Rapidly Increasing Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence and Limited Clinical Disease in 3 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. We aimed to estimate the cumulative incidence of SARS-CoV-2 in three communities, and understand factors associated with infection. Methods Between July 2020 and January 2021, we collected blood samples and demographic, social, medical, and self-reported symptoms information from residents aged 6 months and older over 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 community and evaluated factors associated with serostatus at each visit by univariate and multivariate analysis. Results Overall, 94.8% (2533/2672) of participants completed both study visits. A total of 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% in the urban community of Sotuba, 53.2% in the rural town of Bancoumana, and 37.1% in the rural village of Donéguébougou. Study site and increased age were associated with serostatus at both study visits. There was minimal difference in reported symptoms based on serostatus. Conclusion The true extent of SARS-CoV-2 exposure in Mali is greater than previously reported and may now approach hypothetical ‘herd immunity’ in urban areas. The epidemiology of the pandemic in the region may be primarily subclinical and within background illness rates.

Pre-pandemic SARS-CoV-2 serological reactivity in rural malaria-experienced Cambodians

“…We found in a widely-used, highly specific, and validated enzyme linked-immunosorbent assay that approximately 4 -14% of pre-pandemic Cambodian sera samples were positive for nonneutralizing antibodies to SARS-CoV-2 spike and RBD antigens using various standardized optical density cut-off values (4,13,14). A relationship was noted between increased SARS-CoV-2 seroreactivity and anti-malarial humoral immunity as was also recently shown in Africa (7).…”

“…There are no published SARS-CoV-2 serosurveys in the Greater Mekong Subregion (GMS), aside from screening healthcare workers in two urban hospital-based settings (1,2). These antibody-based studies are necessary to estimate at-risk populations and to direct disease containment measures; however, prior to informing public health decisions, serological assays require careful country-specific calibration as several regions report fluctuating results or high background reactivity in different populations (3)(4)(5). This variability may be attributable to the myriad serological assays, the hypothesized cross-reactivity from 'common cold'-type respiratory coronaviruses (6), prior Plasmodium infections (7)(8)(9), or previously uncharacterized betacoronaviruses in wildlife populations found in the rural GMS (10)(11)(12).…”

SARS-CoV-2 Cross-Reactivity in Prepandemic Serum from Rural Malaria-Infected Persons, Cambodia

“…We found in a widely used, highly specific, and validated ELISA that ≈4%–14% of prepandemic serum samples from malaria-infected persons in Cambodia were positive for nonneutralizing antibodies to SARS-CoV-2 spike and RBD antigens by using various standardized optical density cutoff values ( 4 , 12 , 13 ). We noted a relationship between increased SARS-CoV-2 seroreactivity and antimalarial humoral immunity, which was also recently shown in Africa (S. Lapidus et al, unpub.…”

“…Reactivity to both spike and RBD antigens above cutoff values is required for a positive test with reported sensitivity of 100% (95% CI 92.9%–100%) and specificity of 100% (95% CI 98.8%–100%) ( 12 , 13 ). Prepandemic samples had levels above the set cutoffs for SARS-CoV-2 spike and RBD antigens ( Figure 1 ) varying from 4.4% to 13.8% positivity to both SARS-CoV-2 spike and RBD depending on which cutoff values (calibrated for the Mali or US populations) were used for this assay ( 4 , 12 , 13 ) ( Table ; Figure 1 ; Appendix Table 1).…”

“…We further tested 289 samples to assess whether a relationship existed between antibodies to Plasmodium spp. and SARS-CoV-2 proteins by using 2 known malarial antigens: Plasmodium falciparum apical membrane antigen 1 (AMA-1), which is highly immunogenic and an indicator of parasite exposure, and P. falciparum Pfs25 protein (Pfs25), which is poorly immunogenic and expressed only during the mosquito stages of parasite development ( 4 ) ( Figure 2 , panels B–E). Of note, when we grouped samples by SARS-CoV-2 serostatus, we detected significantly higher levels of AMA-1 antibodies in SARS-CoV-2–seropositive persons than seronegative persons (mean AMA-1 antibody level 3.0 vs. 2.1; p = 0.0003) ( Figure 2 , panel B).…”