What happens to children under 90 days of age infected by Covid-19?

A report from Ann & Robert H. Lurie Children’s Hospital of Chicago shows that infants under 90 days of age who tested positive for COVID-19 tend to be well, with little or no respiratory involvement.

Fever was often found to be the primary or only symptom. Findings were published in The Journal of Pediatrics.

“While there is limited data on infants with COVID-19 from the United States, our findings suggest that these babies mostly have mild illness and may not be at higher risk of severe disease as initially reported from China.” says lead author Leena B. Mithal, MD, MSCI, pediatric infectious diseases expert from Lurie Children’s and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine.

“Most of the infants in our study had fever, which suggests that for young infants being evaluated because of fever, COVID-19 may be an important cause, particularly in a region with widespread community activity. However, evaluation for bacterial infection in young infants with fever remains important.”

The study included 18 infants, none with a significant medical history. Of the 50 percent of these infants who were admitted to the hospital’s general inpatient service, none required oxygen, respiratory support, or intensive care.

Indications for admission were mainly clinical observation, monitoring of feeding tolerance, and ruling-out bacterial infection with empiric intravenous antibiotics in infants younger than 60 days.

Of the infants admitted to the hospital, six out of nine had gastrointestinal (GI) symptoms (poor feeding, vomiting and diarrhea). Upper respiratory tract symptoms of cough and congestion preceded onset of GI symptoms. Young infants also had notably high viral loads in their nasal specimens despite mild clinical illness.

“It is unclear whether young infants with fever and a positive test for SARS-CoV-2 require hospital admission,” says Dr. Mithal. “The decision to admit to the hospital is based on age, need for preemptive treatment of bacterial infection, clinical assessment, feeding tolerance, and adequacy of follow-up.”

There may be opportunities to utilize rapid SARS-CoV-2 testing to determine disposition of clinically well infants with fever.”

Dr. Mithal and colleagues (Drs. Machut, Muller, and Kociolek) also observed an overrepresentation of Latinx ethnicity among their sample of infants with COVID-19 (78 percent).

At the height of the COVID-19 pandemic in Chicago, over 40 percent of cases were in individuals of Latinx ethnicity.

“Although we expected that there would be many infants of Latinx ethnicity with COVID-19, there may be additional factors contributing to the disproportionate majority of Latinx cases we observed in this age group,” says Dr. Mithal.

“Access to sick-visit care in some primary care pediatric offices has been limited, with practices referring symptomatic children to the emergency department. Limited access to telemedicine care also may be a factor.

Finally, there may be a greater likelihood of exposure with extended family living in the home or family members working outside the home during this pandemic.”

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Epidemiology
Pediatric cases reported during the previous outbreaks of SARS in Hong Kong and MERS in South Korean, were very few [28]. In addition, mortality rate of SARS and MERS in the adults was very high, but there were no fatalities in the pediatric cases [28].

These findings indicated that children appeared to have a milder form of the disease caused by the coronaviruses [2]. Current data about COVID-19, in pediatrics is similar to SARS and MERS in case of disease severity and mortality and shows that children of all ages can get COVID-19, but they seem to be affected less commonly than adults [3]6.

The first confirmed pediatric case of SARS-CoV-2 infection was reported in Shenzhen on January 20 [5], and by February 10, a total of 398 confirmed pediatric cases were reported from China, excluding the Hubei Province [2].

It is well known that pediatric cases are generally identified at that time in a familial cluster or and generally are infected by one sick parent or family member. According to a study, 71.2% (183/257) of infected children were reported having a household contact [29].

In another study by Lu, 90.1% of patients were reported to be with family clusters [30]. But at the explosion stage of the outbreak, children may become a significant spreader [31].

The surveillance definitions and criteria are changing during the pandemic, but still data from many different countries, are similar with these studies and the proportion of pediatric cases is within this range.

Less than 1% of the cases were in children younger than 10 years of age in the review of 72,314 cases reported by the Chinese Center for Disease Control and Prevention [32]. According to a study that analyzed 44,672 COVID-19 cases from China by mid-February 2020, 0.9% of patients were less than 10 years of age and 1.2% were between 10 and 20 years of age [33].

According to Statista Research Department, Italy, 1.6% of total patients were from 0 to18 age7. In a systematic literature review (between January 1and March 18, 2020), children were 1 to 5 percent of diagnosed COVID-19 cases [34].

To date, there are about 149,760 laboratory-confirmed cases reported from United States, and only 1.7 percent are in children.6

In a report of 171 pediatric cases, reported by Lu et al., median age of patients was 6,7 year (1 day–15 years) and 60.8% were male.

In this case series, 18.1% of patients were <1 year of age, 23.4% were 1–5 years, 33.9% were 6–10 years, 24.6% were 11–15 years [30]. In Dong’s study, there were 728 confirmed cases and 1407 suspected cases. 17.6% of pediatric cases were <1 year of age, %23 were 1–5 years, 24.5% were 6–10 years, %19.3 were 11–15 years, %15.6 were >15 years.

The median age of all patients was 7 years and 56.6% of patients were male [3]. According to US data, among all 2,572 COVID-19 cases in children, the median age was 11 years (0–17 years).

Approximately one-third of reported pediatric cases 32% were between 15–17 years of age, 27% were between 10-14 years of age. Fifteen percent of cases were aged <1 year, 11% of cases were aged 1–4 years, and 15% of cases were aged 5–9 years.

Males comprised 57% of cases in the population in which sex information was obtained; among 184 cases in children whose information of exposure were available, 9 % had a history of travel, and 91% had a history of contact with a COVID-19 patient in the household or community.6

By 30.03.2020, there were 11535 total cases, of which 117 (1%) were pediatric in Turkey. The mean age was 8 years (1day–17 years). The 13.6% of cases were <1 year. There were 3 neonatal cases. Nearly 53% of cases were male. Patients with a history of contact were 48.7%. Only 1.7% of cases had a history of travel abroad. Turkish citizens comprised 93.1% of cases, but 6.9% were immigrants8.

Clinical findings
According to the available data, COVID-19 in children appears to be usually mild. A minority of children with COVID-19 require hospitalization. By March 6, among 2572 laboratory-confirmed cases of COVID-19 in children reported from the US, the estimated rate of hospitalization differed from 6% to 20%, and 0.58%–2.0% of them were admitted to an ICU.6

In this report, children aged <1 year had the highest percentage (15%–62%) of hospitalization among pediatric patients with COVID-19. Among 95 children aged <1 year with known hospitalization status, 59 (62%) were hospitalized, including five who were admitted to an ICU.

The percentage of patients hospitalized among those aged 1–17 years was lower (estimated range = 4.1%–14%), with little variation among age groups.6

Fever and cough are the most common reported symptoms in children [30]. Fever (subjective or documented), cough, and shortness of breath were more common among adult patients aged 18–64 years (93% reported at least one of these).

In contrast, these signs and symptoms were less frequently reported among pediatric patients (73%). In the case series from the United States, complete information about symptoms was available for 291 children; 56 percent had a fever, 54 percent had a cough, and 13 percent has shortness of breath; at least one symptom was observed in 73% of children6 On the other hand, these ratios were 71%, 80%, and 43%, respectively, in adults. Sore throat, myalgia, headache, and diarrhea were also reported rarely by pediatric patients.6

In another series of 1391 children evaluated for COVID-19 at Wuhan Children’s Hospital, 171 (12%) had confirmed SARS-CoV-2 infection (by identification of RNA). In this report, 15.8% percent of children with confirmed infection were asymptomatic, 19.3% had upper respiratory infection, and 64.9% had pneumonia.

Fever was the most common symptom, occurring at some point in illness in approximately 41.5%.

Other common symptoms included cough (48.5 percent) and pharyngeal erythema (46.2%).

Less common symptoms included fatigue, rhinorrhea/nasal congestion, diarrhea, and vomiting. (changing between 5% and 9%).

A total of 12 asymptomatic patients had radiologic features of pneumonia. A total of 21 patients were in stable condition in the general wards, and 149 were discharged from the hospital [30].

According to Dong et al.’s report, regarding the severity, 94 (4.4%), 1088 (51.0%), and 826 (38.7%) cases were diagnosed as asymptomatic, mild, or moderate, respectively; and accounted for 94.1% of all cases.

Severe and critical cases were 6.7% and 0.7% of patients [3]. The clinical features, laboratory testing, and chest radiograph imaging state the severity of COVID-19 [35]. Similar clinical manifestations have been reported in smaller case series from China [36–38].

According to the surveillance data from Turkey, 50.4% of pediatric cases had a mild disease, and 0.8% had severe disease. Intensive care hospitalization rate was 4.27% and 80% of them were under one year of age.8

Another critical age group in pediatrics is the neonatal period. Neonates are generally associated with milder disease [26,39]. In a report about COVID-19 in the neonatal period, it was found that the clinical symptoms of 33 neonates with or at risk of COVID-19 were obscure, and favorable outcomes were seen.

Of 33 neonates born to COVID 19 mothers, 30 had negative test results, but there were 3 neonates with symptomatic COVID-19. The most seriously ill neonate was possibly symptomatic because of prematurity, asphyxia, and sepsis, rather than SARS-CoV-2 infection [40].

In a case series of neonates, born to COVID-19 mothers, the 2019-nCoV nucleic amplification test results were negative for all neonates; thus there was no evidence of vertical transmission of 2019- nCoV via the placenta and they were all fine, so no antiviral treatment was administered to the neonates [41].

Although most children appear to havemild or moderate disease and recover within one to two weeks of disease onset, severe cases may also be seen, especially who are with underlying conditions.

Children with certain serious underlying conditions and who are <1 year of age are at higher risk for severe disease [3].6 Among 345 children from the United States with laboratory-confirmed COVID-19 and complete information about underlying conditions, 23% had an underlying condition.

Common underlying conditions were chronic pulmonary disease (including asthma), cardiovascular disease, and immunosuppression (e.g., related to cancer, chemotherapy, radiation therapy, hematopoietic cell or solid organ transplant, high doses of glucocorticoids).

Blood disorders, chronic kidney disease undergoing dialysis, chronic liver disease, pregnancy, endocrine disorders (e.g., diabetes mellitus), neurologic and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, intellectual disability, spinal cord injury) are significant reasons for severe disease.

Among the 295 pediatric cases for which information on both hospitalization status and underlying medical conditions was available, 28 of 37 (77%) hospitalized patients, (including patients admitted to an ICU), had one or more underlying medical condition; among 258 patients who were not hospitalized, 30 (12%) patients had underlying conditions.

Three deaths were reported among the pediatric cases included in this analysis; however, the reason for death as COVID-19 is not confirmed yet.6 In the study by Lu et al., during hospitalization, 3 patients required intensive care support and invasive mechanical ventilation; all had coexisting conditions [hydronephrosis, leukemia (for which the patient was receiving maintenance chemotherapy), and intussusception] [30]. Epidemiologic and clinical features of pediatric case series are summarized in Table.

Table 1

Epidemiologic and clinical characteristics of pediatric patients.

		Dong et al.	Lu et al.	CDC/MMWR USA	Turkey*
Total confirmed patients		728 (confirmed) 1407 (suspected)	171	2572	117
Sex, male (%)		56.6	60.8	57	52.9
Median age (yr)		7 (IQR: 2–13)	6.7 (1d–15 yr)	11 (0–17)	8 (1d–17yr)
Age distribution (%)	<1 year 1-5 year 6-10 year 11-15 year >15 years	17.6 23 24.5 19.3 15.6	18.1 23.4 33.9 24.6 Not included	15 11 (1-4 yr) 15 (5-9 yr) 27 (10-14 yr) 32	13.6 20.5 16.2 28.2 21.3
Clinical presentation	Asymptomatic Mild disease Moderate disease Severe illness	4.4 51.0 38.7 7.4	15.8 19.3 – –	– – – –	– 50.4 – 0.8
Mortality (n)		1	1	3	0

Diagnostic criteria
A diagnostic approach for COVID begins with the compatibility of exposure history, symptoms, and findings to the case definition criteria. Case definitions are based on the currently available data. Diagnostic criteria are regularly revised as new information accumulates.

Definitions should be revised according to their local epidemiological data and individual factors. All countries are encouraged to publish definitions used online and in regular situation reports and to document periodic updates to definitions, which may affect the interpretation of surveillance data9.

Pediatric patients should be evaluated according to complaints, clinical findings, and a history of exposure [35]. Firstly it should be stated if a child was in contact with a COVID-19 patientin the last two weeks period or has been to an endemic area for COVID-19.

This information contributes to determine the level of risk, as low, medium, or high. Afterward, suspected cases are explored for the following:

A- the presence of fever, any respiratory symptom, gastrointestinal symptoms like diarrhea.

B- complete blood count should be tested to find out leukopenia, lymphopenia, and

C-reactive protein is also tested in case of an increase.

C- chest screening should be done to find out any infiltration if present. Further examination is carried out for suspected patients. If a case is positive for nCoV-2019 in nasal/pharyngeal swap or blood samples by polymerase chain reaction (PCR) assay OR if samples from the respiratory tract or blood samples are similar to nCoV-2019 is similar genetically, then the case is defined as confirmed [3].

Another critical issue in diagnosis is the method of optimal sampling choice for diagnosing COVID-19 [35]. In a study of 205 patients with COVID-19 who were sampled at various sites, the highest rates of positive viral RNA tests were reported from bronchoalveolar lavage (95 percent, 14 of 15 specimens) and sputum (72 percent, 72 of 104 samples). Still, oropharyngeal swap test results were as low as 32% [22]10.

Laboratory examinations
White blood cell count is normal in general. But leucopenia may be seen, with decreased lymphocyte count. C-reactive protein (CRP) may be normal or increased. Interleukin-6 (IL-6) is also generally high in patients, especially in severe cases.

Procalcitonin (PCT) is normal in most cases, and PCT > 0.5 ng/mL might be a sign of secondary bacterial infection. Elevation of liver enzymes, muscle enzymes, and myoglobin, and increased level of D-dimer might be seen in severe cases [6].

Imaging features
In the early stage of pneumonia cases, chest images show multiple small patchy shadows and interstitial changes, remarkable in the lung periphery. Severe cases can further develop to bilateral multiple ground-glass opacity, infiltrating shadows, and pulmonary consolidation, with infrequent pleural effusion [30].

A Chest CT scan shows pathologic findings more clearly, including ground-glass opacity and segmental consolidation in bilateral lungs, especially in the lung periphery. In children with severe infection, multiple lobar lesions may be present in both lungs.

In the Lu et al.’s study of pediatric cases, the most common radiologic finding was bilateral ground-glass opacity (32.7%). Other findings were local patchy shadowing 18.7%, bilateral patchy shadowing 12.3%, and interstitial abnormalities 1.2% [30]. Pleural effusion was not seen.

In a pediatric case series, among 15 confirmed pediatric COVID-19 cases, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions on their first chest CT images. Small nodular ground-glass opacities were found in 7 cases, and speckled ground-glass opacities were found in 2.

Among the patients whose second PCR test was negative, chest CT images showed fewer lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. The other 9 cases were still positive in the second nucleic acid test. Six of them showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground-glass opacities [42].

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More information: Leena B. Mithal et al, SARS-CoV-2 Infection in Infants Less than 90 Days Old, The Journal of Pediatrics (2020). DOI: 10.1016/j.jpeds.2020.06.047