High transmission of endemic human coronaviruses before and during the COVID-19 pandemic in adolescents in Cebu, Philippines

Abstract

Background: SARS-CoV-2, the causative agent of COVID-19, is a betacoronavirus belonging to the same genus as endemic human coronaviruses (hCoVs) OC43 and HKU1 and is distinct from alpha hCoVs 229E and NL63. In a study of adolescents in the Philippines, we evaluated the seroprevalence to hCoVs, whether pre-pandemic hCoV immunity modulated subsequent risk of SARS-CoV-2 infection, and if SARS-CoV-2 infection affected the transmission of the hCoVs.

Methods: From 499 samples collected in 2021 and screened by SARS-CoV-2 receptor binding domain (RBD) enzyme-linked immunosorbent assay (ELISA), we randomly selected 59 SARS-CoV-2 negative and 61 positive individuals for further serological evaluation. We measured RBD and spike antibodies to the four hCoVs and SARS-CoV-2 by ELISA in samples from the same participants collected pre-pandemic (2018-2019) and mid-pandemic (2021), before COVID-19 vaccination.

Results: We observed over 72% seropositivity to the four hCoVs pre-pandemic. Binding antibodies increased with age to 229E and OC43, suggesting endemic circulation, while immunity was flat across ages for HKU1 and NL63. During the COVID-19 pandemic, antibody level increased significantly to the RBDs of OC43, NL63, and 229E and spikes of all four hCoVs in both SARS-CoV-2 negative and positive adolescents. Those aged 12-15 years old in 2021 had higher antibodies to RBD and spike of OC43, NL63, and 229E than adolescents the same age in 2019, further demonstrating intense transmission of the hCoVs during the pandemic.

Conclusions: We observe a limited impact of the COVID-19 pandemic on endemic hCoV transmission. This study provides insight into co-circulation of hCoVs and SARS-CoV-2.

Keywords: 229E; COVID-19; Endemic coronaviruses; HKU1; NL63; OC43; Philippines; SARS-CoV-2; seroprevalence.

Figure 1.. Seroprevalence to the four hCoVs before the COVID-19 pandemic.

Bar chart (proportion with standard errors) showing seroprevalence to the four endemic CoVs as measured by (A)RBD and (B) spike. Positivity was defined as ELISA OD values more than 3 times the standard deviation of the negative controls (OD >0.2). ELISA OD by age in 2019, stratified by antigen for (C) RBD and (D) spike ELISAs. Colored points and lines show means and data ranges, black lines show linear relationships, with grey shapes indicating the 95% confidence interval. The relationship between age and ELISA OD was estimated with linear regression; slope estimates and p-values are shown.

Figure 2.. Odds of SARS-CoV-2 infection by endemic hCoV ELISA OD prior to the COVID-19 pandemic.

(A) Forest plot of the odds ratios from unadjusted logistic regression of the effect of baseline ELISA OD as measured by RBD or spike on SARS-COV-2 infection. Models adjusted by age, sex, and study site are show in Fig. S2. Odds ratios for SARS-CoV-2 infection, where all measures of pre-COVID-19 antibodies to endemic CoVs were included in the same model, are shown for (B) RBD and (C) spike.

Figure 3.. Change in antibodies to RBDs and spikes of hCoVs from before to during the COVID-19 pandemic.

Comparison of 2019 vs. 2021 ELISA OD values to each RBD (A) and spike antigen (B). ELISA OD values between years were compared with a paired t-test. The difference (d) in ELISA values to each RBD (C) and spike antigen (D) were also compared for adolescents age 12–15 years in 2019 vs. 2021 using a linear model, adjusted for age to account for differences in age distributions between years.

Figure 4.. Changes (Δ) in antibodies to RBDs and spikes of hCoVs between 2019 and 2021 in those with vs. without SARS-CoV-2 infection.

(A) Odds of experiencing a boost (change of >0.2 OD) to each antigen by SARS-CoV-2 infection. Odds ratios were estimated using logistic regression. (B)Magnitude of change in ELISA OD to each antigen by SARS-CoV-2 infection. Differences were estimated using linear regression, with ELISA ODs in 2021 modeled as a function of SARS-CoV-2 infection and ELISA ODs in 2019. (C) Pearson’s correlation coefficients among changes in ELISA ODs of the hCoV antigens. Colors indicate correlation, stars indicate significance: <0.05, *; <0.01, **; <0.001, ***.