Immunopathogenesis of SARS-CoV-2-induced pneumonia: lessons from influenza virus infection

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(2020) 40:39

Inflammation and Regeneration

REVIEW

Open Access

Immunopathogenesis of SARS-CoV-2induced pneumonia: lessons from influenza virus infection Masaaki Miyazawa

Abstract Factors determining the progression of frequently mild or asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection into life-threatening pneumonia remain poorly understood. Viral and host factors involved in the development of diffuse alveolar damage have been extensively studied in influenza virus infection. Influenza is a selflimited upper respiratory tract infection that causes acute and severe systemic symptoms and its spread to the lungs is limited by CD4+ T-cell responses. A vicious cycle of CCL2- and CXCL2-mediated inflammatory monocyte and neutrophil infiltration and activation and resultant massive production of effector molecules including tumor necrosis factor (TNF)-α, nitric oxide, and TNF-related apoptosis-inducing ligand are involved in the pathogenesis of progressive tissue injury. SARSCoV-2 directly infects alveolar epithelial cells and macrophages and induces foci of pulmonary lesions even in asymptomatic individuals. Mechanisms of tissue injury in SARS-CoV-2-induced pneumonia share some aspects with influenza virus infection, but IL-1β seems to play more important roles along with CCL2 and impaired type I interferon signaling might be associated with delayed virus clearance and disease severity. Further, data indicate that preexisting memory CD8+ T cells may play important roles in limiting viral spread in the lungs and prevent progression from mild to severe or critical pneumonia. However, it is also possible that T-cell responses are involved in alveolar interstitial inflammation and perhaps endothelial cell injury, the latter of which is characteristic of SARS-CoV-2-induced pathology. Keywords: SARS-CoV-2, Influenza virus, Pneumonia, Tissue injury, Cytokines, Chemokines, T cells

Background SARS coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The current pandemic started in Wuhan, China in late 2019 and has caused more than 33 million confirmed infected cases and nearly 1 million deaths as of September 27, 2020 (worldometer COVID-19 CORONAVIRUS PANDEMIC https:// www.worldometers.info/coronavirus/). While most cases of SARS-CoV-2 infection are either asymptomatic or mild vis-à-vis clinical signs and symptoms, people with risk factors including obesity, diabetes mellitus, chronic lung disease, heart or renal failure, or those in immunosuppressive states show higher frequencies of developing lifeCorrespondence: [email protected] Department of Immunology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan

threatening pneumonia. However, in relatively rare cases, pneumonia can develop in younger individuals or in those without known risk factors. Factors that determine the progression of SARS-CoV-2 infection into overt pneumonia are poorly understood. For hundreds of years prior to the emergence of h