Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome
inflammation
First Author: Laura Pandolfi
Journal/preprint name: Research Square preprint under consideration at BMC Pulmonary Medicine
Paper DOI: https://doi.org/10.21203/rs.3.rs-49968/v2
Tags: COVID-19 associated alveolitis, bronchoalveolar lavage, IL-6 and IL-8
Summary
Pandolfi et al. assess and compare the broncho-alveolar inflammatory environment between COVID-19 patients admitted to Intensive Care Unit (ICU) and Intermediate Medicine Ward (IMW) at two main COVID-19 centers of Italy (located in Pavia/Milan). Inflammatory cell and cytokine analysis of bronchoalveolar lavage (BAL) samples suggest that hyperactivation of innate immune effectors, particularly neutrophil infiltration, contribute to COVID-19 associated alveolitis in severe cases. Furthermore, elevated levels of pro-inflammatory cytokines (IL-6 and 8) correlate with alveolar inflammatory status and patient clinical outcome.
Research Highlights
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ICU patients showed a significant increase in neutrophils, and relatively lower lymphocyte and macrophage levels, compared to IMW patients. Neutrophil infiltration at alveolar level did not correlate with clinical outcome.
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BAL collected from COVID-19 ICU patients revealed extensive cytopathic damage in all cell types, including loss of nuclear & plasma membrane integrity, pseudopodia formation and cytoplasm vacuolization. Presence of viral particles were also observed in cytopathic epithelial and mononuclear cells.
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Pro-inflammatory IL-6 and IL-8 cytokines were significantly higher in BAL samples derived from ICU compared to IMW COVID-19 patients. Additionally, non-survivors (N=12) had higher IL-6/IL-8 BAL levels compared to survivors (N=16).
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Patients treated with steroids had lower BAL IL-6 compared to patients on tocilizumab or antivirals (remdesivir, lopinavir/ritonavir or hydroxychloroquine).
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Direct correlation between BAL IL-6/IL-8 and neutrophil count. In contrast, IL-6/IL-8 levels inversely correlated with percentage of macrophages. BAL IL-8 also inversely correlated with lymphocyte count.
Impact for COVID-19 research:
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Increased IL-6 and IL-8 levels in broncho-alveolar environment of COVID-19 patients correlates with neutrophil infiltration and is associated with clinical outcome. Steroid treatment could reduce IL-6 levels in severe COVID-19 cases, potentially leading to better outcome.
Methodologies:
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Study Type: Patient cohort
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Key Techniques: Assessment of BAL cell differentials, ultrastructural cell analysis and cytokine profiling
Limitations:
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Small patient cohort (N=33; 28 ICU and 5 IMW). Majority of patients were male.
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Small sample size limited the possibility of additional analysis (e.g. flow cytometric evaluation cell surface activation markers).
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The study is specific to a particular time & place and cannot be generalised.
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Paired assessment of inflammatory cytokines in peripheral blood was not possible due to lack of stored serum samples from acute COVID-19 patients/healthy donors.
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Pre-existing comorbidities may have influenced cellular infiltration and cytokine levels.