Higher BCG‐induced trained immunity prevalence predicts protection from COVID‐19: Implications for ongoing BCG trials

Abstract

Endeavors to identify potentially protective variables for COVID‐19 impact on certain populations have remained a priority. Multiple attempts have been made to attribute the reduced COVID‐19 impact on populations to their Bacillus–Calmette–Guérin (BCG) vaccination coverage ignoring the fact that the effect of childhood BCG vaccination wanes within 5 years while most of the COVID‐19 cases and deaths have occurred in aged with comorbidities. Since the supposed protection being investigated could come from heterologous ‘trained immunity’ (TI) conferred by exposure to Mycobacterium spp. (i.e., environmental and BCG), it is argued that the estimates of the prevalence of TI in populations currently available as latent tuberculosis infection (LTBI) prevalence would be a better variable to evaluate such assertions. Indeed, when we analyze the European populations (24), and erstwhile East and West Germany populations completely disregarding their BCG vaccination coverage, the populations with higher TI prevalence consistently display reduced COVID‐19 impact as compared to their lower TI prevalence neighbors. The TI estimates of the populations not the BCG coverage per se, negatively correlated with pandemic phase‐matched COVID‐19 incidences (r(24): −0.79 to −0.57; p‐value < .004), mortality (r(24): −0.63 to −0.45; p‐value < .03), and interim case fatality rates (i‐CFR) data. To decisively arrive at dependable conclusions about the potential protective benefit gained from BCG vaccination in COVID‐19, the ongoing or planned randomized controlled trials should consciously consider including measures of TI as: (a) all individuals immunized do not respond equally, (b) small study groups from higher background TI could fail to indicate any protective effect.

Do selected lifestyle parameters affect the severity and symptoms of COVID-19 among elderly patients? The retrospective evaluation of individuals from the STOP-COVID registry of the PoLoCOV study

“…The isolation period of patients was taken into account, enabling to assign them to a specific wave of the pandemic, in accordance with the infection pattern in Poland (collectively based on [15] , [23] , [24] ): First (I) wave—from March 1, 2020 to August 30, 2020 (due to the small number of patients in the first wave, they were not included in the current analysis); Second (II) wave—from September 1, 2020 to January 30, 2021; Third (III) wave—from February 1, 2021 to August 30, 2021; Fourth (IV) wave—from September 1, 2021 to December 31, 2021; Fifth (V) wave—from January 1, 2022 to the end of the observation period (May 2022). …”

Revisiting biological sex as a risk factor for COVID-19: a fact or mirage of numbers?

“…Cases Sex Ratio (CSR), Death Sex Ratio (DSR), Mortality Sex Ratio [both in confirmed COVID-19 cases (MSR-COVID-19) and the prevailing pre-pandemic (MSR-PP)] are the calculated ratio of observed male to female in reported COVID-19 cases, reported COVID-19 deaths, and reported mortality rates, respectively. General mathematical and statistical calculations on data, e.g., sum, average, STDEV, ratio, correlation analysis, were performed in Excel as done previously [29,31,39]. A majority of countries (51/70) reported lowered rate of male death rates while a small minority of countries (19/70) displayed no change (4; green boxed) to a higher rate (15) of male mortality in COVID-19, mostly from Africa and Asia.…”

“…General mathematical and statistical calculations on data, e . g ., sum, average, STDEV, ratio, correlation analysis, were performed in Excel as done previously [29,31,39].…”

Effect of BCG on Respiratory Complications Caused by COVID-19: A Scoping Review

“…Importantly, some argue that the BCG vaccination effect is confounded by the fact that people in countries with a BCG vaccination policy have a higher level of exposure to Mycobacterium spp. [51][52][53]…”