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Published in: BMC Pulmonary Medicine 1/2020

Open Access 01-12-2020 | SARS-CoV-2 | Research article

Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome

Authors: Laura Pandolfi, Tommaso Fossali, Vanessa Frangipane, Sara Bozzini, Monica Morosini, Maura D’Amato, Sara Lettieri, Mario Urtis, Alessandro Di Toro, Laura Saracino, Elena Percivalle, Stefano Tomaselli, Lorenzo Cavagna, Emanuela Cova, Francesco Mojoli, Paola Bergomi, Davide Ottolina, Daniele Lilleri, Angelo Guido Corsico, Eloisa Arbustini, Riccardo Colombo, Federica Meloni

Published in: BMC Pulmonary Medicine | Issue 1/2020

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19.

Methods

Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels.

Results

ICU patients showed a marked increase in neutrophils (1.24 × 105 ml− 1, 0.85–2.07), lower lymphocyte (0.97 × 105 ml− 1, 0.024–0.34) and macrophages fractions (0.43 × 105 ml− 1, 0.34–1.62) compared to IMW patients (0.095 × 105 ml− 1, 0.05–0.73; 0.47 × 105 ml− 1, 0.28–1.01 and 2.14 × 105 ml− 1, 1.17–3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05).

Conclusions

Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
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Literature
1.
go back to reference 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. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265–9.CrossRef 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. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265–9.CrossRef
2.
go back to reference Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D'Antiga L. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395:1771–8.CrossRef Verdoni L, Mazza A, Gervasoni A, Martelli L, Ruggeri M, Ciuffreda M, Bonanomi E, D'Antiga L. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395:1771–8.CrossRef
3.
go back to reference Huang C, Wang Y, Li X, Ren L, Zhao J. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.CrossRef Huang C, Wang Y, Li X, Ren L, Zhao J. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506.CrossRef
4.
go back to reference Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46:846–8.CrossRef Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46:846–8.CrossRef
7.
go back to reference 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 Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–20.CrossRef 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 Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708–20.CrossRef
8.
go back to reference Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–8.CrossRef Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–8.CrossRef
9.
go back to reference Mondoni M, Sferrazza Papa GF, Rinaldo R, Faverio P, Marruchella A, D'Arcangelo F, Pesci A, Pasini S, Henchi S, Cipolla G, Tarantini F, Giuliani L, Di Marco F, Saracino L, Tomaselli S, Corsico A, Gasparini S, Bonifazi M, Zuccatosta L, Saderi L, Pellegrino G, Davì M, Carlucci P, Centanni S, Sotgiu G. Utility and safety of bronchoscopy during SARS-CoV-2 outbreak in Italy: a retrospective, multicenter study. Eur Respir J. 2020;56(4):2002767.CrossRef Mondoni M, Sferrazza Papa GF, Rinaldo R, Faverio P, Marruchella A, D'Arcangelo F, Pesci A, Pasini S, Henchi S, Cipolla G, Tarantini F, Giuliani L, Di Marco F, Saracino L, Tomaselli S, Corsico A, Gasparini S, Bonifazi M, Zuccatosta L, Saderi L, Pellegrino G, Davì M, Carlucci P, Centanni S, Sotgiu G. Utility and safety of bronchoscopy during SARS-CoV-2 outbreak in Italy: a retrospective, multicenter study. Eur Respir J. 2020;56(4):2002767.CrossRef
10.
go back to reference Meloni F, Solari N, Cavagna L, Morosini M, Montecucco CM, Fietta AM. Frequency of Th1, Th2 and Th17 producing T lymphocytes in bronchoalveolar lavage of patients with systemic sclerosis. Clin Exp Rheumatol. 2009;27(5):765–72.PubMed Meloni F, Solari N, Cavagna L, Morosini M, Montecucco CM, Fietta AM. Frequency of Th1, Th2 and Th17 producing T lymphocytes in bronchoalveolar lavage of patients with systemic sclerosis. Clin Exp Rheumatol. 2009;27(5):765–72.PubMed
11.
go back to reference McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including Interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19:102537.CrossRef McGonagle D, Sharif K, O'Regan A, Bridgewood C. The role of cytokines including Interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun Rev. 2020;19:102537.CrossRef
12.
go back to reference Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol. 2008;180(9):5771–7.CrossRef Couper KN, Blount DG, Riley EM. IL-10: the master regulator of immunity to infection. J Immunol. 2008;180(9):5771–7.CrossRef
13.
go back to reference Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med. 2020;217(6):e20200652.CrossRef Barnes BJ, Adrover JM, Baxter-Stoltzfus A, et al. Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med. 2020;217(6):e20200652.CrossRef
14.
go back to reference 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. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020;26(6):842–4.CrossRef 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. Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19. Nat Med. 2020;26(6):842–4.CrossRef
15.
go back to reference Alosaimi B, Hamed ME, Naeem A, Alsharef AA, AlQahtani SY, AlDosari KM, Alamri AA, Al-Eisa K, Khojah T, Assiri AM, Enani MA. MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract. Cytokine. 2020;126:154895.CrossRef Alosaimi B, Hamed ME, Naeem A, Alsharef AA, AlQahtani SY, AlDosari KM, Alamri AA, Al-Eisa K, Khojah T, Assiri AM, Enani MA. MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract. Cytokine. 2020;126:154895.CrossRef
17.
go back to reference Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, Lang C, Xiao Q, Xiao K, Yi Z, Qiang M, Xiang J, Zhang B, Chen Y, Gao C. Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br J Haematol. 2020;189:428–37.CrossRef Wan S, Yi Q, Fan S, Lv J, Zhang X, Guo L, Lang C, Xiao Q, Xiao K, Yi Z, Qiang M, Xiang J, Zhang B, Chen Y, Gao C. Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients. Br J Haematol. 2020;189:428–37.CrossRef
18.
go back to reference Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, Zhang P, Liu X, Gao G, Liu F, Jiang Y, Cheng X, Zhu C, Xia Y. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9:1123–30.CrossRef Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, Zhang P, Liu X, Gao G, Liu F, Jiang Y, Cheng X, Zhu C, Xia Y. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9:1123–30.CrossRef
20.
go back to reference Middleton EA, He XY, Denorme F, et al. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020;136(10):1169–79.CrossRef Middleton EA, He XY, Denorme F, et al. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. 2020;136(10):1169–79.CrossRef
Metadata
Title
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome
Authors
Laura Pandolfi
Tommaso Fossali
Vanessa Frangipane
Sara Bozzini
Monica Morosini
Maura D’Amato
Sara Lettieri
Mario Urtis
Alessandro Di Toro
Laura Saracino
Elena Percivalle
Stefano Tomaselli
Lorenzo Cavagna
Emanuela Cova
Francesco Mojoli
Paola Bergomi
Davide Ottolina
Daniele Lilleri
Angelo Guido Corsico
Eloisa Arbustini
Riccardo Colombo
Federica Meloni
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2020
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-020-01343-z

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