Helminth Seropositivity Inversely Correlated with Th1 and Th17 Cytokines and Severe COVID-19

Background/Objectives: The COVID-19 pandemic has significantly impacted global health. However, Africa has reported relatively low numbers of cases and fatalities. Although the pandemic has largely receded, the reasons for its milder course on the African continent have not yet been fully clarified. This study explored the hypothesis that helminth co-infections may have contributed to these observations. Methods: A retrospective cohort study was conducted using 104 plasma samples collected during the third wave of the pandemic in the Ashanti Region of Ghana. Luminex assays were used to measure SARS-CoV-2-specific IgA and IgG, neutralizing antibodies, systemic cytokines and helminth-specific IgG. Results: The results indicated that the highest cumulative seroprevalence of helminths (61.5%) was observed in asymptomatic COVID-19 patients. In comparison, mild and moderate patients had helminth seropositivity rates of 43.8% and 34.5%, respectively, which were 1.4 and 1.8 times lower than those of the asymptomatic group, respectively. Notably, the two severe COVID-19 cases investigated were seronegative for all three of the helminths tested. Strikingly, co-exposure resulted in lower SARS-CoV-2-specific IgA/IgG expression and reduced neutralization potential. However, co-seropositive individuals for helminths and SARS-CoV-2 exhibited a higher expression of Th2 cytokines and IL-10 over Th1 cytokines compared to SARS-CoV-2-positive individuals alone. Conclusion: These data suggest that co-exposure to helminths could mitigate the severity of COVID-19 outcomes by reducing the Th1 and Th17 responses; this highlights the potential protective role of helminthiasis against severe COVID-19. These findings provide valuable insights for the development of public health policies in helminth-endemic regions and underscore the importance of considering helminth co-infections in managing viral infections. It also offers a plausible explanation for the milder disease severity observed in helminth-endemic regions while raising critical considerations regarding vaccine efficacy, as helminth-induced immune modulation may influence the magnitude and quality of vaccine-induced immune responses.