What are the chief predictors of SARS-CoV-2 infection in children?

Children's Health

During the ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19), children have suffered remarkably less than adults. However, there are no reliable predictors for the infection in children.

A new preprint, released on the medRxiv* server, seeks to explore the factors associated with the diagnosis in children. The ability to rapidly diagnose COVID-19 in this age group is essential not only for monitoring progressive disease in individual children, but to avert further transmission chains.

Study aims

The current study is the first to explore the risk factors associated with a positive diagnosis of COVID-19 in children being tested for the virus.

The identification of risk factors for pediatric infection by this virus is thus likely to help case finding and contact tracing in time. Moreover, it may allow healthcare to be better organized in low-resource settings, where many diagnoses rely on clinical factors alone.

Study details

The cohort came from 20 centers across Italy in the early pandemic. The testing included children tested due to symptoms similar to those of COVID-19, those without symptoms but with a history of exposure to a COVID-19 positive subject, and inpatient children tested in hospital screening programs.

According to the testing policy in Italy at the time, tests were indicated for COVID-19 exposed individuals; those with severe acute respiratory distress syndrome (ARDS); children presenting with either fever, cough or shortness of breath without obvious other causes.

Some hospitals tested all children who were hospitalized or children with skin or gut symptoms.

Of the roughly 2,500 children tested, about 2,150 had symptoms suggesting COVID-19, and 52 were asymptomatic contacts. About 300 came from hospital-based testing programs. Only 190 were positive (7.6%)

What were the results?

Over half of those tested because of exposure were positive compared to those screened because of COVID-19-like symptoms, or during hospitalization for any indication, at 7% and 2%, respectively.

Most positives (54%) were in the age group 10-18 years. Almost 80% of positive swabs came from children who had been exposed to a COVID-19 case.

Common symptoms

The most common symptoms were fever and dry cough, presenting in 82% and 32% of positives, respectively.

Notably, 68% and 23% of children who tested negative also had these symptoms. The presence of respiratory symptoms in any relative showed a strong correlation with positive swabs.

Sore throat and strep throat were found in just over a fifth of the positive children but double the number among negatives. This was also true of gut symptoms, though the incidence was much lower at 15% and 27%, respectively.

Neurological symptoms like seizures, irritability, anosmia, headache and ageusia were found in slightly under a fifth but were the only symptom in one child.

Less common symptoms

Flu-like symptoms, including myalgia, nausea, reduced appetite, were found in 17% but always accompanied other symptoms.

Respiratory features were the sole presentation in nine children, or around 6%.

Cutaneous signs led to SARS-CoV-2 detection in six children, but were also accompanied by other symptoms.

Comorbidities were present in below a fifth of both positive and negative children, but heart disease was a little more common among the positives, at around 6% versus 2%.

Neurological symptoms and muscle/joint pain showed the reverse trend, at 20% and 11% among children testing positive, versus 9% and 4%, respectively.

Laboratory findings

Laboratory tests such as lymphocytopenia and high C-reactive protein (CRP) levels were seen among the positive and negative groups, respectively. However, imaging results failed to differentiate between them.

Clinical outcome

Hospitalizations, the need for intensive care and type of respiratory support required, as well as the number of patients who needed it, were similar in both groups. Outcomes were generally favorable in both groups.

Risk factors

The only factors associated with SARS-CoV-2 positive tests were contact with COVID-19 cases, which increased the odds almost 40-fold. Fever and anosmia/ageusia were associated with three- and four-fold higher odds, as was a history of heart disease.

Being 2-9 years old was associated with only one-third the risk of testing positive for the virus relative to those aged 10-18 years.

Being tested positive was not associated with a particular group or presentation, whether the test followed symptomatic presentation or as part of routine screening of hospitalized patients.

Overall, about 10% of children tested positive in each of the centers in this study. Disease severity failed to predict positivity on testing, and most children had mild symptoms irrespective of the eventual test status.  Severe or critical disease was present in 4% of positives and 8% of negatives.

What are the implications?

The findings show that children with COVID-19 display non-specific features at presentation, typically fever, either alone or accompanied by respiratory signs, especially a dry cough. Very young children (below 10 years of age) are typically at a lower risk.

The major finding is that exposure is the single largest risk factor for SARS-CoV-2 positivity among children, as in adults. Thus, all children with a history of contact, fever or specific neurological signs such as anosmia/ageusia.

Symptoms relating to the nervous system, gut and skin are also possible, either in isolation or with other features, as reported by medical specialists from multiple fields.

The current testing guidelines for children may thus miss many cases, being based on the presence of fever or respiratory signs. Laboratory signs in children with the infection are not identical to those in adults, probably because of the typically mild presentation in this group.

Pre-existing cardiac disease was associated with a higher test positivity rate, a finding that needs confirmation from future studies. However, of the 190 children with a positive test, only two required intensive care and all recovered, as expected from earlier studies.

According to [the] CDC, the number of deaths among children under 15 years of age with COVID-19 in United States was much lower than what was reported for children with seasonal influenzas in 2019-2020 (17 for COVID-19 compared to 182 influenza-associated pediatric deaths).”

The different case finding and contact tracing protocols, with the high rate of false negatives using nasal or nasopharyngeal swabs, across regions in Italy, may have clouded the results somewhat. Greater accuracy and acceptability should be urgent goals with respect to the development of tools to diagnose this infection among children, and identify those at risk of severe disease.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

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