Quantitative studies of SARS-CoV-2 have mostly focused on the upper respiratory tract or plasma viral Ribonucleic acid (RNA), with mixed results regarding their correlation with clinical outcomes. There is a lack of data regarding how plasma viral antigen levels relate to clinical outcomes. This study aimed to examine the association between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and host response markers and clinical outcomes. As part of a prospective observational cohort of hospitalized patients with COVID-19, the SARS-CoV-2 N-antigen concentration in the 1st study plasma sample (D0) was measured. These samples were collected within 72 hours of the subjects’ admission to the hospital between March 2020 and August 2021. Plasma N-antigen was correlated with other biomarkers of tissue damage, coagulation, and inflammation in terms of their rank. The correlation between N-antigen plasma concentration at enrollment and the primary outcome of clinical deterioration at 1 week, as assessed by a modified World Health Organization (WHO) ordinal scale, was tested using multiple ordinal regression. The correlation between plasma N-antigen concentration at enrollment and secondary outcomes like ICU admission, mechanical ventilation at 28 days, and death at 28 days was tested using multivariate logistic regression analysis. An externally derived “high antigen” cutoff of N-antigen more than equal to 1,000 pg/mL was also tested for its prognostic discrimination. In this study, 84% of people tested positive for N-antigen on day 0. Adjusted p equal to  0.01 shows a highly significant correlation between plasma N-antigen levels and reactive airway inflammation (RAGE; r=0.61), interleukin 10 (IL-10; r=0.59), and interleukin 10 (IP-10; r=0.59). Each increment of 500 pg/mL in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03-1.08) for worsening WHO ordinal status at week 1, which was the primary outcome of the study. Sensitivity was 77%, specificity was 59% (AUROC=0.68), positive predictive value was 23%, and negative predictive value was 93% when predicting a worse WHO ordinal scale at day 7 compared to baseline. ICU admission and the need for mechanical ventilation at 28 days were independently associated with D0 N-antigen concentration, but mortality did not occur at this time. Understanding the pathogenesis and prognosis of COVID-19 can be greatly aided by measuring plasma N-antigen levels, which is a simple and quick procedure. Taking an N-antigen level early in a patient’s hospital stay may help with risk stratification, particularly in determining which patients are unlikely to develop life-threatening complications.

Source: ccforum.biomedcentral.com/articles/10.1186/s13054-022-04153-3

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