Fig. 2
From: The role of host defences in Covid 19 and treatments thereof
Proposed model for the pathogenesis of Covid 19. 1 - The virus penetrates the airways and infects the bronchial and alveolar epithelium, other routes of invasion are possible (e.g. eye); 2 - The virus starts replication into the cell; 3 - Massive synthesis of viral proteints into the endoplasmic reticulum (ER); 4 - The ORF8 and surface glycoprotein start attacking and destroying the heme of heme proteins (4a) while the ER stress caused by massive protein synthesis activates the physiologic HO-1 response (4b); 5 - The activation of HO-1 fails to work due to substrate (heme) inhibition by viral proteins; 6 - In absence of CO from HO-1 there is no shift of transulfurations to alternative reactions and failure to release H2S; 7 – Hampered H2S release from CBS/CSE (7a) inhibits their persulfide forming activity while destruction of the heme by viral proteins (7b) further decreases H2S effects by inhibiting its persulfidation signalling; 8 - Due to low H2S-induced persulfidation, the KATP channels of leucocytes closes down, which triggers leucocyte adhesion to the endothelium; 9 - The adhesion of leucocytes is followed by massive release of inflammatory cytokines, both local and systemic; 10a - Inflammation induced by cytokines further feeds viral replication amplifying the effects in a vicious loop; 10b - Inflammatory cytokines diffuse systemically and cause or exacerbate pre-existing damges in many organs and functions, mainly hearth and coagulation. Black box: Subjects with a strong HO-1 reaction (4b) are predicted to overcome the viral aggression and to exert an asymptomatic or pauci-symptomatic disease; Subjects with a defective genetic background, e.g. weak expression of the HMOX1 gene coding for HO-1, may suffer critical or fatal Covid 19