Role of BCG and Measles vaccination in protection against COVID-19 infection and severity of the disease: A pilot case-control study

Financial Support: None declared Conflict of Interest: None declared Date of Submission: 29-11-2021 Date of Acceptance: 28-01-2022 Date of Publication: 28-02-2022 Correspondence: Dr. Bijaya Nanda Naik (Email: drbijiya02@gmail.com) Copy Right: The Journal retains the copyrights of this article. However, reproduction is permissible with due acknowledgement of the source. National Journal of Community Medicine│Volume 13│Issue 02│February 2022 Page 108 How to cite this article: Ranjan A, Kumar P, Verma M, Singh C, Pandey S, Naik BN, Nirala SK, Rao R. Role of BCG and Measles vaccination in protection against COVID-19 infection and severity of the disease: A pilot case-control study. Natl J Community Med 2022;13(2):108-113. DOI: 10.55489/njcm1322022160 ORIGINAL RESEARCH ARTICLE pISSN 0976 3325│eISSN 2229 6816 Open Access Article (CC BY-SA) www.njcmindia.org DOI: 10.55489/njcm1322022160 Role of BCG and Measles vaccination in protection against COVID-19 infection and severity of the disease: A pilot case-control study


INTRODUCTION
Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). As of 31 January 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 102,691,967 patients, with 2,222,403 deaths across 215 countries. By this date in India SARS-CoV-2 has infected 10,746,174 patients, with 1, 54,274 deaths. In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. 1 The global spread of COVID-19 is not uniform as some countries are relatively less affected. The reason(s) for such anomalous behaviour is still not fully understood but distinct hypotheses have been proposed. 2 Many studies hypothesize that the countries having BCG & MMR vaccination in their universal immunization program were less affected by COVID-19. 3 There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. 4 Epidemiological studies and randomized trials have shown that BCG vaccination reduces all-cause infant mortality by diminishing deaths due to infections other than tuberculosis. The observation that BCG vaccination could protect against viral infection was strengthened by a study in Guinea-Bissau showing that BCG reduced the incidence of respiratory syncytial virus infection. 5 In contrast, Cecilia S et al believe that current mortality rates of the COVID-19 pandemic do not support a clear negative correlation with Bacillus Calmette-Guerin coverage and that there are alternative explanations for the differences observed between Western and Eastern Germany states. Ongoing randomized controlled trials will provide answers to whether Bacillus Calmette-Guerin reduces the incidence and severity of COVID-19 through its heterologous effects. 6 All the published literature, so far, on the role of BCG and MMR vaccination in reducing the burden of COVID-19 has been based on ecological data. None of the studies has been carried out on individual-level information. Hence, the ecological fallacy could not be ruled out. In this background, we planned this explorative pilot case-control study to understand the role of vaccination with Bacillus Calmette-Guerin (BCG) and Measles on COVID 19 infectivity and severity.

OBJECTIVES
The present study was conducted to understand the role of vaccination with BCG and measles administered as part of MMR vaccine on COVID 19. The study also aimed to find out independent risk factors of COVID 19.

MATERIAL AND METHODS
Study design, duration, and ethics: This explorative pilot case-control study was carried out during December 2020 and January 2021. The ethical approval for this study has been obtained from Institute Ethics Committee, AIIMS, Patna.
Study setting: AIIMS, Patna is one of the Institute of National Importance and is providing dedicated health care during the COVID-19 pandemic. The study was conducted in the Flu clinic and OPD area of AIIMS Patna.

Study population:
The study population included all the COVID-19 patients attending the Flu Clinic at AIIMS, Patna with positive documentation (RT-PCR or Rapid Antigen Test/RAT Positive) during the study period and satisfied the inclusion and exclusion criteria as cases. Controls were selected from the patients attending the OPDs with negative documentation of COVID.

Sampling population
Cases: COVID-19 patient with positive documentation who has attended the Flu Clinic, AIIMS, Patna.

Control:
One age (±5years) and gender-matched control was identified among the patients attending the various OPDs. Control should have documented the negative report (RT-PCR or Rapid Antigen Test/RAT Negative) of COVID-19.
Sample size: Due to lack of prior literature on the association of BCG and COVID-19, 100 reported and documented COVID-19 patients at Flu clinic AIIMS, Patna were considered as cases. One control per case as per the operational definition cited above was selected.
Sampling technique: A total of 100 COVID-19 cases satisfying inclusion and exclusion criteria were selected purposively from the Flu Clinic. After obtaining written informed consent they were included in the study. One control per case was enrolled from the OPD area conveniently matching the age and gender satisfying inclusion and exclusion criteria.

Inclusion and exclusion criteria:
For Cases, we included the COVID-19 positive patients of age ≥18 years, attending the Flu clinic, AIIMS, Patna. We excluded the seriously ill patients not able to communicate. For controls we took documented COVID-19 negative person of age ≥18 years, attending the other OPD clinic at AIIMS, Patna. Seriously, ill patients not able to communicate were excluded.

Study tool
The information was collected using a pre-tested semi-structured interview schedule. The study tool has three sections. The first section contains the general characteristics of the study participants. Section two has basic knowledge of the out prevention and control of COVID-19. Section three contains the information on BCG and Measles vaccination status. The BCG vaccination was ascertained by history and examining the presence of the BCG scar. The measles vaccination was ascertained by history.
Bio-statistical analysis: The information collected was entered in MS Excel and analysis was done using the SPSS version20. The categorical variables were expressed as proportions and percentages. Multivariate binomial logistic regression was performed to ascertain the independent influence status of BCG and Measles vaccination. ODDs ratio was calculated to determine the risk of COVID-19 among nonvaccinated persons. The p-value of 0.05 was considered statistically significant.

Sociodemographic details of participants:
The sociodemographic details of the participants are shown in Table 1. Males (70%) outnumbered females. The maximum number of participants aged more than 60 years.

Sociodemographic Predictors of COVID 19:
The adjusted odds of COVID-19 was found to be significantly higher among individuals having higher educational qualification [ Behavioral details of participants: The behavioral details of participants are shown in Table 2. About 73% of cases and 59% controls were vaccinated with BCG. 10% of control and 36% of cases were vaccinated with MMR. Nearly 22% and 9% of cases and controls respectively had a history of unprotected contact with COVID-19 patients. About 76% of cases and 34% of controls suffered from various comorbidities.    Duration of hospital stay, symptoms, and severity of cases: The majority of cases (62%) were hospitalized for less than 5 days. 68% of cases were categorized as asymptomatic and mild cases and 32% were categorized as moderate and severe cases. This grading was done based on saturation and oxygen requirement at the time of admission.

Behavioral Predictors of COVID
Majority of cases in our study presented with fever (63%) followed by cough (58%) as shown in figure 1.

DISCUSSION
The role of BCG and MMR vaccination in reducing the burden of COVID-19 has been based on ecological data mostly. Hence, the ecological fallacy could not be ruled out. We planned this explorative pilot casecontrol study to understand the role of vaccination  of BCG vaccination exist in 131 countries; 21 countries have no current program of national BCG vaccination, and for 26 countries status is unknown. They interpret that countries with the national program of whole population BCG vaccination appear to have a lower incidence and death rate from Covid-19. This may be due to the known immunological benefits of BCG vaccination. In the absence of a specific vaccination against Covid-19, population-based BCG vaccination may have a role in reducing the impact of this disease and is being studied in a prospective trial. [7][8][9][10][11][12][13][14] In our study, we found that about 59% of controls and 73% cases were BCG vaccinated (

CONCLUSION
BCG vaccination status was not found to be an independent predictor of COVID-19 in our study. Due to low coverage, the role of measles vaccine was difficult to conclude, further research with more sample size required. We also recommend further studies with better study design (cohort, randomized trials) to substantiate the effect of BCG and Measles vaccine on COVID-19. Till then COVID-19 appropriate behaviour has to be followed by all to prevent the spread of SARS-COV-2 infection.