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

Pandolfi, L.; Fossali, T.; Frangipane, V.; Bozzini, S.; Morosini, M.; D'Amato, M.; Lettieri, S.; Urtis, M.; Di Toro, A.; Saracino, L.; Percivalle, E.; Tomaselli, S.; Cavagna, L.; Cova, E.; Mojoli, F.; Bergomi, P.; ottolina, d.; Lilleri, D.; Corsico, A. G.; Arbustini, E.; Colombo, R.; Meloni, F.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. We conducted a prospective study to assess deep lung inflammatory status in patients with moderate to severe COVID-19. 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. ICU patients showed a marked increase in neutrophils (72%, 60-81), lower lymphocyte (8%, 4-12) and macrophages fractions (17%, 11-27) compared to IMW patients (3%, 2-17, 15%, 6-26 and 74%, 58-90, respectively) (p<0.01). Ultrastructural study from ICU patients showed viral-like particles in cytopathic mononuclear cells however extensive cytopathic damage in all cell lineages. Immunostaining with anti-viral capsid and spike antibodies specifically immunoreacted with BAL cells, mostly cytopathic ones. 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). 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