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Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19.
Saris, Anno; Reijnders, Tom D Y; Nossent, Esther J; Schuurman, Alex R; Verhoeff, Jan; Asten, Saskia van; Bontkes, Hetty; Blok, Siebe; Duitman, Janwillem; Bogaard, Harm-Jan; Heunks, Leo; Lutter, Rene; van der Poll, Tom; Garcia Vallejo, Juan J.
  • Saris A; Center for Experimental and Molecular Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands a.saris@amsterdamumc.nl.
  • Reijnders TDY; Infectious Disease, Leiden Universitair Medisch Centrum, Leiden, The Netherlands.
  • Nossent EJ; Center for Experimental and Molecular Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.
  • Schuurman AR; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • Verhoeff J; Amsterdam Cardiovascular Sciences Research Institute, Amsterdam UMC, Amsterdam, The Netherlands.
  • Asten SV; Center for Experimental and Molecular Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.
  • Bontkes H; Department of Molecular Cell Biology & Immunology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • Blok S; Amsterdam institute for infection and immunity, Amsterdam, Netherlands.
  • Duitman J; Department of Molecular Cell Biology & Immunology, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • Bogaard HJ; Amsterdam institute for infection and immunity, Amsterdam, Netherlands.
  • Heunks L; Medical Immunology Laboratory, Department of Clinical Chemistry, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • Lutter R; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
  • van der Poll T; Center for Experimental and Molecular Medicine, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands.
  • Garcia Vallejo JJ; Department of Pulmonary Medicine, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands.
Thorax ; 76(10): 1010-1019, 2021 10.
Article in English | MEDLINE | ID: covidwho-1180971
Preprint
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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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Inflammation Mediators / COVID-19 / Immunity, Cellular Type of study: Observational study / Prognostic study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Thorax Year: 2021 Document Type: Article Affiliation country: Thoraxjnl-2020-216256

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Inflammation Mediators / COVID-19 / Immunity, Cellular Type of study: Observational study / Prognostic study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Thorax Year: 2021 Document Type: Article Affiliation country: Thoraxjnl-2020-216256