2164. Shared and Specific Systemic Cytokine Responses in Infants Hospitalized with SARS-CoV-2 versus RSV Infection
Authors: Cao Raquel Giacomelli , Xu Zhaohui , Ye Fang , Mertz Sara , Cohen Shira H , Pifer Traci , Leber Amy , Sanchez Pablo J , Mejias Asuncion , Ramilo Octavio 
Published: December 2022

Abstract

Background
Cytokines play a major role in the immune response to viral infections, contributing to viral clearance but also mediating immunopathology following infection. We sought to define and compare systemic cytokine responses in infants hospitalized with COVID-19 versus RSV infection (RSVi).

Methods
Prospective study of convenience cohort of infants hospitalized with PCR confirmed SARS-CoV-2 or RSVi, as well as pre-pandemic healthy controls (HC). Blood samples were obtained at enrollment and cytokine analysis performed using a 92-cytokine inflammation panel (Olink platform). Statistical analyses were performed in R environment.

Results
We enrolled 26 infants with COVID-19, 77 with RSVi, and 18 healthy infants as a comparator control group. Oxygen requirement was significantly more frequent in infants with RSVi (p=0.02), while presence of comorbidities was significantly more common in infants with COVID-19 (p=0.01). No statistical differences were identified in terms of length of stay, admission to pediatric intensive care unit, need for mechanical ventilation, and lymphocyte counts (Table 1). Principal component analysis (PCA) revealed clustering of the global cytokine profiles differentiating HC from infants with COVID-19 and RSVi (Figure 1A). Multiple comparison analysis among the three groups yielded 49 significantly different cytokines clustered in three groups. A first cluster that included cytokines such as CCL11, CCL19 and TNFSF12 were lower in both COVID-19 and RSVi compared to HC; a second cluster with CCL8, CXCL8 and CASP8 that were mildly increased in both COVID-19 and RSVi; and a third cluster that included IL6, IL17C and IFN-ɣ were markedly increased in both viral groups compared with HC (ANOVA padj&lt; 0.05) (Figure 1B). Direct comparison between COVID-19 and RSVi (padj&lt; 0.05 and FC &gt;1.5) identified 7 statistically different cytokines. CCL8, CXCL1, CCL20 concentrations were increased in COVID-19, while SIRT2, STAMBP, MMP10 and EIF4EBP1 concentrations were increased in RSVi (Figure 1C-D). Table 1.Demographic and clinical characteristics*Comparisons among RSV, COVID-19 and HC**Comparisons between RSV and COVID-19a 14 out of the 26 patients were tested for coinfectionHC: Healthy control; LOS: length of stay; PICU: pediatric intensive care unit. Comorbidities included prematurity, congenital heart disease, sickle cell disease, overweight, eczema, gastroesophageal reflux. Continuous variables displayed as medians with 25%-75% interquartile ranges (IQ). Mann-Whitney test was used to determine differences between two groups; Kruskal-Wallis test was used to determine differences between three groups. Categorical data expressed as numbers (and percentages) and analyzed by Fisher’s exact test or Chi square test.Figure 1.Cytokines’ concentrations in hospitalized infants with COVID-19 versus RSV infection.
A. Principal Component Analysis (PCA) Plot. Each dot represents an individual patient sample, and similar samples are clustered together according to their cytokine profiles. B. Heat map displaying serum cytokine concentrations in healthy controls (HC), COVID-19 and RSVi. Red represents increased concentrations while blue represents decreased concentrations compared with the HC. C. Heat map and D. Bar plots displaying the differences in serum cytokine concentrations between COVID-19 and RSVi.

Conclusion
Analysis of systemic cytokine profiles identified shared but also distinct cytokine responses in infants with SARS-CoV-2 and RSVi suggesting important differences in the pathogenesis of these viral infections.

Disclosures
Amy Leber, PhD, BioFire: Advisor/Consultant|BioFire: Grant/Research Support|Biorad: Advisor/Consultant|Cepheid: Grant/Research Support Asuncion Mejias, MD, PhD, MsCS, Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Advisor/Consultant|Sanofi-Pasteur: Advisor/Consultant|Sanofi-Pasteur: Honoraria 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.