DISCUSSION
Respiratory viruses are among the leading causes of pediatric morbidity and mortality worldwide. Unlike other viral respiratory diseases, COVID-19 has had a relatively limited impact on children as compared to adults.9 However, as lockdowns are eased and schools reopened, the increased contact between unvaccinated children might change the scenario and increase the circulation of both SARS-CoV2 and other respiratory viruses, including influenza.10
In this cohort comparing the clinical characteristics and outcomes of SARS-CoV2 infection with epidemic influenza in hospitalized pediatric patients in a single referral hospital, we found a higher proportion of asymptomatic infection in children with SARS-CoV2 than in those with influenza. Almost half of infants with SARS-CoV2 infection had no symptoms of COVID-19. However, the greater proportion of asymptomatic infection may be explained by the different sampling approach, with PCR testing performed on all admissions beginning in June.
Fever and cough were the most common manifestations among both groups, but rhinorrhea was rare in patients with COVID-19 while it was common in children with influenza. The absence of nasal symptoms might be suggestive of COVID-19 in pediatric patients with fever and cough. However, most signs and symptoms were similar between the two groups, making clinical distinction unreliable.
In comparison, in a retrospective cohort of 315 pediatric patients with COVID-19 (median age 8.3 years) and 1402 with influenza (median age 3.9 years) in the Unites States, Song et al.11 describe a higher frequency of fever, gastrointestinal symptoms, headache, myalgia and chest pain among hospitalized children with COVID-19. However, patients with COVID-19 were older than those with influenza (median age 8.3 years, versus 3.9 years) which might have biased the reporting of symptoms.
Another retrospective single-center cohort study found a lower Charlson index in the COVID-19 group, as well as a greater frequency of anosmia, dysgeusia, diarrhea and frontal headache, and lower prevalence of dyspnea, conjunctivitis and vomiting. No children were included in this cohort.12
Regarding outcome, hospitalized patients with symptomatic influenza and COVID-19 had a similar risk of invasive mechanical ventilation and death, and one in ten infants had a fatal outcome. This underscores that even though COVID-19 is usually mild in children, it can cause severe disease and death in children with chronic diseases, as has been recognized for influenza for a long time4. Mortality was lowest among children 1 to 9 years old with either influenza or SARS-CoV2 infection, but differences between age groups were not statistically significant. This is consistent with reports from the United States, where the greatest proportion of COVID-19 pediatric deaths occurred in infants and adolescents13 and deaths from influenza are more frequent among those younger than 6 months.14
The aforementioned study by Song et al.11 reported a similar rate of hospitalization, intensive care unit admission and use of mechanical ventilation. Two deaths were reported among patients with influenza while no patients with COVID-19 died.
In France, Piroth et al.15 describe a higher in-hospital mortality for patients with COVID-19 in comparison with those with influenza, based in a nationwide retrospective cohort of hospitalized patients. The proportion of pediatric patients was smaller for COVID-19 than for influenza, but in-hospital mortality was ten-times greater for COVID-19 in those 11-17 years old, and a larger proportion of patients younger than 5 years needed intensive care support for COVID-19 than for influenza.
A systematic review and meta-analysis of studies describing individuals with either influenza or COVID-19 reported a lower frequency of nasal symptoms, pharyngodynia and dyspnea, and a greater prevalence of radiographic abnormalities among patients with COVID-19. Case fatality rate of hospitalized patients was 6.5%, 6% and 3% respectively for individuals with COVID-19, influenza A and influenza B. However, pediatric patients represented a small fraction of the cases and findings were limited by the heterogeneity of the studies.16
Zhang et al.17 describe two cohorts of patients hospitalized with influenza or COVID-19 in two separate locations. One in every five patients with COVID-19 was admitted to ICU and 13% died, while no severe or fatal cases were recorded in the influenza cohort. No data for pediatric patients was reported in this study.
Our study has several limitations worth noting. The single-center nature of the cohort, as well as the frequency of comorbidities among participants, may limit the generalizability of findings. Data on patients with influenza was collected retrospectively from clinical records while the COVID-19 cohort was followed-up prospectively. The different time periods between the two cohorts may account from differences in diagnostic and therapeutic approaches. As mentioned above, all patients admitted to hospital were screened for SARS-CoV2 infection from June 2020, which explains the greater proportions of asymptomatic infections. However, asymptomatic patients were excluded from the outcome analysis to account for this limitation. Non-invasive mechanical ventilation was discouraged for patients with suspected or confirmed COVID-19 to reduce aerosol generation, which might have increased the proportion of patients receiving invasive mechanical ventilation.
In conclusion, influenza and COVID-19 have a similar picture in pediatric patients, which makes diagnostic testing necessary for adequate diagnosis and management and will add to the challenge of co-circulation as SARS-CoV2 becomes endemic. Even though most cases of COVID-19 in children are asymptomatic or mild, the risk of death among hospitalized children with comorbidities is substantial, especially among infants, and is similar to that of patients with influenza. Thus, children should not be left out of preventive and therapeutic development in the COVID-19 pandemic, including vaccine development programs.18