• 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, and Federica Meloni.
• Research Laboratory of Lung Diseases, Section of Cell Biology, IRCCS Policlinico San Matteo Foundation, 27100, Pavia, Italy. l.pandolfi@smatteo.pv.it.
• BMC Pulm Med. 2020 Nov 16; 20 (1): 301.

BackgroundSevere 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.MethodsDiagnostic 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.ResultsICU 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).ConclusionsAlveolitis, 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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