Serum SARS-CoV-2 Antigens for the Determination of COVID-19 Severity

Julien Favresse, Jean-Louis Bayart, Clara David, Constant Gillot, Grégoire Wieërs, Gatien Roussel, Guillaume Sondag, Marc Elsen, Christine Eucher, Jean-Michel Dogné, Jonathan Douxfils

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The diagnostic of SARS-CoV-2 infection relies on reverse transcriptase polymerase chain reactions (RT-PCRs) performed on nasopharyngeal (NP) swabs. Nevertheless, false-negative results can be obtained with inadequate sampling procedures, making the use of other biological matrices worthy of investigation. This study aims to evaluate the kinetics of serum N antigens in severe and non-severe patients and compare the clinical performance of serum antigenic assays with NP RT-PCR. Ninety patients were included in the study and monitored for several days. Disease severity was determined according to the WHO clinical progression scale. Serum N antigen levels were measured with a chemiluminescent assay (CLIA) and the Single Molecular Array (Simoa) assay. Viremia thresholds for severity were determined and proposed. In severe patients, the peak antigen response was observed 7 days after the onset of symptoms, followed by a decline. No real peak response was observed in non-severe patients. Severity thresholds for the Simoa and the CLIA provided positive likelihood ratios of 30.0 and 10.9 for the timeframe between day 2 and day 14, respectively. Sensitive detection of N antigens in serum may thus provide a valuable new marker for COVID-19 diagnosis and evaluation of disease severity. When assessed during the first 2 weeks since the onset of symptoms, it may help in identifying patients at risk of developing severe COVID-19 to optimize better intensive care utilization.

Original languageEnglish
Article number1653
Issue number8
Publication statusPublished - 28 Jul 2022


  • COVID-19/diagnosis
  • COVID-19 Testing
  • Humans
  • Immunologic Tests
  • SARS-CoV-2
  • Sensitivity and Specificity
  • Severity of Illness Index
  • COVID-19
  • prognosis test
  • RT-PCR
  • antigenic assay


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