Association of viral load with TRAIL, IP‐10, CRP biomarker signature and disease severity in children with respiratory tract infection or fever without source: A prospective, multicentre cohort study

• Published in: Journal of medical virology Vol. 95; no. 1; pp. e28113 - n/a
• Main Authors: Papan, Cihan, Argentiero, Alberto, Adams, Ortwin, Porwoll, Marian, Hakim, Ummaya, Farinelli, Edoardo, Testa, Ilaria, Pasticci, Maria B., Mezzetti, Daniele, Perruccio, Katia, Simon, Arne, Liese, Johannes G., Knuf, Markus, Stein, Michal, Yacobov, Renata, Bamberger, Ellen, Schneider, Sven, Esposito, Susanna, Tenenbaum, Tobias
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-01-2023
• Subjects: adenovirus; Apoptosis; Bacterial diseases; Biomarkers; Chemokine CXCL10; Child; Children; Cohort analysis; Combinatorial analysis; CRP; Diagnosis; Fever; host response; host‐protein signature; Humans; Infant; Infections; Influenza; IP‐10; Ligands; Oxygen; Oxygen therapy; Patient Acuity; Prospective Studies; Proteins; Respiratory syncytial virus; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory tract; Respiratory tract diseases; Respiratory tract infection; Respiratory Tract Infections - diagnosis; Rhinovirus; RSV; severity; TRAIL; TRAIL protein; Tumor Necrosis Factor-alpha; Viral Load; Virology; Viruses; CRP; host response; influenza; severity; TRAIL; viral load; RSV; biomarkers; adenovirus; IP-10; rhinovirus; host-protein signature
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.28113

Background
To investigate the association of viral load (VL) with (i) tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL), interferon gamma‐induced protein‐10, C‐reactive protein, and a combinatorial score (BV score), and (ii) clinical severity.
Study Design
In this prospective, multicentre cohort substudy, children with respiratory tract infection or fever without source were enrolled. VL for influenza virus, rhinovirus, respiratory syncytial virus, and adenovirus was measured from nasopharyngeal swabs. The reference standard diagnosis was established based on expert panel adjudication.
Results
Of 1140 recruited patients, 333 had a virus monodetection. VL for the aggregated data set correlated with TRAIL and IP‐10 levels, with the length of oxygen therapy, and inversely with the BV score. At a single viral level, only the influenza VL yielded a correlation with TRAIL, IP‐10 levels, and the BV score. Children with a viral reference standard diagnosis had significantly higher VL than those with bacterial infection (p = 0.0005). Low TRAIL (incidence rate ratio [IRR] 0.6, 95% confidence interval [CI] 0.39–0.91) and young age (IRR 0.62, 95% CI 0.49–0.79) were associated with a longer hospital stay, while young age (IRR 0.33, 95% CI 0.18–0.61), low TRAIL (IRR 0.25, 95% CI 0.08–0.76), and high VL (IRR 1.16, 95% CI 1.00–1.33) were predictive of longer oxygen therapy.
Conclusion
These findings indicate that VL correlates with biomarkers and may serve as a complementary tool pertaining to disease severity.