Reassessing the Performance of the “Step-By-Step” Approach to Febrile Infants 90 Days of Age and Younger in the Context of the COVID-19 Pandemic: A Multicentric Retrospective Study

Abstract

Background: Infants with COVID-19 can often present with fever without source, which is a challenging situation in infants <90 days old. The “step-by-step” algorithm has been proposed to identify children at high risk of bacterial infection. In the context of the COVID-19 pandemic, we aimed to reassess the diagnostic performance of this algorithm. Methods: We performed a multicentric retrospective study in 3 French pediatric emergency departments between 2018 and 2020. We applied the “step-by-step” algorithm to 4 clinical entities: COVID-19, febrile urinary tract infections (FUTI), invasive bacterial infection (IBI), and enterovirus infections. The main outcome was the proportion of infants classified at high risk (ill-appearing, ≤21 days old, with leukocyturia or procalcitonin level ≥0.5 ng/mL). Results: Among the 199 infants included, 40 had isolated COVID-19, 25 had IBI, 60 had FUTI, and 74 had enterovirus infection. All but 1 infant with bacterial infection were classified at high risk (96% for IBI and 100% for FUTI) as well as 95% with enterovirus and 82% with COVID-19. Infants with COVID-19 were classified at high risk because an ill-appearance (72%), an age ≤21 days (27%), or leukocyturia (19%). All these infants had procalcitonin values <0.5 ng/mL and only 1 had C-reactive protein level >20 mg/L. Conclusions: The “step-by-step” algorithm remains effective to identify infants with bacterial infection but misclassifies most infants with COVID-19 as at high risk of bacterial infection leading to unnecessary cares. An updated algorithm based adding viral testing may be needed to discriminate fever related to isolated COVID-19 in infants <90 days old.

Repeated inflammatory markers may be useful for assessing febrile infants aged 29–90 days during early hospital surveillance

“…Fever is a frequent reason for paediatric emergency room (PED) visits. Most are viral infections, but up to 12% of children aged up to 90 days have a serious bacterial infection (SBI) 1,2 . Physical examinations and laboratory tests do not always differentiate between these.…”

“…Paediatricians should be aware of this risk. We recommend hospital surveillance for at least 12–24 h with repeated inflammatory markers 1 . Larger, prospective studies need to assess whether a time variable would improve the efficacy of the Step‐by‐Step approach and improve the management of febrile infant in PEDs.…”

“…The algorithms developed to identify subgroups at higher risks of SBIs in this age group include the validated Step-by-Step, which has identified a lower incidence of undiagnosed SBIs than others. [1][2][3] This approach evaluates the risk of SBIs in febrile infants by their general appearance, age, urinalysis, procalcitonin, C-reactive protein (CRP) and absolute neutrophils counts (ANC). However, it appears to be less sensitive in children with short fevers.…”

“…Most are viral infections, but up to 12% of children aged up to 90 days have a serious bacterial infection (SBI). 1,2 Physical examinations and laboratory tests do not always differentiate between these. The algorithms developed to identify subgroups at higher risks of SBIs in this age group include the validated Step-by-Step, which has identified a lower incidence of undiagnosed SBIs than others.…”

Clinical Course, Laboratory Findings, and Prognosis of SARS-CoV-2 Infection in Infants up to 90 Days of Age: A Single-Center Experience and a Proposal for a Management Pathway

“…Fever without a clear source may be the sole presenting symptom, and in patients aged 90 days or younger, physical examination and laboratory tests may not be consistently differentiate between viral infections, including SARS-CoV-2, and Severe Bacterial Infection (SBI) [ 11 ].…”