Diffuse alveolar damage (DAD) resulting from coronavirus disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD

Abstract

Diffuse alveolar damage (DAD) resulting from coronavirus disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD 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.

Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage. An autopsy study with clinical correlation and review of the literature.

“…Pulmonary histopathologic changes related to ARDS are usually similar regardless of its etiology [4][5][6][7]. This observation can be extended to cases caused by SARS-CoV-2 infection [7].…”

“…Pulmonary histopathologic changes related to ARDS are usually similar regardless of its etiology [4][5][6][7]. This observation can be extended to cases caused by SARS-CoV-2 infection [7]. In 2007 Mandal et al reported abnormalities in platelet homeostasis including an increase in the number of pulmonary MKs in patients with DAD [8].…”

“…Most deaths related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are due to pulmonary damage. Autopsy studies performed on these patients usually reveal DAD in different evolutionary phases [7,. Although no speci c pulmonary pathologic ndings have been observed, thrombosis of major vessels and microcirculation are often highlighted.…”

“…Several studies have shown that platelets participate in lung damage, particularly in acute lung injury [2,3]. MKs are usually not mentioned as a characteristic histopathologic nding associated to acute pulmonary injury [4][5][6][7]. However, a few studies and textbooks point out that their number is increased in the lungs of patients with diffuse alveolar damage (DAD), burns, shock or sepsis [8][9][10][11].…”

Imaging Diagnostics and Pathology in SARS-CoV-2-Related Diseases

“…Most important histological lesions observed during autopsy of patients who died from SARS-CoV-2 infection.LungReferences Diffuse alveolar damage (histological hallmark of SARS-CoV-2 infection)[15][16][17][18][19][20][21][22][23][24] Focal vasculitis and capillaritis associated to microthrombosis as direct viral effect Thrombosis of large and medium-size pulmonary, related to SARS-COV-2-associated coagulopathy (likely secondary to an endothelial damage related to direct viral infection of the endothelial cells) or deriving from the deep veins of the lower extremities. Superimposed bronchopneumonia as result of bacterial superinfectionHeartMyocardial damage and myocarditis associated with increase in troponin levels, related to (a) direct myocardial infection by SARS-CoV-2 (b) hypoxemia due to respiratory failure and (c) inflammatory response correlated to the severe systemic inflammation status.…”