Human-Based Advanced in vitro Approaches to Investigate Lung Fibrosis and Pulmonary Effects of COVID-19

Mirjam Kiener1,2,3, Nuria Roldán1, Carlos Machahua4,3, Arunima Sengupta5, Thomas Geiser4,3, Olivier T. Guenat6,3,5, Manuela Funke-Chambour4,3, Nina Hobi1, Marianna Kruithof‐de Julio1,2,7
1Alveolix AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland
2Department for BioMedical Research DBMR, Urology Research Laboratory, University of Bern, Bern, Switzerland
3Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
4Department for BioMedical Research DBMR, Department of Pulmonary Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
5Organs-on-Chip Technologies, ARTORG Center for Biomedical Engineering, University of Bern, Bern, Switzerland
6Department of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
7Organoid Core, Department for BioMedical Research, University of Bern, Bern, Switzerland

Tóm tắt

The coronavirus disease 2019 (COVID-19) pandemic has caused considerable socio-economic burden, which fueled the development of treatment strategies and vaccines at an unprecedented speed. However, our knowledge on disease recovery is sparse and concerns about long-term pulmonary impairments are increasing. Causing a broad spectrum of symptoms, COVID-19 can manifest as acute respiratory distress syndrome (ARDS) in the most severely affected patients. Notably, pulmonary infection with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the causing agent of COVID-19, induces diffuse alveolar damage (DAD) followed by fibrotic remodeling and persistent reduced oxygenation in some patients. It is currently not known whether tissue scaring fully resolves or progresses to interstitial pulmonary fibrosis. The most aggressive form of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF). IPF is a fatal disease that progressively destroys alveolar architecture by uncontrolled fibroblast proliferation and the deposition of collagen and extracellular matrix (ECM) proteins. It is assumed that micro-injuries to the alveolar epithelium may be induced by inhalation of micro-particles, pathophysiological mechanical stress or viral infections, which can result in abnormal wound healing response. However, the exact underlying causes and molecular mechanisms of lung fibrosis are poorly understood due to the limited availability of clinically relevant models. Recently, the emergence of SARS-CoV-2 with the urgent need to investigate its pathogenesis and address drug options, has led to the broad application ofin vivoandin vitromodels to study lung diseases. In particular, advancedin vitromodels including precision-cut lung slices (PCLS), lung organoids, 3Din vitrotissues and lung-on-chip (LOC) models have been successfully employed for drug screens. In order to gain a deeper understanding of SARS-CoV-2 infection and ultimately alveolar tissue regeneration, it will be crucial to optimize the available models for SARS-CoV-2 infection in multicellular systems that recapitulate tissue regeneration and fibrotic remodeling. Current evidence for SARS-CoV-2 mediated pulmonary fibrosis and a selection of classical and novel lung models will be discussed in this review.

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Tài liệu tham khảo

Fung, 2019, Human coronavirus: host-pathogen interaction, Annu Rev Microbiol., 73, 529, 10.1146/annurev-micro-020518-115759

Li, 2020, Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia, N Engl J Med., 382, 1199, 10.1056/nejmoa2001316

Huang, 2020, Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet, 395, 497, 10.1016/S0140-6736(20)30183-5

Wang, 2020, Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China, JAMA J Am Med Assoc, 323, 1061, 10.1001/jama.2020.1585

2020, Global Economic Prospects, June 2020

Gibson, 2020, COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS, Med J Aust, 213, 54, 10.5694/mja2.50674

Krammer, 2020, SARS-CoV-2 vaccines in development, Nature., 586, 516, 10.1038/s41586-020-2798-3

Kandimalla, 2020, Current status of multiple drug molecules, and vaccines: an update in SARS-CoV-2 therapeutics, Mol Neurobiol., 57, 4106, 10.1007/s12035-020-02022-0

Sanders, 2020, Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review, JAMA J Am Med Assoc., 323, 1824, 10.1001/jama.2020.6019

Han, 2021, Identification of SARS-CoV-2 inhibitors using lung and colonic organoids, Nature, 589, 270, 10.1038/s41586-020-2901-9

Hoffmann, 2020, SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor, Cell, 181, 271, 10.1016/j.cell.2020.02.052

Holwerda, 2020, Identification of an antiviral compound from the pandemic response box that efficiently inhibits sars-cov-2 infection in vitro, Microorganisms., 8, 1, 10.3390/microorganisms8121872

Mulay, 2021, SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery, Cell Rep., 109055, 10.1016/j.celrep.2021.109055

Pizzorno, 2020, Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia, Cell Rep Med., 1, 100059, 10.1016/j.xcrm.2020.100059

Suzuki, 2020, Generation of human bronchial organoids for SARS-CoV-2 research, bioRxiv [Preprint]., 10.1101/2020.05.25.115600

George, 2020, Pulmonary fibrosis and COVID-19: the potential role for antifibrotic therapy, Lancet Respir. Med., 8, 807, 10.1016/S2213-2600(20)30225-3

Guler, 2021, Pulmonary function and radiological features four months after COVID-19: first results from the national prospective observational Swiss COVID-19 lung study, Eur Respir J., 2003690, 10.1183/13993003.03690-2020

Kotton, 2014, Lung regeneration: mechanisms, applications and emerging stem cell populations, Nat Med., 20, 822, 10.1038/nm.3642

Schneider, 2019, On the topological complexity of human alveolar epithelial type 1 cells, Am J Respir Crit Care Med., 199, 1153, 10.1164/rccm.201810-1866LE

Weibel, 2015, On the tricks alveolar epithelial cells play to make a good lung, Am J Respir Crit Care Med., 191, 504, 10.1164/rccm.201409-1663OE

Cañadas, 2020, Lipid-protein protein-protein interactions in the pulmonary surfactant system their role in lung homeostasis, Int J Mol Sci., 21, 3708, 10.3390/ijms21103708

Olajuyin, 2019, Alveolar type 2 progenitor cells for lung injury repair, Cell Death Discov., 5, 63, 10.1038/s41420-019-0147-9

Mason, 1977, Type II alveolar cell. Defender of the alveolus, Am Rev Respir Dis., 115, 81, 10.1164/arrd.1977.115.S.81

Beers, 2017, When is an alveolar type 2 cell an alveolar type 2 cell? A conundrum for lung stem cell biology and regenerative medicine, Am J Respir Cell Mol Biol., 57, 18, 10.1165/rcmb.2016-0426PS

Barkauskas, 2013, Type 2 alveolar cells are stem cells in adult lung, J Clin Invest., 123, 3025, 10.1172/JCI68782

Zacharias, 2018, Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor, Nature., 555, 251, 10.1038/nature25786

Jain, 2015, Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung, Nat Commun., 6, 6727, 10.1038/ncomms7727

de Mello Costa, 2020, Basal-like progenitor cells: a review of dysplastic alveolar regeneration and remodeling in lung repair, Stem Cell Reports., 15, 1015, 10.1016/j.stemcr.2020.09.006

Wang, 2020, EpCAM+CD73+ mark epithelial progenitor cells in postnatal human lung and are associated with pathogenesis of pulmonary disease including lung adenocarcinoma, Am J Physiol Lung Cell Mol Physiol, 319, L794, 10.1152/AJPLUNG.00279.2019

Hegab, 2015, Mimicking the niche of lung epithelial stem cells and characterization of several effectors of their in vitro behavior, Stem Cell Res., 15, 109, 10.1016/j.scr.2015.05.005

Nabhan, 2018, Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells, Science., 359, 1118, 10.1126/science.aam6603

Klingberg, 2013, The myofibroblast matrix: implications for tissue repair and fibrosis, J Pathol., 229, 298, 10.1002/path.4104

Crosby, 2010, Epithelial repair mechanisms in the lung, Am J Physiol Lung Cell Mol Physiol., 298, L715, 10.1152/ajplung.00361.2009

Wynn, 2016, Macrophages in tissue repair, regeneration, and fibrosis, Immunity., 44, 450, 10.1016/j.immuni.2016.02.015

Raslan, 2020, WNT signaling in lung repair and regeneration, Mol Cells., 43, 774, 10.14348/molcells.2020.0059

Sisson, 2010, Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis, Am J Respir Crit Care Med., 181, 254, 10.1164/rccm.200810-1615OC

Piñeiro-Hermida, 2020, Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging, J Cell Biol., 219, 1, 10.1083/jcb.202002120

Waters, 2012, Mechanobiology in lung epithelial cells: measurements, perturbations, and responses, Compr Physiol., 2, 1, 10.1002/cphy.c100090

Ashino, 2000, [Ca(2+)](i) oscillations regulate type II cell exocytosis in the pulmonary alveolus, Am J Physiol Lung Cell Mol Physiol., 279, L5, 10.1152/ajplung.2000.279.1.L5

Dietl, 2001, Mechanisms of surfactant exocytosis in alveolar type II cells in vitro and in vivo, News Physiol Sci, 16, 239, 10.1152/physiologyonline.2001.16.5.239

Edwards, 2001, Stretch stimulation: its effects on alveolar type II cell function in the lung, Comp Biochem Physiol A Mol Integr Physiol., 129, 245, 10.1016/s1095-6433(01)00321-x

Gil, 1979, Alveolar volume-surface area relation in air- and saline-filled lungs fixed by vascular perfusion, J Appl Physiol., 47, 990, 10.1152/jappl.1979.47.5.990

Mercer, 1987, Three-dimensional reconstruction of alveoli in the rat lung for pressure-volume relationships, J Appl Physiol., 62, 1480, 10.1152/jappl.1987.62.4.1480

Tschumperlin, 1999, Alveolar epithelial surface area-volume relationship in isolated rat lungs, J Appl Physiol., 86, 2026, 10.1152/jappl.1999.86.6.2026

Knudsen, 2018, The micromechanics of lung alveoli: structure and function of surfactant and tissue components, Histochem Cell Biol., 150, 661, 10.1007/s00418-018-1747-9

Fredberg, 2006, Stress transmission in the lung: pathways from organ to molecule, Annu Rev Physiol., 68, 507, 10.1146/annurev.physiol.68.072304.114110

Desai, 2008, Mechanical stretch decreases migration of alveolar epithelial cells through mechanisms involving Rac1 and Tiam1, Am J Physiol Lung Cell Mol Physiol., 295, L958, 10.1152/ajplung.90218.2008

Crosby, 2011, Balance of life and death in alveolar epithelial type II cells: proliferation, apoptosis, and the effects of cyclic stretch on wound healing, Am J Physiol Lung Cell Mol Physiol., 301, L536, 10.1152/ajplung.00371.2010

Ito, 2014, Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling, Am J Physiol Lung Cell Mol Physiol., 307, L94, 10.1152/ajplung.00233.2013

Felder, 2019, Impaired wound healing of alveolar lung epithelial cells in a breathing lung-on-a-chip, Front Bioeng Biotechnol., 7, 3, 10.3389/fbioe.2019.00003

van Riet, 2020, In vitro modelling of alveolar repair at the air-liquid interface using alveolar epithelial cells derived from human induced pluripotent stem cells, Sci Rep., 10, 5499, 10.1038/s41598-020-62226-1

Oeckler, 2007, Ventilator-associated lung injury: a search for better therapeutic targets, Eur Respir J, 30, 1216, 10.1183/09031936.00104907

Rocco, 2020, What have we learned from animal models of ventilator-induced lung injury?, Intensive Care Med., 46, 2377, 10.1007/s00134-020-06143-x

Sehlmeyer, 2020, Alveolar dynamics and beyond - the importance of surfactant protein c and cholesterol in lung homeostasis and fibrosis, Front Physiol., 11, 386, 10.3389/fphys.2020.00386

Lentz, 2020, Initial emergency department mechanical ventilation strategies for COVID-19 hypoxemic respiratory failure and ARDS, Am J Emerg Med., 38, 2194, 10.1016/j.ajem.2020.06.082

Ravasio, 2011, Interfacial sensing by alveolar type II cells: a new concept in lung physiology?, Am J Physiol Physiol., 300, C1456, 10.1152/ajpcell.00427.2010

Hobi, 2012, Interfacial stress affects rat alveolar type II cell signaling and gene expression, Am J Physiol Cell Mol Physiol., 303, L117, 10.1152/ajplung.00340.2011

Doyle, 2000, Composition of alveolar surfactant changes with training in humans, Respirology., 5, 211, 10.1046/j.1440-1843.2000.00251.x

Orgeig, 2015, Evolution, development, and function of the pulmonary surfactant system in normal and perturbed environments, Compr Physiol., 6, 363, 10.1002/cphy.c150003

Pastrana-Rios, 1994, A direct test of the “squeeze-out” hypothesis of lung surfactant function. External reflection FT-IR at the air/wave interface, Biochemistry., 33, 5121, 10.1021/bi00183a016

Nag, 1999, SP-B refining of pulmonary surfactant phospholipid films, Am J Physiol Cell Mol Physiol., 277, L1179, 10.1152/ajplung.1999.277.6.L1179

Hobi, 2016, A small key unlocks a heavy door: the essential function of the small hydrophobic proteins SP-B and SP-C to trigger adsorption of pulmonary surfactant lamellar bodies, Biochim Biophys Acta Mol Cell Res., 1863, 2124, 10.1016/j.bbamcr.2016.04.028

Roldan, 2016, Effect of lung surfactant protein SP-C and SP-C-promoted membrane fragmentation on cholesterol dynamics, Biophys J, 111, 1703, 10.1016/j.bpj.2016.09.016

Roldan, 2017, Divide andamp; conquer: surfactant protein SP-C and cholesterol modulate phase segregation in lung surfactant, Biophys J, 113, 847, 10.1016/j.bpj.2017.06.059

Günther, 1999, Surfactant abnormalities in idiopathic pulmonary fibrosis, hypersensitivity pneumonitis and sarcoidosis, Eur Respir J, 14, 565, 10.1034/j.1399-3003.1999.14c14.x

Schmidt, 2001, Alteration of fatty acid profiles in different pulmonary surfactant phospholipids in acute respiratory distress syndrome and severe pneumonia, Am J Respir Crit Care Med., 163, 95, 10.1164/ajrccm.163.1.9903029

Hobi, 2014, Physiological variables affecting surface film formation by native lamellar body-like pulmonary surfactant particles, Biochim Biophys Acta Biomembr., 1838, 1842, 10.1016/j.bbamem.2014.02.015

Li, 2016, Structure, function, and evolution of coronavirus spike proteins, Annu Rev Virol., 3, 237, 10.1146/annurev-virology-110615-042301

Ou, 2020, Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV, Nat Commun., 11, 1620, 10.1038/s41467-020-15562-9

Shang, 2020, Cell entry mechanisms of SARS-CoV-2, Proc Natl Acad Sci USA., 117, 11727, 10.1073/pnas.2003138117

Walls, 2020, Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein, Cell., 181, 281, 10.1016/j.cell.2020.02.058

Wrapp, 2020, Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation, Science., 367, 1260, 10.1126/science.abb2507

Letko, 2020, Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses, Nat Microbiol., 5, 562, 10.1038/s41564-020-0688-y

Zhou, 2020, A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature., 579, 270, 10.1038/s41586-020-2012-7

Millet, 2015, Host cell proteases: critical determinants of coronavirus tropism and pathogenesis, Virus Res., 202, 120, 10.1016/j.virusres.2014.11.021

Simmons, 2005, Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry, Proc Natl Acad Sci USA, 102, 11876, 10.1073/pnas.0505577102

Matsuyama, 2010, Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2, J Virol., 84, 12658, 10.1128/JVI.01542-10

Glowacka, 2011, Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response, J Virol., 85, 4122, 10.1128/JVI.02232-10

Shulla, 2011, A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry, J Virol., 85, 873, 10.1128/JVI.02062-10

Shirato, 2013, Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2, J Virol., 87, 12552, 10.1128/JVI.01890-13

Millet, 2014, Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein, Proc. Natl. Acad. Sci. USA, 111, 15214, 10.1073/pnas.1407087111

Hou, 2020, SARS-CoV-2 reverse genetics reveals a variable infection gradient in the respiratory tract, Cell., 182, 429, 10.1016/j.cell.2020.05.042

Sungnak, 2020, SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes, Nat Med., 26, 681, 10.1038/s41591-020-0868-6

Zou, 2020, Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection, Front Med., 14, 185, 10.1007/s11684-020-0754-0

Muus, 2021, Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics, Nat Med., 27, 546, 10.1038/s41591-020-01227-z

Pan, 2020, Viral load of SARS-CoV-2 in clinical samples, Lancet Infect Dis., 20, 411, 10.1016/S1473-3099(20)30113-4

Wang, 2020, Detection of SARS-CoV-2 in different types of clinical specimens, JAMA, 323, 1843, 10.1001/jama.2020.3786

Zhang, 2020, Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes, Emerg Microbes Infect, 9, 386, 10.1080/22221751.2020.1729071

Martines, 2020, Pathology and pathogenesis of SARS-CoV-2 associated with fatal coronavirus disease, United States, Emerg Infect Dis., 26, 2005, 10.3201/eid2609.202095

Wölfel, 2020, Virological assessment of hospitalized patients with COVID-2019, Nature., 581, 465, 10.1038/s41586-020-2196-x

Zeng, 2020, Pulmonary pathology of early-phase COVID-19 pneumonia in a patient with a benign lung lesion, Histopathology., 77, 823, 10.1111/his.14138

Lukassen, 2020, SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells, EMBO J., 39, e105114, 10.15252/embj.20105114

Lamers, 2020, SARS-CoV-2 productively infects human gut enterocytes, Science., 369, 50, 10.1126/science.abc1669

Ravindra, 2020, Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium, bioRxiv., 1, 10.1101/2020.05.06.081695

Salahudeen, 2020, Progenitor identification and SARS-CoV-2 infection in long-term human distal lung organoid cultures, bioRxiv., 10.1101/2020.07.27.212076

Ziegler, 2020, SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues, Cell., 181, 1016, 10.1016/j.cell.2020.04.035

Blanco-Melo, 2020, Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19, Cell., 181, 1036, 10.1016/j.cell.2020.04.026

Bussani, 2020, Persistence of viral RNA, pneumocyte syncytia and thrombosis are hallmarks of advanced COVID-19 pathology, EBioMedicine., 61, 103104, 10.1016/j.ebiom.2020.103104

Thacker, 2020, Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model, bioRxiv [Preprint], 10.1101/2020.08.10.243220

Tindle, 2020, Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19, bioRxiv Prepr. Serv. Biol., 10.1101/2020.10.17.344002

Youk, 2020, Three-dimensional human alveolar stem cell culture models reveal infection response to SARS-CoV-2, Cell Stem Cell., 27, 905, 10.1016/j.stem.2020.10.004

Huang, 2020, SARS-CoV-2 infection of pluripotent stem cell-derived human lung alveolar type 2 cells elicits a rapid epithelial-intrinsic inflammatory response, Cell Stem Cell, 27, 962, 10.1016/j.stem.2020.09.013

Katsura, 2020, Human lung stem cell-based alveolospheres provide insights into SARS-CoV-2-mediated interferon responses and pneumocyte dysfunction, Cell Stem Cell., 27, 890, 10.1016/j.stem.2020.10.005

Andersen, 2020, The proximal origin of SARS-CoV-2, Nat. Med., 26, 450, 10.1038/s41591-020-0820-9

Hoffmann, 2020, A multibasic cleavage site in the spike protein of SARS-CoV-2 is essential for infection of human lung cells, Mol Cell, 78, 779, 10.1016/j.molcel.2020.04.022

Daly, 2020, Neuropilin-1 is a host factor for SARS-CoV-2 infection, Science., 370, 861, 10.1126/science.abd3072

Lau, 2020, Attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction, Emerg Microbes Infect., 9, 837, 10.1080/22221751.2020.1756700

Ackermann, 2020, Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in covid-19, N Engl J Med., 383, 120, 10.1056/NEJMoa2015432

V'kovski, 2020, Coronavirus biology and replication: implications for SARS-CoV-2, Nat Rev Microbiol., 19, 155, 10.1038/s41579-020-00468-6

Adorni, 2020, Self-Reported symptoms of SARS-CoV-2 infection in a nonhospitalized population in italy: cross-sectional study of the EPICOVID19 web-based survey, JMIR Public Heal Surveill., 6, e21866, 10.2196/21866

Bergquist, 2020, Non-hospitalized adults with COVID-19 differ noticeably from hospitalized adults in their demographic, clinical, social characteristics, SN Compr Clin Med., 2, 1, 10.1007/s42399-020-00453-3

Long, 2020, Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections, Nat Med, 26, 1200, 10.1038/s41591-020-0965-6

Oran, 2020, Prevalence of asymptomatic SARS-CoV-2 infection : a narrative review, Ann Intern Med., 173, 362, 10.7326/M20-3012

Inui, 2020, Chest CT findings in cases from the cruise ship diamond princess with coronavirus disease (COVID-19), Radiol Cardiothorac Imaging., 2, e200110, 10.1148/ryct.2020200110

Tian, 2020, Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) Pneumonia in Two Patients With Lung Cancer, J Thorac Oncol, 15, 700, 10.1016/j.jtho.2020.02.010

Lan, 2020, Positive RT-PCR test results in patients recovered from COVID-19, JAMA., 323, 1502, 10.1001/jama.2020.2783

Rogliani, 2020, Are there pulmonary sequelae in patients recovering from COVID-19?, Respir Res., 21, 286, 10.1186/s12931-020-01550-6

Chen, 2020, Clinical and immunological features of severe and moderate coronavirus disease 2019, J Clin Invest., 130, 2620, 10.1172/JCI137244

Rodriguez-Morales, 2020, Clinical, laboratory and imaging features of COVID-19: a systematic review and meta-analysis, Travel Med Infect Dis., 34, 101623, 10.1016/j.tmaid.2020.101623

Tian, 2020, Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies, Mod Pathol, 33, 1007, 10.1038/s41379-020-0536-x

Zhang, 2020, Viral and host factors related to the clinical outcome of COVID-19, Nature, 583, 437, 10.1038/s41586-020-2355-0

Severe, 2020, Genomewide association study of severe covid-19 with respiratory failure, N Engl J Med., 383, 1522, 10.1056/NEJMoa2020283

Zietz, 2020, Associations between blood type and COVID-19 infection, intubation, and death, Nat Commun., 11, 5761, 10.1038/s41467-020-19623-x

Yao, 2020, D-dimer as a biomarker for disease severity and mortality in COVID-19 patients: a case control study, J Intensive Care., 8, 49, 10.1186/s40560-020-00466-z

Menter, 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, 10.1111/his.14134

Gupta, 2020, Extrapulmonary manifestations of COVID-19, Nat Med., 26, 1017, 10.1038/s41591-020-0968-3

Sorci, 2020, Explaining among-country variation in COVID-19 case fatality rate, Sci Rep., 10, 18909, 10.1038/s41598-020-75848-2

Wang, 2020, Analysis of the clinical characteristics of 77 COVID-19 deaths, Sci Rep, 10, 16384, 10.1038/s41598-020-73136-7

Xu, 2020, Pathological findings of COVID-19 associated with acute respiratory distress syndrome, Lancet Respir Med., 8, 420, 10.1016/S2213-2600(20)30076-X

Bauer, 2006, Acute respiratory distress syndrome and pneumonia: a comprehensive review of clinical data, Clin Infect Dis., 43, 748, 10.1086/506430

Cardinal-Fernández, 2017, Acute respiratory distress syndrome and diffuse alveolar damage. New insights on a complex relationship, Ann Am Thorac Soc., 14, 844, 10.1513/AnnalsATS.201609-728PS

Nienhold, 2020, Two distinct immunopathological profiles in autopsy lungs of COVID-19, Nat Commun., 11, 5086, 10.1038/s41467-020-18854-2

Horwitz, 2020, Trends in COVID-19 risk-adjusted mortality rates, J Hosp Med., 16, 90, 10.12788/jhm.3552

Herridge, 2011, Functional disability 5 years after acute respiratory distress syndrome, N Engl J Med., 364, 1293, 10.1056/NEJMoa1011802

Nöbauer-Huhmann, 2001, Changes in lung parenchyma after acute respiratory distress syndrome (ARDS): assessment with high-resolution computed tomography, Eur Radiol., 11, 2436, 10.1007/s003300101103

Yang, 2003, Induction of proinflammatory cytokines in human lung epithelial cells during Chlamydia pneumoniae infection, Infect. Immun., 71, 614, 10.1128/iai.71.2.614-620.2003

Drakopanagiotakis, 2008, Apoptosis in lung injury and fibrosis, Eur Respir J, 32, 1631, 10.1183/09031936.00176807

Kligerman, 2013, From the radiologic pathology archives: organization and fibrosis as a response to lung injury in diffuse alveolar damage, organizing pneumonia, and acute fibrinous and organizing pneumonia, Radiographics., 33, 1951, 10.1148/rg.337130057

Venosa, 2020, Modeling immune effector responses in alveolar epithelial cell driven lung injury and fibrosis, J Immunol, 204, 74.1, 10.4049/jimmunol.204.Supp.74.14

Yanagi, 2015, Breakdown of epithelial barrier integrity and overdrive activation of alveolar epithelial cells in the pathogenesis of acute respiratory distress syndrome and lung fibrosis, Biomed Res Int., 2015, 573210, 10.1155/2015/573210

Glasser, 2016, Mechanisms of lung fibrosis resolution, Am J Pathol., 186, 1066, 10.1016/j.ajpath.2016.01.018

Naikawadi, 2016, Telomere dysfunction in alveolar epithelial cells causes lung remodeling and fibrosis, JCI Insight., 1, e86704, 10.1172/jci.insight.86704

Hancock, 2018, Muc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice, Nat Commun., 9, 5363, 10.1038/s41467-018-07768-9

Venosa, 2019, Epithelial expression of an interstitial lung disease-associated mutation in surfactant protein-c modulates recruitment and activation of key myeloid cell populations in mice, J Immunol., 202, 2760, 10.4049/jimmunol.1900039

Bilgili, 2019, Telomere abnormalities in the pathobiology of idiopathic pulmonary fibrosis, J Clin Med., 8, 1232, 10.3390/jcm8081232

Yin, 2014, Aging exacerbates damage and delays repair of alveolar epithelia following influenza viral pneumonia, Respir Res., 15, 116, 10.1186/s12931-014-0116-z

Kasper, 2017, Potential contribution of alveolar epithelial type I cells to pulmonary fibrosis, Biosci Rep., 37, 1, 10.1042/BSR20171301

Agostini, 2006, Chemokine/cytokine cocktail in idiopathic pulmonary fibrosis, Proc Am Thorac Soc., 3, 357, 10.1513/pats.200601-010TK

Chambers, 2015, Mechanisms of alveolar epithelial injury, repair, and fibrosis, Ann Thorac Soc, 1, S16, 10.1513/AnnalsATS.201410-448MG

Fujiwara, 2017, Inhibition of cell apoptosis and amelioration of pulmonary fibrosis by thrombomodulin, Am J Pathol., 187, 2312, 10.1016/j.ajpath.2017.06.013

Kim, 2018, Efferocytosis of apoptotic alveolar epithelial cells is sufficient to initiate lung fibrosis, Cell Death Dis., 9, 1056, 10.1038/s41419-018-1074-z

Epstein Shochet, 2020, TGF-β pathway activation by idiopathic pulmonary fibrosis (IPF) fibroblast derived soluble factors is mediated by IL-6 trans-signaling, Respir Res., 21, 56, 10.1186/s12931-020-1319-0

Chilosi, 2002, Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: the role of deltaN-p63, Lab Invest., 82, 1335, 10.1097/01.lab.0000032380.82232.67

Kaarteenaho, 2011, Diffuse alveolar damage: a common phenomenon in progressive interstitial lung disorders, Pulm Med., 2011, 1, 10.1155/2011/531302

Collard, 2016, Acute exacerbation of idiopathic pulmonary fibrosis. An International Working Group Report, Am J Respir Crit Care Med., 194, 265, 10.1164/rccm.201604-0801CI

Tsui, 2003, Severe acute respiratory syndrome: clinical outcome and prognostic correlates, Emerg Infect Dis., 9, 1064, 10.3201/eid0909.030362

Cheung, 2004, The spectrum of pathological changes in severe acute respiratory syndrome (SARS), Histopathology., 45, 119, 10.1111/j.1365-2559.2004.01926.x

Ketai, 2006, Radiology of Severe Acute Respiratory Syndrome (SARS): the emerging pathologic-radiologic correlates of an emerging disease, J Thorac Imaging., 21, 276, 10.1097/01.rti.0000213581.14225.f1

Gu, 2007, Pathology and pathogenesis of severe acute respiratory syndrome, Am J Pathol, 170, 1136, 10.2353/ajpath.2007.061088

Tse, 2004, Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS), J Clin Pathol., 57, 260, 10.1136/jcp.2003.013276

Hwang, 2005, Pulmonary pathology of severe acute respiratory syndrome in Toronto, Mod Pathol., 18, 1, 10.1038/modpathol.3800247

Hui, 2005, Impact of severe acute respiratory syndrome (SARS) on pulmonary function, functional capacity and quality of life in a cohort of survivors, Thorax., 60, 401, 10.1136/thx.2004.030205

Ngai, 2010, The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status, Respirology., 15, 543, 10.1111/j.1440-1843.2010.01720.x

Antonio, 2003, Thin-section CT in patients with severe acute respiratory syndrome following hospital discharge: preliminary experience, Radiology., 228, 810, 10.1148/radiol.2283030726

de Wit, 2016, SARS and MERS: recent insights into emerging coronaviruses, Nat Rev Microbiol., 14, 523, 10.1038/nrmicro.2016.81

Carfì, 2020, Persistent symptoms in patients after acute COVID-19, JAMA., 324, 603, 10.1001/jama.2020.12603

Goërtz, 2020, Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome?, ERJ Open Res., 6, 00542, 10.1183/23120541.00542-2020

Weerahandi, 2020, Post-discharge health status and symptoms in patients with severe COVID-19, medRxiv., 2, 37, 10.1101/2020.08.11.20172742

Shi, 2020, Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study, Lancet Infect Dis, 20, 425, 10.1016/S1473-3099(20)30086-4

Ebner, 2020, Imaging in the aftermath of COVID-19: what to expect, Eur Radiol., 10.1007/s00330-020-07465-6.

Zhao, 2020, Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery, EClinicalMedicine, 25, 100463, 10.1016/j.eclinm.2020.100463

Lerum, 2020, Dyspnoea, lung function and CT findings three months after hospital admission for COVID-19, Eur Respir J., 10.1183/13993003.03448-2020.

Liang, 2020, Three-month follow-up study of survivors of coronavirus disease 2019 after discharge, J Korean Med Sci., 35, e418, 10.3346/jkms.2020.35.e418

Shah, 2021, A prospective study of 12-week respiratory outcomes in COVID-19-related hospitalisations, Thorax., 76, 402, 10.1136/thoraxjnl-2020-216308

Sonnweber, 2020, Cardiopulmonary recovery after COVID-19 - an observational prospective multi-center trial, Eur Respir J., 10, 2003481, 10.1183/13993003.03481-2020

van der Sar-van der Brugge, 2020, Pulmonary function and health-related quality of life after COVID-19 pneumonia, Respir Med., 176, 106272, 10.1016/j.rmed.2020.106272

Chuprin, 2013, Cell fusion induced by ERVWE1 or measles virus causes cellular senescence, Genes Dev., 27, 2356, 10.1101/gad.227512.113

Muñoz-Espín, 2014, Cellular senescence: from physiology to pathology, Nat Rev Mol Cell Biol., 15, 482, 10.1038/nrm3823

Childs, 2015, Cellular senescence in aging and age-related disease: from mechanisms to therapy, Nat Med., 21, 1424, 10.1038/nm.4000

Hansel, 2020, Cellular senescence in the lung: the central role of senescent epithelial cells, Int J Mol Sci., 21, 1, 10.3390/ijms21093279

Vitiello, 2020, COVID-19 patients with pulmonary fibrotic tissue: clinical pharmacological rational of antifibrotic therapy, SN Compr Clin Med., 2, 1, 10.1007/s42399-020-00487-7

Jenkins, 2017, An official american thoracic society workshop report: use of animal models for the preclinical assessment of potential therapies for pulmonary fibrosis, Am J Respir Cell Mol Biol., 56, 667, 10.1165/rcmb.2017-0096ST

Trethewey, 2018, The role of occupational and environmental exposures in the pathogenesis of idiopathic pulmonary fibrosis: a narrative literature review, Medicina, 54, 108, 10.3390/medicina54060108

Padilla-Carlin, 2011, Pulmonary inflammatory and fibrotic responses in Fischer 344 rats after intratracheal instillation exposure to Libby amphibole, J Toxicol Environ Health A., 74, 1111, 10.1080/15287394.2011.586940

Shoeb, 2019, Initiation of pulmonary fibrosis after silica inhalation in rats is linked with dysfunctional shelterin complex and DNA damage response, Sci Rep., 9, 471, 10.1038/s41598-018-36712-6

Jin, 2020, Radiation-induced lung fibrosis: preclinical animal models and therapeutic strategies, Cancers., 12, 1, 10.3390/cancers12061561

Nureki, 2018, Expression of mutant Sftpc in murine alveolar epithelia drives spontaneous lung fibrosis, J Clin Invest., 128, 4008, 10.1172/JCI99287

Nathan, 2016, Germline SFTPA1 mutation in familial idiopathic interstitial pneumonia and lung cancer, Hum Mol Genet., 25, 1457, 10.1093/hmg/ddw014

Seibold, 2011, A common MUC5B promoter polymorphism and pulmonary fibrosis, N Engl J Med., 364, 1503, 10.1056/NEJMoa1013660

Boutanquoi, 2020, TRIM33 prevents pulmonary fibrosis by impairing TGF-β1 signalling, Eur Respir J, 55, 1901346, 10.1183/13993003.01346-2019

Miyazaki, 1995, Expression of a tumor necrosis factor-alpha transgene in murine lung causes lymphocytic and fibrosing alveolitis. A mouse model of progressive pulmonary fibrosis, J Clin Invest., 96, 250, 10.1172/JCI118029

Kolb, 2001, Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis, J Clin Invest., 107, 1529, 10.1172/JCI12568

Karkampouna, 2014, Novel ex vivo culture method for the study of dupuytren's disease: effects of TGFβ type 1 receptor modulation by antisense oligonucleotides, Mol Ther Nucleic Acids., 3, e142, 10.1038/mtna.2013.69

Gerckens, 2019, Generation of human 3D Lung Tissue Cultures (3D-LTCs) for disease modeling, J Vis Exp., 10.3791/58437

Alsafadi, 2017, An ex vivo model to induce early fibrosis-like changes in human precision-cut lung slices, Am J Physiol Lung Cell Mol Physiol., 312, L896, 10.1152/ajplung.00084.2017

Roach, 2018, A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies in idiopathic pulmonary fibrosis, Sci Rep., 8, 342, 10.1038/s41598-017-18555-9

Lehmann, 2018, Differential effects of nintedanib and pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis, Respir Res., 19, 175, 10.1186/s12931-018-0876-y

Wasnick, 2019, Restored alveolar epithelial differentiation and reversed human lung fibrosis upon Notch inhibition, bioRxiv [Preprint]., 10.1101/580498

Montigaud, 2019, Development of an ex vivo respiratory pediatric model of bronchopulmonary dysplasia for aerosol deposition studies, Sci Rep., 9, 5720, 10.1038/s41598-019-42103-2

Sundarakrishnan, 2018, Engineered cell and tissue models of pulmonary fibrosis, Adv Drug Deliv Rev., 129, 78, 10.1016/j.addr.2017.12.013

Liu, 2015, Mechanosignaling through YAP and TAZ drives fibroblast activation and fibrosis, Am J Physiol Lung Cell Mol Physiol., 308, L344, 10.1152/ajplung.00300.2014

Asano, 2017, Matrix stiffness regulates migration of human lung fibroblasts, Physiol Rep., 5, 1, 10.14814/phy2.13281

Wilkinson, 2017, Development of a three-dimensional bioengineering technology to generate lung tissue for personalized disease modeling, Stem Cells Transl. Med., 6, 622, 10.5966/sctm.2016-0192

Surolia, 2019, Vimentin intermediate filament assembly regulates fibroblast invasion in fibrogenic lung injury, JCI insight., 4, e123253, 10.1172/jci.insight.123253

Strikoudis, 2019, Modeling of fibrotic lung disease using 3d organoids derived from human pluripotent stem cells, Cell Rep., 27, 3709, 10.1016/j.celrep.2019.05.077

Yanagihara, 2020, Current models of pulmonary fibrosis for future drug discovery efforts, Expert Opin Drug Discov., 15, 931, 10.1080/17460441.2020.1755252

Schruf, 2020, Recapitulating idiopathic pulmonary fibrosis related alveolar epithelial dysfunction in a human iPSC-derived air-liquid interface model, FASEB J., 34, 7825, 10.1096/fj.201902926R

Huh, 2010, Reconstituting organ-level lung functions on a chip, Science., 328, 1662, 10.1126/science.1188302

Low, 2020, Organs-on-chips: into the next decade, Nat Rev Drug Discov., 10.1038/s41573-020-0079-3.

Jain, 2018, Primary human lung alveolus-on-a-chip model of intravascular thrombosis for assessment of therapeutics, Clin Pharmacol Ther., 103, 332, 10.1002/cpt.742

Felder, 2014, The potential of microfluidic lung epithelial wounding: towards in vivo-like alveolar microinjuries, Integr Biol, 6, 1132, 10.1039/c4ib00149d

Felder, 2012, Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium, Lab Chip., 12, 640, 10.1039/c1lc20879a

Asmani, 2018, Fibrotic microtissue array to predict anti-fibrosis drug efficacy, Nat Commun., 9, 2066, 10.1038/s41467-018-04336-z

Stucki, 2015, A lung-on-a-chip array with an integrated bio-inspired respiration mechanism, Lab Chip., 15, 1302, 10.1039/c4lc01252f

Stucki, 2018, Medium throughput breathing human primary cell alveolus-on-chip model, Sci Rep., 8, 14359, 10.1038/s41598-018-32523-x

Leist, 2020, Cell and animal models of SARS-CoV-2 pathogenesis and immunity, Dis Model Mech., 13, dmm046581, 10.1242/dmm.046581

Bao, 2020, The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice, Nature., 583, 830, 10.1038/s41586-020-2312-y

Sun, 2020, A mouse model of SARS-CoV-2 infection and pathogenesis, Cell Host Microbe., 28, 124, 10.1016/j.chom.2020.05.020

Jiang, 2020, Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2, Cell., 182, 50, 10.1016/j.cell.2020.05.027

Winkler, 2020, SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function, Nat Immunol., 21, 1327, 10.1038/s41590-020-0778-2

Dinnon, 2020, A mouse-adapted model of SARS-CoV-2 to test COVID-19 countermeasures, Nature., 586, 560, 10.1038/s41586-020-2708-8

Gu, 2020, Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy, Science., 369, 1603, 10.1126/science.abc4730

Shi, 2020, Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2, Science, 368, 1016, 10.1126/science.abb7015

Kim, 2020, Infection and Rapid Transmission of SARS-CoV-2 in Ferrets, Cell Host Microbe., 27, 704, 10.1016/j.chom.2020.03.023

Park, 2020, Antiviral efficacies of FDA-approved drugs against SARS-CoV-2 infection in ferrets, MBio., 11, 1, 10.1128/mBio.01114-20

Chan, 2020, Simulation of the clinical and Pathological Manifestations of Coronavirus Disease 2019 (COVID-19) in a Golden Syrian Hamster Model: implications for disease pathogenesis and transmissibility, Clin Infect Dis., 71, 2428, 10.1093/cid/ciaa325

Chandrashekar, 2020, SARS-CoV-2 infection protects against rechallenge in rhesus macaques, Science., 369, 812, 10.1126/science.abc4776

Lu, 2020, Comparison of nonhuman primates identified the suitable model for COVID-19, Signal Transduct Target Ther., 5, 157, 10.1038/s41392-020-00269-6

Munster, 2020, Respiratory disease in rhesus macaques inoculated with SARS-CoV-2, Nature., 585, 268, 10.1038/s41586-020-2324-7

Rockx, 2020, Comparative pathogenesis of COVID-19, MERS, and SARS in a nonhuman primate model, Science., 368, 1012, 10.1126/science.abb7314

Yu, 2020, Age-related rhesus macaque models of COVID-19, Anim Model Exp Med., 3, 93, 10.1002/ame2.12108

Ehaideb, 2020, Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review, Crit Care., 24, 594, 10.1186/s13054-020-03304-8

Chu, 2020, Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: an observational study, Lancet Microbe., 1, e14, 10.1016/S2666-5247(20)30004-5

Abo, 2020, Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors, bioRxiv [Preprint], 10.1101/2020.06.03.132639

Emeny, 1979, Regulation of the interferon system: evidence that Vero cells have a genetic defect in interferon production, J Gen Virol., 43, 247, 10.1099/0022-1317-43-1-247

Jia, 2005, ACE2 receptor expression and severe acute respiratory syndrome coronavirus infection depend on differentiation of human airway epithelia, J Virol., 79, 14614, 10.1128/JVI.79.23.14614-14621.2005

Krüger, 2020, Drug inhibition of SARS-CoV-2 replication in human pluripotent stem cell-derived intestinal organoids, Cell Mol Gastroenterol Hepatol., 11, 935, 10.1016/j.jcmgh.2020.11.003

Monteil, 2020, Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2, Cell., 181, 905, 10.1016/j.cell.2020.04.004

Stanifer, 2020, Critical role of type III interferon in controlling SARS-CoV-2 infection in human intestinal epithelial cells, Cell Rep., 32, 107863, 10.1016/j.celrep.2020.107863

Zhao, 2020, Recapitulation of SARS-CoV-2 infection and cholangiocyte damage with human liver ductal organoids, Protein Cell, 11, 771, 10.1007/s13238-020-00718-6

Jonsdottir, 2016, Coronaviruses and the human airway: a universal system for virus-host interaction studies, Virol J, 13, 24, 10.1186/s12985-016-0479-5

V'kovski, 2021, Disparate temperature-dependent virus-host dynamics for SARS-CoV-2 and SARS-CoV in the human respiratory epithelium, PLoS Biol., 19, e3001158, 10.1371/journal.pbio.3001158

Si, 2020, Human organ chip-enabled pipeline to rapidly repurpose therapeutics during viral pandemics, bioRxiv., 2115, 212, 10.1101/2020.04.13.039917

Fuchs, 2003, Differentiation of human alveolar epithelial cells in primary culture: morphological characterization and synthesis of caveolin-1 and surfactant protein-C, Cell Tissue Res., 311, 31, 10.1007/s00441-002-0653-5

Tamò, 2018, Generation of an alveolar epithelial type II cell line from induced pluripotent stem cells, Am J Physiol Lung Cell Mol Physiol., 315, L921, 10.1152/ajplung.00357.2017

Chen, 2017, A three-dimensional model of human lung development and disease from pluripotent stem cells, Nat Cell Biol., 19, 542, 10.1038/ncb3510

Hekman, 2020, Actionable cytopathogenic host responses of human alveolar type 2 cells to SARS-CoV-2, Mol Cell., 80, 1104, 10.1016/j.molcel.2020.11.028

Duan, 2020, Modeling COVID-19 with human pluripotent stem cell-derived cells reveals synergistic effects of anti-inflammatory macrophages with ACE2 inhibition against SARS-CoV-2, Res Square [Preprint], 10.21203/rs.3.rs-62758/v1

Jacob, 2019, Derivation of self-renewing lung alveolar epithelial type II cells from human pluripotent stem cells, Nat. Protoc., 14, 3303, 10.1038/s41596-019-0220-0

Chan, 2003, SARS: prognosis, outcome and sequelae, Respirology., 8, S36, 10.1046/j.1440-1843.2003.00522.x

Rogers, 2018, MUC5B promoter polymorphism and development of acute respiratory distress syndrome, Am J Respir Crit Care Med., 198, 1342, 10.1164/rccm.201801-0140LE

Bastard, 2020, Autoantibodies against type I IFNs in patients with life-threatening COVID-19, Science., 370, eabd4585, 10.1126/science.abd4585

Zhang, 2020, Inborn errors of type I IFN immunity in patients with life-threatening COVID-19, Science, 370, eabd4570, 10.1126/science.abd4570

Lamers, 2021, An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells, EMBO J., 40, e105912, 10.15252/embj.2020105912

Haji Abdolvahab, 2021, Potential role of interferons in treating COVID-19 patients, Int Immunopharmacol., 90, 107171, 10.1016/j.intimp.2020.107171

Guenat, 2020, Clinically relevant tissue scale responses as new readouts from organs-on-a-chip for precision medicine, Annu Rev Anal Chem, 13, 111, 10.1146/annurev-anchem-061318-114919

Deinhardt-Emmer, 2021, SARS-CoV-2 causes severe epithelial inflammation and barrier dysfunction, J Virol., 10.1128/JVI.00110-21.

Wu, 2020, Transcriptional and proteomic insights into the host response in fatal COVID-19 cases, Proc Natl Acad Sci USA., 117, 28336, 10.1073/pnas.2018030117

Lok, 2002, Murine gammaherpes virus as a cofactor in the development of pulmonary fibrosis in bleomycin resistant mice, Eur Respir J, 20, 1228, 10.1183/09031936.02.00272902

Wang, 2017, Respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model, Mol Med Rep., 16, 310, 10.3892/mmr.2017.6558

Huang, 2019, Macrophage PPAR-γ suppresses long-term lung fibrotic sequelae following acute influenza infection, PLoS ONE., 14, e0223430, 10.1371/journal.pone.0223430

Miller, 2017, In vitro models to study human lung development, disease and homeostasis, Physiology., 32, 246, 10.1152/physiol.00041.2016

Johansen, 2020, Animal and translational models of SARS-CoV-2 infection and COVID-19, Mucosal Immunol., 13, 877, 10.1038/s41385-020-00340-z

Krimmling, 2017, Comparison of mono- and co-infection by swine influenza A viruses and porcine respiratory coronavirus in porcine precision-cut lung slices, Res Vet Sci., 115, 470, 10.1016/j.rvsc.2017.07.016

Hui, 2020, Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures, Lancet Respir Med., 8, 687, 10.1016/S2213-2600(20)30193-4

Lehmann, 2017, Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosis ex vivo, Eur Respir J, 50, 1602367, 10.1183/13993003.02367-2016

Liu, 2019, Use of precision cut lung slices as a translational model for the study of lung biology, Respir Res., 20, 162, 10.1186/s12931-019-1131-x

Barosova, 2020, Use of epialveolar lung model to predict fibrotic potential of multiwalled carbon nanotubes, ACS Nano., 14, 3941, 10.1021/acsnano.9b06860

Berkers, 2019, Rectal organoids enable personalized treatment of cystic fibrosis, Cell Rep., 26, 1701, 10.1016/j.celrep.2019.01.068

Karkampouna, 2021, Patient-derived xenografts and organoids model therapy response in prostate cancer, Nat. Commun., 12, 1117, 10.1038/s41467-021-21300-6

Sanchez-Esteban, 2001, Mechanical stretch promotes alveolar epithelial type II cell differentiation, J. Appl. Physiol., 91, 589, 10.1152/jappl.2001.91.2.589

Liu, 2016, MAPK-Mediated YAP activation controls mechanical-tension-induced pulmonary alveolar regeneration, Cell Rep., 16, 1810, 10.1016/j.celrep.2016.07.020