COVID-19-associated acute respiratory distress syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayesha Javid, MBBS[2] Usman Ali Akbar, M.B.B.S.[3]

Overview

Acute Respiratory Distress Syndrome (ARDS) is a form of non-cardiogenic pulmonary edema attributed to the breakdown of alveolar membrane and capillaries leading to hypoxia. The treatment of ARDS has evolved over the last decade. The management of COVID-19 related ARDS are stratified according to the classification of ARDS. Among patients with COVID-19, ARDS developed in 20% after a median of eight days after onset of symptoms; mechanical ventilation was implemented in 12.3%. The mortality rate of COVID-19 related ARDS is higher in elderly patients. Given the importance of heterogeneity in the ARDS profile, appropriate intervention at an appropriate time is needed to help to prevent the deterioration of lung function. Recent advances observed from the RECOVERY trial has further strengthened the notion that the use of dexamethasone in patients on a ventilator can reduce the mortality rate of patients by one-third. The treatment of COVID-19 related ARDS is evolving with time and different treatment options are now available for the management of ARDS.

Historical Perspective

Classification

Several authors in a case report highlighted the nonuniformity of patients with COVID-19-associated ARDS and proposed the existence of two primary phenotypes:[1]

Pathophysiology

Clinical Features

  • Clinical presentations of COVID-19 range from asymptomatic (81.4%), through mildly symptomatic with or without seasonal flu-like symptoms, to severe pneumonia (13.9%).[7]
  • Patients with dyspnea can revert to an asymptomatic phase or progress to ARDS, requiring positive pressure oxygen therapy and intensive care therapy [18] in 17–19.6% of symptomatic patients.[8]

Differentiating COVID-associated ARDS from other Diseases

COVID-19 associated ARDS must be differentiated from other diseases that also cause ARDS by the following parameters:

Epidemiology and Demographics

Prevalence of ARDS in patients with COVID-19
Date of publication Country Author Total Number of patients Prevalence
January 24,2020 China Huang C et al.[12] 41 29.26 %

(16.13-45.53)

January 29,2020 China Nanshan Chen et al.[13] 99
17.17 %

(10.33-26.06)

March 13, 2020 China Chaomin Wu et al.[14] 201 41.8 %
May 14, 2020 Multiple Zhang et al.[15] 4203 18.4%


Age

  • Patients of all age groups may develop ARDS.
  • It is more commonly observed among patients aged ≥65 years old.

Gender

  • Some case studies report that men are more commonly affected by ARDS than women.
  • In a Chinese public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016).[16]

Race

  • A large study in the United States reported that that African Americans were at a higher risk of ARDS than white individuals.[17]

Risk Factors

  • In a retrospective study conducted in China, following risk factors were the main predisposing factors for the development of ARDS:[14]
    • Older age (≥65 years old)
    • High fever (≥39 °C)
    • Comorbidities (eg, hypertension, diabetes)
    • Neutrophilia
    • Lymphocytopenia (as well as lower CD3 and CD4 T-cell counts)
    • Elevated end-organ related indices (eg, AST, urea, LDH)
    • Elevated inflammation-related indices (high-sensitivity C-reactive protein and serum ferritin)
    • Elevated coagulation function–related indicators (PT and D-dimer)

Natural History, Complications and Prognosis

Natural History

The natural history of ARDS is hallmarked by three histopathological phases—exudative, proliferative, and fibrotic phase—each correlated to distinctive clinical manifestations.[18]

Exudative Phase Proliferative Phase Fibrotic Phase
  • The exudative phase typically encompasses the first 5 to 7 days of illness after exposure to one or more precipitation factors.
  • The proliferative phase generally lasts from day 7 to day 21.
  • Histopathologically, reparative processes take place in the injured alveoli, including organization of exudates, a shift to lymphocyte-predominant infiltrates, and proliferation of type II pneumocytes.
  • In this phase, patients may recover from acute respiratory distress despite the persistence of residual symptoms. Patients who do not recover during this phase develop progressive lung injury and early changes of fibrosis.
  • The fibrotic phase occurs 3 to 4 weeks following the initial pulmonary insult.
  • Histopathologically, extensive fibrosis is prominent in the alveolar interstitium and duct, with disruption of acinar architecture and emphysema-like changes.
  • The evidence for pulmonary fibrosis on biopsy is associated with increased mortality.

Complications

Common complications include:

Other complications include:

Prognosis

  • The survival rate for patients with COVID-19 with ARDS is approximately 25%.[30]
  • Factors associated with increased mortality in patients with COVID-19 pneumonia included age ≥65 years, presence of cardiovascular or cerebrovascular disease, lymphopenia, and elevation in troponin I levels.[31]
  • Despite major progress in the care of patients with ARDS, survivors are at high risk for cognitive decline, depression, post-traumatic stress disorder, and physical deconditioning.[32]


Diagnosis

Diagnostic Criteria

  • COVID-19 ARDS is diagnosed when someone with confirmed COVID-19 infection meets the Berlin 2012 ARDS diagnostic criteria of:[33]
  1. Acute hypoxemic respiratory failure.
  2. Presentation within 1 week of worsening respiratory symptoms.
  3. Bilateral airspace disease on chest x-ray, computed tomography (CT) or ultrasound that is not fully explained by effusions, lobar or lung collapse, or nodules.
  4. Cardiac failure is not the primary cause of acute hypoxemic respiratory failure.

Symptoms

Physical Examination

  • The physical exam findings of a patient with ARDS vary according to the underlying cause and typically develop within 24 to 48 hours of the precipitating illness or injury and progress over the course of 1 to 2 weeks. However, ARDS related to COVID-19 has sometimes late-onset. Common physical findings include:

Vital Signs

Skin

Lungs

Heart

Extremities

Laboratory Findings

Imaging Findings

Chest-X ray

On Chest X-ray following findings can be seen.

  • Ground-glass opacification and consolidation
  • Early findings on the chest radiograph include normal or diffuse alveolar opacities (consolidation), which are often bilateral and which obscure the pulmonary vascular markings.
  • Later, these opacities progress to more extensive consolidation that is diffuse, and they are often asymmetrical.
Bilateral alveolar consolidation with panlobar change, with typical radiological findings of ARDS. Source: Dr. Edgar Lorente

Chest CT-Scan

Multifocal ground glass, mainly in the periphery of both lungs. Source: Dr. Elshan Abdullayev

Treatment

Medical Therapy

Fluid and electrolytes management

Corticosteroids

Mechanical Ventilation

Anticoagulant or thrombolytic therapy

Prevention

Primary Prevention

  • The best way to prevent being infected by COVID-19 is to avoid being exposed to this virus by adopting the following practices for infection control:
    • Wash hands often with soap and water for at least 20 seconds.
    • Use an alcohol-based hand sanitizer containing at least 60% alcohol in case soap and water are not available.
    • Avoid touching the eyes, nose, and mouth without washing hands.
    • Avoid being in close contact with people sick with COVID-19 infection.
    • Stay home while being symptomatic to prevent spread to others.
    • Cover mouth while coughing or sneezing with a tissue paper, and then throw the tissue in the trash.
    • Clean and disinfect the objects and surfaces which are touched frequently.
  • There is currently no vaccine available to prevent COVID-19.

Secondary Prevention

References

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