A Pathophysiological Perspective on COVID-19's Lethal Complication: From Viremia to Hypersensitivity Pneumonitis-like Immune Dysregulation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus responsible for our recent coronavirus disease 2019 pandemic, is driving a lung immunopathology that strongly resembles a severe form of hypersensitivity pneumonitis (HP). A review of recent Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and SARS-CoV-2 medical reports, as well as described characteristics of HP, lead us to postulate a theory for SARS-CoV-2 severe disease. We propose that the novel SARS-CoV-2 can act as a trigger and substrate of an HP-like severe immune reaction especially in genetically vulnerable individuals in addition to those with immune senescence and dysregulation. Accordingly, the purpose of our letter is to shift the emphasis of concern surrounding immune activity from viral infection to an HP-like severe immune reaction. We review similarities in disease presentation between infection and allergy, relevant immunopathology, and outline phases of SARS-CoV-2 disease with perspectives on therapy and critical care. Altogether, the favored course is to begin treatments that address the disease at the earliest phase before immune dysregulation leading to uncontrolled pulmonary inflammation.