@article {Saristhoraxjnl-2020-216256, author = {Anno Saris and Tom D Y Reijnders and Esther J Nossent and Alex R Schuurman and Jan Verhoeff and Saskia van Asten and Hetty Bontkes and Siebe Blok and Janwillem Duitman and Harm-Jan Bogaard and Leo Heunks and Rene Lutter and Tom van der Poll and Juan J Garcia Vallejo}, editor = {, and , and Nossent, Esther J and Duitman, Janwillem and Saris, Anno and Vries, Heder De and Meijboom, Lilian J and Bos, Lieuwe D and Blok, Siebe G and Schuurman, Alex R and Reijnders, Tom DY and Hugenholtz, F and Vallejo, Juan Garcia and Bontkes, Hetty and Vlaar, Alexander PJ and Wiersinga, Joost and Lutter, Ren{\'e} and Poll, Tom van der and Bogaard, Harm Jan and Heunks, Leo and de Bruin, S and Schuurman, AR and Koing, R and van Agtmael, AG Algera, MA and Baarle, FEHP van and Bax, DJC and Beudel, M and Bogaard, H J and Bomers, M and Bos, LDJ and Botta, M and de Brabander, J and de Bree, GJ and Bugiani, M and Bulle, EB and Chouchane, O and Cloherty, APM and Elbers, LM Fleuren, PE and Geerlings, SE and Geerts, BF and Geijtenbeek, TBH and Girbes, ARJ and Goorhuis, A and Grobusch, MP and Hafkamp, FMJ and Hagens, LA and Hamann, J and Harris, V C and Hemke, R and Hermans, SM and Heunks, LMA and Hollmann, MW and Horn, J and Hovius, JW and de Jong, MD and van Mourik, N and Nellen, JF and Paulus, F and Reijnders, TDY and Peters, E and van der Poll, T and preckel, B and Prins, JM and Raasveld, S J and Schinkel, M and Schultz, MJ and Sigaloff, K and Smit, MR and Stijnis, C and Stilma, W and Teunissen, CE and Thoral, P and Tsonas, AM and van der Valk, M and veelo, D P and de Vries, H and van Vugt, M and Wouters, D and Zwinderman, A H and Brouwer, M C and Wiersinga, W J and Vlaar, APJ and van de Beek, D}, title = {Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19}, elocation-id = {thoraxjnl-2020-216256}, year = {2021}, doi = {10.1136/thoraxjnl-2020-216256}, publisher = {BMJ Publishing Group Ltd}, 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{\textperiodcentered}3\% and 83{\textperiodcentered}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.}, issn = {0040-6376}, URL = {https://thorax.bmj.com/content/early/2021/05/13/thoraxjnl-2020-216256}, eprint = {https://thorax.bmj.com/content/early/2021/05/13/thoraxjnl-2020-216256.full.pdf}, journal = {Thorax} }