Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome
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RESEARCH ARTICLE
Open Access
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome Laura Pandolfi1*† , Tommaso Fossali2†, Vanessa Frangipane1, Sara Bozzini1, Monica Morosini1, Maura D’Amato1, Sara Lettieri3, Mario Urtis4, Alessandro Di Toro4, Laura Saracino5, Elena Percivalle6, Stefano Tomaselli5, Lorenzo Cavagna7, Emanuela Cova8, Francesco Mojoli9, Paola Bergomi2, Davide Ottolina2, Daniele Lilleri10, Angelo Guido Corsico3, Eloisa Arbustini4, Riccardo Colombo2 and Federica Meloni3
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. Keywords: Bronchoalveolar lavage, COVID-19, Cytokines, Lung, SARS-CoV-2
* Correspondence: [email protected] † Laura Pandolfi and Tommaso Fossali contributed equally to this work. 1 Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100 Pavia, Italy Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or f
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