BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?

Abstract

Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed. Here we discuss the plausibility of two of them: the universal vaccination with Bacillus Calmette-Guerin (BCG) and the widespread use of the antimalarial drug chloroquine (CQ). Both have been amply discussed in the recent literature with positive and negative conclusions: we felt that a comprehensive presentation of the data available on them would be useful. The analysis of data for countries with over 1000 reported COVID-19 cases has shown that the incidence and mortality were higher in countries in which BCG vaccination is either absent or has been discontinued, as compared with the countries with universal vaccination. We have performed a similar analysis of the data available for CQ, a widely used drug in the African continent and in other countries in which malaria is endemic; we discuss it here because CQ has been used as the drug to treat COVID-19 patients. Several African countries no longer recommend it officially for the fight against malaria, due to the development of resistance to Plasmodium, but its use across the continent is still diffuse. Taken together, the data in the literature have led to the suggestion of a possible inverse correlation between BCG immunization and COVID-19 disease incidence and severity.

Fig. 1. Impact of BCG immunization on incidences of COVID19.

a and b represent the number of incident and deaths per million ofpopulation across countries employing continuous universal vaccination, some that have discontinued vaccination, and some that never adopted BCGvaccination. c Age specific incident cases per million of population for these three types of countries. d Age specific mean number of incident cases permillion along with standard deviations are presented for different types of countries.

Fig. 2. Impact of BCG immunization on death toll due to COVID19.

a Age specific death cases per million of population for countries employing continuous universal vaccination, some that have discontinued vaccination, and some that never adopted BCG vaccination. b Age specific mean numberof death cases per million along with standard deviations are presented for different types of countries.

Fig. 3. Efficacy of BCG strain against COVID19.

a Types of BCG strain. b Number of COVID19 confirmed and c deaths cases observed forvarious BCG strains.

Fig. 4. Distribution of Chloroquine use in African Countries.

a Distribution of Chloroquine usage in African Countries, with interval ofconfidence. b Visualization of the data in panel A. c The map shows the occurrence of chloroquine resistance in the Plasmodium parasite, from darkblue (resistance at high levels) to light blue (no resistance). Countries in cyan are devoid of any malaria, but in those countries, chloroquine orhydroxychloroquine are still used for some autoimmune or inflammatory condition. Countries, where high chloroquine resistance occurs, are still among thehighest consumers of chloroquine, notwithstanding the adverse recommendation by most health authorities.