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

Abstract

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, IFNγ, 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 Toxoplasmaassociated increased lymphocytic PD-1 expression. So, toxoplasmosis can be considered as an unrecognized independent risk factor for COVID-19 severity.

Exploring the Association Between Latent Toxoplasma gondii Infection and COVID-19 in Hospitalized Patients: First Registry-Based Study

“…However, in another study, Sharaf-El-Deen demonstrated that the prevalence of toxoplasmosis was significantly higher in patients with COVID-19 (admitted to the Isolation Department of Shibin El-Kom Hospital, Egypt) than in healthy individuals. Their findings also showed the number of T. gondii positive cases was statistically significantly higher in the severe patient group compared with the moderate group [ 28 ]. In a study from the north of Iran, Ghaffari et al .…”

Frequency of exposure to Toxoplasma gondii in COVID-19 patients. a systematic review and meta-analysis

“…The studies' quality was evaluated using the JBI Critical Appraisal Tools for cross-sectional research. All the studies were of moderate quality (Table S3) (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Egger's test for the evaluation of publication bias obtained a value of p = 0.4301 (t = 0.82, df = 11).…”

COVID-19-associated opportunistic infections: a snapshot on the current reports

“…Reactivation of latent toxoplasmosis has been reported in a number of patients who received immunosuppressive therapy, such as corticosteroids [154][155][156][157][158], JAKs inhibitors [159,160], TNF-α blockers [161][162][163] and IL-17A blockers [164], and the most common sequels were ocular [154][155][156][160][161][162] and cerebral [157][158][159]163] toxoplasmosis. In a case-control study among 100 COVID-19 patients in Egypt, a significantly higher prevalence of toxoplasmosis was detected among mild to moderate COVID-19 patients than the healthy control group [165]. Indeed, T. gondii seropositive cases exhibited a significant increase in lymphocytic expression of programmed death-1 (PD-1), which is a marker that correlates with proinflammatory status.…”