High sera levels of SARS-CoV-2 N antigen are associated with death in hospitalized COVID-19 patients

J Med Virol. 2023 Nov;95(11):e29247. doi: 10.1002/jmv.29247.


The presence of free severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid-antigen in sera (N-antigenemia) has been shown in COVID-19 patients. However, the link between the quantitative levels of N-antigenemia and COVID-19 disease severity is not entirely understood. To assess the dynamics and clinical association of N-antigen sera levels with disease severity in COVID-19 patients, we analyzed data from patients included in the French COVID cohort, with at least one sera sample between January and September 2020. We assessed N-antigenemia levels and anti-N IgG titers, and patient outcomes was classified in two groups, survival or death. In samples collected within 8 days since symptom onset, we observed that deceased patients had a higher positivity rate (93% vs. 81%; p < 0.001) and higher median levels of predicted N-antigenemia (2500 vs. 1200 pg/mL; p < 0.001) than surviving patients. Predicted time to N-antigen clearance in sera was prolonged in deceased patients compared to survivors (23.3 vs 19.3 days; p < 0.0001). In a subset of patients with both sera and nasopharyngeal (NP) swabs, predicted time to N-antigen clearance in sera was prolonged in deceased patients (p < 0.001), whereas NP viral load clearance did not differ between the groups (p = 0.07). Our results demonstrate a strong relationship between N-antigenemia levels and COVID-19 severity on a prospective cohort.

Keywords: COVID-19; antigenemia; hospitalized; serological marker; severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • COVID-19*
  • Humans
  • Patient Acuity
  • Prospective Studies
  • SARS-CoV-2


  • Antibodies, Viral