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. 2023 Oct 18;228(8):1042-1054.
doi: 10.1093/infdis/jiad197.

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

Jennifer A Brown  1   2 , Anthony Hauser  3   4 , Irene A Abela  3   5 , Chloé Pasin  3   5 , Selina Epp  5 , Tsepang Mohloanyane  5 , Bienvenu L Nsakala  6 , Alexandra Trkola  5 , Niklaus D Labhardt  1   2   7 , Roger D Kouyos  3   5 , Huldrych F Günthard  3   5
Affiliations

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

Jennifer A Brown et al. J Infect Dis. .

Abstract

Background: Serological data on endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Africa are scarce. Here, we report on (1) endemic HCoV seasonality, (2) SARS-CoV-2 seroprevalence, and (3) correlates of SARS-CoV-2 seropositivity and strength of SARS-CoV-2 and endemic HCoV serological responses among adults living with human immunodeficiency virus (HIV).

Methods: Plasma samples were collected from February 2020 to July 2021 within an HIV cohort in Lesotho. We used the AntiBody CORonavirus Assay (ABCORA) multiplex immunoassay to measure antibody responses to endemic HCoV (OC43, HKU1, NL63, and 229E) and SARS-CoV-2 antigens.

Results: Results for 3173 samples from 1403 adults were included. Serological responses against endemic HCoVs increased over time and peaked in winter and spring. SARS-CoV-2 seropositivity reached >35% among samples collected in early 2021 and was associated with female sex, obesity, working outside the home, and recent tiredness or fever. 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 immunoglobulin G response to SARS-CoV-2.

Conclusions: These results add to our understanding of the impact of biological, clinical, and social/behavioral factors on serological responses to coronaviruses in southern Africa.

Keywords: COVID-19; HIV; coronavirus; serology; southern Africa.

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Conflict of interest statement

Potential conflicts of interest . J. A. B. has received funds from the University of Basel Research Fund. I. A. A. has received honoraria from MSD and Sanofi, a travel grant from Gilead Sciences, and a grant from Promedica Foundation. A. T. has received honoraria from Roche Diagnostics for consultant activity; grants from the Swiss National Science Foundation (SNSF), the Swiss HIV Cohort Study, Pandemiefonds, University of Zurich Foundation; and unrestricted research grants from Gilead Sciences. N. D. L. reports receiving travel grants to attend scientific conferences from Gilead Sciences and grants from SNSF, Fondation Botnar, the Botnar Center for Child Health, the Swiss Agency for Development and Cooperation, and Moritz Straus Stiftung. R. D. K. has received grants from SNSF, the National Institutes of Health, and Gilead Sciences. H. F. G. reports having received honoraria from Gilead Sciences, Merck, ViiV, GSK, Janssen, Johnson and Johnson, and Novartis for serving on data and safety monitoring boards and/or advisory boards and has received a travel grant from Gilead Sciences. In addition, he has received grants from SNSF, the Swiss HIV Cohort Study, the Yvonne Jacob Foundation, and the National Institutes of Health and unrestricted research grants from Gilead Sciences, all paid to the institution. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Seasonality of endemic human coronavirus (HCoV) seroprevalence (2364 samples from 1062 individuals). Antibody reactivity to HCoV antigen is depicted as logarithmic fold change over the empty bead control (LFOE). Results are adjusted for age, sex, and body mass index. Dark red lines along the x-axis indicate the estimated seasonality, with red ribbons indicating 95% confidence intervals for each immunoglobulin (Ig) type/HCoV pairing. Vertical red lines show the estimated peaks. P values refer to likelihood ratio tests assessing the statistical significance of adding a seasonality parameter, that is, of assuming periodic variation of LFOE. Abbreviation: S1, spike glycoprotein subunit 1.
Figure 2.
Figure 2.
Correlation of sex, age, and body mass index (BMI) with serological response to endemic human coronaviruses (HCoVs) (2364 samples from 1062 individuals). Effect sizes with 95% confidence intervals are indicated. Correlations are assessed for sex (reference, male), age category (reference, age <40 years), and BMI category (reference, 18.5–25; BMI calculated as weight in kilograms divided by height in meters squared). Adjusted results consider age, sex, and BMI. Abbreviations: Ig, immunoglobulin; LFOE, logarithmic fold change over the empty bead control; S1, spike glycoprotein subunit 1.
Figure 3.
Figure 3.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence from February 2020 through July 2021 (3173 samples from 1403 individuals). A, Number of samples tested for SARS-CoV-2 seropositivity and AntiBody CORonavirus Assay (ABCORA) test outcome over time. B, SARS-CoV-2 seroprevalence among tested samples over time. Light gray area indicates the 95% confidence interval.
Figure 4.
Figure 4.
Association of demographic, clinical, and behavioral/social factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity (885 samples from 885 individuals). The association of demographic, clinical, and behavioral/social factors (assessed at the time of the first sample) with SARS-CoV-2 seropositivity across all included samples of the respective individual was assessed by logistic regression. Adjusted results use all included variables as covariates. P values refer to the adjusted analyses. Abbreviations: ART, antiretroviral therapy; BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); HIV, human immunodeficiency virus: VL, viral load; WHO, World Health Organization.
Figure 5.
Figure 5.
Association of self-reported recent symptoms with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity (3037 samples from 1345 individuals). The association of symptoms reported for the past 2 weeks at a given visit with SARS-CoV-2 seropositivity at the respective visit (removing samples taken after a positive AntiBody CORonavirus Assay (ABCORA) diagnosis) was assessed using a mixed-effect logistic regression. Separate analyses were conducted for each symptom, using all symptom responses, as well as sex, age category, and body mass index category as covariates for the adjusted odds ratio. P values refer to the adjusted analyses.
Figure 6.
Figure 6.
Association of strength of response to endemic human coronaviruses (HCoVs) at 1 visit with strength of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) response at the subsequent visit (120 samples from 120 individuals). Sample pairs were included if they tested negative for SARS-CoV-2 at the first and positive at the subsequent visit. Adjustment was made for age, sex, and body mass index. A, Multivariate Bayesian model. B, Univariate analysis with coloring indicating the effect on the antibody response to SARS-CoV-2 and full colored blocks indicating when the 95% credibility interval does not cross 0. Abbreviations: Ig, immunoglobulin; N, nucleocapsid; RBD, receptor-binding domain; S1 and S2, spike glycoprotein subunits 1 and 2.
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