Proteomic Analysis Fails to Differentiate SARS-CoV-2 Antigenemia in Convalescent Patients

Overview

In a cohort of 100 individuals assessed approximately 3 and 12 months after acute SARS-CoV-2 infection, plasma antigenemia was detected in a minority but did not correlate with long COVID symptoms or distinct proteomic or immune cell profiles. Proteomic and single-cell analyses failed to distinguish between patients with and without detectable viral antigens during convalescence.

Background

Long COVID (LC) is a post-infectious syndrome characterized by persistent symptoms lasting at least 3 months after acute SARS-CoV-2 infection. The pathogenesis is multifactorial, potentially involving immune dysregulation and viral persistence. Previous studies have detected SARS-CoV-2 antigens in convalescent plasma, suggesting antigenemia as a possible biomarker for LC. However, antigenemia has also been observed in asymptomatic individuals, and its clinical significance remains unclear.

Data Highlights

Key Findings

• At 3 months post-infection, 18% of patients had detectable SARS-CoV-2 antigens in plasma; at 12 months, 14% remained antigenemic.
• Spike antigen was the most frequently detected antigen compared to S1 and N antigens at both time points.
• There was no significant difference in antigenemia rates between patients with long COVID symptoms and those fully recovered at either 3 or 12 months.
• Proteomic analysis of plasma and single-cell protein expression on immune cells showed no significant differences between antigenemic and non-antigenemic individuals.
• Patients treated with remdesivir during acute infection had a lower rate of antigenemia at 3 months, but this difference was not observed at 12 months.
• Hospitalized patients had a lower rate of antigen detection at 3 months compared to non-hospitalized patients, with no difference at 12 months.

Clinical Implications

Detection of SARS-CoV-2 antigens in plasma during convalescence does not appear to correlate with long COVID symptomatology or distinct immune profiles, limiting its utility as a biomarker for LC. Clinicians should consider that antigenemia may persist in a subset of patients without clinical sequelae. Antiviral treatment during acute infection may transiently reduce antigenemia but does not affect long-term antigen persistence.

Conclusion

SARS-CoV-2 antigenemia persists in a minority of convalescent patients but does not distinguish those with long COVID from those without symptoms. Proteomic and immune cell analyses do not reveal distinct signatures associated with antigen persistence, suggesting limited clinical relevance of antigenemia during recovery.

References

1. National Academies of Sciences, Engineering, and Medicine 2024 -- Defining Long COVID
2. IRIS Study, Stanford University 2020 -- Infection Recovery in SARS-CoV-2
3. Prior Studies 2021-2023 -- SARS-CoV-2 Antigen Detection in Convalescent Plasma
4. Current Study -- Proteomic Analysis of Single Cells and Plasma in SARS-CoV-2 Convalescence