SARS-CoV-2 Genetic Variability and Non-Specific Immunity Associated with the Use of Different BCG Strains-A Molecular and Clinical Approach

Abstract

The effect of BCG vaccination against tuberculosis on the reduction in COVID-19 infection is related to the effect of the BCG vaccine on the immunomodulation of non-specific immunity. In the early stages of the pandemic, countries with universal BCG vaccination programs registered a low number of new cases of COVID-19, with the situation now reversed, as exemplified by India. The high genetic variability of SARS-CoV-2, a known characteristic of RNA viruses, causing the occurrence of SARS-CoV-2 variants may have led to the virus adapting to overcome the initial immune protection. The strains from the United Kingdom (B1.1.7), Brazil (B1.1.28 and B1.1.33), South Africa (B.1.351), and India (B.1.617) are characterized by a greater ability to spread in the environment, in comparison with the original infectious agent of SARS-CoV-2. It should be remembered that the large variation in the genetic makeup of SARS-CoV-2 may result in future changes in its pathogenicity, immunogenicity and antigenicity, and therefore it is necessary to carefully study the mutations occurring within the virus to determine whether the current vaccines will remain effective. However, most studies show that monoclonal antibodies produced after vaccination against COVID-19 are effective against the newly developed variants.

Keywords: BCG vaccinations; COVID-19; SARS-CoV-2; WHO recommendation; genetic variability; tuberculosis; variants.

Figure 1

Human SARS-CoV-2 structure. SARS-CoV-2 is composed of 4 structural proteins: membrane protein (M), spike protein (S), envelope protein (E) and nucleoprotein (N), which is responsible for the formation of the capsid. The genetic material of SARS-CoV-2 is a single-stranded positive-sense RNA. Created with BioRender.com (accessed on 8 May 2021).

Figure 2

Mechanism of SARS-CoV-2 viral entry. Viral S glycoprotein contains two subunits: S1 and S2, with S1 constituting receptor binding domain (RBD). S1 subunit associates with host cell’s receptor ACE2 with the participation of TMPRSS2, which leads to conformational changes in S1 subunit and endosomal reaction. Subsequently, S2 subunit activates host cell fusion with viral particles, leading to viral replication. Abbreviations: ACE2—angiotensin-converting enzyme 2; RBD—receptor binding domain; TMPRSS2—transmembrane protease serine 2. Created with BioRender.com (accessed on 8 May 2021).

Figure 3

Novel genetic variants of SARS-CoV-2 have been described and their origin is marked on the map. Additionally, mutations responsible for the occurrence of British and South African variants are marked. Created with BioRender.com (accessed on 8 May 2021).

Figure 4

BCG vaccine against tuberculosis includes six strains: Pasteur 1173 P2, Danish 1331, Glaxo 1077, Tokyo 172-1, Russian BCG-I and Moreau RDJ. Apart from preventing tuberculosis, BCG vaccine exhibits immunomodulatory effects, resulting in activation of non-specific immunity, macrophage activation and proinflammatory cytokine release by NK cells. Such response after vaccination was shown to be associated with reduction in severe cases of COVID-19 and COVID-19-related mortality. Abbreviations: BCG—Bacillus Calmette–Guérin; NK—natural killer. Created with BioRender.com (accessed on 8 May 2021).