Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study

Abstract

Background COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.Methods We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.Findings All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.Interpretation The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.

Neutrophils and COVID-19: Nots, NETs, and knots

“…Strikingly, however, some autopsy series reported no cases with intra-alveolar neutrophils (e.g., 0/80; Edler et al, 2020), even as others reported intra-alveolar neutrophils in 81.5% of their cases (31/38, excluding five cases with "abscesses"; Carsana, 2020). The latter finding is comparable to what Veras et al saw (60%) in their series (Veras et al, 2020 Preprint).…”

“…Aside from the three cases noted by Barnes et al (2020), I found English-language reports of open autopsies of 277 people who succumbed to COVID-19 in Italy (Carsana, 2020), Germany (Edler et al, 2020), Switzerland, and the United States (Magro et al, 2020; five additional references will be provided on request). The following tabulation excludes cases where the terms "sepsis," "purulence," or "abscess" were mentioned.…”

Spinal Epidural Abscess in COVID-19 patients

“…COVID-19 primarily is a respiratory tract infection with signi cant systemic impaction on cardiovascular, neurologic, gastrointestinal, hematopoietic, hemostatic, and immune systems [17][18][19]. It is now widely accepted that a sort of disseminated intravascular coagulation (DIC) may develop with platelet consumption and hemorrhagic risk [19][20][21]. Recent studies show that the SARS-COV-2 provokes a diffuse damage to the vascular endothelium [20,21].…”

“…It is now widely accepted that a sort of disseminated intravascular coagulation (DIC) may develop with platelet consumption and hemorrhagic risk [19][20][21]. Recent studies show that the SARS-COV-2 provokes a diffuse damage to the vascular endothelium [20,21]. In a large autoptic series [21], all cases presented more or less degree of endothelial damage and arteriolar thrombosis was evident in 87% of cases.…”

Transcriptional Profiling of Leukocytes in Critically Ill COVID19 Patients: Implications for Interferon Response and Coagulation

“…One of the key clinical features of COVID19 is upregulation of the pro-thrombotic phenotype and microvascular complications, leading to COVID19-associated coagulopathy (7). This is characterized by venous, arterial, and microvascular thrombosis despite the use of anti-coagulant therapies (32)(33)(34)(35)(36)(37)(38). Our study provides compelling evidence of COVID19 associated changes in coagulation-related gene expression levels that may exacerbate thrombosis caused by endothelial cell injury and platelet activation in COVID19+ ICU patients (7).…”