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. 2022 Oct 21;25(10):105105.
doi: 10.1016/j.isci.2022.105105. Epub 2022 Sep 9.

Recent infection with HCoV-OC43 may be associated with protection against SARS-CoV-2 infection

A H Ayesha Lavell  1   2 , Jonne J Sikkens  1   2 , Arthur W D Edridge  2   3 , Karlijn van der Straten  2   3   4 , Ferdyansyah Sechan  2   3 , Melissa Oomen  2   3 , David T P Buis  1   2 , Michiel Schinkel  2   5 , Judith A Burger  2   3 , Meliawati Poniman  2   3 , Jacqueline van Rijswijk  2   3 , Menno D de Jong  2   3 , Godelieve J de Bree  2   4 , Edgar J G Peters  1   2 , Yvo M Smulders  1   2 , Rogier W Sanders  2   3   6 , Marit J van Gils  2   3 , Lia van der Hoek  2   3 , Marije K Bomers  1   2
Affiliations

Recent infection with HCoV-OC43 may be associated with protection against SARS-CoV-2 infection

A H Ayesha Lavell et al. iScience. .

Abstract

Antibodies against seasonal human coronaviruses (HCoVs) are known to cross-react with SARS-CoV-2, but data on cross-protective effects of prior HCoV infections are conflicting. In a prospective cohort of healthcare workers (HCWs), we studied the association between seasonal HCoV (OC43, HKU1, 229E and NL63) nucleocapsid protein IgG and SARS-CoV-2 infection during the first pandemic wave in the Netherlands (March 2020 - June 2020), by 4-weekly serum sampling. HCW with HCoV-OC43 antibody levels in the highest quartile, were less likely to become SARS-CoV-2 seropositive when compared with those with lower levels (6/32, 18.8%, versus 42/97, 43.3%, respectively: p = 0.019; HR 0.37, 95% CI 0.16-0.88). We found no significant association with HCoV-OC43 spike protein IgG, or with antibodies against other HCoVs. Our results indicate that the high levels of HCoV-OC43-nucleocapsid antibodies, as an indicator of a recent infection, are associated with protection against SARS-CoV-2 infection; this supports and informs efforts to develop pancoronavirus vaccines.

Keywords: Immunology; Molecular physiology; Virology.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
HCoV anti-NCt IgG over time in SARS-CoV-2 seronegative and seropositive participants (A–H) Scatter plots of HCoV IgG against C-terminal nucleocapsid protein (NCt) concentrations over time. To determine fluctuation in antibody concentration, we calculated the difference between the highest and lowest concentration of each participant. A 10% difference in concentration equals 1 unit in standardized antibody concentration.
Figure 2
Figure 2
Different levels of HCoV anti-NCt IgG and the probability of SARS-CoV-2 infection (A–D) Plots comparing seasonal HCoV IgG against C-terminal nucleocapsid protein (NCt) concentrations (x-axis) against SARS-CoV-2 status (right y-axis), with fitted binomial spline model with four knots represented by blue line; indicating the probability of seroconversion against SARS-CoV-2 (left y-axis). For further analysis, concentrations of HCoV anti-NCt IgG were divided into quartiles (represented by dotted vertical lines on x-axes).
Figure 3
Figure 3
Different levels of baseline HCoV anti-NCt IgG and the incidence of SARS-CoV-2 infection The figure displays Kaplan-Meier survival curves of participants with highest quartile (high) HCoV IgG against C-terminal nucleocapsid protein (NCt) concentrations (red) and those with lower (low) HCoV anti-NCt IgG concentrations (blue), and the incidence of SARS-CoV-2-infection.
Figure 4
Figure 4
HCoV-OC43 anti-NCt IgA and IgG during and after acute infection HCoV-OC43 anti-NCt IgA (A) and IgG (B) optical density (OD) in ELISA determined in sera of 14 participants from the GRACE observational study (Edridge et al., 2020; Ieven et al., 2018). V1: serum collected during the acute phase of HCoV-OC43-infection, V2: serum collected 28–35 days later. (C) OD fold change from V1 to V2 for IgA and IgG, individual values plotted with median and IQR.
Figure 5
Figure 5
SARS-CoV-2 anti-S IgG in COVID naive individuals (A-D) Comparison of IgG against SARS-CoV-2 spike (S) in MFI between participants with highest quartile (high) seasonal HCoV anti-C-terminal nucleocapsid protein (NCt) IgG levels against lower (low) three quartiles at baseline. Participants were SARS-CoV-2 negative at baseline and the second measurement. Data are represented as individual values, median and interquartile range (IQR). ns: not significant, assessed by Mann–Whitney U test.
Figure 6
Figure 6
SARS-CoV-2 anti-RBD IgG in COVID naive individuals (A-D) Comparison of antibodies against SARS-CoV-2 receptor-binding domain (RBD) in MFI between participants with highest quartile (high) seasonal HCoV anti-C-terminal domain of nucleocapsid protein (NCt) IgG levels against lower (low) three quartiles at baseline. Participants were SARS-CoV-2 negative at baseline and the second measurement. Data are represented as individual values, median and interquartile range (IQR). ns: not significant, assessed by Mann–Whitney U test.
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