Immunological profiling in long COVID: overall low grade inflammation and T-lymphocyte senescence and increased monocyte activation correlating with increasing fatigue severity

Frontiers in Immunology

Immunology

Hemmo A. Drexhage¹  Daniel G. Aynekulu Mersha¹  Annemarie J. M. Wijkhuijs¹  L. Martine Bek²  Rita J. G. van den Berg-Emons²  Majanka H. Heijenbrok-Kal³  Gerard M. Ribbers³  Merel E. Hellemons⁴  Julia C. Berentschot⁴  Joachim G. J. V. Aerts⁴  Rudi W. Hendriks⁴  Marion P. G. Koopmans⁵  Corine H. GeurtsvanKessel⁵  Jolanda J. C. Voermans⁵  Maaike de Bie⁶  Willem A. Dik⁶  Nicole M. A. Nagtzaam⁶ 

[1] Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands;Department of Rehabilitation Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands;Department of Rehabilitation Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands;Rijndam Rehabilitation, Rotterdam, Netherlands;Department of Respiratory Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands;Department of Viroscience, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands;Laboratory Medical Immunology, Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands;

关键词: COVID-19;    long COVID;    fatigue;    inflammation;    monocytes;    T-lymphocytes;   

DOI  :  10.3389/fimmu.2023.1254899

 received in 2023-07-07, accepted in 2023-09-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundMany patients with SARS-CoV-2 infection develop long COVID with fatigue as one of the most disabling symptoms. We performed clinical and immune profiling of fatigued and non-fatigued long COVID patients and age- and sex-matched healthy controls (HCs).MethodsLong COVID symptoms were assessed using patient-reported outcome measures, including the fatigue assessment scale (FAS, scores ≥22 denote fatigue), and followed up to one year after hospital discharge. We assessed inflammation-related genes in circulating monocytes, serum levels of inflammation-regulating cytokines, and leukocyte and lymphocyte subsets, including major monocyte subsets and senescent T-lymphocytes, at 3-6 months post-discharge.ResultsWe included 37 fatigued and 36 non-fatigued long COVID patients and 42 HCs. Fatigued long COVID patients represented a more severe clinical profile than non-fatigued patients, with many concurrent symptoms (median 9 [IQR 5.0-10.0] vs 3 [1.0-5.0] symptoms, p<0.001), and signs of cognitive failure (41%) and depression (>24%). Immune abnormalities that were found in the entire group of long COVID patients were low grade inflammation (increased inflammatory gene expression in monocytes, increased serum pro-inflammatory cytokines) and signs of T-lymphocyte senescence (increased exhausted CD8+ TEMRA-lymphocytes). Immune profiles did not significantly differ between fatigued and non-fatigued long COVID groups. However, the severity of fatigue (total FAS score) significantly correlated with increases of intermediate and non-classical monocytes, upregulated gene levels of CCL2, CCL7, and SERPINB2 in monocytes, increases in serum Galectin-9, and higher CD8+ T-lymphocyte counts.ConclusionLong COVID with fatigue is associated with many concurrent and persistent symptoms lasting up to one year after hospitalization. Increased fatigue severity associated with stronger signs of monocyte activation in long COVID patients and potentially point in the direction of monocyte-endothelial interaction. These abnormalities were present against a background of immune abnormalities common to the entire group of long COVID patients.

【 授权许可】

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Copyright © 2023 Berentschot, Drexhage, Aynekulu Mersha, Wijkhuijs, GeurtsvanKessel, Koopmans, Voermans, Hendriks, Nagtzaam, de Bie, Heijenbrok-Kal, Bek, Ribbers, van den Berg-Emons, Aerts, Dik and Hellemons