INFLUENCE OF PRE-EXISTING IMMUNE ACTIVATION BY PARASITES ON SARS-CoV-2 IMMUNE RESPONSE

Abstract

Introduction: Despite the high burden of COVID-19 worldwide, the number of COVID-19 related cases and deaths are markedly low in Africa compared to other continents. Mechanisms explaining this occurrence deserve investigation. Severity of COVID-19 is characterized by hyper-inflammatory reaction as a result of imbalance in inflammatory and inhibitory processes of anti-SARS-CoV-2 immune responses, which leads to ARDS, multi-organ failure and death. Parasitic infections on the other hand, have been documented to be potential immune-modulators and drivers of Th-2 immune response characterized by IL-4, IL-10 and IL-13, anti-inflammatory cytokines. Given the inverse burden of COVID-19 and parasitic infection in Africa, the study hypothesized that previous exposure to parasitic infection have the potential to reduce COVID-19 disease severity by modulating immune responses to SARS-CoV-2. The current study sought to explore the impact of past exposure to parasitic infection on the cytokines responses to SARS-CoV-2 using an in-vitro model. Methods: The study involved 39 children and 39 adult participants whose blood samples were collected in 2017. The participants were selected based on levels of anti-Plasmodium falciparum schizont IgG antibodies in circulation as measured using ELISA, as a proxy of exposure to Plasmodium falciparum. The participants were then screened for exposure to soil transmitted helminthes (STH) including Ascaris lumbricoides, Trichuris trichiura and hookworm antigens using ELISA assays. Multiplex luminex assay covering 45 cytokines was used to measure levels of cytokines circulating in participants’ plasma and amount of cytokines released by of their PBMCs after stimulation with SARS-CoV-2 spike proteins. All data analysis was done in R version 4.2.1. Comparison between circulating and stimulated cytokines in children and adults was done using unpaired Wilcox test. Univariate linear regression was conducted to vi assess the effect of prior exposure to parasitic infection on circulating and stimulated cytokines levels. Results: Chemokine and cytokines that are important in disease clearance were detected at higher level in the culture supernatant after PBMCs stimulation with SARS-CoV-2 spike protein. Exposure to parasitic infections had a negative correlation with cytokines that are associated with poor COVID-19 clinical outcome including IL-5, IL-1RA, RANTES, TNF-beta, IL-4, IL-18, IFN-gamma, TNF-alpha, IL-1 alpha, IL-1 beta, IL-10, PDGF-BB, GM-CSF and IL-9. Additionally, exposure to parasitic infections had a positive correlation with cytokines that have been associated with recovery in COVID-19 including Brain-derived neurotrophic factor (BDNF) and IFN-α. However, positive correlation was observed even with cytokines that are associated with COVID-19 disease severity including IP-10, IL-8, IL-23 and IL-22. Conclusion: This study suggests that prior exposure to parasitic infections could have an influence on the cytokines released when an individual’s PBMCs are stimulated with SARS-CoV-2 spike protein. It is possible that the reduced production of cytokines associated with poor prognosis in COVID-19 by PBMC in people with prior exposure to some parasitic infections such as soil transmitted helminthes (STH) may result to less severe disease and hence explain the lower rates of clinical cases of the COVID-19 in