Abstract
Introduction: Few studies of children with long COVID (post-COVID-19 condition) or post-acute sequelae of SARS CoV-2 (PASC) have been reported. Those terms describe symptoms that persist for weeks or months or as new symptoms that develop after SARS-CoV-2 infection. This condition might be found to various degrees in the severity of COVID-19. This study aimed to describe long COVID in confirmed SARS-CoV-2-infected children.
Design: An observational cross-sectional study.
Setting: Tertiary care hospital between January and November 2021.
Participants: Children, age 5–17 years, with virologically confirmed COVID?19.
Methods: This study was conducted by completing an electronic form after informed consent was obtained. The subject’s characteristics and parent’s or guardian’s phone numbers were retrieved from the pediatric COVID-19 registry. Parents were contacted to complete a structured electronic questionnaire about the long COVID symptoms noticed in their children. Descriptive statistics were displayed in percentages and median.
Results: Parent contact numbers were documented in 125/135 children who fulfilled the study criteria. There were 61 parents (48.8%) who gave consent, while the rest either did not respond or refused. There were 16 children reported as deceased primarily due to chronic renal disease and leukemia. Of the 45 children enrolled, the median (IQR) age was 11 years (5.3–17.6); 51.1% were female; and 75.6% had comorbidities. Two-thirds developed long COVID symptoms, most frequently in the age 5-9 years group, and mostly fatigue (45.2%), decreased appetite (38.7%), and muscle aches (32.3%). All patients with moderate to severe and more than half asymptomatic to mild COVID-19 developed long COVID.
Conclusion: Most children had long COVID symptoms similar to adults despite being otherwise asymptomatic or having mild COVID-19.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome – Coronavirus-2 (SARS-CoV-2) remains a concern worldwide, impacting all ages, including children and adolescents. Fewer cases of COVID-19 have been found in children and adolescents than in adults – approximately 14% of all confirmed COVID-19 cases globally. Death caused by COVID-19 in children and adolescents occurred in 0.3% of all cases reported.1-3 In Indonesia, 13% of all COVID-19 cases and 1% of the total deaths caused by COVID-19 were of children and adolescents.4 Although the incidence is low, children (especially adolescents) with COVID-19 may be a source of infection to those around them, including vulnerable populations such as older adults.5
Clinical manifestations of COVID-19 in children and adolescents have been mostly mild and usually do not cause complications as severe as those found in adults. Similar to adults, symptoms of COVID-19 in children and adolescents could persist from several weeks to months after SARS-CoV-2 infection, which could interfere with daily activities.6,7 When a confirmed COVID-19 case experiences symptoms without signs of improvement or manifests as acute symptoms after signs of improvement, these are known as long COVID or post COVID-19 condition.8,9 Long COVID describes symptoms that persist for weeks or months after the primary infection. There is no standard definition for the syndrome and no agreement on the duration of the symptoms that justifies the diagnosis, ranging from 4 to 12 weeks after acute infection.10
Children (older than age 6 years) with a history of COVID-19 who were hospitalized with allergic diseases, with obesity, or with multisystem involvement have a higher risk of experiencing long COVID.11 The long-term consequences of COVID-19 in the pediatric population remain obscure with somewhat limited studies, and there have been no reports of long COVID in children and adolescents in Indonesia. Therefore, this study aimed to describe the persistent symptoms of children and adolescents with previously confirmed COVID-19.
Methodology
Study Design, Participants, and Procedures
An observational, cross-sectional study was conducted on children with a confirmed diagnosis of COVID-19 (ICD code-10 U07.1) based on nasopharyngeal swab by polymerase chain reaction SARS CoV-2. The purposive sampling technique used data obtained from medical records and patient registries in the Dr. Hasan Sadikin General Hospital between January and November 2021. The inclusion criteria were children age 5 to 17 years during the COVID-19 pandemic and the ability to contact and confirm with parents/legal guardians who could be reached by telecommunication media (eg, phone, short message service [SMS], or WhatsApp). We excluded unwilling parents and deceased children. The parents/guardians with contact details available were contacted and some consented to participate in this study. Written informed consent of the parents/guardians who agreed to participate was then obtained. After obtaining consent, the parents/guardians completed the structured electronic questionnaire form, which aimed to gather information about any symptoms related to long COVID reported by the children or noticed by the parents. We defined long COVID as symptoms that persist for 1 to 3 months, 3 to 6 months, and more than 6 months after being diagnosed with COVID-19. The symptoms were classified as general; respiratory; cardiovascular; cognitive disorder; neurological; gastrointestinal; musculoskeletal; psychological; ear, nose and throat; eye; urinary; and dermatological.
Data Management and Statistical Analysis
Data obtained included age, gender, nutritional status, severity of COVID-19, hospital admission (inpatient or outpatient) and comorbidity. The findings of the present study were summa-rized using descriptive statistics analysis; frequency (n) with percentage (%) for categorical variables and median with interquartile range (IQR) for numerical variables.
Ethical Considerations
This study was approved by the Research Ethics Committee of the Hasan Sadikin General Hospital (LB.02.01/X.6.5/312/2021) with permission from the Director of Hasan Sadikin General Hospital. To protect privacy, the children’s names were blinded during the data processing.
Results
In total, 245 children were diagnosed with confirmed COVID-19 documented at Hasan Sadikin General Hospital between January and November 2021. There were 32 children who died during hospitalization; 78 children were under age 5 years, and 10 children had invalid contact numbers. Of the 125 children contacted, 64 did not respond, and 16 children had died after discharge due to underlying disease. Of the 125 confirmed COVID-19 cases, 45 (36%) children were enrolled in this study (Figure 1). There were 31/45 (68.9%) children who developed long COVID-19 symptoms, mainly age 5-9 years (48.4%), and the majority suffered from comorbidities (74.2%). The children’s ages ranged from 5 to 17 years, with a median (IQR) age of 11-years (5.3–17.3), and a majority were female (54.8%). Five (11.1%) children were re-hospitalized because of comorbidities that required inpatient treatment. Various clinical manifestations occurred as initial symptoms of COVID-19, with most children experiencing fatigue (64.5%). Other common initial symptoms were fever (54.8%), headache (51.6%), and insomnia (38.7%). Four children (12.9%) needed intensive care during hospitalization for COVID-19. There were 27 (87.1%) children who did not receive antiviral therapy during SARS CoV-2 infection, and one (3.2%) child received convalescent plasma because of chronic kidney disease (Figure 1).
Most of the children with long COVID were asymptomatic or had mild symptoms (64.4%) during the SARS CoV-2 infection, seven (22.5%) children presented as moderate cases, and four (13.1%) presented as severe cases. The most common long COVID symptoms were fatigue (45.2%), decreased appetite (38.7%), and muscle aches (32.3%) in all periods. There were 15 children (48.3%) who had symptoms of long COVID that persisted for more than 6 months. Only five children experienced more than ten symptoms, all with comorbidity (eg, asthma, leukemia, obesity, head injury and thalassemia (Tables 1, 2, 3).
Characteristic of study participants (n=45)
Long COVID condition of study participants (n=31)
Symptoms of long COVID
There were similar percentages of all age groups and genders developing long COVID symptoms. As many as 83.3% who had severe and moderate malnutrition and 90% with normal nutritional status developed long COVID, while fewer children who were overweight (20%) or obese (33%) developed long COVID symptoms. All moderate to severe and more than half asymptomatic to mild (62.5% and 50%, respectively) children with COVID-19 developed long COVID. Children with comorbidity were more prone to develop long COVID (73.5%) (Table 4).
Characteristics of children developing long COVID
Discussion
This study revealed that most children had experienced at least one of the long COVID symptoms, and most had some comorbidity. The term ‘long COVID’ or ‘post COVID condition’ or ‘PASC’ was defined as any consequences of physical and mental health that present more than 4 weeks after SARS CoV-2 infection or new symptoms that develop with unexplained causes that could persist for months to years.8 Symptoms of long COVID may overlap with symptoms of an underlying comorbidity. Children with comorbidities of chronic disease might also have had symptoms aside from COVID-19 infection. Chronic disease did not increase the severity of COVID-19 infection in children.12-14 In this study, more than half of children with primarily asymptomatic and mild COVID-19 infection developed long COVID (62.5% and 50%, respectively); however, prolonged symptoms could affect children after SARS-CoV-2 infection, even children with mild or no acute COVID-19 symptoms.15-17 A study found that children who experienced COVID-19 had more prevalent long-lasting symptoms than those who had not been infected.18 A few studies have shown the longevity of COVID-19 symptoms persistence in children. Children with symptomatic COVID-19 have a shorter duration of symptoms (approximately 6 days). In comparison, older individuals correlate with a longer duration of illness, with headache and fatigue as the most reported complaints.19
The pathophysiology of long COVID remains unclear, but it may be related to multifactorial components. The potential mechanisms include pathophysiological changes due to the specific viral infection, immunologic abnormalities, and acute inflammation, increasing the severity of the illness.20 The most common symptoms of long COVID were fatigue, decreased appetite, abdominal pain, headache and sleep problems. Our results confirm previous studies where the most common symptoms of long COVID in children and adolescents were mood swings, fatigue, sleep disorders, headaches and respiratory problems. Children previously diagnosed with COVID-19 tended to have persistent dyspnea, anosmia/ageusia, and fever compared to those who were not.21 Another study of 58 children found fatigue, shortness of breath, and weakness to be the most common long COVID symptoms.22
Persistent symptoms of long COVID can affect school performance and daily activities in children. Some of the children in our study experienced a lack of concentration (19.3%), frequent absent-mindedness (16.1%), and learning difficulties (9.6%). Children with persistent symptoms may have difficulties related to cognitive dysfunction after COVID-19, thus affecting their quality of life. Isolation and quarantine regulations during COVID-19 also impacted the quality of life in addition to the disease-related symptoms, especially in adolescents.23,24 Cognitive impairment after a SARS CoV-2 infection may be associated with systemic inflammation during the acute phase, which may persist and cause depression and general psychopathology. High levels of cytokines and specific immune responses after COVID-19 infection have an essential role in cognitive impairment related to depression.25,26
The risk factors associated with persistent COVID-19 symptoms in children were similar in adults, including age, gender, severity of COVID-19, nutritional status, and comorbidities. Various studies have reported that overweight and obese children had an increased risk of a longer duration of COVID-19 symptoms.19,21,27,28 In contrast, a recent study found pre-infection undernutrition status increased the risk of long COVID.29 Our study found children with malnutrition and normal nutritional status have a greater tendency to have long COVID symptoms compared to overweight and obese children. Our study found children with long COVID had persistent symptoms for 1–3 months. This result is in accord with other studies that revealed children with long COVID had symptoms that persisted for 10–12 weeks. Pediatric studies have previously described a recovery time of 4 weeks to 3 months.7,30,31 In this study, over half of the children with PASC were age ≥10 years. Current systematic reviews in children and adolescents showed ages over 10 years, multisystem inflammatory syndrome, or severe symptoms as the risk factors for a higher prevalence of long COVID. Multiple organs and systems affected by multisystem inflammatory syndrome are associated with the development of long COVID in children. Patients complaining of more symptoms during SARS CoV-2 infection were more likely to have long COVID later.11,32 Another study also found an effect of the severity of COVID-19 symptoms and comorbidities.21 Similar to this study, children who had more severe COVID-19 and comorbidity tended to have long COVID symptoms.
Our study had similar long-term effects as those of adults after COVID-19 infection. We assume that symptoms reported in our study were likely to be due to COVID-19 infection; is it a condition, or is it a different entity as a disease? There is still no definitive treatment for long COVID. Recently, COVID-19 vaccination is said to be associated with a decreased risk of long COVID, and some studies suggest it might have a therapeutic effect on long COVID. Vaccination was expected to prevent long COVID by reducing the severity of initial symptoms of COVID-19 and producing additional antibodies by vaccination. The population of most studies were adults, and there is little data on the effect of COVID-19 vaccination on long COVID in children.33,34 During this study period, COVID-19 vaccination had yet to be introduced to children in Indonesia. Further study was needed to assess the association between COVID-19 vaccination and long COVID in children.
We note that this study had several limitations. Only 45 (36%) of 109 eligible candidates participated (not counting the deceased children). This low participation might potentially have adversely affected the findings. The questionnaire based on the evaluation of clinical symptoms was less objective. This, in concordance with Zimmermann et al,35 showed the majority relied on self- or parent-reported symptoms as clinical assessments, and objective parameters for the symptoms were subjective. Further studies should be conducted in cohorts with direct observation of the children. In this study, we identified that almost 70% of children had comorbidities, which results in the symptoms being indistinguishable between long COVID or due to underlying comorbidities. Moreover, symptoms attributed to long COVID are nonspecific and may have resulted from other conditions.
Conclusion
Children could also experience long COVID after being diagnosed with COVID-19 despite being asymptomatic or having only mild symptoms. Long COVID mainly occurs in children aged 5–9 years, with the most common symptoms being fatigue, decreased appetite, and muscle aches. Comorbidities might obscure symptoms of long COVID.
Acknowledgements
The authors would like to express our gratitude for the parents / guardians of the patients and for the Pediatric COVID-19 team of Dr. Hasan Sadikin General Hospital.
- Received June 17, 2023.
- Revision received August 11, 2024.
- Accepted August 19, 2024.
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