Helminth coinfection and COVID-19: An alternate hypothesis

In their recently published commentary, Bradbury and colleagues [1] drew attention to the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions.Helminth infections are known to be powerful modulators of the human immune response, and numerous studies now highlight the effects this may have on human infectious, inflammatory, and metabolic diseases.We believe, however, that any interaction between pre-existing helminth infection and the subsequent severity of COVID-19 need not necessarily be a negative one, and theoretical and empirical evidence suggests that helminths may indeed have a mitigating effect.One of the clear predictors of severe COVID-19 that has emerged during the pandemic has been the presence of obesity, metabolic syndrome, or type 2 diabetes mellitus (T2DM) in patients contracting the virus.[2] These conditions are associated with the second week "cytokine storm" phenomenon [3] that often results in the need for ventilatory support and increased mortality, including in younger patients.These metabolic diseases are characterised by an inflammatory milieu, with increased levels of proinflammatory cytokines, many of which are also implicated in the severe form of COVID-19.Elevated levels of acute phase reactants and proinflammatory cytokines including IFN-γ, IL-1β, IL-6, IL-12, IL-17, IL-18, IL-27, and TNF have been shown to be predictors of clinical deterioration and the onset of severe disease.Lymphopaenia (and, in particular, a reduction in regulatory T cells [Treg] numbers) and eosinopaenia are also closely associated with disease severity.[4] Epidemiological studies over the past decade have consistently reported an inverse relationship between a variety of chronic helminth infections and the presence of metabolic syndrome and T2DM, particularly in transitional societies in which both conditions are prevalent.[5] Recent reports have shown reduced levels of proinflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-12, IL-18, IL-23, IL-27, G-CSF, and GM-CSF in subjects with coexisting helminth infection and T2DM and a partial reversal of this effect following treatment of the worm infection.[6] In addition, chronic helminth infections are associated with increased numbers of Treg cells, M2 macrophages, and eosinophils.It is therefore feasible to propose that a reduced capacity for the production of proinflammatory cytokines and increased numbers of regulatory immune cells due to the immunomodulatory effects of pre-existing helminth infection could result in a reduced risk of severe COVID-19.