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Vaccine . Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infecti

tetano

Editor, Senior Moderator
Vaccine


. 2022 Mar 9;S0264-410X(22)00272-9.
doi: 10.1016/j.vaccine.2022.03.009. Online ahead of print.
Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?


Lotus L van den Hoogen[SUP] 1 [/SUP], Gaby Smits[SUP] 2 [/SUP], Cheyenne C E van Hagen[SUP] 3 [/SUP], Denise Wong[SUP] 3 [/SUP], Eric R A Vos[SUP] 3 [/SUP], Michiel van Boven[SUP] 3 [/SUP], Hester E de Melker[SUP] 3 [/SUP], Jeffrey van Vliet[SUP] 2 [/SUP], Marjan Kuijer[SUP] 2 [/SUP], Linde Woudstra[SUP] 2 [/SUP], Alienke J Wijmenga-Monsuur[SUP] 2 [/SUP], Corine H GeurtsvanKessel[SUP] 4 [/SUP], Susanne P Stoof[SUP] 5 [/SUP], Daphne Reukers[SUP] 6 [/SUP], Lisa A Wijsman[SUP] 6 [/SUP], Adam Meijer[SUP] 6 [/SUP], Chantal B E M Reusken[SUP] 6 [/SUP], Nynke Y Rots[SUP] 6 [/SUP], Fiona R M van der Klis[SUP] 2 [/SUP], Robert S van Binnendijk[SUP] 2 [/SUP], Gerco den Hartog[SUP] 2 [/SUP]



Affiliations

Abstract

Background: With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination.
Methods: Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) without COVID-19 vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech).
Results: The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥ 14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥ 7 days after the second dose (p = 0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in infection-naïve participants.
Conclusions: Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.

Keywords: COVID-19; Multiplex immunoassay; Nucleoprotein; SARS-CoV-2; Serosurveillance; immunoglobulin G.
 
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