key: cord-0860891-97zekfm8 authors: Caminati, M.; Furci, F.; Senna, G.; Delfino, G.; Poli, A.; Bovo, C.; Patella, Vincenzo title: BCG vaccination and COVID-19: much ado about nothing? date: 2020-07-15 journal: Med Hypotheses DOI: 10.1016/j.mehy.2020.110109 sha: af7f0875df9a0f2c21e41553c96c2f17082fa51d doc_id: 860891 cord_uid: 97zekfm8 nan We read with great interest the article "Relation between BCG coverage rate and COVID-19 infection worldwide" by Macedo et al [1] , which provides a worldwide overview of vaccination programmes and COVID-19 burden in different countries, and postulates that BCG may protect from COVID-19. By relying on speculation more than on evidence the current scientific debate seems to value the idea of a BCG-related lower susceptibility to COVID-19 [2] . As a proof of concept, different authors reported a limited COVID-19 burden in BCG vaccinated countries [2] [3] [4] [5] . The hypothesis is certainly supported by a strong immunological rationale. In fact, BCG vaccination may contribute to polarize the physiological immune reaction toward a Th1 pattern and exert an additional protective role against viruses [6] . However, when looking at the different distribution of COVID-19 outbreak worldwide according to BCG coverage, several confounding factors should be considered. The low temperature facilitates the virus spread. The most affected countries experienced the COVID-19 pandemic during their wintertime [7] , which could explain the difference between the northern and southern hemisphere besides BCG vaccination. Furthermore, depending on the local health care system, case identification resources, including COVID-19 swabs, may vary in different countries, which is relevant when sizing the impact of a viral infection. In Europe, where the above-mentioned variables are quite homogeneous, COVID-19 outbreak is still lower where BCG vaccination is regularly provided [8] . It is the case of Eastern Countries (except Portugal). However, the population mean age in BCG unvaccinated states is significantly higher in comparison to vaccinated ones (respectively 40.9-SD 3.1-vs 37.8-SD 5.7-years; t-test: p=0.031), as well as the mean life expectancy (respectively 81.6-SD 1.7 vs 75.0-SD 2.6 years; t-test: p<0,001) [8] . This evidence is not negligible when considering that most of COVID-19 fatal cases were registered in patients older than 70. Whitney test: p=0.003). The difference is remarkable when considering its relevance in facilitating the infection from human to human [9] . The same effect can be exerted by the international commercial exchanges and air traffic, which is much more relevant in European Western Countries, primarily interested by the COVID-19 outbreak. In the light of the above-mentioned determinants, the hypothetic relevance of BCGvaccination as a protection from COVID-19, although fascinating, remains quite controversial and further focused research is required besides speculation. Relation Between BCG Coverage Rate and COVID-19 Infection Worldwide. Med Hypotheses Considering BCG vaccination to reduce the impact of COVID-19 Otazu GH Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study Is BCG vaccination affecting the spread and severity of COVID-19? Allergy. 2020. Online ahead of print Association of BCG vaccination policy with prevalence and mortality of COVID-19 Defining trained immunity and its role in health and disease Effects of temperature and humidity on the daily new cases and new deaths of COVID-19 in 166 countries An official website of the European Union Int A geographic analysis of population density thresholds in the influenza pandemic of 1918-19 Not applicable The authors declare no conflicts of interest.