Seroprofiling of Antibodies Against Endemic Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 in a Human Immunodeficiency Virus Cohort in Lesotho: Correlates of Antibody Response and Seropositivity

Abstract

Background Serological data on endemic human coronaviruses (HCoVs) and SARS-CoV-2 in southern Africa are scarce. Here, we report on i) endemic HCoV seasonality, ii) SARS-CoV-2 seroprevalence, and iii) predictive factors for SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and HCoV serological response during a 17-month period at the start of the COVID-19 pandemic among adults living with HIV. Methods Plasma samples were collected from February 2020 to July 2021 within an outpatient HIV cohort in Lesotho. We used the ABCORA multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens. Results Results of 3’173 samples from 1’403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter/spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex (p = 0.004), obesity (p < 0.001), working outside the home (p = 0.02), and recent tiredness (p = 0.005) or fever (p = 0.007). Positive correlations were observed between the strength of response to endemic HCoVs and to SARS-CoV-2, and between older age or obesity and the IgG response to SARS-CoV-2. Conclusions These results add to our understanding of the impact of biological, clinical, and social/behavioural factors on serological responses to coronaviruses in southern Africa.

Cross-protective HCoV immunity reduces symptom development during SARS-CoV-2 infection

“…Previous work by us and others strongly suggests a beneficial effect of HCoV immunity in reducing SARS-CoV-2 acquisition and disease severity ( 21 , 22 , 25 , 27 , 28 ), while other studies found no or little effect ( 33 , 34 ). Here, we considered that the discrepancy in results may in part be due to a different relative timing of SARS-CoV-2 and HCoV infections in individual cohorts, as HCoV infections have a pronounced seasonality with the four HCoV strains fluctuating annually and geographically ( 29 , 36 , 37 ). We concluded that a pairwise analysis of pre-infection samples and early post-infection SARS-CoV-2 seropositive samples in a population from the same geographic region during the same time period is needed to provide a controlled framework for studying the impact of HCoV immunity on SARS-CoV-2 antibody responses.…”

“…Although SARS-CoV-2 is not closely related to endemic human coronaviruses (HCoVs), sequence homologies exist and give rise to both cross-reactive antibody and T cell responses ( 18 – 26 ). Indeed, research from others and us has highlighted that pre-existing immunity to HCoVs may limit disease severity either directly ( 27 ) or by supporting the development of SARS-CoV-2-specific humoral ( 22 , 27 – 29 ) and cellular ( 21 ) responses. Cross-reactive HCoV T cell responses ( 21 , 30 ) and cross-reactive HCoV antibodies ( 31 , 32 ) have been postulated to underlie the milder presentation of COVID-19 in children.…”

“…Cross-reactive HCoV T cell responses ( 21 , 30 ) and cross-reactive HCoV antibodies ( 31 , 32 ) have been postulated to underlie the milder presentation of COVID-19 in children. Despite growing evidence, the impact of HCoV immunity on SARS-CoV-2 infection remains to be determined as it has not been observed in all settings ( 29 , 33 , 34 ). The disparity may have several reasons.…”

“…Cross-reactivity can be assumed to be less effective than the later developing specific immunity and may thus depend on a high anti-HCoV activity which may only be maintained for a short period after an HCoV infection. Similarly, the effects of different HCoVs may vary, and geographic and temporal shifts in HCoV prevalence ( 29 , 35 – 37 ) may influence HCoV immunity to SARS-CoV-2 infection, necessitating tightly controlled study settings to unravel and confirm cross-talks. Binding and neutralizing SARS-CoV-2 antibody levels in plasma provide strong correlates of vaccine efficacy ( 38 – 41 ); however, localized mucosal antibodies present at the port of entry may provide the most rapid and effective measure in limiting virus acquisition ( 42 – 46 ).…”