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[Preprint]. 2023 Dec 29:2023.10.24.23297114.

doi: 10.1101/2023.10.24.23297114.

Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection

Michael J Peluso¹, Zoe N Swank^{2

3

4}, Sarah A Goldberg⁵, Scott Lu⁵, Thomas Dalhuisen⁵, Ella Borberg^{2

3

4}, Yasmeen Senussi^{2

3

4}, Michael A Luna¹, Celina Chang Song¹, Alexus Clark¹, Andhy Zamora¹, Megan Lew¹, Badri Viswanathan⁵, Beatrice Huang¹, Khamal Anglin⁵, Rebecca Hoh¹, Priscila Y Hsue⁶, Matthew S Durstenfeld⁶, Matthew A Spinelli¹, David V Glidden⁵, Timothy J Henrich⁷, J Daniel Kelly⁵, Steven G Deeks¹, David R Walt^{2

3

4}, Jeffrey N Martin⁵

Affiliations

¹ Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, CA, USA.
² Harvard Medical School, Boston, MA, USA.
³ Department of Pathology, Brigham & Women's Hospital, Boston, MA, USA.
⁴ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
⁵ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
⁶ Division of Cardiology, University of California, San Francisco, San Francisco, CA, USA.
⁷ Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA.

PMID: 37961239
PMCID: PMC10635183
DOI: 10.1101/2023.10.24.23297114

Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection

Michael J Peluso et al. medRxiv. 2023.

[Preprint]. 2023 Dec 29:2023.10.24.23297114.

doi: 10.1101/2023.10.24.23297114.

Authors

Affiliations

¹ Division of HIV, Infectious Diseases, and Global Medicine, University of California, San Francisco, San Francisco, CA, USA.
² Harvard Medical School, Boston, MA, USA.
³ Department of Pathology, Brigham & Women's Hospital, Boston, MA, USA.
⁴ Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
⁵ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA.
⁶ Division of Cardiology, University of California, San Francisco, San Francisco, CA, USA.
⁷ Division of Experimental Medicine, University of California, San Francisco, San Francisco, CA, USA.

PMID: 37961239
PMCID: PMC10635183
DOI: 10.1101/2023.10.24.23297114

Update in

Plasma-based antigen persistence in the post-acute phase of COVID-19.
Peluso MJ, Swank ZN, Goldberg SA, Lu S, Dalhuisen T, Borberg E, Senussi Y, Luna MA, Chang Song C, Clark A, Zamora A, Lew M, Viswanathan B, Huang B, Anglin K, Hoh R, Hsue PY, Durstenfeld MS, Spinelli MA, Glidden DV, Henrich TJ, Kelly JD, Deeks SG, Walt DR, Martin JN. Peluso MJ, et al. Lancet Infect Dis. 2024 Jun;24(6):e345-e347. doi: 10.1016/S1473-3099(24)00211-1. Epub 2024 Apr 8. Lancet Infect Dis. 2024. PMID: 38604216 Free PMC article. No abstract available.

Abstract

Background: Persistent symptoms among some persons who develop COVID-19 has led to the hypothesis that SARS-CoV-2 may, in some form or location, persist for long periods following acute infection. Several studies have shown data in this regard but are limited by non-representative and small study populations, short duration since acute infection, and lack of a true-negative comparator group to assess assay specificity.

Methods: We evaluated adults with RNA-confirmed COVID-19 at multiple time points following acute infection (pandemic-era participants) and adults with specimens collected prior to 2020 (pre-pandemic era). Using once-thawed plasma, we employed the Simoa^® (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens.

Results: Compared to 250 pre-pandemic participants who had 2% assay positivity, detection of any SARS-CoV-2 antigen was significantly more frequent among 171 pandemic-era participants at three different time periods in the post-acute phase of infection. The absolute difference in SARS-CoV-2 plasma antigen prevalence was +11% (95% CI: +5.0% to +16%) at 3.0-6.0 months post-onset of COVID-19; +8.7% (95% CI: +3.1% to +14%) at 6.1 to 10.0 months; and +5.4% (95% CI: +0.42% to +10%) at 10.1-14.1 months. Hospitalization for acute COVID-19 and, among the non-hospitalized, worse self-reported health during acute COVID-19 were associated with greater post-acute phase antigen detection.

Conclusions: Compared to uninfected persons, there is an excess prevalence of SARS-CoV-2 antigenemia in SARS-CoV-2-infected individuals up to 14 months after acute COVID-19. These findings motivate an urgent research agenda regarding the short-term and long-term clinical manifestations of this viral persistence.

Keywords: COVID-19; Long COVID; antigen; post-acute sequelae of SARS-CoV-2; viral persistence.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest MJP reports consulting for Gilead Sciences and AstraZeneca, outside the submitted work. DRW 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 Mass General Brigham and Harvard University in accordance with their conflict-of-interest policies.

Figures

**Figure 1.**
Prevalence of SARS-CoV-2 antigen positivity in plasma among participants in the post-acute phase of COVID-19 in comparison to pre-pandemic participants. P-values represent chi-square and Fisher’s 2-sided exact test as appropriate. (a) Prevalence of any SARS-CoV-2 antigen positivity (Spike, S1 or nucleocapsid); (b) Spike antigen prevalence; (c) Nucleocapsid antigen presence; and (d) S1 antigen presence.

**Figure 2.**
Quantitative measurement of SARS-CoV-2 spike, S1, and nucleocapsid antigens in plasma among all pandemic-era participants during the post-acute phase of SARS-CoV-2 infection. Dashed lines indicate limit of quantification for each antigen. Y-axis refers to log-transformed concentration of antigen in picograms per mL.

**Figure 3.**
Individual participant-level profiles of quantitative measurement of SARS-CoV-2 spike, S1, and nucleocapsid antigens in plasma during the post-acute phase of SARS-CoV-2 infection, limited to participants with at least one positive antigen. Blue indicates spike, green nucleocapsid, and red S1. Horizontal dotted lines represent the assay limit of detection for each antigen. Vertical dotted lines indicate receipt of SARS-CoV-2 vaccine. Y-axis refers to log-transformed concentration of antigen in picograms per mL.

See this image and copyright information in PMC

References

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This is a preprint.

Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection

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Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

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References

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