PT  - JOURNAL ARTICLE
AU  - Anno Saris
AU  - Tom D Y Reijnders
AU  - Esther J Nossent
AU  - Alex R Schuurman
AU  - Jan Verhoeff
AU  - Saskia van Asten
AU  - Hetty Bontkes
AU  - Siebe Blok
AU  - Janwillem Duitman
AU  - Harm-Jan Bogaard
AU  - Leo Heunks
AU  - Rene Lutter
AU  - Tom van der Poll
AU  - Juan J Garcia Vallejo
ED  - ,
TI  - Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19
AID  - 10.1136/thoraxjnl-2020-216256
DP  - 2021 Oct 01
TA  - Thorax
PG  - 1010--1019
VI  - 76
IP  - 10
4099  - http://thorax.bmj.com/content/76/10/1010.short
4100  - http://thorax.bmj.com/content/76/10/1010.full
SO  - Thorax2021 Oct 01; 76
AB  - 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.The data that support the findings of this study are available from the corresponding author, AS, upon reasonable request.