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Pulmonary Arterial Thrombosis Is a Novel and Underreported Feature in Severe COVID-19 with Fatal Outcome: Results from a Prospective Single-Centre Clinicopathological Case Series

2020; RELX Group (Netherlands); Linguagem: Inglês

10.2139/ssrn.3586685

1556-5068

Sigurd Lax, Kristijan Skok, Peter Zechner, Harald H. Kessler, Norbert Kaufmann, Camillo Koelblinger, Klaus Vander, Ute Bargfrieder, Michael Trauner,

Liver Disease Diagnosis and Treatment

Background: COVID-19 caused by the novel SARS-CoV-2 has rapidly become pandemic and has an estimated mortality rate of 3·4% of infected individuals. However, the pathological changes of organ systems and clinicopathological basis for severe and fatal outcomes are still poorly understood.Methods: Autopsies were performed in a single centre on 11 out of 48 deceased COVID-19 patients (age 66-91, mean 80.5 years; 8 males, 3 females) as defined by WHO and all key organs subjected to systematic macroscopic, histopathological and viral (SARS-CoV2 RT-PCR) analysis. Pathological and clinical features including co-morbidities, co-medication and laboratory values were correlated.Findings: Both lungs were affected by different stages of diffuse alveolar damage (DAD) including oedema, hyaline membranes and proliferation of pneumocytes and fibroblasts depending on the duration of the disease. Most strikingly, pulmonary artery thrombosis was found in various degrees in all 11 cases and associated with haemorrhagic infarction in eight and bronchopneumonia in six cases. In liver, pre-existing steatosis, chronic congestion, portal fibrosis, lymphocytic infiltrates and ductal proliferation were noted; Kupffer cell proliferation, lobular cholestasis and acute liver cell necrosis may be COVID-19 related, necrosis may be caused by central vein thrombosis. Further frequent findings included renal proximal tubular injury, focal pancreatitis, lymphocyte depletion of spleen and lymph nodes as well as adrenocortical hyperplasia. Post mortem, viral RNA was detectable in swabs from pharynx, bronchi and colonic mucosa but not from bile.Interpretation: COVID-19 predominantly involves the lungs by causing DAD which leads to acute respiratory insufficiency and if overcome to pulmonary fibrosis. Rapid deterioration with fatal outcome may be caused by pulmonary arterial thrombosis frequently leading to pulmonary haemorrhage, infarction and subsequent bronchopneumonia. The pattern of tissue and organ damage shows similarities to SARS1.Funding Statement: No funding source was used for this study. Declaration of Interests: Sigurd Lax declares no conflict of interest with this topic. He served as speaker and member of advisory board for Roche, Astra-Zeneca, Novartis and Biogena with respect to oncology. He is standing member of the editorial board of the WHO for the 5th edition of classification of tumours and senior editorial consultant for Virchows Archiv. Michael Trauner served as a speaker and/or consultant and/or advisory board member for Albireo, BiomX, Boehringer Ingelheim, Bristol-Myers Squibb, Falk, Genfit, Gilead, Intercept, MSD, Novartis, Phenex, Regulus and Shire, and received travel support from AbbVie, Falk, Gilead, and Intercept, as well as grants/research support from Albireo, Cymabay, Falk, Gilead, Intercept, MSD, and Takeda. He is also co-inventor of patents on the medical use of 24-norursodeoxycholic acid.The other authors have no conflicts of interest.Ethics Approval Statement: All performed procedures and investigations were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.