MMR Vaccine: A protective weapon against #COVID-19 (The possibility of using MMR to boost Immune system and reduce Covid 19 associated Morbidity and Mortality)

By Bincy M Biju (M.Sc. Biotechnology) and Dr. Chiradeep Sarkar (Assistant Professor, Department of Biotechnology) at G.N.Khalsa College (Autonomous), Mumbai, India.

[Note: Numbers mentioned in parenthesis relate to References that are mentioned at the end of this article]

Zoonotic disease or zoonosis is a type of disease that is transmitted from animals or birds to humans. Zoonotic outbreak tends to occur due to the destruction of animal habitats and increased interaction of humans & animals. Such outbreaks spread worldwide due to increased traveling & globalization of markets.

By the end of 2019, an unidentified cluster of pneumonia emerged in Wuhan, Hubei Province, China [1] and a global outbreak occurred, affecting 12,286,264 individuals worldwide (updated as on 11th July 2020) [2]. International Committee on Taxonomy of Viruses (ICTV) named novel coronavirus as SARS-CoV-2 [3], followed by WHO naming this disease as COVID-19. In COVID-19 patients, SARS-CoV-2 was isolated from bronchoalveolar lavage fluid (BALF) [4], and after analysis was considered as a member of β-CoV’s family [4,5]. Coronavirus is an enveloped, positive sense single-stranded RNA virus which is divided into 4 subfamilies: α, β, γ, δ- CoV’s and causing respiratory, enteric, hepatic and neurological diseases [6,7]. This virus enters into the cell by interacting with human angiotensin, converting enzyme 2 (ACE2) receptor which is expressed in kidney, lungs, heart and intestine [8,9,10].

Coronavirus or COVID-19 show 5 different types of outcomes: mild to medium case (80.9%), severe case (13.8%), critical case (4.7%), asymptomatic case (1.2%), death (2.3%) [11]. Most common symptoms are fever, cough and fatigue while less common symptoms are sputum production, headache, hemoptysis and diarrhea. Patients also show normal or decreased white blood cell count and consolidation in bilateral multiple lobular and subsegmental areas [1,10,11]. The main transmission route is respiratory droplets and contact transmission [12]. Children below 10-years-old, obese people, smokers, people with asthma, diabetes, cancer, cardiovascular disease are more susceptible to infection [13-17].

Anti-viral compounds such as Ribavirin, Lopinavir/ritonavir, Remdesivir, Nelfinavir, Arbidol, chloroquine can be used for the treatment of COVID-19 [18-23]. Vaccines could be the best option to control COVID-19 as vaccines stimulate Helper T-cells to produce cytokines which in turn triggers Killer T-cells and other natural killer cells to recognize and mount immune response against the virus-infected cells and thus helping in an increased immune response against a particular pathogen. Vaccine candidate(s) for COVID-19 though will be available only after exhaustive clinical trials for safety and efficacy and probably enter the market by mid-2021 according to many experts.

There is, however, a growing evidence, that live attenuated vaccines given during childhood also confer beneficial Non-Specific Effects (NSE) and can reduce both morbidity and mortality due to unrelated infections [24,25]. A paper by Fidel Jr. and Noverr proposes, based on various empirical studies, that live attenuated vaccines like MMR (Measles, Mumps, Rubella) can induce “trained” non-specific innate immune cells for improved host responses and reduce COVID-19 associated lung inflammation and sepsis. Moreover, in immunocompetent individuals, MMR does not show any contraindications [26].

According to Salman and Salem, combined vaccination with varicella, Hepatitis B, MMR, Poliomyelitis and Rotavirus can be used to reduce the fatality and recover quickly against COVID-19. MMR vaccine has been used before to develop enhanced immunity against other virus strains like HPV (Human Papilloma Virus) [27].

In another recent preprint paper by Young et.al, sequence homology was identified in fusion proteins of SARS-CoV-2 with measles and mumps viruses. Moreover, the macro domain (ADP-ribose-1-phosphatase) of the SARS-CoV-2 and Rubella virus showed 29% Amino acid sequence homology. As an initial test of the hypothesis, the study concluded that age-groups that lacked MMR- induced immunity had the poorest outcome in COVID-19 and COVID-19 disease burden correlates with Rubella antibody titres potentially induced by SARS-CoV-2 sequence homology.   Hence, the emerging hypothesis indicates that MMR vaccine can provide protection by reducing its adverse effects [28].

Thus, vaccination strategies with attenuated vaccines like MMR warrants more detailed clinical studies/trials as a safe and time-appropriate therapeutic intervention in reducing the worst aspects of COVID-19.

References

  1. Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y et.al. (2020), Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia, N. Engl. J. Med, 382(13): 1199-1207, DOI:1056/NEJMoa2001316.
  2. https://www.who.int/
  3. Yu WB, Tang GD, Zhang L, Corlett RT (2020), Decoding the Evolution and Transmission of the Novel Pneumonia Coronavirus (SARS-CoV-2) / HCoV-19) using whole genome data, bioRxiv, 41(3): 247-257, DOI: 24272/j.issn.2095-8137.2020.022.
  4. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X et.al. (2020), A Novel Coronavirus From Patients With Pneumonia in China, 2019, N.Engl.J.Med, 382(8): 727-733, DOI: 1056/NEJMoa2001017
  5. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR (2020), A Pneumonia outbreak associated with a New Coronavirus of Probable Bat Origin, Nature, 579(7798): 270-273, DOI: 1038/s41586-020-2012-7. 
  6. Weiss SR and Leibowitz JL (2011), Coronavirus Pathogenesis, Advances in Virus Research, 81: 85-164, DOI: 1016/B978-0-12-385885-6.00009-2
  7. De Wilde A.H,Snijder E.J,Kikkert M, van Hemert M.J (2018), Host Factors in Coronavirus Replication. In Roles of Host Gene and Non-Coding RNA Expression in Virus Infection; Tripp, R.A., Tompkins, S.M., Eds., Springer International Publishing: Cham, Switzerland, 149: 1- 42, DOI: 1007/82_2017_25
  8. Li W, Moore M.J, Vasilieva N, Sui J, Wong S.K, Berne M.A, et al. (2003), Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus, Nature, 426: 450-454, DOI: 1038/nature02145.
  9. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, et al. (2000), A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res., 87(5): E1–E9, DOI: 1161/01.res.87.5.e1
  10. Zhonghualiuxingbingxuezazhi (2020),The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China, Europe PMC, 41(2):145–151, DOI: 3760/cma.j.issn.0254-6450.2020.02.003
  11. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. (2020), Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, The Lancet, 395 (10223): 497–506, DOI: https://doi.org/10.1016/S0140-6736(20)30183-5
  12. Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, et.al. (2020), A rapid advice guideline for the diagnosis and treatment of 2019 Novel Corona Virus (2019-nCoV) infected pneumonia (standard version), nature, military medical research, 7(4), DOI: https://doi.org/10.1186/s40779-020-0233-6.
  13. Yang Y, Lu Q, Liu M, Wang Y, Zhang A, Jalali N, et al. (2020), Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China, medRxiv, DOI:https://www.medrxiv.org/content/10.1101/2020.02.10.20021675v2
  14. World Health Organization. Novel Coronavirus (2019-nCoV) Advice for the Public: Myth Buster. Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public/myth-busters(accessed on 23 March 2020).
  15. Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. (2020), Cancer patients in SARS-CoV-2 infection: A nationwide analysis in China, The Lancet Oncology, 21(3): 335-337, DOI: 1016/S1470-2045(20)30096-6
  16. Zou X, Chen K, Zou J, Han P, Hao J, Han Z (2020), Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to Wuhan 2019-nCoV infection. Frontiers of Medicine, 14(2):185-192, DOI: 1007/s11684-020-0754-0
  17. Jia X, Yin C, Lu S, Chen Y, Liu Q, Bai J, Lu Y (2020), Two Things about COVID-19 Might Need Attention, Preprints, DOI: 20944/preprints202002.0315.v1
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  21. Yamamoto N, Yang R, Yoshinaka Y, Amari S, Nakano T, Cinatl J, et.al. (2004), HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus, Biochemical and Biophysical Research Communications, 318(3): 719–725, DOI: 1016/j.bbrc.2004.04.083
  22. Khamitov RA, Loginova S, Shchukina VN, Borisevich SV, Maksimov VA, Shuster AM (2008), Antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures, Vopr. Virusol,53(4):9–13, https://pubmed.ncbi.nlm.nih.gov/18756809/
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  24. Aaby P and Benn CS (2019), Developing the concept of beneficial non-specific effect of live vaccines with epidemiological studies, Clin Microbiol Infect, 25(12):1459–1467, DOI: 1016/j.cmi.2019.08.011
  25. Moorlag SJCFM, Arts RJW, Crevel R, Netea MG (2019), Non-specific effect of BCG vaccine on viral infection, Clin Microbiol Infect, 25(12): 1473-1478, DOI: 1016/j.cmi.2019.04.020
  26. Paul L. Fidel Jr., Mairi C. Noverr (2020), Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure to Dampen Septic Inflammation Associated with COVID-19 Infection?, mBio, 11(3): e00907-20, DOI: 1128/mBio.00907-20
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  28. Young A, Neumann B, Mendez RF, Reyahi A, Joannides A, Modis Y, Franklin RJM, (2020), Homologous protein domain in SARS-CoV2 and measles, mumps and rubella viruses: preliminary evidence that MMR vaccine might provide protection against COVID-19, medRxiv, DOI: https://doi.org/10.1101/2020.04.10.20053207.

More about the Authors

Dr. Chiradeep Sarkar is an Assistant Professor at the Department of Biotechnology at G.N. Khalsa College which is an Autonomous Institute based in Matunga, Mumbai, India. Chiradeep is an avid reader, western rock music lover and a traveler with a scientific temperament.
Email:  chiradeep_sarkar@yahoo.com
Bincy M Biju has done her M. Sc. in Biotechnology from G.N. Khalsa College, University of Mumbai, India in 2019. Bincy plans to pursue her PhD from the US in the near future.
Email: bincymary3016@gmail.com
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MMR Vaccine: A protective weapon against #COVID-19 (The possibility of using MMR to boost Immune system and reduce Covid 19 associated Morbidity and Mortality)
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