Post-mortem lung biopsies in fatal Covid-19 acute respiratory distress syndrome: a prospective cohort study of 169 patients (HISTOCOVID).

Background: Refractory acute respiratory distress syndrome (ARDS) is the leading cause of death in patients with Covid-19. Large studies of lung pathology in patients who died of Covid-19-ARDS may help to understand the mechanisms of death and to guide further research.

Methods: This prospective multicentre cohort study included 338 post-mortem, percutaneous, lung biopsies from 169 patients who died of Covid-19-ARDS between 22/04/2020 and 08/03/2021 in 26 intensive care units in France. The biopsies were done at the bedside by the intensivist immediately after death, using a 14G needle and following anatomical landmarks. A pathologist examined all biopsies, describing all elementary lesions and establishing a final histopathological diagnosis.

Results: Lung parenchyma was evaluable in 155/169 (92%) patients. Early, proliferative-phase diffuse alveolar damage (DAD) was the most common finding (39%), followed by late proliferative-phase DAD (32%) and exudative-phase DAD (18%); fibrotic-phase DAD was present in three (2%) patients. Organising pneumonia (OP) and acute fibrinous and organising pneumonia (AFOP) were evidenced in 21 (13%) and 16 (9%) patients, respectively. Unclassified interstitial lesions were seen in 33 (21%) patients. Microthrombi were uncommon (6%).

Conclusions: DAD was the most common pathological pattern, whereas collagen fibrosis and microthrombi were rare. A quarter of patients had evidence of OP or AFOP. This substantial prevalence of corticosteroid-sensitive patterns suggests that selected patients with refractory Covid-19-ARDS might benefit from higher doses or longer courses of corticosteroids.

Clinicaltrials: gov NCT04675281. Registered 19 December 2020.