Pulmonary Post-Mortem Findings in a Large Series of COVID-19 Cases from Northern Italy (preprint)

Importance: The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness.Objective: To determine the histological patterns in lung tissue of patients with severe COVID-19.Design and Participants: Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed.Results: The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstitium. Electron microscopy revealed viral particles within cytoplasmic vacuoles of pneumocytes.Conclusions and Relevance: The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.Funding Statement: No FundingDeclaration of Interests: No Conflict of InterestEthics Approval Statement: Tissue samples were taken as part of routine autopsies

Liver histopathology in COVID 19 infection is suggestive of vascular alteration (preprint)

COVID-19 breakout in Italy has caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection very few information are available about liver involvement in COVID-19 infection, that could possibly evocate a systemic disease targeting a lot of organs. Since now there are no reports of large series of histological evaluation of liver morphology in this setting. Knowledge of histological liver findings connected to clinical data is crucial in management of this disease. Post-mortem wedge liver biopsies from 48 patients died for COVID-19 infection were available from two main hospitals located in northern Italy, Lombardy; all sample were obtained during autopsies. No patient has a significant clinical complain of liver disease or signs of liver failure before and during hospitalization; for each of them laboratory data focused on liver were available. All liver samples showed minimal inflammation features; on the other side, many histological pictures compatible with vascular alterations were observed, characterized by portal vein braches number increase associated with lumen massive dilatation, partial or complete recent luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally severely enlarged and fibrotic. Our preliminary results concerning histological liver involvement in COVID-19 infection confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage; histopatological findings are highly suggestive for marked alteration of intrahepatic blood vessel network secondary to systemic alterations induced by virus that could target, besides lung parenchyma, cardiovascular system, coagulation cascade or endothelial layer of blood vessels.

THE PATHOGENESIS OF THROMBOEMBOLIC DISEASE IN COVID-19 PATIENTS: COULD BE A CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME? (preprint)

Background The most severely COVID-19 patients need intensive care and show increased risk of thromboembolic events. Although some patients meet the diagnostic criteria for the Disseminated Intravascular Coagulation, the pathogenesis of the diffuse thrombotic status remains unclear. The aim of the present study is to evaluate the presence of antiphospholipid antibodies (aPL) in sera of deceased patients with autoptic proven thrombotic microangiopathy to evaluate if some patients may have developed Catastrophic Antiphospholipid Syndrome (CAPS). Methods Thirty-five patients were enrolled. The available medical history, comorbidities, therapies, laboratory and autopsy findings were collected post-mortem from clinical records. IgA, IgG and IgM anti cardiolipin (ACA) and anti {beta}2 glycoprotein 1 ({beta}2GP1) antibodies, IgG and IgM anti phosphatidylserine/prothrombin (PS/PT) antibodies were tested for all the patients. Results 3/35 (8.6%) patients were slightly positive for aPL: one for ACA IgG and two for ACA IgM but values were low (< 3X the cut off). No patients tested positive for ACA IgA neither for {beta}2GP1 isotypes. 3/35 (8.6%) patients were positive for PS/PT, one for IgG and two for IgM, but values were less than 2X the cut off. No patients showed simultaneous positivity for ACA and PS/ PT. Conclusions It is difficult to categorize the vascular events into a conventional disease: we did not find significant association with anti-phospholipid antibodies. It is most likely that several factors contribute to trigger the hypercoagulability status and the thromboembolism but, on the basis our results, CAPS is probably not involved into the pathogenesis of these phenomena.

Liver and COVID 19 Infection: A Very Preliminary Lesson Learnt from Histological Post-mortem Findings in 48 patients (preprint)

COVID-19 breakout in Italy has caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection very few information are available about liver involvement in COVID-19 infection, that could possibly evocate a systemic disease targeting a lot of organs. Since now there are no reports of large series of histological evaluation of liver morphology in this setting. Knowledge of histological liver findings connected to clinical data is crucial in management of this disease.Post-mortem wedge liver biopsies from 48 patients died for COVID-19 infection were available from two main hospitals located in northern Italy, Lombardy; all sample were obtained during autopsies. No patient has a significant clinical complain of liver disease or signs of liver failure before and during hospitalization; for each of them laboratory data focused on liver were available. All liver samples showed minimal inflammation features; on the other side, many histological pictures compatible with vascular alterations were observed, characterized by portal vein braches number increase associated with lumen massive dilatation, partial or complete recent luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally severely enlarged and fibrotic. Our preliminary results concerning histological liver involvement in COVID-19 infection confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage; histopatological findings are highly suggestive for marked alteration of intrahepatic blood vessel network secondary to systemic alterations induced by virus that could target, besides lung parenchyma, cardiovascular system, coagulation cascade or endothelial layer of blood vessels.

Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy (preprint)

Importance. The analysis of lung tissues of patients with COVID-19 may help understand pathogenesis and clinical outcomes in this life-threatening respiratory illness. Objective. To determine the histological patterns in lung tissue of patients with severe COVID-19. Design and participants. Lungs tissues of 38 cases who died for COVID-19 in two hospital of Northern Italy were systematically analysed. Hematoxylin-eosin staining, immunohistochemistry for the inflammatory infiltrate and cellular components, electron microscopy were performed. Results. The features of the exudative and proliferative phases of Diffuse Alveolar Disease (DAD) were found: capillary congestion, necrosis of pneumocytes, hyaline membrane, interstitial oedema, pneumocyte hyperplasia and reactive atypia, platelet-fibrin thrombi. The inflammatory infiltrate was composed by macrophages in alveolar lumens and lymphocytes mainly in the interstitium. Electron microscopy revealed viral particles within cytoplasmic vacuoles of pneumocytes. Conclusions and relevance. The predominant pattern of lung lesions in COVID-19 patients is DAD, as described for the other two coronavirus that infect humans, SARS-CoV and MERS-CoV. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequently found. The main relevant finding is the presence of platelet-fibrin thrombi in small arterial vessels; this important observation fits into the clinical context of coagulopathy which dominates in these patients and which is one of the main targets of therapy.