Elevated markers of gut leakage and inflammasome activation in COVID‐19 patients with cardiac involvement

Background A high proportion of COVID‐19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS‐CoV‐2 and the renin‐angiotensin system, as well as inflammatory mechanisms have been suggested to play a...

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Bibliographic Details
Published in:Journal of Internal Medicine 2021-04, Vol.289 (4), p.523-531
Main Authors: Hoel, H., Heggelund, L., Reikvam, D. H., Stiksrud, B., Ueland, T., Michelsen, A. E., Otterdal, K., Muller, K. E., Lind, A., Muller, F., Dudman, S., Aukrust, P., Dyrhol‐Riise, A. M., Holter, J. C., Trøseid, M.
Format: Article
Language:English
Subjects:
ACE2
Acute-Phase Proteins - metabolism
Angiotensin
Angiotensin-converting enzyme 2
Basale medisinske, odontologiske og veterinærmedisinske fag: 710
Basic medical, dental and veterinary science disciplines: 710
Calcium-binding protein
Carrier Proteins - metabolism
CCR9
CCR9 protein
Chemokine receptors
Chemokines, CC - metabolism
Coronary artery disease
Correlation of Data
COVID-19
COVID-19 - complications
COVID-19 - immunology
Damage
Digestive system
Digestive tract
Fatty acid-binding protein
Fatty acids
Gastrointestinal Microbiome - immunology
gut
heart
Heart diseases
Heart Diseases - immunology
Heart Diseases - virology
Homing
Humans
inflammasome
Inflammasomes
Inflammasomes - metabolism
Inflammation
Interleukin-18 - metabolism
Interleukin-1beta - metabolism
Intestinal microflora
Intestinal Mucosa - immunology
Intestinal Mucosa - microbiology
Intestinal Mucosa - physiopathology
Intestine
LBP
Leakage
Lipopolysaccharides
Lymphocytes
Lymphocytes T
Markers
Medical disciplines: 700
Medisinske Fag: 700
Membrane Glycoproteins - metabolism
Microbiota
Microorganisms
Natriuretic Peptide, Brain - blood
Original
Peptide Fragments - blood
Peptidyl-dipeptidase A
Plasma levels
Proteins
Receptors
Regulatory proteins
Renin
SARS-CoV-2 - pathogenicity
SARS-CoV-2 - physiology
Severe acute respiratory syndrome coronavirus 2
Troponin
Troponin - blood
VDP
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Summary:Background A high proportion of COVID‐19 patients have cardiac involvement, even those without known cardiac disease. Downregulation of angiotensin converting enzyme 2 (ACE2), a receptor for SARS‐CoV‐2 and the renin‐angiotensin system, as well as inflammatory mechanisms have been suggested to play a role. ACE2 is abundant in the gut and associated with gut microbiota composition. We hypothesized that gut leakage of microbial products, and subsequent inflammasome activation could contribute to cardiac involvement in COVID‐19 patients. Methods Plasma levels of a gut leakage marker (LPS‐binding protein, LBP), a marker of enterocyte damage (intestinal fatty acid binding protein, IFABP), a gut homing marker (CCL25, ligand for chemokine receptor CCR9) and markers of inflammasome activation (IL‐1β, IL‐18 and their regulatory proteins) were measured at three time points (day 1, 3–5 and 7–10) in 39 hospitalized COVID‐19 patients and related to cardiac involvement. Results Compared to controls, COVID‐19 patients had elevated plasma levels of LBP and CCL25 but not IFABP, suggesting impaired gut barrier function and accentuated gut homing of T cells without excessive enterocyte damage. Levels of LBP were twice as high at baseline in patients with elevated cardiac markers compared with those without and remained elevated during hospitalization. Also, markers of inflammasome activation were moderately elevated in patients with cardiac involvement. LBP was associated with higher NT‐pro‐BNP levels, whereas IL‐18, IL‐18BP and IL‐1Ra were associated with higher troponin levels. Conclusion Patients with cardiac involvement had elevated markers of gut leakage and inflammasome activation, suggestive of a potential gut‐heart axis in COVID‐19.
ISSN:0954-6820
1365-2796
1365-2796
DOI:10.1111/joim.13178