A 7-week-old baby presents to the Emergency Department (ED) with a one-day history of coryza and cough. Parents have recorded a temperature of 38°C at home.
In triage, she is noted to be alert and feeding well. Her initial observations show a temperature of 38.2°C, HR 152 bpm, RR 45/min, and oxygen saturation 97% in room air.
You perform a viral swab test at ED which comes back positive for SARS-CoV-2. What would be your initial management of this infant?
Background
Infants under three months old with a fever pose diagnostic uncertainty, with clinicians often favouring a cautious approach to investigating and treating invasive bacterial infection (IBI). Infants with positive viral swabs may be able to forgo invasive testing and potentially limit antibiotic use; however, no current guidelines support this.
Evans, J., Umana, E. and Waterfield, T., 2024. Respiratory viral testing for young febrile infants presenting to emergency care: a planned secondary analysis of the Febrile Infants Diagnostic assessment and Outcome (FIDO) prospective observational cohort study. Archives of Disease in Childhood, 109(12), pp.988-993.
The aim of FIDO study was to assess the risk of invasive bacterial infection in these infants, and whether having a positive viral swab may help risk stratification.
Who were the patients?
This is a secondary analysis of data collected from the FIDO (Febrile Infant Diagnostic assessment and Outcome) study, a prospective observational cohort study across 35 paediatric emergency departments in the UK and Ireland.
Patients were eligible if they were:
- aged 90 days or younger
- with a fever ≥38°C in the ED or Assessment Unit
- or with a history of fever ≥38°C recorded by anyone via any thermometer in the 24 hours before presentation.
What was the intervention?
This was an observational study rather than a test of a specific intervention; sites followed their local practice for febrile infants.
Infants identified as eligible for the study underwent respiratory viral testing (for SARS-CoV-2, Influenza, or RSV) and blood/CSF cultures at the clinical discretion of ED staff. The initial assessment and clinical findings were recorded prospectively in a case report form (CRF). Seven days after discharge, the research team completed a subsequent CRF detailing the investigation results and length of stay.
What were the results?
Primary outcome
A total of 1821 infants were recruited for the FIDO study, of which 1395 (77%) underwent respiratory viral testing at presentation and were included. 339 of the 1395 patients (24.3%) had a positive viral test:
- 220 for SARS-CoV-2
- 70 for RSV
- 72 for Influenza
- 23 patients tested positive for multiple viruses
There were 45 cases of IBI (3.2%) recorded in infants with viral testing. 40 of these cases occurred in infants with negative viral testing, giving a rate of 3.8% in this cohort, while 5 cases of IBI were noted in children with positive viral testing, giving an IBI rate of 1.5%. This difference was statistically significant, suggesting that in febrile infants aged 90 days or less, a positive respiratory viral test is potentially associated with a decreased risk of IBI.
When looking specifically at infants aged 28 days or less, 335 underwent respiratory viral testing, with 36 returning positive. In total, 19 cases of IBI were noted—3 cases in infants who had positive respiratory viral testing (8.3%) and 16 in infants with negative viral testing (5.4%). This difference was not statistically significant, telling us that in febrile infants aged 28 days or less, a positive respiratory viral test is not associated with a decreased or increased risk of IBI.
For infants over 28 days, 1060 underwent respiratory viral testing, of which 303 were positive. 2 cases of IBI were noted in children with positive viral tests (0.7%) versus 24 in infants with negative viral testing (3.2%). This difference was statistically significant, telling us that in febrile infants aged 29 to 90 days, a positive respiratory viral test may be associated with a decreased risk of IBI.
Secondary outcomes
A subgroup analysis of IBI rates was performed for the following groups:
- age (≤28 days vs >28 days)
- presence of respiratory symptoms (cough and coryza)
- global assessment (well and unwell appearing).
Out of 1395 infants with available data, there were 1065 well-appearing infants in the cohort. Rate of IBI was 19/817 (2.3%) for infants with negative viral swabs versus 3/248 (1.2%) for infants with positive viral swabs. Viral swab result was not associated with a lower IBI rate in this subgroup.
There were also 330 unwell-appearing infants. The rate of IBI was 2/91 (2.2%) for infants with a positive respiratory viral test versus 21/239 (8.8%) for infants with a negative respiratory viral test. Results showed that a positive respiratory viral swab was associated with a lower rate of IBI in this subgroup.
In infants presenting with respiratory symptoms, having a positive respiratory viral test was not associated with a significantly different risk of IBI (1.3% in infants with a positive test versus 2.2% in infants with a negative test.
Results showed that IBI rates remained the same throughout all seasons, while viral testing rates were highest in winter and spring.
CASP Checklist for Cohort studies
- Does this address a clearly focused issue?
Yes - Was the cohort recruited in an acceptable way? Yes. This prospective study looked at all febrile infants presenting to the EDs involved who underwent respiratory viral testing.
- Was the exposure accurately measured to minimise bias? Yes.
- Was the outcome accurately measured to minimise bias? Yes. Subgroup analyses were performed to assess potential differences between different age groups, clinical appearance, and the presence of respiratory symptoms. There was no comment regarding age and appearance together, as it would be interesting to know rates of IBI in those who are well-appearing and have been>28 days with a positive viral swab.
- Have the authors identified all-important confounding factors? Yes. They also acknowledge the limitations of the study design and variability in clinical practice between participating centres.
- Was the follow-up of subjects complete and accurate? No. Reattendance and potential IBI diagnosis were assessed via hospital chart review. This may lead to potential underestimation of IBIs.
- What are the results? A positive respiratory viral test was associated with a lower risk of IBI in older infants. In infants aged 28 days or less, a positive respiratory viral test was not associated with a lower risk of IBI. In well-appearing infants, a positive respiratory viral result was not associated with a decrease in the rate of IBI. In unwell=appearing infants a positive respiratory viral test was associated with decreased rate of IBI.
- Do you believe the results? Yes
- Can the results be applied to a local population? This was a large, multicentre trial based in the UK and Ireland, and as such, these results are relevant for clinicians, particularly from these countries or similar settings. The results may not apply to clinicians working in significantly different healthcare settings or in regions where respiratory viral testing isn’t as readily available.
- Do the results fit with other evidence available? Yes
What did the authors conclude and what does it mean for current practice?
The presence of positive tests of SARS-CoV-2, RSV, or influenza in well-appearing older infants was associated with low rates of IBI; rapid point-of-care testing could be utilized in this group to aid risk stratification and avoid further invasive testing and antibiotic administration.
What about that well-appearing seven-week-old infant with a fever of 38.2⁰C with a positive SARS-CoV-2 test? FIDO secondary analysis suggests that you could obviate the need for additional invasive testing and parenteral antibiotics. This could potentially enhance antimicrobial stewardship and patients and family experiences without the risk of missing an invasive bacterial infection.
A note from the author – Etimbuk Umana
Large international multicenter studies have reported low IBI rates in febrile infants who test positive for viruses. While these studies typically included all virus types, not just respiratory viruses, current febrile infant guidelines do not recommend viral testing because its role in the diagnostic pathway remains unclear. Our study evaluated how positive viral tests affect IBI rates in young febrile infants presenting to emergency care in the UK and Ireland. We specifically examined COVID-19, RSV, and Influenza testing respiratory viruses that emergency clinicians can rapidly detect using point-of-care (POC) tests to inform decision-making. This approach may be especially relevant during winter when COVID-19, RSV, and Influenza are more prevalent. In infants older than 28 days, we found that a positive respiratory viral test indicated a 0.7% risk of IBI in the low-risk group comparable to findings from Aronson and StepbyStep CDA (0.6% and 0.7% respectively). The PECARN original derivation found a 0.2% IBI risk in its low-risk population. These findings suggest that infants meeting these criteria might need only limited investigation with observation, though urinalysis should still be considered to detect possible UTIs. Implementing this age-based and viral testing approach would require readily available POC testing to support quick clinical decisions. While shared decision making would be essential when limiting investigations, further research through randomised control trials of POC respiratory viral testing could better determine its value in diagnosing febrile infants.
