| Summary: | Colonization of SARS-CoV-2 with specific bacteria may either protect or increase the risk of disease severity. This study aimed to identify microbial organisms in the lower respiratory tract and their association with SARS-CoV-2 infection. This was a cross-sectional study conducted between May 2020 and August 2021 at the Tamale Public Health Laboratory in the Northern part of Ghana. RT-PCRs for SARS-CoV-2 and bacteriological cultures were performed on sputum samples collected from suspected COVID-19 patients. Biochemical identification and antimicrobial susceptibility tests were performed on the bacterial isolates. A total of 380 participants were recruited into the study. Most participants were within the 21–30 years age group (29.6%). RT-PCR testing detected SARS-CoV-2 in 118 (31.1%) patients. Headache was found to be associated with SARS-CoV-2 (<i>p</i> = 0.033). Sputum cultures yielded 187 (49.2%) positive bacteria growths. <i>Klebsiella</i> spp. (20.5%), <i>Moraxella catarrhalis</i> (7.9%), and <i>Pseudomonas</i> spp. (6.3%) were the most commonly isolated bacteria. <i>M. catarrhalis</i>, <i>Serratia</i> spp., and <i>Stenotrophomonas maltophilia</i> were significantly associated with SARS-CoV-2 infection. Most of the isolates were resistant to 3rd generation cephalosporins. This study has demonstrated the association between specific bacteria and SARS-CoV-2 infection. Clinicians should investigate possible bacterial co-infections in the management of COVID-19 cases.
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