Measurement of circulating viral antigens post-SARS-CoV-2 infection in a multicohort study

Swank Z 1 , Borberg E 1 , Chen Y 2 , Senussi Y 1 , Chalise S 1 , Manickas-Hill Z 3 Show all authors , Yu XG 4 , Li JZ 5 , Alter G 6 , Henrich TJ 7 , Kelly JD 8 , Hoh R 9 , Goldberg SA 10 , Deeks SG 9 , Martin JN 10 , Peluso MJ 9 , Talla A 11 , Li X 11 , Skene P 11 , Bumol TF 11 , Torgerson TR 11 , Czartoski JL 12 , McElrath MJ 12 , Karlson EW 13 , Walt DR 14 , RECOVER consortium authors

Affiliations 

  • 1 Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
  • 2 Harvard Medical School, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA
  • 3 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA
  • 4 Harvard Medical School, Boston, MA, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA
  • 5 Harvard Medical School, Boston, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA
  • 6 Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA
  • 7 Division of Experimental Medicine, University of California, San Francisco, CA, USA
  • 8 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, CA, USA; San Francisco VA Medical Center, San Francisco, CA, USA
  • 9 Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, CA, USA
  • 10 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
  • 11 Allen Institute for Immunology, Seattle, WA, USA
  • 12 Fred Hutchinson Cancer Center, Seattle, WA, USA
  • 13 Harvard Medical School, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
  • 14 Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: [email protected]
Clin Microbiol Infect, 2024 Dec;30(12):1599-1605.
PMID: 39389851 DOI: 10.1016/j.cmi.2024.09.001

Abstract

OBJECTIVES: To determine the proportion of individuals with detectable antigen in plasma or serum after SARS-CoV-2 infection and the association of antigen detection with postacute sequelae of COVID-19 (PASC) symptoms.

METHODS: Plasma and serum samples were collected from adults participating in four independent studies at different time points, ranging from several days up to 14 months post-SARS-CoV-2 infection. The primary outcome measure was to quantify SARS-CoV-2 antigens, including the S1 subunit of spike, full-length spike, and nucleocapsid, in participant samples. The presence of 34 commonly reported PASC symptoms during the postacute period was determined from participant surveys or chart reviews of electronic health records.

RESULTS: Of the 1569 samples analysed from 706 individuals infected with SARS-CoV-2, 21% (95% CI, 18-24%) were positive for either S1, spike, or nucleocapsid. Spike was predominantly detected, and the highest proportion of samples was spike positive (20%; 95% CI, 18-22%) between 4 and 7 months postinfection. In total, 578 participants (82%) reported at least one of the 34 PASC symptoms included in our analysis ≥1 month postinfection. Cardiopulmonary, musculoskeletal, and neurologic symptoms had the highest reported prevalence in over half of all participants, and among those participants, 43% (95% CI, 40-45%) on average were antigen-positive. Among the participants who reported no ongoing symptoms (128, 18%), antigen was detected in 28 participants (21%). The presence of antigen was associated with the presence of one or more PASC symptoms, adjusting for sex, age, time postinfection, and cohort (OR, 1.8; 95% CI, 1.4-2.2).

DISCUSSION: The findings of this multicohort study indicate that SARS-CoV-2 antigens can be detected in the blood of a substantial proportion of individuals up to 14 months after infection. While approximately one in five asymptomatic individuals was antigen-positive, roughly half of all individuals reporting ongoing cardiopulmonary, musculoskeletal, and neurologic symptoms were antigen-positive.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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