Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan, China

Abstract

Aims: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), infection has been deemed as a global pandemic by the World Health Organisation. While diffuse alveolar damage (DAD) is recognised to be the primary manifestation of COVID-19 pneumonia, there has been little emphasis on the progression to the fibrosing phase of DAD. This topic is of great interest, due to growing concerns regarding the potential long-term complications in prolonged survivors.

Methods and results: Here we report a detailed histopathological study of 30 autopsy cases with COVID-19 virus infection, based on minimally invasive autopsies performed between February and March, 2020. The mean age was 69 years, with 20 (67%) males and 10 (33%) females and frequent (70.0%) underlying comorbidities. The duration of illness ranged from 16 to 82 (median = 42) days. Histologically, the most common manifestation was diffuse alveolar damage (DAD) in 28 (93.3%) cases which showed predominantly acute (32%), organising (25%) and/or fibrosing (43%) patterns. Patients with fibrosing DAD were one decade younger (P = 0.034) and they had a longer duration of illness (P = 0.033), hospitalisation (P = 0.037) and mechanical ventilation (P = 0.014) compared to those with acute DAD. Patients with organising DAD had a longer duration of illness (P = 0.032) and hospitalisation (P = 0.023) compared to those with acute DAD.

Conclusions: COVID-19 pneumonia patients who develop DAD can progress to the fibrosing pattern. While we observed fibrosing DAD in fatal cases, whether or not surviving patients are at risk for developing pulmonary fibrosis and the frequency of this complication will require further clinical and radiological follow-up studies.

Keywords: COVID-19 pneumonia; SARS-CoV-2; diffuse alveolar damage; fibrosis; lung pathology.

Figure 1.

Acute and organising diffuse alveolar damage (DAD) patterns in coronavirus disease 2019 (COVID-19) patients. A, Acute phase of DAD, with hyaline membranes; B, acute DAD hyaline membranes accompanied by interstitial neutrophil infiltrates; C, organising DAD with polypoid plugs of loose connective tissue within distal alveolar spaces. The myxoid appearance of the loose connective tissue contrasts with the dense eosinophilic appearance of the collagen in perivascular interstitial fibrous connective tissue (top right); D, Masson trichrome stain shows mainly pale blue staining of the myxoid connective tissue of organising DAD; E, loose myxoid connective tissue of organising DAD situated on alveolar ducts surrounds empty air space forming small cysts; F, Masson trichrome stains show mainly pale blue staining of the myxoid connective tissue of the alveolar duct fibrosis in organising DAD.

Figure 2.

Fibrosing diffuse alveolar damage (DAD) patterns in coronavirus disease 2019 (COVID-19) patients. A, Abundant fibrosis with mainly dense eosinophilic collagen expands the interstitium. Mild interstitial chronic inflammation is also present; B, the dense collagen is highlighted by the Masson trichrome stain. In this image the rounded fibrotic area is centred on an alveolar duct; C, dense eosinophilic fibrosis surrounds three alveolar ducts and forms small cystic spaces; D, the abundant dense collagen in the alveolar duct fibrosis is highlighted by the dark blue staining with the Masson trichrome stain; E, these alveolar walls are markedly thickened by dense fibrosis and interstitial chronic inflammation. While the alveolar architecture is preserved, small cysts are present retaining some features of alveolar duct fibrosis. F, Masson trichrome stain shows dark blue staining of the dense collagen, causing thickening of the alveolar walls.