Information on severe acute respiratory syndrome MESHD coronavirus-2 (SARS-CoV-2) spread in Africa is limited by fragile 2 surveillance systems and insufficient diagnostic capacity. 3 We assessed the coronavirus disease MESHD-19 (COVID-19)-related diagnostic workload in Benin, Western Africa, 4 characterized SARS-CoV-2 genomes from 12 acute cases of COVID-19, used those together with public data to 5 estimate SARS-CoV-2 transmission TRANS dynamics in a Bayesian framework, validated a widely used diagnostic dual target 6 RT-PCR kit donated to African countries, and conducted serological analyses in 68 sera from confirmed COVID-19 7 cases and from febrile patients sampled before the predicted SARS-CoV-2 introduction. 8 We found a 15-fold increase in the monthly laboratory workload due to COVID-19. Genomic surveillance showed 9 introductions of three distinct SARS-CoV-2 lineages. SARS-CoV-2 genome-based analyses yielded an R0 TRANS estimate of 10 4.4 (95% confidence interval: 2.0-7.7), suggesting intense spread of SARS-CoV-2 in Africa. RT-PCR-based tests 11 were highly sensitive but showed variation of internal controls and between diagnostic targets. Commercially available 12 SARS-CoV-2 ELISAs SERO showed up to 25% false-positive results depending on antigen and antibody SERO types, likely due 13 to unspecific antibody SERO responses elicited by acute malaria MESHD according to lack of SARS-CoV-2-specific neutralizing 14 antibody SERO responses and relatively higher parasitemia MESHD in those sera. 15 We confirm an overload of the diagnostic capacity in Benin and provide baseline information on the usability of 16 genome-based surveillance in resource-limited settings. Sero-epidemiological studies SERO Sero-epidemiological studies SERO needed to assess SARS-CoV-2 17 spread may be put at stake by low specificity of tests in tropical settings globally. The increasing diagnostic challenges 18 demand continuous support of national and supranational African stakeholders.