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.

Background/Objectives: Although the COVID-19 pandemic has largely concluded, the varied trajectories it has followed in different regions of the world remain incompletely understood. Intensive research is needed to fully grasp its course and the implications for future global health challenges. Notably, the milder trajectory of the COVID-19 pandemic in Sub-Saharan Africa has defied initial predictions. An emerging body of evidence suggests that, in addition to the continent’s younger average age and the lower prevalence of relevant comorbidities, co-infections with helminths may have also impressively shaped the pandemic’s milder trajectory in the region. Indeed, helminths are renowned for their ability to modulate human immune responses, which, while potentially beneficial in limiting excessive inflammation, could also diminish vaccine efficacy and impede viral clearance. This study investigated different aspects of the intricate interactions between COVID-19 and Lymphatic Filariasis (LF), a helminth infection caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi, and Brugia timori and endemic to various regions in Sub-Saharan Africa and the tropics. Methods: For this purpose, samples of a larger and ongoing clinical trial (ethical approval codes: CHRPE/AP/525/17 and 325/21; trial registration number ISRCTN14042737) were collected from 222 individuals from endemic areas of Ghana, along with comprehensive clinical and demographic data. The samples include LF patients (n = 222) grouped according to their Lymphoedema (LE) stages, as well as COVID-19 vaccinated (n = 81) and non-vaccinated individuals (n = 141). All vaccinated participants received the COVID-19 vaccine ChAdOx1-S (also known as Vaxzevria) developed by the University of Oxford and AstraZenca. The expressions of SARS-CoV-2 and filarial-specific antibodies (IgG, IgA) were accessed using ELISA, while Luminex-based immunoassays were employed to measure the expression of SARS-CoV-2 variant-specific neutralizing antibodies. The interplay between vaccine responses and demographic factors was analyzed using group comparisons with the Kruskal-Wallis or Mann-Whitney U tests. Results: The results indicate that a remarkable portion of unvaccinated individuals (56% IgA seropositive, 39% IgG seropositive) developed antibodies against SARS-CoV-2 despite no confirmed infection. Notably, the study identified a robust antibody response to COVID-19 vaccination, which was independent of the degree of LF pathology or parasitic status. An important observation was the reduced SARS-CoV-2 antibody response in individuals seropositive for Ascaris lumbricoides (p = 0.0264), highlighting an interaction between roundworm infection and COVID-19. Conclusions: The study concludes that the ChAdOx1-S COVID-19 vaccine (AstraZeneca) triggers a strong immune response in LF patients; however, filarial and/or soil-transmitted helminth seropositivity might influence the COVID-19 infection-induced response. These findings emphasize the complexity of infectious disease dynamics in co-infected populations and the need to decipher parasite-induced immunomodulatory mechanisms on COVID-19 vaccination.

Introduction: Despite extensive research on COVID-19 vaccines, comparative data on the long-term humoral response across multiple vaccine platforms and heterologous regimens remain limited. SARS-CoV-2 continues to circulate and cause infections globally, highlighting the need to monitor the durability of vaccine-induced immunity. To better understand how different COVID-19 vaccination strategies shape long-term humoral immunity, we conducted a longitudinal study of the vaccines used on the European continent. Methods: The present study investigated the humoral immune response in 331 participants between January 2021 and January 2023, who received mRNA (BNT162b2–BioNTech/Pfizer, mRNA-1273–Moderna), vector-based (ChAdOx1-S–AstraZeneca, Gam-COVID-Vac–Gamaleya Research Institute), inactivated virus (BBIBP-CorV–Sinopharm) vaccines, or a heterologous combination (ChAdOx1-S followed by mRNA), with all participants receiving an mRNA booster 6–8 months after primary vaccination. SARS-CoV-2 IgA, IgG, and IgG-subclasses were measured using ELISA, while neutralizing antibodies were assessed via a multiplex immunoassay, at four different time points: after the first and second dose, six months post-second dose and after the third dose. Results: After two doses, mRNA and ChAdOx1-S-mRNA vaccination induced the highest antibody levels and neutralization potential, followed by the ChAdOx1-S and Gam-COVID-Vac vaccines. The BBIBP-CorV group showed the lowest performance. Antibody levels declined in all participants six months post-vaccination. Booster vaccination (3 ^rd dose) induced high and comparable neutralizing antibody responses in all groups, regardless of the initial two-dose vaccine regimen. The booster vaccine induced increased SARS-CoV-2-specific IgG4 levels, particularly in participants who received two doses of mRNA-1273 as primary vaccination. The IgG subclass response was more influenced by the type of vaccine used for the two-dose primary vaccination than by the mRNA vaccine used for boosting. Conclusion: Altogether, these findings underscore the importance of booster doses and provide valuable insight into the longevity and quality of humoral responses, including the durability and breadth of neutralizing antibodies, across different vaccination strategies.

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.

Introduction: COVID-19 vaccines are the most successful medical interventions to reduce disease severity and mortality. Various vaccine platforms with unique properties have been developed. The course of the pandemic was contrary to the initial predictions, relatively mild in sub-Saharan Africa. Besides other contributing factors, helminths may also play a role due to their immunomodulatory properties. This study aimed to investigate antibody responses in onchocerciasis-infected individuals after multiple doses of different COVID-19 vaccines, comparing mRNA and vector-based vaccines, accounting for co-infections, and contrasting the findings with those from healthy endemic controls..Methods: For this purpose, samples of onchocerciasis-infected individuals (n=110) from a larger and ongoing clinical trial were collected during the COVID-19 pandemic (December 2022) in northwestern Ghana. Participants were grouped according to their COVID-19 vaccine status as unvaccinated, incomplete (1 dose), and complete (2 doses). Helminth-specific and SARS-CoV-2-specific antibodies were quantified using ELISA, while a multiplex immunoassay was used to determine SARS-CoV-2 variant-specific neutralizing antibodies. Non-parametric statistical tests including Kruskal-Wallis and Mann-Whitney-U test were used for group comparison.Results: The data indicated a high SARS-CoV-2 seroprevalence among both, COVID-19 unvaccinated and vaccinated participants, despite the lack of a confirmed infection. Unvaccinated participants (n=44) showed 86% and 77% seropositivity for spike-specific IgA and IgG, respectively. Incompletely (n=22) and completely (n=36) COVID-19 vaccinated groups showed 63% and 50% nucleocapsid seropositivity, indicating viral exposure. The study identified elevated antibody levels following COVID-19 vaccination despite underlying onchocerciasis infection compared to the unvaccinated control group. However, comparable SARS-CoV-2 IgG levels were detected among mRNA and vector-based vaccinated individuals, as well as a higher breakthrough infection rate (NCP-seropositivity) in mRNA vaccinees. Interestingly, active-infected onchocerciasis individuals (Microfilaria positive) showed a reduced vaccine-induced IgG response after complete COVID-19 vaccination. Moreover, helminths may modify the vaccine- or infection-induced SARS-CoV-2 IgG subclass response, as the lack of IgG1 and the expression of IgG4 was associated with microfilaria and soil-transmitted helminth seropositivity.Conclusion: The study concluded that COVID-19 vaccines trigger a strong humoral immune response despite underlying onchocerciasis infection. However, parasitic status or microfilaria load may dampen vaccine-induced responses. These findings highlight the complexity of investigating vaccine responses in the presence of an undeterminable infection history, co-infections and polyparasitism in helminth-endemic areas and emphasize the need to further explore parasite-immunomodulatory mechanisms on COVID-19 vaccine efficacy for future vaccine development.