Fiction and Facts about BCG Imparting Trained Immunity against COVID-19

Abstract

The Bacille Calmette-Guérin or BCG vaccine, the only vaccine available against Mycobacterium tuberculosis can induce a marked Th1 polarization of T-cells, characterized by the antigen-specific secretion of IFN-γ and enhanced antiviral response. A number of studies have supported the concept of protection by non-specific boosting of immunity by BCG and other microbes. BCG is a well-known example of a trained immunity inducer since it imparts ‘non-specific heterologous’ immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the recent pandemic. SARS-CoV-2 continues to inflict an unabated surge in morbidity and mortality around the world. There is an urgent need to devise and develop alternate strategies to bolster host immunity against the coronavirus disease of 2019 (COVID-19) and its continuously emerging variants. Several vaccines have been developed recently against COVID-19, but the data on their protective efficacy remains doubtful. Therefore, urgent strategies are required to enhance system immunity to adequately defend against newly emerging infections. The concept of trained immunity may play a cardinal role in protection against COVID-19. The ability of trained immunity-based vaccines is to promote heterologous immune responses beyond their specific antigens, which may notably help in defending against an emergency situation such as COVID-19 when the protective ability of vaccines is suspicious. A growing body of evidence points towards the beneficial non-specific boosting of immune responses by BCG or other microbes, which may protect against COVID-19. Clinical trials are underway to consider the efficacy of BCG vaccination against SARS-CoV-2 on healthcare workers and the elderly population. In this review, we will discuss the role of BCG in eliciting trained immunity and the possible limitations and challenges in controlling COVID-19 and future pandemics.

Trained Immunity, BCG and SARS-CoV-2 General Outline and Possible Management in COVID-19

“…During the COVID-19 pandemic, the hypothesis, partly supported by observations, was suggested that countries without widespread BCG prophylaxis experienced an increased incidence of the disease [ 45 ]. Using knowledge of the trained immunity phenomenon and the experience of previous observational studies, many authors have attempted to understand the effect of BCG vaccination on the course and severity of SARS-CoV-2 infection [ 46 ]. Various studies have been conducted on different populations and with different scientific methodologies.…”

“…The only route of administration of BCG used in humans is intradermal administration. Studies in non-human primates have shown greater efficacy of other drug administration routes, including intravenous or nasal delivery, which may be important for infections with the virus affecting the respiratory system [ 46 , 63 , 66 , 67 ].…”

Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens

“…Thus, inducers of trained immunity may provide a "head start" to fight novel pathogens that attenuate transmission, progression, or severity of infection. For instance, a plethora of evidence on the protective role of BCG resulted in at least 25 clinical trials in the early stage of the COVID-19 pandemic [19].…”

“…The trained immune response is manifested by metabolic reprogramming and epigenetic modifications happening at the transcriptional level compared to the gene recombination and clonal expansion, a hallmark feature of adaptive immunity [17] [18]. The onset of innate immune memory upon a secondary challenge is faster and typically takes minutes to hours, resulting in elevated innate response mediated by the secretion of higher levels of proinflammatory cytokines, reactive oxygen species (ROS), and phagocytosis [19]. The epigenetic modifications by acetylation and methylation of histone confer easy gene transcription and consequent overexpression that elicits an antipathogen response.…”

Effectiveness of vaccination in reducing hospitalization and mortality rates in dialysis patients with Omicron infection in China: A single-center study

“…It is reported that around 23.3 million deaths have been prevented by vaccination from 2011 to 2020. 18 , 19 , 20 In the current global COVID-19 pandemic, the most cost-effective solution to reduce the global burden of COVID-19 is the implementation of safe and effective vaccines. 21 Consequently, various types of vaccines have been rapidly developed, produced, and utilized.…”