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Open Access 01-01-2021 | Autopsy | Review and Perspectives

The pulmonary pathology of COVID-19

Authors: Hans Bösmüller, Matthias Matter, Falko Fend, Alexandar Tzankov

Published in: Virchows Archiv | Issue 1/2021

Abstract

The lung is the main affected organ in severe coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2, and lung damage is the leading cause of death in the vast majority of patients. Mainly based on results obtained by autopsies, the seminal features of fatal COVID-19 have been described by many groups worldwide. Early changes encompass edema, epithelial damage, and capillaritis/endothelialitis, frequently combined with microthrombosis. Subsequently, patients with manifest respiratory insufficiency exhibit exudative diffuse alveolar damage (DAD) with hyaline membrane formation and pneumocyte type 2 hyperplasia, variably complicated by superinfection, which may progress to organizing/fibrotic stage DAD. These features, however, are not specific for COVID-19 and can be found in other disorders including viral infections. Clinically, the early disease stage of severe COVID-19 is characterized by high viral load, lymphopenia, massive secretion of pro-inflammatory cytokines and hypercoagulability, documented by elevated D-dimers and an increased frequency of thrombotic and thromboembolic events, whereas virus loads and cytokine levels tend to decrease in late disease stages, when tissue repair including angiogenesis prevails. The present review describes the spectrum of lung pathology based on the current literature and the authors’ personal experience derived from clinical autopsies, and tries to summarize our current understanding and open questions of the pathophysiology of severe pulmonary COVID-19.

Wu F, Zhao S, Yu B, Chen YM, Wang W, Song ZG, Hu Y, Tao ZW, Tian JH, Pei YY, Yuan ML, Zhang YL, Dai FH, Liu Y, Wang QM, Zheng JJ, Xu L, Holmes EC, Zhang YZ (2020) A new coronavirus associated with human respiratory disease in China. Nature 579:265–269. https://doi.org/10.1038/s41586-020-2008-3CrossRefPubMedPubMedCentral

Maiese A, Manetti AC, La Russa R, Di Paolo M, Turillazzi E, Frati P, Fineschi V (2020) Autopsy findings in COVID-19-related deaths: a literature review. Forensic Sci Med Pathol. https://doi.org/10.1007/s12024-020-00310-8

Omori R, Matsuyama R, Nakata Y (2020) The age distribution of mortality from novel coronavirus disease (COVID-19) suggests no large difference of susceptibility by age. Sci Rep 10:16642. https://doi.org/10.1038/s41598-020-73777-8CrossRefPubMedPubMedCentral

Magadum A, Kishore R (2020) Cardiovascular manifestations of COVID-19 infection. Cells 9. https://doi.org/10.3390/cells9112508

Yang J, Tian C, Chen Y, Zhu C, Chi H, Li J (2020) Obesity aggravates COVID-19: an updated systematic review and meta-analysis. J Med Virol. https://doi.org/10.1002/jmv.26677

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, Du B, Li LJ, Zeng G, Yuen KY, Chen RC, Tang CL, Wang T, Chen PY, Xiang J, Li SY, Wang JL, Liang ZJ, Peng YX, Wei L, Liu Y, Hu YH, Peng P, Wang JM, Liu JY, Chen Z, Li G, Zheng ZJ, Qiu SQ, Luo J, Ye CJ, Zhu SY, Zhong NS, China Medical Treatment Expert Group for C (2020) Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 382:1708–1720. https://doi.org/10.1056/NEJMoa2002032CrossRefPubMed

Basso C, Calabrese F, Sbaraglia M, Del Vecchio C, Carretta G, Saieva A, Donato D, Flor L, Crisanti A, Dei Tos AP (2020) Feasibility of postmortem examination in the era of COVID-19 pandemic: the experience of a Northeast Italy University Hospital. Virchows Arch 477:341–347. https://doi.org/10.1007/s00428-020-02861-1CrossRefPubMed

D'Onofrio V, Donders E, Vanden Abeele ME, Dubois J, Cartuyvels R, Achten R, Lammens M, Dendooven A, Driessen A, Augsburg L, Vanrusselt J, Cox J (2020) The clinical value of minimal invasive autopsy in COVID-19 patients. PLoS One 15:e0242300. https://doi.org/10.1371/journal.pone.0242300CrossRefPubMedPubMedCentral

Li Y, Wu J, Wang S, Li X, Zhou J, Huang B, Luo D, Cao Q, Chen Y, Chen S, Ma L, Peng L, Pan H, Travis WD, Nie X (2020) Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan, China. Histopathology. https://doi.org/10.1111/his.14249

10.

Calabrese F, Pezzuto F, Fortarezza F, Hofman P, Kern I, Panizo A, von der Thusen J, Timofeev S, Gorkiewicz G, Lunardi F (2020) Pulmonary pathology and COVID-19: lessons from autopsy. The experience of European Pulmonary Pathologists. Virchows Arch 477:359–372. https://doi.org/10.1007/s00428-020-02886-6CrossRefPubMedPubMedCentral

11.

Lax SF, Skok K, Zechner P, Kessler HH, Kaufmann N, Koelblinger C, Vander K, Bargfrieder U, Trauner M (2020) Pulmonary arterial thrombosis in COVID-19 with fatal outcome : results from a prospective, single-center, clinicopathologic case series. Ann Intern Med 173:350–361. https://doi.org/10.7326/M20-2566CrossRefPubMed

12.

Menter T, Haslbauer JD, Nienhold R, Savic S, Hopfer H, Deigendesch N, Frank S, Turek D, Willi N, Pargger H, Bassetti S, Leuppi JD, Cathomas G, Tolnay M, Mertz KD, Tzankov A (2020) Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology 77:198–209. https://doi.org/10.1111/his.14134CrossRefPubMedPubMedCentral

13.

Wichmann D, Sperhake JP, Lutgehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, Mushumba H, Kniep I, Schroder AS, Burdelski C, de Heer G, Nierhaus A, Frings D, Pfefferle S, Becker H, Bredereke-Wiedling H, de Weerth A, Paschen HR, Sheikhzadeh-Eggers S, Stang A, Schmiedel S, Bokemeyer C, Addo MM, Aepfelbacher M, Puschel K, Kluge S (2020) Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med 173:268–277. https://doi.org/10.7326/M20-2003CrossRefPubMed

14.

Kommoss FKF, Schwab C, Tavernar L, Schreck J, Wagner WL, Merle U, Jonigk D, Schirmacher P, Longerich T (2020) The pathology of severe COVID-19-related lung damage. Dtsch Arztebl Int 117:500–506. https://doi.org/10.3238/arztebl.2020.0500CrossRefPubMed

15.

Schaller T, Hirschbuhl K, Burkhardt K, Braun G, Trepel M, Markl B, Claus R (2020) Postmortem examination of patients with COVID-19. JAMA 323:2518–2520. https://doi.org/10.1001/jama.2020.8907CrossRefPubMedPubMedCentral

16.

Polak SB, Van Gool IC, Cohen D, von der Thusen JH, van Paassen J (2020) A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression. Mod Pathol 33:2128–2138. https://doi.org/10.1038/s41379-020-0603-3CrossRefPubMed

17.

Ye Z, Zhang Y, Wang Y, Huang Z, Song B (2020) Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review. Eur Radiol 30:4381–4389. https://doi.org/10.1007/s00330-020-06801-0CrossRefPubMed

18.

Pernazza A, Mancini M, Rullo E, Bassi M, De Giacomo T, Rocca CD, d'Amati G (2020) Early histologic findings of pulmonary SARS-CoV-2 infection detected in a surgical specimen. Virchows Arch 477:743–748. https://doi.org/10.1007/s00428-020-02829-1CrossRefPubMed

19.

Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY (2020) Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. J Thorac Oncol 15:700–704. https://doi.org/10.1016/j.jtho.2020.02.010CrossRefPubMedPubMedCentral

20.

Bosmuller H, Traxler S, Bitzer M, Haberle H, Raiser W, Nann D, Frauenfeld L, Vogelsberg A, Klingel K, Fend F (2020) The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation. Virchows Arch 477:349–357. https://doi.org/10.1007/s00428-020-02881-xCrossRefPubMedPubMedCentral

21.

Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D (2020) Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med 383:120–128. https://doi.org/10.1056/NEJMoa2015432CrossRefPubMedPubMedCentral

22.

Borczuk AC, Salvatore SP, Seshan SV, Patel SS, Bussel JB, Mostyka M, Elsoukkary S, He B, Del Vecchio C, Fortarezza F, Pezzuto F, Navalesi P, Crisanti A, Fowkes ME, Bryce CH, Calabrese F, Beasley MB (2020) COVID-19 pulmonary pathology: a multi-institutional autopsy cohort from Italy and New York City. Mod Pathol 33:2156–2168. https://doi.org/10.1038/s41379-020-00661-1CrossRefPubMed

23.

Valdivia-Mazeyra MF, Salas C, Nieves-Alonso JM, Martin-Fragueiro L, Barcena C, Munoz-Hernandez P, Villar-Zarra K, Martin-Lopez J, Ramasco-Rueda F, Fraga J, Jimenez-Heffernan JA (2020) Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature. Virchows Arch. https://doi.org/10.1007/s00428-020-02926-1

24.

Hariri LP, North CM, Shih AR, Israel RA, Maley JH, Villalba JA, Vinarsky V, Rubin J, Okin DA, Sclafani A, Alladina JW, Griffith JW, Gillette MA, Raz Y, Richards CJ, Wong AK, Ly A, Hung YP, Chivukula RR, Petri CR, Calhoun TF, Brenner LN, Hibbert KA, Medoff BD, Hardin CC, Stone JR, Mino-Kenudson M (2021) Lung histopathology in coronavirus disease 2019 as compared with severe acute respiratory sydrome and H1N1 influenza: a systematic review. Chest 159:73–84. https://doi.org/10.1016/j.chest.2020.09.259CrossRefPubMed

25.

Edler C, Schroder AS, Aepfelbacher M, Fitzek A, Heinemann A, Heinrich F, Klein A, Langenwalder F, Lutgehetmann M, Meissner K, Puschel K, Schadler J, Steurer S, Mushumba H, Sperhake JP (2020) Dying with SARS-CoV-2 infection-an autopsy study of the first consecutive 80 cases in Hamburg, Germany. Int J Legal Med 134:1275–1284. https://doi.org/10.1007/s00414-020-02317-wCrossRefPubMed

26.

Skok K, Vander K, Setaffy L, Kessler HH, Aberle S, Bargfrieder U, Trauner M, Lax SF (2020) COVID-19 autopsies: procedure, technical aspects and cause of fatal course. Experiences from a single-center. Pathol Res Pract 217:153305. https://doi.org/10.1016/j.prp.2020.153305CrossRefPubMedPubMedCentral

27.

Pandolfi L, Fossali T, Frangipane V, Bozzini S, Morosini M, D'Amato M, Lettieri S, Urtis M, Di Toro A, Saracino L, Percivalle E, Tomaselli S, Cavagna L, Cova E, Mojoli F, Bergomi P, Ottolina D, Lilleri D, Corsico AG, Arbustini E, Colombo R, Meloni F (2020) Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome. BMC Pulm Med 20:301. https://doi.org/10.1186/s12890-020-01343-zCrossRefPubMedPubMedCentral

28.

Bradley BT, Maioli H, Johnston R, Chaudhry I, Fink SL, Xu H, Najafian B, Deutsch G, Lacy JM, Williams T, Yarid N, Marshall DA (2020) Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series. Lancet 396:320–332. https://doi.org/10.1016/S0140-6736(20)31305-2CrossRefPubMedPubMedCentral

29.

Desai N, Neyaz A, Szabolcs A, Shih AR, Chen JH, Thapar V, Nieman LT, Solovyov A, Mehta A, Lieb DJ, Kulkarni AS, Jaicks C, Xu KH, Raabe MJ, Pinto CJ, Juric D, Chebib I, Colvin RB, Kim AY, Monroe R, Warren SE, Danaher P, Reeves JW, Gong J, Rueckert EH, Greenbaum BD, Hacohen N, Lagana SM, Rivera MN, Sholl LM, Stone JR, Ting DT, Deshpande V (2020) Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection. Nat Commun 11:6319. https://doi.org/10.1038/s41467-020-20139-7CrossRefPubMedPubMedCentral

30.

Nienhold R, Ciani Y, Koelzer VH, Tzankov A, Haslbauer JD, Menter T, Schwab N, Henkel M, Frank A, Zsikla V, Willi N, Kempf W, Hoyler T, Barbareschi M, Moch H, Tolnay M, Cathomas G, Demichelis F, Junt T, Mertz KD (2020) Two distinct immunopathological profiles in autopsy lungs of COVID-19. Nat Commun 11:5086. https://doi.org/10.1038/s41467-020-18854-2CrossRefPubMedPubMedCentral

31.

Carsana L, Sonzogni A, Nasr A, Rossi RS, Pellegrinelli A, Zerbi P, Rech R, Colombo R, Antinori S, Corbellino M, Galli M, Catena E, Tosoni A, Gianatti A, Nebuloni M (2020) Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study. Lancet Infect Dis 20:1135–1140. https://doi.org/10.1016/S1473-3099(20)30434-5CrossRefPubMedPubMedCentral

32.

Del Valle DM, Kim-Schulze S, Huang HH, Beckmann ND, Nirenberg S, Wang B, Lavin Y, Swartz TH, Madduri D, Stock A, Marron TU, Xie H, Patel M, Tuballes K, Van Oekelen O, Rahman A, Kovatch P, Aberg JA, Schadt E, Jagannath S, Mazumdar M, Charney AW, Firpo-Betancourt A, Mendu DR, Jhang J, Reich D, Sigel K, Cordon-Cardo C, Feldmann M, Parekh S, Merad M, Gnjatic S (2020) An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med 26:1636–1643. https://doi.org/10.1038/s41591-020-1051-9CrossRefPubMed

33.

Polidoro RB, Hagan RS, de Santis SR, Schmidt NW (2020) Overview: systemic inflammatory response derived from lung injury caused by SARS-CoV-2 infection explains severe outcomes in COVID-19. Front Immunol 11:1626. https://doi.org/10.3389/fimmu.2020.01626CrossRefPubMedPubMedCentral

34.

Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JCT, Fogerty AE, Waheed A, Goodarzi K, Bendapudi PK, Bornikova L, Gupta S, Leaf DE, Kuter DJ, Rosovsky RP (2020) COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood 136:489–500. https://doi.org/10.1182/blood.2020006520CrossRefPubMedPubMedCentral

35.

Nagpal P, Narayanasamy S, Vidholia A, Guo J, Shin KM, Lee CH, Hoffman EA (2020) Imaging of COVID-19 pneumonia: patterns, pathogenesis, and advances. Br J Radiol 93:20200538. https://doi.org/10.1259/bjr.20200538CrossRefPubMed

36.

Harrison AG, Lin T, Wang P (2020) Mechanisms of SARS-CoV-2 transmission and pathogenesis trends. Immunol 41:1100–1115. https://doi.org/10.1016/j.it.2020.10.004CrossRef

37.

Henkel M, Weikert T, Marston K, Schwab N, Sommer G, Haslbauer J, Franzeck F, Anastasopoulos C, Stieltjes B, Michel A, Bremerich J, Menter T, Mertz K, Tzankov A, Sauter A (2020) Lethal COVID-19: Radiological-pathological correlation of the lungs. Radiol Cardiothorac Imaging 2:e200406. https://doi.org/10.1148/ryct.2020200406CrossRefPubMedPubMedCentral

38.

Barisione E, Grillo F, Ball L, Bianchi R, Grosso M, Morbini P, Pelosi P, Patroniti NA, De Lucia A, Orengo G, Gratarola A, Verda M, Cittadini G, Mastracci L, Fiocca R (2020) Fibrotic progression and radiologic correlation in matched lung samples from COVID-19 post-mortems. Virchows Arch. https://doi.org/10.1007/s00428-020-02934-1

39.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W (2020) Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395:565–574. https://doi.org/10.1016/S0140-6736(20)30251-8CrossRefPubMedPubMedCentral

40.

van den Brand JM, Smits SL, Haagmans BL (2015) Pathogenesis of Middle East respiratory syndrome coronavirus. J Pathol 235:175–184. https://doi.org/10.1002/path.4458CrossRefPubMed

41.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S (2020) SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 181:271–280 e278. https://doi.org/10.1016/j.cell.2020.02.052CrossRefPubMedPubMedCentral

42.

Lee IT, Nakayama T, Wu CT, Goltsev Y, Jiang S, Gall PA, Liao CK, Shih LC, Schurch CM, McIlwain DR, Chu P, Borchard NA, Zarabanda D, Dholakia SS, Yang A, Kim D, Chen H, Kanie T, Lin CD, Tsai MH, Phillips KM, Kim R, Overdevest JB, Tyler MA, Yan CH, Lin CF, Lin YT, Bau DT, Tsay GJ, Patel ZM, Tsou YA, Tzankov A, Matter MS, Tai CJ, Yeh TH, Hwang PH, Nolan GP, Nayak JV, Jackson PK (2020) ACE2 localizes to the respiratory cilia and is not increased by ACE inhibitors or ARBs. Nat Commun 11:5453. https://doi.org/10.1038/s41467-020-19145-6CrossRefPubMedPubMedCentral

43.

Mossel EC, Wang J, Jeffers S, Edeen KE, Wang S, Cosgrove GP, Funk CJ, Manzer R, Miura TA, Pearson LD, Holmes KV, Mason RJ (2008) SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells. Virology 372:127–135. https://doi.org/10.1016/j.virol.2007.09.045CrossRefPubMed

44.

Skok K, Stelzl E, Trauner M, Kessler HH, Lax SF (2020) Post-mortem viral dynamics and tropism in COVID-19 patients in correlation with organ damage. Virchows Arch. https://doi.org/10.1007/s00428-020-02903-8

45.

Dittmayer C, Meinhardt J, Radbruch H, Radke J, Heppner BI, Heppner FL, Stenzel W, Holland G, Laue M (2020) Why misinterpretation of electron micrographs in SARS-CoV-2-infected tissue goes viral. Lancet 396:e64–e65. https://doi.org/10.1016/S0140-6736(20)32079-1CrossRefPubMedPubMedCentral

46.

Tzankov A, Jonigk D (2020) Unlocking the lockdown of science and demystifying COVID-19: how autopsies contribute to our understanding of a deadly pandemic. Virchows Arch 477:331–333. https://doi.org/10.1007/s00428-020-02887-5CrossRefPubMed

47.

Ko CJ, Harigopal M, Gehlhausen JR, Bosenberg M, McNiff JM, Damsky W (2020) Discordant anti-SARS-CoV-2 spike protein and RNA staining in cutaneous perniotic lesions suggests endothelial deposition of cleaved spike protein. J Cutan Pathol 48:47–52. https://doi.org/10.1111/cup.13866CrossRefPubMed

48.

Szabolcs M, Sauter JL, Frosina D, Geronimo JA, Hernandez E, Selbs E, Rapkiewicz AV, Rekhtman N, Baine MK, Jager E, Travis WD, Jungbluth AA (2021) Identification of immunohistochemical reagents for in situ protein expression analysis of coronavirus-associated changes in human tissues Appl Immunohistochem. Mol Morphol 29:5–12. https://doi.org/10.1097/PAI.0000000000000878CrossRef

49.

Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet 395:1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5CrossRefPubMedPubMedCentral

50.

Walsh KA, Jordan K, Clyne B, Rohde D, Drummond L, Byrne P, Ahern S, Carty PG, O'Brien KK, O'Murchu E, O'Neill M, Smith SM, Ryan M, Harrington P (2020) SARS-CoV-2 detection, viral load and infectivity over the course of an infection. J Inf Secur 81:357–371. https://doi.org/10.1016/j.jinf.2020.06.067CrossRef

51.

Seetulsingh P, Kannangara CI, Richman P (2020) Undetectable SARS-CoV-2 in a nasopharyngeal swab but persistent viral RNA from deep lung swabs: findings from an autopsy. BMJ Case Rep 13. https://doi.org/10.1136/bcr-2020-237446

52.

Rodel J, Egerer R, Suleyman A, Sommer-Schmid B, Baier M, Henke A, Edel B, Loffler B (2020) Use of the variplex SARS-CoV-2 RT-LAMP as a rapid molecular assay to complement RT-PCR for COVID-19 diagnosis. J Clin Virol 132:104616. https://doi.org/10.1016/j.jcv.2020.104616CrossRefPubMedPubMedCentral

53.

Sethuraman N, Jeremiah SS, Ryo A (2020) Interpreting diagnostic tests for SARS-CoV-2. JAMA 323:2249–2251. https://doi.org/10.1001/jama.2020.8259CrossRefPubMed

54.

Dao Thi VL, Herbst K, Boerner K, Meurer M, Kremer LP, Kirrmaier D, Freistaedter A, Papagiannidis D, Galmozzi C, Stanifer ML, Boulant S, Klein S, Chlanda P, Khalid D, Barreto Miranda I, Schnitzler P, Krausslich HG, Knop M, Anders S (2020) A colorimetric RT-LAMP assay and LAMP-sequencing for detecting SARS-CoV-2 RNA in clinical samples. Sci Transl Med 12. https://doi.org/10.1126/scitranslmed.abc7075

55.

Schaefer IM, Padera RF, Solomon IH, Kanjilal S, Hammer MM, Hornick JL, Sholl LM (2020) In situ detection of SARS-CoV-2 in lungs and airways of patients with COVID-19. Mod Pathol 33:2104–2114. https://doi.org/10.1038/s41379-020-0595-zCrossRefPubMed

56.

Magro CM, Mulvey J, Kubiak J, Mikhail S, Suster D, Crowson AN, Laurence J, Nuovo G (2020) Severe COVID-19: a multifaceted viral vasculopathy syndrome. Ann Diagn Pathol 50:151645. https://doi.org/10.1016/j.anndiagpath.2020.151645CrossRefPubMedPubMedCentral

57.

Martines RB, Ritter JM, Matkovic E, Gary J, Bollweg BC, Bullock H, Goldsmith CS, Silva-Flannery L, Seixas JN, Reagan-Steiner S, Uyeki T, Denison A, Bhatnagar J, Shieh WJ, Zaki SR, Group C-PW (2020) Pathology and pathogenesis of SARS-CoV-2 associated with fatal coronavirus disease, United States. Emerg Infect Dis 26:2005–2015. https://doi.org/10.3201/eid2609.202095CrossRefPubMedPubMedCentral

58.

Duarte-Neto AN, Monteiro RAA, da Silva LFF, Malheiros D, de Oliveira EP, Theodoro-Filho J, Pinho JRR, Gomes-Gouvea MS, Salles APM, de Oliveira IRS, Mauad T, Saldiva PHN, Dolhnikoff M (2020) Pulmonary and systemic involvement in COVID-19 patients assessed with ultrasound-guided minimally invasive autopsy. Histopathology 77:186–197. https://doi.org/10.1111/his.14160CrossRefPubMed

59.

Fox SE, Akmatbekov A, Harbert JL, Li G, Quincy Brown J, Vander Heide RS (2020) Pulmonary and cardiac pathology in African American patients with COVID-19: an autopsy series from New Orleans. Lancet Respir Med 8:681–686. https://doi.org/10.1016/S2213-2600(20)30243-5CrossRefPubMedPubMedCentral

60.

Gattinoni L, Chiumello D, Rossi S (2020) COVID-19 pneumonia: ARDS or not? Crit Care 24:154. https://doi.org/10.1186/s13054-020-02880-zCrossRefPubMedPubMedCentral

61.

Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM (2005) A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med 11:875–879. https://doi.org/10.1038/nm1267CrossRefPubMedPubMedCentral

62.

Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM (2005) Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 436:112–116. https://doi.org/10.1038/nature03712CrossRefPubMedPubMedCentral

63.

Iba T, Connors JM, Levy JH (2020) The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res 69:1181–1189. https://doi.org/10.1007/s00011-020-01401-6CrossRefPubMed

64.

Calfee CS, Delucchi K, Parsons PE, Thompson BT, Ware LB, Matthay MA, Network NA (2014) Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med 2:611–620. https://doi.org/10.1016/S2213-2600(14)70097-9CrossRefPubMedPubMedCentral

65.

Kikkert M (2020) Innate immune evasion by human respiratory RNA viruses. J Innate Immun 12:4–20. https://doi.org/10.1159/000503030CrossRefPubMed

66.

Hadjadj J, Yatim N, Barnabei L, Corneau A, Boussier J, Smith N, Pere H, Charbit B, Bondet V, Chenevier-Gobeaux C, Breillat P, Carlier N, Gauzit R, Morbieu C, Pene F, Marin N, Roche N, Szwebel TA, Merkling SH, Treluyer JM, Veyer D, Mouthon L, Blanc C, Tharaux PL, Rozenberg F, Fischer A, Duffy D, Rieux-Laucat F, Kerneis S, Terrier B (2020) Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science 369:718–724. https://doi.org/10.1126/science.abc6027CrossRefPubMedPubMedCentral

67.

Zhang Q, Bastard P, Liu Z, Le Pen J, Moncada-Velez M, Chen J, Ogishi M, Sabli IKD, Hodeib S, Korol C, Rosain J, Bilguvar K, Ye J, Bolze A, Bigio B, Yang R, Arias AA, Zhou Q, Zhang Y, Onodi F, Korniotis S, Karpf L, Philippot Q, Chbihi M, Bonnet-Madin L, Dorgham K, Smith N, Schneider WM, Razooky BS, Hoffmann HH, Michailidis E, Moens L, Han JE, Lorenzo L, Bizien L, Meade P, Neehus AL, Ugurbil AC, Corneau A, Kerner G, Zhang P, Rapaport F, Seeleuthner Y, Manry J, Masson C, Schmitt Y, Schluter A, Le Voyer T, Khan T, Li J, Fellay J, Roussel L, Shahrooei M, Alosaimi MF, Mansouri D, Al-Saud H, Al-Mulla F, Almourfi F, Al-Muhsen SZ, Alsohime F, Al Turki S, Hasanato R, van de Beek D, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Oler AJ, Tompkins MF, Alba C, Vandernoot I, Goffard JC, Smits G, Migeotte I, Haerynck F, Soler-Palacin P, Martin-Nalda A, Colobran R, Morange PE, Keles S, Colkesen F, Ozcelik T, Yasar KK, Senoglu S, Karabela SN, Rodriguez-Gallego C, Novelli G, Hraiech S, Tandjaoui-Lambiotte Y, Duval X, Laouenan C, Clinicians C-S, Clinicians C, Imagine CG, French CCSG, Co VCC, Amsterdam UMCC-B, Effort CHG, Group N-UTCI, Snow AL, Dalgard CL, Milner JD, Vinh DC, Mogensen TH, Marr N, Spaan AN, Boisson B, Boisson-Dupuis S, Bustamante J, Puel A, Ciancanelli MJ, Meyts I, Maniatis T, Soumelis V, Amara A, Nussenzweig M, Garcia-Sastre A, Krammer F, Pujol A, Duffy D, Lifton RP, Zhang SY, Gorochov G, Beziat V, Jouanguy E, Sancho-Shimizu V, Rice CM, Abel L, Notarangelo LD, Cobat A, Su HC, Casanova JL (2020) Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science 370. https://doi.org/10.1126/science.abd4570

68.

Lupu L, Palmer A, Huber-Lang M (2020) Inflammation, thrombosis, and destruction: the three-headed cerberus of trauma- and SARS-CoV-2-induced ARDS. Front Immunol 11:584514. https://doi.org/10.3389/fimmu.2020.584514CrossRefPubMedPubMedCentral

69.

Vestweber D, Winderlich M, Cagna G, Nottebaum AF (2009) Cell adhesion dynamics at endothelial junctions: VE-cadherin as a major player Trends. Cell Biol 19:8–15. https://doi.org/10.1016/j.tcb.2008.10.001CrossRef

70.

Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG, Calfee CS (2019) Acute respiratory distress syndrome. Nat Rev Dis Primers 5:18. https://doi.org/10.1038/s41572-019-0069-0CrossRefPubMedPubMedCentral

71.

Vadasz I, Raviv S, Sznajder JI (2007) Alveolar epithelium and Na,K-ATPase in acute lung injury. Intensive Care Med 33:1243–1251. https://doi.org/10.1007/s00134-007-0661-8CrossRefPubMedPubMedCentral

72.

Islam A, Khan MA (2020) Lung transcriptome of a COVID-19 patient and systems biology predictions suggest impaired surfactant production which may be druggable by surfactant therapy. Sci Rep 10:19395. https://doi.org/10.1038/s41598-020-76404-8CrossRefPubMedPubMedCentral

73.

Maneta-Peyret L, Kitsiouli E, Lekka M, Nakos G, Cassagne C (2001) Autoantibodies to lipids in bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome. Crit Care Med 29:1950–1954. https://doi.org/10.1097/00003246-200110000-00017CrossRefPubMed

74.

Uthman IW, Gharavi AE (2002) Viral infections and antiphospholipid antibodies. Semin Arthritis Rheum 31:256–263. https://doi.org/10.1053/sarh.2002.28303CrossRefPubMed

75.

Borghi MO, Beltagy A, Garrafa E, Curreli D, Cecchini G, Bodio C, Grossi C, Blengino S, Tincani A, Franceschini F, Andreoli L, Lazzaroni MG, Piantoni S, Masneri S, Crisafulli F, Brugnoni D, Muiesan ML, Salvetti M, Parati G, Torresani E, Mahler M, Heilbron F, Pregnolato F, Pengo M, Tedesco F, Pozzi N, Meroni PL (2020) Anti-phospholipid antibodies in COVID-19 are different from those detectable in the anti-phospholipid syndrome. Front Immunol 11:584241. https://doi.org/10.3389/fimmu.2020.584241CrossRefPubMedPubMedCentral

76.

Zhang Y, Xiao M, Zhang S, Xia P, Cao W, Jiang W, Chen H, Ding X, Zhao H, Zhang H, Wang C, Zhao J, Sun X, Tian R, Wu W, Wu D, Ma J, Chen Y, Zhang D, Xie J, Yan X, Zhou X, Liu Z, Wang J, Du B, Qin Y, Gao P, Qin X, Xu Y, Zhang W, Li T, Zhang F, Zhao Y, Li Y, Zhang S (2020) Coagulopathy and antiphospholipid antibodies in patients with COVID-19. N Engl J Med 382:e38. https://doi.org/10.1056/NEJMc2007575CrossRefPubMed

77.

Streetley J, Fonseca AV, Turner J, Kiskin NI, Knipe L, Rosenthal PB, Carter T (2019) Stimulated release of intraluminal vesicles from Weibel-Palade bodies. Blood 133:2707–2717. https://doi.org/10.1182/blood-2018-09-874552CrossRefPubMedPubMedCentral

78.

Higgins SJ, De Ceunynck K, Kellum JA, Chen X, Gu X, Chaudhry SA, Schulman S, Libermann TA, Lu S, Shapiro NI, Christiani DC, Flaumenhaft R, Parikh SM (2018) Tie2 protects the vasculature against thrombus formation in systemic inflammation. J Clin Invest 128:1471–1484. https://doi.org/10.1172/JCI97488CrossRefPubMedPubMedCentral

79.

Parikh SM, Mammoto T, Schultz A, Yuan HT, Christiani D, Karumanchi SA, Sukhatme VP (2006) Excess circulating angiopoietin-2 may contribute to pulmonary vascular leak in sepsis in humans. PLoS Med 3:e46. https://doi.org/10.1371/journal.pmed.0030046CrossRefPubMedPubMedCentral

80.

Smadja DM, Guerin CL, Chocron R, Yatim N, Boussier J, Gendron N, Khider L, Hadjadj J, Goudot G, Debuc B, Juvin P, Hauw-Berlemont C, Augy JL, Peron N, Messas E, Planquette B, Sanchez O, Charbit B, Gaussem P, Duffy D, Terrier B, Mirault T, Diehl JL (2020) Angiopoietin-2 as a marker of endothelial activation is a good predictor factor for intensive care unit admission of COVID-19 patients. Angiogenesis 23:611–620. https://doi.org/10.1007/s10456-020-09730-0CrossRefPubMed

81.

Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, Merdji H, Clere-Jehl R, Schenck M, Fagot Gandet F, Fafi-Kremer S, Castelain V, Schneider F, Grunebaum L, Angles-Cano E, Sattler L, Mertes PM, Meziani F, Group CT (2020) High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study Intensive. Care Med 46:1089–1098. https://doi.org/10.1007/s00134-020-06062-xCrossRef

82.

Severe Covid GG, Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, Fernandez J, Prati D, Baselli G, Asselta R, Grimsrud MM, Milani C, Aziz F, Kassens J, May S, Wendorff M, Wienbrandt L, Uellendahl-Werth F, Zheng T, Yi X, de Pablo R, Chercoles AG, Palom A, Garcia-Fernandez AE, Rodriguez-Frias F, Zanella A, Bandera A, Protti A, Aghemo A, Lleo A, Biondi A, Caballero-Garralda A, Gori A, Tanck A, Carreras Nolla A, Latiano A, Fracanzani AL, Peschuck A, Julia A, Pesenti A, Voza A, Jimenez D, Mateos B, Nafria Jimenez B, Quereda C, Paccapelo C, Gassner C, Angelini C, Cea C, Solier A, Pestana D, Muniz-Diaz E, Sandoval E, Paraboschi EM, Navas E, Garcia Sanchez F, Ceriotti F, Martinelli-Boneschi F, Peyvandi F, Blasi F, Tellez L, Blanco-Grau A, Hemmrich-Stanisak G, Grasselli G, Costantino G, Cardamone G, Foti G, Aneli S, Kurihara H, ElAbd H, My I, Galvan-Femenia I, Martin J, Erdmann J, Ferrusquia-Acosta J, Garcia-Etxebarria K, Izquierdo-Sanchez L, Bettini LR, Sumoy L, Terranova L, Moreira L, Santoro L, Scudeller L, Mesonero F, Roade L, Ruhlemann MC, Schaefer M, Carrabba M, Riveiro-Barciela M, Figuera Basso ME, Valsecchi MG, Hernandez-Tejero M, Acosta-Herrera M, D'Angio M, Baldini M, Cazzaniga M, Schulzky M, Cecconi M, Wittig M, Ciccarelli M, Rodriguez-Gandia M, Bocciolone M, Miozzo M, Montano N, Braun N, Sacchi N, Martinez N, Ozer O, Palmieri O, Faverio P, Preatoni P, Bonfanti P, Omodei P, Tentorio P, Castro P, Rodrigues PM, Blandino Ortiz A, de Cid R, Ferrer R, Gualtierotti R, Nieto R, Goerg S, Badalamenti S, Marsal S, Matullo G, Pelusi S, Juzenas S, Aliberti S, Monzani V, Moreno V, Wesse T, Lenz TL, Pumarola T, Rimoldi V, Bosari S, Albrecht W, Peter W, Romero-Gomez M, D'Amato M, Duga S, Banales JM, Hov JR, Folseraas T, Valenti L, Franke A, Karlsen TH (2020) Genomewide association study of severe COVID-19 with respiratory failure. N Engl J Med 383:1522–1534. https://doi.org/10.1056/NEJMoa2020283CrossRef

83.

Klok FA, Kruip M, van der Meer NJM, Arbous MS, Gommers D, Kant KM, Kaptein FHJ, van Paassen J, Stals MAM, Huisman MV, Endeman H (2020) Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thromb Res 191:148–150. https://doi.org/10.1016/j.thromres.2020.04.041CrossRefPubMedPubMedCentral

84.

Guan SP, Seet RCS, Kennedy BK (2020) Does eNOS derived nitric oxide protect the young from severe COVID-19 complications? Ageing Res Rev 64:101201. https://doi.org/10.1016/j.arr.2020.101201CrossRefPubMedPubMedCentral

85.

Libby P, Luscher T (2020) COVID-19 is, in the end, an endothelial disease. Eur Heart J 41:3038–3044. https://doi.org/10.1093/eurheartj/ehaa623CrossRefPubMedPubMedCentral

86.

Komorowski M, Aberegg SK (2020) Using applied lung physiology to understand COVID-19 patterns. Br J Anaesth 125:250–253. https://doi.org/10.1016/j.bja.2020.05.019CrossRefPubMedPubMedCentral

87.

Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J (2020) Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res 220:1–13. https://doi.org/10.1016/j.trsl.2020.04.007CrossRefPubMedPubMedCentral

88.

Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, Whitmore A, Heise MT, Baric RS (2018) Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio 9. https://doi.org/10.1128/mBio.01753-18

89.

Zilow G, Joka T, Obertacke U, Rother U, Kirschfink M (1992) Generation of anaphylatoxin C3a in plasma and bronchoalveolar lavage fluid in trauma patients at risk for the adult respiratory distress syndrome. Crit Care Med 20:468–473. https://doi.org/10.1097/00003246-199204000-00006CrossRefPubMed

90.

Hoth JJ, Wells JD, Jones SE, Yoza BK, McCall CE (2014) Complement mediates a primed inflammatory response after traumatic lung injury. J Trauma Acute Care Surg 76:601–608; discussion 608-609. https://doi.org/10.1097/TA.0000000000000129CrossRefPubMedPubMedCentral

91.

Lisman T (2018) Platelet-neutrophil interactions as drivers of inflammatory and thrombotic disease. Cell Tissue Res 371:567–576. https://doi.org/10.1007/s00441-017-2727-4CrossRefPubMed

92.

Sorensen OE, Borregaard N (2016) Neutrophil extracellular traps - the dark side of neutrophils. J Clin Invest 126:1612–1620. https://doi.org/10.1172/JCI84538CrossRefPubMedPubMedCentral

93.

Porto BN, Stein RT (2016) Neutrophil extracellular traps in pulmonary diseases: too much of a good thing? Front Immunol 7:311. https://doi.org/10.3389/fimmu.2016.00311CrossRefPubMedPubMedCentral

94.

Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair C, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS (2020) Neutrophil extracellular traps (NETs) as markers of disease severity in COVID-19. medRxiv. https://doi.org/10.1101/2020.04.09.20059626

95.

Middleton EA, He XY, Denorme F, Campbell RA, Ng D, Salvatore SP, Mostyka M, Baxter-Stoltzfus A, Borczuk AC, Loda M, Cody MJ, Manne BK, Portier I, Harris ES, Petrey AC, Beswick EJ, Caulin AF, Iovino A, Abegglen LM, Weyrich AS, Rondina MT, Egeblad M, Schiffman JD, Yost CC (2020) Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood 136:1169–1179. https://doi.org/10.1182/blood.2020007008CrossRefPubMedPubMedCentral

96.

Folco EJ, Mawson TL, Vromman A, Bernardes-Souza B, Franck G, Persson O, Nakamura M, Newton G, Luscinskas FW, Libby P (2018) Neutrophil extracellular traps induce endothelial cell activation and tissue factor production through interleukin-1alpha and cathepsin G. Arterioscler Thromb Vasc Biol 38:1901–1912. https://doi.org/10.1161/ATVBAHA.118.311150CrossRefPubMedPubMedCentral

97.

Teuwen LA, Geldhof V, Pasut A, Carmeliet P (2020) COVID-19: the vasculature unleashed. Nat Rev Immunol 20:389–391. https://doi.org/10.1038/s41577-020-0343-0CrossRefPubMed

98.

Roschewski M, Lionakis MS, Sharman JP, Roswarski J, Goy A, Monticelli MA, Roshon M, Wrzesinski SH, Desai JV, Zarakas MA, Collen J, Rose K, Hamdy A, Izumi R, Wright GW, Chung KK, Baselga J, Staudt LM, Wilson WH (2020) Inhibition of Bruton tyrosine kinase in patients with severe COVID-19. Sci Immunol 5. https://doi.org/10.1126/sciimmunol.abd0110

99.

Herold S, Mayer K, Lohmeyer J (2011) Acute lung injury: how macrophages orchestrate resolution of inflammation and tissue repair. Front Immunol 2:65. https://doi.org/10.3389/fimmu.2011.00065CrossRefPubMedPubMedCentral

100.

Huang X, Xiu H, Zhang S, Zhang G (2018) The role of macrophages in the pathogenesis of ALI/ARDS. Mediat Inflamm 2018:1264913–1264918. https://doi.org/10.1155/2018/1264913CrossRef

101.

Liao M, Liu Y, Yuan J, Wen Y, Xu G, Zhao J, Cheng L, Li J, Wang X, Wang F, Liu L, Amit I, Zhang S, Zhang Z (2020) Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med 26:842–844. https://doi.org/10.1038/s41591-020-0901-9CrossRefPubMed

102.

Zhang D, Guo R, Lei L, Liu H, Wang Y, Wang Y, Qian H, Dai T, Zhang T, Lai Y, Wang J, Liu Z, Chen T, He A, O'Dwyer M, Hu J (2020) COVID-19 infection induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes. J Leukoc Biol 109:13–22. https://doi.org/10.1002/JLB.4HI0720-470RCrossRefPubMed

103.

Merad M, Martin JC (2020) Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol 20:355–362. https://doi.org/10.1038/s41577-020-0331-4CrossRefPubMed

104.

Quan C, Li C, Ma H, Li Y, Zhang H (2020) Immunopathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS): potential infection-associated hemophagocytic lymphohistiocytosis. Clin Microbiol Rev 34. https://doi.org/10.1128/CMR.00074-20

105.

Prilutskiy A, Kritselis M, Shevtsov A, Yambayev I, Vadlamudi C, Zhao Q, Kataria Y, Sarosiek SR, Lerner A, Sloan JM, Quillen K, Burks EJ (2020) SARS-CoV-2 infection-associated hemophagocytic lymphohistiocytosis. Am J Clin Pathol 154:466–474. https://doi.org/10.1093/ajcp/aqaa124CrossRefPubMed

106.

Haslbauer JD, Perrina V, Matter M, Dellas A, Mihatsch MJ, Tzankov A (2020) Retrospective post-mortem SARS-CoV-2 RT-PCR of autopsies with COVID-19-suggestive pathology supports the absence of lethal community spread in Basel, Switzerland, before February 2020. Pathobiology:1–11. https://doi.org/10.1159/000512563

107.

McGonagle D, Sharif K, O'Regan A, Bridgewood C (2020) The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev 19:102537. https://doi.org/10.1016/j.autrev.2020.102537CrossRefPubMedPubMedCentral

108.

Channappanavar R, Perlman S (2017) Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 39:529–539. https://doi.org/10.1007/s00281-017-0629-xCrossRefPubMedPubMedCentral

109.

Mehta AK, Gracias DT, Croft M (2018) TNF activity and T cells. Cytokine 101:14–18. https://doi.org/10.1016/j.cyto.2016.08.003CrossRefPubMed

110.

Trotta T, Di Gioia S, Piro D, Lepore S, Cantatore S, Porro C, Castellani S, Petrella A, Fortunato F, Maffione AB, Conese M (2013) Effect of acute lung injury on VLA-4 and CXCR4 expression in resident and circulating hematopoietic stem/progenitor cells. Respiration 85:252–264. https://doi.org/10.1159/000341172CrossRefPubMed

111.

Salvucci O, Basik M, Yao L, Bianchi R, Tosato G (2004) Evidence for the involvement of SDF-1 and CXCR4 in the disruption of endothelial cell-branching morphogenesis and angiogenesis by TNF-alpha and IFN-gamma. J Leukoc Biol 76:217–226. https://doi.org/10.1189/jlb.1203609CrossRefPubMed

112.

Ackermann M, Mentzer SJ, Kolb M, Jonigk D (2020) Inflammation and intussusceptive angiogenesis in COVID-19: everything in and out of flow. Eur Respir J 56:2003147. https://doi.org/10.1183/13993003.03147-2020CrossRefPubMedPubMedCentral

113.

Lee GS, Filipovic N, Miele LF, Lin M, Simpson DC, Giney B, Konerding MA, Tsuda A, Mentzer SJ (2010) Blood flow shapes intravascular pillar geometry in the chick chorioallantoic membrane. J Angiogenes Res 2:11. https://doi.org/10.1186/2040-2384-2-11CrossRefPubMedPubMedCentral

114.

von Stillfried S, Bulow RD, Rohrig R, Knuchel-Clarke R, Boor P, DeRegCovid (2020) Autopsy registry can facilitate COVID-19 research EMBO Mol Med 12:e12885. 10.15252/emmm.202012885

Title: The pulmonary pathology of COVID-19
Authors: Hans Bösmüller
Matthias Matter
Falko Fend
Alexandar Tzankov
Publication date: 01-01-2021
Publisher: Springer Berlin Heidelberg
Keywords: Autopsy
SARS-CoV-2
Acute Respiratory Distress-Syndrome
COVID-19
Pathology
Published in: Virchows Archiv / Issue 1/2021
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-021-03053-1

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Springer Medicine

The pulmonary pathology of COVID-19

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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