The complexity of respiratory disease associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection: From immunopathogenesis to respiratory therapy

Abstract

Summary Covid‐19, a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, may present with polymorphic symptomatology and subclinical, neurological, gastrointestinal, dermatological, renal and severe acute respiratory manifestations. The diffuse alveolar damage caused by the disease presents with fibrin deposition, oedema, lymphocytic inflammatory infiltrate, destruction of epithelial cells, hyaline membrane formation and occasional angiogenesis formation of microthrombi. A common radiological finding is bilateral ground glass opacity, present even in mild cases. Severe cases occur mainly among the elderly and individuals with underlying comorbidities. Here, we provide an overview of the pathophysiology of the disease associated with SARS‐CoV‐2 infection, interaction of the virus with the immune system, and subsequent dysfunctional immune response, essential for progression of Covid‐19. We also discuss the role of the nervous system as a possible aggravating agent of the respiratory condition and propose a protocol for airway management based on the pathophysiological and immunological characteristics of the disease. Finally, we highlight the implications of such approaches for future therapeutic intervention.

Muscle dysfunction in the long coronavirus disease 2019 syndrome: Pathogenesis and clinical approach

“… 39 , 40 This is because the local immune response in the lungs results in diffuse alveolar damage and consequent accumulation of inflammatory exudate, fibrin deposition, hyaline membrane formation, alveolar epithelial desquamation, granulation tissue formation, collagen deposition, and decreased alveolar‐capillary permeability, compromising gas exchange. 41 , 42 , 43 , 44 Hypoxaemia is characterised by a deficit of oxygen in the blood, thereby impairing the oxygen supply to the muscle tissue (hypoxia), compromising biological functions. 45 In vivo studies have demonstrated that hypoxia inhibits muscle protein synthesis and increases degradation, with protein synthesis inhibition being the main mechanism associated with muscle mass reduction.…”

“…The literature shows that patients with COVID‐19 can develop acute respiratory distress syndrome, characterised by severe hypoxaemia and the need for oxygen therapy and ventilatory support 39,40 . This is because the local immune response in the lungs results in diffuse alveolar damage and consequent accumulation of inflammatory exudate, fibrin deposition, hyaline membrane formation, alveolar epithelial desquamation, granulation tissue formation, collagen deposition, and decreased alveolar‐capillary permeability, compromising gas exchange 41–44 . Hypoxaemia is characterised by a deficit of oxygen in the blood, thereby impairing the oxygen supply to the muscle tissue (hypoxia), compromising biological functions 45 .…”

Classical and alternative receptors for SARS‐CoV‐2 therapeutic strategy

“…ACE2 serves as a primary receptor for the SARS‐CoV‐2 spike protein (S protein) to bind and enter human cells 15 ,. 16 The receptor‐binding domain of the virus S protein binds to ACE2 causes SARS‐CoV‐2 to undergo endocytosis and exposes it to endosomal proteases leading to viral infection in the host 17–19 . Zhou et al 20 .…”

“…The S2 subunit of the viral S protein consists of two heptad repeat (HR) regions (HR1 and HR2) and a fusion peptide region 18 ,. 19 Within the endosome, the S1 subunit is cleaved, exposing the fusion peptide, thus allowing the viral fusion to the cellular membrane as the S2 region folds to pull together the HR1 and HR2 regions 18,19 . Then, proceed to membrane fusion and viral entry into the host 25 ,.…”

Chest Computed Tomography Is an Efficient Method for Initial Diagnosis of COVID-19: An Observational Study

“…Coronavirus disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by a flu-like syndrome, with the most common initial symptoms being fever, cough, sore throat, fatigue, headache, anosmia, myalgias, and diarrhea ( 1 – 6 ). Although many individuals develop a mild form of the infection and have a good prognosis, COVID-19 can progress to more severe forms with the development of pneumonia, pulmonary oedema, acute respiratory distress syndrome, multiple organ and system dysfunction, and death ( 7 – 9 ). Severe acute respiratory syndrome (SARS) is an important complication in patients with severe disease, and it sets in as soon as individuals progress to dyspnoea and hypoxemia ( 6 ).…”