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SARS-CoV-2 antigen levels linked to patient outcomes

August 29, 2022 – The amount of SARS-CoV-2 antigen measured in the blood of patients hospitalized with COVID-19 is associated with disease severity and other clinical outcomes, according to a new study published in the Annals of Internal Medicine. Following the ACTIV-3 trial of COVID-19 therapeutics in people hospitalized with COVID-19, researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health , and their collaborators analyzed levels of SARS-COV-2 antigen in blood samples taken from study participants and assessed the association of these levels with disease progression. Higher levels of viral antigen in the blood, which could indicate continued replication of SARS-CoV-2, correlates with more severe disease. The authors suggest that SARS-CoV-2 antigen levels show promise as a biomarker, or measurable substance, for predicting which patients hospitalized with COVID-19 have a higher risk of worse outcomes.

Colorized scanning electron micrograph of a cell infected with the Omicron strain of SARS-CoV-2 virus particles (red), isolated from a patient specimen. NIAID

The ACTIV-3 trial enrolled people hospitalized with COVID-19 between August 2020 and November 2021. Participants provided a baseline blood sample and were then randomized to receive either an investigational COVID-19 treatment or a placebo . All participants received the antiviral remdesivir unless contraindicated. In this follow-up analysis, researchers examined 2,540 baseline blood samples from participants for SARS-CoV-2 antigen levels.

Researchers assessed the relationship between each participant’s SARS-CoV-2 blood antigen levels and their time to discharge from hospital, as well as their lung symptoms on day five of the trial, whether they remained the same, worsened or improved since registration. With all of this information in hand, the researchers performed statistical analyzes to determine if plasma antigen levels were associated with participants’ lung function when they gave the blood sample and if they could predict how the participants would work out over time. Additionally, the researchers examined the relationship between a number of viral and participant characteristics and antigen levels.

The analysis revealed a strong correlation between higher SARS-CoV-2 antigen levels (≥1000 nanograms per liter) and poorer lung function at enrollment. It is important to note that participants with higher levels of SARS-CoV-2 antigen in the blood at registration

generally had decreased lung function by day five, regardless of disease severity at study entry, and took longer to be discharged from hospital. High levels of blood antigens were also correlated with some known risk factors for worsening the disease, such as being male. Three additional characteristics of participants were found to be correlated with lower antigen levels: presence of antibodies to SARS-CoV-2, exposure to remdesivir prior to enrollment, and longer length of hospitalization prior to enrollment. registration. Finally, participants infected with the delta variant had higher antigen levels than those infected with earlier circulating strains. The researchers concluded that blood antigen levels are likely a marker of ongoing viral replication and could be useful in predicting a patient’s disease progression and likely outcomes once admitted to the hospital. The authors note that these results suggest that a precision medicine approach could be useful in future clinical trials of antiviral therapy. For example, antigen levels could help determine which patients are most likely to benefit from therapies aimed at fighting the virus.


roger et al. The association of baseline plasma SARS-CoV-2 nucleocapsid antigen level and outcomes in patients hospitalized with COVID-19. Annals of Internal Medicine DOI: 10.7326/M22-0924 (2022).


H. Clifford Lane, MD, associate director of clinical research and special projects, NIAID, is available for comment.

NIAID conducts and supports research—at the NIH, in the United States, and around the world—to study the causes of infectious and immune-mediated diseases and to develop better ways to prevent, diagnose, and treat these diseases. Press releases, fact sheets, and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): The NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit

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