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Published on: December 19, 2020
Diffuse alveolar damage (DAD) resulting from coronavirus disease 2019 Infection is Morphologically Indistinguishable
Kristine E Konopka1, Teresa Nguyen1, Jeffrey M Jentzen1
1Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Insights
Diffuse alveolar damage (DAD) is the main lung finding in fatal COVID-19 cases, regardless of medical intervention. COVID-19 DAD shows no unique features differentiating it from DAD caused by other conditions.
Area of Science:
- Pulmonary Pathology
- Infectious Disease Histology
Background:
- Diffuse alveolar damage (DAD) is common in fatal COVID-19 cases.
- Atypical vascular findings have been reported alongside DAD in COVID-19.
- The impact of medical interventions on lung histology in COVID-19 requires further investigation.
Purpose of the Study:
- To assess lung autopsy findings in hospitalized COVID-19 patients and community deaths.
- To compare histological features between COVID-19 patients and controls.
- To determine if COVID-19-related DAD has unique pathological characteristics.
Main Methods:
- Autopsy lung sections from COVID-19 inpatients, community deaths, and controls were reviewed by pathologists.
- Pathologists assessed for DAD and other histological features.
- Cohorts were compared to evaluate the impact of medical intervention and identify unique features.
Main Results:
- DAD was present in most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients.
- SARS-CoV-2-positive patients showed more focal perivascular inflammation/endothelialitis than controls.
- No significant differences were found in hyaline membranes, fibrin thrombi, or airspace organization; fibrinoid necrosis, hemorrhage, and capillaritis were absent.
Conclusions:
- DAD is the primary histological finding in fatal COVID-19, irrespective of hospitalization or mechanical ventilation.
- COVID-19-related DAD lacks distinctive morphological features to differentiate it from DAD of other etiologies.
Aims:
Diffuse alveolar damage (DAD) is a ubiquitous finding in inpatient coronavirus disease 2019 (COVID-19)-related deaths, but recent reports have also described additional atypical findings, including vascular changes. An aim of this study was to assess lung autopsy findings in COVID-19 inpatients, and in untreated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individuals who died in the community, in order to understand the relative impact of medical intervention on lung histology. Additionally, we aimed to investigate whether COVID-19 represents a unique histological variant of DAD by comparing the pathological findings with those of uninfected control patients.
Methods And Results:
Lung sections from autopsy cases were reviewed by three pulmonary pathologists, including two who were blinded to patient cohort. The cohorts included four COVID-19 inpatients, four cases with postmortem SARS-CoV-2 diagnoses who died in the community, and eight SARS-CoV-2-negative control cases. DAD was present in all but one SARS-CoV-2-positive patient, who was asymptomatic and died in the community. Although SARS-CoV-2-positive patients were noted to have more focal perivascular inflammation/endothelialitis than control patients, there were no significant differences in the presence of hyaline membranes, fibrin thrombi, airspace organisation, and 'acute fibrinous and organising pneumonia'-like intra-alveolar fibrin deposition between the cohorts. Fibrinoid vessel wall necrosis, haemorrhage and capillaritis were not features of COVID-19-related DAD.
Conclusions:
DAD is the primary histological manifestation of severe lung disease in COVID-19 patients who die both in hospital and in the community, suggesting no contribution of hyperoxaemic mechanical ventilation to the histological changes. There are no distinctive morphological features with which to confidently differentiate COVID-19-related DAD from DAD due to other causes.
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