Figure 4. In fatal COVID-19 outcomes, antibody responses to SARS-CoV-2 are highly correlated with antibody responses to the endemic beta-coronavirus spike proteins.

(A) Correlation between SARS-CoV-2 and endemic coronavirus responses. Spearman’s rank correlations (ρ) are shown for each pair of antigens, split by sample group. There is a positive correlation between all SARS-CoV-2 antigens in all cohorts exposed to SARS-CoV-2. Significant correlations are found between SARS-CoV-2 antigens and endemic beta-HCoVs (HCoV-OC43 and HCoV-HKU1) in the SARS-CoV-2 antibody-positive blood donor and antenatal groups as well as the ICU fatal outcome group. These correlations are absent in the asymptomatic and nonfatal outcome from severe COVID-19 groups. The correlation between endemic beta-HCoVs and SARS-CoV-2 antigens is considerably weaker in the larger positive blood donor and antenatal cohorts than in the ICU fatal outcome group. Responses to the SARS-CoV-2 spike (B) and RBD (C) correlate with beta-coronavirus spike responses in individuals with fatal COVID-19 outcomes. Correlations are shown with a linear model fit between the concentration of 2 SARS-CoV-2 antigens and the endemic viruses HCoV-OC43 and HCoV-HKU1. The best fit line is shown in blue with 95% confidence intervals in gray; the dotted gray division denotes a 1:1 response to both antigens. There is a strong positive association between SARS-CoV-2 spike/RBD and the endemic HCoVs in the fatal outcomes from severe COVID-19 group, which is absent in the similarly sized asymptomatic and nonfatal outcomes from severe COVID-19 groups.