511 - RSV vs Adenovirus: The Inflammatory CRP–Severity Paradox

Publication Number: 3492.511

Judy Teran, Michigan State University College of Human Medicine, East Lansing, MI, United States; Lanah Almatroud, Michigan State University College of Human Medicine, Ypsilanti, MI, United States; Rashed Hasan, Hurley Medical Center, Flint, MI, United States

Background: Inflammatory C-reactive protein (CRP) is commonly measured in children with lower respiratory tract infection (LRTI), yet its pattern and interpretation across different viral pathogens remains uncertain.

Objective: To compare CRP levels and clinical severity profiles between respiratory syncytial virus (RSV) and adenovirus infections in hospitalized children. Our hypothesis was that RSV is associated with more clinical respiratory severity, but less evidence of inflammation as reflected in the CRP.

Design/Methods: This retrospective cohort study included children admitted to a regional pediatric referral center between 2019 and 2024 with laboratory-confirmed RSV or adenovirus lower respiratory tract infections, identified through multiplex respiratory PCR. Cases were identified using ICD-10 diagnostic codes consistent with lower respiratory tract infection. Outcomes assessed were median CRP (mg/L), pediatric intensive care unit (PICU) admission, respiratory failure, severe disease (defined as the need for respiratory support, including non-invasive and invasive ventilation), and pneumonia. Comparisons of these outcomes were made using Mann-Whitney U and χ² tests.

Results: Among 11,640 encounters seen in the emergency department for cough, respiratory distress, and/or apnea between 2019 and 2024 (median age: 26 months [IQR: 9-71]), the most common single pathogens were Rhinovirus/Enterovirus (4,732 [40%]), RSV (1,708 [14%]), and Adenovirus (1,154 [10%]). Coinfection with two or more pathogens occurred in 4,970 (42%). Among the 11,640 encounters, 2,950 (25.3%) had CRP measured at presentation, with a median value of 14 mg/L [IQR: 4-48].

Among 626 children (RSV, n = 369; adenovirus, n = 257), overall, the CRP was significantly lower in RSV (median 10.8 mg/L) compared to adenovirus (16.9 mg/L; p = 0.0004). The pattern of lower CRP in RSV persisted in 2024 compared to the total group [Figure 1 and Figure 2]. Despite this, RSV cases had substantially higher severity indices: PICU admission 67.2% vs. 35.4% (p < 0.001), respiratory failure 65.9% vs. 25.7% (p < 0.001), and pneumonia 40.4% vs. 22.6%. This pattern defines a CRP-Severity Paradox, in which RSV evokes profound respiratory compromise despite minimal systemic inflammation, whereas adenovirus provokes higher CRP but milder respiratory outcomes.

Conclusion(s): CRP elevation reflects inflammatory phenotype, not clinical severity, in pediatric viral lower respiratory infection. RSV causes severe hypoxemic respiratory failure with relatively low systemic inflammation. Clinicians should rely on physiologic assessment-not CRP-for triage and management decisions.

Figure 1. Comparison of C-Reactive Protein (CRP) Levels in RSV-Positive vs. Adenovirus-Positive Encounters
Violin plots compare CRP concentrations for RSV (blue) and adenovirus (orange) infections across all years (left) and in 2024 (right). Adenovirus-positive cases exhibited higher CRP levels (p = 0.0007 overall; p = 0.0017 in 2024), indicating stronger systemic inflammation. Boxplots display medians and interquartile ranges, while the width of the violins represents data density.

Figure 2. Median C-Reactive Protein (CRP) Levels with 95% Confidence Intervals in RSV-Positive and Adenovirus-Positive Encounters
Median CRP values were consistently lower in RSV-positive cases than in adenovirus-positive cases, both across all years and in 2024. Error bars represent 95% confidence intervals, illustrating higher and more variable CRP responses among adenovirus infections.