompromised individuals.<h4>Importance</h4>SARS-CoV-2 is responsible for a global pandemic, driven in part by the emergence of new viral variants. Where do these new variants come from? One model is that long-term viral persistence in infected individuals allows for viral evolution in response to host pressures, resulting in viruses more likely to replicate efficiently in humans. In this study, we characterize replication in several hospitalized and long-term infected individuals, documenting efficient pathways of viral evolution."],"journal":["mBio"],"pubmed_title":["SARS-CoV-2 evolution during prolonged infection in immunocompromised patients."],"pmcid":["PMC10936176"],"funding_grant_id":["K23 AI 121485","CDC BAA 200-2021-10986, 75D30121C11102/000HCVL1-2021-55232","R33 HL137063","K23 AI121485","R01 AI140442","P30 AI045008","R61 HL137063","GGHE-KP-2021-001","R61/33-HL137063, AI140442-supplement for SARS-CoV-2, P30-AI045008"],"pubmed_authors":["Rodino KG","Bushman FD","Moncla LH","Marques AD","Cook EJ","Graham-Wooten J","Fitzgerald AS","Collman RG","Sobel Leonard A","Kelly BJ","Everett JK"],"additional_accession":[]},"is_claimable":false,"name":"SARS-CoV-2 evolution during prolonged infection in immunocompromised patients.","description":"Prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in immunocompromised patients provides an opportunity for viral evolution, potentially leading to the generation of new pathogenic variants. To investigate the pathways of viral evolution, we carried out a study on five patients experiencing prolonged SARS-CoV-2 infection (quantitative polymerase chain reaction-positive for 79-203 days) who were immunocompromised due to treatment for lymphoma or solid organ transplantation. For each timepoint analyzed, we generated at least two independent viral genome sequences to assess the heterogeneity and control for sequencing error. Four of the five patients likely had prolonged infection; the fifth apparently experienced a reinfection. The rates of accumulation of substitutions in the viral genome per day were higher in hospitalized patients with prolonged infection than those estimated for the community background. The <i>spike</i> coding region accumulated a significantly greater number of unique mutations than other viral coding regions, and the mutation density was higher. Two patients were treated with monoclonal antibodies (bebtelovimab and sotrovimab); by the next sampled timepoint, each virus population showed substitutions associated with monoclonal antibody resistance as the dominant forms (<i>spike</i> K444N and <i>spike</i> E340D). All patients received remdesivir, but remdesivir-resistant substitutions were not detected. These data thus help elucidate the trends of emergence, evolution, and selection of mutational variants within long-term infected immunocompromised individuals.<h4>Importance</h4>SARS-CoV-2 is responsible for a global pandemic, driven in part by the emergence of new viral variants. Where do these new variants come from? One model is that long-term viral persistence in infected individuals allows for viral evolution in response to host pressures, resulting in viruses more likely to replicate efficiently in humans. In this study, we characterize replication in several hospitalized and long-term infected individuals, documenting efficient pathways of viral evolution.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-07-01T03:21:44.081Z","creation":"2026-07-01T03:07:42.352Z"},"accession":"S-EPMC10936176","cross_references":{"pubmed":["38364100"],"doi":["10.1128/mbio.00110-24"]}}