620 - Infants hospitalized with SARS-CoV-2 versus RSV infection exhibit different systemic cytokine profiles

Cytokines play an essential role in the immune response to viral infections exhibiting considerable antagonistic and synergistic effects that regulate both local and systemic inflammatory responses.

Objective: To define and compare systemic cytokine responses in infants hospitalized with COVID-19 and RSV infection (RSVi).  

Design/Methods: This was a prospective study of a convenience cohort of infants hospitalized with PCR confirmed SARS-CoV-2 or RSV infection, as well as pre-pandemic healthy controls (HC). Clinical parameters and 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 121 infants, 26 with COVID-19, 77 with RSVi and 18 healthy infants as a comparator control group. Presence of comorbidities was significantly more common in infants with COVID-19 (26.9%) (p=0.01), while oxygen requirement was significantly more frequent in infants with RSVi (49%) (p=0.02). No statistical differences were identified in terms of lymphocyte counts, length of stay, pediatric intensive care unit admission, and need for mechanical ventilation. Viral coinfection was observed in 14% and 23% of infants with COVID-19 and RSVi, respectively, including rhinovirus/enterovirus, adenovirus, parainfluenza virus, and other coronaviruses (Table 1). Principal component analysis (PCA) revealed clustering of the global cytokine profiles separating HC from infants with COVID-19 and RSVi (Figure 1A). Multiple comparison analysis among the three groups yielded 49 significantly different cytokines that clustered in three groups (Figure 1B). A first cluster that included cytokines such as CCL11, CCL19 and TNFSF12 that were lower in both COVID-19 and RSVi compared with 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 that were markedly increased in both viral groups compared with HC (ANOVA padj< 0.05). Direct comparison between COVID-19 and RSVi (padj< 0.05 and FC >1.5) identified 7 statistically different cytokines. Chemoattractant cytokines, such as CCL8, CXCL1, CCL20 were increased in COVID-19, while immunoregulatory cytokines, including SIRT2, STAMBP, MMP10 and EIF4EBP1 were increased in RSVi (Figure 1C-D).

Conclusion(s):

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.