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Histopathology of COVID-19 Is Typical of Acute Respiratory Distress Syndrome

Key findings

  • This systematic review examined case series and case reports that examined lung histopathology in patients with COVID-19 (n=171), H1N1 influenza (n=287) or severe acute respiratory syndrome (SARS, n=64)
  • The predominant histological pattern among COVID-19 patients was acute-phase diffuse alveolar damage (DAD, 88%)
  • That figure was similar to the rates of acute-phase DAD observed in patients with H1N1 influenza (90%) or SARS (98%)
  • There was evidence of transition to the organizing phase of DAD in 52% of COVID-19 patients
  • Pulmonary microthrombi were reported in 57% of COVID-19 patients, nearly identical to the rate in SARS (58%)

The massive burden of respiratory failure associated with COVID-19 has led to an urgent inquiry into its pulmonary pathology. Some authors have suggested the disease is characterized by novel acute lung injury patterns and propose new phenotypes for COVID-19–related acute respiratory distress syndrome (ARDS).

By conducting a systemic review, Massachusetts General Hospital researchers have determined that COVID-19 falls along the spectrum of known ARDS histopathology, primarily manifesting as acute-phase diffuse alveolar damage. Lida Hariri, MD, PhD, pulmonary pathologist in the Department of Pathology; Mari Mino-Kenudson, MD, director of Pulmonary Pathology; James Stone, MD, PhD, director of Autopsy and Cardiovascular Pathology; Crystal M. North, MD, MPH, physician in the Division of Pulmonary and Critical Care; and colleagues report their findings in Chest.

Study Methods

The researchers searched MEDLINE and PubMed for pathology, autopsy and biopsy studies of COVID-19 published up to June 24, 2020, including foreign-language articles. For context, they did the same for studies of two other pandemic viral illnesses: H1N1 influenza in 2009 and severe acute respiratory syndrome (SARS) in 2003.

They identified:

  • COVID-19—26 case series and case reports representing 171 patients from nine countries. 82% had full or lung-only autopsies, and 18% had postmortem biopsies
  • H1N1—20 articles representing 287 patients from 12 countries. 81% had full or lung-only autopsies, and 19% had pre- or postmortem biopsies
  • SARS—Eight articles representing 64 patients from four countries. 89% had full or lung-only autopsies, 9% had para-mortem biopsies, and one patient (2%) underwent pre-mortem surgical lung biopsy

Key Histologic Features

Diffuse alveolar damage (DAD) lies on the severe end of the spectrum of acute lung injury and is the traditional histopathologic correlate of ARDS. Acute-phase DAD was the predominant pulmonary pathology in:

  • 88% of COVID-19 cases
  • 90% of H1N1 cases
  • 98% of SARS cases

"Pure" acute fibrinous and organizing pneumonia (AFOP) is characterized by "fibrin balls" within the alveolar spaces and no hyaline membranes (the latter warrant a diagnosis of DAD). Pure AFOP was a rare finding:

  • 4% of COVID-19 cases
  • 0.3% of H1N1 cases
  • No SARS case

Organizing fibrosis was usually described as being either focal or in the setting of mixed acute and subacute (organizing) phases of DAD. It was detected in:

  • 52% of COVID-19 cases
  • 40% of H1N1 cases
  • 47% of SARS cases

Microthrombi were described in:

  • 57% of COVID-19 cases
  • 24% of H1N1 cases
  • 58% of SARS cases

Pulmonary thrombosis (medium or large vessels) was evident in:

  • 15% of COVID-19 cases
  • 6% of H1N1 cases
  • 28% of SARS cases

Continued Scrutiny Needed

Histopathologic details are still lacking from COVID-19 patients who:

  • Recover from severe acute lung injury
  • Have milder respiratory disease and radiologic abnormalities and do not require intubation
  • Have radiologic abnormalities and never develop symptoms

There may be a spectrum of acute lung injury in COVID-19 patients, and its extent remains to be determined.

of COVID-19 patients had acute-phase diffuse alveolar damage as the predominant pulmonary pathology

of COVID-19 patients showed transition to the subacute organizing phase of diffuse alveolar damage

of COVID-19 patients had microthrombi

of COVID-19 patients had pulmonary thrombosis

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