Circulation of SARS-CoV-2 and Co-Infection with Plasmodium falciparum in Equatorial Guinea

<b>Background/Objectives:</b> The impact of COVID-19 in Africa has been controversial. Data from African countries are heterogeneous and generally scarce. Many regions are also highly endemic for other infectious diseases like malaria, and it has been suggested that the low incidence and mortality of COVID-19 in malaria-endemic regions could have been related to cross-immunity between malaria and SARS-CoV-2. The aim of this study was to determine the prevalence of SARS-CoV-2 and circulating variants as well as the frequency of co-infections with malaria in Equatorial Guinea. <b>Methods:</b> We conducted antigen tests for SARS-CoV-2 and microscopy malaria examinations in 1556 volunteer participants at six health centres in Bioko and Bata from June to October 2021 and performed SARS-CoV-2 whole-genome sequencing on positive samples to determine the diversity and origin of circulating variants. <b>Results:</b> We report 3.03% of SARS-CoV-2 and 22.25% of malaria prevalence over the sampling period; SARS-CoV-2 cases were found at a similar frequency in all age groups, whereas malaria was most frequent in children and teenagers. Six cases of malaria and SARS-CoV-2 co-infection were found, representing 0.37% prevalence. Genome sequences of 43 SARS-CoV-2 isolates are reported, most of which belong to the lineage Delta and, according to pandemic-scale phylogenies, were introduced from Europe on multiple occasions. <b>Conclusions:</b> This study is relevant in providing first-time estimates of the real prevalence of SARS-CoV-2 in this malaria-endemic country, with the identification of circulating variants, their origin, and co-occurrence with malaria. These data regarding the impact of the pandemic and co-infection with endemic diseases are relevant in future pandemics preparedness.