SARS-CoV-2 Plasma Antibody and Nucleocapsid Antigen Status Predict Outcomes in Outpatients With COVID-19

Clin Infect Dis. 2024 Oct 15;79(4):920-927. doi: 10.1093/cid/ciae324.

Abstract

Background: 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.

Methods: 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.

Results: 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]).

Conclusions: Absence of spike Ab and presence of plasma N Ag predicted hospitalization/death and delayed symptom improvement in COVID-19 outpatients.

Clinical trials registration: NCT04518410.

Keywords: COVID-19; SARS-CoV-2; biomarker; nucleocapsid; spike antibody.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral* / blood
  • Biomarkers / blood
  • COVID-19* / blood
  • COVID-19* / immunology
  • COVID-19* / mortality
  • Coronavirus Nucleocapsid Proteins / immunology
  • Female
  • Hospitalization* / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Outpatients
  • Phosphoproteins
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • Coronavirus Nucleocapsid Proteins
  • spike protein, SARS-CoV-2
  • Biomarkers
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • Phosphoproteins

Associated data

  • ClinicalTrials.gov/NCT04518410