Parasite immunomodulatory role in reducing the prevalence of COVID-19 in endemic regions

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Bagus Hermansyah
Dini Agustina
Siti Zulaikha
Ali Habibi


Nearly 35 million cases and one million deaths over the nine months of the COVID-19 pandemic have been reported worldwide. Africa and some countries with endemic parasitic infections had a low incidence of COVID-19. By contrast, the United States and several European countries, having a non-endemicity of parasitic infections, recorded a high incidence of COVID-19. Some parasites have an immunomodulatory mechanism that can induce an immune tolerance state in the infected persons by balancing pro-inflammatory and anti-inflammatory responses. Emerging reports also stated that COVID-19 and helminth co-infections may have more hidden outcomes than predictable ones. Hence, the aim of this literature review is to show and identify that an increase in the number of regulatory immune cells due to the immunomodulatory role of a pre-existing parasitic infection could reduce the risk of COVID-19. This study explored the existing literature to determine the role of parasitic infections in modulating the immune response and possibly reduce the risk of COVID-19 infection in endemic countries. The mechanism of immunomodulation by parasites is the increased numbers of Treg cells, M2 macrophages, eosinophils, the Th2 cytokines IL-4 and IL-5, and the pro-inflammatory downregulation of IFN λ, TNF α, and IL-6, which play an essential role in inducing cytokine storms in COVID-19 infection. This condition will probably occur in an individual with parasitic infection in a community with limited facilities and infrastructure to treat parasitic infections, particularly in developing countries. To conclude, in endemic areas, the immunomodulatory effect of parasitic infection to reduce the risk of COVID-19 cases/deaths is a possibility if the host is immunocompetent. Herein, the current knowledge on the immunomodulatory role of COVID-19 and helminth co-infections will be discussed.

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How to Cite
Hermansyah, B., Agustina, D. ., Zulaikha, S., & Habibi, A. . (2022). Parasite immunomodulatory role in reducing the prevalence of COVID-19 in endemic regions. Universa Medicina, 41(1), 90–99.
Review Article


Balkhair AA. COVID-19 pandemic: a new chapter in the history of infectious diseases. Oman Med J 2020;35:2–3. DOI: 10.5001/omj.2020.41.

Amawi H, Deiab IA, Aljabali AAA, Dua K, Tambuwala MM. COVID-19 pandemic: an overview of epidemiology, parthenogenesis, diagnostics and potential vaccines and therapeutics. Ther Deliv 2020;11:245–68. doi: 10.4155/tde-2020-0035.

Baloch S, Baloch MA, Zheng T, Pei X. The coronavirus disease 2019 (COVID-19) pandemic. Tohoku J Exp Med 2020;2019:271–8. DOI: 10.1620/tjem.250.271.

World Health Organization. Coronavirus disease (COVID-19) global epidemiological situation. Geneva : World Health Organization;2020.

Ghosh D, Jason S. Stumhofer. Do you see what I see: recognition of protozoan parasites by Toll-like receptors. Curr Immunol Rev 2014;9:129–40. DOI: 10.2174/1573395509666131203225929.

Torgerson PR, Devleesschauwer B, Praet N, et al. World Health Organization estimates of the global and regional disease burden of 11 foodborne parasitic diseases, 2010: a data synthesis. PLOS Med 2015;12:e1001920. DOI: 10.1371/JOURNAL. PMED.1001920.

Wang H, Naghavi M, Allen C, et al. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388:1459–544. DOI: 10.1016/S0140-6736(16)31012-1.

World Heakth Organizations. Prevention and control of intestinal parasitic infections: WHO Technical Report Series N° 749. Geneva: World Health Organization;2016.

Maizels RM, Smits HH, McSorley HJ. Modulation of host immunity by helminths: the expanding repertoire of parasite effector molecules. Immunity 2018;49:801–18. DOI: 10.1016/j.immuni.2018. 10.016.

Ssebambulidde K, Segawa I, Abuga KM, et al. Parasites and their protection against COVID-19 ecology or immunology? medRxiv 2020;DOI: 10.1101/2020.05.11.20098053.

Hasseldam H, Hansen CS, Johansen FF. Immunomodulatory effects of helminths and protozoa in multiple sclerosis and experimental autoimmune encephalomyelitis. Parasite Immunol 2013;35:103–8. DOI: 10.1111/pim.12023.

Anthony RM, Rutitzky LI, Urban JF, Jr, Stadecker MJ, Gause WC. Protective immune mechanisms in helminth infection. Nat Rev Immunol 2007;7:975. DOI: 10.1038/NRI2199.

World Health Organization Regional Office for Africa. Coronavirus (COVID-19). World Health Organization Regional Office for Africa;2021.

Hays R, Pierce D, Giacomin P, Loukas A, Bourke P, McDermott R. Helminth coinfection and COVID-19: an alternate hypothesis. PLoS Negl Trop Dis 2020;14: e0008628.

Gutman JR, Lucchi NW, Cantey PT, et al. Malaria and parasitic neglected tropical diseases: potential syndemics with COVID-19? Am J Trop Med Hyg 2020;103:572–7. DOI: 10.4269/ajtmh.20-0516.

Chanda-Kapata P, Kapata N, Zumla A. COVID-19 and malaria: a symptom screening challenge for malaria endemic countries. Int J Infect Dis 2020;94:151–3. DOI: 10.1016/j.ijid.2020.04.007.

Zumla A, Kapata N, Ihekweazu C, Ippolito G, Ntoumi F. Is Africa prepared for tackling the COVID-19 (SARS-CoV-2) epidemic. Lessons from past outbreaks, ongoing pan-African public health efforts, and implications for the future. Int J Infect Dis 2020;93:233–6. DOI: 10.1016/j.ijid.2020.02.049.

Rodriguez C. The global helminth belt and Covid-19: the new eosinophilic link. Qeios 2020. DOI: 10.32388/IWKQH9.2.

Bradbury RS, Piedrafita D, Greenhill A, Mahanty S. Will helminth co-infection modulate COVID-19 severity in endemic regions? Nat Rev Immunol 2020;20:342. DOI: 10.1038/s41577-020-0330-5.

Saboyá MI, Catalá L, Nicholls RS, Ault SK. Update on the mapping of prevalence and intensity of infection for soil-transmitted helminth infections in Latin America and the Caribbean: a call for action. PLoS Negl Trop Dis 2013;7:e2419. DOI: 10.1371/journal.pntd.0002419.

Abdeltawabi MS, El Seddik N, Salem HK. World wide epidemiology of helminths infection. In: Rodrigo L, editor. Human helminthiasis. In Tech;2017. DOI: 10.5772/67273.

World Health Organization. World malaria report 2019. Global Malaria Programme;2019.

Centers for Disease Control and Prevention. Parasites. Atlanta: Centers for Disease Control and Prevention;2020.

World Health Organization. Ending the neglect to attain the sustainable development goals: a road map for neglected tropical diseases 2021-2030. Geneva: World Health Organization;2021.

Centers for Disease Control and Prevention. Toxoplasmosis: epidemiology & risk factors. Atlanta: Centers for Disease Control and Prevention;2019.

Lykins J, Wang K, Wheeler K, et al. Understanding toxoplasmosis in the United States through “large data” analyses. Clin Infect Dis 2016;63:468–75. DOI: 10.1093/CID/CIW356.

Nogareda F, Le Strat Y, Villena I, De Valk H, Goulet V. Incidence and prevalence of Toxoplasma gondii infection in women in France, 1980-2020: model-based estimation. Epidemiol Infect 2014;142:1661–70. DOI: 10.1017/S0950268813002756.

Ryan ET, Hill DR, Solomon T, Aronson N, Endy TP. Hunter’s tropical medicine and emerging infectious diseases.10th ed. Edinburg: Elsevier;2020.

Beshir KB, Grignard L, Hajissa K, et al. Emergence of undetectable malaria parasites: A threat under the radar amid the COVID-19 pandemic? Am J Trop Med Hyg 2020;103:558–60. DOI: 10.4269/ajtmh.20-0467.

Mahase E. China coronavirus: WHO declares international emergency as death toll exceeds 200. BMJ 2020;368:m408. DOI: 10.1136/bmj.m408.

Wolday D, Gebrecherkos T, Arefaine ZG, et al. Effect of co-infection with intestinal parasites on COVID-19 severity: a prospective observational cohort study. EClinicalMedicine 2021;39:101054. doi: 10.1016/j.eclinm.2021.101054.

Manderson L. Introduction to syndemics: a critical systems approach to public and community health by Merrill Singer [book review]. Med Anthropol Q 2012;26:643–5. DOI: 10.1111/maq.12012_3.

Ludvigsson JF. Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults. Acta Paediatr 2020;109:1088–95. DOI: 10.1111/apa.15270.

World Health Organization. The potential impact of health service disruptions on the burden of malaria: a modelling analysis for countries in Sub-saharan Africa. Geneva: World Health Organization;2020.

Sambo LG, Kirigia JM. Investing in health systems for universal health coverage in Africa. BMC Int Health Hum Rights 2014;14:28. DOI: 10.1186/s12914-014-0028-5.36.

Abdoli A. Helminths and COVID-19 co-infections: a neglected critical challenge. ACS Pharmacol Transl Sci 2020;3:1039–41. DOI: 10.1021/ACSPTSCI.0C00141.

Jankowiak Ù, Rozsa L, Tryjanowski P, M¸ller AP. A negative covariation between toxoplasmosis and CoVID-19 with alternative interpretations. Sci Rep 2020;10:12512.

Hagge DA, Parajuli P, Kunwar CB, et al. Opening a can of worms: leprosy reactions and complicit soil-transmitted helminths. E Bio Medicine 2017;23:119–24. DOI: 10.1016/j.ebiom.2017.08.026.

Bigna JJ, Tochie JN, Tounouga DN, et al. Global, regional, and country seroprevalence of Toxoplasma gondii in pregnant women: a systematic review, modelling and meta-analysis. Sci Rep 2020;10:12102. DOI: 10.1038/s41598-020-69078-9.

European Centre for Disease Prevention and Control. COVID-19 cases and deaths worldwide. Soina, Sweden: European Centre for Disease Prevention and Control;2020.

Hillyer JF. Parasites and parasitology in this SARS-CoV-2, COVID-19 world: an American Society of Parasitologists Presidential Address. J Parasitol 2020;106:859–68. DOI: 10.1645/20-158.

Parodi A, Cozzani E. Coronavirus disease 2019 (COVID 19) and malaria: Have anti glycoprotein antibodies a role? Med. Hypotheses 2020;143: 110036. DOI: 10.1016/j.mehy.2020.110036.

White MPJ, McManus CM, Maizels RM. Regulatory T-cells in helminth infection: induction, function and therapeutic potential. Immunology 2020;160:248–60. DOI: 10.1111/IMM.13190

Gomes LR, Martins YC, Ferreira-Da-Cruz MF, Daniel-Ribeiro CT. Autoimmunity, phospholipid-reacting antibodies and malaria immunity. Lupus 2014;23:1295–8. DOI: 10.1177/0961203314546021.

Hussein MIH, Albashir AAD, Elawad OAMA, Homeida A. Malaria and COVID-19: unmasking their ties. Malar J 2020;19:457. doi: 10.1186/s12936-020-03541-w.

Melchor SJ, Ewald SE. Disease tolerance in Toxoplasma infection. Front Cell Infect Microbiol 2019;9:185. doi: 10.3389/fcimb.2019.00185.

Schmid-Hempel P. Immune defence, parasite evasion strategies and their relevance for ‘macroscopic phenomena’ such as virulence. Philos Trans R Soc B Biol Sci 2009;364:85. DOI: 10.1098/RSTB.2008.0157.

Chowdhury MA, Hossain N, Kashem MA, Shahid MA, Alam A. Immune response in COVID-19: A review. J Infect Public Health 2020;13:1619–29. DOI: 10.1016/J.JIPH.2020.07.001.

Mueller SN, Rouse BT. Immune responses to viruses. Clin Immunol 2008;421. DOI: 10.1016/B978-0-323-04404-2.10027-2.

Wait LF, Dobson AP, Graham AL. Do parasite infections interfere with immunisation? A review and meta-analysis. Vaccine 2020;38:5582–90. DOI: 10.1016/J.VACCINE.2020.06.064.

Cruz AA, Cooper PJ, Figueiredo CA, et al. Global issues in allergy and immunology: Parasitic infections and allergy. J Allergy Clin Immunol 2017;140:1217–28. DOI: 10.1016/J.JACI.2017.09. 005.