Details

Autor(en) / Beteiligte

• Michels, Erik H A
• Appelman, Brent
• de Brabander, Justin
• van Amstel, Rombout B E
• van Linge, Christine C A
• Chouchane, Osoul
• Reijnders, Tom D Y
• Schuurman, Alex R
• Sulzer, Titia A L
• Klarenbeek, Augustijn M
• Douma, Renée A
• Bos, Lieuwe D J
• Wiersinga, W Joost
• Peters-Sengers, Hessel
• van der Poll, Tom

Titel

Host Response Changes and Their Association with Mortality in COVID-19 Patients with Lymphopenia

Ist Teil von

• American journal of respiratory and critical care medicine, 2024-02, Vol.209 (4), p.402

Ort / Verlag

United States

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Lymphopenia in coronavirus disease (COVID-19) is associated with increased mortality. To explore the association between lymphopenia, host response aberrations, and mortality in patients with lymphopenic COVID-19. We determined 43 plasma biomarkers reflective of four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, cytokine release, and chemokine release. We explored if decreased concentrations of lymphocyte-derived proteins in patients with lymphopenia were associated with an increase in mortality. We sought to identify host response phenotypes in patients with lymphopenia by cluster analysis of plasma biomarkers. A total of 439 general ward patients with COVID-19 were stratified by baseline lymphocyte counts: normal (>1.0 × 10 /L;  = 167), mild lymphopenia (>0.5 to ⩽1.0 × 10 /L;  = 194), and severe lymphopenia (⩽0.5 × 10 /L;  = 78). Lymphopenia was associated with alterations in each host response domain. Lymphopenia was associated with increased mortality. Moreover, in patients with lymphopenia (  = 272), decreased concentrations of several lymphocyte-derived proteins (e.g., CCL5, IL-4, IL-13, IL-17A) were associated with an increase in mortality (at  < 0.01 or stronger significance levels). A cluster analysis revealed three host response phenotypes in patients with lymphopenia: "hyporesponsive" (23.2%), "hypercytokinemic" (36.4%), and "inflammatory-injurious" (40.4%), with substantially differing mortality rates of 9.5%, 5.1%, and 26.4%, respectively. A 10-biomarker model accurately predicted these host response phenotypes in an external cohort with similar mortality distribution. The inflammatory-injurious phenotype showed a remarkable combination of relatively high inflammation and organ damage markers with high antiinflammatory cytokine levels yet low proinflammatory cytokine levels. Lymphopenia in COVID-19 signifies a heterogenous group of patients with distinct host response features. Specific host responses contribute to lymphopenia-associated mortality in COVID-19, including reduced CCL5 levels.