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

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 (T2) branch of the immune system, which decreases ACE2-receptor expression (i.e. receptors SARS-CoV-2 uses to infect host cells), balances the inflammatory T1/T17 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.