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. 2024 Dec;30(12):1599-1605.
doi: 10.1016/j.cmi.2024.09.001. Epub 2024 Oct 9.

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

Zoe Swank  1 , Ella Borberg  1 , Yulu Chen  2 , Yasmeen Senussi  1 , Sujata Chalise  1 , Zachary Manickas-Hill  3 , Xu G Yu  4 , Jonathan Z Li  5 , Galit Alter  6 , Timothy J Henrich  7 , J Daniel Kelly  8 , Rebecca Hoh  9 , Sarah A Goldberg  10 , Steven G Deeks  9 , Jeffrey N Martin  10 , Michael J Peluso  9 , Aarthi Talla  11 , Xiaojun Li  11 , Peter Skene  11 , Thomas F Bumol  11 , Troy R Torgerson  11 , Julie L Czartoski  12 , M Juliana McElrath  12 , Elizabeth W Karlson  13 , David R Walt  14 ; RECOVER consortium authors
Collaborators, Affiliations

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

Zoe Swank et al. Clin Microbiol Infect. 2024 Dec.

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.

Keywords: COVID-19; Multicohort study; Postacute sequelae of COVID-19; Retrospective cohort study; SARS-CoV-2 antigens.

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Conflict of interest statement

Conflict of Interest

MJP reports consulting fees from Gilead Sciences and AstraZeneca, and Research support from Aerium Therapeutics, outside the submitted work. SGD reports consulting for Enanta Pharmaceuticals and Pfizer and research support from Aerium Therapeutics, outside the submitted work. JZL has consulted for Abbvie and received research funding from Merck. David Walt has a financial interest in Quanterix Corporation, a company that develops an ultra-sensitive digital immunoassay platform. He is an inventor of the Simoa technology, a founder of the company, and also serves on its Board of Directors. Dr. Walt's interests were reviewed and are managed by Brigham and Women's Hospital and Partners Healthcare in accordance with their conflict-of-interest policies.

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