Methods
We searched the published literature for multiple combinations of different organs, and names for infectious conditions of those organs and novel CoVs. We only included articles written in the English language and published after 2002. We included both animal and human research studies. The search methodology resulted in nearly 2000 articles. During the further review, we limited the number of articles by eliminating articles that lacked direct relevance. We populated tables with disease manifestations in various organs (Table 1, Table 2, Table 3, Table 4, Table 5, Table 6, Table 7, Table 8 ).
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.