Pulmonary Manifestations

Last reviewed February 22, 2022

On this page:

• Overview
• Guidelines
• Key Literature
• Resources
• Multimedia

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.

Overview

While COVID-19 may affect multiple organ systems, symptoms are most often located in the respiratory tract. Lung damage is severe in advanced COVID-19 and is the leading cause of mortality in a majority of patients (Guan, April 2020; Stokes, June 2020; Struyf, July 2020). COVID-19 affects all aspects of the respiratory system, including the conducting airways, the respiratory airways and alveoli, the pulmonary vascular endothelium, pulmonary blood flow and the neuromuscular breathing apparatus (Brosnahan, September 2020).

Pulmonary symptoms can be divided into four stages, including:

1. Early stage, characterized by edema, epithelial damage, and inflammation of capillaries and endothelium (day 0-1);
2. The exudative diffuse alveolar damage stage (days 1-7);
3. The organizing pneumonia stage (1 week to several weeks); and
4. The fibrotic stage (weeks to months) (Bösmüller, February 2021).

In a case series of patients who recovered from severe COVID-19, nearly a quarter of them had persistent radiographic abnormalities characteristic of fibrosis a year after hospitalization (Wu, July 2021). It is unknown if COVID-19 will result in progressive and irreversible lung fibrosis (Michalsky, September 2021).

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 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 mm Hg (Gandhi, April 2020). Notably, some clinicians 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 that CT findings of patients with COVID-19 are nonspecific, 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, low lung elastance and low response to positive end-expiratory pressure; some patients may then progress to acute respiratory distress syndrome (ARDS), characterized by high elastance and low compliance, and a high positive end-expiratory pressure 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; 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 patients with COVID-19 in the United States between March-February 2020, the overall case fatality rate for patients with COVID-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 co-infection of the respiratory tract in hospitalized patients with COVID-19 have varied across studies and have 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, August 2020). Given that 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, low quality evidence). If patients receive an antibacterial, it is important to perform a microbiologic evaluation via bacterial culture of respiratory samples, as well as a daily evaluation for de-escalation/cessation of therapy. In terms of fungal coinfections, several recent reports describe COVID-19–associated pulmonary aspergillosis. COVID-19–associated mucormycosis is less common than other COVID-19–associated fungal infections, but emerging reports from India highlight the importance of considering this infection in specific settings. Several risk factors have been implicated in the pathogenesis of COVID-19–associated mucormycosis, most importantly, uncontrolled diabetes and overzealous use of steroids (Sen, July 2021). Further information is available on our Co-Infection and Antimicrobial Stewardship page.

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 and studies with the highest level of evidence, with the most generalizable results. For details on thrombosis in COVID-19, including venous thromboembolism, please see our thrombosis page.

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Guidelines

Guidelines for managing pulmonary manifestations and complications of COVID-19 have been published by IDSA and the American Thoracic Society.

 

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Key Literature

Three-month pulmonary function and radiological outcomes in COVID-19 survivors: a longitudinal patient cohort study (Liao, November 2020).

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. 

Patient population: 

• 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. 

 

Primary endpoint: 

• To investigate pulmonary function and radiological outcomes in a group of former COVID-19 patients. 

 

Key findings: 

• 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). 

 

Limitations: 

• 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. 

 

COVID-19 pneumonia: Diagnostic and prognostic role of CT based on a retrospective analysis of 214 consecutive patients from Paris, France (Guillo, August 2020).

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%.

Study population:

• 214 hospitalized patients in France with a positive RT-PCR for SARS-CoV-2 and a chest CT scan within 24 hours of admission.

Primary endpoint:

• To evaluate the diagnostic and prognostic performance of CT in patients referred for COVID19 suspicion, depending on symptoms and date of onset.

Key findings:

• 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.

Limitations:

• 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. 

Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020

(Stokes, June 2020).

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.

Study population:

• 1,320,488 laboratory-confirmed COVID-19 cases reported to CDC between January 22-May 30, 2020

Primary endpoint:

• To describe the demographic characteristics, underlying health conditions, symptoms, and outcomes of patients with COVID-19

Key findings:

• 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%).

Limitations:

• 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. 

COVID-19 CT Findings: A Systematic Review and Meta-analysis (Bao, June 2020).

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.

Study population:

• Adult patients with COVID-19 and CT scan results.

Primary endpoint:

• 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.

Key findings:

• 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%).

Limitations:

• 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.

 

The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia (Kunhua, June 2020).

Overall, in this retrospective study, patients with severe or critical disease had more abnormalities and chest CT abnormalities than those with non-severe disease.

Study population:

• 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.

Primary endpoint:

• To investigate the clinical and CT features associated with severe and critical COVID-19 compared to non-severe

Key findings:

• 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).

Limitations:

• 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.

Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China (Wu, February 2020).

Overall, in this epidemiologic study, 14% of cases had dyspnea and required oxygenation support, while 5% developed respiratory failure.

Study population:

• 72,314 patients with confirmed or suspected COVID-19 in China.

Primary endpoint:

• To describe the epidemiologic characteristics of the COVID-19 outbreak in China.

Key findings:

• 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).

Limitations:

• 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.

Other Literature

China Abnormal pulmonary function in COVID-19 patients at time of hospital discharge (Mo, June 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). 

 

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