High plasma antigen levels are associated with greater severity of lung involvement and outcomes in hospitalized Covid-19 patients, suggests a new study published in the Annals of Internal Medicine.^1,2

Rogers et al examined 2540 adult patients who were hospitalized with acute Covid-19 with symptoms for ≤12 days. Their median age was 57 years and men comprised nearly 60% of the study population.

The study subjects were part of the ACTIV-3 (Accelerating COVID-19 Therapeutic Interventions and Vaccines, Inpatient Monoclonal Antibodies and Other Therapies) platform trial, also called TICO (Therapeutics for Inpatients With COVID-19), from August 2020 to November 2021 when the delta variant was the predominant strain globally. In the ACTIV-3/TICO trial, participants were randomly assigned to receive one of five experimental antivirals or a placebo. Remdesivir was administered to all if not contraindicated.

In the current multicenter follow-up cross-sectional study conducted in 10 countries, the researchers aimed to investigate the association of baseline plasma SARS-CoV-2 nucleocapsid (N) antigen levels with the time of discharge, including clinical outcomes on Day 5, specifically for pulmonary symptoms.

At the start of the study, 11% patients needed noninvasive ventilation or high-flow nasal cannula, while 25% were breathing room air. Most patients needed oxygen supplementation. Around 80% of them were unvaccinated.

Overall, 57% of patients had plasma antigen levels of ≥1000 ng/L at the time of their recruitment in the study, while in 5%, the antigen levels could not be quantified. The mean plasma antigen level was increased 3.10-times among patients receiving oxygen supplementation via high-flow nasal cannula or noninvasive ventilation than in those who were breathing room air. The antigen levels were increased almost 3-folds in patients who required ≥4 L of conventional oxygen supplementation. Among patients who required less than 4 L of conventional oxygen supplementation, the antigen levels were increased 1.77 fold.

The plasma antigen levels were raised 6.42-folds in patients who were deficient in anti-spike antibodies. The plasma antigen levels were nearly doubled (1.73-fold) among those who were infected with the delta SARS-CoV-2 variant.

The plasma antigen levels and the severity of pulmonary symptoms at baseline were strongly correlated. The pulmonary function worsened 5 times among patients who had plasma antigen levels of ≥1000 ng/L with odds ratio of 5.06. They also had prolonged length of hospital stay with a median duration of 7 days vs 4 days.

The male patients tended to have higher baseline antigen levels with OR of 1.26. Other factors associated with higher baseline antigen levels were shorter time since hospitalization, fewer days of remdesivir administration and renal impairment. But no such association was observed for body mass index (BMI), ethnicity, race and immunocompromising diseases.

This study shows that more than half of patients with Covid-19 have high plasma N antigen levels. There was a significant correlation between high baseline plasma antigen levels and severity of pulmonary involvement and patient outcomes. It has also identified various risk factors associated with higher antigen levels at presentation. The higher antigen levels are likely suggestive of ongoing viral replication and therefore can be predictive of disease outcomes in hospitalized patients with Covid-19. “Because plasma antigen level is associated with antibody status, time in hospital, and exposure to antiviral therapy, it is likely that it reflects true viral replication”, noted the authors. They also point out that the lack of a point-of-care test to measure plasma antigen is a limitation of their study.

References

1. Rogers et al. The association of baseline plasma SARS-CoV-2 nucleocapsid antigen level and outcomes in patients hospitalized with COVID-19. Ann Intern Med. 2022 Aug.30. DOI: 10.7326/M22-0924.
2. National Institutes of Health (NIH) Press release, August 29, 2022.