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High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in
Anders Tveita1,2, Sarah Louise Murphy3,4, Jan Cato Holter3,5
1Department of Internal Medicine, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway.
Insights
Elevated levels of homeostatic chemokines CCL19 and CCL21 indicate immune dysregulation in severe COVID-19 patients. These markers correlate with disease severity and mortality, suggesting a role in COVID-19 pathogenesis.
Area of Science:
- Immunology
- Virology
- Pathophysiology
Background:
- Immune dysregulation contributes to severe COVID-19.
- Homeostatic chemokines CCL19 and CCL21 are implicated in inflammation.
- Limited data exists on CCL19 and CCL21 regulation in SARS-CoV-2 infection.
Purpose of the Study:
- Investigate CCL19 and CCL21 levels in COVID-19 patients.
- Determine the correlation between chemokine levels and disease severity.
- Explore potential regulatory mechanisms of these chemokines.
Main Methods:
- Serial blood samples from 414 hospitalized COVID-19 patients.
- Analysis of circulating CCL19 and CCL21 during hospitalization and follow-up.
- In vitro assays and public RNAseq data analysis.
Main Results:
- Consistent increase in circulating CCL19 and CCL21 levels observed.
- High chemokine levels correlated with disease severity (respiratory failure, ICU need, mortality).
- High CCL21 at admission linked to persistent pulmonary function impairment at 3 months.
Conclusions:
- CCL19 and CCL21 serve as markers of immune dysregulation in COVID-19.
- Aberrant chemokine regulation may be triggered by tissue inflammation.
- Further research is needed on chemokine source, regulation, and lung effects in COVID-19.
Background:
Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients.
Methods:
Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms.
Results:
A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up.
Conclusions:
Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19.
Clinical Trials Registration:
NCT04321616 and NCT04381819.
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