The mystery of BCG vaccine in protection against SARS-CoV-2

Years after the beginning of the COVID-19 pandemic, the whole world has been affected. While infection rates have decreased over the years, the beginning of the pandemic still saw exponential increase in global infections, jumpstarting the campaign to design vaccines. While we now have these vaccines available, back then we lacked protection against the virus. The Bacillus Calmette-Guerin (BCG) vaccine is currently widely used in the prevention of tuberculosis, yet its use does not end there. Literature associates BCG with protection against various parasites, fungal infections, and bacterial infections. Its ability to provide such broad protection has been attributed to its induction of trained immunity. The immune system has two arms, adaptive and innate immunity. The innate immune response is the first line of defense and elicits fast, non-specific responses. The adaptive immune response, while slower to respond, acts in a specific manner by building immunological memory of the infectious agent. In trained immunity, innate immune cells appear to gain a memory-like ability and in turn can provide greater protection against different pathogens. Many studies have investigated the protective abilities of BCG against different pathogens with some yielding contradicting results. In fact, recent literature has been split regarding the ability of BCG to provide protection against SARS-CoV-2. An important distinctive factor between these studies is the BCG strain used, and so I hypothesize that BCG-Pasteur contains a unique genomic factor(s) that allows protection against SARS-CoV-2. Investigating the effects of differing BCG vaccine strains (Tice vs. Pasteur) on the immune response could be the key in better understanding the range of protection this vaccine can provide.