A study by researchers from Malawi and United Kingdom reveals a significant discrepancy between predicted coronavirus disease (COVID-19) mortality in the observed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence rates in health care workers and reported deaths in urban Malawi in southeastern Africa, indicating early exposure, but a slow progression of the outbreak. Their findings are currently available on the medRxiv* preprint server.
The ongoing COVID-19 pandemic, caused by SARS-CoV-2, had a dramatic impact worldwide due to high mortality rates in Asia, the United States, and Europe. As a result of specific socio-economic conditions, high prevalence of human immunodeficiency virus (HIV), and challenged health system infrastructure, it was predicted that the pandemic in Africa would be swift and dire.
However, in low-income countries like Malawi, there are no reliable estimates of the actual burden of COVID-19 infection and death, primarily due to limited testing capacity. Due to the latter, initial testing efforts focused on case identification in patients with COVID-19-like symptoms, as well as inbound travelers.
Such unrestricted nature of the COVID-19 epidemic in Malawi enables the comparison of its trajectory in a low-income setting with reports from high-income settings. Moreover, it has been shown that the rate of asymptomatic SARS-CoV-2 infection among health care workers actually reflects community transmission rather than in-hospital exposure.
Consequently, researchers from Malawi-Liverpool-Wellcome Trust Clinical Research Programme, the University of Malawi and Queen Elizabeth Central Hospital in Blantyre, Malawi, as well as from the University of Liverpool and Liverpool School of Tropical Medicine in the UK, conducted a SARS-CoV-2 serological survey among health care workers in Blantyre city to appraise the cumulative incidence of SARS-CoV-2 infection in urban Malawi.
Map of Blantyre showing geospatial distribution of seropositive results using the low local assay cut-off, Black dot, negative; Red dot, positive; Orange dot, indeterminate
Measuring SARS-CoV-2 IgG antibodies
A total of five hundred (otherwise asymptomatic) health care workers were recruited from Blantyre City in Malawi between May 22, 2020, and June 19, 2020. Peripheral blood samples were taken from all study participants in serum separation tubes.
A commercial enzyme-linked immunosorbent assay (ELISA) that targets viral spike protein and nucleoprotein was utilized for measuring SARS-CoV-2 IgG antibodies in serum. For control purposes, the researchers ran local negative samples to verify the specificity of the assay.
Finally, in order to appraise the seroprevalence of SARS CoV-2 antibodies, the researchers have adjusted the proportion of positive results based on the local specificity of the assay. A Bayesian model was used to produce a posterior distribution of seroprevalence that takes into account uncertainty associated with finite sample size.
High and widespread local transmission
A total of 84 study participants tested positive for SARS-CoV-2 antibodies, and the adjusted seroprevalence rate of SARS-CoV-2 antibodies was 12.3%. This implies that local transmission was rather high and that SARS-CoV-2 may have been circulating for some time in Blantyre.
Furthermore, healthcare workers with a positive SARS-CoV-2 antibody test result came from different parts of the city, suggesting that local viral transmission was indeed widespread across the city.
The use of age-stratified infection fatality estimates has revealed that, at the observed adjusted seroprevalence, the number of predicted deaths was eight times the number of reported deaths. When this is extrapolated to entire Malawi, it predicts more than five thousand deaths; nevertheless, only 51 deaths have been reported by July 16, 2020.
As a result, these crude estimates emphasize a sizeable discrepancy between the predicted deaths informed by infection fatality rates from elsewhere and the actual number of reported lethal outcomes due to COVID-19 in Malawi.
Outbreak following a different trajectory
"Our data could suggest that Malawi is relatively early in the epidemic and that COVID-19 cases are likely to continue to rise sharply in the coming weeks, but the serology also suggests that large numbers of cases must be either asymptomatic or only show mild disease", explain study authors.
Moreover, the discrepancy between the predicted mortality and currently reported numbers may also suggest that Malawi may be faced with a large number of misclassified or underreported deaths. Nonetheless, other countries have also shown low mortality and case fatality rates (most notably South Africa with abundant testing capacity).
This may suggest that the impact of COVID-19 in Africa is potentially less severe or following a different trajectory when compared to experiences in China, the United States, and Europe. Some of the reasons might include climate, population demography, and prior cross-reactive immunity.
In any case, the development of locally parameterized mathematical models should be prioritized in future research endeavors to increase the accuracy of trajectory prediction in sub-Saharan Africa. This will, in turn, open the door for improved evidence-based policy decision-making and public health response planning.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
⚠️PREPRINT ALERT ⚠️Fascinating data from #Malawi with high levels of COVID immunity found in healthcare workers despite relatively low cases and deaths (at the time of writing). Data like this is vital for us to improve the models used to predict SARS-CoV-2 impact in Africa. https://t.co/4kT3Bcaqfm
One more study in (urban) East Africa, pointing to fairly high Covid-19 rates of infection, but seemingly low mortality. https://t.co/6iVoDiPNMB
Important data on which to base better mathematical models to estimate the #COVID19 epidemic in urban southern African countries. Reported deaths 8x lower than predicted from European models. Excellent work from @MlwTrust @kjambo @Stephengordon14 and team https://t.co/OGbzh66tga
Congrats to @kjambo & @MlwTrust team for this important work. Adjusted #SARSCoV2 seroprevalence 12.3% (95% CI 9.0-15.7) among 500 asymptomatic healthcare workers in Blantyre #Malawi. 1/3 https://t.co/dKJR0mmxC0