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Presence and Duration of Symptoms in Febrile Infants With and Without SARS-CoV-2 Infection

McLaren, Son H. MD, MS*; Dayan, Peter S. MD, MSc*; Zachariah, Philip MD, MS; McCann, Teresa A. MD; Lubell, Tamar R. MD*

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The Pediatric Infectious Disease Journal: November 2020 - Volume 39 - Issue 11 - p e372-e374
doi: 10.1097/INF.0000000000002858

Abstract

Detailed data about the presence and duration of symptoms in infants with SARS-CoV-2 have not been well described. Herein, we provide data demonstrating the typically benign symptomatology and clinical course of febrile infants with SARS-CoV2 infection, which will inform and comfort parents and clinicians who are confronted with this illness.

Available data on SARS-CoV-2 infection suggest that although children may experience milder clinical symptoms than adults,1,2 those under 1 year of age may experience more severe symptoms when compared with older children.3,4 In a small case series, however, we noted only mild disease in otherwise well-appearing febrile infants with SARS-CoV-2.5 That case series included retrospective data and did not provide detailed information on the duration of specific symptoms. In this study, we aimed to compare the presence and duration of symptoms in febrile infants ≤60 days old with and without SARS-CoV-2.

MATERIALS AND METHODS

We conducted a prospective cohort study of febrile infants ≤60 days old with SARS-CoV-2 testing who were evaluated in the emergency department (ED) or transferred from affiliated hospitals from March 1, 2020 to May 15, 2020. As per hospital policy, all patients admitted starting March 25, 2020 were tested for SARS-CoV-2 regardless of the admission diagnosis. Fever was defined as temperature ≥38°C within 48 hours of presentation in the ED. The local ethics committee approved this study, with the requirement for verbal consent. In the ED or on the day of hospital admission, we conducted phone interviews with parents and treating physicians to obtain data on demographics, medical history, presence and duration of presenting symptoms, and initial physical examination findings.

The primary outcome was the duration of individual symptoms as determined by daily phone follow-up conducted until the infant was symptom-free for 48 hours or for up to 21 days post index ED visit. Symptoms were entered retrospectively if the parent was not reachable on a given day. Additionally, we conducted 7- and 14-day calls and 14-day medical record reviews to determine the presence of severe outcomes during the course of illness, defined as acute respiratory distress syndrome, respiratory failure, development of sepsis or shock, requirement for intensive care unit–level of care or death. Medical records were also reviewed at least 6 weeks after each index visit to assess for the development of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). Missed eligible infants and those who declined follow-up calls were identified but not analyzed. We used descriptive statistics to summarize the data. As no a priori hypotheses were made and as the sample was small, we did not conduct further analyses.

RESULTS

Of 40 febrile infants screened, 33 (83%) had SARS-CoV-2 testing completed, and of those, 23 (70%) were prospectively enrolled. Median age was 41 days (interquartile range: 18–50 days). All but one had complete telephone follow-up, and all had complete medical record reviews.

Seven of the 23 enrolled infants tested positive for SARS-CoV-2, while 16 tested negative. Initial clinical presentations of infants with and without SARS-CoV-2 frequently overlapped, with SARS-CoV-2-positive infants more frequently reporting cough (3/7 or 43% versus 2/16 or 13%) and nasal congestion (3/7 or 43% versus 3/16 or 19%) (see Table, Supplemental Digital Content 1, https://links.lww.com/INF/E82). Removing all those with urinary tract infections (n = 6), who may have unique symptom profiles, did not meaningfully change the findings (data available upon request). Table 1 shows that in those who had specific symptoms, the duration of cough, nasal congestion and the presence of any symptom appeared longer in those with SARS-CoV-2 infection. This potential difference was observed even when those with urinary tract infections were removed. No infants experienced cyanotic or apneic episodes.

Table 1. - Symptomatology of Febrile Infants by SARS-CoV-2 Status
SymptomTable 1. Presence and Duration of SymptomsTable 1.
All Infants SARS-CoV-2-negative Infants SARS-CoV-2-positive Infants
n/N (%) Median (IQR), d n/N (%) Median (IQR), d n/N (%) Median (IQR), d
Fever 23/23 (100) 1 (1, 2) 16/16 (100) 1 (1, 2) 7/7 (100) 1 (1, 1)
Cough 9/23 (39) 4 (1, 12) 4/16 (25) 2 (1, 11)Table 1. 5/7 (71) 6 (3, 16)
Rhinorrhea 5/23 (22) 2 (2, 4) 4/16 (25) 2 (1, 3)Table 1. 1/7 (14) 5 (5, 5)Table 1.
Nasal congestion 10/23 (43) 6 (2, 15) 5/16 (31) 3 (2, 16) 5/7 (71) 9 (2, 18)
Difficulty breathing 6/23 (26) 2 (2, 5) 3/16 (19) 2 (1, 3)Table 1. 3/7 (43) 2 (2, 9)Table 1.
Feeding difficulty 9/23 (39) 3 (2, 6) 4/16 (25) 4 (2, 6)Table 1. 5/7 (71) 3 (2, 5)
Vomiting 5/23 (22) 2 (1, 5) 3/16 (19) 1 (1, 2)Table 1. 2/7 (29) 5 (2, 7)Table 1.
Diarrhea 11/23 (48) 3 (1, 4) 8/16 (50) 2 (1, 4) 3/7 (43) 3 (1, 11)Table 1.
Abnormal activity levelTable 1. 17/23 (74) 2 (1, 5) 12/16 (75) 2 (1, 4) 5/7 (71) 2 (1, 12)
Decreased urine output 3/23 (13) 4 (2, 5)Table 1. 1/16 (6) 5 (5, 5)Table 1. 2/7 (29) 3 (2, 4)Table 1.
Conjunctivitis 2/23 (9) 2 (1, 2)Table 1. 1/16 (6) 1 (1, 1)Table 1. 1/7 (14) 2 (2, 2)Table 1.
Any symptoms 23/23 (100) 6 (2, 11) 16/16 (100) 5 (2, 9) 7/7 (100) 13 (7, 23)
*For each symptom, only infants who had the symptom for at least 1 day are included. However, for “any symptom,” duration of illness is calculated by taking the absolute difference between the onset of any symptom listed above and the last day of any symptom, which may include symptom-free days in between.
†n/N indicates the number of infants reporting the symptom over (1) the total number of infants (second column), (2) the number of infants with negative SARS-CoV-2 test (fourth column), or (3) the number of infants with positive SARS-CoV-2 test (sixth column).
‡We report minimum instead of 25th percentile and maximum instead of 75th percentile due to small number of infants (n < 5). For n = 1, minimum and maximum will be the same numbers.
§Abnormal activity level defined as fussiness, sleepiness, or irritability.

There were no infants with bacteremia, bacterial meningitis or severe outcomes (see Table, Supplemental Digital Content 2, https://links.lww.com/INF/E83). No therapies targeting COVID-19 were given. One infant who tested negative for SARS-CoV-2 was diagnosed with septic arthritis. None of the SARS-CoV-2-positive infants returned to the index ED within 6 weeks with symptoms concerning for MIS-C However, a SARS-CoV-2-negative infant subsequently underwent outpatient cardiology and rheumatology evaluation for MIS-C given prolonged fever lasting 9 days. Inflammatory markers, electrocardiogram and echocardiogram findings were all negative. Antibodies for COVID-19 were not sent, but the infant’s symptoms were deemed not to be consistent with MIS-C. No severe outcomes were observed among the missed eligible patients.

DISCUSSION

In this prospective cohort study of febrile infants ≤60 days old, we noted that symptomatology was typically benign for those with and without acute SARS-CoV-2 infection during the study period. In febrile infants with SARS-CoV-2 infection who had respiratory symptoms, these symptoms were, by comparison, somewhat prolonged. This symptom duration, however, was not unlike that in prior studies of infants with acute upper respiratory infections,6 suggesting that clinicians and parents can expect the course of SARS-CoV-2 illness in febrile but otherwise well infants to be similar to that for other likely viral illnesses.

Limitations of our study include a small sample size, which precluded comparative statistical analyses. However, this preliminary descriptive investigation provides in-depth information regarding the clinical course of infants with and without SARS-CoV-2, which may provide useful guidance for both parents and clinicians. Second, there was a lack of universal SARS-CoV-2 testing early in the pandemic for discharged infants and an inability to assess for the presence of other viral infections. Finally, we did not conduct a prolonged prospective follow-up to assess for the development of MIS-C and may have missed infants presenting to other clinical settings.

REFERENCES

1. Zimmermann P, Curtis N. COVID-19 in children, pregnancy and neonates: a review of epidemiologic and clinical features. Pediatr Infect Dis J. 2020; 39:469–477
2. De Rose DU, Piersigilli F, Ronchetti MP, et al.; Study Group of Neonatal Infectious Diseases of The Italian Society of Neonatology (SIN). Novel coronavirus disease (COVID-19) in newborns and infants: what we know so far. Ital J Pediatr. 2020; 46:56
3. Lu X, Zhang L, Du H, et al.; Chinese Pediatric Novel Coronavirus Study Team. SARS-CoV-2 infection in children. N Engl J Med. 2020; 382:1663–1665
4. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatrics. 2020; 145:e20200702
5. McLaren SH, Dayan PS, Fenster DB, et al. Novel coronavirus infection in febrile infants aged 60 days and younger. Pediatrics. 2020; 146:e20201550
6. Neumann RP, Hilty M, Xu B, et al. Nasal microbiota and symptom persistence in acute respiratory tract infections in infants. ERJ Open Res. 2018; 4:00066-2018
Keywords:

fever; SARS-CoV-2; infants

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