Acute Immune Mediated Lung Injury in COVID 19: A Review

There are many gaps in our present understanding of the of the SARS CoV 2 related matters like its PAMPs,(pathogen associated molecular patterns),antigenic profile, immune evasive mechanisms and also other host related matters, like PRR s(pattern recognizing receptors) and the deranged host defense mechanisms, that cause self-damage. These constraints come in way of accurately delineating the pathogenesis of COVID19 lung disease. Hence is the speculative nature of any concept trying to explain the same. An integrated approach is embarked upon, taking into account the known clinical, radiological, laboratory, and autopsy findings, in search of clues that may suggest a possible mechanism, that explains the underlying lung damage in COVID 19. It is seen that no single mechanism or syndrome could explain fully the pathology and pathogenesis of lung damage in COVID19. Hence, multiple mechanisms consistent with each known facet of the pathology are explored. Thus the inflammatory damage of the alveolar tissue is sought to be explained by the3 complement activation pathways i.e. the alternative pathway, the MBL/Lectin pathway/ and Tissue factor/extrinsic pathway(of the classical complement activation), the contact cascade involving the kallikrein-kinin pathway, and the cytokine mediated pro and anti inflammatory mechanisms. The vascular pathology like hemorrhages and small blood vessel micro-thrombi as observed at autopsy , are viewed from the point of view of simple activation of the coagulation cascade to small vessel vasculitis (leucocytoclastic vasculitis) and coagulative micro angiopathy. Besides, the role of TM-PC-EPCR SYSTEM (Thrombomodulin-Protein C-EPCR System) is explored. The points in favour and against of each of the above are discussed.The central role played by the macrophage polymorphism is focused in the context of the simultaneous presence of active inflammation in the lung tissue and the interstetium and healing by interstitial fibrosis, seen in the lungs of COVID 19 patients. The role played by the other humoral and cellular elements of both innate and adaptive immunity is briefly reviewed. The uniqueness and diversified features of COVID 19 lung pathology, suggests two things - that the immune mediated damage seems more probable than could be explained by the viral infectivity and that the pathology seems to stem from a mixture of different underlying and overlapping syndromes. Hence, the author prefers to call all the COVID 19 related features of lung pathology as “Acute immune mediated Lung injury". (AILI) than trying to bunch them under a single syndrome.