BCG vaccination potential for COVID-19: an analytical approach

ABSTRACT

In order to assess the possible protective potential of BCG vaccination as regards to COVID-19, we have analyzed BCG vaccination status and SARS CoV-2 morbidity and mortality in China and we have also examined other studies performed in other countries to assess the potential of booster doses of BCG vaccination for adults. We have concluded that BCG vaccination early in life is highly unlikely to be a tool that might prevent SARS CoV-2 infection in adults. Furthermore, we have suggested that BCG vaccination potential benefit to decrease COVID-19 morbidity and mortality in children is confounded by many factors, e.g. age limitations of exposure and other vaccines. However, BCG vaccination booster doses in adults might be of protective value until the results of well-designed clinical trials are published to confirm, or refute, this potential.

KEYWORDS:

• COVID-19
• SARS CoV-2
• BCG vaccination

Multiple reports hypothesized a possible causal relationship between receiving BCG vaccination early in life, and a lesser incidence of COVID-19 associated morbidity and mortality.^1–4 China was the first country to report COVID-19 and was considered as one of the heavily affected countries and it. The author would like to explore and argue this hypothesis using it as an example.

According to the WHO global tuberculosis report 2019,⁵ it is stated that in 2018, among 180 countries for which data were collected, 153 countries have properly reported administration of BCG vaccination as a standard part of childhood immunization programs, of which 113 countries reported a coverage rate of ≥90% (Figure 1). In the same report, China has accomplished a 99% BCG vaccination coverage rate, to be considered as one of the top countries providing this rate all over the world. Moreover, the reported estimates for the global BCG coverage according to the WHO monitoring system for vaccine-preventable diseases have revealed that BCG vaccination coverage in China to be either 99% or 100% for the years 2009 to 2018.⁶ Thus, we may reasonably consider that all children living in China, currently 10 y old or younger, are efficiently covered and immunized by BCG vaccination.

Figure 1. A database of global BCG vaccination policies and practices

Source: The BCG World Atlas 3rd Edition, http://www.bcgatlas.org/, accessed December 21, 2020.

Interestingly, an early report from the Chinese Center for Disease Control and Prevention reported 416 laboratory-confirmed pediatric COVID-19 cases; aged 0–9 y.⁷ Moreover, other researchers who examined 2143 pediatric Chinese COVID-19 patients, both laboratory-confirmed as well as suspected cases, concluded that children at all ages appeared susceptible to COVID-19 and it is also reported that the proportion of severe and critical cases was 10.6%, 7.3%, 4.2% for the age group of <1, 1–5, 6–10, respectively. Notably, an observation that the majority of COVID-19 pediatric patients were less severe in their medical condition than adults’ cases has been suggested by those researchers to be more likely related to their relative isolation at home which might have decreased their opportunities to be exposed to SARS CoV-2.⁸

Thus, basing on the presented analysis, the author suggests that stating that BCG vaccination could prevent COVID-19 infection or that countries which have adopted childhood BCG vaccination might reason for a lower morbidity or mortality of COVID-19 for adults immunized at birth, is highly unlikely as revealed by the incidence of pediatric and adults’ morbidity and mortality rates which were reported in China. This suggestion comes in agreement with a recent analysis in 18 countries that showed no effect of BCG vaccination in early life on Covid-19 case fatality rate or number of deaths per population⁹ and we also agree with a similar conclusion shown by a Swedish study which has evaluated BCG’s effect without the biases and confounders associated with cross-country comparisons.¹⁰ However, booster doses of BCG vaccination given once a month for three consecutive months have previously showed a benefit against adult upper respiratory tract infections in the elderly¹¹ and it might^12,13 prove the same benefits against COVID-19 if administered to unimmunized or previously immunized adults waiting for the results of the several undergoing clinical trials to confirm or refute this potential [ClinicalTrials.gov]. Similarly, BCG vaccination might or might not have some ameliorative benefits for immunized children affected by COVID-19¹⁴ and this suggested positive association might be difficult to be properly investigated because of multiple confounding factors, e.g. age limitations of SARS CoV-2 exposure and/or the potential benefit coming from other concomitantly administered vaccines.^15,16 Interestingly, a recent innovative small study has revealed that five functionally immune subjects, ranging in age from 21 to 41, vaccinated with MMR II vaccine and having mumps titers of 182 AU/ml or above tested negative in SARS CoV-2 nasopharyngeal swabs and/or SARS-CoV-2 antibody tests despite several days of extensive exposure to an actively symptomatic person who was positive for SARS-CoV-2, for example, a housemate or a spouse. Moreover, the authors suggested that mumps titers related to the MMR II vaccine are significantly and inversely correlated with the severity of COVID-19-related symptoms.¹⁷

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.