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Chronic Viral Reactivation and Associated Host Immune Response and Clinical Outcomes in Acute COVID-19 and Post-Acute Sequelae of COVID-19
bioRxiv
16 Nov 2024
PMID: 39605478
Abstract
Chronic viral infections are ubiquitous in humans, with individuals harboring multiple latent viruses that can reactivate during acute illnesses. Recent studies have suggested that SARS- CoV-2 infection can lead to reactivation of latent viruses such as Epstein-Barr Virus (EBV) and cytomegalovirus (CMV), yet, the extent and impact of viral reactivation in COVID-19 and its effect on the host immune system remain incompletely understood. Here we present a comprehensive multi-omic analysis of viral reactivation of all known chronically infecting viruses in 1,154 hospitalized COVID-19 patients, from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, who were followed prospectively for twelve months. We reveal significant reactivation of Herpesviridae , Enteroviridae , and Anelloviridae families during acute stage of COVID-19 (0-40 days post- hospitalization), each exhibiting distinct temporal dynamics. We also show that viral reactivation correlated with COVID-19 severity, demographic characteristics, and clinical outcomes, including mortality. Integration of cytokine profiling, cellular immunophenotyping, metabolomics, transcriptomics, and proteomics demonstrated virus-specific host responses, including elevated pro-inflammatory cytokines (e.g. IL-6, CXCL10, and TNF), increased activated CD4+ and CD8+ T-cells, and upregulation of cellular replication genes, independent of COVID-19 severity and SARS-CoV-2 viral load. Notably, persistent Anelloviridae reactivation during convalescence (≥3 months post-hospitalization) was associated with Post-Acute Sequelae of COVID-19 (PASC) symptoms, particularly physical function and fatigue. Our findings highlight a remarkable prevalence and potential impact of chronic viral reactivation on host responses and clinical outcomes during acute COVID-19 and long term PASC sequelae. Our data provide novel immune, transcriptomic, and metabolomic biomarkers of viral reactivation that may inform novel approaches to prognosticate, prevent, or treat acute COVID- 19 and PASC.Chronic viral infections are ubiquitous in humans, with individuals harboring multiple latent viruses that can reactivate during acute illnesses. Recent studies have suggested that SARS- CoV-2 infection can lead to reactivation of latent viruses such as Epstein-Barr Virus (EBV) and cytomegalovirus (CMV), yet, the extent and impact of viral reactivation in COVID-19 and its effect on the host immune system remain incompletely understood. Here we present a comprehensive multi-omic analysis of viral reactivation of all known chronically infecting viruses in 1,154 hospitalized COVID-19 patients, from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, who were followed prospectively for twelve months. We reveal significant reactivation of Herpesviridae , Enteroviridae , and Anelloviridae families during acute stage of COVID-19 (0-40 days post- hospitalization), each exhibiting distinct temporal dynamics. We also show that viral reactivation correlated with COVID-19 severity, demographic characteristics, and clinical outcomes, including mortality. Integration of cytokine profiling, cellular immunophenotyping, metabolomics, transcriptomics, and proteomics demonstrated virus-specific host responses, including elevated pro-inflammatory cytokines (e.g. IL-6, CXCL10, and TNF), increased activated CD4+ and CD8+ T-cells, and upregulation of cellular replication genes, independent of COVID-19 severity and SARS-CoV-2 viral load. Notably, persistent Anelloviridae reactivation during convalescence (≥3 months post-hospitalization) was associated with Post-Acute Sequelae of COVID-19 (PASC) symptoms, particularly physical function and fatigue. Our findings highlight a remarkable prevalence and potential impact of chronic viral reactivation on host responses and clinical outcomes during acute COVID-19 and long term PASC sequelae. Our data provide novel immune, transcriptomic, and metabolomic biomarkers of viral reactivation that may inform novel approaches to prognosticate, prevent, or treat acute COVID- 19 and PASC.
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Details
- Title
- Chronic Viral Reactivation and Associated Host Immune Response and Clinical Outcomes in Acute COVID-19 and Post-Acute Sequelae of COVID-19
- Creators
- Cole Maguire - The University of Texas at AustinJing Chen - Boston Children's HospitalNadine Rouphael - Emory UniversityHarry Pickering - University of California, Los AngelesHoang Van PhanAbigail Glascock - Chan Zuckerberg Initiative (United States)Victoria Chu - University of California, San FranciscoRavi Dandekar - University of California, San FranciscoDavid Corry - Baylor College of MedicineFarrah Kheradmand - Baylor College of MedicineLindsey R Baden - Brigham and Women's HospitalRafick Selaky - University Hospitals of ClevelandGrace A McComsey - University Hospitals of ClevelandElias K Haddad - Drexel UniversityCharles B Cairns - Drexel UniversityBali Pulendran - Palo Alto UniversityAna Fernandez SesmaViviana Simon - Icahn School of Medicine at Mount SinaiJordan P Metcalf - University of Oklahoma Health Sciences CenterNelson I Agudelo HiguitaWilliam B Messer - Oregon Health & Science UniversityMark M DavidKari C Nadeau - Stanford UniversityMonica Kraft - University of ArizonaChris Bime - University of ArizonaJoanna Schaenman - University of California, Los AngelesDavid Erle - University of California, San FranciscoCarolyn S Calfee - University of California, San FranciscoMark A Atkinson - University of FloridaScott C Brackenridge - University of FloridaLauren I R Ehrlich - The University of Texas at AustinRuth R Montgomery - Yale UniversityAlbert C Shaw - Yale UniversityCatherine L Hough - Oregon Health & Science UniversityLinda N Geng - Stanford UniversityDavid A Hafler - Yale UniversityAlison D Augustine - National Institute of Allergy and Infectious DiseasesPatrice M Becker - National Institute of Allergy and Infectious DiseasesBjoern Peters - La Jolla Institute for ImmunologyAl Ozonoff - Boston Children's HospitalSeunghee Hee Kim-Schulze - Icahn School of Medicine at Mount SinaiFlorian Krammer - Icahn School of Medicine at Mount SinaiSteve Bosinger - Emory UniversityWalter Eckalbar - University of California, San FranciscoMatthew C Altman - University of WashingtonMichael Wilson - University of California, San FranciscoLeying Guan - Yale UniversitySteven H Kleinstein - Yale UniversityKinga K Smolen - Boston Children's HospitalElaine F Reed - University of California, Los AngelesOfer Levy - Broad InstituteHolden Maecker - Stanford UniversityPeter Hunt - University of California, San FranciscoHanno Steen - Boston Children's HospitalJoann Diray-Arce - Boston Children's HospitalCharles R Langelier - University of California, San FranciscoEsther Melamed - The University of Texas at AustinIMPACC Network
- Publication Details
- bioRxiv
- Publisher
- American Physical Society (APS)
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Emergency Medicine
- Other Identifier
- 991021969000704721