Helminth coinfection and COVID-19: An alternate hypothesis

Hays, Russell; Pierce, Doris R.; Giacomin, Paul; Loukas, Alex; Bourke, Peter; McDermott, Robyn

doi:10.1371/journal.pntd.0008628

Cited by 49 publications

(53 citation statements)

References 14 publications

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“…One of them stipulates that helminths could worsen COVID-19 severity, due to their immunomodulatory effects involving type 2 immune response (52, 53). An alternative hypothesis is that pre-exposure to helminths infection could reduce the risk of severe COVID-19 outcomes, through a downregulation in the production of proinflammatory cytokines involved in the hyperinflammation of the lungs and ‘cytokine storm’ commonly observed in severe and fatal COVID-19 disease (18, 19).…”

Section: Discussionmentioning

confidence: 99%

“…We selected prevalence of malaria, soil-transmitted helminths, filariasis and schistosomiasis as indicators of prior exposure to endemic infections based on the literature (18,19,48,57) and on consultation with parasitology experts. Prior exposure to malaria was measured using age-standardised predicted parasite prevalence rate for children two to ten years of age for Plasmodium falciparum , and in all ages for Plasmodium vivax .…”

Section: Supplementary Filementioning

confidence: 99%

“…Parasites such as Plasmodium spp. and soil-transmitted helminths, to which many LIC populations are exposed since early childhood, have immunomodulatory effects (18, 19). Access to improved water and sanitation may be a distal factor related to exposure to these parasites.…”

Section: Introductionmentioning

confidence: 99%

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Country differences in transmissibility, age distribution and case-fatality of SARS-CoV-2: a global ecological analysis

Favas

Jarrett

Ratnayake

et al. 2021

Preprint

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Introduction SARS-CoV-2 has spread rapidly across the world yet the first pandemic waves in many low-income countries appeared milder than initially forecasted through mathematical models. Hypotheses for this observed difference include under-ascertainment of cases and deaths, country population age structure, and immune modulation secondary to exposure to endemic parasitic infections. We conducted a country-level ecological study to describe patterns in key SARS-CoV-2 outcomes by country and region and to explore possible associations of the potential explanatory factors with these outcomes. Methods We collected publicly available data at country level and compared them using standardisation techniques. We then explored the association between exposures and outcomes using alternative approaches: random forest (RF) regression and linear (LM) regression. We adjusted for potential confounders and plausible effect modifications. Results Altogether, data on the mean time-varying reproduction number (mean R_t) were available for 153 countries, but standardised averages for the age of cases and deaths and for the case-fatality ratio (CFR) could only be computed for 61, 39 and 31 countries respectively. While mean R_t was highest in the WHO Europe and Americas regions, median age of death was lower in the Africa region even after standardisation, with broadly similar CFR. Population age was strongly associated with mean R_t and the age-standardised median age of observed cases and deaths in both RF and LM models. The models highlighted other plausible roles of population density, testing intensity and co-morbidity prevalence, but yielded uncertain results as regards exposure to common parasitic infections. Conclusions The average age of a population seems to be an important country-level factor explaining both transmissibility and the median age of observed cases and deaths, even after age-standardisation. Potential associations between endemic infections and COVID-19 are worthy of further exploration but seem unlikely, from this analysis, to be key drivers of the variation in observed COVID-19 epidemic trends. Our study was limited by the availability of outcome data and its causally uncertain ecological design, with the observed distribution of age amongst reported cases and deaths suggesting key differences in surveillance and testing strategy and capacity by country and the representativeness of case reporting of infection. Research at subnational and individual level is needed to explore hypotheses further.

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Section: Discussionmentioning

confidence: 99%

Section: Supplementary Filementioning

confidence: 99%

See 1 more Smart Citation

Country differences in transmissibility, age distribution and case-fatality of SARS-CoV-2: a global ecological analysis

Favas

Jarrett

Ratnayake

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…On one hand, down regulation of the host's immune response through parasite-induced microbiome changes may result in suboptimal antiviral immunity, resulting in increased SARS-CoV-2 replication. Along these lines, it was suggested that the "potential negative effects may influence recommendations on deworming" (Hays et al, 2020). On the other hand, intestinal parasites may down-regulate the host immune and chronic inflammatory conditions, such as autoimmunity (McSorley and Maizels, 2012;Wammes et al, 2014;Chabé et al, 2017;Burrows et al, 2019;Ryan et al, 2020), potentially protecting from severe COVID-19.…”

Section: Impact Of Parasite-driven Microbiome Change On the Pathogenesis Of Covid-19mentioning

confidence: 99%

“…This notion is supported by the fact that enteric helminth protect against pulmonary virus infection through interaction with microbiota (McFarlane et al, 2017). Though Bradbury et al (2020) suggest that helminth co-infection might hasten COVID-19 severity, an alternative hypotheses suggested that helminths might indeed reduce the severity of SARS-CoV-2 infection (Fonte et al, 2020;Hays et al, 2020;Mbow et al, 2020). The later hypotheses are corroborated by the observed low fatality rate of COVID-19 in SSA setting and elsewhere in LMICs with potential high parasite loads (Fonte et al, 2020;Mbow et al, 2020).…”

Section: Impact Of Parasite-driven Microbiome Change On the Pathogenesis Of Covid-19mentioning

confidence: 99%

Interrogating the Impact of Intestinal Parasite-Microbiome on Pathogenesis of COVID-19 in Sub-Saharan Africa

et al. 2021

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Immunomodulation of COVID‐19 severity by helminth co‐infection: Implications for COVID‐19 vaccine efficacy

Akelew

Henok

Ebrahim

et al. 2021

Immunity Inflam & Disease

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), an emerging virus in late 2019 causing coronavirus disease 2019 (COVID‐19), has caused a catastrophic effect, resulting in an unprecedented global crisis. The immunopathology of COVID‐19 appears to be clearly associated with a dysregulated immune response leading to organ failure and death. Similarly, over two billion people worldwide are infected with helminth, with those living in low‐middle‐income countries disproportionately affected. Helminth infections have been shown to possess immunomodulatory effects in several conditions. Helminth co‐infection in COVID‐19 patients is one of the potential reasons for global attention to answer why COVID‐19 severity is still lower in helminth endemic countries. Recent studies have shown that helminth endemic countries showed fewer cases and deaths so far and helminth co‐infection might reduce the severity of COVID‐19. Moreover, lessons from other diseases with helminth co‐infection have been shown to substantially reduce vaccine efficacy that could also be implicated for COVID‐19. This immunomodulatory effect of helminth has intended and unintended consequences, both advantageous and disadvantageous which could decrease the severity of COVID‐19 and COVID‐19 vaccine efficacy respectively. Herewith, we discuss the overview of COVID‐19 immune response, immunomodulatory effects of helminth co‐infections in COVID‐19, lessons from other diseases, and perspectives on the efficacy of COVID‐19 vaccines.

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Helminth coinfection and COVID-19: An alternate hypothesis

Cited by 49 publications

References 14 publications

Country differences in transmissibility, age distribution and case-fatality of SARS-CoV-2: a global ecological analysis

Country differences in transmissibility, age distribution and case-fatality of SARS-CoV-2: a global ecological analysis

Interrogating the Impact of Intestinal Parasite-Microbiome on Pathogenesis of COVID-19 in Sub-Saharan Africa

Immunomodulation of COVID‐19 severity by helminth co‐infection: Implications for COVID‐19 vaccine efficacy

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