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

Abstract

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.

Genetic susceptibility of COVID-19: a systematic review of current evidence

“…Thus, research should investigate the relationship between age and polymorphisms for TMPRSS2 2. We found 6 germline deleterious variants (p.Val160Met, p.Gly181Arg, p.Arg240Cys, p.Gly259Ser, p.Pro335Leu, and p.Gly432Ala) in the TMPRSS2 coding region 12 Junejo et al [ 41 ] Review Pakistan/Turkey COVID-19 patients Loss of ACE2 function is related to acute lung injury because the ACE2 downregulation can result in RAS dysfunction, and endorse the inflammation that causes vascular permeability 13 Kachuri et al [ 42 ] Research study USA COVID-19 patients ACE2 gene Sars-Cov-2 uses the ACE2 receptor for cell entry 14 LoPresti et al [ 43 ] Review USA COVID-19 patients ACE2 gene, TMPRSS2 gene, HLA-B*46:01 HLA-B*15:03 may be protective 15 Sanchez-Gonzalez et al [ 44 ] Report USA COVID-19 patients Telomeres In addition to people with immune senescence and dysregulation, SARS-CoV-2 can stimulate an HP-like severe immune reaction, especially in genetically vulnerable individuals. Telomeres typically shorten as the person gets older, but different rates of shortening may allow for measuring chronological versus biological aging.…”

“…Consistent with the general conclusion, there are several genetic patterns of susceptibility for COVID-19, including: ACE2, TMPRSS2, Cathepsin, FURIN, MX dynamin-like GTPase 1 (MX1), Basigin (BSG), IFN-γ, IL-17A/F, HLA, cytokine storm, TLR genes, p.Ser1103, Tyr-SCN5A, p.Arg514Gly, p.Val160Met, p.Gly181Arg, p.Arg240Cys, p.Gly259Ser, p.Pro335Leu, p.Gly432Ala, Telomeres, and immune complexes (ICs) [ 18 , 19 , 30 , 32 , 33 , 38 – 40 , 43 , 44 , 51 ]. Our review demonstrated that genetic risk factors can affect the treatment and prevention of COVID-19.…”

Pathogenesis and Mechanism of Gastrointestinal Infection With COVID-19

“…There are very few reports about SARS-CoV-2 infection leading to viremia ( 42 , 43 ). Recently, in a case, researchers isolated and cultured a live SARS-CoV-2 virus strain from the stool of an advanced patient and believed that SARS-CoV-2 might be able to migrate from the lungs to the blood circulation to the digestive tract ( 44 ).…”

COVID 19 – Possible interrelations with respiratory comorbidities caused by occupational exposure to various hazardous bioaerosols. Part II. Clinical course, diagnostics, treatment and prevention

“…A study by Sanchez-Gonzales et al [4], published in July 2020, posed the hypothesis that SARS-CoV-2 may act as a trigger and substrate of severe hypersensitivity pneumonitis (HP) with immune dysregulation, especially in a genetically susceptible patient. In both diseases, e.g.…”

“…Knowledge about the interrelations between this 'new' disease, and 'old' diseases that trouble humans for centuries, is very important as it has been evidenced that such conditions as hypertension, diabetes mellitus, cardiovascular diseases, and obesity [1,3] occur commonly as comorbidities among COVID-19 patients and aggravate the course of the disease. As SARS-CoV-2 attacks primarily the respiratory system and the severe manifestation of COVID-19 is interstitial pneumonia [1,3,4], the interrelations between this disease and other respiratory diseases are of special interest.…”