999. Nasal Mucosal Cytokines: Potential Biomarkers for Pediatric Pneumonia Severity and Etiology
Authors: Sayegh Rouba , Yun Ki Wook , Xu Zhaohui , Wallihan Rebecca , Marzec Sarah , Leber Amy , Everhart Kathy , Cohen Daniel M , Desai Ankita P , Alter Sherman J , Ambroggio Lilliam , Florin Todd A , Keaton Meghan , Mertz Sara , Shah Samir S , Ruddy Richard , Jones Desiree , El-assal Osama , Mejias Asuncion , Ramilo Octavio 
Published: December 2021

Abstract

Background
Community acquired pneumonia (CAP) is a leading cause of mortality in children &lt; 5 years, but our understanding of disease pathogenesis remains limited. The objective of this study was to define the local host immune response in the respiratory tract by measuring nasal mucosal cytokine (NMC) concentrations (conc.). We hypothesized that NMC represent a potential biomarker to help assessing disease severity and pathogen classification.

Methods
We leveraged nasopharyngeal (NP) samples and clinical data from an observational multicenter study [Children’s Hospital’s Initiative for Research in Pneumonia (CHIRP)] conducted between 2015 and 2018. We measured conc. of 92 NMC using the Olink immunoassay. NMC conc. were compared by severity-defined by need for hospitalization, mild (outpatient) and severe (inpatient), and by identified pathogen using Mann-Whitney U test.

Results
This substudy included 182 children with CAP (mild=61; severe=121) and 30 healthy controls (HC). The pathogens identified included: 101 viruses; 32 bacteria (pyogenic=10; atypical=22); 12 with &gt;1 pathogen; and 37 with no pathogen. Children with severe CAP had greater CCL23 and MCP-3 conc. than those with mild disease (p=0.012; p=0.011 respectively). When comparing NMC profiles of children with CAP of viral and bacterial etiology, the viral group had greater conc. of proinflammatory cytokines IL-6 and TNF, (p=0.0002; p=0.0098 respectively). Further subgroup analysis showed that CAP secondary to influenza virus had greater conc. of IL-6, TNF, and antiviral INF-γ and IP-10 compared with CAP caused by pyogenic bacteria. IL-6 and MCP1-4 were significantly increased in the influenza group compared to the atypical bacteria group.
Quantification of NMC in children with CAP based on disease severity

NMC
nasal mucosal cytokine; CAP: community acquired pneumonia; NPX: normalized protein expression, arbitrary unit used in Olink assay that is log 2 scale. Mann-Whitney test was used to determine differences between mild and severe pneumonia
Quantification of NMC in children with CAP based on pathogen classification

NMC: nasal mucosal cytokine; CAP: community acquired pneumonia; NPX: normalized protein expression, arbitrary unit used in Olink assay that is log 2 scale. Mann-Whitney test was used to determine differences between bacterial CAP and viral CAP.

Conclusion
Children with severe CAP had higher monocyte chemoattractant NMC conc. than children with mild disease. Children with viral CAP, particularly influenza, had a more robust mucosal response including both proinflammatory and antiviral NMC than children with bacterial CAP. These findings show differences in NMC conc. based on etiology and disease severity. Further studies are needed to determine whether NMC are reliable predictive biomarkers of CAP etiology and severity.

Disclosures
Lilliam Ambroggio, PhD, MPH, Pfizer Inc (Grant/Research Support) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member) Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member)