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Background: Although comprehensive public health measures such as mass quarantine have been taken internationally, this has generally been ineffective, leading to a high infection and mortality rate. Despite the fact that the COVID-19 pandemic has been downgraded to epidemic status in many countries, the real number of infections is unknown, particularly in low-income countries. However, precision shielding is used in COVID-19 management, and requires estimates of mass infection in key groups. As a result, rapid tests for the virus could be a useful screening tool for asymptomatic virus shedders who are about to come into contact with sensitive groups. In Africa and other low- and middle-income countries there is high rate of COVID-19 under-diagnosis, due to the high cost of molecular assays. Exploring alternate assays to the reverse transcriptase polymerase chain reaction (RT-PCR) for COVID-19 diagnosis is highly warranted. Aim: This review explored the feasibility of using alternate molecular, rapid antigen, and serological diagnostic assays to accurately and precisely diagnose COVID-19 in African populations, and to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR diagnostic challenges in Africa. Method: We reviewed publications from internet sources and searched for appropriate documents available in English. This included Medline, Google Scholar, and Ajol. We included primary literature and some review articles that presented knowledge on the current trends on SARS-CoV-2 diagnostics in Africa and globally. Results: Based on our analysis, we highlight the utility of four different alternatives to RT-PCR. These include two isothermal nucleic acid amplification assays (loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA)), rapid antigen testing, and antibody testing for tackling difficulties posed by SARS-CoV-2 RT-PCR testing in Africa. Conclusion: The economic burden associated COVID-19 mass testing by RT-PCR will be difficult for low-income nations to meet. We provide evidence for the utility and deployment of these alternate testing methods in Africa and other LMICs.