Expression of TRAIL, IP-10, and CRP in children with suspected COVID-19 and real-life impact of a computational signature on clinical decision-making: a prospective cohort study

Abstract

Purpose We evaluated the host-response marker score “BV” and its components TRAIL, IP-10, and CRP in SARS-CoV-2 positive children, and estimated the potential impact on clinical decision-making. Methods We prospectively analyzed levels of TRAIL, IP-10, CRP, and the BV score, in children with suspected COVID19. Classifcation of infectious etiology was performed by an expert panel. We used a 5-point-questionnaire to evaluate the intention to treat with antibiotics before and after receiving test results. Results We screened 111 children, of whom 6 (5.4%) were positive for SARS-CoV-2. A total of 53 children were included for the exploratory analysis. Median age was 3.1 years (interquartile range [IQR] 1.3–4.3), and 54.7% (n=29) were girls. A viral and a bacterial biomarker pattern was found in 27/53 (50.9%) and 15/53 (28.3%), respectively. BV scores difered between COVID-19, children with other viral infections, and children with bacterial infections (medians 29.5 vs. 9 vs. 66; p=0.0006). Similarly, median TRAIL levels were diferent (65.5 vs. 110 vs. 78; p=0.037). We found no diferences in IP-10 levels (555 vs. 504 vs. 285; p=0.22). We found a concordance between physicians’ “unlikely intention to treat” children with a viral test result in most cases (n=19/24, 79.2%). When physicians expressed a “likely intention to treat” (n=15), BV test revealed 5 bacterial, viral, and equivocal scores each. Antibiotics were withheld in three cases (20%). Overall, 27/42 (64%) of pediatricians appraised the BV test positively, and considered it helpful in clinical practice. Conclusion Host-response based categorization of infectious diseases might help to overcome diagnostic uncertainty, support clinical decision-making and reduce unnecessary antibiotic treatment.