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The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject.
While COVID-19 may affect multiple organ systems, symptoms are most often located in the respiratory tract (Guan, April 2020; Stokes, June 2020; Struyf, July 2020). Approximately 80% of symptomatic patients present with mild disease: symptoms of fever, runny nose, sore throat or dry cough (Wu, Feb 2020). Chest X-rays can appear normal (Wong, March 2020; Guan, April 2020).
Moderate to severe disease is characterized by pneumonia. The definition of these categories varies across countries: in general moderate disease is characterized by dyspnea/evidence of evidence of lower respiratory disease with a SpO2 of ≥ 94% on ambient air, while severe disease is characterized by tachypnea, hypoxemia, and lung infiltrates on imaging with an SpO2 <94% on ambient air or a PaO2/FiO2 <300 mmHg (Gandhi, April 2020). Notably, some providers have reported patients with hypoxia but relatively mild or no dyspnea (Tobin, June 2020). This phenomenon has been termed “silent hypoxia” or “happy hypoxia,” and may mask the severity of the illness and delay medical care.
In moderate to severe disease, classic early findings on CT scan include multifocal, bilateral ground glass opacities with or without consolidation predominantly involving the peripheral and lower lobes (Wang, February 2020; Chung, February 2020; Bao, June 2020). A prospective analysis in Wuhan revealed bilateral lung opacities on 40 of 41 chest CTs in patients with COVID-19 (98%), and described their most typical findings as lobular and subsegmental areas of consolidation (Huang, January 2020). Of these patients, only 55% had dyspnea and would be considered moderate-to-severe. Given the CT findings of patients with COVID-19 are non-specific, and patients with moderate to severe disease can present with normal CT scans, the American College of Radiology does not recommend chest CT be used in isolation to confirm or exclude a diagnosis of COVID-19.
Patients with respiratory manifestations of SARS-CoV-2 infection may progress to hypoxemic respiratory failure. Initially after the onset of respiratory distress it seems patients have good lung compliance and low lung elastance, and low response to positive end-expiratory pressure (PEEP); some patients may then progress to acute respiratory distress syndrome, characterized by high elastance and low compliance, and a high PEEP response (Marini, April 2020). It appears endothelial damage occurs that leads to pulmonary vasoregulation disruption and the promotion of ventilation-prefusion mismatch. Rates of intensive care unit admission and mechanical ventilation vary between reports, likely due to differences in the age, threshold for admission and mechanical ventilation, and when the study was done relative to the timing of the pandemic. In one of the largest epidemiologic studies to date, in 72,314 patients with symptomatic COVID-19, 19% developed respiratory failure and 5% required mechanical ventilation; 25% of patients with severe or critical disease required mechanical ventilation (Wu, Feb 2020). In a study in New York of 5,700 patients with COVID-19 who were hospitalized, 20% had hypoxemic respiratory failure requiring mechanical ventilation. In a CDC report of 4,226 with COVID-19 in the United States between March-February 2020, the overall case fatality rate for patients with COVIUD-19 was 2.3%, but for those who required mechanical ventilation secondary to hypoxemic respiratory failure it was >50% (Bialek, March 2020).
Rates of primary bacterial coinfection of the respiratory tract in hospitalized patients with COVID-19 have varied across studies and been confounded by the lack of a systemic evaluation for bacterial superinfection, but the majority have noted low rates (Adler, June 2020; Garcia-Vidal, July 2020; Calcagno, Aug 2020). Given the clinical presentation and imaging of patients with moderate to severe COVID-19 can be similar to that of bacterial pneumonia, it can be difficult to differentiate between the two; the Society of Critical Care Medicine does recommend patients receiving mechanical ventilation for respiratory failure receive empiric antibiotics (weak recommendation). If patients receive antibacterial it is important a microbiologic evaluation via bacterial culture of respiratory samples also be performed, and a daily evaluation for de-escalation/cessation of therapy.
Here we review select key epidemiologic literature evaluating pulmonary manifestations in patients with COVID-19. Multiple studies on this topic have been published; here we have focused on the largest studies/studies with the highest level of evidence, with the most generalizable results. For details of thrombosis in COVID-19, including venous thromboembolism, please see our thrombosis section.
Three-month pulmonary function and radiological outcomes in COVID-19 survivors: a longitudinal patient cohort study (Liao, November 2020).
- 172 former COVID-19 patients at a Shenzen, China, hospital who underwent high resolution computed tomography of the thorax and pulmonary function tests at a follow-up clinic visit 3 months after hospital discharge.
- The median patient age was 47.5 (IQR 28-67) years.
- The median duration from hospital discharge to radiological and pulmonary function test was 90 (IQR 88-95) days.
- To investigate pulmonary function and radiological outcomes in a group of former COVID-19 patients.
- Of the 172 patients, median forced expiratory volume in 1 second was 104.70 (IQR 96.78-113.76), forced vital capacity was 128.49 (IQR 119.20-139.49) and FEV1/FVC% was 81.39 (IQR 77.33-85.09).
- Younger patients showed significantly lower FEV1 % predicted (pred) and FVC % pred and higher FEV1/FVC than older age groups (p=0.002, 0.003 and <0.001, respectively).
- Patients who smoked had significantly lower FEV1 % pred and FVC % pred (p=0.04 and 0.03, respectively).
- Underweight patients had lower FVC % pred and higher FEV1/FVC% than patients with higher BMI (p=0.01 and 0.001, respectively).
- FVC % pred was significantly higher in patients with hypertension or headache as initial symptoms (both p=0.03), but lower in those that had fever as an initial symptom (p= 0.04).
- Abnormal pulmonary function was found in 11 (6.40%) patients, and abnormal small airway function (FEF25-75%) in 12 (6.98%). Six (3.49%) patients had obstructive ventilation impairment and six (3.49%) had restrictive ventilatory impairment.
- Of 142 COVID-19 patients with CT scans performed, 122 (85.91%) showed residual CT abnormalities and 52 (36.62%) showed chronic and fibrotic changes. Patients with severe COVID-19 had higher CT scores than non-severe cases (2.00 versus 0.00, p<0.001).
- Small sample size in a single institution, which may limit generalizability of results.
- Due to the lack of pulmonary function tests at admission or during hospitalization, authors did not assess the changes in pulmonary function tests or CT scans.
- A longer follow-up time than 3 months may be needed to see the true pulmonary effects of COVID-19 infection.
Overall, in this observational study of 172 former COVID-19 hospital patients 3 months after discharge, 11 patients (6.4%) presented with abnormalities in pulmonary function tests, and 85.91% in chest CT scans, with fibrous stripes and ground-glass opacity being the most common patterns.
COVID-19 pneumonia: Diagnostic and prognostic role of CT based on a retrospective analysis of 214 consecutive patients from Paris, France (Guillo, August 2020).
- 214 hospitalized patients in France with a positive RT-PCR for SARS-CoV-2 and a chest CT scan within 24 hours of admission.
- To evaluate the diagnostic and prognostic performance of CT in patients referred for COVID19 suspicion, depending on symptoms and date of onset.
- Of 214 patients (mean age 59 ± 19 years), 129 had at least one positive RT-PCR result.
- Sensitivity, specificity, negative and positive predictive values were 79% (95% CI: 71–86%), 84% (74–91%), 72% (63–81%) and 88% (81–93%) for initial CT reading and 81% (74–88 %), 91% (82–96%), 76% (67–84 %) and 93% (87–97%), for expert reading.
- CT sensitivity was higher for the 123 patients having symptoms for > 5 days, with sensitivity and specificity of 93% (85–97%) and 88% (74–96%), respectively for the expert reading.
- The number of RT-PCR assays was uneven, with only 26 % of individuals with an initial negative RT-PCR having further tests. This may have negatively affected CT specificity.
Overall, in this retrospective study, the initial sensitivity and specificity of CT scans in patients with COVID-19 was 79% and 84%. This increased when patients were symptomatic for 5 days to a sensitivity and specificity of 93% and 88%.
Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020
- 1,320,488 laboratory-confirmed COVID-19 cases reported to CDC between January 22-May 30, 2020
- To describe the demographic characteristics, underlying health conditions, symptoms, and outcomes of patients with COVID-19
- Among 599,636 (45%) cases with known information, 33% of persons were Hispanic or Latino of any race, 22% were non-Hispanic black, and 1.3% were non-Hispanic American Indian or Alaska Native.
- Overall, 184,673 (14%) patients were hospitalized, 29,837 (2%) were admitted to an intensive care unit (ICU), and 71,116 (5%) died.
- Symptom status (symptomatic versus asymptomatic) was reported for 616,541 (47%) cases; among these, 22,007 (4%) were asymptomatic.
- Among 373,883 (28%) cases with data on individual symptoms, 70% noted fever, cough, or shortness of breath; 36% reported muscle aches, and 34% reported headache; 8% persons reported loss of smell or taste.
- 1% reported fever, 50.3% reported cough, 28.5% reported shortness of breath, 6.1% reported a runny nose.
- Among the 1,320,488 cases, outcomes for hospitalization, ICU admission, and death were available for 46%, 14%, and 36%, respectively.
- Overall, 184,673 (14%) patients were hospitalized, including 29,837 (2%) admitted to the ICU; 71,116 (5%) patients died.
- Death was most commonly reported among persons aged ≥80 years regardless of the presence of underlying conditions (with underlying conditions 50%; without 30%).
- Complete data was not available for the entire cohort; this may influence the results.
- Data on mechanical ventilation or other forms of respiratory support was not available.
- Asymptomatic cases were not well-captured in the study.
- The study only included patients if case investigations were performed; this may have led to reporting bias.
Overall, in this large epidemiologic study of primarily symptomatic persons with COVID-10, cough was the most common individual symptom, followed by fever; over a quarter of patients had shortness of breath.
COVID-19 CT Findings: A Systematic Review and Meta-analysis (Bao, June 2020).
- Adult patients with COVID-19 and CT scan results.
- To provide a precise estimate of detection of COVID-19 by chest CT and report on the most common imaging findings on chest CT imaging.
- 13 studies were included in the systematic review.
- The pooled positive rate of the CT imaging was 89.76%.
- When only evaluating thin-section chest CT, the pooled positivity rate was 90.35%.
- CT signs included:
- Ground glass opacities (83.31%);
- Ground glass opacities with mixed consolidation (58.42%);
- Adjacent pleura thickening (52.46%);
- Interlobular septal thickening (48.46%);
- Air bronchograms (46.46%);
- Crazy paving pattern (14.81%);
- Pleural effusion (5.88%); and
- Bronchiectasis (5.42%).
- The most anatomic distributions were bilateral lung infection (78.2%) and peripheral distribution (76.95%).
- 8% of patients had three or more lobes involved (70.81%).
- Different CT scanners may have affected the quality of the images produced.
- Most of the studies did not differentiate between mild, moderate, and severe disease.
- Publication bias was present in some subgroups of imaging findings.
Overall, in this systematic review and meta-analysis, the majority of patients with COVID-19 had positive CT imaging findings, with the most common being bilateral and peripheral ground glass opacities.
The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia (Kunhua, June 2020).
- 83 patients with COVID-19 pneumonia, including 25 severe/critical cases and 58 non-severe cases.
- Severe/critical patients met any of the following:
- Respiratory rate > 30 breaths/minute;
- Finger of oxygen saturation < 93% in a resting state;
- Arterial oxygen tension (Pao2)/inspiratory oxygen fraction (Fio2) of 300 mm Hg or less (1 mm Hg = 0.133 kPa);
- Respiratory failure occurred and mechanical ventilation required;
- Shock occurred; or
- Other organ failure requiring ICU monitoring and treatment.
- To investigate the clinical and CT features associated with severe and critical COVID-19 compared to non-severe
- The common chest CT features of both groups included GGO (81/83, 97.6%), linear opacities (54/83, 65.1%), consolidation (53/83, 63.9%), interlobular septal thickening (52/83, 62.7%), and crazy-paving pattern (30/83, 36.1%).
- The occurrence rates of consolidation, linear opacities, crazy-paving pattern, and bronchial wall thickening in severe/critical patients were significantly higher than those of non-severe
- The CT scores of the severe/critical patients were significantly higher than those of non-severe patients (P < 0.001).
- The sample size of the severe/critical group was relatively small.
- None of the patients had a lung biopsy or autopsy to reflect the histopathological changes.
Overall, in this retrospective study, patients with severe or critical disease had more abnormalities and chest CT abnormalities than those with non-severe disease.
Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China (Wu, February 2020).
- 72,314 patients with confirmed or suspected COVID-19 in China.
- To describe the epidemiologic characteristics of the COVID-19 outbreak in China.
- Of 72,314 cases, 44,672 were classified as confirmed (62%; diagnosis based on positive viral nucleic acid test result on throat swab samples), 16,186 as suspected (22%; diagnosis based on symptoms and exposures only), and 10,567 as clinically diagnosed (15%; this designation is only used in Hubei Province).
- Spectrum of disease was reported for 44,415 cases:
- 81% were mild (no or mild pneumonia);
- 14% were severe (dyspnea, respiratory frequency ≥30/min, blood oxygen saturation ≤93%, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300, and/or lung infiltrates >50% within 24 to 48 hours); and
- 5% were critical (respiratory failure, septic shock, and/or multiple organ dysfunction or failure).
- Complete data was not available for the entire cohort.
- It is not clear how many patients had proven SARS-CoV-2 infection.
- Information on respiratory support, including mechanical ventilation, was not available.
Overall, in this epidemiologic study, 14% of cases had dyspnea and required oxygenation support, while 5% developed respiratory failure.
China Abnormal pulmonary function in COVID-19 patients at time of hospital discharge (Mo, April 2020).
This study assessed the pulmonary function in 110 discharged COVID-19 patients, which included 24 cases of mild illness, 67 cases of pneumonia and 19 cases of severe pneumonia. The mean age was 49.1 years. The mean ± SD duration from onset of disease to pulmonary function test was 20±6 days in those with mild illness, 29±8 days in cases with pneumonia and 34±7 days in cases that presented severe pneumonia. Anomalies were noted in diffusing capacity of the lung for carbon monoxide (DLCO) % pred in 51 cases (47.2%), total lung capacity % pred in 27 (25.0%), forced expiratory volume in 1 s % pred in 15 (13.6%), forced vital capacity % pred in 10 (9.1%), FEV1/FVC in 5 (4.5%) and small airway function in 8 (7.3%). A significant difference in impaired diffusing capacity existed among the different groups of severity, which accounted for 30.4% in mild illness, 42.4% in pneumonia and 84.2% in severe pneumonia, respectively (p<0.05).