Abstract
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.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions
From March 7 to April 30, a total of 45 bronchoalveolar lavage (BAL) samples were collected from 5 Intermediate Medicine Ward (IMW) and 28 Intensive care unit (ICU) patients with proven COVID-19 infection
We assessed BAL cell differentials in ICU and in IMW patients that presented a median of total cells of 0.25 × 106 ml− 1 (0.15–0.52) and 0.3 × 106 ml− 1 (0.15– 0.52), respectively (p > 0.999)
Summary
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. Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), detected in Wuhan (China) in December 2019 [1], spread rapidly around the world, reaching pandemic proportions in March 2020. The typical clinical manifestation is severe pneumonia with hyperactivation of the inflammatory cascade and progression to acute respiratory distress syndrome (ARDS) in about 30% of patients [2,3,4]. Most research papers have focused on the inflammatory status at the plasma level of COVID-19 patients [3,4,5,6,7]. Limited data are available about alveolar inflammatory status in COVID-19 patients because of concerns in relation to using bronchoscopy to avoid aerosol generation
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