2160. Mucosal Antiviral Cytokine Responses Are Impaired in Children and Adolescents with Severe COVID-19
Authors: Quintero Ana M , Cohen Shira H , Xu Zhaohui , Ye Fang , Mertz Sara , Massey Kaitlyn N , Peachey Colin L , Pifer Traci , Leber Amy , Sanchez Pablo J , Ramilo Octavio , Mejias Asuncion 
Published: December 2022

Abstract

Background
The factors associated with severe COVID-19 in pediatric patients remain poorly understood. We sought to determine whether mucosal innate immunity cytokines were associated with disease severity in children and adolescents with acute COVID-19.

Methods
Single-center, prospective study including children and adolescents &lt; 21 years of age hospitalized because of symptomatic COVID-19 from 3/2020 to 1/2021, and age, sex and race matched pre-pandemic (2016-2019) healthy controls. Nasopharyngeal (NP) samples were obtained at enrollment for measurement of SARS-CoV-2 viral loads by rt-PCR and cytokine concentrations using a 92-plex inflammation/antiviral panel (Olink). Disease severity was assessed by the need for supplemental oxygen or PICU admission, and patients classified as severe and non-severe based on these two parameters. Statistical analyses were performed in R studio and Benjamini-Hochberg applied to adjust for multiple comparisons.

Results
Of the 75 children with acute COVID-19 (median IQR age: 3.4 [0.2-15.3] years), 28 (37%) were classified as severe COVID-19 (19 PICU; 25 supplemental oxygen) and 47 (63%) were non-severe. Children with severe COVID-19 were predominantly male and had an underlying condition more frequently than those with non-severe disease (79% vs 49% respectively; p&lt; 0.01, Table 1). SARS-CoV-2 viral loads were comparable between groups, yet patients with severe COVID-19 had significantly higher concentrations of C-reactive protein (p=0.04), more frequent lymphopenia (p=0.03) and cardiac involvement (p=0.04), and received COVID-19 directed therapies more commonly (p&lt; 0.001). Comparative analyses identified 24 cytokines that were significantly different between children with acute COVID-19 versus 45 healthy controls. Of those, concentrations of IFN-γ (p=0.004), CXCL10 (p=0.01), CXCL11 (p=0.02) and CCL19 (p=0.02) were significantly lower in children with severe versus those with non-severe COVID-19 (Fig 1). Table 1.Demographic and clinical characteristics in children with symptomatic COVID-19*Bolded p-values indicates statistical significance. Abbreviations: N, number. CRP, C-Reactive protein; PICU, pediatric intensive care unit.**Other including the following underlying conditions: prematurity, endocrine conditions, immunocompromising conditions, prematurity, trisomy 21 and complex care. Ł Lymphopenia defined as an ALC of &lt;4,500 cells/μl in infants, and &lt;1,500 cells /μl in children &gt;12 months of age
Continuous variables displayed as medians and 25%-75% interquartile ranges (IQR), Mann-Whitney test was used to determine differences between two groups; Kruskal-Wallis & Dunn’s multiple test correction was used to determine differences between three groups (p-values*). Categorical data expressed as numbers and proportions (in parenthesis) and analyzed by Fisher’s exact test or Chi square test. Figure 1.Nasal mucosal concentrations of antiviral/regulatory cytokines in children with symptomatic COVID-19 according to disease severity

Conclusion
Mucosal concentrations of antiviral/regulatory cytokines were decreased in children with severe COVID-19. These findings suggest that impaired mucosal innate immune responses might favor SARS-CoV-2 disease progression and severity in children.

Disclosures
Amy Leber, PhD, BioFire: Advisor/Consultant|BioFire: Grant/Research Support|Biorad: Advisor/Consultant|Cepheid: Grant/Research Support Octavio Ramilo, MD, Adagio: Advisor/Consultant|Bill & Melinda Gates Foundation: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Lilly: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Honoraria Asuncion Mejias, MD, PhD, MsCS, AstraZeneca: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant|Sanofi-Pasteur: Honoraria.