PULMONARY MANIFESTATIONS

SARS-CoV
Patients infected with SARS-CoV initially had features of atypical pneumonia. Cough was a common presenting symptom in up to 74% of patients8, 9, 10 (Table 1). Other symptoms suggestive of an upper respiratory tract infection (e.g., rhinitis) were less frequent.11 Approximately 50% of patients developed hypoxia during hospitalization, and up to 26% progressed to acute respiratory distress syndrome (ARDS) requiring mechanical ventilation.8 , 12 The elderly and patients with multiple comorbidities had particularly high (more than 15.7%) mortality.12 , 13 Unilateral, focal, peripheral areas of consolidations on imaging were identified in upwards of 78% of patients.10 Histopathology revealed diffuse serous, fibrinous and hemorrhagic inflammation. SARS-CoV RNA has been detected in type II alveolar cells, interstitial cells and bronchial epithelial cells, suggesting infection of both proximal and distal epithelium of the lung.13 Most patients received antibacterial antibiotics, with or without the use of ribavirin and corticosteroids.9, 10, 11
Angiotensin-converting enzyme 2 (ACE2) serves as a functional receptor to SARS-CoV.13 , 14 SARS-CoV also disrupts the urokinase pathway, which controls fibrin levels through extracellular remodeling, and is associated with pulmonary hemorrhage and fibrosis.15 SARS-CoV also triggers the production of high levels of proinflammatory cytokines contributing to excessive inflammation in the lungs. Hence, anticytokine and chemokine immunotherapy may be effective for minimizing collateral damage.12

MERS-CoV
Common presenting symptoms of MERS include dyspnea in up to 92% and cough in 83% of patients 16 , 17 (Table 1). In a study including 47 patients, all patients presented with an abnormal chest radiograph, 89% needed ICU admissions, and 72% required mechanical ventilation. The case fatality rate was 60%, and the rate increased with age.16 Most patients received antibiotics, and a small minority received corticosteroids, ribavirin and intravenous immunoglobulin.17 In a small case series, antiviral therapy was not beneficial.18 MERS-CoV also induces overexpression of inflammatory cytokines and/or chemokines.19

COVID-19
A dry cough is a common symptom in COVID-19 infection, present in up to 68% of patients 20 (Table 1). Sore throat and sputum production are uncommon (5% or less).21 The presence of dyspnea is predictive of ICU admission.21 In early descriptions of hospitalized patients in China, all patients had an abnormal chest computed tomography.20 , 22 Ground glass opacities are common (56%), followed by consolidation and interstitial abnormalities.21 In a large Chinese study, the course was complicated by ARDS in 3.4% patients, 6.1% required mechanical ventilation, and the case fatality rate was 1.4-2.1%.21 Other studies noted a higher incidence of ARDS among hospitalized patients (29%), and higher mortality (15%).20 , 22 Respiratory failure tends to have a delayed onset, occurring approximately 1 week after the onset of symptoms. Patients with critical illness were on average older (median age 66 versus [vs.] 51 noncritically patients) and had more comorbidities.20 Patients who received invasive mechanical ventilatory support were more likely to be male and obese.23 Histopathology of the lung shows diffuse alveolar damage, denuded alveolar lining cells and interstitial fibrosis.24 There is also evidence of a higher incidence of thromboembolism in COVID-19 patients and an association between elevated D-dimer levels and mortality.25 Additionally, preliminary evidence suggests that heparin use may result in lower 28-day mortality rates when compared to in COVID-19 patients not receiving this therapy.26
Currently, it is speculated that respiratory compromise due to COVID-19 is driven by cytokine-mediated injury of the lung and that interventions to reduce the activity of specific inflammatory mediators may improve outcomes.27 , 28 COVID-19 also uses ACE2 receptor to enter into cells so therapies targeting this receptor may serve as a potential treatment option.29, 30, 31, 32 There is no standard of care for the prevention or treatment of respiratory compromise in COVID-19 yet. Medications including glucocorticoids, IL-6 antagonists, Janus kinase inhibitors, antivirals and chloroquine and/or hydroxychloroquine are currently being studied as possible therapeutic options.33