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The copyright holder for this this version posted August 1, 2020 . . https://doi.org/10.1101 Abstract 25
In low-income countries, like Malawi, important public health measures including social 27 distancing or a lockdown, have been challenging to implement owing to socioeconomic 28 constraints, leading to predictions that the COVID-19 pandemic would progress rapidly. 29
However, due to limited capacity to test for severe acute respiratory syndrome coronavirus 2 30 (SARS-CoV-2) infection, there are no reliable estimates of the true burden of infection and 31 death. We, therefore, conducted a SARS-CoV-2 serosurvey amongst health care workers 32 (HCW) in Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection in 33 urban Malawi. 34 35
Five hundred otherwise asymptomatic HCWs were recruited from Blantyre City (Malawi) 37 from 22 nd May 2020 to 19 th June 2020 and serum samples were collected all participants. A 38 commercial ELISA was used to measure SARS-CoV-2 IgG antibodies in serum. We run 39 local negative samples (2018 -2019) to verify the specificity of the assay. To estimate the 40 seroprevalence of SARS CoV-2 antibodies, we adjusted the proportion of positive results 41 based on local specificity of the assay. 42 43
Eighty-four participants tested positive for SARS-CoV-2 antibodies. The HCW with a 45 positive SARS-CoV-2 antibody result came from different parts of the city. The adjusted 46 seroprevalence of SARS-CoV-2 antibodies was 12.3% ]. Using age-stratified 47 infection fatality estimates reported from elsewhere, we found that at the observed adjusted 48 seroprevalence, the number of predicted deaths was 8 times the number of reported deaths. 49 . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.
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The copyright holder for this this version posted August 1, 2020 . . https://doi.org/10.1101 3 50
The high seroprevalence of SARS-CoV-2 antibodies among HCW and the discrepancy in the 52 predicted versus reported deaths, suggests that there was early exposure but slow progression 53 of COVID-19 epidemic in urban Malawi. This highlights the urgent need for development of 54 locally parameterised mathematical models to more accurately predict the trajectory of the 55 epidemic in sub-Saharan Africa for better evidence-based policy decisions and public health 56 response planning. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint
The copyright holder for this this version posted August 1, 2020. February 2020 (2). Due to poor socio-economic conditions, high HIV prevalence, an increase 78 in non-communicable diseases and challenged health system infrastructure, it was predicted 79 that the African pandemic would progress rapidly. As of 16 th July 2020, however, the number 80 of COVID-19 cases was 665,522 and deaths 14,434 (1, 2), much lower than predicted by 81 mathematical models (3). The unrestricted nature of the COVID-19 epidemic in Malawi provides an opportunity to 95 compare its trajectory in a low-income setting with what has been reported in high income 96 settings. It has been shown that the rate of asymptomatic SARS-CoV-2 infection among 97
Health Care Workers (HCW) reflects general community transmission rather than in-hospital 98 exposure (5). We, therefore, conducted a SARS-CoV-2 serosurvey amongst HCW in 99 . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.
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The copyright holder for this this version posted August 1, 2020. . https://doi.org/10. 1101 Blantyre city to estimate the cumulative incidence of SARS-CoV-2 infection in urban 100
Methods 103
The study was conducted at the Malawi-Liverpool-Wellcome Trust Clinical Research 105 programme in Blantyre, Malawi, between 22 nd May 2020 to 19 th June 2020. Participants were 106
HCWs from Blantyre City, both clinical and non-clinical. Inclusion criteria for the study 107 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint
The copyright holder for this this version posted August 1, 2020. . https://doi.org/10.1101/2020.07.30.20164970 doi: medRxiv preprint uncertainty arising from test sensitivity and specificity, we used a Bayesian model to produce 125 a posterior distribution of seroprevalence that incorporates uncertainty associated with a finite 126 sample size (7). The geospatial data was plotted using using RStudio (Version 1.3.959). 127
128 Results 129
We recruited 500 asymptomatic HCW median age 31 (range 20-64 years). The average 131 household size for the participants was 4 [Confidence Interval (CI) 3-5]. Three hundred and 132 thirty-one were clinical HCWs and 169 non-clinical HCWs ( Table 1) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint
The copyright holder for this this version posted August 1, 2020. 153 Eighty-four participants tested positive for SARS-CoV-2 antibodies at the local low cut-off, 154 while 39 participants tested positive for SARS-CoV-2 antibodies at the local conservative 155 high cut-off (Figure 1 and Table 1 ). After adjusting for test sensitivity and specificity, the 156 overall seroprevalence of SARS-CoV-2 antibodies was 12.3% ] at low cut-off 157 and 5.9% ] at conservative high cut-off. This suggests that local transmission was 158 high and that SARS-CoV-2 may have been circulating for some time in Blantyre. 159
To estimate the potential geographical spread of SARS-CoV-2, we plotted the geographical 161 coordinates of place of residence for the individuals with a positive antibody on the map of 162
Blantyre City. We found that the HCW with a positive SARS-CoV-2 antibody result came 163 from different parts of the city (Figure 2) . This suggests that SARS-CoV-2 local transmission 164 was widespread across the city. (Table 2) . We adjusted the population estimates 170 by inflating them to take into account population annual population growth rate of 2% from 171 2018 to 2020 (9). We assumed that there was a uniform risk of infection at all age groups and 172 that the seroprevalence was similar to the general population. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint
The copyright holder for this this version posted August 1, 2020. To our knowledge, this seroprevalence study among HCW is among the first to report 185 estimates of SARS-CoV-2 exposure in an African urban low-income setting. It provides 186 insights into the potentially unique trajectory of the COVID-19 epidemic in sub-Saharan 187 Africa (SSA), using data from urban Malawi. We observe a high seroprevalence of SARS-188
CoV-2 antibodies amongst HCW. It has been reported elsewhere that HCW accounted for a 189 high proportion of cases early in the SARS-CoV-2 outbreak when transmission was 190 increasing sharply and personal protective equipment (PPE) provision was patchy (10-12). 191
Our data could suggest that Malawi is relatively early in the epidemic and that cases are likely to continue to rise sharply in the coming weeks, but the serology also 193 suggests that large numbers of cases must be either asymptomatic or only show mild disease. 194 195 The discrepancy between the predicted compared reported mortality at the observed 196 seroprevalence estimate, may also suggest that there are large numbers of underreported or 197 misclassified deaths in Malawi. However, even in countries like South Africa with relatively 198 abundant testing capacity and strong health systems there is relatively low mortality with a 199 . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.
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The copyright holder for this this version posted August 1, 2020 . . https://doi.org/10.1101 case fatality ratio of 1.5 (13). This may imply that the impact of SARS-CoV-2 in Africa is 200 potentially much less severe or is following a different trajectory than that experienced in 201
China, Americas and Europe, where case fatality ratios were commonly above 5 (1). This 202 warrants further investigation. 203 204 However, the reasons behind the discrepancy in the COVID-19 pandemic trajectory between 205 SSA and elsewhere might include population demography, climate and prior cross-reactive 206 immunity (14). In Malawi, for example, the population is younger (median age 17 years old) 207 (9), and the elderly who mostly experience worse outcomes in other settings (8) is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint
The copyright holder for this this version posted August 1, 2020 . . https://doi.org/10.1101 CoV-2 than that reported but with slow progression of the COVID-19 epidemic. 225
Development of locally parameterised mathematical models should be prioritised to more 226 accurately predict the trajectory of the epidemic in SSA. This will allow better evidence-227 based policy decision-making and public health response planning. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint
The copyright holder for this this version posted August 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint
The copyright holder for this this version posted August 1, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint
The copyright holder for this this version posted August 1, 2020. 