TY - JOUR
T1 - Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response
AU - Blankestijn, Jelle M
AU - Baalbaki, Nadia
AU - Bazdar, Somayeh
AU - Beekers, Inés
AU - Beijers, Rosanne J H C G
AU - van den Bergh, Joop P
AU - Bloemsma, Lizan D
AU - Cornelissen, Merel E B
AU - Dekker, Tamara
AU - Duitman, Jan Willem
AU - Houweling, Laura
AU - Jacobs, John J L
AU - van der Lee, Ivo
AU - Linders, Paulien M A
AU - Noij, Lieke C E
AU - Nossent, Esther J
AU - van de Pol, Marianne A
AU - Sondermeijer, Brigitte M
AU - Geelhoed, J J Miranda
AU - Weersink, Els J M
AU - Golebski, Korneliusz
AU - Abdel-Aziz, Mahmoud I
AU - Maitland-van der Zee, Anke H
AU - P4O2 Consortium
PY - 2024/9
Y1 - 2024/9
N2 - Background: Months after infection with severe acute respiratory syndrome coronavirus 2, at least 10% of patients still experience complaints. Long-COVID (coronavirus disease 2019) is a heterogeneous disease, and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood. Objectives: We sought to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease. Methods: Blood was collected from 77 patients with long-COVID from the Precision Medicine for more Oxygen (P4O2) COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analyzed for differences in clinical features, pulmonary function tests, and gene ontology term enrichment. Results: Clustering revealed 2 distinct clusters on a transcriptome level. Compared with cluster 2 (n = 65), patients in cluster 1 (n = 12) showed a higher rate of preexisting cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during severe acute respiratory syndrome coronavirus 2 infection (median, 3 vs 8 days), lower FEV
1/forced vital capacity (72% vs 81%), and lower diffusion capacity of the lung for carbon monoxide (68% vs 85% predicted). Gene ontology term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, whereas genes involved with the adaptive immune response were upregulated in cluster 2. Conclusions: This study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient.
AB - Background: Months after infection with severe acute respiratory syndrome coronavirus 2, at least 10% of patients still experience complaints. Long-COVID (coronavirus disease 2019) is a heterogeneous disease, and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood. Objectives: We sought to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease. Methods: Blood was collected from 77 patients with long-COVID from the Precision Medicine for more Oxygen (P4O2) COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analyzed for differences in clinical features, pulmonary function tests, and gene ontology term enrichment. Results: Clustering revealed 2 distinct clusters on a transcriptome level. Compared with cluster 2 (n = 65), patients in cluster 1 (n = 12) showed a higher rate of preexisting cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during severe acute respiratory syndrome coronavirus 2 infection (median, 3 vs 8 days), lower FEV
1/forced vital capacity (72% vs 81%), and lower diffusion capacity of the lung for carbon monoxide (68% vs 85% predicted). Gene ontology term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, whereas genes involved with the adaptive immune response were upregulated in cluster 2. Conclusions: This study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient.
KW - DLCO
KW - Long-COVID
KW - Transcriptomics
KW - lung function
KW - phenotyping
U2 - 10.1016/j.jaci.2024.04.032
DO - 10.1016/j.jaci.2024.04.032
M3 - Article
SN - 0091-6749
VL - 154
SP - 807
EP - 818
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -