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By mid-September 2020, over 1.33 million confirmed COVID-19 cases and 32 thousand deaths had been reported in Africa. Global research on COVID-19 went 'viral' with a record 3487 research contributions comprising of 2062 journal papers and 1425 preprints published within the first three months following the outbreak of COVID-19. Surprisingly, the silence of the African research community has been unprecedented – contributing a paltry 0.6% (22 contributions), a figure nearly matched by Colombia (18 publications). Until now, a comprehensive perspective on the reasons for this subdued research response, and COVID-19 themes critical to Africa has been missing. We posit that while a milieu of factors accounts for this silence, unprecedented research opportunities exist to support COVID-19 decision and policy formulation in Africa. The subdued response reflects weak research systems, characterized by deep-rooted challenges, including severe lack of research expertise, funding, and infrastructure, coupled with poor working conditions. Hence, Africa's contribution to research on infectious diseases, including COVID-19, remains weak. Perceptions and attitudes among researchers and policy-makers on COVID-19, and the role of science in decision and policy-making also exist. Moreover, COVID-19 and earlier severe acute respiratory syndromes are considered as 'imported diseases' originating from outside Africa. Thus, notions may exist that the control methods will come from outside Africa through 'technology-transfer' or 'capacity-building'. Yet local COVID-19 research is needed to address knowledge gaps, including; (1) potential novel transmission of SARS-CoV-2, (2) adaption of generic COVID-19 control measures to suit African settings, (3) occurrence and persistence of SARS-CoV-2 in solid waste, wastewaters, on-site sanitation systems, and drinking water, and (4) the 'human factor' including the role of gender, perceptions, myths, attitudes, and religious beliefs in the transmission and control of COVID-19. Therefore, there is a need to: (1) strengthen local research capacity and evaluation systems, (2) consider biosafety and ethical issues, (3) initiate cross-disciplinary research and global collaboration on COVID-19, and (4) integrate science communication in COVID-19 programs. Image 1 • COVID-19 infections in Africa continue to rise, with over 1 million confirmed cases. • Current COVID-19 control and potential novel transmission pose challenges in Africa. • Surprisingly, Africa's research response to COVID-19 is subdued and unprecedented. • Weak research, lack of expertise, perceptions and attitudes account for the silence. [ABSTRACT FROM AUTHOR]