Publication date: Jul 17, 2024

Reliable biomarkers of coronavirus disease 2019 (COVID-19) outcomes are critically needed. We evaluated associations of spike antibody (Ab) and plasma nucleocapsid antigen (N Ag) with clinical outcomes in nonhospitalized persons with mild-to-moderate COVID-19. Participants were nonhospitalized adults with mild-to-moderate COVID-19 enrolled in ACTIV-2 between January and July 2021 and randomized to placebo. We used quantitative assays for severe acute respiratory syndrome coronavirus 2 spike Ab and N Ag in blood and determined numbers of hospitalization/death events within 28 days and time to symptom improvement. Of 209 participants, 77 (37%) had quantifiable spike Ab and 139 (67%) quantifiable N Ag. Median age was 50 years; 111 (53%) were female, 182 (87%) White, and 105 (50%) Hispanic/Latino. Higher risk of hospitalization/death was seen with unquantifiable (22/132 [16. 7%]) versus quantifiable (1/77 [1. 3%]) spike Ab (risk ratio [RR], 12. 83 [95% confidence interval {CI}, 1. 76-93. 34]) and quantifiable (22/139 [15. 8%]) vs unquantifiable (1/70 [1. 4%]) N Ag (RR, 11. 08 [95% CI, 1. 52-80. 51]). Increasing risk of hospitalizations/deaths was seen with increasing N Ag levels. Time to symptom improvement was longer with unquantifiable versus quantifiable spike Ab (median, 14 [interquartile range {IQR}, 8 to >27] vs 8 [IQR, 4-22] days; adjusted hazard ratio [aHR], 0. 66 [95% CI, .45-. 96]) and with quantifiable versus unquantifiable N Ag (median, 12 [7 to >27] vs 10 [5-22] days; aHR, 0. 79 [95% CI, .52-1. 21]). Absence of spike Ab and presence of plasma N Ag predicted hospitalization/death and delayed symptom improvement in COVID-19 outpatients.

Semantics

Original Article