Antigen Biomarkers Could Predict Disease Progression of Hospitalized COVID-19 Patients

Viral antigen levels in blood plasma can provide clinically important patient outcomes among hospitalized patients with COVID-19.

Antigen biomarkers for SARS-CoV-2 could predict the severity and outcomes of patients hospitalized from COVID-19, according to new research published in the Annals of Internal Medicine.1

“SARS-CoV-2 antigen levels hold promise as a biomarker, or a measurable substance, to predict which patients hospitalized with COVID-19 have a higher risk of worse outcomes,” the authors said in a press release.1

Mortality rates have stayed high among patients hospitalized from COVID-19—between 6% and 27%. The cross-sectional ACTIV-3 trial aimed to predict the severity of the disease among hospitalized patients by exploring the association between antigen levels and disease progression.2

Enrolled patients spread among 114 international centers were hospitalized for COVID-19 (experiencing 12 days or less of symptoms), between August 2020 and November 2021.1,2 Participants donated a baseline blood sample, then randomly received either a COVID-19 experimental therapeutic or placebo. All qualified patients concurrently took the antiviral medication remdesivir.1

Researchers analyzed COVID-19 antigen levels in 2540 blood samples as follow-up. They identified relationships between antigen levels and time between hospitalization and discharge, day 5 pulmonary symptoms (worsen, stay the same, or improve since enrollment), and number of viral characteristics.­1

Using statistical analyses, the team explored the association between baseline pulmonary health and antigen levels in the blood sample. With this information, they strived to predict future health outcomes.1

The results showed that baseline pulmonary measurements were strongly associated with plasma antigen levels. A more severe pulmonary illness was indicated by higher antigen levels.2 The mean antigen levels in severe cases were 3.1 times greater.2

“SARS-CoV-2 N antigen can be detected in plasma in more than 95% of participants at baseline and is highly associated both with the severity of pulmonary illness at presentation and clinically important outcomes,” the study authors wrote.2

Antigen levels that were equal or greater than 1000 nanograms per liter were also associated with worse pulmonary function at baseline. After 5 days, those with higher antigen levels were more likely to have worse pulmonary function, and in turn, they were released from the hospital later.1

Other factors that impacted the baseline antigen levels included being male, taking remdesivir for fewer days before enrollment, and renal impairment.1,2

The study was limited because plasma samples were drawn at enrollment into the study. This was regardless of whether the participant was already in the hospital or not. Additionally, no point-of-care tests are available to measure plasma antigen levels.2

“These results suggest that a precision medicine approach to inpatient COVID-19 clinical trials is needed, with a substantial portion of patients hospitalized with acute SARS-CoV-2 infection potentially more likely to benefit from antiviral therapy,” the authors concluded in the study.2


  1. NIH/National Institute of Allergy and Infectious Diseases. SARS-CoV-2 antigen levels linked to patient outcomes. EurekAlert! August 29, 2022. Accessed on August 31, 2022.
  2. The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19. Annals of Internal Medicine. August 30, 2022. Accessed on August 31, 2022.