SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping

Abstract

The current pandemic of COVID-19 has caused severe morbidity and mortality across the globe. People with a smoking history have severe disease outcomes by COVID-19 infection. Epidemiological studies show that old age and pre-existing disease conditions (hypertension and diabetes) result in severe disease outcome and mortality amongst COVID-19 patients. Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host's lung epithelium. Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment. The viral entry has been shown to cause 'cytokine storm' involving excessive production of pro-inflammatory cytokines/chemokines including IL-6, TNF-α, IFN-γ, IL-2, IL-7, IP-10, MCP-3 or GM-CSF, which is augmented by smoking. Future research could target these inflammatory-immunological responses to develop effective therapy for COVID-19. This mini-review provides a consolidated account on the role of inflammation and immune responses, proteases, and epithelial permeability by smoking and vaping during SARS-CoV2 infection with future directions of research, and provides a list of the potential targets for therapies particularly controlling cytokine storms in the lung.

Keywords: ACE2; COVID-19; E-cigarettes; Inflammation; SARS-CoV2; Smoking; Vaping.

Fig. 1

Factors responsible for higher susceptibility of smokers/vapers against COVID-19. In normal individuals, the muco-ciliary epithelium and the mucous layers act as the first line of defence against the foreign pathogen (in this case SARS-CoV2). On smoking, this layer is damaged and so is the flow of the peri-ciliary fluid (mucous; indicated by arrows) which makes them more prone to infections. Smokers are also shown to have higher surface expression of ACE2 receptors (binding sites for SARS-CoV2) which allows the entry of pathogens into the host cell and protects the virus against the host surveillance. In normal individuals, the viral infection could be checked by the, (a) cytokine release from the type II pneumocytes, goblet, nasal epithelial/ciliated and oral mucosal cells and (b) immune cell (macrophages, neutrophils and lymphocytes) infiltration at the site of infection, to contain further spread. Smoking weakens the immune system enabling easy entry into the host cell, rapid multiplication of the virus followed by hyperinflammatory response triggered by ‘cytokine storm’ in the host body eventually leading to damaged lung tissue

Fig. 2

Potential drug targets and strategies being tested to contain SARS-CoV-2 infection. SARS-CoV2 has a high binding affinity to ACE2 receptors found in abundance in the type II pneumocytes in the lung alveolar epithelium. This could be targeted by ACE inhibitors/ARBs. On binding to the ACE2 receptors, TMPRSS2 protease cleaves the viral S protein and enable the engulfment of the viral body into the cell. Here the viral proteases enable the fusion of the endosomal membrane and release of viral RNA (genome) into the host’s cytoplasm. TMPRSS2 inhibitors or antimalarial drugs (chloroquine/hydroxychloroquine) can prevent this engulfment. The viral RNA now hijacks the host’s translational machinery to express viral proteins and further enables viral replication and packaging. This is the site of action for various antiviral drugs being tested in clinical trials at present. The viral RNA and protein get packaged as virions which are ultimately released into the extracellular space, where it leads to release of pro-inflammatory cytokines/chemokines and infiltration of immune cells. It is speculated that the heightened immune response is responsible for the disease severity in COVID-19 patients, thus immune-modulation is one of the alternate to be used to prevent serious outcomes. Alternate approaches like targeting viral structural targets or use of convalescent plasma to induce passive immunity are other strategies which are being explored at present