Background/Objectives: Helminth infections, particularly prevalent in low- and middle-income countries, have been extensively studied for their effects on human health. With the emergence of new infectious diseases like SARS-CoV-2 and Ebola, their impact on disease outcomes become more apparent. While individual studies have explored the impact of helminth co-infections on disease severity and vaccine efficacy, the findings are often inconsistent and context-dependent. Furthermore, the long-term effects of helminth-mediated immunosuppression on vaccine efficacy and its broader implications for co-infections in endemic regions remain not fully understood. Methods: This systematic review conducted in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines synthesizes the current evidence, identifies patterns, and highlights areas needing further research, offering a cohesive understanding of the topic. PubMed, Scopus, Google Scholar, and Cochrane Library were searched to include studies published from 2003 to February 2025. Results: Co-infection reveals a dual role of helminths in modulating immune responses, with both beneficial and detrimental interactions reported across studies. It may confer benefits against respiratory viral infections by muting hyper-inflammation associated with the severity of conditions like COVID-19, Influenza, and RSV. However, they can exacerbate disease outcomes in most bacteria and blood-borne viral conditions by impairing immune functions, such as neutrophil recruitment and antibody response, leading to more severe infections and higher viral loads. The stage of helminth infection also appears critical, with early-stage infections sometimes offering protection, while late-stage infections may worsen disease outcomes. Helminth infection can also negatively impact vaccine efficacy by suppressing B cell activity, reducing antibody levels, and decreasing vaccine effectiveness against infectious diseases. This immunosuppressive effect may persist after deworming, complicating efforts to restore vaccine efficacy. Maternal helminth infections also significantly influence neonatal immunity, affecting newborn vaccine responses. Conclusions: There is a need for targeted interventions and further research in helminth-endemic regions to mitigate the adverse effects on vaccine efficacy and improve public health outcomes.

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.