key: cord-0844898-ukv6zl69 authors: Yarden Bilavski, Havazelet; Balanson, Sarit; Damouni Shalabi, Ranaa; Dabaja‐Younis, Halima; Grisaru‐Soen, Galia; Youngster, Ilan; Glikman, Daniel; Ben Shimol, Shalom; Somech, Eli; Tasher, Diana; Stein, Michal; Gottesmanm, Giora; Megged, Orli; Livni, Gilat title: Benign course and clinical features of COVID‐19 in hospitalised febrile infants up to 60 days old date: 2021-06-30 journal: Acta Paediatr DOI: 10.1111/apa.15993 sha: b6fb78b59a7cb758a391330d42c9519d865031be doc_id: 844898 cord_uid: ukv6zl69 AIM: Minimal data exist regarding the severity of COVID‐19 in febrile infants under 60 days old. This multicentre prospective study explored the clinical course and outcomes of this hospitalised patient population, as, to date, the best approach has not been specifically addressed. METHODS: This study focused on the clinical features, laboratory parameters and outcomes of febrile infants up to 60 days old who tested positive for the virus and were hospitalised in Israel from March 2020 to January 2021. The data were extracted from a real‐time prospective surveillance network for COVID‐19 that includes 20 of the country's 26 hospitals. RESULTS: We identified 75 febrile young infants (60% female) with COVID‐19 at a median age of 28 days (range 8–56 days). Of these, 84% had an unremarkable medical history, 29% had respiratory symptoms, and 96% had a mild illness. The Rochester criteria showed that 44% were considered at high‐risk for serious bacterial infections, and we found that eight infants actually had concomitant bacterial infections. Outcomes were excellent, and no complications or fatalities were reported. CONCLUSION: The excellent outcomes of young febrile infants with COVID‐19 closely resembled other respiratory viral aetiologies of fever in this age group, and there were no fatalities. Millions of people have been infected, hospitalised and died during the COVID-19 pandemic. 1 However, children have mostly had mild symptoms and respiratory disease and have fully recovered within one to two weeks requiring minimal supportive care. 2 There have also been rare cases of multi-system inflammatory disease during convalescence, but this phenomenon has primarily been observed in children, not infants. Febrile infants up to 60 days old are a unique subclass of the paediatric population. Managing fever in this age group is challenging due to the relatively high rates of serious bacterial infections (SBIs), compounded by a lack of specific signs and symptoms that enable us to discriminate SBIs from simple viral infections. 3 Therefore, these infants traditionally require more comprehensive evaluation, usually performed with risk stratification criteria, such as the Rochester or Boston criteria. 4-7 COVID-19 data in these infants have been lacking, and the appropriate approach to febrile infants infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been specifically addressed. Our aim was to describe the clinical and laboratory characteristics of febrile infants up to 60 days old with COVID-19 and to assess the risk of concomitant bacterial infections in accordance with highrisk and low-risk criteria for SBIs. This study included all febrile infants aged two to 60 days old hospitalised from 10 March 2020 to 10 January 2021 with a fever of at least 38°C and a positive polymerase chain reaction (PCR) result for SARS-CoV-2. They were identified from Israel's Paediatric Surveillance Network for COVID-19, which is a real-time prospective surveillance network that comprises 20 of the country's 26 hospitals and covers all regions. Cases were included if febrile infants up to 60 days old had positive PCR samples which were obtained from the oral cavity and/or nasopharynx. Disease severities were based on Dong et al. 8 Mild disease only involved acute upper respiratory traction infections. Moderate disease included pneumonia without hypoxemia. Severe illness included desaturations below 92%. Critical illness involved acute respiratory distress syndrome or respiratory failure. 8 The Israeli national evaluation guidelines for young febrile infants are based on the Rochester criteria, which help clinicians identify patients with a low risk for SBIs, who do not necessarily require empiric antibiotic treatment nor hospitalisation. 9 A prospective multicentre study by the American Academy of Pediatrics reported that these criteria had high discriminative power. 10 The criteria used to define low risk include unremarkable medical history, appearing to be well, with no focal signs of infection, a while blood cell count of 5000-15,000/micL, with an absolute band count of less than 1500/ micL, normal urinalysis and no mucoid or bloody diarrhoea. However, some modifications are made in many paediatric settings, including most Israeli hospitals. These include C-reactive protein (CRP) levels, when available, and exclude absolute band counts, which are no longer reported in most Israeli hospitals. Lumbar punctures are performed at the physicians' discretion. SBIs were defined as the presence of bacterial meningitis, bacteraemia, a urinary tract infection (UTI), musculoskeletal infection, pneumonia or bacterial enteritis. The data collected included the test date, recent contact with COVID-19 patients and age, sex and ethnicity. The medical history Conclusion: The excellent outcomes of young febrile infants with COVID-19 closely resembled other respiratory viral aetiologies of fever in this age group, and there were no fatalities. • Minimal data exist regarding COVID-19 in very young infants and this multicentre prospective Israeli study focused on 75 infants up to 60 days old. • We found that 84% had an unremarkable medical history, 29% had respiratory symptoms, 96% had a mild illness, and 44% had a high-risk for serious bacterial infections. • The outcomes closely resembled other respiratory viral aetiologies of fever at this age, with excellent results and no fatalities. covered the perinatal course, prematurity, previous hospitalisation, congenital malformations and background illnesses, including heart disease, chronic lung disease, immune deficiency or malignancy. Signs and symptoms included fever, cough, rhinorrhoea, respiratory distress weakness, diarrhoea, vomiting, conjunctivitis, nausea, rashes and irritability. Laboratory data comprised complete blood count parameters, CRP, blood, urine and cerebrospinal cultures. Disease outcome data included severity, length of hospitalisation, complications, intensive care unit admission and mortality. The data are presented as means and standard deviations (SD) or medians and interquartile ranges (IQR) for continuous variables, and frequencies and proportions for categorical variables. The study was approved by the local institutional ethics review board, the Helsinki Committee at Rabin Medical Centre. Caregiver consent was not required. There were 75 febrile infants up to 60 days old who tested positive for the virus and Table 1 summarises their demographic, clinical and laboratory characteristics. Their median age was 28 (range 8-56) days, and 41 (54%) were 28 days or less. Virus test results were available for the caregivers of 36 patients, and they were all positive. Most infants (84%) had an unremarkable medical history, but 8% had congenital malformations or underlying conditions. Of these six infants, four had congenital heart defects, one had a renal malformation, and one had a chromosomal abnormality. Two patients had previously been hospitalised for UTIs, one for early postnatal dyspnoea and one for cyanotic heart disease, namely, Tetralogy of Fallot. The duration of fever was reported for 93% infants, and the mean was 1.3 days. Mild respiratory symptoms, mainly cough and rhinorrhoea, were observed in 29%. Leukocyte counts of <5000/ micL or >15,000/micL were noted in 13% and 14% of infants, respectively. Absolute lymphocyte counts of <1500/micL were documented in 7%, while absolute neutrophil counts of <1500micL or >10,000micL were documented in 17% and 4%, respectively. CRP was measured in 72 infants: 97% were below 5mg/dL, and 96% were below 2mg/dL. It was notable that all three neonates with a CRP of >2mg/dL had a concomitant SBI. The median hospitalisation duration was 2.0 (range 1-13) days. It is important to note that some neonates were not discharged when medically fit, due to quarantine or administrative issues related to COVID-19 regulations. No complications were documented, and there were no intensive care admissions or fatalities. COVID-19 disease severity was mild in 96%. One had moderate disease due to shortness of breath without hypoxemia. The other two had severe disease and were treated with supplemental oxygen for a short period: one was otherwise healthy, and one had Tetralogy of Fallot. When the Rochester criteria were applied, 44% infants were considered at high-risk for SBI and 77% were empirically treated with antibiotics until negative culture results. Concomitant bacterial infections were found in 11% of the infants: seven had UTIs and the other one had Salmonella gastroenteritis. Of these eight, seven were under 28 days old and five had a high risk for SBIs. No bacteraemia or meningitis were reported. We believe that this was the first nationwide study on the clinical course and outcomes of young febrile infants up to 60 days old with COVID-19. The 75 infants had short, uneventful disease courses with favourable outcomes. Very young infants with fever are vulnerable to infectious diseases and deserved particular attention and a carefully designed clinical approach. [4] [5] [6] Almost all (96%) of the infants in our cohort had mild disease. The two infants with severe disease, one with cyanotic heart disease and one who was otherwise healthy, had short, uneventful disease The main strength of this study was its multicentred and prospective Our data suggest that the clinical course and outcomes of infants under 60 days of age with COVID-19 closely resembled other respiratory viral aetiologies for neonatal fever. Furthermore, this age group was not associated with an increased risk of secondary SBIs. Large, prospective studies are needed to develop clinical management recommendations for COVID-19 in this age group. The authors have no conflicts of interest to declare. 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