Effect of co-infection with intestinal parasites on COVID-19 severity: A prospective observational cohort study.

Abstract

<i>Background:</i> Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a spectrum of clinical presentations. Evidence from Africa indicates that significantly less COVID-19 patients suffer from serious symptoms than in the industrialized world. We and others previously postulated a partial explanation for this phenomenon, being a different, more activated immune system due to parasite infections. Here, we aimed to test this hypothesis by investigating a potential correlation of co-infection with parasites with COVID-19 severity in an endemic area in Africa. <i>Methods:</i> Ethiopian COVID-19 patients were enrolled and screened for intestinal parasites, between July 2020 and March 2021. The primary outcome was the proportion of patients with severe COVID-19. Ordinal logistic regression models were used to estimate the association between parasite infection, and COVID-19 severity. Models were adjusted for sex, age, residence, education level, occupation, body mass index, and comorbidities. <i>Findings:</i> 751 SARS-CoV-2 infected patients were enrolled, of whom 284 (37.8%) had intestinal parasitic infection. Only 27/255 (10.6%) severe COVID-19 patients were co-infected with intestinal parasites, while 257/496 (51.8%) non-severe COVID-19 patients were parasite positive (<i>p</i><0.0001). Patients co-infected with parasites had lower odds of developing severe COVID-19, with an adjusted odds ratio (aOR) of 0.23 (95% CI 0.17-0.30; <i>p</i><0.0001) for all parasites, aOR 0.37 ([95% CI 0.26-0.51]; <i>p</i><0.0001) for protozoa, and aOR 0.26 ([95% CI 0.19-0.35]; <i>p</i><0.0001) for helminths. When stratified by species, co-infection with <i>Entamoeba</i> spp., <i>Hymenolepis nana, Schistosoma mansoni</i>, and <i>Trichuris trichiura</i> implied lower probability of developing severe COVID-19. There were 11 deaths (1.5%), and all were among patients without parasites (<i>p</i> = 0.009). <i>Interpretation:</i> Parasite co-infection is associated with a reduced risk of severe COVID-19 in African patients. Parasite-driven immunomodulatory responses may mute hyper-inflammation associated with severe COVID-19. <i>Funding:</i> European and Developing Countries Clinical Trials Partnership (EDCTP) - European Union, and Joep Lange Institute (JLI), The Netherlands. <i>Trial registration:</i> Clinicaltrials.gov: NCT04473365.