key: cord-0973572-7769w8jv
authors: Shoji, Kensuke; Akiyama, Takayuki; Tsuzuki, Shinya; Matsunaga, Nobuaki; Asai, Yusuke; Suzuki, Setsuko; Iwamoto, Noriko; Funaki, Takanori; Ohmagari, Norio
title: Clinical Characteristics of Hospitalized COVID-19 in Children: Report From the COVID-19 Registry in Japan
date: 2021-09-06
journal: J Pediatric Infect Dis Soc
DOI: 10.1093/jpids/piab085
sha: f38778efeada924f3d86ada4c652e5c78f9cf73d
doc_id: 973572
cord_uid: 7769w8jv

A total of 1038 pediatric patients with COVID-19 were identified. Among these, 308 (30%) had asymptomatic COVID-19. The overall outcome was good, and no patients died. A significant rate of patients aged <24 months and ≥13 years were found in the symptomatic group.

The details of COVIREGI-JP have been previously described [5] . Briefly, hospitalized patients who were positive for SARS-CoV-2 based on nucleic acid amplification (NAT) test or rapid antigen test were enrolled in the registry.

This was a retrospective observational study using the data from COVIREGI-JP. Pediatric patients under 18 years of age who were enrolled in COVIREGI-JP between January 1, 2020 and February 28, 2021, were included in the present study. The demographic and epidemiological data, such as age, sex, underlying diseases, history of COVID-19 exposure, vital signs, signs and symptoms, treatment, duration of hospitalization, and outcomes, were extracted from the database.

Clinical and epidemiological data were compared between symptomatic and asymptomatic patients as well as among patients in specific age categories. Fisher's exact test was used for the comparison of categorical variables, and the Mann-Whitney U test was used for 2 group comparisons of continuous variables, respectively. A 2-sided P value of <.05 was considered to indicate statistical significance. All statistical analyses were performed by the R statistical software version 4.0.5.

The National Center for Global Health and Medicine ethics review committee and the National Center for Child Health and Development ethics committee approved the study (NCGM-G-003494-0 and NCCHD-2020-313, respectively).

During the study period, a total of 36 430 patients with SARS-CoV-2 infection who were hospitalized in 572 institutions were registered in COVIREGI-JP. Among these, 1038 pediatric patients were hospitalized with SARS-CoV-2 infection. The background characteristics of these pediatric patients are summarized in Table 1 . Briefly, the median cohort age was 9.0 years, 169 (16.3%) patients were younger than 24 months of age, and 571 (55.0%) patients were male. The rate of patients with underlying conditions was very low (n = 60 [5.8%]). Although the cohort included only hospitalized cases, 308 (29.7%) of the patients were asymptomatic at the time of admission.

The comparison of asymptomatic and symptomatic patients is shown in Table 1 . The distribution of age was significantly different between the asymptomatic and symptomatic groups (P < .001). Specifically, the rates of patients aged <24 months and ≥13 years were higher in the symptomatic group than in the asymptomatic group. Although not statistically significant, the rate of patients with any underlying disease was higher in the symptomatic group than in the asymptomatic group (n = 49 [6.7%] vs n = 11 [3.6%], P = .057). Other characteristics including sex and immunosuppressive conditions were similar between the 2 groups.

The comparisons of laboratory data between the symptomatic and asymptomatic patients categorized according to age (Supplementary Figure S1 ) revealed that the majority of laboratory data were comparable between the asymptomatic and symptomatic groups.

We performed supplementary analyses to compare disease severity according to the different "wave periods. " We divided the patients into 2 groups: patients hospitalized from January 2020 to September 2020 and those hospitalized from October 2020 to February 2021. The number of patients who required supplemental oxygenation was similar in the 2 groups, 5/312 (1.6%) and 10/418 (2.4%), respectively (P = .601).

The clinical characteristics of the symptomatic patients are shown in Table 2 . In this group, the most commonly observed symptoms were cough (n = 271 [37.1%]) and runny nose (n = 215 [29.5%]). Fever ≥38.0℃ was observed in only 75 (10%) of the symptomatic patients. Several symptoms, such as diarrhea, dysgeusia, and olfactory dysfunction, were more commonly observed in older patients than in younger patients.

The clinical interventions and outcomes of the symptomatic pediatric SARS-CoV-2 infection patients are summarized in Supplementary Table S1 and Supplementary Digital Content.

Only 15 (2.1%) patients required noninvasive oxygen support, and no patient needed invasive mechanical ventilation or extracorporeal membrane oxygenation. The outcomes were good and there was no mortality. Although the majority of the patients had asymptomatic or mild SARS-CoV-2 infection, the median duration of hospitalization was 8 (interquartile range, 6-9) days; the duration of hospitalization was not different between the symptomatic and asymptomatic patients (8 [5] [6] [7] [8] [9] ) and 8 [6] [7] [8] [9] days, respectively).

In this nationwide observational study of hospitalized pediatric patients with SARS-CoV-2 infection conducted in Japan, our analyses revealed that neonates and young infants tended to be symptomatic.

Our analyses revealed that the rate of symptomatic patients was relatively high in neonates and young infants compared to the other age groups. Whether young children, such as neonates or infants, are at risk of developing symptoms has not been extensively investigated. A national prospective surveillance study in France revealed that fever was more common in pediatric patients aged <90 days than in those from other age groups [6] . Additionally, a study reported that dyspnea, sore throat, and cough were more common in newborn patients than in infants, which might be related to an immature immune system [7] . Consistent with these reports, our results indicate that symptoms might be more common in very young patients.

In the current study, the outcome of hospitalization was excellent, with no patient deaths. International, multicenter cohort studies in Europe and Latin America show that intensive care unit admission rate range between 8.2% and 12.7% in pediatric patients with SARS-CoV-2 infection and that the mortality rate ranges between 0.7% and 4.2% in hospitalized pediatric patients [1, 2] . The cause underlying the excellent outcome observed in the current cohort is not clear but one potential explanation is the rarity of MIS-C in Japan. MIS-C, which is a severe inflammatory condition that emerges several weeks after SARS-CoV-2 infection, can be severe and even fatal; however, MIS-C appears to be more common in Black, Caucasian, and Latin American ethnic groups and has been rarely reported in Asians [8] . In fact, only two cases of MIS-C have been reported in Japan [9, 10] . Moreover, the low proportion of patients with an underlying condition in our cohort could be a potential explanation of the excellent outcome. Those patients with underlying diseases and/or their family members might have faithfully adhered to infection control measures, including social distancing, hand hygiene, universal masking, or home isolation, which may have also contributed to the very low proportion of patients with underlying conditions. Although the majority of pediatric patients in Japan had asymptomatic or mild SARS-CoV-2 infection, the median hospitalization duration was longer than 1 week. The COVIREGI-JP did not include information regarding the primary reason for admission. However, mild or asymptomatic SARS-CoV-2 positive patients were admitted to the hospital for isolation purposes, especially in the early stage of the COVID-19 pandemic. In addition, we received many pediatric hospitalized cases for isolation because both parents of some children were hospitalized with severe COVID-19, and no other family members could take care of the children. Thus, we believe that the primary reason for hospitalization among asymptomatic pediatric patients was isolation. There are many disadvantages associated with hospitalization in children. Therefore, it may be necessary to reconsider the current indications for hospitalization and in-hospital isolation duration for pediatric patients with SARS-CoV-2 infection in Japan.

The present study has several limitations. First, participation in this registry was voluntary; therefore, the data might not have reflected the overall epidemiology of pediatric SARS-CoV-2 infection in Japan. Second, COVIREGI-JP included only hospitalized patients and not outpatients. Therefore, the findings of the present study cannot be generalized to outpatient settings. Third, the prevalence of symptoms across age groups should be carefully interpreted. Younger children are not going to be able to accurately describe symptoms such as dysgeusia or olfactory dysfunction. Thus, the prevalence of these symptoms in younger children would have been underestimated. Fourth, COVIREGI-JP did not have information on long-term outcomes of acute infection, such as MIS-C and the increasingly reported long COVID [11] .

In conclusion, our analyses of the clinical and epidemiological data of COVIREGI-JP revealed that the majority of pediatric patients had mild or asymptomatic SARS-CoV-2 infection and that neonates and young infants tended to be symptomatic.

Supplementary materials are available at the Journal of the Pediatric Infectious Diseases Society online.

Financial support. This work was supported by the Health and Labor Sciences Research Grant entitled "Research for risk assessment and implementation of crisis management functions for emerging and re-emerging infectious diseases (19HA1003). " Potential conflicts of interest. All authors declare that they do not have any potential, perceived, or real conflicts of interest. All authors have submitted the ICMJE Form for Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

COVID-19 and multisystem inflammatory syndrome in Latin American Children: a multinational study

Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2

Clinical characteristics of asymptomatic and symptomatic pediatric coronavirus disease 2019 (COVID-19): a systematic review

Clinical epidemiology of hospitalized patients with COVID-19 in Japan: report of the COVID-19 REGISTRY JAPAN

Factors associated with severe SARS-CoV-2 infection

The younger the milder clinical course of COVID-19: even in newborns?

Multisystem inflammatory syndrome in children related to COVID-19: a systematic review

A case of multisystem inflammatory syndrome in children in a Japanese boy: with discussion of cytokine profile

Multisystem inflammatory syndrome associated with SARS-CoV-2 in a Japanese girl

Preliminary evidence on long COVID in children