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

BMC Pulm Med. 2020 Nov 16;20(1):301. doi: 10.1186/s12890-020-01343-z.

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.

MeSH terms

  • Adenosine Monophosphate / analogs & derivatives
  • Adenosine Monophosphate / therapeutic use
  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Alanine / analogs & derivatives
  • Alanine / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antiviral Agents / therapeutic use
  • Betacoronavirus
  • Bronchoalveolar Lavage
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology*
  • Bronchoalveolar Lavage Fluid / virology
  • COVID-19
  • COVID-19 Drug Treatment
  • Coronavirus Infections / drug therapy
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / therapy
  • Drug Combinations
  • Female
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Inflammation / immunology*
  • Intensive Care Units
  • Interleukin-10 / immunology
  • Interleukin-6 / immunology*
  • Interleukin-8 / immunology*
  • Italy
  • Leukocytes / immunology*
  • Leukocytes, Mononuclear / virology
  • Lopinavir / therapeutic use
  • Lung / cytology
  • Lung / immunology*
  • Lung / virology
  • Lymphocytes / immunology
  • Macrophages, Alveolar / immunology*
  • Male
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Neutrophils / immunology
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / therapy
  • Prognosis
  • Prospective Studies
  • Respiration, Artificial / methods
  • Ritonavir / therapeutic use
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / metabolism
  • Survival Rate
  • Virion / metabolism
  • Virion / ultrastructure

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Drug Combinations
  • Interleukin-6
  • Interleukin-8
  • Spike Glycoprotein, Coronavirus
  • lopinavir-ritonavir drug combination
  • spike protein, SARS-CoV-2
  • Interleukin-10
  • Lopinavir
  • remdesivir
  • Adenosine Monophosphate
  • Hydroxychloroquine
  • tocilizumab
  • Ritonavir
  • Alanine