Epidemiological and Immunological Relevance of Sars-CoV 2 and Helminth in Coinfection

Akshita Kumar,M.Sc. Biochemistry

The therapeutic function of helminths in the modulation and/or deregulation of immune responses in COVID-19 patients has recently been a contentious topic. Richard Bradbury (School of Health and Life Sciences, Federation University, Berwick, Victoria, Australia) and his colleagues (Bradbury et al. 2020) initially proposed that helminths might inadvertently cause severe COVID-19 infections in people, based on the notion that helminths inhibit the important Th1 immune response, which is critical in treating some bacterial and viral infections. Another finding claimed that Covid-19 related morbidity and mortality could be intensified by Helminth infection.

COVID-19 and the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have recently emerged as serious dangers to human health globally. The worldwide infection rate, mortality rate, and recovery rate were expected to reach 146,520,027, 3,103,334, and 124,259,424, respectively, by April 24, 2021. 

Patients with COVID-19 have unusually high plasma concentrations of pro-inflammatory T lymphocyte (Th1) immune cells and cytokines. The activation of numerous white blood cells (monocytes, neutrophils, dendritic cells, macrophages, NK cells, B cells, and T cells), tissue cells (endothelial and epithelial cells), and bacteria and viruses cause the “cytokine storm,” which is a predictor of illness severity and catastrophic consequences. COVID-19 severity is thought to be exacerbated by environmental pollution, which activates pro-inflammatory Th1 immune responses and inadvertently dampens the immunomodulatory function of helminths in COVID-19 patients. Air pollution, strong oxidative stress and inflammation producing factor, has been linked to unfavourable changes in the host immune system and cytokine production as well as COVID-19 severity. 

Speaking of Helminths, they have a strong immunomodulatory effect by stimulating anti-inflammatory and regulatory immunological responses in T helper type 2 cells (Th2). They are known to inhibit Th1 pro-inflammatory immune cells and activate anti-inflammatory Th2 immune responses.

Sars CoV-2

Patients with co-infections or comorbidities such as obesity, HIV/AIDS, TB, hypertension, metabolic syndrome, diabetes, cardiovascular illness, renal disease, and respiratory disease are at the highest risk of having severe COVID-19. SARS-CoV-2 spike protein interacts with the ACE2 receptor to enhance cell entrance, whereas TMPRSS2 is involved in priming and cleavage of SARS-CoV-2 spike protein, allowing viral and cellular membrane fusion and virus entry into cells. 

Various mutants of Sars CoV-2 have been identified worldwide. The Centers for Disease Control and Prevention (CDC) categorised many mutations in the SARS-CoV-2 spike protein as variations of concern and high consequence because they can substantially increase viral infectivity and pathogenicity. During the early stages of COVID-19, SARS-CoV-2 infects mature human intestinal cells, particularly ACE2 receptor-expressing enterocytes of the small intestines, which may cause gastrointestinal symptoms such as abdominal discomfort, vomiting, and diarrhoea.

SARS-CoV-2 may have the capacity to bind to airborne atmospheric particles according to studies, which might be a reason for the high incidence of indirect transmission rates in humans.

Helminth infection

The majority of people are infected with soil-transmitted intestinal nematodes and Enterobius vermicularis. Helminthic infections (the most common neglected tropical illnesses) mostly affect the intestines, but they can also affect the blood, lungs, liver, and brain. Low socioeconomic level, a lack of clean water, inadequate sanitation, and poor hygiene are all risk factors for soil-transmitted intestinal helminth infection.

Correlation between Helminth infection and Covid-19

COVID-19 fatality rates vary by continent, area, and country, with much higher rates in Europe and the United States of America (non-helminth endemic regions as defined by the WHO), places with well-developed health systems. COVID-19 lethality levels are low in helminth infested locations with weak economies and limited health care services.

The immunomodulatory effect of helminths was proposed as a possible explanation for the reduced fatality rates. Age, population genetics, unavailability of diagnostic testing, SARS-CoV-2 mutations, and ambient humidity and temperature that inhibit virus replication might all play a role in these results.

Helminths regulate Th1 and Th2 immune responses by increasing the activity of alternatively activated macrophages (AAMs), FOXP3+ Treg cells, and regulatory B cells, resulting in the production of anti-inflammatory cytokines. As a consequence of the immunomodulatory effects of pre-existing helminth infection, it is possible to hypothesise that a reduced capacity for the generation of proinflammatory cytokines and an increase in the number of regulatory immune cells might result in a lower risk of severe COVID-19.

Although the relationship between helminth infection and viral pneumonia is unclear, there is some evidence that helminth infection may help to reduce the inflammatory process in the lungs during viral infections. Although some studies have shown that helminth infection may affect responses to viral vaccination and infection, there is no strong clinical evidence that it worsens the consequence.

As observed in situations of co-infections between helminths and TB, chronic helminth infections can bias the host immune response toward anti-inflammatory Th2 immunity, suppressing the essential pro-inflammatory Th1 immune response that is critical for fighting intracellular pathogens.

Eosinophil levels are extremely low in COVID-19 patients. Helminth infections cause the synthesis of IL-5, which is linked to a high number of eosinophils. In reaction to helminth larvae throughout the lungs, eosinophils have immunoregulatory and antiviral effects in the body. A robust Th2 immune response and large amounts of eosinophils may help in the battle against Sars CoV-2 infection.

Conclusion

The Th2/Th3 immune response to helminths is linked to reduced lung inflammation and damage, as well as lower levels of angiotensin-converting enzyme 2 (ACE2) receptor expression. However, air contaminants are linked to an increase of ACE2 receptors on the respiratory epithelial cell surface.

Helminth-induced immunosuppression decreases vaccine effectiveness and weakens important Th1 cytokine production immunological responses, which are critical for fighting early-stage infections. Continuous air pollution exposure, which is known to increase Th1 pro-inflammatory cytokine production to the degree that helminth immunosuppressive actions are hampered, might reverse this.

Again, reduced helminth activity can be detrimental to the SARS-CoV-2 inflammatory response. This “yin and yang” method appears to be complicated and deserves further investigation. Additional research in a cohort of SARS-CoV-2 infected patients living in helminth and air pollution endemic locations are needed to provide more understanding and to effect mass periodic deworming programmes and entomological research.

Also read: Tarantula toxin- the Key to Future Chronic pain medications?

Source:

Ragalathan Naidoo, Terisha Ghazi, Anil A.et al.SARS-CoV-2 and helminth co-infections, and environmental pollution exposure: An epidemiological and immunological perspective.Environment International,Volume 156,2021, https://doi.org/10.1016/j.envint.2021.106695.

Bradbury, R.S., Piedrafita, D., Greenhill, A. et al. Will helminth co-infection modulate COVID-19 severity in endemic regions?. Nat Rev Immunol 20, 342 (2020). https://doi.org/10.1038/s41577-020-0330-5

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About the Author: Lucknow based postgraduate in Biochemistry. An inquisitive science enthusiast with an inclination towards scientific writing aiming to be a scientist.

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