Dysregulated Innate Immune and Inflammatory Responses in SARS-CoV-2 Infection and COVID-19 Severity

Abstract

Pathogenic coronaviruses (CoVs) have caused human respiratory infections and severe disease outbreaks in the past two decades. Recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans shows high transmissibility causing a wide range of clinical outcomes, named coronavirus disease-2019 (COVID-19), which emerged into an ongoing pandemic. Innate immune sensing of SARS-CoV-2 infection is critical for mounting antiviral and inflammatory responses to restrict the viral spread and initiate lung tissue repair processes. However, excessive cytokine and chemokine levels and dysregulated inflammatory immune cell function in the lungs are associated with respiratory failure and severe COVID-19. Thus, there is a tremendous need for understanding SARS-CoV-2-host interactions determining the aberrant inflammatory responses and loss of respiratory function. In this article, we discuss host innate immune responses determining dysregulated inflammation and immunopathology during SARS-CoV-2 infection. We also provide the perspective for the inflammatory cell death contribution for this immunopathology. Virus-induced acute host responses are complex, and elucidating this complex mechanism facilitates safe therapeutic interventions to alleviate inflammation-mediated immunopathology during pathogenic virus infections.

Real-World Effectiveness of Nirmatrelvir/Ritonavir and Dexamethasone Among Hospitalized Patients with COVID-19: A Prospective Cohort Study

“…From the clinical course of the asymptomatic incubation period, disease onset with respiratory symptoms, disease progression and severe disease phase, the patients experienced SARS-CoV-2 infection, immune responses, dysregulated inflammation and inflammation-mediated immunopathology. 31 , 36 Anti-viral therapy was inadequate to cure the COVID-19 deterioration process, especially with immunopathology, and should be combined with anti-inflammatory therapy. Anti-viral and anti-inflammatory treatments were proposed to combine to fight against COVID-19.…”