Elevated plasma levels of SARS-CoV-2 antigen are associated with increased severity of illness

1. Elevated plasma SARS-CoV-2 antigen is associated with increased severity of pulmonary illness in hospitalized COVID-19 patients. 

2. Elevated plasma SARS-CoV-2 antigen is also associated with clinically important outcomes in hospitalized COVID-19 patients.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Mortality rates for adult patients hospitalized with coronavirus disease 2019 (COVID-19) are high. Although, they range from 6% to 27% according to various large published clinical trials. The precise mortality rates for SARS-CoV-2 infection in hospitalized patients, therefore, remain uncertain. Detection of nasal swab nucleocapsid (N) antigen has been proposed to be used to diagnose acute SARS-CoV-2 infection and may reflect systemic viral replication. Thus, there is a knowledge gap in understanding the association between antigen level and subsequent short-term prognosis. The present study found that the plasma viral antigen can be quantified in early samples in hospitalized patients and is highly associated with both baseline severity of illness and clinically important patient outcomes. This study was limited by the antigen level being measured at the time of study entry as opposed to the time of hospital admission and the fact that some persons had received treatment with remdesivir before study entry. Although, the median time from hospitalization to enrollment was only one day. Nevertheless, these study’s findings are still significant, as they demonstrate that plasma viral antigen is significantly associated with the severity of COVID-19 illness.

Click to read the study in AIM

Relevant Reading: Contribution of Individual- and Neighborhood-Level Social, Demographic, and Health Factors to COVID-19 Hospitalization Outcomes

In-Depth [cross-sectional study]: This cross-sectional study was conducted with 2,540 participants in the Therapeutics for Inpatients with COVID-19 (TICO) platform trial from August 2020 to November 2021, at 114 centers in 10 countries. Patients who were hospitalized for acute COVID-19 within 12 days of symptom onset were eligible for the study. Patients who did not fulfill this criterion were excluded from the study. The primary outcome measured was baseline plasma viral N antigen and associations between baseline patient characteristics and viral factors and baseline plasma antigen levels. Based on the primary analysis, baseline pulmonary severity of illness was strongly associated with plasma antigen level. The mean plasma antigen level was 3.10-fold higher among those requiring non-invasive ventilation or high-flow nasal cannula compared with those only on room air (95% Confidence Interval [CI], 2.22 to 4.34). Plasma antigen level was also 6.42-fold higher in those who lacked antispike antibodies (95% CI, 5.37 to 7.66) and in those with the delta variant (1.73 fold, 95% CI 1.41 to 2.13). Other factors associated with a higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. Plasma antigen level of 1000 ng/L or greater was also significantly associated with a higher odds of worsened pulmonary status at day 5 (Odds Ratio, 5.06; 95% CI, 3.41 to 7.50]), as well as a longer time to hospital discharge (Median, 7 vs. 4 days; Sub-hazard Ratio, 0.51; 95% CI, 0.45 to 0.57). Overall, this study demonstrates that the elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes, such as requiring oxygen support and type of COVID variant.

Image: PD

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