Preprint Chronic Viral Reactivation and Associated Host Immune Response and Clinical Outcomes in Acute COVID-19 and [PASC], 2024, Maguire+

[SNT Gatchaman]

Chronic Viral Reactivation and Associated Host Immune Response and Clinical Outcomes in Acute COVID-19 and Post-Acute Sequelae of COVID-19

Spoiler: 58 Authors

Cole Maguire; Jing Chen; Nadine Rouphael; Harry Pickering; Hoang Van Phan; Abigail Glascock; Victoria Chu; Ravi Dandekar; David Corry; Farrah Kheradmand; Lindsey R. Baden; Rafick Selaky; Grace A. McComsey; Elias K. Haddad; Charles B. Cairns; Bali Pulendran; Ana Fernandez-Sesma; Viviana Simon; Jordan P. Metcalf; Nelson I. Agudelo Higuita; William B. Messer; Mark M. David; Kari C. Nadeau; Monica Kraft; Chris Bime; Joanna Schaenman; David Erle; Carolyn S. Calfee; Mark A. Atkinson; Scott C. Brackenridge; Lauren I. R. Ehrlich; Ruth R. Montgomery; Albert C. Shaw; Catherine L. Hough; Linda N. Geng; David A. Hafler; Alison D. Augustine; Patrice M. Becker; Bjoern Peters; Al Ozonoff; Seunghee H. Kim-Schulze; Florian Krammer; Steve Bosinger; Walter Eckalbar; Matthew C. Altman; Michael Wilson; Leying Guan; Steven H. Kleinstein; IMPACC Network; Kinga K. Smolen; Elaine F. Reed; Ofer Levy; Holden Maecker; Peter Hunt; Hanno Steen; Joann Diray-Arce; Charles R. Langelier; Esther Melamed

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.


Link | PDF (Preprint: BioRxiv) [Open Access]

 

[Turtle]

Wow!!!

Could I have a virus passport please?

Maybe there are some good subgroup ideas for ME/CFS too in this paper.

I'll isolate as much as I can, not adding Covid to my virus-passport.

 

[Murph]

this is by Kathryn Melamed, now of UT Austin. She was publishing on me/cfs before covid, with systrom:

https://www.s4me.info/threads/unexp...traction-2019-by-melamed-systrom-et-al.11176/

This paper has impressive scale. It particularly finds persistent anelloviruses, and there was an interesting paper on one of them quite recently:

https://www.s4me.info/threads/over-representation-of-torque-teno-mini-virus-9-ttmv9-in-a-subgroup-of-patients-with-me-cfs-2024-giménez-orenga-oltra-et-al.39619/#post-546478

They're ubiquitous in humans but not (yet) known to cause disease directly. They are more often used as markers of immune function (e.g. in this paper high annellovirus shows immune systems damaged by HIV and then low virus shows recovery from HIV)

 

[duncan]

It's possible this study inadvertently demonstrates a concept of immune tolerance, and by extension, its implications. I am not referring to it as it pertains to protecting embryos. In some circles, in theory at least - and if I'm not mistaken - this framing of immune tolerance relates to how it can potentially ensue following a viral infection. It allows for the eventual tolerance of that pathogen while awakening latent viruses, and wholly or partly muting immune responses normally generated by the host [that are typically mined through lab work].

In effect, it gives rise to a sort of antigen-triggered immunodeficiency - but without any of the usual conventional immune signatures. I think a key here is appreciating that with this theory, it's not the complete absence of an immune response, but rather its suppression.

I find it an interesting idea, although I\m not sure I buy into it. I think it was more fashionable in some veterinary circles back in the late 40's and 50's.

ETA: If there is merit to the concept, I suspect it becoming unfashionable in conventional medical circles had more to do with politics than science.