Immunological Signatures Driving COVID-19 Severity in Ghanaians: Insights from Upper Airway Transcriptome Analysis

The immunological signatures driving COVID-19 severity in Ghanaians are not well understood. We, therefore, performed bulk transcriptome sequencing of nasopharyngeal samples from SARS-CoV-2-infected Ghanaians with mild and severe COVID-19 and healthy controls to characterize immune signatures at the primary SARS-CoV-2 infection site and identified drivers of disease severity. Generally, a heightened antiviral response was observed in SARS-CoV-2-infected Ghanaians compared with uninfected controls. COVID-19 severity was associated with a dysregulated inflammatory response occasioned by overexpression of IL1A, S100A7, CRNN, and IL23A proinflammatory cytokines and hyperactivation of the NF-κB pathway through MAL signaling. SAMD9L was also among the differentially regulated interferon-stimulated genes (ISGs) in our mild and severe disease cohorts, suggesting that it may be playing a critical role in SARS-CoV-2 pathogenesis. We noted differences in antiviral gene expression by comparing our data with a publicly available dataset from a non-African (Indians) (GSE166530) cohort. Overall, the study identifies immune signatures driving COVID-19 severity in Ghanaians that could serve as potential prognostic markers. It further provides preliminary evidence suggesting differences in antiviral response at the upper respiratory interface in sub-Saharan Africans (Ghanaians) and non-Africans (Indians), which could be contributing to the differences in disease outcomes. Further studies using a larger dataset from different populations will expand on these findings.