Susceptibility to COVID-19, the most devastating global pandemic, appears to vary widely across different population groups. Exposure to toxoplasmosis has been proposed as a theory to explain the diversity of these populations. The aim of the present study was to investigate the possible association between latent toxoplasmosis and COVID-19 and its probable correlation with markers of oxidative stress, C-reactive protein (CRP) and ferritin. In a case-control study, blood samples were collected from 91 confirmed (48 non-pneumonic; NP, and 43 pneumonic; P) COVID-19 patients and 45 healthy controls. All participants were tested for IgG anti-Toxoplasma gondii antibodies and oxidative stress markers (nitric oxide [NO], superoxide dismutase [SOD] and reduced glutathione [GSH]), and CRP and serum ferritin levels were determined. In COVID-19 patients, IgG anti-T. gondii antibodies were found in 54% compared to 7% in the control group, with the difference being statistically significant (P ˂ 0.001). However, no significant correlation was found between the severity of COVID-19 and latent T. gondii infection. Latent toxoplasmosis had a strong influence on the risk of COVID-19. NO and SOD levels were significantly increased in COVID-19 patients, while GSH levels decreased significantly in them compared to control subjects (P ˂ 0.001 for both values). CRP and ferritin levels were also significantly elevated in P COVID-19 patients infected with toxoplasmosis. This is the first study to look at the importance of oxidative stress indicators in co-infection between COVID-19 and T. gondii. The high prevalence of latent toxoplasmosis in COVID-19 suggests that T. gondii infection can be considered a strong indicator of the high risk of COVID-19.

Department of Chest Diseases College of Medicine Beni Suef University Beni Suef Egypt

Department of Gastroenterology Hepatology and infectious diseases College of Medicine Beni Suef University Beni Suef Egypt

Department of Medical Parasitology College of Medicine Beni Suef University Beni Suef Egypt

Department of Zoology Faculty of Science Beni Suef University Beni Suef Egypt

Research Institute of Medical Entomology General Organisation for Teaching Hospitals and Institutes Giza Egypt

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Abbasi M., Daneshpour M.S., Hedayati M., Mottaghi A., Pourvali K., Azizi F. 2018: The relationship between MnSOD Val16Ala gene polymorphism and the level of serum total antioxidant capacity with the risk of chronic kidney disease in type 2 diabetic patients: a nested case-control study in the Tehran lipid glucose study. Nutr. Metab. (London). 15: 25. PubMed DOI

Abdoli A., Falahi S., Kenarkoohi A. 2022: COVID-19-associated opportunistic infections: a snapshot on the current reports. Clin. Exp. Med. 22: 327-346. PubMed DOI

Abed A.A., Kalaf A.K. 2023: Serological detection for toxoplasmosis among patients with Covid-19 in Thi-Qar Province. Inst. Razi. Archives 78: 675-680.

Al-Khshab E.M. 2010: Some antioxidants level in seropositive toxoplasmosis woman in Mosul. Tikrit J. Pure Sci. 15: 17-22.

Ali M.S., Saheb E.J. 2022: Serum levels of C-reactive protein and ferritin in COVID-19 patients infected with Toxoplasma gondii. Ann. Parasitol. 68: 47-54.

Bamorovat M., Sharifi I., Aflatoonian M.R., Karamoozian A., Tahmouresi A., Jafarzadeh A., Heshmatkhah A., Sharifi F., Salarkia E., Khaleghi T. 2022: Prophylactic effect of cutaneous leishmaniasis against COVID-19: a case-control field assessment. Int. J. Infect. Dis. 122: 155-161. PubMed DOI

Baraboutis I.G., Gargalianos P., Aggelonidou E., Adraktas A. 2020: Initial real-life experience from a designated COVID-19 centre in Athens, Greece: a proposed therapeutic algorithm. SN. Compr. Clin. Med. 2: 689-693. PubMed DOI

Binici I., Alp H.H., Huyut Z., Gurbuz E., Gunbatar H., Akmese Ş., Karahocagilm K., Akbayh.İ. 2023: The status of antioxidants and oxidative damage in patients with COVID-19. Ahi Evran. Med. J. 7: 114-123. DOI

Bradbury R.S., Piedrafita D., Greenhill A., Mahanty S. 2020: Will helminth co-infection modulate COVID-19 severity in endemic regions? Nat. Rev. Immunol. 20: 342-342. PubMed DOI

Can H., Alak S.E., Köseoğlu A.E., Döşkaya M., Ün C. 2020: Do Toxoplasma gondii apicoplast proteins have antigenic potential? An in silico study. Comput. Biol. Chem. 84: 107158. PubMed DOI

Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., Qiu Y., Wang J., Liu Y., Wei Y. 2020: Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet 395: 507-513. PubMed DOI

Cristiana F., Elena A., Nina Z. 2014: Superoxide dismutase: therapeutic targets in SOD related pathology. Health 6: 975-988. DOI

Denkers E.Y., Kim L., Butcher B.A. 2003: In the belly of the beast: subversion of macrophage proinflammatory signalling cascades during Toxoplasma gondii infection. Cell Microbiol. 5: 75-83. PubMed DOI

El-Sayed A., Aleya L., Kamel M. 2021: COVID-19: a new emerging respiratory disease from the neurological perspective. Environ. Sci. Pollut. Res. Int. 28: 40445-40459. PubMed DOI

Ellman G.L. 1959: Tissue sulfhydryl groups. Arch. Biochem. Biophys. 82: 70-77. PubMed DOI

Fekadu A., Shibre T., Cleare A.J. 2010: Toxoplasmosis as a cause for behaviour disorders-overview of evidence and mechanisms. Folia Parasitol. 57: 105. PubMed DOI

Flegr J. 2013: Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis. J. Exp. Biol. 216: 127-133. PubMed DOI

Flegr J. 2021: Toxoplasmosis is a risk factor for acquiring SARS-CoV-2 infection and a severe course of COVID-19 in the Czechand Slovak population: a preregistered exploratory internet cross-sectional study. Parasit. Vectors 14: 508. PubMed DOI

Galván-Ramírez M.D.I. L., Salas-Lais A.G., Muñoz-Medina J.E., Fernandes-Matano L., Pérez L.R.R., Franco de León K. 2023: Association of toxoplasmosis and COVID-19 in a Mexican population. Microorganisms 11: 1441. PubMed DOI

Gao Y., Li T., Han M., Li X., Wu D., Xu Y., Zhu Y., Liu Y., Wang X., Wang L. 2020: Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19. J. Med. Virol. 92: 791-796. PubMed DOI

Geraili A., Badirzadeh A., Sadeghi M., Mousavi S.M., Mousavi P., Shahmoradi Z., Hosseini S.M., Hejazi S.H., Rafiei-Sefiddashti R. 2023: Toxoplasmosis and symptoms severity in patients with COVID-19 in referral centers in Northern Iran. J. Parasit. Dis. 47: 185-191. PubMed DOI

Ghaffari S., Kalantari N., Gorgani-Firouzjaee T., Bayani M., Jalali F., Daroonkola M.A. 2021: Is COVID-19 associated with latent toxoplasmosis? Environ. Sci. Pollut. Res. Int. 28: 67886-67890. PubMed DOI

Golabi S., Ghasemi S., Adelipour M., Bagheri R., Suzuki K., Wong A., Seyedtabib M., Naghashpour M. 2022: Oxidative stress and inflammatory status in COVID-19 outpatients: a health center-based analytical cross-sectional study. Antioxidants 11: 606. PubMed DOI

Halliwell B. 2012: Free radicals and antioxidants: updating a personal view. Nutr. Rev. 70: 257-265. PubMed DOI

Halonen S., Weiss L. 2013: Toxoplasmosis. Handb. Clin. Neurol. 114: 125-145. PubMed DOI

Hemphill A., Müller N., Müller J. 2019: Comparative pathobiology of the intestinal protozoan parasites Giardia lamblia, Entamoeba histolytica, and Cryptosporidium parvum. Pathogens 8: 116. PubMed DOI

Iesa M., Osman M., Hassan M., Dirar A., Abuzeid N., Mancuso J., Pandey R., Mohammed A., Borad M., Babiker H. 2020: SARS-CoV-2 and Plasmodium falciparum common immunodominant regions may explain low COVID-19 incidence in the malaria-endemic belt. New Microbes. New. Infect. 38: 100817. PubMed DOI

Jabłonska E., Kiersnowska-Rogowska B., Ratajczak W., Rogowski F., Sawicka-Powierza J. 2007: Reactive oxygen and nitrogen species in the course of B-CLL. Adv. Med. Sci. 52: 154-158.

Jankowiak Ł., Rozsa L., Tryjanowski P., Møller A.P. 2020: A negative covariation between toxoplasmosis and CoVID-19 with alternative interpretations. Sci. Rep. 10: 12512. PubMed DOI

Khaleel F.M., Hameed A.S., Dawood A.S. 2020: Evaluation of antioxidant (GSH, Vitamin A, E, C) and MDA in Iraqi women with toxoplasmosis. Ind. J. Forensic. Med. Toxicol. 14: 1446-1449.

Kiran T., Karaman U., Arici Y., Yildiz S. 2019: Comparison of malondialdehyde, nitric oxide, adenosine deaminase and glutathione levels in patients with Entamoeba coli, Enterobius vermicularis, Giardia intestinalis, Demodex spp. positive, hydatid cyst and Toxoplasma gondii serum positive. Ann. Med. Res. 26: 1420. DOI

Li Y., Hu Y., Yu J., Ma T. 2020: Retrospective analysis of laboratory testing in 54 patients with severe-or critical-type 2019 novel coronavirus pneumonia. Lab. Invest. 100: 794-800. PubMed DOI

Marchioro A.A., Colli C.M., de Souza C.Z., da Silva S.S., Tiyo B.T., Evangelista F.F., Higa L., Conchon-Costa I., Falavigna-Guilherme A.L. 2018: Analysis of cytokines IFN-γ, TNF-α, TGF-β and nitric oxide in amniotic fluid and serum of pregnant women with toxoplasmosis in southern Brazil. Cytokine 106: 35-39. PubMed DOI

Martínez Chamorro E., Díez Tascón A., Ibánez Sanz L., Ossaba Vélez S., Borruel Nacenta S. 2021: Diagnóstico radiológico del paciente con COVID-19. Radiología 63: 56-73. PubMed DOI

Meftahi G.H., Jangravi Z., Sahraei H., Bahari Z. 2020: The possible pathophysiology mechanism of cytokine storm in elderly adults with COVID-19 infection: the contribution of "inflame-aging". Inflamm. Res. 69: 825-839. PubMed DOI

Mehri F., Rahbar A., Ghane E., Souri B., Esfahani M. 2021: The comparison of oxidative markers between Covid-19 patients and healthy subjects. Arch. Med. Res. 52: 843-849. PubMed DOI

Miller C., Smith N.C., Johnson A.M. 1999: Cytokines, nitric oxide, heat shock proteins and virulence in Toxoplasma. Parasitol. Today 15: 418-422. PubMed DOI

Mo P., Xing Y., Xiao Y., Deng L., Zhao Q., Wang H., Xiong Y., Cheng Z., Gao S., Liang K. 2021: Clinical characteristics of refractory coronavirus disease 2019 in Wuhan, China. Clin. Infect. Dis. 73: e4208-e4213. PubMed DOI

Mohammed M.A., Rajab K.I., Al-Rawi K.F., Al-Darwesh M.Y. 2020: Evaluation of some antioxidants and oxidative stress index in seropositive toxoplasmosis in pregnant women in Ramadi City of Iraq. Sys. Rev. Pharm. 11: 701-705.

Montazeri M., Nakhaei M., Fakhar M., Pazoki H., Pagheh A.S., Nazar E., Zakariaei Z., Mirzaeian H., Sharifpour A., Banimostafavi E.S. 2022: Exploring the association between latent Toxoplasma gondii infection and COVID-19 in hospitalized patients: first registry-based study. Acta. Parasitol. 67: 1172-1179. PubMed DOI

Mooiweer E., Luijk B., Bonten M.J., Ekkelenkamp M.B. 2011: C-Reactive protein levels but not CRP dynamics predict mortality in patients with pneumococcal pneumonia. J. Infect. 62: 314-316. PubMed DOI

Nicola M., Alsafi Z., Sohrabi C., Kerwan A., Al-Jabir A., Iosifidis C., Agha M., Agha R. 2020: The socio-economic implications of the coronavirus pandemic (COVID-19): a review. Int. J. Surg. 78: 185-193. PubMed DOI

Paraboni M.L.R., Manfredini V., Schreiner G.E., Gonçalves I.L., Silveira C., Commodaro A.G., Belfort Jr R. 2022: Comparative study of oxidative stress and antioxidative markers in patients infected with Toxoplasma gondii. Parasitol. Int. 91: 102645. PubMed DOI

Parlog A., Schlüter D., Dunay I.R. 2015: Toxoplasma gondii induced neuronal alterations. Parasite. Immunol. 37: 159-170. PubMed DOI

Paules C.I., Marston H.D., Fauci A.S. 2020: Coronavirus infections - more than just the common cold. JAMA 323: 707-708. PubMed DOI

Pepys M.B., Hirschfield G.M. 2003: C-reactive protein: a critical update. J. Clin. Invest. 111: 1805-1812. DOI

Pisoschi A.M., Pop A. 2015: The role of antioxidants in the chemistry of oxidative stress: a review. Eur. J.Med. Chem. 97: 55-74. PubMed DOI

Roe K. 2021: The symptoms and clinical manifestations observed in COVID-19 patients/long COVID-19 symptoms that parallel Toxoplasma gondii infections. J. Neuroimmune Pharmacol. 16: 513-516. PubMed DOI

Sala G., Miyakawa T. 2020: Association of BCG vaccination policy with prevalence and mortality of COVID-19 (preprint). https://doi.org/10.1101/2020.03.30.20048165 DOI

Sharaf-El-Deen S.A. 2021: Toxoplasma gondii as a possible risk factor for COVID-19 severity: a case-control study. Egypt. J. Med. Microbiol. 30: 125-132. DOI

Silvagno F., Vernone A., Pescarmona G.P. 2020: The role of glutathione in protecting against the severe inflammatory response triggered by COVID-19. Antioxidants 9: 624. PubMed DOI

Sina S., Mohammad J.M., Reza S., Anita M., Soudabeh E., Hadi M. 2021: Determination of parasitic burden in the brain tissue of infected mice in acute toxoplasmosis after treatment by fluconazole combined with sulfadiazine and pyrimethamine. Eur. J. Med. Res. 26: 65. PubMed DOI

Sinha P., Matthay M.A., Calfee C.S. 2020: Is a "cytokine storm" relevant to COVID-19? JAMA Intern. Med. 180: 1152-1154. PubMed DOI

Tay M.Z., Poh C.M., Rénia L., MacAry P.A., Ng L.F. 2020: The trinity of COVID-19: immunity, inflammation and intervention. Nat. Rev. Immunol. 20: 363-374. PubMed DOI

Türkoğlu Ş.A., Yaman K., Orallar H., Camsari C., Karabörk Ş., Ayaz E. 2018: Acute toxoplasmosis and antioxidant levels in the liver, kidney and brain of rats. Ann. Parasitol. 64: 241-247.

Tonin A., Weber A., Ribeiro A., Camillo G., Vogel F., Moura A., Bochi G., Moresco R., Da Silva A. 2015: Serum levels of nitric oxide and protein oxidation in goats seropositive for Toxoplasma gondii and Neospora caninum. Comp. Immunol. Microbiol. Infect. Dis. 41: 55-58. PubMed DOI

Velavan T.P., Meyer C.G. 2020: Mild versus severe COVID-19: laboratory markers. Int. J. Infect. Dis. 95: 304-307. PubMed DOI

Weeratunga P., Herath T.U., Kim T.-H., Lee H.-C., Kim J.-H., Lee B.-H., Lee E.-S., Chathuranga K., Chathuranga W.G., Yang C.-S. 2017: Dense Granule Protein-7 (GRA-7) of Toxoplasma gondii inhibits viral replication in vitro and in vivo. J. Microbiol. 55: 909-917. PubMed DOI

Wolday D., Tasew G., Amogne W., Urban B., Schallig H.D., Harris V., Rinke de Wit T.F. 2021: Interrogating the impact of intestinal parasite-microbiome on pathogenesis of COVID-19 in Sub-Saharan Africa. Front. Microbiol. 12: 614522. PubMed DOI

World Health Organization 2020: Clinical management of COVID-19: interim guidance, 27 May 2020. DOI

World Health Organization 2023: COVID-19 weekly epidemiological update, Edition 154, 3 August 2023.

Worwood M. 1990: Ferritin. Blood Rev. 4: 259-269. PubMed DOI

Yaghoubi N., Youssefi M., Jabbari Azad F., Farzad F., Yavari Z., Zahedi Avval F. 2022: Total antioxidant capacity as a marker of severity of COVID-19 infection: possible prognostic and therapeutic clinical application. J. Med. Virol. 94: 1558-1565. PubMed DOI

Young B., Gleeson M., Cripps A.W. 1991: C-reactive protein: a critical review. Pathology 23: 118-124. PubMed DOI

Zumla A., Hui D.S., Azhar E.I., Memish Z.A., Maeurer M. 2020: Reducing mortality from 2019-nCoV: host-directed therapies should be an option. Lancet 395: e35-e36. PubMed DOI