Characterization and Treatment of SARS-CoV-2 in Nasal and Bronchial Human Airway Epithelia

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2020 Aug 25

PMID 32835306

Citations 129

Authors

Andres Pizzorno

Blandine Padey

Thomas Julien

Sophie Trouillet-Assant

Aurelien Traversier

Elisabeth Errazuriz-Cerda

Julien Fouret

Julia Dubois

Alexandre Gaymard

Francois-Xavier Lescure

Victoria Duliere

Pauline Brun

Samuel Constant

Julien Poissy

Bruno Lina

Yazdan Yazdanpanah

Olivier Terrier

Manuel Rosa-Calatrava

Affiliations

Soon will be listed here.

Abstract

In the current COVID-19 pandemic effective treatments represents a major challenge. However, the scarcity of biologically relevant pre-clinical models of SARS-CoV-2 infection imposes a significant barrier for scientific and medical progress, including the rapid transition of potentially effective treatments to the clinical setting. We use reconstituted human airway epithelia to isolate and then characterize the viral infection kinetics, tissue-level remodeling of the cellular ultrastructure, and transcriptional early immune signatures induced by SARS-CoV-2 in a physiologically relevant model. Our results emphasize distinctive transcriptional immune signatures between nasal and bronchial HAE, both in terms of kinetics and intensity, hence suggesting putative intrinsic differences in the early response to SARS-CoV-2 infection. Most important, we provide evidence in human-derived tissues on the antiviral efficacy of remdesivir monotherapy and explore the potential of the remdesivir-diltiazem combination as an option worthy of further investigation to respond to the still-unmet COVID-19 medical need.

Citing Articles

Comparison of characteristics and immune responses between paired human nasal and bronchial epithelial organoids.

Zhu L, Yang W, Luo J, Lu D, Hu Y, Zhang R Cell Biosci. 2025; 15(1):18.

PMID: 39920853 PMC: 11806626. DOI: 10.1186/s13578-024-01342-1.

Phenotypic evolution of SARS-CoV-2 spike during the COVID-19 pandemic.

Furnon W, Cowton V, De Lorenzo G, Orton R, Herder V, Cantoni D Nat Microbiol. 2025; 10(1):77-93.

PMID: 39753670 PMC: 11726466. DOI: 10.1038/s41564-024-01878-5.

Cytokine production in an model of SARS-CoV-2 lung infection.

Vorobyeva D, Potashnikova D, Maryukhnich E, Rusakovich G, Tvorogova A, Kalinskaya A Front Immunol. 2024; 15:1448515.

PMID: 39497823 PMC: 11532052. DOI: 10.3389/fimmu.2024.1448515.

Impaired mucosal IgA response in patients with severe COVID-19.

Yaugel-Novoa M, Noailly B, Jospin F, Pizzorno A, Traversier A, Pozzetto B Emerg Microbes Infect. 2024; 13(1):2401940.

PMID: 39358866 PMC: 11451292. DOI: 10.1080/22221751.2024.2401940.

Distinct Responses of Cystic Fibrosis Epithelial Cells to SARS-CoV-2 and Influenza A Virus.

Pagani I, Venturini A, Capurro V, Nonis A, Ghezzi S, Lena M Am J Respir Cell Mol Biol. 2024; 72(3):308-319.

PMID: 39311876 PMC: 11890075. DOI: 10.1165/rcmb.2024-0213OC.

References

Goldsmith C, Tatti K, Ksiazek T, Rollin P, Comer J, Lee W . Ultrastructural characterization of SARS coronavirus. Emerg Infect Dis. 2004; 10(2):320-6. PMC: 3322934. DOI: 10.3201/eid1002.030913. View

Sheahan T, Sims A, Graham R, Menachery V, Gralinski L, Case J . Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017; 9(396). PMC: 5567817. DOI: 10.1126/scitranslmed.aal3653. View

Knoops K, Kikkert M, van den Worm S, Zevenhoven-Dobbe J, van der Meer Y, Koster A . SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol. 2008; 6(9):e226. PMC: 2535663. DOI: 10.1371/journal.pbio.0060226. View

Liu Y, Yan L, Wan L, Xiang T, Le A, Liu J . Viral dynamics in mild and severe cases of COVID-19. Lancet Infect Dis. 2020; 20(6):656-657. PMC: 7158902. DOI: 10.1016/S1473-3099(20)30232-2. View

de Wilde A, Raj V, Oudshoorn D, Bestebroer T, van Nieuwkoop S, Limpens R . MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-α treatment. J Gen Virol. 2013; 94(Pt 8):1749-1760. PMC: 3749523. DOI: 10.1099/vir.0.052910-0. View

Jazaeri Farsani S, Deijs M, Dijkman R, Molenkamp R, Jeeninga R, Ieven M . Culturing of respiratory viruses in well-differentiated pseudostratified human airway epithelium as a tool to detect unknown viruses. Influenza Other Respir Viruses. 2014; 9(1):51-7. PMC: 4280819. DOI: 10.1111/irv.12297. View

Sheahan T, Sims A, Leist S, Schafer A, Won J, Brown A . Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020; 11(1):222. PMC: 6954302. DOI: 10.1038/s41467-019-13940-6. View

Lescure F, Bouadma L, Nguyen D, Parisey M, Wicky P, Behillil S . Clinical and virological data of the first cases of COVID-19 in Europe: a case series. Lancet Infect Dis. 2020; 20(6):697-706. PMC: 7156120. DOI: 10.1016/S1473-3099(20)30200-0. View

Mouton W, Albert-Vega C, Boccard M, Bartolo F, Oriol G, Lopez J . Towards standardization of immune functional assays. Clin Immunol. 2019; 210:108312. DOI: 10.1016/j.clim.2019.108312. View

10.

Wang Y, Wang Y, Chen Y, Qin Q . Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures. J Med Virol. 2020; 92(6):568-576. PMC: 7228347. DOI: 10.1002/jmv.25748. View

11.

Lu R, Zhao X, Li J, Niu P, Yang B, Wu H . Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020; 395(10224):565-574. PMC: 7159086. DOI: 10.1016/S0140-6736(20)30251-8. View

12.

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G . A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020; 382(19):1787-1799. PMC: 7121492. DOI: 10.1056/NEJMoa2001282. View

13.

Thevarajan I, Nguyen T, Koutsakos M, Druce J, Caly L, van de Sandt C . Breadth of concomitant immune responses prior to patient recovery: a case report of non-severe COVID-19. Nat Med. 2020; 26(4):453-455. PMC: 7095036. DOI: 10.1038/s41591-020-0819-2. View

14.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View

15.

Prescott J, Hall P, Acuna-Retamar M, Ye C, Wathelet M, Ebihara H . New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells. PLoS One. 2010; 5(6):e11159. PMC: 2887373. DOI: 10.1371/journal.pone.0011159. View

16.

Lamballerie C, Pizzorno A, Dubois J, Julien T, Padey B, Bouveret M . Characterization of cellular transcriptomic signatures induced by different respiratory viruses in human reconstituted airway epithelia. Sci Rep. 2019; 9(1):11493. PMC: 6685967. DOI: 10.1038/s41598-019-48013-7. View

17.

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M . Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020; 30(3):269-271. PMC: 7054408. DOI: 10.1038/s41422-020-0282-0. View

18.

Boda B, Benaoudia S, Huang S, Bonfante R, Wiszniewski L, Tseligka E . Antiviral drug screening by assessing epithelial functions and innate immune responses in human 3D airway epithelium model. Antiviral Res. 2018; 156:72-79. PMC: 7113743. DOI: 10.1016/j.antiviral.2018.06.007. View

19.

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z . Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229):1054-1062. PMC: 7270627. DOI: 10.1016/S0140-6736(20)30566-3. View

20.

Pizzorno A, Terrier O, Lamballerie C, Julien T, Padey B, Traversier A . Repurposing of Drugs as Novel Influenza Inhibitors From Clinical Gene Expression Infection Signatures. Front Immunol. 2019; 10:60. PMC: 6361841. DOI: 10.3389/fimmu.2019.00060. View