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Review
. 2020 Oct 20;2020(1):234-248.
doi: 10.1093/emph/eoaa037. eCollection 2020.

Old friends meet a new foe: A potential role for immune-priming parasites in mitigating COVID-19 morbidity and mortality

Tara J Cepon-Robins  1 , Theresa E Gildner  2
Affiliations
Review

Old friends meet a new foe: A potential role for immune-priming parasites in mitigating COVID-19 morbidity and mortality

Tara J Cepon-Robins et al. Evol Med Public Health. .

Abstract

The novel virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and the associated Coronavirus Disease 2019 (COVID-19) represent a pathogen to which human beings have limited to no evolved immune response. The most severe symptoms are associated with overactive inflammatory immune responses, leading to a cytokine storm, tissue damage, and death, if not balanced and controlled. Hypotheses within Evolutionary Medicine, including the Hygiene/Old Friends Hypothesis, provide an important lens through which to understand and possibly control this overactive immune response. In this article, we explore the role that infection with soil-transmitted helminths (STHs; i.e. intestinal parasitic worms) may play in dampening SARS-CoV-2 symptoms and mitigating the worst COVID-19 outcomes. Specifically, STHs stimulate the immunosuppressive and regulatory T-helper 2 (TH2) branch of the immune system, which decreases ACE2-receptor expression (i.e. receptors SARS-CoV-2 uses to infect host cells), balances the inflammatory TH1/TH17 branches of the immune system triggered by SARS-CoV-2 infection, and reduces inflammation through the release of anti-inflammatory/regulatory cytokines. Because STHs are common and affect the most vulnerable and marginalized members of society, it is especially important to consider how these parasites may impact COVID-19 outcomes. Areas experiencing endemic STH infections are often characterized by a lack of preventative infrastructure and medical care, which may further exacerbate risk of SARS-CoV-2 infection and COVID-19 development. For this reason, we also explore biocultural factors that contribute to disease outcomes for both SARS-CoV-2 and STH infections. Biocultural and Evolutionary Medicine perspectives on COVID-19 are crucial for understanding the global impact of the disease. Lay summary: An evolutionary perspective is required to understand the global impact and various presentations of COVID-19. We consider how coinfection with soil-transmitted helminths (common parasitic worms that coevolved with humans) may suppress inflammatory immune activity, thereby potentially reducing COVID-19 disease severity. Structural and lifestyle factors shaping coinfection patterns are also discussed.

Keywords: COVID-19; Hygiene Hypothesis; Old Friends Hypothesis; biocultural perspectives; mismatch paradigm; soil-transmitted helminths.

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Figures

Figure 1.
Figure 1.
Lifestyle factors linked with elevated rates of chronic inflammatory conditions and reduced rates of STH infection. The physiological effects of decreased STH infection are hypothesized to contribute to both increased chronic inflammation and the risk of severe COVID-19 symptoms, while chronic inflammatory conditions have been identified as risk factors for worse COVID-19 disease outcomes
Figure 2.
Figure 2.
(A) SARS-CoV-2 infects the host through angiotensin-converting enzyme (ACE) 2 receptors which are elevated in inflammatory conditions. Infection triggers the TH1 response, which produces proinflammatory cytokines. When overproduced, TH1 cytokines trigger the hyperinflammatory TH17 response [17, 18]. These responses inhibit Treg cell differentiation, which is needed to suppress inflammatory cytokines. A cytokine storm occurs when proinflammatory cytokines proliferate uncontrollably. (B) The TH2 response to STHs suppresses inflammation through the production of anti-inflammatory and regulatory cytokines, as well as by balancing the TH1 pathway through the production of CD4+ T cells and Treg cells [8, 43, 44]. The TH17 response is less likely to be induced and the cytokine storm should not occur [66]. STHs are associated with reduction in inflammatory comorbidities [8, 34], further reducing likelihood of a cytokine storm and ACE2 receptor presence [69–71]. The TH2 response may also directly reduce ACE2 receptor presence [10, 72]
Figure 3.
Figure 3.
Structural, population-level factors associated with an increased risk for both STH and SARS-CoV-2 infection. These structural factors interact and reinforce one another, contributing to rapid disease spread, increased infection susceptibility, few treatment options, and general poor health. It is expected that STH and SARS-CoV-2 infection risk are both negatively affected by these socio-ecological factors. These two infection types are also hypothesized to interact, such that the immunosuppressive effects of STH infection may increase the risk of initial SARS-CoV-2 infection and make it more difficult to fight off infection
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