Tokyo Women's Medical University Journal (Jul 2021)
Secondary Publication: The Pathophysiology of COVID-19 (Coronavirus Disease 2019) Caused by the Infection of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2)
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a wide range of clinical manifestations, including acute respiratory distress syndrome, severe inflammation, abnormal blood coagulation, and cytokine storm syndrome. SARS-CoV-2 uniquely facilitates its entry and expansion in host cells through the spike protein consisting of S1 (receptor binding domain) and S2 (fusion peptide domain). The S1 binds to angiotensin-converting enzyme 2 (ACE2), the host cell receptor. The cleavage at the boundary of S1 and S2 by Furin protease and subsequent digestion within the S2 by TMPRSS2 activate the S2 fusion peptides, which are necessary for the entry of SARS-CoV-2 into host cells. After infection, SARS-CoV-2 RNA genome encodes viral proteins including structural proteins, RNA polymerases/helicases, and modulators of host- defense system, which inhibit type I interferon-related immune signaling and signal transducer and activator of transcription 1 (STAT1) signaling. In contrast, SARS-CoV-2 infection activates the proinflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor α (TNFα). In severe cases of COVID-19, these alterations in immune signaling may induce a state of systemic immune dysfunction. Recent studies also revealed the involvement of hematopoietic cells and alteration of cellular metabolic state in COVID-19. We here review the pathogenesis of COVID-19, primarily focusing on the molecular mechanism underlying SARS-CoV-2 infection and the resulting immunological and hematological alterations. This is the secondary publication of "The pathophysiology of COVID-19 (Coronavirus Disease 2019) caused by the infection of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) " published in the Journal of Tokyo Women's Medical University (in Japanese) 91 (1): 11-18, 2021.
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