Toxoplasmosis and symptoms severity in patients with COVID-19 in referral centers in Northern Iran.

Toxoplasmosis has been categorized as one of the long-lasting protozoan parasitic infections. It affects almost one-third of the world's population. In recent years, several documented studies have elucidated that infected individuals have a remarkably higher incidence of distinct health problems and show various adverse effects. In the PCR-positive COVID-19 patients in Gonbad-e-Kavus, Kalaleh, and Minoodasht counties in the northern part of Iran from June 2021 to December 2021, we sought to investigate any potential relationships between the severity of COVID-19 symptoms and acute and latent toxoplasmosis caused by Toxoplasma gondii (T. gondii). Whole blood samples of 161 COVID-19 patients with positive PCR. The samples were centrifuged to separate serum and screened for two important antibodies against T. gondii (IgM and IgG) by using ELISA kits for human anti-T. gondii IgM and IgG. Anti-T. gondii IgM and IgG antibodies were detected in 8/161 (5.0%) and 42/161 (26.1%) COVID-19 patients, respectively. No significant relationships were found between Toxoplasma IgM and IgG results with clinical signs, age, sex, contact with animals, comorbidities, and also the mortality rate of people with COVID-19. These findings showed that acute and latent toxoplasmosis infections are common among patients with COVID-19; however, no significant associations were found between toxoplasma infections and the symptoms of COVID-19. Therefore, toxoplasmosis is not considered a risk factor for COVID-19.

First description of congenital toxoplasmosis after maternal coinfection with Toxoplasma gondii and severe acute respiratory syndrome coronavirus 2: a case report.

BACKGROUND: Congenital toxoplasmosis can be associated with serious clinical consequences from fetus to adulthood. Hence, early detection is required to minimize severe sequelae through appropriate therapy. We describe the first case of a congenital toxoplasmosis after maternal coinfection with Toxoplasma gondii and severe acute respiratory syndrome coronavirus 2 and the challenging serological diagnosis of the disease in this context. CASE PRESENTATION: A Caucasian boy was born at 27 weeks 2 days of gestation by cesarean section due to maternal COVID-19-related respiratory failure. Postpartum serological screening of the mother revealed a previously unrecognized active Toxoplasma gondii infection. The premature child initially tested negative for anti- Toxoplasma gondii immunoglobulin A and M antibodies 1, 2 and 4 weeks after birth, whereas immunoglobulin G antibodies were only weakly positive with no evidence of child-specific production. Neither neurological nor ophthalmological abnormalities were detected. Approximately 3 months after birth, serological testing indicated a congenital toxoplasmosis by presence of immunoglobulin A and M, in combination with a child-specific immunoglobulin G synthesis. Additionally, cerebrospinal fluid was tested positive for Toxoplasma gondii DNA. Although no clinical manifestations of congenital toxoplasmosis were detected, an antiparasitic therapy was initiated to minimize the risk of late sequelae. There were no hints for a transplacental transmission of severe acute respiratory syndrome coronavirus 2. CONCLUSION: This case raises the awareness of possible coinfections with the risk of transplacental transmission in cases of maternal coronavirus disease 2019. The report emphasizes the need for screening vulnerable patients for toxoplasmosis in general and especially in the context of pregnancy. It becomes evident that prematurity can complicate the serological diagnosis of congenital toxoplasmosis due to a delayed antibody response. Repeated testing is recommended to carefully monitor children at risk and especially those with a history of preterm birth.

[Toxoplasmosis in the practice of a neurologist]. / Toksoplazmoz v praktike nevrologa.

Toxoplasmosis is a zoonotic protozoal disease characterized by a chronic course, polymorphism of clinical manifestations, predominant damage to the central nervous system, organs of vision, liver and lungs. The causative agent of the disease is the obligate intracellular parasite Toxoplasma gondii, which circulates widely in the external environment and has a large circle of intermediate hosts. Toxoplasmosis is classified by the method of infection (congenital or acquired), by pathogenesis (acute or chronic), by manifestation (latent or with the manifestation of symptoms). According to the state of the human immune system, the disease can occur without immunodeficiency, while the patient has a chronic lifelong carrier, and with immunodeficiency. People with HIV most commonly present with cerebral toxoplasmosis. The article presents a case of the development of toxoplasmosis in a patient in the absence of a burdened history.

ROLE OF IFNgamma IN PATHOGENESIS OF SARS-CoV-2 INFECTION.

To date, there is no consensus explaining the relationship between varying concentrations of IFNgamma and the severity of infection caused by SARS-CoV-2. The aim of this article was to analyze and formulate conclusions from the selected studies and publications, which, in sum, provide a potentially reasonable view on the role of IFNgamma in COVID-19 pathogenesis. This article highlights current data on the immunological role of IFNgamma which affects differentiation of naive T helper cells, acting as a polarizing factor. It activates the major histocompatibility complex (MHC) class I and II, by increasing the expression of MHC I/II subunits, inhibiting replication of the viral particles by initiating activation of interferon-stimulated genes followed by subsequent synthesis of antiviral proteins. Moreover, IFNgamma activates the production of cytokines by T cells, enhancing cytotoxic activity of the T killers. IFNgamma exerts immunostimulatory and immunomodulatory effects via STAT1, SOCS1 and PIAS genes, thus regulating activation of the JAK-STAT signaling pathway. A number of studies were considered where the patterns of changes in serum IFNgamma concentration were examined in viral infections and SARS-CoV-2. We performed a systemic analysis of the results of studies that showed a relationship between high concentrations of IFNgamma and COVID-19 severity. In a number of studies, the significantly high levels of IFNgamma in COVID-19 patients were often associated with a poor outcome of the disease. The median values of the IFNgamma concentration in severe COVID-19 were found to be significantly higher compared to the results obtained in the cases of moderate severity. It shows an increase, in parallel with viral load in the nasopharyngeal samples upon worsening of the clinical condition. Based on the data on the decreased IFNgamma concentrations in convalescent patients, the mechanism of antagonism between IFNgamma and IL-4 is considered, where the decreases serum concentrations of IFNgamma along with increasing level of IL-4 may be an indirect proof of normal adaptive immune response with subsequent development of antibodies to SARS-CoV-2 and gradual elimination of the virus from the body. Moreover, the evidence is discussed that the patients harboring some parasitic infections (Toxoplasma gondii, Cryptosporidium, Blastocystis hominis, Giardia duodenalis, Entamoeba histolytica) with persistently elevated level of IFNgamma are at reduced risk for severe course of COVID-19. Copyright © 2022, SPb RAACI.

Recurrent and De Novo Toxoplasmosis Retinochoroiditis following Coronavirus Disease 2019 Infection or Vaccination.

This study reports three cases of toxoplasmosis retinochoroiditis following coronavirus disease 2019 (COVID-19) infection or vaccination from the national Canadian COVID-19 Eye Registry between December 2020 and September 2021. A 56-year-old male presented 15 days after a positive COVID-19 test with toxoplasmosis retinochoroiditis. He later relapsed 8 days following a first Pfizer-BioNTech vaccine dose. Two patients presented with toxoplasmosis retinochoroiditis following COVID-19 vaccination: A 58-year-old female presenting 4 days following a first Pfizer-BioNTech vaccine dose with anterior uveitis and a posterior pole lesion discovered 3 months later and a 39-year-old female presenting 17 days after a first Moderna vaccine dose. Resolution was achieved with oral clindamycin, oral trimethoprim/sulfamethoxazole, and topical prednisolone acetate 1%. Patients were offered prophylactic trimethoprim/sulfamethoxazole for subsequent doses without relapse. Following COVID-19 infection or vaccination, patients may be at risk for toxoplasmosis retinochoroiditis. Prophylactic antibiotics for future doses may be offered to patients with known ocular toxoplasmosis to prevent recurrence.

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

PURPOSE: This study aimed to determine the possible association between Toxoplasma gondii infection and COVID-19 outcomes among 133 patients with an RT-PCR-positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hospitalized at Imam Khomeini Hospital, Sari, Mazandaran Province, northern Iran, during August to November 2020. METHODS: A questionnaire was used to collect baseline data from the patients who were registered to the Iranian National Registry Center for Toxoplasmosis (INRCT). Also, blood samples were taken from each patient for detecting anti-T. gondii antibodies and T. gondii DNA using enzyme-linked immunosorbent assay (ELISA) and conventional-PCR methods, respectively. Variables related to the COVID-19 severity and outcomes were indicated based on multiple multinomial logistic regression models. RESULTS: Of 133 patients enrolled in the INRCT with COVID-19 through RT-PCR, 50 (37.59%), 52 (39.1%), and 31 (23%) suffered from mild, moderate, and severe COVID-19, respectively. 57.1% of the patients who died had severe COVID-19, while among those with other outcomes, only 18.60% had severe COVID-19 (P < 0.05). Anti-T. gondii IgG was detected in 109/133 (81.95%) patients, which was not statistically significant (P > 0.05). Among those with negative and positive anti-T. gondii IgG, 2 (8.30%) and 29 (26.60%) had severe COVID-19, respectively (P > 0.05). T. gondii DNA and anti-T. gondii IgM were not found in any of the patients. Moreover, all deaths occurred in those with moderate or severe COVID-19 and a positive anti-T. gondii IgG. CONCLUSION: To our knowledge, this is the first registry-based study concerning T. gondii infection among patients with COVID-19. Our data show the high rate of latent T. gondii infection among COVID-19 with different severity. However, there is no significant relationship between latent T. gondii infection and COVID-19 severity and outcomes. Thus, conducting multicenter studies in different geographic regions of the world could offer a better understanding of this relationship.

High-Throughput Screening to Identify Inhibitors of Plasmodium falciparum Importin α.

The global burden of malaria and toxoplasmosis has been limited by the use of efficacious anti-parasitic agents, however, emerging resistance in Plasmodium species and Toxoplasma gondii threatens disease control worldwide, implying that new agents/therapeutic targets are urgently needed. Nuclear localization signal (NLS)-dependent transport into the nucleus, mediated by members of the importin (IMP) superfamily of nuclear transporters, has shown potential as a target for intervention to limit viral infection. Here, we show for the first time that IMPα from P. falciparum and T. gondii have promise as targets for small molecule inhibitors. We use high-throughput screening to identify agents able to inhibit P. falciparum IMPα binding to a P. falciparum NLS, identifying a number of compounds that inhibit binding in the µM-nM range, through direct binding to P. falciparum IMPα, as shown in thermostability assays. Of these, BAY 11-7085 is shown to be a specific inhibitor of P. falciparum IMPα-NLS recognition. Importantly, a number of the inhibitors limited growth by both P. falciparum and T. gondii. The results strengthen the hypothesis that apicomplexan IMPα proteins have potential as therapeutic targets to aid in identifying novel agents for two important, yet neglected, parasitic diseases.