Low systemic IFN response and high viral load are associated with COVID-19 disease severity in unvaccinated patients in Kenya, 2022-2023

Cellular and humoral responses, as well as virus replication kinetics, may affect the severity of COVID-19. This study examined systemic and mucosal immune responses as well as viral load in unvaccinated SARS-CoV-2 patients. Forty-eight COVID-19-positive, grouped into asymptomatic, moderate and severe disease, and 48 COVID-19-negative individuals at Moi Teaching and Referral Hospital in Kenya were included. Severe patients showed higher viral loads and systemic antispike IgG compared to moderate and asymptomatic individuals. Asymptomatic individuals had higher mucosal anti-spike IgG and receptor binding domain (RBD) levels compared to severe patients. Systemic IFN-α mRNA transcript was expressed at higher levels in asymptomatic individuals compared to patients with severe COVID-19 and healthy individuals. Severe patients had significantly lower expression of IFN-γ mRNA transcript levels in both blood and mucosa, as well as significantly lower systemic IFI-16 mRNA transcript levels. These results suggest that mucosal anti-spike and RBD IgG may offer protection, while systemic antibodies indicate disease progression. Suppressed interferon responses, both mucosal and systemic, were linked to severe disease. To conclude, viral load, IFN, anti-viral, and systemic IgGs could help predict COVID-19 outcomes and aid in developing personalized treatment strategies.