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Does SARS-CoV-2 Lead to Misstep-by-Steps in Febrile Infants?

February 16, 2024

Written by Andy Hogan

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In febrile infants with SARS-CoV-2 infection, current risk stratification tools for identifying invasive bacterial infections (IBIs) demonstrate high negative predictive values at the cost of decreased sensitivity.

SARS-CoV-2 and misstep-by-steps in febrile infants?
Recognizing febrile infants at high-risk for IBIs is a critical skill for emergency clinicians due to the high mortality and morbidity of these conditions. Tools like the Step-by-Step approach, the PECARN rule and the AAP guideline for “Well Appearing Febrile Infants” were developed to risk stratify these vulnerable patients. The cornerstone of these tools is assessment of serum inflammatory markers (IMs), including procalcitonin and C-reactive protein (CRP). Unfortunately, these tools were developed before the emergence of SARS-CoV-2, a virus infamous for both its widespread prevalence and effects on IM levels.

This secondary analysis of the PERN & PERC COVID-19 cohorts assessed diagnostic accuracy of serum IM combinations used in four prominent risk stratification methods (Figure) for febrile infants ≤90 days old.

Serum IM threshold combinations (excerpted from Table 2 in the source article)

The analysis included 563 infants, of whom 300 were SARS-CoV-2-positive, and 19 were diagnosed with IBI. Procalcitonin, CRP, and ANC values were not available for every patient, which limited the analysis. Notably, none of the 3 SARS-CoV-2-positive infants diagnosed with IBI underwent procalcitonin testing. Resultantly, sensitivity could only be determined for the IM combination of CRP ≤20 mg/L and ANC ≤5200/uL. In this group (n=303), sensitivity for IBI was 0.67 in SARS-CoV-positive infants vs. 0.92 in those testing negative. Conversely, specificity increased in patients with SARS-CoV-2 infection using each of the 4 strategies. Using all 4 methods, NPV remained 0.95-0.99 among all comers.

How will this change my practice?
The biggest concern for an emergency clinician is misidentifying a patient with an IBI as low risk. Ultimately, more infants who test positive for SARS-CoV-2 will probably be misclassified as ‘high-risk’ for IBI when these tools are used. That said, clinicians should be reassured that SARS-CoV-2-positive patients stratified as ‘low-risk’ are unlikely to have IBI.

Editor’s note: Bear in mind, viral infection may lower inflammatory markers, reducing the diagnostic accuracy of these tests. ~Clay Smith

Inflammatory Markers in Febrile Young Infants With and Without SARS-CoV-2 Infections. Pediatrics. 2024;153(2):e2023063857. doi:10.1542/peds.2023-063857