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Serological markers of SARS-CoV-2 infection; anti-nucleocapsid antibody positivity may not be the ideal marker of natural infection in vaccinated individuals

Published:August 09, 2021DOI:https://doi.org/10.1016/j.jinf.2021.08.012
      We write in response to correspondence from Whitaker et al. in this Journal (
      • Whitaker H.J.
      • Elgohari S.
      • Rowe C.
      • Otter A.D.
      • Brooks T.
      • Linley E.
      • et al.
      Impact of COVID-19 vaccination program on seroprevalence in blood donors in England, 2021.
      ). The authors demonstrate increases in seropositivity for SARS-CoV-2 antibodies against the spike protein as the roll out of COVID-19 vaccines continues, whilst parallel assessment of nucleocapsid antibodies remained stable. This study is an example of the use of parallel assessment of spike (S) and nucleocapsid (N) antibodies to discriminate between natural infection and vaccine related seropositivity (
      • Okba N.M.A.
      • Müller M.A.
      • Li W.
      • Wang C.
      • GeurtsvanKessel C.H.
      • Corman V.M.
      • et al.
      Severe acute respiratory syndrome coronavirus 2−Specific antibody responses in coronavirus disease patients.
      ) (
      • Dörschug A.
      • Frickmann H.
      • Schwanbeck J.
      • Yilmaz E.
      • Mese K.
      • Hahn A.
      • et al.
      Comparative assessment of sera from individuals after S-Gene RNA-based SARS-CoV-2 vaccination with spike-protein-based and nucleocapsid-based serological assays.
      ). This approach remains attractive, but as the pandemic rolls on it is worth considering the paucity of evidence about the impact of vaccination on antibody production in response to a subsequent natural infection.
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