Early Immune Factors Associated With the Development of Post-Acute Sequelae of SARS-CoV-2 Infection in Hospitalized and Non-Hospitalized Individuals

Authors

Jacqueline M Leung
Michelle J Wu
Pouya Kheradpour
Chen Chen
Katherine A Drake
Gary Tong
Vanessa K Ridaura
Howard C Zisser
William A Conrad
Natalia Hudson
Jared Allen
Christopher Welberry
Celine Parsy-Kowalska
Isabel Macdonald
Victor F Tapson
James N Moy
Christopher R deFilippi
Ivan O Rosas
Mujeeb Basit
Jerry A Krishnan
Sairam Parthasarathy
Bellur S Prabhakar
Mirella Salvatore
Charles C Kim

Publication Date

1-1-2024

Journal

Frontiers in Immunology

DOI

10.3389/fimmu.2024.1348041

PMID

38318183

PMCID

PMC10838987

PubMedCentral® Posted Date

1-22-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, COVID-19, SARS-CoV-2, Post-Acute COVID-19 Syndrome, Immunologic Factors, Autoantibodies, Disease Progression, COVID-19, PASC, long COVID, autoantibody, double-negative B cells

Abstract

BACKGROUND: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown.

METHODS: We enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood samples collected shortly after study enrollment to investigate early immune signatures associated with the development of PASC.

RESULTS: During the first week of COVID-19, we observed a large number of differences in the immune profile of individuals who were hospitalized for COVID-19 compared to those individuals with COVID-19 who were not hospitalized. Differences between individuals who did or did not later develop PASC were, in comparison, more limited, but included significant differences in autoantibodies and in epigenetic and transcriptional signatures in double-negative 1 B cells, in particular.

CONCLUSIONS: We found that early immune indicators of incident PASC were nuanced, with significant molecular signals manifesting predominantly in double-negative B cells, compared with the robust differences associated with hospitalization during acute COVID-19. The emerging acute differences in B cell phenotypes, especially in double-negative 1 B cells, in PASC patients highlight a potentially important role of these cells in the development of PASC.

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