Abstract Body

We describe how SARS-CoV-2 tropism for alveolar type II pneumocytes is associated with a physiological immunothrombosis in the adjacent closely juxtaposed alveolar capillary network and associated arteriolar and venular territory thrombosis.
This a a mechanism to constrain viral replication and generally keeps virus replication limited to the alveolar territory. However, in severe COVID-19 pneumonia, the failure of initial innate immune responses may trigger severe myeloid related inflammation, Robust SARS-CoV-2 antibody responses in the second week of infection may also enhance antibody dependent immune responses in the alveolus to further exacerbate immunothrombosis.

We dubbed this immunopathology as pulmonary intravascular coagulopathy (PIC) that is largely confined to the lungs and is linked to local intra-pulmonary macrophage activation (McGonagle et al Autoimmunity Rev 2020 & Lancet Rheumatology 2020). This immunopathology is distinct from the well-recognised disseminated intravascular coagulation (DIC) and associated macrophage activation syndrome (MAS) that can also be linked to infection but the latter triggers systemic thrombosis and concomitant bleeding whereas PIC is mostly confined to the lungs. We described who this PIC pathology is linked to vasculitiic type pathology in both the lung and systemic circulation.

The fact that immunomodulatory therapy including steroids, anti-cytokine therapy and JAK inhibition show efficacy in severe COVID-19 is likely down to absence of active endothelial infection but rather a dampening of lung tissue immunothrombosis in the post-viral replication phase of COVID-19. An accurate determination of when viral replication stops is incomplete and has implications for optimal therapy for this novel recognised respiratory virus immunopathology