Toxoplasma gondii as a possible risk factor for COVID-19 severity: a case-control study

Background: COVID-19 is a worldwide pandemic that stroke almost all countries of the world causing thousands of deaths and disabilities and burdened the economy of countries. One of the main criteria of the immune response against COVID-19 is the “immune exhaustion”, due to increased expression of T cell suppressor molecules e.g. programmed death-1 (PD-1), that leads to flaring of viral multiplication and disastrous clinical outcomes. This immune exhaustion is not restricted to COVID-19 but is also a common complication of chronic infections with the widely spreading protozoan, Toxoplasma (T.) gondii. Thus, theoretically, the toxoplasmosis-associated immune exhaustion can worsen that of COVID-19 and consequently increases its severity. However, the studies on this theory are still insufficient. Objective: this work was designed to answer two questions. Does T. gondii co-infection affect the severity of COVID-19 manifestations? Is this action related to T. gondii-induced PD-1 changes? Methodology: Covid-19+patients with moderate and severe conditions were screened for T. gondii IgG and compared to healthy controls. Serum levels of IL-1β, IL-6, TNFα, IFN-γ, IL-1α cytokines were assessed to evaluate COVID-19 severity and prognosis. Lymphocytic expression of PD-1 was assessed by flowcytometry. Results: We recorded a higher incidence of toxoplasmosis among COVID-19 patients especially patients with severe/critical manifestations. T. gondii positive cases exhibited a statistically significant increase in lymphocytic expression of PD-1 that correlated positively with the proinflammatory and bad prognosis cytokines. With fixation of other risk factors for severity, toxoplasmosis still scored a significant value. Conclusion: toxoplasmosis increased the severity of COVID-19. These effects can be related to the Toxoplasma-associated increased lymphocytic PD-1 expression. So, toxoplasmosis can be considered as an unrecognized independent risk factor for COVID-19 severity.