Association of Salivary Micro Ribonucleic Acid Levels With the Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may impact immune-related micro ribonucleic acids (miRNAs). The role of salivary miRNAs as predictors of severe infection in children is unknown. This study sought to examine the relationship between SARS-CoV-2 severity and salivary miRNA levels in children. A convenience sample of 400 children with SARS-CoV-2 infection was prospectively evaluated between March 2021 and February 2022 at two U.S. children's hospitals. Saliva swabs were obtained. Levels of 3 miRNAs previously implicated in SARS-CoV-2 pathophysiology were measured with quantitative polymerase chain reaction (miR-1273c, miR-296-5p, and miR-4495). The primary outcome measure was the occurrence of severe illness, including respiratory failure, shock, or death from a related cause within 1 month of evaluation. Disease resolution was determined through chart review and caretaker phone calls 4 weeks after the initial visit. Saliva samples from 395 (severe = 105) participants (mean age: 7.4 ± 5.9 years, 51.7% female, 54.7% African American) were analyzed. Children with severe outcomes had lower levels of miR-296-5p (fold difference: 0.361, d = 0.111, p = 0.046). Multivariable adjusted logistic regression analysis demonstrated an inverse association between severe outcomes and levels of miR-296-5p (adjusted odds ratio = 0.89; 95% confidence interval [0.81, 0.98], p = 0.021) while controlling for age, sex, race, weight, insurance, diabetes, asthma, fever, and symptom duration. The model had an area under curve of 0.744 (sensitivity = 0.71, specificity = 0.66). Measurement of saliva miRNA in conjunction with demographic and clinical characteristics may aid in the prediction of severe illness. Larger, longitudinal studies to assess the utility of salivary miRNAs in SARS-CoV-2 and other viral infections are needed.

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