This work was supported in part by Ricerca Corrente (Linea 1 and 3), Finalizzata (grant numbers: COVID-2020-12371675 and COVID-2020-12371675), supported by the Italian Ministry of Health. The splenic white pulps of all 4 of the group 2 cases showed lymphoid hypoplasia with congested red pulp (Figure 6A1 and 6A2), and Table 3). B3, Tubulointerstitial inflammation and (B4) glomerular sclerosis were observed. C2, CD68+ cells displaying features of hemophagocytosis (arrow). The kidneys of all patients generally had normal shape with reduced volume and size. , Amendola A, Ciccosanti F, et al.   IH Summary of Patient Demographics at Baseline, Demographics, Comorbidities, Duration of Hospital Stay, and Autopsy Cause of Death. Scale bars: A1, A2, B2–C2, 7 µm; B1, 100 µm. B1, Active myocarditis was characterized by mononuclear, predominantly lymphocytic infiltrate, associated with focal myocytes necrosis (B2). Experimental: Cohort 1A Lenacapavir, Failing ARV Regimen, and OBR Functional Monotherapy Period: Participants will receive oral lenacapavir 600 mg, 600mg, and 300 mg tablets on Days 1, 2, and 8 respectively while continuing their failing regimen (previous Antiretroviral (ARV) regimen). Nonlung samples were not subject to transmission electron microscopy. N.Iscrizione Cognome Nome Comune Sede Email Pec SOSPESO SOLO ALBO; N.Iscrizione Cognome Nome Comune Sede Email Pec SOSPESO SOLO ALBO; 2824/11 : ARNETOLI: FRANCO: REGGELLO Un libro è un insieme di fogli, stampati oppure manoscritti, delle stesse dimensioni, rilegati insieme in un certo ordine e racchiusi da una copertina.. Il libro è il veicolo più diffuso del sapere. , Sperhake JP, Lütgehetmann M, et al. Search for other works by this author on: Correspondence: R. Nardacci, PhD, INMI-I.R.C.C.S. , Wagner L, Stephan M, von Hörsten S. Carsana Giemsa and/or Grocott methenamine silver stains were performed where necessary. Parenchymal multifocal damage with intraalveolar exudative and proliferative inflammation (Figure 1A2), with fibrin, hyaline membranes (Figure 1A3) consistent with a diagnosis of diffuse alveolar damage (Table 3). 00146 - Roma Both acute exudative inflammatory process and fibrous proliferative phase were found. ... Il composto 11a somministrato per via intraperitoneale (5 mg/kg) ed endovenosa (5 mg/kg) ha mostrato, rispettivamente, un'emivita (T1/2) di 4,27 ore e 4,41 ore, un'elevata concentrazione massima (Cmax = 2394 ng/mL), una biodisponibilità dell'87,8% quando il composto 11a veniva somministrato per via intraperitoneale.   B Abbreviation: H&E, haematoxylin and eosin. B3, Fibrinous, hemorrhagic areas with myofibers disarray were present. Tel. They also allow a more accurate diagnosis to be made and minimize the chances of missing an accurate diagnosis due to sampling error. Images were captured with a digital camera (Tietz Video and Image Processing Systems). B–D, Numerous viral particles are enclosed in single-membrane vacuoles (arrow). , Lucas SB, Youd E, Swift B, Osborn M. Baiocchini Macroscopic inspection of the liver of all patients showed parenchyma congestion.   S , Hirsch JS, Narasimhan M, et al.   C Pathological findings in lung. We demonstrated a significant upregulation of the chemokine receptor CXCR3, which is not only responsible for T cells extravasating from blood vessels and migration [20], but it has been also implicated in pulmonary fibrosis [21]. Performing whole-body autopsies in patients who die of COVID-19 remains challenging due to infection control regulations and other logistical reasons [11, 12]. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.   L Tel. ); and Regione Lazio Gruppi di Ricerca (grant number E56C18000460002 to M. P.). A, SARS-CoV-2 particles are visible in virus-containing compartments in type II pneumocytes (arrows). Tissues from the lung, heart, liver, kidney, spleen, and bone marrow (but not the brain) were examined. On 12 March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic as it rapidly spread worldwide [1]. To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Studies of other viral infections of the respiratory tract have shown that liver injury may be immune mediated or a result of direct cytopathic damage [27]. Because SARS-CoV-2 is classified as a biosafety level 3 (BSL3) organism, specific operating procedures for BSL3 pathogens were also followed. Histology of spleen and bone marrow. As of 19 August 2020, globally there have been 21 300 000 COVID-19 cases with 760 000 deaths reported to the WHO, of which Italy has reported 250 000 COVID-19 cases with 35 000 deaths [1]. These are thought to be underpinned by an excessive immune response [19]. C1, Macrophages (CD68+) are present in bone marrow tissue. s.s. 11 - frazione villabella, 37047, san bonifacio (vr) meb srl. Tang Abbreviation: COPD, chronic obstructive pulmonary disease. Patients without comorbidities also showed greater hepatic injury. National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS. del 19/02/2020 e con Delibera n. 205/D.G. , Wolf M, Walz A, Loetscher P. Kruschinski T-cell activation is modulated by dipeptidyl peptidase-4 (DPP4) [16] and thus the expression of CD26/DPP4 and CXCR3/CD183 was analyzed on lung tissues from group 2 patients (Figure 2). The first human cases of coronavirus disease-2019 (COVID-19), caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), were reported at the end of December 2019 in Wuhan, China. A recent [33] histopathological examination of brain specimens obtained from COVID-19 patients who died up to 32 days after symptom onset found only hypoxic changes and no specific brain changes attributable to SARS-CoV-2. Whether these findings represent liver or kidney damage caused directly by SARS-CoV-2 itself or are a reflection of the consequences of an abnormal and excessive inflammatory response, requires definition [26]. Lazzaro Spallanzani (1729–1799) found that boiling broth would sterilize it and kill any microorganisms in it. , Penninger JM, Li Y, Zhong N, Slutsky AS. In addition, using electron microscopy we identified viral particles in the cytoplasm of type II pneumocytes—the main target of viral infection [18].   T Pulmonary and cardiovascular involvement were dominant pathological features. Rosalind Elsie Franklin (25 July 1920 – 16 April 1958) was an English chemist and X-ray crystallographer whose work was central to the understanding of the molecular structures of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, coal, and graphite. Nardacci Patient demographic and clinical information was extracted from case records of 22 consecutive patients with COVID-19 who died and were autopsied. Organizing pneumonia with fibrosis and type II pneumocyte hyperplasia, amphophilic cytoplasm, large nuclei, and prominent nucleoli, were indicative of cytopathic virus-induced changes (Figure 1A3 and 1A4). Hier sollte eine Beschreibung angezeigt werden, diese Seite lässt dies jedoch nicht zu. Microvascular damage and thrombosis were also a prominent feature in cases with and without comorbidities. We only looked for evidence of SARS-CoV-2 in lung samples. A3, Intense staining is seen in the type II pneumocytes (arrows). Ingresso di servizio per gli artisti e i disabili: via Luigi Pierantoni, 6 Z. receive support from European and Developing Countries Clinical Trials Partnership, Pan-African Network For Rapid Research, Response, Relief and Preparedness for Infectious Disease Epidemics, funded by the European Union Horizon 2020 Framework Programme for Research and Innovation. Klemann Kidney injury has been reported in nearly 30% of COVID-19 patients [25]. Pericarditis (fibrinous or fibrous) was seen mainly in group 2 patients (Figure 4B4). The authors gratefully acknowledge the excellent support of the National Institute for Infectious Diseases (INMI) pathology team: Alessia Brenna, Marco Canali, Roberta Chiappini, Mario Moauro, Nicolina Rotiroti, and Wilfredo von Lorch, who risked SARS-CoV-2 infection in performing the autopsies and collecting the samples; Professor Sebastian Lucas, emeritus Professor, St Thomas Hospital, London, UK; Roberta Nardacci and Delia Goletti, Professors at Saint Camillus International University of Health and Medical Sciences in Rome; We gratefully acknowledge the assistance of members of the INMI COVID-19 study group (see Supplementary Material). It is thus possible that this is associated with an aberrant type I immune response involving the CXCR3/ligand pathway. Descriptions of the pathological features of coronavirus disease-2019 (COVID-19) caused by the novel zoonotic pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emanate from tissue biopsies, case reports, and small postmortem studies restricted to the lung and specific organs. There were some limitations of our study. Autopsies were performed at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Abbreviation: H&E, haematoxylin and eosin. SARS-CoV-2 qualitative reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 infection was performed on the following samples: ocular, nasopharyngeal, oropharyngeal, lung, and rectal swabs. Published by Oxford University Press for the Infectious Diseases Society of America. Depois da enfermeira, foram vacinados o operador sanitário Omar Altobelli e a diretora do laboratório de virologia do Spallanzani, Maria Rosaria Capobianchi, no mesmo local. A4, Inflammatory infiltration was observed.   R presentazione domande: 03/09/2020 Financial support. Interestingly, spherules, very small vesicles containing single viral particles (Figure 3B and 3C), were also observed. Scale bars: A2, 14 µm; A3–B3, 7 µm; B4, 21 µm. Lo studio clinico, finalizzato alla valutazione dell’efficacia e della sicurezza nella riduzione della replicazione del virus SARS-CoV-2, sarà svolto presso l’Istituto nazionale per le malattie infettive “Lazzaro Spallanzani”, con il coinvolgimento anche dell’Istituto clinico Humanitas di Milano, e coinvolgerà 450 pazienti suddivisi in modo randomizzato al trattamento con Raloxifene. Via Lazzaro Spallanzani, 1A 00161 - Roma Tel. The myocardium appeared pale and flabby. del 27/02/2020; Bando di partecipazione pubblicato sul B.U.R.Lazio n. 91 del 21/07/2020 e per estratto sulla G.U.R.I. Pathological findings in liver and kidney. In Italy, the first confirmed cases of COVID-19, reported on 31 January 2020, were 2 tourists from Wuhan, China. Potential conflicts of interest. Copyright © 2021 Infectious Diseases Society of America. Genomic and transcriptomic landscape of conjunctival melanoma. Active myocarditis (Figure 4B1) characterized by mononuclear, predominantly lymphocytic, infiltrate, and was associated with focal myocytes necrosis (Figure 4B2), fibrinous, and hemorrhagic areas with myofibers disarray (Figure 4B3). Moser Au niveau mondial le nombre total de cas est de 96 984 258, le nombre de guérisons est de 53 508 849, le nombre de décès est de 2 077 803.   G Immunohistochemistry showed the presence of both CD4+ and CD8+ T lymphocytes (Supplementary Figure 1B2 and 1B3). Teatro di Roma - Teatro Nazionale | p. iva 02067821005, Le conversazioni del Cantiere dell'immaginazione, RADIO INDIA presenta Sette concerti di Capodanno, Scuola di Teatro e Perfezionamento Professionale del Teatro di Roma. Teatro di Roma - Teatro Nazionale | p. iva 02067821005 Via de’ Barbieri, 21 - 00186 - … Spallanzani,” Via Portuense, 292-0149 Rome, Italy (, Department of Infection, Division of Infection and Immunity, University College London, National Institute for Health Research Biomedical Research Centre, University College London Hospitals National Health Service Foundation Trust, Laboratory of Cellular and Developmental Biology, Department of Biology, University of Rome Tor Vergata, Coronavirus disease (COVID-19) situation reports, Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, Clinical and immunological features of severe and moderate coronavirus disease-2019, Pathological findings of COVID-19 associated with acute respiratory distress syndrome, Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies, Postmortem lung findings in a patient with asthma and coronavirus disease 2019, Renal histopathological analysis of 26 postmortem findings of patients with COVID-19 in China, Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study, Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings of lungs and other organs suggesting vascular dysfunction, Caution should be exercised for the detection of SARS-CoV-2, especially in the elderly, Autopsy slowdown hinders quest to determine how coronavirus kills, A call to action: the need for autopsies to determine the full extent of organ involvement associated with COVID-19, Liver sinusoidal endothelial cells (LSECs) modifications in patients with chronic hepatitis C, Autophagy plays an important role in the containment of HIV-1 in nonprogressor-infected patients, Cut to the chase: a review of CD26/dipeptidyl peptidase-4’s (DPP4) entanglement in the immune system, Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study, -CoV-2 cytopathogenesis in cultured cells and in COVID-19 autoptic lung, evidences of lipid involvement, The pathogenesis and treatment of the ‘cytokine storm’ in COVID-19, Chemokines: multiple levels of leukocyte migration control, Regulation of pulmonary fibrosis by chemokine receptor CXCR3, CD26 (dipeptidyl-peptidase IV)-dependent recruitment of T cells in a rat asthma model, Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target, Cardiac involvement in COVID-19 patients: risk factors, predictors, and complications: a review, kidney is a target for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, Liver injury during highly pathogenic human coronavirus infections, COVID-19 and liver dysfunction: current insights and emergent therapeutic strategies, Multiple organ infection and the pathogenesis of SARS, Thrombocytopenia in patients with severe acute respiratory syndrome (review), Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy, SARS-CoV-2 and viral sepsis: observations and hypotheses, Neurological manifestations of COVID-19: a systematic review, Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis, Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. Clicca qui per sapere come raggiungerci, Iscriviti e partecipa alla Community del Teatro di Roma. Microscopic changes seen were hypertrophy of myocytes and variable degrees of interstitial and vascular fibrosis (Figure 4A3 and 4A4). Tissue samples were processed using hematoxylin and eosin staining (H&E), Masson trichrome stain, Perls stain, reticulin stain, periodic acid-Schiff reaction (PAS) and diastase-PAS. Dirección editorial Arlette Sandoval Espinoza Whole-body autopsies offer several advantages over limited sampling using biopsies and tissues obtained post mortem [4–7]. Hier sollte eine Beschreibung angezeigt werden, diese Seite lässt dies jedoch nicht zu. del 31/12/2019 modificata con Delibera n. 154/D.G. Acknowledgments. Cerca nel più grande indice di testi integrali mai esistito. Other, very small vesicles contain single viral particles (arrowheads). , Normandin E, Bhattacharyya S, et al. , Haslbauer JD, Nienhold R, et al.   N Puoi affitare gli spazi del Teatro di Roma. Nardacci Our lung pathology findings were similar to those seen in a study of postmortem lung tissues from northern Italy of 33 males and 5 female patients, with an average age of 69 years (range 32–86) [17]. Extrapulmonary manifestations included hepatic, kidney, splenic, and bone marrow involvement, and microvascular injury and thrombosis were also detected. El Texto del estudiante de Ciencias Naturales 7.° básico es una creación del Departamento de Estudios Pedagógicos de Ediciones SM, Chile. Of these, 18 had other medical comorbidities (designated group 1). Patients with COVID-19 who do not have comorbidities appear to have similar pathological manifestations as those with comorbidities [31]. This supports the observation that anticoagulant treatment can reduce mortality in COVID-19 [30]. For permissions, e-mail: journals.permissions@oup.com. L. F., R. N., A. Cardiac involvement in severe COVID-19 pathogenesis has been well documented [23], and cardiac risk factors have been identified as risk factors for increased mortality [24]. A case report, also from China, described findings in a postmortem biopsy specimen which showed diffuse alveolar damage and interstitial mononuclear inflammatory infiltrates [5]. Whole-body complete autopsy studies from across a wide range of geographical background, age, ethnic group, and comorbidities [10, 34, 35] are required to define the pathogenesis and the complete spectrum of pathology in COVID-19. Spazio riservato alla stampa e alle televisioni. Megakaryocytes hyperplasia (Figure 6B2) was seen in 2 patients of group 2 (Table 3). Numerous strongly positive CD26+ cells are seen in the alveolar septa. viale dell'industria 15, 36071, arzignano (vi) meb srl . Scale bars: A1 and B1, 100 µm; A2, A3, and B4, 7 µm; A4, B2, and B3, 14 µm. A. Regarder des films en streaming complet sur votre smart TV, console de jeu, PC, Mac, smartphone, tablette et bien plus. Supplementary materials are available at The Journal of Infectious Diseases online. Lungotevere Vittorio Gassman (già lungotevere dei Papareschi), 1   B Whole-body autopsy studies of COVID-19 patients have been sparse. A2 and A3, Light microscopic analysis shows parenchymal multifocal damage with intraalveolar inflammation, fibrin, and hyaline membranes consistent with a diagnosis of diffuse alveolar damage. denominazione indirizzo des_comuni cod_provincia telefono_principale url_sito; peretti franco: via novara 27: abbiategrasso: mi: 0294967604 : motosprint snc di luca montanino e c. These included myocardial ischemic or inflammatory changes, hypertensive changes of the left ventricular cavity, and valvular calcification of the mitral annulus and aortic valve (Figure 4A2). B4, Pleural fibrosis. , Bai H, Chen X, Gong J, Li D, Sun Z. Solomon A1 and A2, Lymphoid hypoplasia is visible in the splenic white pulp. Numerous CD26+ cells were found in the alveolar septa (Figure 2A1–2A3) with intense staining seen in the type II pneumocytes (Figure 2A3). The 4 younger patients without preexisting medical conditions also had similar findings despite absence of comorbidities and displayed all the histopathological hallmarks of widespread vascular injury, including liver, kidney, spleen, and bone marrow involvement. Delibera di indizione del Concorso n. 1186/D.G. Z., G. I., M. P., and F. D. N. contributed equally. Endocardium showed punctuate petechial hemorrhages. The brain was not examined. via ludovico lazzaro zamenhof 699, 36100, vicenza (vi) meb srl. Thus, the CXCR3 cytokine axis could be considered a potential therapeutic target in development of targeted host-directed therapies for COVID-19. via di campotrentino, 38121, trento (tn) gruppo giovannini srl. Whole-body autopsy allows examination of most body organs to define the extent of COVID-19 pathology, and also allows adequate tissue to be obtained for further pathological and molecular evaluation and for research purposes. Deparaffinized and rehydrated sections were used for immunohistochemistry. Our observations add further information on the pathology examination findings of COVID-19. Aghagoli Scale bars: A, 1 µm; B–D, 200nm.   R A3 and A4, Hyperplasia of type II pneumocyte, characterized by amphophilic cytoplasm, large nuclei, and prominent nucleoli, are shown (arrows). A4, Positive cells are also seen entrapped with fibrin in the vascular lumen. Supporting the call for action to conduct full autopsies on patients who die of COVID-19 for determining the extent of organ involvement [12, 13], we conducted a comprehensive postmortem full autopsy examination of 22 patients. All authors: No reported conflicts of interest. Lungs from all patients were increased in volume, firm, edematous, and congested with diffuse pleural thickening and pleural effusion. Four patients were healthy prior to hospital admission and had no known medical comorbidities or any cause of immunosuppression (designated group 2). Abbreviation: H&E, haematoxylin and eosin. To further define the pathology caused by SARS-CoV-2 across all body organs, we performed autopsies on 22 patients with COVID-19 (18 with comorbidities and 4 without comorbidities) who died at the National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS Hospital, Rome, Italy. Whilst the COVID-19 cases in our study were from a range of age, sex, and comorbidities, we cannot accurately say our findings are fully representative of COVID-19 pathology in the large numbers who have died in Italy. films en VF ou VOSTFR et bien sûr en HD. 06 684 00 03 11 / 14 Clicca qui per sapere come raggiungerci. Positive cells entrapped with fibrin clots in the vascular lumen were also observed (Figure 2A4). Clicca qui per sapere come raggiungerci, Teatro India A main feature was the presence of numerous inflammatory cells consisting of granulocytes (CD15+) (Supplementary Figure 1A1 and 1A2), macrophages (CD68+) (Supplementary Figure 1A3 and 1A4), and T lymphocytes (CD3+) infiltrating into alveolar septa and clustering around capillary vessels (Supplementary 1B1). The myocardium appeared pale and flabby, and endocardium showed punctuate petechial hemorrhages (Figure 4A1). “L. Laura Falasca, Roberta Nardacci, Daniele Colombo, Eleonora Lalle, Antonino Di Caro, Emanuele Nicastri, Andrea Antinori, Nicola Petrosillo, Luisa Marchioni, Gianluigi Biava, Gianpiero D’Offizi, Fabrizio Palmieri, Delia Goletti, Alimuddin Zumla, Giuseppe Ippolito, Mauro Piacentini, Franca Del Nonno, COVID-19 INMI Study Group, Postmortem Findings in Italian Patients With COVID-19: A Descriptive Full Autopsy Study of Cases With and Without Comorbidities, The Journal of Infectious Diseases, Volume 222, Issue 11, 1 December 2020, Pages 1807–1815, https://doi.org/10.1093/infdis/jiaa578. SARS-CoV-2 infection causes multisystem disease and significant pathology in most organs in patients with and without comorbidities. I. B3, Vascular injury including vessel vasculitis and vascular edema. In our autopsy study, we found that COVID-19 predominantly causes acute lung injury and diffuse alveolar damage, which is associated with multisystem involvement and significant pathology across most body organs in patients with and without comorbid disease. He also found that new microorganisms could settle only in a broth if the broth was exposed to the air. Histological changes in heart. The study was approved by the local ethics committee (approval number 9/2020). These findings were similar in patients with or without preexisting medical comorbidities. Menter Autopsies were performed in a specific COVID-19 designated autopsy room with airflow control and airborne infection control procedures, including use of appropriated personal protective equipment (ie, National Institute for Occupational Safety and Health-certified disposable N-95 respirator). Largo di Torre Argentina, 52 Scegli gli spettacoli on line. Zhang , Rehrig JH, Shrestha GS, et al. Reports from individual or small autopsy case studies [4–6] or limited postmortem studies [7–9] show that SARS-CoV-2, like SARS-CoV-1 in 2003, is a multisystem disease that predominantly affects the respiratory and cardiovascular system.

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