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Summary Background One year after the coronavirus disease 2019 (COVID-19) pandemic, the focus of attention has shifted to the emergence and spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VOCs). The aim of the study was to assess the frequency of VOCs in patients followed for COVID-19 at Kinshasa university hospital (KUH) during the 3rd and 4th waves of the pandemic in Kinshasa. Hospital mortality was compared to that of the first two waves. Method The present study included all patients in whom the diagnosis of SARS-CoV-2 infection was confirmed by the polymerase chain reaction (PCR). The laboratory team sequenced a subset of all SARS-CoV-2 positive samples with high viral loads define as Ct Results During the study period, the original strain of the virus was no longer circulating. The Delta VOC was predominant from June (92%) until November 2021 (3rd wave). The Omicron VOC, which appeared in December 2021, became largely predominant one month later (96%) corresponding the 4th wave. In-hospital mortality associated with COVID-19 fell during the 2nd wave (7% vs. 21% 1st wave), had risen during the 3rd (16%) wave before falling again during the 4th wave (7%) (p Conclusion The Delta (during the 3rd wave) and Omicron VOCs (during the 4th wave) were very predominant among patients followed for Covid-19 in our hospital. Contrary to data in the general population, hospital mortality associated with severe and critical forms of COVID-19 had increased during the 3rd wave of the pandemic in Kinshasa.