Table 1 Pulmonary manifestations of SARS-CoV, MERS-CoV and COVID-19.
SARS (only studies with large study population included)
Study Lee et al (2003)N = 138, confirmed casesRetrospective study Lang et al (2003)N = 3, confirmed casesClinicopathologic study Liu et al (2004)N = 53, confirmed casesRetrospective study Peiris et al (2003)N = 75, confirmed casesProspective study
Clinical features • Preexisting chronic pulmonary disease (2.1%)
• Fever (100%)
• Cough (57.3%)
• Sputum (29%)
• Sore throat (23.2%) Coryza (22.5%)
• Inspiratory crackles Fever (3/3)Dyspnea (3/3)Mildly productive cough (1/3)Death within 9-15 days of illness • Fever (98%)
• Cough (68% on admission to isolation, 74% after hospitalization, 26% productive)
4.5 ± 1.9 days after fever onset
• Dyspnea (40% on admission to isolation)
• O2 saturation <90% on room air (51% on hospitalization, 11% on admission to isolation) • Fever (100%), recurred in 85% at mean 8.9 days
• Cough (29%)
• Spontaneous pneumomediastinum (12%) during follow-up
• Sore throat (11%)
• Shortness of breath (4%)
• O2 saturation < 90% on room air (44mean 9.1 days after symptom onset)
Key findings on investigations CXR• Consolidation (78.3% at fever onset, eventually 100%)
• 54.6% unilateral, focal
• 45.4% multifocal or bilateral
• Peripheral zone predominant
CT• Progression of chest CT infiltrates 7-10 days after admission, resolution with treatment
• lll-defined peripheral GGO, usually subpleural • Leukopenia (2/3)
• Lymphopenia (2/3)
• CXR: Bilateral interstitial infiltrates • Abnormal CXR (59% on admission, 98% anytime)
• 63% patients – first unifocal infiltrates at 4.5 ± 2.1 days
• 37% patients - started as multifocal infiltrates at 5.8 ± 1.3 days after fever onset Initial CXR abnormal: 71%• One lung zone: 49%
• Multizonal: 21%
Chest CT abnormal (55% of 33)• One lobe: 55%
• Multilobar: 46%
• Focal ground-glass opacification: 24%
• Consolidation: 36%
• Both: 39%
Radiologic worsening in 80% at mean 7.4 days
Histopathology • Gross: Lung consolidation
• Early phase: Pulmonary edema with hyaline membrane formation
• Organizing phase: Cellular fibromyxoid organizing exudates in alveoli
• Scanty lymphocytic interstitial infiltrate
• Vacuolated and multinucleated pneumocytes
• Viral inclusions not detected. • Gross: Diffuse hemorrhage on lung surface
• Serous, fibrinous and hemorrhagic inflammation in alveoli with desquamation of pneumocytes and hyaline-membrane formation
• Capillary engorgement and capillary microthrombosis, thromboemboli in bronchial arterioles
• Hemorrhagic necrosis lymphocyte depletion in lymph nodes and spleen
• Viral RNA detected in type II alveolar cells, interstitial cells and bronchiolar epithelial cells N/A N/A
Key study findings and message • 23.2% ICU admission, at day 6 (mean)
• 13.8% mechanical ventilation rate
• 3.6% crude mortality rate
• ICU patients more likely to be of older age (P = 0.009) Severe immunological damage to lung tissue causes clinical features • Fever most common and earliest symptom
• 23% mechanical ventilation rate • 83.33% of patients with GGO developed ARDS
• 20% mechanical ventilation
• 17% ICU admission
• Recurrence of fever (univariate) and age (multivariate) risk factors for ARDS and ICU admission
MERS
Study Assiri et al (2013)N = 47, confirmed casesRetrospective study Arabi et al (2014)N = 12, (11 confirmed cases, 1 probable)Case series Al-Abdley et al (2019)N = 33, confirmed casesRetrospective study Almekhlafi et al (2016)N = 31, confirmed casesRetrospective study
Clinical features • Preexisting chronic lung disease (26%)
• Smokers (23%)
• Fever (98%)
• Cough (83%)
• Dry (47%)
• Productive (36%)
• Dyspnea (72%)
• Sore throat (21%)
• Rhinorrhea (4%) • Preexisting chronic lung disease (8%)
• Dyspnea (92%)
• Cough (83%)
• Fever (67%)
• Wheezing (17%)
• Productive cough (17%)
• Rhinorrhea (8%)
• Hemoptysis (8%)
• Sore throat (8%) • Preexisting chronic lung disease (12%)
• Fever (75.7%)
• Cough (72%)
• Dyspnea (59%)
• Sore throat (12%)
Rhinorrhea (9%) • Cough (100%)
• Tachypnea (100%)
• Fever (87.1%)
• Sore throat (25.8%)
• Crackles (93.5 %)
Rhonchi (32.3 %)
Key findings on investigations CXR abnormality (100%) – ARDS pattern CXR, CT: lobular to bilateral extensive ARDS pattern N/A CXR abnormality (96.4%)
Key study findings and message • 89% ICU admission
• 72% mechanical ventilation
• 60% case fatality rate 100% invasive mechanical ventilation, mean duration 100 days • Dyspnea before admission was associated with a more severe outcome (P < 0.001)
Prolonged MERS-CoV detection in URT in diabetics (P = 0.049) • 87.1 % invasive mechanical ventilation (87.1%)
• 74.2% overall ICU mortality rate
• Mortality in ICU associated with older age, severe disease and organ failure.
COVID-19
Study Huang et al (2020)N = 41, confirmed casesRetrospective study Wang et al (2020)N = 138, confirmed casesRetrospective study Guan et al (2020)N = 1099, confirmed casesRetrospective study Zhang et al (2020)N = 1, confirmed casesClinicopathologic study
Clinical features • Smoker (7%)
• Preexisting COPD (2%)
• Fever 98%
• Dry cough (76%)
• Dyspnea (55%), mean 8 days after onset
• Sputum (28%)
• Hemoptysis (5%)
• ARDS (29%), mean 9 days after onset
• ↑RR >24/min (29%) • Preexisting COPD (2.9%)
• Fever 98.6%
• Dry cough (59.4)
• Sputum (26.8%)
• Dyspnea, mean 5 days after onset
• ARDS (19.6%), mean 8 days after onset • Preexisting chronic pulmonary disease (1.1%)
• Fever (43.8% on admission, 88.7% during hospitalization)
• Cough (67.8%)
• Sputum (33.7%)
• Sore throat (13.9%)
• Nasal congestion (4.8%)
• Hemoptysis (0.9%)
• ARDS (3.4%)
• 1.4% case fatality rate
• 4 days median incubation period • Fever
• Cough
• ARDS requiring mechanical ventilation within 1 week
Key findings on investigations Abnormal chest CT (100%); (98% bilateral) • ↓PaO2
• ↓PaO2:FiO2 • Abnormal CXR (59.1%)
• Abnormal Chest CT (86.2%)
• Ground glass opacity most common (56.4%)
• No lung imaging findings in 17.9% patients with nonsevere disease and in 2.9% with severe disease CT: Patchy bilateral ground glass opacities
Histopathology N/A N/A N/A • Diffuse alveolar damage with organizing changes of fibrous plugs, with interstitial fibrosis and chronic inflammatory infiltrates
• Denuded alveolar lining with pneumocyte type II hyperplasia
• Virus detected on alveolar epithelial cells including desquamated cells, not in blood vessels
Key study findings and message • ICU patients had more areas of consolidation
• 10% mechanical ventilation rate, mean 10.5 days after onset
• 5% ECMO rate • High-flow O2 therapy in 11.1% ICU patients, noninvasive ventilation in 41.7%, and invasive ventilation in 47.2%
• Older patients (P < 0.001), patients with more comorbidities, dyspnea and anorexia more likely to require ICU care
• Mortality: 4.3% • Mechanical ventilation needed (6.1%)
• Radiographic abnormalities often absent Histopathologic findings consistent with diffuse alveolar damage
ARDS, acute respiratory distress syndrome; CXR, chest x-ray; ECMO, extracorporeal membrane oxygenation; GGO, ground glass opacities; ICU, intensive care unit; MERS-CoV, middle east respiratory syndrome coronavirus; RR, respiratory rate; SARS-COV, severe acute respiratory syndrome coronavirus; URT, upper respiratory tract.