Rapidly increasing SARS-CoV-2 seroprevalence and limited clinical disease in three Malian communities: a prospective cohort study

Abstract

Background: The extent of SARS-CoV-2 exposure and transmission in Mali and the surrounding region is not well understood, although infection has been confirmed in nearly 14,000 symptomatic individuals and their contacts since the first case in March 2020. We aimed to estimate the cumulative incidence of SARS-CoV-2 in three Malian communities, and understand factors associated with infection.

Methods: Between 27 July 2020 and 29 January 2021, we collected blood samples along with demographic, social, medical and self-reported symptoms information from residents aged 6 months and older in three study communities at two study visits. SARS-CoV-2 antibodies were measured using a highly specific two-antigen ELISA optimized for use in Mali. We calculated cumulative adjusted seroprevalence for each site and evaluated factors associated with serostatus at each visit by univariate and multivariate analysis.

Findings: Overall, 94.8% (2533/2672) of participants completed both study visits. A total of 50.3% (1343/2672) of participants were male, and 31.3% (837/2672) were aged <10 years, 27.6% (737/2672) were aged 10-17 years, and 41.1% (1098/2572) were aged ≥18 years. The cumulative SARS-CoV-2 exposure rate was 58.5% (95% CI: 47.5 to 69.4). This varied between sites and was 73.4% (95% CI: 59.2 to 87.5) in the urban community of Sotuba, 53.2% (95% CI: 42.8 to 63.6) in the rural town of Bancoumana, and 37.1% (95% CI: 29.6 to 44.5) in the rural village of Donéguébougou. This equates to an infection rate of approximately 1% of the population every three days in the study communities between visits. Increased age and study site were associated with serostatus at both study visits. There was minimal difference in reported symptoms based on serostatus.

Interpretation: The true extent of SARS-CoV-2 exposure in Mali is greater than previously reported and now approaches hypothetical herd immunity in urban areas. The epidemiology of the pandemic in the region may be primarily subclinical and within background illness rates. In this setting, ongoing surveillance and augmentation of diagnostics to characterize locally circulating variants will be critical to implement effective mitigation strategies like vaccines.

Funding: This project was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institute of Biomedical Imaging and Bioengineering, and National Cancer Institute.

Figure 1:. Study flow chart

Visit 1 was completed between 29 July and 16 October 2020 at the Sotuba site, 29 July and 24 September 2020 at the Bancoumana site, and 28 July and 27 August 2020 at the Donéguébougou site. Visit 2 was completed between 21 December 2020 and 26 January 2021 at the Sotuba site, 28 December 2020 and 29 January 2021 at the Bancoumana site, and 14 December 2020 and 15 January 2020 at the Donéguébougou site. A total of 94.7% (2532/2672) of participants completed visit 2.

Figure 2:. Seroprevalence of SARS-CoV-2 antibodies in Mali.

Seroprevalence adjusted for population age distribution and assay sensitivity and specificity [15]. Error bars represent 95% confidence intervals. Asterisk represents p<0.0001 in comparison between sites. Longitudinal SARS-CoV-2 antibody reactivity spike protein and RBD at study sites: Sotuba (top row), Bancoumana (middle row) and Donéguébougou (bottom row). RBD: receptor binding domain, OD: optical density Visit 1: 28 July to 16 October 2020 Visit 2: 14 December 2020 to 29 January 2021

Figure 2:. Seroprevalence of SARS-CoV-2 antibodies in Mali.

Seroprevalence adjusted for population age distribution and assay sensitivity and specificity [15]. Error bars represent 95% confidence intervals. Asterisk represents p<0.0001 in comparison between sites. Longitudinal SARS-CoV-2 antibody reactivity spike protein and RBD at study sites: Sotuba (top row), Bancoumana (middle row) and Donéguébougou (bottom row). RBD: receptor binding domain, OD: optical density Visit 1: 28 July to 16 October 2020 Visit 2: 14 December 2020 to 29 January 2021

Figure 3:. Effect of selected co-variates on seropositivity at A) visit 1 (n=2646, July to October 2020) and B) visit 2 (n=2343, December 2020 to January 2021) by multiple logistic regression

Site, age, sex and symptom categories were included a priori. Other co-variates were included if p<0.05 in univariate analysis (Supplementary Table 3 and 4). 173/2646 participants aged >12 months were seropositive at visit 1. 724/2343 participants aged >12 months were seropositive at visit 1. Infants aged 6-12 months underwent limited history collection and were not included in analysis.