Discussion
This is a descriptive study which aimed to investigate the
characteristics of subjects with severe and mild COVID-19 pneumonia.
According to the study results, BCG vaccination status is not related to
clinical condition in COVID-19 pneumonia, whereas, increasing age and
low-income are the factors associated with severe COVID-19 pneumonia.
BCG vaccine, a live attenuated bacterial vaccine derived from
Mycobacterium bovis, is recommended in countries with a high incidence
of tuberculosis.6 Beyond immunisation against
tuberculosis, BCG vaccine provides improved immune response against some
viral pathogens including respiratory syncytial virus, influenza A virus
and herpes simplex virus type 2. These nonspecific immune effects, known
as trained immunity, occur via epigenetic reprogramming of monocytes and
production of IL-1β, TNF and IL-6 during subsequent viral
infection.7 Observational studies on clinical
reflection of the immunopathogenesis of BCG vaccine report that BCG
vaccination and presence of a BCG scar among infants reduce the risk of
respiratory tract infections.8,9
Countries’ vaccination policies gained importance during the COVID-19
pandemic. Analyses of the relationship between countries’ BCG
vaccination databases and their COVID-19 statistics suggest that BCG
vaccination significantly reduces COVID-19 mortality rates, and that the
earlier a country establishes a BCG vaccination policy, the lower
COVID-19 deaths per million inhabitants. National BCG vaccination
policies are also thought to be related to flattened COVID-19 growth
curves.4,10 Another report which analyzed data of 210
countries and territories have shown that BCG-vaccination policy was
associated with lower COVID-19 morbidity and mortality rates, but not
with case-fatality rate. High median age, low per capita gross domestic
production adjusted to purchasing power and high per capita health
expenditure were found to be related to higher morbidity and mortality
rates in COVID-19.11 In Turkey, national
BCG-immunisation programme has been implemented since 1953 for control
of tuberculosis. BCG vaccination rates reached 94.4% in 2013.12,13
The study population consisted of BCG-vaccinated and -unvaccinated
COVID-19 pneumonia cases in order to compare the severity of the disease
in the two groups. BCG-vaccinated and -unvaccinated groups were similar
in terms of body-mass index, gender distribution, smoking status and
presence of diabetes and hypertension. However they were significantly
different in terms of age and income; such as, BCG-unvaccinated group
was significantly older compared to BCG-vaccinated group and nearly all
subjects in BCG-unvaccinated group were low-income. A possible
explanation for low income of people without BCG vaccination is people
migrating from rural to urban areas in search of employment and earn
living. As the major outcome of the study, in severe COVID-19 pneumonia
patients, the rate of cases not vaccinated with BCG was significantly
higher than in patients with mild COVID-19 pneumonia. However, the most
important confounding factor in the study was the uneven distribution of
income between the unvaccinated group and the vaccinated group.
Accordingly, logistic analysis revealed that increasing age and low
income level were predictive of severe disease, whereas BCG vaccination
status is not related to the severity of COVID-19 pneumonia.
This is the first study to evaluate severity of clinical condition with
BCG-vaccination status in COVID-19 pneumonia patients. Previous reports
are based on analysis of COVID-19 statistics and countries’ national BCG
vaccination policies. However, international comparisons of COVID-19
epidemiology are difficult because the ways in which countries record
COVID-19 cases and deaths are different depending on the polymerase
chain reaction results or clinical decision. Population characteristics
of countries such as population density, median age, and urban
population and mainly SARS-CoV-2 test rates are major confounders that
may lead to misjudgement of BCG vaccination policy is
beneficial.14 According to a report published very
recently, there was no statistically significant difference in the
SARS-CoV-2 positive test results between the BCG-vaccinated group and
the non-vaccinated group.15 Also in Brazil, which has
been carrying out the BCG vaccination program since 1920, the morbidity
and mortality rates of COVID-19 disease have reached today’s distressing
levels, also questions any protective role of BCG vaccination in the
COVID-19 outbreak.
Second most important finding of the present study is that increasing
age and low-income are the predictors of severe disease in COVID-19
pneumonia. Age is reported as main risk factor for disease severity and
mortality in COVID-19 since the beginning of the
outbreak.16-23 The relationship between low-income and
serious COVID-19 emerged mainly after news that low-income minority
residents were most affected, from the USA, especially New York City.
According to various reports from different states non-Hispanic black
patients were disproportionately hospitalized with diagnosis of
COVID-19. However, the absence of any difference in intensive care unit
admission and mortality rates in black patients suggests that the
distinction in SARS-CoV-2 infection rates is due to socioeconomic
inequalities rather than racial and ethnic
differences.24,25 In line with previous reports on the
importance of socioeconomic inequalities in COVID-19, in the present
study, low income was an independent predictor of severe disease.
Most prevalent comorbidities reported in serious or critically ill
subjects with COVID-19 are diabetes mellitus, chronic lung disease and
cardiovascular disease.16-18,20,21 The percentage of
COVID-19 cases with at least one underlying health condition was higher
among those hospitalized compared to
non-hospitalized.17 Yet, data from countries may vary
for different reasons, like health policies implemented in the
countries, proportion of elderly population, prevalance of concomitant
diseases and whether or not comorbidities are under control. Prompt
measures taken by Turkish Government early in the epidemic may be the
reason why comorbid disease rates were not an independent predictor of
severe COVID-19 pneumonia in the present study. Because immediately
after the first COVID-19 case was detected in Turkey, people with
chronic illness were considered on leave in public and private sector.
The major strength of the present study is that severity of COVID-19
pneumonia is assessed in BCG vaccinated and unvaccinated inhabitants of
the same country, which implements national BCG vaccination policy.
Another strength of the study is that all patients are evaluated in a
single center, providing homogeneity in clinical evaluation of patients.
Main limitation of the study is the relatively low number of subjects.
However, since BCG vaccine is administered regularly in the country, the
number of individuals who have not been vaccinated is limited in the
country.
Acknowledgements: KA and TN had full access to all of the data
in the study and takes responsibility for the integrity of the data and
the accuracy of the data analysis. KA constructed hypothesis for
research, KA, TN, and PÖ contributed substantially to the study design,
TN, and PÖ contributed substantially to data collection, KA, and TN
performed data analysis and interpretation. KA, TN, and PÖ substantially
contributed to the writing of the manuscript. KA, TN, and PÖ approved
final manuscript. No funding was received for the study.