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. A retrospective cohort study was conducted using 104 archived plasma samples collected during the third wave of the pandemic in the Ashanti Region of Ghana. ELISA and Luminex assays were used to measure SARS-CoV-2-specific IgA and IgG, neutralizing antibodies, and helminth-specific IgG levels. The results indicated that the highest cumulative seroprevalence of helminths (61.5%) was observed in asymptomatic SARS-CoV-2-infected individuals. In comparison, mild and moderate COVID-19 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 helminths tested. Strikingly, co-exposure resulted in lower SARS-CoV-2-specific IgA/IgG expression and reduced neutralization potential. However, in the plasma of individuals co-seropositive for helminths and SARS-CoV-2, a significantly higher expression of Th2 cytokines and IL-10 over Th1 was observed compared to those who were SARS-CoV-2 positive alone. These data suggest that co-exposure to helminths could mitigate severe COVID-19 outcomes by reducing the Th1 and Th17 responses. Our study highlights the potential protective role of helminth co-infection against severe COVID-19, suggesting that helminth-induced immune modulation may improve clinical outcomes. These findings provide valuable insights for public health policies in helminth-endemic regions and underscore the importance of considering helminth co-infections in managing viral infections.

Background: The interaction between helminth and viral infections has important implications for understanding viral disease outcomes and vaccine efficacy in helminth-endemic regions. We previously demonstrated that helminth seropositivity is associated with reduced Th1/Th17 cytokine levels and reduced COVID-19 severity; however, the underlying immunological mechanisms remain unclear. This study further investigated these mechanisms by assessing how helminth antigens influence SARS-CoV-2-induced T-cell responses in individuals infected with filarial parasites in vitro. Methods: Peripheral blood mononuclear cells (PBMCs) from 43 participants, including Onchocerca volvulus-infected individuals, filarial lymphedema patients, and non-endemic controls, were stimulated in vitro with SARS-CoV-2 peptides and Ascaris lumbricoides antigens. Results: Fluorescence-activated cell sorting analysis showed a significant reduction in SARS-CoV-2-induced CD154 expression on CD4⁺ T cells but an increase on CD8⁺ T cells in O. volvulus-infected participants (p < 0.0001). A. lumbricoides antigens alone did not induce significant T-cell activation in O. volvulus-infected individuals. However, SARS-CoV-2 peptides strongly activated CD4⁺CD154⁺ T cells response (p = 0.0074), but co-stimulation with A. lumbricoides antigens markedly reduced CD3⁺ and CD4⁺CD154⁺ T-cell expression frequencies (p = 0.0329 and p = 0.0452). A. lumbricoides-specific IgG correlated inversely with SARS-CoV-2-induced CD4⁺CD154⁺ expression (r = −0.6025, p = 0.0049), whereas SARS-CoV-2-specific IgG was positively associated with CD4⁺CD154⁺ and CD8⁺CD154⁺ T-cell responses (β = 0.532, p = 0.016 and β = 0.509, p = 0.022). Conclusion: These findings demonstrate that helminth antigens modulate functional SARS-CoV-2-induced T-cell responses, offering a potential mechanism through which helminth co-infections shape antiviral immunity, vaccine efficacy, and clinical disease outcomes.

Background: Ghana exhibits geographic variation across northern and southern regions alongside differences between urban and rural communities, which may influence SARS-CoV-2 exposure and immune response. This study aimed to assess the differences in seroprevalence, and seroconversion status after exposure to SARS-CoV-2 in selected urban and rural Ghanaian communities. Methods: A longitudinal study design was employed. Serum samples (n = 987) were collected during a baseline survey (August 2023–February 2024) with longitudinal follow-up (n = 212) sampling after one year (August 2024-February 2025) among consenting community participants aged ≥10 years selected through household-based sampling in urban and rural settings. Socio-demographic data, clinical symptoms, and vaccination status were collected using structured questionnaires. Serum samples were inactivated and tested with semi-quantitative Anti-SARS-CoV-2 IgG ELISA assays targeting spike (S) and nucleocapsid (N) proteins. Presence of SARS-CoV-2 neutralizing antibodies in serum was determined by a surrogate virus neutralization assay. Results: Of 987 participants aged 10–88 years (67.3% female), SARS-CoV-2 seroprevalence was comparable between urban (47.4%) and rural (47.7%) areas. Among the 212 participants followed longitudinally, 50.9% (108 participants) had both infection or vaccine-induced anti-spike and infection-induced anti-nucleocapsid antibodies after one year, indicating sustained immune responses from prior exposure or vaccination. There was a significant increase in paired spike and nucleocapsid antibody responses between baseline and follow-up (McNemar’s test, χ²(1) = 104.00, p < 0.0001), reflecting ongoing immune boosting despite evidence of antibody waning. Neutralizing antibodies, were detected in 147/148 (99.3%) individuals at timepoint-1 and in all 12 (100%) selected individuals for follow-up at timepoint-2, demonstrating robust functional immunity. Conclusion: This study demonstrates widespread serological evidence of prior SARS-CoV-2 exposure and vaccine-induced immunity in both urban and rural Ghana. Functional neutralising antibodies were detected in a longitudinal subset, suggesting persistence of antibody-mediated protection in some individuals. Larger longitudinal studies with repeated functional immune assessments are needed to better define durable protection in West African settings.