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

Swank, Z; Borberg, E; Chen, Y; et al., Clinical Microbiology and Infection

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Published

September 2024

Journal

Clinical Microbiology and Infection

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. 

Authors

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

Keywords

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

Short Summary

RECOVER researchers studied how COVID affects people over time. They wanted to know if parts of the SARS-CoV-2 virus (which causes COVID-19), called antigens, stay in people's blood long after a COVID infection. They also wanted to see if these antigens are linked to Long COVID. Long COVID is when a person has 1 or more symptoms that last for at least 3 months after getting COVID. First, the researchers took blood samples from adults who had COVID. These samples were taken a few days after getting sick and up to 14 months later. Then, they looked for 3 types of antigens that are usually in the blood after having COVID: the S1 subunit of the spike protein, the nucleocapsid protein, and the full-length spike protein. The full-length spike protein was the most common antigen found in adults who had COVID, especially in those who had blood taken between 4 and 7 months after getting COVID.

The study also looked at 34 common Long COVID symptoms, like trouble breathing, muscle pain, and brain fog. Many participants said that they had at least 1 Long COVID symptom for 1 month or more after getting sick. In the group with the most common kinds of symptoms, 2 out of 5 people had antigens in their blood. In the group without symptoms, about 1 out of 5 people had antigens in their blood. This study shows that the 3 antigens researchers found might be linked to Long COVID. People with symptoms were twice as likely to have these antigens in their blood for a long time. The results also show that parts of the SARS-CoV-2 virus can stay in the blood for up to 14 months after an infection. This is true for people who have long-term symptoms. But, it is also true in some people who do not have long-term symptoms.

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