Effect of Co-Infection with Intestinal Parasites on COVID-19 Severity: A Prospective Observational Cohort Study

Background: COVID-19 symptomatology in Africa appears significantly less serious 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. We investigated this hypothesis in an endemic area in Africa. Methods: Ethiopian COVID-19 patients were enrolled and screened for intestinal parasites. The primary outcome was the proportion of patients with severe COVID-19. Logistic regression models were used to estimate the association between parasite infection, and COVID-19 severity. Models were adjusted for sex, age, residence, and comorbidities. Findings: 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 appeared parasite positive (p<0.0001). Patients co-infected with parasites had lower odds of developing severe COVID-19, with an adjusted odds ratio (aOR) of 0·14 (95% CI 0·09–0·24; p<0·0001) for all parasites, aOR 0·20 ([95% CI 0·11–0·38]; p<0·0001) for protozoa, and aOR 0·13 ([95% CI 0·07–0·26]; p<0·0001) for helminths. When stratified by species, co-infection with Entamoeba spp. , Hymenolopis nana, and Schistosoma mansoni implied lower probability of developing severe COVID-19. There were 11 deaths (1·5%), and all were among patients without parasites (p=0·009). Interpretation: 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. Funding: European and Developing Countries Clinical Trials Partnership (EDCTP) and Joep-Lange Institute. Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The study protocol was reviewed and approved by the Health Research Ethics Review Committee of Mekelle University College of Health Sciences (No.: ERC 1769/2020), the Ethiopian Public Health Institute (No: EPHI 6.13/814), and Eka Kotebe General Hospital (No.: EK/150/5/32). Written informed consent was obtained by all participants, or their guardians, for participation in the study.