key: cord-0704987-694qp9cz authors: Remmelink, M.; De Mendoca, R.; D'Haene, N.; De Clercq, S.; Verocq, C.; Lebrun, L.; Lavis, P.; Racu, M. L.; Trepant, A. L.; Maris, C.; Rorive, S.; Goffard, J. C.; De Witte, O.; Peluso, L.; Vincent, J. L.; Decaestecker, C.; Taccone, F. S.; Salmon, I. title: Unspecific post-mortem findings despite multiorgan 1 viral spread in COVID-19 patients date: 2020-05-28 journal: nan DOI: 10.1101/2020.05.27.20114363 sha: 7019deee98d06c637ebe3cce68f5486ccd755333 doc_id: 704987 cord_uid: 694qp9cz Background Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients. Methods We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in lung and other organs. Results Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e. lung, heart, spleen, liver, colon, kidney and brain). Conclusions In conclusion, autopsies revealed a great heterogeneity of COVID-19-related organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs. organs. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. In conclusion, autopsies revealed a great heterogeneity of COVID-19-related organ 63 injury and the remarkable absence of any specific viral lesions, even when RT-PCR 64 identified the presence of the virus in many organs. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. In this post-mortem study, we included the first 17 adult patients (>18 years) who 97 died in our hospital (either in a COVID-19 unit or an intensive care unit) from March 98 13, 2020 with confirmed SARS-CoV-2 infection (i.e. positive RT-PCR assay on 99 nasopharyngeal swab and/or broncho-alveolar lavage specimen). Autopsies were 100 performed 72 to 96 hours after death to ensure the safety of the autopsy team. Exclusion criteria were lack of family consent and a delay of more than five days 102 after death. The study protocol was approved by the local ethics committee 103 (P2020/218). Data collection 106 We collected demographics, comorbidities, relevant clinical data, the results of chest 107 computed tomography scan, and if available, microbiological tests and medical 108 treatments (e.g. hydroxychloroquine, antivirals or antibiotics, and use of organ 109 support). Acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) 110 were defined according to standard definitions (8, 9). Post-mortem procedure 113 The Belgian Sciensano guidelines were integrated into our post-mortem procedure 114 (10). Personal protective equipment consisted of two superposed disposable latex 115 gloves, plastic sleeves, FFP3 mask, scrub hat, clear face visor, surgical gown plus 116 plastic apron, rubber boots. In the post-mortem room, dirty and clean circulations 117 were used in the airlocks to allow decontamination. For 11 cases, brain samples were 118 obtained using a safety procedure with drills and protective devices to avoid air 119 dispersion, as described in the Additional file 1 (Additional Material). 120 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. nodes, heart, spleen, bone marrow, kidney, bladder, liver, stomach, colon, and brain. For the lungs, we collected six samples per lobe (i.e. a total of 30 samples), except for 126 two patients who had undergone lobectomy for cancer and from whom only 18 127 samples were taken. For safety reasons, complete brain removal was not allowed, but, Since no antibody against SARS-CoV-2 has been validated for IHC on FFPE tissues, 145 we selected an anti-SARS-nucleocapsid protein antibody. Standard IHC was applied 146 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (Table S1) . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. 244 SARS-CoV-2 RNA was detected in at least one organ from every patient (Figure 4) . In the lung, RT-PCR was positive in 16 patients, with threshold cycle (Ct) values 246 varying from 16.02 to 33.03. Viral RNA was also detected in the heart (n=14), the 247 liver (n=14), the bowel (n=14), the spleen (n=11), and the kidney (n=10) as well as in 248 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. . https://doi.org/10.1101/2020.05.27.20114363 doi: medRxiv preprint We did not observe specific viral organ injury, such as myocarditis, hepatitis or (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Availability of data and materials 381 The data that support the findings of this study are available from the corresponding 382 author on reasonable request. Participant data without names and identifiers will be 383 made available after approval from the corresponding author and local Ethics 384 Committee. The research team will provide an email address for communication once 385 the data are approved to be shared with others. The proposal with detailed description 386 of study objectives and statistical analysis plan will be needed for evaluation of the 387 reasonability to request for our data. Additional materials may also be required 388 during the process. Competing interests 391 The authors declare that they have no competing interests. This study received financial support from Fonds Y. Boël (Brussels, Belgium), Fonds 395 Erasme pour la Recherche Médicale (Brussels, Belgium), and "Appel à projet Spécial 396 COVID-19 -ULB" (Brussels, Belgium). The CMMI is supported by the European 397 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 28, 2020. . https://doi.org/10.1101/2020.05.27.20114363 doi: medRxiv preprint Clinical Characteristics 424 of Coronavirus Disease 2019 in China SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a 427 clinically proven protease inhibitor Autopsy Findings and Venous Thromboembolism in Patients With COVID-430 19: A Prospective Cohort Study. Ann Intern Med. 2020. Epub ahead of print Endothelial cell infection and endotheliitis in COVID-19 Clinical characteristics 436 of 113 deceased patients with coronavirus disease 2019: retrospective study Epub ahead of print COVID-19 associated with acute respiratory distress syndrome COVID-19 442 autopsies Acute respiratory distress syndrome: the 445 Berlin Definition All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted May 28, 2020. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted May 28, 2020. . https://doi.org/10.1101/2020.05.27.20114363 doi: medRxiv preprint Additional files: Critical care-autopsy-Covid-Additional file 1.doc Procedure to obtain brain samples Critical care-autopsy-Covid-Additional file 2.doc Additional table S1