With input from Dr Monica Vasudev

1382:  BCG vaccination and COVID-19

1.    The innateimmune system represents the first line of defense against many novelpathogens against which humans may have little to no immunity.

2.    Recentlarge-scale epidemiological studies suggest that countries in which Bacillus Calmette-Guerin(BCG) vaccination is widespread have lower mortality rates from COVID-19.

3.    Somevaccines are capable of improving innate immune responses toinfections other than those caused by the target pathogen. This is termed as trainedimmunity. It occurs as a result of epigenetic changes in macrophages andneutrophils. These cells are short-lived, but novel research suggeststhat similar changes take place in long-lived hematopoietic stem cells. Thiscould account for lasting memory within the innate immune system [Cell StemCell. 2020;26(5):793] 

Trained immunity

1.    Cells ofthe innate immune system can be trained by past infection,exposure to vaccines such as BCG, or contact with microbial components such asLPS. This gives way to enhanced response to the original or another trigger.

2.    Epigeneticreprogramming of transcriptional pathways has a role in the trained state.

3.    Trainedmonocytes and neutrophils have a short life span. However, the long-lived marrowhematopoietic stem cells (HSCs) conserve epigenetic memory of previousinfections. They have self-renewal potential that helps maintain lifelongproduction of innate immune cells.

4.    Randomizedtrials in Guinea-Bissau revealed that BCG vaccination at birth given tolow-weight infants led to significant reduction in infectious disease mortalitywithin the first month and first year.

5.    Inducedtrained immunity can help cancer therapies and sepsis-associated immuneparalysis.

6.    It has alsobeen approved for treatment of bladder cancer. Large-scale epidemiologicalstudies have shown that national programs in BCG vaccination reduce COVID-19related mortality.

Evidences 

Trainedimmunity is a form of non-specific memory-like immune response incited by somepathogens and vaccines, such as BCG, which can provide antigen-independentprotection against several pathogens. The BCG vaccine has been in use forprotection against tuberculosis for almost a century now. The vaccine reduces mortality caused by infections not related to Mycobacterium tuberculosis in children. Thisappears to be due to the induction of trained immunity.

Investigatorsassessed the number of positive cases and deaths in different countries andcorrelated them with the inclusion of BCG vaccination at birth in theirnational vaccination programs. The countries where BCG vaccination is given atbirth had a lower contagion rate and lesser deaths fromCOVID-19, pointing tovaccine-induced trained immunity that could provide some protection against SARS-CoV-2.(Front Immunol. 2020;11:970. )

Escobarand colleagues reviewed evidence for a biological basis of BCG cross-protectionfrom severe COVID-19. There appeared to be a strong correlation between the BCGindex, an estimate of the degree of universal BCG vaccination deployment in acountry, and COVID-19 mortality in socially similar European countries (r2 =0.88; P = 8×10-7). A 10% rise in the BCG index was associated with a10.4% reduction in COVID-19 mortality.

Resultsfailed to confirm the null hypothesis of no association between BCG vaccinationand COVID-19 mortality, and suggested that BCG vaccine could have a protective role.(Proc Natl Acad Sci U S A. 2020;117(30):17720)

Dr KK Aggarwal

President CMAAO, HCFI and Past NationalPresident IMA