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

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

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 × 10(5) ml(− 1), 0.85–2.07), lower lymphocyte (0.97 × 10(5) ml(− 1), 0.024–0.34) and macrophages fractions (0.43 × 10(5) ml(− 1), 0.34–1.62) compared to IMW patients (0.095 × 10(5) ml(− 1), 0.05–0.73; 0.47 × 10(5) ml(− 1), 0.28–1.01 and 2.14 × 10(5) 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-020-01343-z.