Background
As of 19 August 2021, more than 209 million people globally have been infected with the severe acute respiratory syndrome (SARS-CoV-2), resulting in more than 4.39 million deaths [
1,
2]. The potential risk from SARS-CoV-2 to Africa was identified early in the global pandemic [
3]. As the epicentre of transmission moved from East Asia to West Asia, to Europe, and then to North America, there was speculation as to the likely impact of the pandemic on the African continent with its high rates of infectious diseases including HIV, poverty, and undernutrition, as well as a fragile healthcare system [
3,
4]. However, so far, evidence has shown that the epidemiology of the COVID-19 pandemic in sub-Saharan Africa has been different from the Americas, China, and Europe [
1]. Available seroprevalence data indicate that SARS-CoV-2 has circulated more widely in African populations than can be deduced from the number of reported confirmed cases, hospitalisations, and deaths [
5‐
8]. This has led to speculations that SARS-CoV-2 could have circulated longer in sub-Saharan Africa than the first confirmed cases, but current evidence is limited. Others have speculated that a high prevalence of circulating seasonal coronaviruses could have induced some cross-reactive protective immunity [
9].
In Malawi, though there were initial plans by the government in April 2020 to implement a national lockdown of social and commercial activities, these were never implemented [
10]. As such, unlike other countries in the region, there were no systematic lockdowns but only some curfew restrictions. Schools were officially closed (from 23 March 2020 to 7 September 2020), and many social gathering settings (including restaurants and places of worship) voluntarily closed or had significantly reduced services as a requirement from the government [
11]. Malawi closed its borders and airports from April 2020 to September 2020, with limited essential traffic allowed in and out of the country [
12]. As of 18 August 2021, 58,861 people were confirmed to have been infected by SARS-CoV-2 in Malawi, resulting in 2012 deaths, and 265,491 people had been fully vaccinated with either the AstraZeneca (AZD1222) or Jansen vaccines [
1]. However, due to limited testing, the true burden of COVID-19 in Malawi remains unclear.
Blood donor serosurveys are well-used surrogates for population surveillance of infectious diseases and have been used together with healthcare worker serosurveys to estimate and monitor the extent of the SARS-CoV-2 pandemic in several countries [
5‐
8]. Here, we report results of a national serosurvey using archived serum samples from blood transfusion donors across Malawi from January 2020 to July 2021, generated using a World Health Organization (WHO)-recommended anti-SARS-CoV-2 receptor-binding domain total antibody assay with high sensitivity and specificity, supported by SARS-CoV-2 pseudovirus neutralisation assays to explore variant specificity. We aimed to estimate the magnitude of SARS-CoV-2 population exposure, describe the kinetics of the exposure, approximate the period of SARS-CoV-2 introduction into the population, and determine the viral variants responsible for the epidemic waves.
Discussion
Our study provides important insights into the dynamics of the COVID-19 epidemic in both urban and rural Malawi, with relevance to the southern African region. The seroprevalence estimates from this serosurvey are very high compared to the reported national surveillance figures for confirmed asymptomatic and symptomatic cases, but they do reflect the emergence and magnitude of the first and second COVID-19 epidemic waves in Malawi. They also provide evidence against the speculation that SARS-CoV-2 had been circulating more widely in Malawi before the first detected case in April 2020 or that circulation of endemic coronaviruses [
9] had generated cross-reactive antibody responses. Data from pseudovirus neutralisation assays suggests that the second wave was predominantly driven by the beta variant and highlights poor cross-protection from the first wave on the second wave.
We report a high seroprevalence of 51.5% nationally in February 2021, mirroring the upsurge in confirmed COVID-19 cases, hospitalisations, and death in Malawi experienced during this period [
1,
4]. This is consistent with a study in South African blood donors that reported seroprevalence rates ranging from 31.8 to 62.5% in January 2021 [
22]. So far, the epidemic trajectory in Malawi as determined by the national confirmed COVID-19 cases, deaths, and hospitalisations has paralleled the epidemic trajectory in South Africa [
1]. This is likely due to frequent human migration between the two countries, specifically in the last 12 months during which there has been an influx of groups of returning residents from South Africa to Malawi. This movement of people coincided with rapid surges in COVID-19 cases in the first and second epidemic waves in Malawi [
23]. These findings support the need for a consolidated and standardised regional public health effort in Southern Africa to effectively reduce the risk of further epidemic waves across the region.
Genomic surveillance data from Malawi and South Africa suggests that this high seroprevalence in the second wave is, at least in part, driven by the emergence of the beta variant [
20]. In agreement, our neutralisation data showed that a higher proportion of sera collected from the second wave (February 2021) had neutralising activity against the beta variant than sera from the first wave (June to October 2020), indicating antibody responses driven by infection with the beta variant rather than the original variant (D614G WT). This is consistent with previous studies showing that homologous convalescent sera retain higher in vitro neutralisation potency than heterologous convalescent sera against the infecting virus [
16,
21,
24,
25]. It is also noteworthy that 19% of the second wave sera that were positive for antibodies to the SARS-CoV-2 RBD showed no neutralisation against the beta variant or D614G WT, highlighting a disconnect between qualitative antibody detection and functional activity. This discordance is likely due to low anti-RBD antibody titres as they have been shown to be associated with poor in vitro neutralisation [
21]. It could also be due to infections from other variants of interest/concern.
The temporal kinetics of the SARS-CoV-2 seroprevalence in this serosurvey suggests that the first epidemic wave was largely confined to urban areas. This differs from the second wave, which was more rapid not only in its growth but also in its geographic spread, as shown by the high seroprevalence even in the rural areas. This is consistent with national surveillance reports showing that confirmed COVID-19 cases in the first wave were primarily from the three major cities, Blantyre, Lilongwe, and Mzuzu, but in the second wave, there was an increase in reported cases in rural areas [
26]. Considering that no vaccine was being administered in Malawi between December 2020 and 11 March 2021, the poor cross-protection of first wave sera on the beta variant could in part have contributed to the rapid emergence and spread of this variant in the population. On the other hand, in other settings, high seroprevalence is being driven by high vaccination coverage, but in Malawi, as of July 2021, the coverage was less than 2% of the eligible population; hence, it is highly unlikely that the high seroprevalence was driven by vaccination.
This study has considerable strengths, including consistent monthly sampling, use of well-validated assays, and national geographical representation. There are however some important limitations. First, inherent in using a blood donor sampling frame is that they are not representative of the general population. To mitigate this, the seroprevalence estimates were weighted for population structure based on the official Malawi 2018 Population and Housing Census projection data for the study period. However, we were unable to evaluate the association between the behaviour of blood donors and risk of acquisition to SARS-CoV-2 infection, as this may bias the measured results away from the true population seropositivity. Population-based serosurvey is the ideal, and these could be highly recommended for future studies. Second, in some individuals, SARS-CoV-2 antibodies wane over time to undetectable levels leading to false negatives, especially in those who had asymptomatic COVID-19 [
27,
28]. Therefore, the seroprevalence estimates are likely an underestimate of the cumulative exposure within this sampled population. However, the sampling bias and waning of antibody levels are unlikely to substantially alter the temporal trends reported in this study.
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