Fibrotic progression and radiologic correlation in matched lung samples from COVID-19 post-mortems

Abstract

Data on the pathology of COVID-19 are scarce; available studies show diffuse alveolar damage; however, there is scarce information on the chronologic evolution of COVID-19 lung lesions. The primary aim of the study is to describe the chronology of lung pathologic changes in COVID-19 by using a post-mortem transbronchial lung cryobiopsy approach. Our secondary aim is to correlate the histologic findings with computed tomography patterns. SARS-CoV-2-positive patients, who died while intubated and mechanically ventilated, were enrolled. The procedure was performed 30 min after death, and all lung lobes sampled. Histopathologic analysis was performed on thirty-nine adequate samples from eight patients: two patients (illness duration < 14 days) showed early/exudative phase diffuse alveolar damage, while the remaining 6 patients (median illness duration—32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrotic phase diffuse alveolar damage, one of which with honeycombing). Immunohistochemistry for SARS-CoV-2 nucleocapsid protein was positive predominantly in early-phase lesions. Histologic patterns and tomography categories were correlated: early/exudative phase was associated with ground-glass opacity, mid/proliferative lesions with crazy paving, while late/fibrous phase correlated with the consolidation pattern, more frequently seen in the lower/middle lobes. This study uses an innovative cryobiopsy approach for the post-mortem sampling of lung tissues from COVID-19 patients demonstrating the progression of fibrosis in time and correlation with computed tomography features. These findings may prove to be useful in the correct staging of disease, and this could have implications for treatment and patient follow-up.

Body Localization of ACE-2: On the Trail of the Keyhole of SARS-CoV-2

“…In addition, autoptic results revealed that in about 48% of cases the predominant histopathological finding were capillary congestion, microthrombi as well as moderate intra-alveolar fibrin exudation resultant in exudative disseminate alveolar damage and superimposed bronchopneumonia ( 135 ). A more widespread histological pattern of alveolar damage with greater fibrotic evolution in the lungs was observed in patients who died after a long period of mechanical ventilation ( 136 ). In few cases, an intra-alveolar deposition of neutrophilic granulocytes, probably due to superimposed bacterial infection, was also detected ( 137 ).…”

Pathophysiology and Imaging Findings of COVID-19 Infection: An Organ-system Based Review

“…Barisione, et al performed a study on transbronchial biopsy autopsy specimens in patients who succumbed to COVID-19. Their data demonstrated phases of alveolar damage secondary to SARS-CoV-2, with the final phase culminating in interstitial fibroblast proliferation with sparse collagen fiber deposition ( 19 ). These data are in concert with recent radiology data demonstrating the development of pulmonary fibrosis on chest CT. Fang, et al presented a case series of 12 patients in the recovery period of severe COVID-19 infection in which there was gradually development of increasing fibrosis ( 20 ).…”

“…he novel SARS-CoV-2 virus is responsible for the Coronavirus-19 (COVID- 19) illness, which has affected millions worldwide and continues to spread. The virus was first identified in connection with an outbreak of pneumonia in Wuhan City, Hubei province, China in December 2019 (1,2).…”

Nebulised heparin for patients on ventilation: implications for COVID-19 pneumonia

“…Pulmonary coagulopathy is once again receiving attention because pulmonary thrombosis is frequently seen in patients with COVID-19 pneumonia, 7 , 8 causing increased dead space and severe hypoxaemia. The promising findings of the CHARLI study 3 underline the importance of considering studies of nebulised heparin in patients with COVID-19 pneumonia, 9 and some studies have already been registered on ClinicalTrials.gov ( NCT04397510 , NCT04530578 ).…”