CONTEXT

Long-term health effects after coronavirus disease 2019 (COVID-19) have been increasingly reported but their prevalence and significance in the pediatric population remains uncertain.

OBJECTIVE

To present the prevalence and characteristics of the long-term clinical features of COVID-19 (long COVID) in the global pediatric population.

DATA SOURCES

PubMed, Embase, Web of Science, Cochrane Library, WHO COVID-19 database, google scholar, medRxiv, bioRxiv, and multiple national public health databases.

STUDY SELECTION

Published articles and preprints from December, 2019 to December, 2022 investigating the epidemiology and characteristics of persistent clinical features at least 3 months after COVID-19 in children and adolescents (0–19 years old) were included.

DATA EXTRACTION

Study characteristics and detailed description of long COVID were extracted into a predefined form.

RESULTS

Twenty seven cohorts and 4 cross-sectional studies met the inclusion criteria and involved over 15 000 pediatric participants. A total of more than 20 persistent symptoms and clinical features were reported among children and adolescents. 16.2% (95% confidence interval 8.5% to 28.6%) of the pediatric participants experienced 1 or more persistent symptom(s) at least 3 months post COVID-19. Female gender might be associated with developing certain long COVID symptoms.

LIMITATIONS

Included studies presented with great heterogeneity because of significant variations in the definition of “long COVID,” follow up duration, and method. There could be nonresponse and other potential bias.

CONCLUSIONS

Persistent clinical features beyond 3 months among children and adolescents with proven COVID-19 are common and the symptom spectrum is wide. High-quality, prospective studies with proper controls are necessary in the future.

Given that more than 758 million coronavirus disease 2019 (COVID-19) cases have been confirmed worldwide with rates still escalating,1  increasing attention is being paid to the long-term effects of COVID-19 on population health. Several long-term clinical features post-COVID-19 have been observed, mainly in the adult population,2  involving multiple organs and systems.3,4  A clinical case definition for post-COVID-19 condition (long COVID) was developed by the World Health Organization (WHO) with multiple stakeholders in October 2021 that can be applied to all settings.5 

During the early stages of the COVID-19 pandemic, neonates, children, and adolescents aged less than 19 years occupied a small proportion (1% to 10%) of the total reported COVID-19 cases.6,7  They were also more likely to present with a milder clinical course and more favorable short-term outcomes compared with adults.610  However, with the subsequent surge of cases caused by the Δ and ο variants, and the fact that a large proportion of children under 12 years old still remain unvaccinated globally, the number of neonates, children, and adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been increasing significantly.1113  With the increased epidemiologic burden of COVID-19, the long-term health effects of SARS-CoV-2 infection on this vulnerable group requires greater attention. It was thought at first that the pediatric population was relatively spared from the long-term effects of COVID-19 after infection,14  but this changed rapidly with increasing reports and studies of pediatric patients not fully recovering from acute COVID-19.1520  Furthermore, since it was first reported in April 2020, multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19,2124  also called pediatric inflammatory multisystem syndrome,22  has become increasingly recognized and widely studied worldwide. Not only can MIS-C lead to serious clinical acute presentation in the short term, it can also impact pediatric patients’ long-term health. For example, MIS-C can cause the formation of coronary artery aneurysm that can negatively impact cardiac function.25  However, long-term health data on neonates, children, and adolescents infected with SARS-CoV-2 (including MIS-C patients) are limited and of varying quality.

Our objective for this review was to synthesize and evaluate current evidence on the characteristics of the long-term clinical features of SARS-CoV-2 infection, defined as persistent or new onset clinical features and laboratory findings at least 3 months after the index infection, in the global pediatric population (0–19 years old) so as to inform clinical practice and public health policy making.

We evaluated the long-term clinical features of SARS-CoV-2 infection in neonates, children, and adolescents defined as new, recurring, or persistent signs, symptoms, and laboratory findings that occur 3 or more months after a confirmed infection with SARS-CoV-2 in neonates, children, and adolescents 19 years old or younger. We also evaluated other factors associated with the development of long-term symptoms and/or laboratory findings in children and adolescents’ postinfection.

A systematic and comprehensive search of published papers was conducted in PubMed, Embase, Web of Science, Cochrane Library, WHO COVID-19 Database, China National Knowledge Infrastructure Database, WanFang Database, Latin American and Caribbean Health Sciences Literature, and Google Scholar, covering a timeline from December 1, 2019 to February 16, 2022. Then, we did a supplementary search in December, 2022 for the most updated literature. Although the WHO criteria for “long COVID” was not established until October 2021, there might be earlier studies reporting post-COVID signs and symptoms that met the later-established WHO criteria. Therefore, we decided to search the databases since December 2019, the beginning of the COVID-19 pandemic, so as to ensure capturing all qualified studies. Preprints from medRxiv (https://www.medrxiv.org), bioRxiv (https://www.biorxiv.org), and ChinaXiv (http://www.chinaxiv.org/home.htm) were also covered. Complementary searches were conducted manually through the search of national public health websites, the United States Centers for Disease Control and Prevention, and news of World Health Organization (WHO). All reference lists of retrieved articles were examined for relevant papers. There was no language restriction.

Search strategies were developed for each database with a combination of controlled vocabulary and free text (ie, MeSH terms, Emtree terms). The following search terms were included: “severe acute respiratory syndrome coronavirus 2,” “novel coronavirus 2019,” “2019 nCoV,” “COVID-19,” combined with “children,” “neonates,” “infants,” “adolescents,” “pregnancy,” “pregnant women,” “long,” “long-term,” “post,” “post-acute,” “chronic,” “persistent,” “prolonged,” “follow-up,” “outcome,” “consequence,” “sequalae,” and “complication.” An information specialist with extensive experience in systematic reviews was consulted. Specific search queries for each database are provided in Supplemental Tables 47.

All search results were uploaded into Covidence Systematic Review Software (Veritas Health Innovation, 2016) for the screening process.

In this systematic review, we included cross-sectional and cohort studies investigating the prevalence and/or presentations of the long-term effects of SARS-CoV-2 infection in the general population of neonates, children, and adolescents (0–19 years old) postinfection. Studies that included participants beyond the age group and those did not report on age-disaggregated data were excluded. Studies only focusing on a subgroup of the pediatric population, eg, MIS-C, immunodeficiency children, were excluded. SARS-CoV-2 infection status should be confirmed by laboratory testing, ie, polymerase chain reaction (PCR) test, serology antibody test. Long-term effects and outcomes were defined in this review as persistent clinical features ≥3 months after the COVID-19 diagnosis. We included all studies reporting long COVID signs and symptoms at least 1 month from SARS-CoV-2 infection at the very beginning, and then further screened these studies’ follow-up details. For studies with participants followed less than 3 months, if they reported disaggregated data for those with a follow-up duration ≥ 3months, they were included. Their subgroup data for those with ≥ 3 months follow-up were extracted and analyzed.

Case series, review articles, opinion articles, communications not presenting on data or description of long-term outcome of COVID-19 in neonates, children, and adolescents, as well as interventional, quasi-experimental and modeling papers were excluded. Studies with possible duplication of cases demonstrated by overlapping time periods and same institutions, cities, and countries from where reported cases are from were also excluded unless they reported the results of different lengths of follow-up.

After search results had been uploaded into Covidence, duplicates were identified with Covidence’s automatic deduplication function. A team member (L.J.) then manually reviewed identified records to confirm duplication. The final deduplicated library was used for title-abstract screening. Two review authors (L.J. and X.L.) independently reviewed each title and abstract. A decision whether to obtain the full text of the abstract based on the inclusion and exclusion criteria specified above was made using designations of “include,” “exclude,” or “unclear.” The full text article was obtained if at least 1 reviewer marked the study as “include” or “unclear.” For studies not written in English (French, Spanish, Portuguese, Italian, and German), if a decision could not be made by reading the English abstract, our colleagues who could read Chinese (L.J. and X.L.) and French (L.J.) and Google Translate helped with translating them into English.

In reference to the criteria specified in the earlier section, the decision was made by the same reviewers to include or exclude the study. Disagreement between the 2 reviewers were discussed, and if no consensus was reached, a third reviewer (J.N. or K.T.) casted the deciding vote to resolve the conflict.

Two reviewers (L.J. and X.L.) independently reviewed and extracted study data using a predefined form after selection of eligible studies by the full-text screening process. Data extracted included: study title, authors, year and month of publication, country, language of the study, study design, study period, setting, population (general population, neonates, children and adolescents specific), sample size, race, age, gender, comorbidities, SARS-CoV-2 infection confirmation method, severity of acute SARS-CoV-2 infection (eg, asymptomatic, mild, moderate, or severe symptoms, MIS-C or pediatric inflammatory multisystem syndrome diagnosis; hospitalization, ICU admission), duration of follow-up, follow-up method, persistent or new symptoms reported at follow-up, physical examination or laboratory findings at follow-up, and other clinical conditions related to post-COVID-19 infection (eg, readmission, quality of life score, etc).

For each dichotomous outcome, the weighted mean prevalence (in proportion) and the 95% confidence interval (CI) were calculated. If multiple measures are reported for an outcome, the measure most commonly reported across all studies was used. Only self- and caregiver-reported symptoms reported by 2 or more studies were included in the meta-analyses to generate a pooled estimate. Descriptive analyses and meta-analyses were performed using SPSS Statistics 22 and Comprehensive Meta-analysis version 2.2.027, respectively. A random-effect model was used for the meta-analyses as it best accommodated the moderate to high level of variation among included studies.

The characteristics, biases, and results of the included studies were summarized using a narrative approach. Statistical heterogeneity across studies was evaluated using the I2 statistic. I2 values equal to or above 50% signified “significant” heterogeneity. In addition, heterogeneity was tested using the χ-square test and visual inspection of the forest plot. Meta regression using the metagen and metareg functions of the meta package in R (Version 4.0.3) was used to identify the linear relationship between demographics and medical history with long COVID symptoms.26  The results are presented as point estimates of coefficient and 95% CIs. The level of statistical significance is set at 5% (P < .05) for all statistical analyses.

We consider cross-sectional studies and studies collecting long COVID symptoms in a retrospective fashion are predisposed to a higher risk of recall bias on this topic, given that their participants needed to recall the nature, duration, and intensity of any new, persistent, or recurring symptom they had experienced after SARS-CoV-2 infection. Therefore, we only assessed cohort studies that prospectively identified or collected participants’ persistent clinical features after SARS-CoV-2 infection for their methodological quality.

The study quality assessment tool for observational studies developed by the National Heart Lung and Brain Institute and the Research Triangle Institute International was used (Supplemental Table 8).27  Quality was assessed according to the study question (ie, was the objective and study population clearly defined), methods (ie, study population selection, sample size, measurement of exposure and outcome), and results (eg, length and loss of follow-up). Two reviewers (L.J. and K.T.) independently assessed each included study for methodological quality and assigned an overall quality rating for each study (ie, low, moderate, high risk of bias). A final rating for each study was decided by comparing the rating of both reviewers. A third reviewer (X.L. or J.N.) was consulted to resolve any disagreements.

Our preliminary and updated systemic literature search yielded 4660 results, of which, 243 passed initial screening; full articles were then obtained and reviewed. An additional 6 articles were identified via manual searching and reference-checking. Twenty seven cohort studies (19 prospective cohorts18,20,2844  and 8 retrospective cohort studies4552 ) along with 4 cross-sectional studies5356  on the pediatric population with a post-COVID-19 follow-up duration of at least 3 months or disaggregated data for participants followed-up for ≥3 months were included in our final systematic review (Fig 1). Studies’ characteristics are summarized in Table 1.

Nineteen cohort studies prospectively collected information related to any persistent clinical features or laboratory findings in participants with a laboratory-confirmed SARS-CoV-2 infection. The majority of selected studies were from Europe (13 in total). One study was conducted in multiple countries.37  The remaining were from Iran (2), Australia (1), China (1), and the United States (1) (Table 1). The total number of children and adolescents (0–19 years old) with confirmed COVID-19 diagnosis and were followed-up for long COVID for at least 3 months was over 15 000, ranging from 15 to 11 950 in each study. The follow-up time varied from 3 to over 12 months. Four studies20,34,38,40  mainly reported results from participants with a follow-up duration of greater than 12 months. Eight studies exclusively included children and adolescents who were hospitalized because of SARS-CoV-2 infection29,32,33,38,39,41,43,44 ; however, in 1 study from China,33  hospitalized COVID-19 children were either asymptomatic or only with mild symptoms. The participants of remaining studies were either mainly outpatients during their acute infection stage or recruited from the community. Two studies included a mixed adult and children or adolescent population and reported their results separately.30,36  Two studies had an overlapping study population34,42 : they were part of the Children and Young People with Long COVID Study (the CLoCk study), a national, matched, longitudinal cohort study describing the clinical phenotype and rate of post-COVID physical and mental problems in children and adolescents in England, and reported the 3-month and up to 12-month follow up results for adolescents aged 11 to 17 years, respectively. Five studies included a matched control group of SARS-CoV-2 tested negative counterparts to compare the prevalence and/or clinical features of persistent symptoms and signs between groups.33,34,36,37,42  Two studies collected information from routine data from the health insurance system.36,43  Four studies collected data via questionnaires or data collection forms18,34,35,42  and 6 studies via telephone interview.20,29,32,37,38,40  The remaining 7 studies collected data through clinical assessment and evaluation.28,30,31,33,39,41,44 

For included cohort studies identifying persistent symptoms after acute SARS-CoV-2 retrospectively, 3 studies47,49,50  used telephone interview to collect data from pediatric patients with a previous SARS-CoV-2 infection, mainly about the existence, nature, and duration of persistent symptoms after recovering from acute COVID-19. The remaining 5 studies recruited children and adolescents who already presented with persistent symptoms after SARS-CoV-2 infection as the study initiated and evaluated and/or followed these participants afterward.45,46,48,51,52  Information such as the time elapsed from COVID-19 diagnosis to the emergence of new, persistent symptoms was collected retrospectively in these studies. The majority of included cross-sectional and retrospective cohort studies used questionnaires, surveys, and telephone interviews to identify long-term clinical features of COVID-19.

Six prospective cohort studies were evaluated to have potentially high risk of bias, 8 with moderate risk, and 5 with low risk of bias (Supplemental Fig 4). However, certain items were unachievable. For example, assessors were typically not blinded to the SARS-CoV-2 infection status of participants. Furthermore, the recruitment process, response rate, sample size justification, and power descriptions were not clearly described in the majority of studies. Some items cannot effectively distinguish studies with different levels of quality. For instance, all included studies had a follow-up duration of at least 3 months and were rated as “low risk of bias” on “sufficient follow-up frame.”

More than 20 persistent or new onset symptoms after the acute infection of SARS-CoV-2 were reported in children and adolescents, including fatigue, depression, sleep disturbance, cough, throat pain, gastrointestinal symptoms, etc.

The vast majority of included studies described these self- or caregiver-reported symptoms as “persistent” or “long-term” symptoms after COVID-19. Among them, some specified these symptoms did not exist before the index SARS-CoV-2 infection (ie, described as “new,” “novel”), whereas others did not. Therefore, we used the term “persistent symptoms” in our review to represent them. There was a very limited number of studies that had reported signs and laboratory findings after COVID-19 in the general pediatric population and their findings were very diverse. (Table 2)

We were able to perform a meta-analysis on 12 cohort studies prospectively identifying and collecting information related to the persistent clinical features 3 months after acute SARS-CoV-2 infection in a general pediatric COVID-19 population, including more than 6000 children and adolescents. The other 7 cohort studies were not included in the meta-analysis mainly because they only provided quantitative results for laboratory findings only or they reported the incidence rate of persistent symptoms instead of their absolute numbers. The pooled proportion of postacute COVID-19 symptoms in children and adolescents recovered from COVID-19 are presented in Fig 2. There were 16.2% (95% CI 8.5%–28.6%) of children and adolescents with a laboratory-confirmed diagnosis of COVID-19 that experienced 1 or more persistent symptom(s) in their latest follow-up, which was ≥3 months postinfection (the follow-up duration ranged between 3 to 13 months). The 5 most prevalent long-term clinical manifestations after COVID-19 in this pediatric population were sore throat (2 studies, N = 3106; pooled estimate = 14.8%, 95% CI 4.8%–37.5%), persistent fever (4 studies, N = 5128; pooled estimate = 10.9%, 95% CI 2.4%–38.2%), sleep disturbance (3 studies, N = 697; pooled estimate = 10.3%, 95% CI 4.9%–20.4%), fatigue (8 studies, N = 6110; pooled estimate = 9.4%, 95% CI 4.1%–20.2%), and muscle weakness (2 studies, N = 196; pooled estimated = 8.7%, 95% CI 5.5%–13.6%), followed by cough (8 studies, N = 5890; 6.8%, 95% CI 2.4%–17.7%), headache (7 studies, N = 5809; 4.6%, 95% CI 1.2%–16.2%), dyspnea (5 studies, N = 5560; 95% CI 4.3%, 95% CI 1.1%–15.1%), abdominal pain (4 studies, N = 3718; 3.7%, 95% CI 2.3–5.8%) and diarrhea (2 studies, N = 3564; 3.5%, 95% CI 1.3%–8.9%). (Figs 2 and 3)

Sensitivity Analysis

We were able to conduct a sensitivity analysis by pooling the data from 2 studies of low risk of bias37,42  and 5 studies of moderate risk of bias18,29,30,35,44  together. The 5 most prevalent long-term symptoms reported by these studies included persistent fever (2 studies, N = 559; pooled estimate = 7.9%), fatigue (5 studies, N = 5654; pooled estimate = 7.4%), altered smell and/or taste (4 studies, N = 5433; pooled estimate = 6.1%), dyspnea (5 studies, N = 5560; pooled estimate = 4.3%) and headache (4 studies, N = 5493; pooled estimate = 3.9%). (Supplemental Fig 5)

Subgroup Analyses

Then, we performed a subgroup analysis of the included prospective cohort studies according to their length of follow-up: 3 to 6 months, 6 to 12 months, and ≥12 months. Studies whose follow-up duration cannot be disaggregated to fit into these 3 subgroups were excluded from this analysis. The clinical spectrum of long COVID symptoms were quite different for these subgroups. Four studies (N = 5158) had a follow-up duration of 3 to 6 months, with sore throat, persistent fever, muscle weakness, fatigue and cough the most common persistent symptoms at the time of follow-up. Three studies (N = 668) had a follow-up duration of 6 to 12 months, with sleep disturbance, weight loss, persistent fever, fatigue, and muscle weakness as the 5 most commonly reported long-term symptoms after COVID-19. Only 1 study (N = 360) followed all its participants for any long COVID symptoms for over 12 months and found fatigue, palpitation, arthralgia, and muscle pain the most frequently reported at that time. (Supplemental Fig 6)

None of the included studies were from low-income countries. Seven studies collected data from 7 upper middle-income countries (Argentina, China, Costa Rica, Czech Republic, Iran, Russia, and Paraguay).29,33,35,3739,44  One of these studies was a multinational study also including participants from high-income countries, and it did not provide data for individual countries.37  Pooled data from 4 studies29,35,38,44  reported that 33.4% (95% CI 17.3%–54.7%) of their pediatric participants had long COVID. The most commonly reported symptoms in studies from upper middle-income countries were muscle weakness (1 study, N = 58; 10.3%, 95% CI 4.7%–21.1%), fatigue (3 studies, N = 914; 9.5%, 95% CI 4.0%–20.8%), sleep disturbance (2 studies, N = 559; 7.9%, 95% CI 6.0%–10.5%), and dyspnea (3 studies, N = 611; 5.6%, 95% CI 1.3%–20.9%). Twenty cohort and 4 cross-sectional studies were from high-income countries (HICs). We were able to pool the data from 7 prospective cohort studies from HICs18,20,30,32,4042  together, which reported that 14.4% (95% CI 6.7%–28.2%) of participants had long COVID. The most commonly reported symptoms from HICs were nasal congestion (1 study, N = 41; 34.2%, 95% CI 21.4%–49.7%), persistent fever (3 studies, N = 3244; 25.6%, 95% CI 10.5%–50.3%), sleep disturbance (1 study, N = 138; 18.8%, 95% CI 13.2%–26.2%), cough (4 studies, N = 3395; 17.9%, 95% CI 7.4%–37.3%) and fatigue (4 studies, N = 3312; 16.2%, 95% CI 7.4%–32.1%). (Supplemental Figs 7 and 8)

Seven studies only recruited the pediatric population for follow-up, whereas 2 studies had a mixed adult and child or adolescent population. The most commonly reported long-term symptoms from studies included exclusively children and adolescents were sore throat, fatigue, persistent fever, muscle weakness, and sleep disturbance. For the 2 studies including a mixed adult and children population, the spectrum of reported persistent symptoms were limited, with sleep disturbance, weight loss, cough, skin rash, and persistent fever as the leading complaints from the pediatric participants. (Supplemental Fig 9)

We planned to identify potential risk factors associated with long COVID by using meta-regression analysis, which is recommended to contain at least 5 studies per potential risk factor to ensure a reliable result.57  In our included prospective studies, only gender was presented in 9 studies. Female gender was found to be associated with a higher risk of developing certain long COVID symptoms, ie, sleep disturbance and headache (P < .01). (Supplemental Table 7) The other risk factors, such as race, morbidity, and severity of disease during acute SARS-CoV-2 infection, were reported in less than 5 included studies and could not be analyzed by meta-regression for their potential relationship with developing long COVID in the pediatric population.

Our findings demonstrate that less than one fifth (16.2%, 95% CI 8.5%–28.6%) of children and adolescents (0–19y) with COVID-19 continue to present with at least 1 persistent symptom(s) beyond 3 months postinfection. A wide spectrum of symptoms, physical, and laboratory findings was reported. Sore throat, persistent fever, sleep disturbance, fatigue, and muscle weakness were among those most commonly reported.

First reported in 2020, long COVID, also known as post-COVID-19 syndrome or condition,5,5860 postacute sequelae of SARS-CoV-2,61  and chronic COVID syndrome,62  represents a group of symptoms that develop or persist after the acute phase of SARS-CoV-2 infection. Hypotheses for long COVID included persisting reservoirs of SARS-CoV-2 in tissues, immune dysregulation, autoimmunity, dysfunctional signaling in the brainstem and/or vagus nerve, etc.63  However, many definitions of long COVID exist (Table 3).5,5860  Current clinical definitions for long COVID are generally broad and sensitive to ensure that as many patients affected by long COVID are provided access to services and support as possible. However, asymptomatic patients and patients with undetectable levels of antibodies during testing may be left out, leading to an underestimation of the prevalence of long COVID. Furthermore, case definitions also serve other purposes, such as research. Broad definitions of long COVID can also hamper comparison between studies. High heterogeneity was observed in the inclusion criteria of individual studies, resulting in varying prevalence of long COVID. Differences mainly include the diagnostic method of acute COVID-19 infection (clinical diagnosis versus laboratory testing), duration of the post-COVID period, and the inclusion or exclusion of symptoms presented before COVID-19.

Estimates of the prevalence of long COVID vary considerably among studies, as reflected by varying case definitions and follow-up durations, as well as high I2 and wide 95% CIs, suggesting great heterogeneity among studies. Systematic reviews focusing on the persistent symptoms of COVID-19 in the adult population reported similar issues.15,64  There are several additional explanations for the high heterogeneity observed between studies. Firstly, the study design of included studies varies greatly. Even though we only included cohort studies prospectively collected information related to long COVID in a general pediatric population in our meta-analysis, there were still large differences among their study details. For instance, some studies only included hospitalized patients,29,32,33,38,39,41,43,44,47  whereas others had a mixed population recruited from both the community and/or the hospital setting. Some studies recruited participants through the review of medical records, and therefore, only included symptomatic patients who had sought medical help. Some studies recruited participants from the community. Only very few studies were population-based studies53,65  in which children and adolescents who tested positive in SARS-CoV-2 confirmatory tests were identified for further follow-up via national registry or by contacting households or schools randomly selected in the community. This approach included both asymptomatic and symptomatic cases and may better reflect the true prevalence of long COVID. This is of particular importance as the proportion of asymptomatic infection in neonates, children, and adolescents are higher compared with the adult population.66  Secondly, various data collection methods were used by individual studies. The majority of studies developed a study specific standardized survey or interview questionnaire, whereas only a number of studies used in-person clinical assessment at the clinic. Thirdly, there exist many definitions of long COVID and methods of describing or reporting these symptoms. For instance, fatigue may be described as fatigue in general in some studies, but others may describe and categorize fatigue as feeling tired after sleep or feeling tired after exercise, etc.

There are a large number of studies on long COVID in the adult population.2,4,67  They have identified a large number of long-term physical and psychological signs and symptoms after recovering from COVID-19, including weakness, fatigue, concentration impairment, headache, dyspnea, depression, anxiety, etc. From the included studies in our review, we identified more than 20 long COVID clinical features in the pediatric population, relating to multiple organs and systems. Although the specific sequence may differ according to study design and follow-up duration, the symptoms most commonly reported by children and adolescents after at least 3 months recovering from COVID-19 were sore throat, persistent fever, sleep disturbance, fatigue, and muscle weakness. Our finding is not completely consistent with existing systematic reviews on this topic. The most common long COVID symptoms (≥1 months after laboratory-confirmed SARS-CoV-2 infection) found in a systematic review including children and adolescents63  were mood symptoms, fatigue, sleep disorders, headache, and respiratory symptoms, which are similar with our findings. Such discrepancy can be explained by the different inclusion criteria of studies. From our systematic literature search, we noticed the design and focus of each individual study differed significantly. Some researchers focused on specific post-COVID-19 signs and symptoms (eg, ophthalmology findings,68  dysphonia, and dysphagia69 ) or a specific population (eg, MIS-C) within children and adolescents recovering from COVID-19. Some studies adopted a broad approach and identified a large number of long-term symptoms in the pediatric COVID-19 population. Therefore, we only included studies focusing on a more general pediatric COVID-19 population in our current analysis. We decided to exclude studies using a self-reporting platform and to include only cohort studies prospectively followed up their participants for any persistent symptoms and/or laboratory findings to minimize selection and recall bias.

There are considerable gaps in terms of evidence on long-term effects of COVID-19 in low and middle income countries (LMICs) because of lack of fundings and resources, as well as limited capacities to diagnose and monitor long COVID. In a systematic review examining the worldwide prevalence of long COVID,70  only a third of included studies were from LMICs, and they found the pooled estimated prevalence of long COVID in the United States and Europe (most studies from HICs) was lower than that in Asia (most studies were from China and India). Research on long-term effects of COVID-19 in the pediatric population from LMICs is further limited and of varying quality. We were able to pool the data from 4 studies (3 of moderate risk of bias, 1 of high risk of bias) conducted in upper-middle-income countries in this review and found the prevalence of long-COVID in neonates, children, and adolescents were higher comparing to their counterparts in HICs, with quite different clinical presentations as well. However, because of the relatively low quality of these studies, as well as the great heterogeneity observed, we still could not draw a conclusion on the disease burden and clinical spectrum of long COVID in the pediatric population between LMICs and HICs.

Persistent clinical features after recovering from acute COVID-19 have been shown to decline over time both in adults and in children and young people. Pinto Pereira et al34  examined within-individual change in symptom profile of the CLoCk cohort population and found the prevalence of 11 common symptoms at baseline declined greatly by 12-month follow-up. For children and young people who first described 1 of their symptoms at 6-month follow-up, there was also a decline in prevalence by 12 months. Similarly, it has also been observed in adults that persistent post-COVID-19 symptoms declined with time.71  Therefore, we conducted a subgroup analysis by different follow-up durations and found the spectrum of persistent, new symptoms after SARS-CoV-2 infection differed for the follow-up duration of 3 to 6 months, 6 to 12 months, and greater than 12 months. But our subgroup analysis by follow-up duration covered different study populations, and the trend we revealed that long COVID symptoms may change with time could be confounded by various factors. Future within-individual studies are needed to investigate the dynamic of persistent clinical features and symptoms in the pediatric population.

Only 6 studies included in our systematic review had a control group without a previous history of COVID, 5 of which collected persistent symptoms after SARS-CoV-2 infection in a prospective manner. The CLoCk study conducted in the United Kingdom found that nearly all symptoms reported by children with a positive SARS-CoV-2 test result were also reported by those who tested negative.34,42  Certain nonspecific symptoms, such as psychological alterations, appetite, and weight changes may be related to the pandemic, eg, lockdown, school closure, etc, rather than COVID-19 infections. These symptoms may also present after other viral infections. Two recent cohort studies with a large sample size found SARS-CoV-2-positive children were more likely to report long COVID conditions compared with those who tested negative. Roessler et al72  matched 11 950 children and adolescents with laboratory-confirmed COVID-19 with a control cohort and found a significantly higher incidence rate for all health outcomes combined in the COVID-19 cohorts. Funk et al37  also matched SARS-CoV-2 positive children and adolescents with those who tested negative and found the positive group were more likely to report post-COVID-19 conditions at 90 days than their SARS-CoV-2 negative counterparts. Behnood et al73  conducted a meta-analysis of controlled and uncontrolled studies on persistent symptoms following COVID-19 in children and young people and found the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. These contradictory findings highlighted the importance of a control group in future studies to adjust for confounders and avoid potential bias. Furthermore, long COVID may be diagnosed subjectively (eg, nonspecific complains), or objectively (eg, laboratory and imaging). It would be ideal to standardize the data collection process by using a structured and validated survey or questionnaire to reduce variability. This will also help to standardize terminologies used and to ensure that validated tools are used.

In mixed studies with an adult-dominant population, female gender, the presence of comorbidities, increasing age, and ethnic minorities were found to be significantly at higher risk of long COVID.4  However, evidence in children and adolescents are still limited. Merzon et al74  examined the demographic, clinical, and socioeconomic factors associated with long COVID in children aged 5 to 18 years. They found children with long COVID were more likely to be severely symptomatic, required hospitalization, and experienced recurrent acute infection within 180 days. In our analysis, we used male to female ratio as one of the factors included in the meta-regression to investigate the potential association of certain gender with the development of COVID-19. We found female gender is a potential risk factors for developing certain long COVID symptoms (sleeping disturbance and headache) in children and adolescents at least 3 months after the acute infection phase. To be noteworthy, the number of qualified studies that provided detailed information of potential risk factors is limited in our systematic review; therefore, we were not able to investigate their association with long COVID. In general, little is still known about whether a certain population is more likely to develop long COVID postinfection. Future research should collect detailed information on pre-existing medical conditions and signs and symptoms before, during, and after COVID-19. With such information, researchers may better identify long-term effects attributed to SARS-CoV-2 infection and the risk factors for developing long COVID in the pediatric population.

There are various potential biases in included studies. We only included studies that prospectively followed up pediatric participant for their persistent post-COVID symptoms in our analyses to minimize recall bias. However, the majority of these studies conducted their follow-ups by contacting the participants regularly, eg, monthly or quarterly, instead of using a “real-time” reporting system or platform that the participants could report their symptoms actively and reasonably quickly, hence leaving open the potential of some recall bias. A couple of studies conducted follow-ups via telephone interviews or questionnaires with various response rates, which may lead to nonresponse bias. The fact that asymptomatic or mild COVID-19 cases might also not get tested should not be ignored. Particularly, during the early stages of the COVID-19 pandemic when testing was still limited, it was not uncommon for the diagnosis of SARS-CoV-2 infection to be based on reported clinical symptoms and contact or travel history.15,17  Even after PCR tests are widely applied in diagnosing SARS-CoV-2 infection, its accuracy (ie, false positive and negative rates) may still have an unknow impact on identifying a proper study population and the accuracy of the study’s results.

Bias may also exist when investigating the association between various demographic factors and the risk of developing long COVID, eg, race and ethnicity. Although we included studies from multiple countries, most studies with the information of race came from the United States, the United Kingdom, and Italy. Certain races and ethnic groups may be over- or under-reported because of various reasons (eg, over-/under-representative in the study population, different classification system, or terms used in different contexts, etc). A precise and detailed definition and/or description of these factors was missing or unclear in many of the original studies, precluding any firm conclusions as to the contribution of race and ethnicity to persistent symptoms after COVID-19.

Furthermore, the definition of “long COVID” in the pediatric group is still vague. A large number of studies defined long COVID by clinical features persisting for at least 1-month postinfection and lacked follow-up data of a longer duration. Most reported studies also did not systematically collect information on laboratory features among evaluated children, and the latter information was mainly restricted to hospitalized children. While conducting this systematic review, we found that studies of long COVID in the pediatric population with a follow-up of at least 3 months for analysis only accounts for a third of the total studies on this topic. Within our included studies, only some of them clearly described the duration of each symptom during follow-up and they did not report new onset symptoms and persistent symptoms separately. The limited number of studies with sufficient follow-up length and data, as well as the considerable heterogeneity observed among studies, made it challenging to pool these data and estimate the prevalence and symptom spectrum of long COVID in the pediatric population. Therefore, our conclusions should be interpreted with caution.

Recently, recurrent infection of SARS-CoV-2 has become increasingly common because of the emergence of new variants. Other viral infections are also common. The majority of current studies did not collect or provide information related to other concurrent viral infection during follow-up, nor did they take recurrent COVID-19 into consideration. Establishing the relationship between “new, persistent, and/or recurring” symptoms during follow-up and previous SARS-CoV-2 infection remains a big challenge for long COVID studies.

It is not surprising that current studies on long COVID in the pediatric population were subjected to great heterogeneity, biases, and limitations given the rush to getting information out and the thirst for COVID-19 studies among the journals. We feel that it is extremely important that academia better communicate, collaborate, and support each other in designing and conducting high quality studies in such an outbreak situation in the future.

We found less than one fifth of children and adolescents with a confirmed COVID-19 diagnosis continue presenting with at least 1 persistent clinical feature that cannot be explained by alternative diagnosis beyond 3 months after the acute phase of infection. Long COVID in children and adolescents has been reported with a very wide symptom spectrum and with great heterogeneity among studies included in this review. The presentation of long COVID may change with time. There is the need for high quality, prospective, and well controlled studies to address these issues. In the interim, preventing COVID-19 infection and vaccinations for children and adolescents must remain a priority.

We thank Dr Gagan Gupta (UNICEF) and Dr Jonathan Klein (University of Chicago and IPA) for their review and useful comments on the manuscript; and Ms Daina Als for her administrative support in the preparation of this paper.

Drs Bhutta and Tang conceptualized the study, supervised the whole process including its design, and critically reviewed and revised the manuscript for important intellectual content; Dr Jiang designed the study, conducted the systematic literature search, designed the data collection, extracted data from literature, and drafted the initial manuscript; BSc Li and Ms Nie also conducted the literature search, extracted data from literature, conducted the data analysis, and critically reviewed and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

FUNDING: Unrestricted support for this review was provided by a grant from UNICEF (New York) through the International Pediatric Association with additional core support from the Centre for Global Child Health, Toronto. The sponsor did not participate in the work.

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose.

CI

confidence interval

MIS-C

multisystem inflammatory syndrome in children

PCR

polymerase chain reaction

WHO

World Health Organization

1
The World Health Organization
.
WHO coronavirus disease (COVID-19) dashboard
.
Available at: https://covid19.who.int. Accessed February 28, 2023
2
Lopez-Leon
S
,
Wegman-Ostrosky
T
,
Perelman
C
, et al
.
More than 50 long-term effects of COVID-19: a systematic review and meta-analysis
.
Sci Rep
.
2021
;
11
(
1
):
16144
3
Ahmad
MS
,
Shaik
RA
,
Ahmad
RK
, et al
.
“LONG COVID”: an insight
.
Eur Rev Med Pharmacol Sci
.
2021
;
25
(
17
):
5561
5577
4
Michelen
M
,
Manoharan
L
,
Elkheir
N
, et al
.
Characterising long COVID: a living systematic review
.
BMJ Glob Health
.
2021
;
6
(
9
):
e005427
5
The World Health Organization
.
A clinical case definition of post COVID-19 condition by a Delphi consensus
.
6
Dong
Y
,
Mo
X
,
Hu
Y
, et al
.
Epidemiology of COVID-19 among children in China
.
Pediatrics
.
2020
;
145
(
6
):
e20200702
7
CDC COVID-19 Response Team
.
Coronavirus disease 2019 in children - United States, February 12-April 2, 2020
.
MMWR Morb Mortal Wkly Rep
.
2020
;
69
(
14
):
422
426
8
Tagarro
A
,
Epalza
C
,
Santos
M
, et al
.
Screening and severity of coronavirus disease 2019 (COVID-19) in children in Madrid, Spain [published online ahead of print April 8, 2020]
.
JAMA Pediatr
.
doi: 10.1001/jamapediatrics.2020.1346
9
Götzinger
F
,
Santiago-García
B
,
Noguera-Julián
A
, et al;
ptbnet COVID-19 Study Group
.
COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study
.
Lancet Child Adolesc Health
.
2020
;
4
(
9
):
653
661
10
Hoang
A
,
Chorath
K
,
Moreira
A
, et al
.
COVID-19 in 7780 pediatric patients: a systematic review
.
EClinicalMedicine
.
2020
;
24
:
100433
11
The United States Centers for Disease Control and Prevention
.
COVID data tracker
.
Available at: https://covid.cdc.gov/covid-data-tracker/#demographics. Accessed February 28, 2023
12
Siegel
DA
,
Reses
HE
,
Cool
AJ
, et al;
MAPW1
.
Trends in COVID-19 cases, emergency department visits, and hospital admissions among children and adolescents aged 0-17 years - United States, August 2020-August 2021
.
MMWR Morb Mortal Wkly Rep
.
2021
;
70
(
36
):
1249
1254
13
Chadeau-Hyam
M
,
Wang
H
,
Eales
O
, et al
.
REACT-1 study round 14: high and increasing prevalence of SARS-CoV-2 infection among school-aged children during September 2021 and vaccine effectiveness against infection in England [published online ahead of print October 22,2021]
.
medRxiv
.
doi: 10.1016/j.eclinm.2022.101419
14
Molteni
E
,
Sudre
CH
,
Canas
LS
, et al
.
Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2
.
Lancet Child Adolesc Health
.
2021
;
5
(
10
):
708
718
15
Ludvigsson
JF
.
Case report and systematic review suggest that children may experience similar long-term effects to adults after clinical COVID-19
.
Acta Paediatr
.
2021
;
110
(
3
):
914
921
16
Radtke
T
,
Ulyte
A
,
Puhan
MA
,
Kriemler
S
.
Long-term symptoms after SARS-CoV-2 infection in children and adolescents
.
JAMA
.
2021
;
326
(
9
):
869
871
17
Brackel
CLH
,
Lap
CR
,
Buddingh
EP
, et al
.
Pediatric long-COVID: an overlooked phenomenon?
Pediatr Pulmonol
.
2021
;
56
(
8
):
2495
2502
18
Say
D
,
Crawford
N
,
McNab
S
,
Wurzel
D
,
Steer
A
,
Tosif
S
.
Post-acute COVID-19 outcomes in children with mild and asymptomatic disease
.
Lancet Child Adolesc Health
.
2021
;
5
(
6
):
e22
e23
19
Buonsenso
D
,
Munblit
D
,
De Rose
C
, et al
.
Preliminary evidence on long COVID in children
.
Acta Paediatr
.
2021
;
110
(
7
):
2208
2211
20
Matteudi
T
,
Luciani
L
,
Fabre
A
, et al
.
Clinical characteristics of paediatric COVID-19 patients followed for up to 13 months
.
Acta Paediatr
.
2021
;
110
(
12
):
3331
3333
21
European Centre for Disease Control and Prevention
.
Rapid Risk Assessment: Paediatric Inflammatory Multisystem Syndrome and SARS-CoV-2 Infection in Children
.
Stockholm, Sweden
:
European Centre for Disease Control and Prevention
;
2020
22
Royal College of Paediatrics and Child Health
.
Guidance: Paediatric Multisystem Inflammatory Syndrome Temporally Associated With COVID-19
.
London, UK
:
Royal College of Paediatrics and Child Health
;
2020
23
The World Health Organization
.
Multisystem inflammatory syndrome in children and adolescents with COVID-19
.
24
The United States Centers for Disease Control and Prevention
.
Multisystem inflammatory syndrome (MIS-C)
.
Available at: https://www.cdc.gov/mis-c/hcp/. Accessed February 28, 2023
25
Jiang
L
,
Tang
K
,
Levin
M
, et al
.
COVID-19 and multisystem inflammatory syndrome in children and adolescents
.
Lancet Infect Dis
.
2020
;
20
(
11
):
e276
e288
26
Baker
WL
,
White
CM
,
Cappelleri
JC
,
Kluger
J
,
Coleman
CI
;
Health Outcomes, Policy, and Economics (HOPE) Collaborative Group
.
Understanding heterogeneity in meta-analysis: the role of meta-regression
.
Int J Clin Pract
.
2009
;
63
(
10
):
1426
1434
27
National Heart, Lung, and Blood Institute
.
Quality assessment tool for observational cohort and cross-sectional studies
.
28
Isoldi
S
,
Mallardo
S
,
Marcellino
A
, et al
.
The comprehensive clinic, laboratory, and instrumental evaluation of children with COVID-19: a 6-months prospective study
.
J Med Virol
.
2021
;
93
(
5
):
3122
3132
29
Asadi-Pooya
AA
,
Nemati
H
,
Shahisavandi
M
, et al
.
Long COVID in children and adolescents
.
World J Pediatr
.
2021
;
17
(
5
):
495
499
30
Blomberg
B
,
Mohn
KG
,
Brokstad
KA
, et al;
Bergen COVID-19 Research Group
.
Long COVID in a prospective cohort of home-isolated patients
.
Nat Med
.
2021
;
27
(
9
):
1607
1613
31
Sirico
D
,
Di Chiara
C
,
Costenaro
P
, et al
.
Left ventricular longitudinal strain alterations in asymptomatic or mildly symptomatic paediatric patients with SARS-CoV-2 infection
.
Eur Heart J Cardiovasc Imaging
.
2022
;
23
(
8
):
1083
1089
34219155
32
Sterky
E
,
Olsson-Åkefeldt
S
,
Hertting
O
, et al
.
Persistent symptoms in Swedish children after hospitalisation due to COVID-19
.
Acta Paediatr
.
2021
;
110
(
9
):
2578
2580
33
Tian
X
,
Bai
Z
,
Cao
Y
, et al
.
Evaluation of clinical and immune responses in recovered children with mild COVID-19
.
Viruses
.
2022
;
14
(
1
):
85
34
Pinto Pereira
SM
,
Shafran
R
,
Nugawela
MD
, et al
.
Natural Course of Health and Well-being in Non-hospitalised Children and Young People After Testing for SARS-CoV-2: A Prospective Follow-up Study Over 12 Months
.
Europe
:
The Lancet Regional Health –
;
2023
:
25
35
Osmanov
IM
,
Spiridonova
E
,
Bobkova
P
, et al;
and the Sechenov StopCOVID Research Team
.
Risk factors for post-COVID-19 condition in previously hospitalised children using the ISARIC Global follow-up protocol: a prospective cohort study
.
Eur Respir J
.
2022
;
59
(
2
):
2101341
36
Roessler
M
,
Tesch
F
,
Batram
M
, et al
.
Post-COVID-19-associated morbidity in children, adolescents, and adults: a matched cohort study including more than 157,000 individuals with COVID-19 in Germany
.
PLoS Med
.
2022
;
19
(
11
):
e1004122
37
Funk
AL
,
Kuppermann
N
,
Florin
TA
, et al;
Pediatric Emergency Research Network–COVID-19 Study Team
.
Post-COVID-19 conditions among children 90 days after SARS-CoV-2 infection
.
JAMA Netw Open
.
2022
;
5
(
7
):
e2223253
e2223253
38
Pazukhina
E
,
Andreeva
M
,
Spiridonova
E
, et al;
Sechenov StopCOVID Research Team
.
Prevalence and risk factors of post-COVID-19 condition in adults and children at 6 and 12 months after hospital discharge: a prospective, cohort study in Moscow (StopCOVID)
.
BMC Med
.
2022
;
20
(
1
):
244
39
Esmaeilzadeh
H
,
Sanaei Dashti
A
,
Mortazavi
N
,
Fatemian
H
,
Vali
M
.
Persistent cough and asthma-like symptoms post COVID-19 hospitalization in children
.
BMC Infect Dis
.
2022
;
22
(
1
):
244
40
Buonsenso
D
,
Munblit
D
,
Pazukhina
E
, et al;
FIMP-Roma
.
Post-COVID condition in adults and children living in the same household in Italy: a prospective cohort study using the ISARIC global follow-up protocol
.
Front Pediatr
.
2022
;
10
:
834875
41
Bogusławski
S
,
Strzelak
A
,
Gajko
K
, et al
.
The outcomes of COVID-19 pneumonia in children—clinical, radiographic, and pulmonary function assessment
.
Pediatric Pulmonology
.
2023
;
58
(
4
):
1042
1050
42
Stephenson
T
,
Pinto Pereira
SM
,
Shafran
R
, et al;
CLoCk Consortium
.
Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): a national matched cohort study
.
Lancet Child Adolesc Health
.
2022
;
6
(
4
):
230
239
43
Doshi
JA
,
Sheils
NE
,
Buresh
J
, et al
.
SARS-CoV-2 sequelae and postdischarge health care visits over 5 months follow-up among children hospitalized for COVID-19 or MIS-C
.
Pediatr Infect Dis J
.
2022
;
41
(
12
):
e513
e516
44
Öztürk
GK
,
Beken
B
,
Doğan
S
,
Akar
HH
.
Pulmonary function tests in the follow-up of children with COVID-19
.
Eur J Pediatr
.
2022
;
181
(
7
):
2839
2847
45
Werner
S
,
Doerfel
C
,
Biedermann
R
, et al
.
The CSHQ-DE questionnaire uncovers relevant sleep disorders in children and adolescents with long COVID
.
Children (Basel)
.
2022
;
9
(
9
):
1419
46
Rao
S
,
Lee
GM
,
Razzaghi
H
, et al
.
Clinical features and burden of postacute sequelae of SARS-CoV-2 infection in children and adolescents
.
JAMA Pediatr
.
2022
;
176
(
10
):
1000
1009
47
Bossley
CJ
,
Kavaliunaite
E
,
Harman
K
,
Cook
J
,
Ruiz
G
,
Gupta
A
.
Post-acute COVID-19 outcomes in children requiring hospitalisation
.
Sci Rep
.
2022
;
12
(
1
):
8208
48
Gonzalez-Aumatell
A
,
Bovo
MV
,
Carreras-Abad
C
, et al
.
Social, academic, and health status impact of long COVID on children and young people: an observational, descriptive, and longitudinal cohort study
.
Children (Basel)
.
2022
;
9
(
11
):
1677
49
Trapani
G
,
Verlato
G
,
Bertino
E
, et al
.
Long COVID-19 in children: an Italian cohort study
.
Ital J Pediatr
.
2022
;
48
(
1
):
83
50
Bergia
M
,
Sanchez-Marcos
E
,
Gonzalez-Haba
B
, et al
.
Comparative study shows that 1 in 7 Spanish children with COVID-19 symptoms were still experiencing issues after 12 weeks
.
Acta Paediatr
.
2022
;
111
(
8
):
1573
1582
51
Horikoshi
Y
,
Shibata
M
,
Funakoshi
H
,
Baba
S
,
Miyama
S
.
Post coronavirus disease 2019 condition in children at a children’s hospital in Japan
.
Pediatr Int
.
2023
;
65
(
1
):
e15458
52
Di Gennaro
L
,
Valentini
P
,
Sorrentino
S
, et al
.
Extended coagulation profile of children with long Covid: a prospective study
.
Sci Rep
.
2022
;
12
(
1
):
18392
53
Kikkenborg Berg
S
,
Dam Nielsen
S
,
Nygaard
U
, et al
.
Long COVID symptoms in SARS-CoV-2-positive adolescents and matched controls (LongCOVIDKidsDK): a national, cross-sectional study
.
Lancet Child Adolesc Health
.
2022
;
6
(
4
):
240
248
54
Haddad
A
,
Janda
A
,
Renk
H
, et al
.
Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: a prospective observational cohort study
.
EBioMedicine
.
2022
;
84
:
104245
55
La Regina
DP
,
Pepino
D
,
Nenna
R
, et al;
On Behalf Of The Long Covid Research Group
.
Pediatric COVID-19 follow-up with lung ultrasound: a prospective cohort study
.
Diagnostics (Basel)
.
2022
;
12
(
9
):
2202
56
Tarantino
S
,
Graziano
S
,
Carducci
C
,
Giampaolo
R
,
Grimaldi Capitello
T
.
Cognitive difficulties, psychological symptoms, and long lasting somatic complaints in adolescents with previous SARS-CoV-2 infection: a telehealth cross-sectional pilot study
.
Brain Sci
.
2022
;
12
(
8
):
969
57
Tarsilla
M
.
Cochrane handbook for systematic reviews of interventions
.
J Multidiscip Eval
.
2010
;
6
(
14
):
142
148
58
The World Health Organization
.
A clinical case definition for post COVID-19 condition in children and adolescents by expert consensus
.
59
The United States Centers for Disease Control and Prevention
.
Long COVID or post COVID conditions
.
60
National Institute for Health and Care Excellence
.
COVID-19 Rapid Guideline: Managing the Long-term Effects of COVID-19 [NG188]
.
London, UK
:
National Institute for Health and Care Excellence
;
2021
61
Proal
AD
,
VanElzakker
MB
.
Long COVID or post-acute sequelae of COVID-19 (PASC): an overview of biological factors that may contribute to persistent symptoms
.
Front Microbiol
.
2021
;
12
:
698169
62
Baig
AM
.
Chronic COVID syndrome: need for an appropriate medical terminology for long-COVID and COVID long-haulers
.
J Med Virol
.
2021
;
93
(
5
):
2555
2556
63
Loreche
AM
,
Pepito
VCF
,
Dayrit
MM
.
Long Covid: a call for global action
.
Public Health Challenges
.
2023
;
2
(
1
):
e69
64
Lopez-Leon
S
,
Wegman-Ostrosky
T
,
Ayuzo Del Valle
NC
, et al
.
Long-COVID in children and adolescents: a systematic review and meta-analyses
.
Sci Rep
.
2022
;
12
(
1
):
9950
65
Dumont
R
,
Richard
V
,
Lorthe
E
, et al;
SEROCoV-KIDS Study Group
.
A population-based serological study of post-COVID syndrome prevalence and risk factors in children and adolescents
.
Nat Commun
.
2022
;
13
(
1
):
7086
66
Viner
RM
,
Mytton
OT
,
Bonell
C
, et al
.
Susceptibility to SARS-CoV-2 infection among children and adolescents compared with adults: a systematic review and meta-analysis
.
JAMA Pediatr
.
2021
;
175
(
2
):
143
156
67
Groff
D
,
Sun
A
,
Ssentongo
AE
, et al
.
Short-term and long-term rates of postacute sequelae of SARS-CoV-2 infection: a systematic review
.
JAMA Netw Open
.
2021
;
4
(
10
):
e2128568
68
Burgos-Blasco
B
,
Güemes-Villahoz
N
,
Morales-Fernandez
L
, et al
.
Retinal nerve fibre layer and ganglion cell layer changes in children who recovered from COVID-19: a cohort study
.
Arch Dis Child
.
2022
;
107
(
2
):
175
179
69
Halfpenny
R
,
Stewart
A
,
Carter
A
, et al
.
Dysphonia and dysphagia consequences of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS)
.
Int J Pediatr Otorhinolaryngol
.
2021
;
148
:
110823
70
Chen
C
,
Haupert
SR
,
Zimmermann
L
,
Shi
X
,
Fritsche
LG
,
Mukherjee
B
.
Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review
.
J Infect Dis
.
2022
;
226
(
9
):
1593
1607
71
Castanares-Zapatero
D
,
Kohn
L
,
Dauvrin
M
, et al
.
Long COVID: pathophysiology-epidemiology and patient needs
.
Available at: https://database.inahta.org/article/20213. Accessed February 26, 2023
72
Roessler
M
,
Tesch
F
,
Batram
M
, et al
.
Post COVID-19 in children, adolescents, and adults: results of a matched cohort study including more than 150,000 individuals with COVID-19 [published online ahead of print October 22,2021]
.
medRxiv
.
doi: https://doi.org/10.1101/2021.10.21.21265133
73
Behnood
SA
,
Shafran
R
,
Bennett
SD
, et al
.
Persistent symptoms following SARS-CoV-2 infection amongst children and young people: a meta-analysis of controlled and uncontrolled studies
.
J Infect
.
2022
;
84
(
2
):
158
170
74
Merzon
E
,
Weiss
M
,
Krone
B
, et al
.
Clinical and socio-demographic variables associated with the diagnosis of long COVID syndrome in youth: a population-based study
.
Int J Environ Res Public Health
.
2022
;
19
(
10
):
5993
75
Doležalová
K
,
Tuková
J
,
Pohunek
P
.
The respiratory consequences of COVID-19 lasted for a median of 4 months in a cohort of children aged 2-18 years of age
.
Acta Paediatr
.
2022
;
111
(
6
):
1201
1206

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