Abstract
Background: Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses.
Methods: This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma.
Findings: Paired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the ƴδ T cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma.
Interpretation: The bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response.
Keywords: COVID-19; pneumonia; respiratory infection; viral infection.
【저자키워드】 COVID-19, viral infection, Pneumonia, respiratory infection, 【초록키워드】 viral infection, immune response, intensive care, severe COVID-19, Immune profile, Local, CD4, ICU, Peripheral blood, T cell, Bronchoalveolar lavage fluid, pathophysiology, Lungs, plasma, T cell receptor, BALF, patients, Blood, T cell activation, marker, Prolonged, CD8 T cell, fatal COVID-19, pulmonary immune response, effector memory, responses, Cell, inflammatory mediator, bronchoalveolar, examined, died, proportion, analysed, reduced, unique, expressed, expressing, purified, Increased, these cell, were measured, activated T cell, patients with COVID-19, 【제목키워드】 Immune profile, airway, Blood, cellular, Critically ill patient, with COVID-19,