In this study, FWS was a common feature present in infants under 90 days old with SARS-CoV-2 infection. First communications of COVID-19 in infants were limited to mild respiratory symptoms, but new presentations have been described as the pandemic has progressed [7, 17–21]. FWS in young infants has recently been described as part of the spectrum of COVID-19[11, 12]. As several viral infections, SARS-CoV-2 may be responsible for FWS in young infants, so SARS-CoV-2 should be ruled out in areas with community transmission[1, 3, 4].
In this study, 2/27 (7%) infants with FWS and SARS-CoV-2 infection were associated with bacterial infections. Two UTIs were observed in two patients; one of them with apneic episodes, and the other with also a S. mitis bacteremia. This last child was diagnosed after this episode with Swachman-Diamond Syndrome and severe neutropenia, so he had a high risk of invasive bacterial infection. Otherwise, no other SBI occurred. SBI in under-90-day-old infants occurs in 5%-15% of the cases in FWS[1, 3, 22]. Differentiating which children with FWS have SBI may be challenging, mainly in young infants. Several algorithms based on analytical and clinical variables have been developed throughout the years to differentiate infants with low- and high-risk of having SBI [1, 3, 22]. Rapid tests to identify some of the most frequent viruses like influenza or respiratory syncytial virus are usually included in the initial approach of the FWS because SBI occurrence is significantly lower in infants with viral infections than in infants without viral infection[1, 2, 4, 23]. Accordingly, the approach to young infants with FWS in the ED during a SARS-CoV-2 pandemic or outbreak should include the detection of SARS-CoV-2 in the initial microbiological study.
On the other hand, UTI was observed in this series according to previous studies where UTI prevalence is more than 5% in infants with FWS and a confirmed viral infection. Detection of SARS-CoV-2 should not lead to automatically rule out SBI. Infants can shed respiratory viruses for several days after the disease is solved [24–27], which can induce a misclassification of children. In this study, one child tested positive for RT-PCR several days after diagnosis. It is unclear if this test means that the child was infective, or if we detected only residual nucleic acid. Some of the infants who presented positive RT-PCR at admission might have undergone the infection days before. Serological tests that would confirm this in some infants were not available.
Viral coinfections were not observed in this study. However, only six children had a test performed for other viruses different from SARS-CoV-2. Due to the exceptional situation in which the hospitals were working during the peak of the epidemic, most laboratories were overloaded, and the COVID-19 study was prioritized. The prevalence of viral coinfections in this specific population and the implications in the management at ED should be further evaluated.
In general, the evolution was good, and only one infant needed PICU admission. Three out of 6 children studied presented pneumonia in the CXR, but only the child admitted to PICU received treatment with an agent with presumed antiviral activity against SARS-CoV-2 (azithromycin). Even in this population of young infants with FWS, SARS-CoV-2 infection presents a good outcome and a low rate of PICU admission.
Lymphopenia was a remarkable feature in this population, as observed in older children and adults.[28, 29] Lymphopenia has been suggested to be an indicator of severity in COVID-19.[28, 29] However, due to the low rate of severe cases of this series, the association of lymphopenia with severity in infants with FWS is not evaluable.
CRP and procalcitonin were low in all children with SARS-CoV-2 infection without bacterial coinfection, except in one infant with FWS and no bacterial isolation who showed a PCR of 64 mg/L and PCT of 0.4 ng/L.
CRP was almost universally low, and procalcitonin was always below 0.5 mcg/mL. In this study, SARS-CoV-2 was not associated with high CRP o procalcitonin levels, unlike in other inflammatory syndromes associated with COVID-19.[15, 19] Therefore, acute phase reactants seem to remain useful to evaluate the risk of a potential SBI in young infants during COVID-19 outbreaks.
This study may be biased, as the SARS-CoV-2 test has not been done uniformly in young febrile infants as part of a protocol, but instead guided by the case definition determined by the national authorities in each step of the pandemic, and the best judgment of the attending physician. Therefore, some cases may have been missed. Infants with comorbidities may have been tested more often, as the high proportion of comorbidities suggest. Similarly, standardized recommendations for doing CXR at admission were not in place. This precludes any recommendation about the convenience of doing CXR in infants with FWS and SARS-CoV-2 infection. We had no information on maternal status before delivery, so congenital transmission cannot be ruled out, although it is really unlikely with current evidence. Because of the pandemic situation Microbiologic Departments were under overwork and Threshold Cycle (CT) values were not available in this study.
In conclusion, the rate of SBI among infants less than 90 days of age with SARS-CoV2 and FWS was similar to other viral infections in this age group.
Standardized markers to discard SBI seem to remain useful in this population. COVID-19 should be ruled out in infants with FWS in areas with community transmission of SARS-CoV-2, but the outcome is generally good.