Immunotherapy of COVID-19 with Bacille Calmette - Guerin: Where is the missing red herring?

Abstract

Coronavirus Disease 2019 (COVID-19) morbidity and mortality was found to be less severe in countries where Bacille Calmette - Guerin (BCG) vaccination of the population is carried out. Conjugating Purified Protein Derivative (PPD) onto tumour cells and injecting into BCG primed mice was found to enhance anti-tumour immune response. We had proposed earlier that in vitro activated autologous anti-tumour T-cells bearing Major Histocompatibility Complex (MHC) II on their surface, if pulsed with PPD and re-infused in a BCG - primed patient, can activate PPD - specific helper T-cells and the focused secretion of lymphokines like the IL-2 can selectively amplify the antitumor T-cell response by their proliferation and activation in a specific manner bypassing the suppression exerted by the anti-idiotypic and suppressor cells. The prime - boost strategy with the BCG-PPD system can also be applied to the immunoprophylaxis and immunotherapy of COVID-19. The autologous anti-Corona virus B and T lymphocytes can be activated in vitro by inactivated virus or mitogens like Concanavalin A to express MHC class II molecules on their surface and pulsed with PPD for carrier targeting in vivo. Such PPD - pulsed activated (MHC-II+ve) anti-viral lymphocytes if transfused back into a patient already vaccinated with BCG during childhood or primed with BCG during adulthood 2 weeks before transfusion, could lead to a high magnitude of selective in vivo amplification of specific anti-viral lymphocytes, which can mount adequate and appropriate immune response to get rid of the virus and cure the patient from COVID-19. Conjugating antigens to PPD and injecting into BCG primed humans may also be helpful for immunoprophylaxis against COVID-19. Thus, PPD may prove to be the red herring in the BCG therapy of COVID-19.