Abstract
Helminth infections are among the most common infectious diseases in underdeveloped countries. Helminths suppress the host immune responses and consequently mitigate vaccine efficacy and increase severity of other infectious diseases. Helminth co-infections might suppress the efficient immune response against SARS-CoV-2 at the early stage of the infection and may increase morbidity and mortality of COVID-19.
Keywords: SARS-CoV-2, COVID-19, helminth, coinfection, type 2 immunity, immunoregulation
It late 2019, a pneumonia due to coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, and immediately spread worldwide to become a pandemic problem. The disease has diverse sequels among older individuals (>60 years old) and patients who have co-morbidities or co-infections, such as pulmonary diseases, chronic kidney diseases, diabetes, hypertension, and cardiovascular diseases.1
Helminth infections are among the most common infectious diseases, particularly in underdeveloped countries.2 Schistosomiasis and soil-transmitted helminths (STHs) (known as ascariasis, hookworm, and trichuriasis) are the most common helminth infections worldwide (Table 1).2 In 2016, the global burden of STH was accounted to be above 3 million disability-adjusted life-years (DALYs).3 Typically, most STH result in a chronic manifestation with minor clinical symptoms.2 It is well-documented that chronic infection alters the immune system toward type 2 immunity (e.g., interleukin (IL)-4, IL-5, IL-9, and IL-13).4 The consequence of this immune modulation is suppression of the essential immune response against intracellular pathogens.5,6 Therefore, in individuals with helminth infections, the susceptibility and severity to infectious diseases, such as HIV/AIDS, tuberculosis, and malaria, have increased.5 As reviewed elsewhere, helminth infections are more common among developing or underdeveloped regions of the world, such as sub-Saharan Africa, East Asia, and the Indian subcontinent.2,5 In these regions, the prevalence of major infectious diseases, including HIV/AIDS, malaria, and tuberculosis, are higher than that in other parts of the world.2,5 Studies indicate that helminth co-infection can increase morbidity and mortality of these infections and that de-worming can revert this phenomenon.5,7−9 Hence, the concurrence of SARS-CoV-2 and helminths in a population with either HIV/AIDS, malaria, and tuberculosis can lead to more severe outcomes than single infections.
Table 1. Worldwide Prevalence of the Most Common Human Helminth Infectionsa.
| helminth species | disease or condition in humans | estimate prevalence worldwide | habitat of adult worm in humans |
|---|---|---|---|
| Nematodes | |||
| Ascaris lumbricoides and A. suum | ascariasis | 804 million | small intestine |
| Trichuris trichiura | trichuriasis | 477 million | large intestine |
| Enterobius vermicularis | enterobiasis (oxyuriasis) | >200 million | |
| Toxocara canis | visceral or ocular larva migrans | unknown | N/A |
| Necator americanus | necatoriasis | 472 million | small intestine |
| Ancylostoma duodenale | ancylostomiasis | ||
| Ancylostoma ceylanicum | |||
| Strongyloides stercoralis | strongyloidiasis | 30–100 million | |
| Wuchereria bancrofti | lymphatic filariasis | 44 million | lymphatic vessels |
| Brugia malayi or Brugia timori | |||
| Onchocerca volvulus | onchocerciasis (river blindness) | 17 million | subcutaneous tissue |
| Trichinella spiralis | trichinellosis | 0.066 million | small intestine |
| Trematodes | |||
| Schistosoma mansoni | intestinal schistosomiasis | 206 million | mesenteric veins |
| Schistosoma hematobium | urogenital schistosomiasis | venous plexus of urinary bladder | |
| Schistosoma japonicum | intestinal schistosomiasis | mesenteric veins | |
| Fasciola hepatica | fascioliasis | 80 million | bile ducts |
| Clonorchis sinensis | clonorchiasis | bile ducts and gall bladder | |
| Opisthorchis spp. | opisthorchiasis | ||
| Paragonimus spp. | paragonimiasis | lungs | |
| Cestodes | |||
| Echinococcus granulosus | hydatid disease | 0.8 million | N/A |
| Echinococcus multilocularis | alveolar echinococcosis | 0.019 million | N/A |
| Cysticercus cellulosae (Taenia solium larva) | cysticercosis and neurocysticercosis | 1 million | N/A |
| Taenia solium | intestinal taeniasis | 0.38 million | small intestine |
N/A, not applicable. There is no development of adult worms in humans. Reproduced from ref (2). Copyright 2020 Gazzinelli-Guimaraes and Nutman.
Development of an efficient vaccine is one of the main preventive strategies against SARS-CoV-2 infection. However, the immunomodulatory effects of helminth infections can mitigate vaccination efficacy.10 For example, the poor immunogenicity of BCG vaccination was detected in a helminth-infected Ethiopian population.11 It is notable that BCG vaccination could protect against severe SARS-CoV-2 infection by mechanisms related to trained immunity.12 In a murine model, efficacy of flu vaccination declined in helminth-infected animals via an IL-10-dependent manner. Interestingly, previous helminth infections also impaired vaccination efficacy.13 The results of a recent meta-analysis regarding parasite infections and immunization revealed that chronic helminthiasis has more negative impact on immunization than acute disease.14 As such, infections with parasites at the time of vaccination led to worse immunization outcomes.14
Older individuals, people with comorbidities, or patients with immunocompromising conditions are at higher risk of severe SARS-CoV-2 infection.1 Vaccination is more challenging in these populations because the immunogenicity of vaccines is diminished overall in these groups.10 Therefore, in these populations, either vaccines against SARS-CoV-2 or other diseases may have less immunogenicity when concomitant with helminth infections.
Pregnant women are a population vulnerable to congenital infections due to modulation of their immunological responses that occurs over the three trimesters of pregnancy.6 Pregnancy also increases susceptibility to helminth infections.6 As such, the synergistic immunoregulatory effects of helminth infections and pregnancy can increase susceptibility to congenital infectious diseases.6 Although limited data are available about congenital transmission of SARS-CoV-2, an increase in susceptibility and severity of SARS-CoV-2 infection as well as congenital transmission is plausible in pregnant women with helminth infections. Helminth infections are also linked with malnourishment, which reduced efficient immune response against pathogens.6 Therefore, co-infection with SARS-CoV-2 and helminths may have more hidden outcomes than predictable ones.15 It should be noted that another recent hypothesis proposed that helminth co-infection may also have a mitigating effect in COVID-19 severity.16 Hence, more research in animal models and clinical studies are needed to clarify the interaction between helminth and SARS-CoV-2 co-infection.
Conclusions
Our conclusions are as follows: (1) Helminth co-infection may suppress the efficient immune response against SARS-CoV-2 in the early stage of the infection, and thereby may increase morbidity and mortality of COVID-19. (2) Helminth infections can suppress the immune responses and can mitigate SARS-CoV-2 vaccine efficacy. (3) The synergistic immunoregulatory effects of helminth infection and pregnancy may increase susceptibility to congenital transmission of COVID-19. (4) Treatment and prevention of helminth infections in endemic regions might decrease the morbidity and mortality of COVID-19.
Glossary
Abbreviations
- COVID-19
coronavirus disease 2019
- SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
- STHs
soil-transmitted helminths
- DALYs
disability-adjusted life-years
- IL
interleukin
The author declares no competing financial interest.
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