Biomarkers of Systemic Inflammation in Ugandan Infants and Children Hospitalized With Respiratory Syncytial Virus Infection

Abstract

Background: Optimizing outcomes in Respiratory Syncytial Virus (RSV) pneumonia requires accurate diagnosis and determination of severity that, in resource-limited settings, is often based on clinical assessment alone. We describe host inflammatory biomarkers and clinical outcomes among children hospitalized with RSV lower respiratory tract infection (LRTI) in Uganda and controls with rhinovirus and pneumococcal pneumonia. Methods: 58 children hospitalized with LRTI were included. We compared 37 patients with RSV, 10 control patients with rhinovirus, and 11 control patients with suspected pneumococcal pneumonia. Results: Patients in the RSV group had significantly lower levels of C-Reactive Protein (CRP) and Chitinase-3-Like Protein 1 (CHI3L1) than the pneumococcal pneumonia group (p<0.05 for both). Among children with RSV, higher admission levels of CRP predicted prolonged time to resolution of tachypnea, tachycardia, and fever. Higher levels of CHI3L1 were associated with higher composite clinical severity scores and predicted prolonged time to resolution of tachypnea and tachycardia, time to wean oxygen, and time to sit. Higher levels of Lipocalin-2 (LCN2) predicted prolonged time to resolution of tachypnea, tachycardia and time to feed. Higher admission levels of all three biomarkers were predictive of a higher total volume of oxygen administered during hospitalization (p<0.05 for all comparisons). Of note, CHI3L1 and LCN2 appeared to predict clinical outcomes more accurately than CRP, the inflammatory biomarker most widely used in clinical practice. Conclusions: Our findings suggest that CHI3L1 and LCN2 may be clinically informative biomarkers in childhood RSV LRTI in low-resource settings.

Proteomic characteristics of bronchoalveolar lavage fluid in critical COVID‐19 patients

“…TNC is reported to be a extracellular proinflammatory factor that responses to virus infection [27,28] and associated with lung organogenesis [29]. LCN2, known as neutrophil gelatinase-associated lipocalin, is an attractive biomarker of inflammation and virus infection [30][31][32]. CHI3L1 plays a critical role in multiple virus-induced airway inflammation and could be a potential therapeutic candidate for attenuating Th2-associated immunopathology [32][33][34][35].…”

“…LCN2, known as neutrophil gelatinase-associated lipocalin, is an attractive biomarker of inflammation and virus infection [30][31][32]. CHI3L1 plays a critical role in multiple virus-induced airway inflammation and could be a potential therapeutic candidate for attenuating Th2-associated immunopathology [32][33][34][35]. LTF has a host-protective effect against virus infection through inhibiting the attachment of a virus to the cells, replication of the virus in the cells, and enhancement of systemic immune functions [36,37].…”

Identification of COVID-19 prognostic markers and therapeutic targets through meta-analysis and validation of Omics data from nasopharyngeal samples

“…A subset of upregulated proteins is secretory including S100A12, S100A8, S100A9, SERPINB3, DEFA3, LCN2 and TXN. LCN2, which came up in our study was previously shown to be an important biomarker for viral infection (72,73), and was also reported to be upregulated in transcriptomic and proteomic studies in COVID-19 patients (74,75). It has been shown that virus replication and inflammation goes down when thioredoxin reductase, a reducing agent of TXN is inhibited using auranofin, pointing towards the importance of redox environment during SARS-CoV2 pathogenesis (76), akin to many inflammatory responses which are governed by the redox status of the cell (77).…”

Identification of Neutrophil-Related Factor LCN2 for Predicting Severity of Patients With Influenza A Virus and SARS-CoV-2 Infection

“…However, Warszawska et al (2013) report that LCN2 deactivates macrophages through an IL-10/STAT3-dependent mechanism and worsens pneumococcal pneumonia outcomes, which may be due to differences cell subset and bacterial strain. Besides, LCN2 can be as a biomarker of systemic inflammation in infants hospitalized with respiratory syncytial virus (RSV) infection ( Sawatzky et al, 2019 ) and as a biomarker of inflammation, monocyte activation, and cardiac stretch during activation of the renin-angiotensin-aldosterone system in human immunodeficiency virus ( Bogorodskaya et al, 2019 ). In this study, we found that neutrophil is one of the main drivers of inflammatory response after virus infection.…”