Trained immunity as a novel approach against COVID‐19 with a focus on Bacillus Calmette–Guérin vaccine: mechanisms, challenges and perspectives

Abstract

COVID‐19 is a severe health problem in many countries and has altered day‐to‐day life in the whole world. This infection is caused by the SARS‐CoV‐2 virus, and depending on age, sex and health status of the patient, it can present with variety of clinical symptoms such as mild infection, a very severe form or even asymptomatic course of the disease. Similarly to other viruses, innate immune response plays a vital role in protection against COVID‐19. However, dysregulation of innate immunity could have a significant influence on the severity of the disease. Despite various efforts, there is no effective vaccine against the disease so far. Recent data have demonstrated that the Bacillus Calmette–Guérin (BCG) vaccine could reduce disease severity and the burden of several infectious diseases in addition to targeting its primary focus tuberculosis. There is growing evidence for the concept of beneficial non‐specific boosting of immune responses by BCG or other microbial compounds termed trained immunity, which may protect against COVID‐19. In this manuscript, we review data on how the development of innate immune memory due to microbial compounds specifically BCG can result in protection against SARS‐CoV‐2 infection. We also discuss possible mechanisms, challenges and perspectives of using innate immunity as an approach to reduce COVID‐19 severity.

Deadly COVID-19 among the elderly: Innate immune memory helping those most in need

“…Pre-existing underlying health conditions such as diabetes, atherosclerosis, hypertension, cancer, immunocompromised states, chronic kidney disease, and overweight/obesity substantially increase COVID-19 mortality and morbidity. 1 In addition, COVID-19 severity drastically increases with advancing age. 2,3 In patients with severe disease, COVID-19 induces a complex dysregulation of both innate and adaptive immune responses, that sometimes result in a combination of inappropriate systemic inflammation (leading to pulmonary edema and respiratory insufficiency), as well as defects in specific components of the immune responses (e.g., interferon [IFN] pathway defects, lymphopenia), contributing to disease severity.…”

COVID-19 pandemic: SARS-CoV-2 specific vaccines and challenges, protection via BCG trained immunity, and clinical trials

“…Although several reports have claimed that BCG is not effective in fighting COVID-19 [ 56–59 ], a growing number of studies have shown that countries with routine BCG vaccination programs have significantly fewer reported cases and deaths caused by COVID-19 [ 27 , 28 , 30 , 60–62 ]. However, these observational studies need to be further confirmed by clinical trials.…”

“…Currently, there is no direct evidence to support the use of the BCG vaccine for the prevention of coronavirus infections [ 31 ]. However, the available data show that the BCG vaccine provides nonspecific protection against lethal infections that are not related to the vaccine’s target pathogen by inducing trained nonspecific innate immune cells to improve host responses against subsequent infections [ 28 , 32 , 33 ]. Although induction of trained immunity (TI) by BCG vaccination leads to beneficial heterologous effects, the mechanisms underlying its persistence and magnitude remain unknown.…”

Immunological Approaches to the Treatment of Novel Coronavirus Infection (Review)

“…Several countries are conducting randomized clinical trials in vulnerable populations to study the possibility of increasing protection against COVID-19 through BCG vaccination. In addition, it is important to determine which BCG strain and which vaccine can produce the strongest immunity [193,194].…”