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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 4  |  Page : 433-436

Exploring the role of bacillus calmette–guerin vaccination in protection against COVID-19


1 Department of Telemedicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Community Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission03-Sep-2021
Date of Decision22-Sep-2021
Date of Acceptance22-Oct-2021
Date of Web Publication14-Dec-2021

Correspondence Address:
Meenu Singh
Department of Telemedicine, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmy.ijmy_179_21

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  Abstract 


Background: In recent studies, it has been established that countries having Bacillus Calmette-Guerin (BCG) vaccination programs reported less COVID-19 cases and deaths per population Preliminary studies suggest that BCG vaccination could upregulate the vaccine-induced immunity against SARS-CoV-2. Hence, the recent study was aimed to determine the association of BCG vaccine with the development of COVID-19 in health care workers. Methods: The participants included in the study were healthcare workers (doctors, paramedics, and other supporting staff) working in the high and low-risk zones of COVID-19 in the hospital. The Graph Pad statistical analysis tool was used to determine the association of preliminary BCG vaccination with their COVID-19 status. Results: A total of 200 health care workers working in different departments of the hospital were enrolled in the study. The relative risk of COVID-19 positivity in BCG vaccinated versus unvaccinated was 0.79 (0.50–1.25). There was also a significant negative correlation between two groups. The relative risk of COVID-19 positivity in those with a BCG scar was 0.63 (0.44–0.92). The relative risk of COVID-19 infection in those with a history of tuberculosis was 1.08 (0.56–2.09). Conclusion: The present study did not support the beneficial effect of BCG vaccine in protection against the development of COVID-19 disease.

Keywords: Bacillus Calmette-Guerin, COVID-19, tuberculosis


How to cite this article:
Chauhan A, Singh M, Agarwal A, Jaiswal N, M Lakshmi P V, Singh M. Exploring the role of bacillus calmette–guerin vaccination in protection against COVID-19. Int J Mycobacteriol 2021;10:433-6

How to cite this URL:
Chauhan A, Singh M, Agarwal A, Jaiswal N, M Lakshmi P V, Singh M. Exploring the role of bacillus calmette–guerin vaccination in protection against COVID-19. Int J Mycobacteriol [serial online] 2021 [cited 2022 Jan 21];10:433-6. Available from: https://www.ijmyco.org/text.asp?2021/10/4/433/332350




  Introduction Top


The COVID-19 pandemic originated in China, and it has quickly spread over all continents affecting most countries in the world. India has been taking multipronged measures in controlling COVID-19 pandemic, as highlighted in published research.[1] Worldwide studies have been carried out to determine the beneficial role of Bacillus Calmette-Guerin (BCG) vaccination in combating COVID-19. It has also been established in recent studies that countries having BCG vaccination programs reported less COVID-19 cases and deaths per population,[2],[3] emphasizing the role of immune response developed through BCG vaccination in the prevention of COVID-19.[4] However, there are other studies reporting no protective role of BCG vaccination in childhood in preventing COVID-19 morbidity and mortality in adults.[5] In a recent study conducted in European countries by the National Institutes of Health determined a strong correlation between BCG vaccination and reduction of morbidity and mortality due to COVID-19 after adjusting for confound ours.[6] Similar results were reported in Spain and Portugal with high mortality rates due to COVID-19 were associated with no TB vaccination programs.[7] There are ongoing randomized controlled trials (RCTs) to determine the cross-protective effects of BCG vaccine in reducing the severity and incidence of COVID-19. The results of the phase III randomized clinical trial ACTIVATE (NCT03296423) have confirmed the protective role of BCG vaccination against new infection in elderly (>65 years).[8] In recent preclinical murine studies, SARS-CoV-2-specific antibody and T-cell responses were determined when a formulation of BCG with spike protein was injected in mice.[9] The recent review by Moorlang et al. have published an article on the non-specific effects of BCG vaccine on viral infections. The review reported that there are numerous epidemiological, clinical, and immunological studies that demonstrated there is reduction in mortality and morbidity when vaccinated to BCG.[10] Importantly, the evidence suggests that BCG protects against viral pathogens comes from experimental studies in mice showing that BCG offers protection against various DNA and RNA viruses, including herpes and influenza viruses.[9] In conclusion, these preliminary studies suggest that BCG vaccination could upregulate the vaccine-induced immunity against SARS-CoV-2. The authors of the recent study have emphasized for more investigations to determine the role of BCG vaccine in COVID-19 for its appropriate use worldwide.[11] Hence, the recent study was aimed to determine the association of BCG vaccine with the development of COVID-19 in health care workers in a tertiary care hospital in northern India.


  Methodology Top


The study was conducted in PGIMER Chandigarh after taking Ethical approval from the Institutes Ethics Committee (Reference No. NK/6290/Study/020) dated June 25, 2020. The participants included in the study were healthcare workers (doctors, paramedics, and other supporting staff) working in the high and low-risk zones of COVID-19 in hospital. The participants were included randomly from any department of the institute after taking their informed consent through their registered mobile numbers, WhatsApp, or Google forms Appendix 1. The detailed information pertaining to designations, department, COVID-19 status, quarantine status, status of BCG vaccination, post-BCG vaccination scar, other comorbidities, and history of tuberculosis was collected from the enrolled participant through WhatsApp/messages/voice calling or addressing Google forms through E-mail. The information regarding their COVID-19 status was determined with the type of test done (reverse transcription-polymerase chain reaction [PCR] test or rapid antigen card test). The statistical analysis was done through Graph pad PRISM version 5.01 software (GraphPad Software, 2365 Northside Dr. Suite 560 San Diego, CA 92108) determining the association of BCG vaccine status with their COVID-19 status through relative risk and odds ratio. Spearman correlation was conducted to determine correlation between the COVID-19 and BCG immunization status, BCG scar, or history of tuberculosis.


  Results Top


A total of 200 health care workers working in different departments/specialties of the hospital were enrolled in the study. The age range of the participants was 22–59 years, with a mean age of31.9 years. The study participants comprised 105 females and 95 males. The demographic and clinical details of the included participants are highlighted in [Table 1]. Out of the 200 participants enrolled, most were paramedics, i.e., 112 working in COVID and non-COVID wards, ICUs, Laboratories, etc. There were 70 participants positive for COVD 19 enrolled in the study (severe-2, moderate-5, mild-63). Sixty-five percent (130/200) of the study participants reported using full personal protective equipment during their duty hours, whereas 76.5% (153/200) reported only using an N95 mask. Among 200 enrolled participants, 157 (78.5%) health workers reported to be immunized for BCG vaccination. Out of 157, BCG immunized health workers, 133 (84.7%) have reported BCG scar developed on their arm [Table 1]. The relative risk of COVID-19 positivity in BCG vaccinated versus unvaccinated, as diagnosed by the PCR kit was 0.79 (0.50–1.25). The relative risk of COVID-19 positivity in those with a BCG scar was 0.63 (0.44–0.92). The relative risk of COVID-19 infection in those with a history of tuberculosis was 1.08 (0.56–2.09) [Figure 1] and [Table 2]. The study also resulted the significant negative correlation between the COVID-19 and BCG Scar status of the participant (r = −0.17, P = 0.01) which was not significant when COVID-19 correlated with the history of tuberculosis or BCG status of the participant [Figure 2].
Figure 1: Comparison Graph: (a) COVID 19 and BCG immunization (b) COVID 19 and BCG scar (c) Covid 19 and h/o tuberculosis

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Figure 2: Correlation Graph: (a) COVID 19 and BCG immunization (b) COVID 19 and BCG scar (c) Covid 19 and h/o tuberculosis.

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Table 1: Demographic and clinical details of the enrolled participants

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Table 2: Strength of association between coronavirus disease 2019 positivity and Bacillus Calmette-Guerin immunization, Bacillus Calmette-Guerin scar, and history of tuberculosis

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  Discussion Top


The relative risk for COVID-19 positivity was not statistically different in those with and without the history of BCG vaccination. However, there was a statistically significant decreased risk of COVID-19 in those with a BCG scar which also showed a significant negative correlation. The BCG scar is indicative of uptake of the vaccine in the population and can be taken as a surrogate marker for the development of the non-specific immunity that BCG vaccination induces.[3] It is obvious to have the BCG scar who are immunized for BCG vaccination. But the present study has reported 15.3% of the BCG immunized individuals resistant to the development of BCG scar. These findings of BCG scar failure is a worldwide well-known phenomenon of the prevalence of 1%–20%.[10],[12] Our is the first study to report the negative correlation of the COVID-19 positivity and prior history of BCG scar which also reported their association. While RCTs have been registered to determine the effect of BCG immunization on COVID-19 infections, the results are unlikely to be available before May 2021.[13],[14] The implications of these findings are significant. The WHO has recommended the usage of BCG vaccine for experimental settings only. This is to prevent the shortage of the vaccine for routine immunization of infants in countries with high TB burden. Furthermore, since the protective effects of the vaccine have not been confirmed by RCTs, and are hence attributable to confounders, it is likely that immunization campaigns with the BCG vaccine may lull the population into a false sense of security.[15],[16] Indeed, concerns regarding the impact of pressure of the rising demand of the BCG vaccine on infant vaccination has caused the Japanese Vaccinology society to publish guidelines urging authorities to abstain from advertising unproven claims of benefit. The manufacturing of the vaccine is currently poised to meet the demand of infant vaccination only and cannot meet adult demands. VPM1002 is a modified strain of BCG, manufactured by the Max Plank Institute of Infection Biology, Berlin, after the passage of Mycobacterium bovis in bile-containing media for 13 years.[17] It is genetically modified for the immune system to better recognize it. It is currently under Phase III trial for its protective effects against COVID-19, and if found effective, can be manufactured on a large scale for adult immunization.[18] A systematic review of case series has shown some cases to have co-infection of drug-resistant TB and COVID-19.[19] COVID-19 Pneumonia with the pulmonoray tuberculosis has been diagnosed with chest CT in aged person with full recovery.[20] There are also specific investigations, i.e., CRP, LDH, lymphocyte, and neutrophil counts, which have shown a correlation with the COVID-19 critical cases.[21]

The results of our study did not fully support the hypothesis that immunization with BCG confers some degree of protection against respiratory viruses like the Coronavirus, even decades after immunization. However, this effect has been demonstrated in our study by those who have a BCG scar. The results of our study have also been supported by a recent review by Gonzalez-Perez et al., highlighting the potential use of BCG for the treatment of respiratory infectious diseases and ongoing SARS-CoV-2 clinical trials.[22] The merits of our study are the recruitment of participants from high-risk groups who were likely exposed to the circulating virus. The drawback is the cross-sectional design, with no follow-up to ascertain future development of COVID-19 positivity. The BCG scar is reported by the participant themselves but not evaluated by any physician. The study could have been done on large sample size. While the implementation and specific guidelines for adult BCG immunization should rest upon the results from the ongoing trials, these data underscore the value of newborn BCG immunization that is prevalent in countries with high tuberculosis burden. The present study correlates the development of scar in BCG immunized individuals with a lower number of COVID-19 patients but does not support the beneficial effect of BCG vaccine in protection against the development of COVID-19 disease.

Ethical clearance

Ethical clearance was obtained from the Institutes Ethics Committee (Reference No. NK/6290/Study/020).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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