Introduction: Information on the quality of health of children and younger persons (CYPs) after SARS-COV-2 infection remains scarce, especially from Asia. In this study, we utilised an online survey to investigate Long COVID prevalence in CYPs in Singapore.
Method: The study was an anonymised online survey of physical and functional symptoms, made available from 14 October 2022 to 15 January 2023. Caregivers of CYPs aged 0 to 18 years were invited to complete the survey on behalf of their CYPs. Participants provided demographic information and their history of SARS-CoV-2 infection status to allow classification into cases and controls for analysis.
Results: A total of 640 completed responses were analysed, 471 (73.6%) were cases and 169 (26.4%) were controls. The prevalence of Long COVID ≥3 months post-infection was 16.8%. This decreased to 8.7% ≥6 months post-infection. Cases had higher odds of developing Long COVID (odds ratio [OR] 2.42, 95% confidence interval [CI] 1.31–4.74). The most common symptoms of Long COVID were persistent cough (7.4%), nasal congestion (7.6%) and fatigue (3.0%). Male gender was significantly associated with higher odds of Long COVID (adjusted OR 1.71 [1.04–2.83]). Vaccinated CYPs had lower odds of Long COVID but this was not statically significant (adjusted OR 0.65, 95% CI 0.34–1.25).
Conclusion: About 1 in 6 CYPs in Singapore developed Long COVID with persistence of 1 or more symptoms ≥3 months post-infection, and approximately half will recover by 6 months. Male gender was associated with higher odds of Long COVID, and vaccination could potentially be protective against Long COVID in CYPs.
What is New
- The prevalence of Long COVID was 16.8% at 3 months in children with SARS-CoV-2 infection in multi-ethnic Singapore. This dropped to 8.7% at 6 months post-infection.
- Persistent cough, nasal congestion and fatigue were the most common symptoms.
- Male gender was predictive of Long COVID.
- Children with COVID-19 infection have more than twice the odds of developing persistent symptoms compared to children without previous COVID-19 infection.
- It is important to screen for persistent symptoms in children who have COVID-19 infection.
On 5 May 2023, more than 3 years since the start of the COVID-19 pandemic, the World Health Organization (WHO) declared that COVID-19 no longer constituted a public health emergency. Despite high numbers of children and younger persons (CYPs) having acute COVID-19,1 information on the quality of health and well-being of CYPs after SARS-COV-2 infection remains scarce, especially from Asia. Of interest is the phenomenon of Long COVID or postacute sequelae of COVID-19 (PASC), a heterogenous, multisystemic condition, for which there are various definitions. In October 2021, WHO proposed a clinical definition for Long COVID in adults, stating that it generally occurs within 3 months from the onset of COVID-19, with symptoms lasting at least 2 months which cannot be explained by alternative diagnosis.2 A research definition of Long COVID in CYPs was developed by Delphi consensus process, stating that Long COVID occurs in CYPs with a history of confirmed SARS-CoV-2 infection, with 1 or more persistent physical symptoms for a minimum duration of 12 weeks with an impact on everyday functioning.3
Singapore is an island city-state in Southeast Asia with a resident population of 4.1 million as of 2022, and a CYP population below 20 years of 788,573 (19.4%).4 After its first case of COVID-19 on 23 January 2020,5 Singapore adopted a stringent COVID-19 testing, isolation and control strategy. A nationwide lockdown, termed as circuit breaker, was implemented from 7 April 2020 to 1 June 2020, during which all schools were closed as students shifted to home-based learning. Up until April 2022,6,7 close contacts of individuals with COVID-19 had to observe legally enforced stay-at-home restrictions with daily antigen rapid tests (ARTs), also known as health risk warning. Both polymerase chain reaction (PCR) (health facilities only) and ART testing were widely used for the diagnosis of COVID-19 over the course of the pandemic. ART kits were distributed widely to households in Singapore with self-testing recommended for anyone with symptoms of acute respiratory infections. All positive tests were required by law to be notified to the Ministry of Health.
Singapore experienced several waves of SARS-CoV-2 infections, driven by the delta variant (B.1.6172) from September 2021 to December 2021, followed by a larger wave from January 2022 to April 2022, driven by the omicron BA.1/BA.2 variant.8 Subsequent Omicron waves of BA.4/BA.5 and XBB followed. The pandemic vaccination programme for CYPs started in May 2021, with the introduction of mRNA COVID-19 vaccines for those aged 12–17 years. This was followed by a roll-out of mRNA vaccines to children aged 5–11 years in December 2021. In January 2022, a third mRNA vaccine dose (BNT162b2) as booster was recommended for children aged 12–17 years who had completed their second dose more than 5 months previously.9 Finally, in October 2022, COVID-19 vaccination was implemented for those aged 6 months to 4 years.
In this study, we utilised an online survey to collect data on the prevalence of Long COVID in CYPs in Singapore. We investigated factors associated with the development of Long COVID, including the protective effect of COVID-19 vaccination.
Study design, setting and population
The study was an anonymised online survey which was made available from 14 October 2022 to 15 January 2023. Caregivers of CYPs aged 0 to 18 years residing in Singapore were invited via hospital posters and social media advertisements to complete the online survey on behalf of their CYPs. The survey was based on a modified version of the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Paediatric COVID-19 questionnaire.10 Information recorded included basic demographic details; type of housing as a proxy for socioeconomic status; type and doses of COVID-19 vaccine received; date and details of prior SARS-CoV-2 infection, including type of diagnostic test (PCR or ART), symptoms and treatment. Clinical information regarding 28 physical and functional symptoms were recorded (present or absent, duration and severity assessed on a 5-category Likert scale). Caregivers of all CYPs, regardless of prior SARS-CoV-2 infection, were assessed using the same measures. Controls (SARS-CoV-2 negative CYPs) were asked specifically to complete survey questions based on their status during the 3 months prior to date of survey completion.
Case, control, vaccination and Long COVID definitions
Cases were defined as CYPs who reported confirmed SARS-CoV-2 infection via ART or PCR. Controls were individuals who reported not ever having a positive ART or PCR test from the start of the pandemic until the point of survey completion. CYPs were considered vaccinated if they had received 2 doses of COVID-19 vaccine 2 weeks prior to COVID-19 infection. For our main outcome analysis, we used the research definition of Long COVID in CYPs based on Stephenson et al.,3 i.e. a history of confirmed SARS-CoV-2 infection, with 1 or more persistent physical symptoms for a minimum duration of 3 months with an impact on everyday functioning.
Statistical methods and analysis
Univariable and multivariable analyses were performed to compare the prevalence of persistent symptoms in cases compared to controls. Factors included in the multivariable analysis were age, gender, ethnicity, type of residence (as a proxy for socioeconomic status), presence of comorbidities, and prior SARS-CoV-2 infection. Multivariable logistic regression was performed to assess the association between specific factors and the development of Long COVID in CYP with prior SARS-CoV-2 infection. Potential factors included in the model were predetermined before analysis from existing literature.11-13 They included prior SARS-CoV-2 infection, vaccination status prior to infection, gender, age, ethnicity, type of symptoms, number of symptoms and hospitalisation during acute SARS-CoV-2 infection. We stratified the analyses into 2 age groups to reflect key educational stages (0–6 years and 7–18 years).
Pearson chi-square or Fisher exact tests were used to evaluate for differences between 2 categorical variables, Wilcoxon rank-sum test was used to determine if there was a difference between the medians of 2 groups. A P value of less than 0.05 was taken to be statistically significant. SPSS Statistics for Windows version 17.0 (SPSS Inc, Chicago, IL, US) was used.
The above study was approved by the institutional review board (CIRB 2022/2296). Requirement for informed consent was waived in view of the anonymised nature of the survey.
Demographics and SARS-CoV-2 status
A total of 643 responses were recorded from 14 October 2022 to 15 January 2023. Of these, 3 caregivers had incomplete information about their child’s prior SARS-CoV-2 infection and were excluded from further analysis. Of the 640 CYPs, the median age was 6 years (interquartile range [IQR] 3–10 years). Chinese ethnicity made up 455 (71.1%) of total respondents, followed by Malays (n=82, 12.8%), Indians (n=53, 8.3%) and others, including Eurasians and those of mixed ethnicity (n=50, 7.8%). Four hundred and thirty-four (67.8%) of CYPs reside in government-subsidised housing, and the mean number of household members was 4.5 (1–12). Seventy-four (11.6%) CYPs had physician-diagnosed medical conditions (comorbidities); the 3 most common preexisting comorbidities were allergic rhinitis (n=16, 2.5%), eczema (n=16, 2.5%) and asthma (n=10, 1.6%). The demographic details of cases and controls did not differ significantly as shown in Table 1.
The study was made up of 471 (73.6%) cases, of whom 370 (78.6%) were confirmed by ART alone, 21 (4.5%) by PCR alone, and 80 (17.0%) by a combination of ART and PCR. Four hundred and thirty-six (92.6%) had 1 prior SARS-CoV-2 infection, 26 (5.5%) had 2 prior infections, and 9 (1.8%) had 3 or more previous infections. Most of the cases (96.8%) were infected from January 2022 during the first Omicron wave (BA.1/2/4/5 and XBB). The median number of symptoms experienced by cases during acute SARS-CoV-2 infection was 3 (IQR 2–4), with fever (n=373, 79.2%), cough (n=256, 54.5%), rhinorrhoea (n=249 52.9%), sore throat (n=209, 44.4%) and fatigue (n=154 (32.7%) as the most common symptoms. Twenty-two (4.7%) of cases had asymptomatic infection. Eighteen (3.8%) of cases required hospitalisation for acute SARS-CoV-2 infection, 2 (0.4%) required oxygen supplementation, and 2 (0.4%) required intensive care.
Prevalence and clinical manifestation of Long COVID
The prevalence of at least 1 persistent symptom lasting beyond 3 months (Long COVID) in cases was 16.8% (Table 2). Compared to controls, cases had higher odds of developing Long COVID (OR 2.42, 95% CI 1.31–4.74). These odds remained significant after multivariable adjustment (OR 2.43, 95% CI 1.31–4.51). The most common persistent symptoms experienced by CYPs with Long COVID were persistent cough (7.4%), nasal congestion or runny nose (7.6%), and fatigue (3.0%). Persistent cough and nasal congestion or runny nose were significantly more likely in cases compared to controls (OR 2.76, 95% CI 1.06–7.18; OR 3.39, 95% CI 1.18–9.76, respectively) (Table 2). Higher rates of difficulty breathing, palpitations, dizziness or light headedness, insomnia, hypersomnia, loss of concentration, memory problems, fatigue or tiredness and skin rash were also reported by CYPs with COVID-19 after 3 months, but these were not significantly different statistically from controls (Table 2).
The overall odds of cases reporting at least 1 symptom as severe or very severe were higher in cases than controls but this was not statistically significant (OR 1.49, 95% CI 0.70–3.17) (Table 2). Long COVID symptoms with higher point estimate odds of being reported as being severe or very severe included nasal congestion (OR 3.69, 95% CI 0.46–29.43), persistent cough (OR 6.21, 95% CI 0.81–47.59 ), prolonged school absence beyond 2 and 4 weeks (OR 1.25, 95% CI 0.67–2.32 and OR 1.08, 95% CI 0.44–2.63, respectively) (Table 2).
Prevalence of Long COVID symptoms up to 6 months post-infection
Fig. 1(a) shows the reported prevalence of Long COVID symptoms (1, 2 and 3 symptoms) at 3, 4 and 6 months post-infection. There was a consistent downward trend of CYPs with Long COVID from 3 to 6 months regardless of the number of persistent symptoms. Prevalence of CYPs with Long COVID due to 1 persistent symptom had decreased progressively from 16.8% to 8.7%. The proportion of cases at 6 months post-infection who still reported at least 1, 2 and 3 symptoms were 8.7%, 3.8% and 1.3%, respectively. The proportion of cases at 3 months and 6 months post-infection who had reported persistent cough decreased progressively from 7.4% to 2.1%, and those who had reported fatigue also decreased from 3.0% to 1.1% (Fig. 1(b)). Of 474 CYPs with prior COVID-19 infection, 64 (13.5%) reported that they have not fully recovered from COVID-19.
Fig. 1(a). Prevalence of persistent symptoms beyond 3, 4 and 6 months in children and younger persons (CYPs) with prior SARS-CoV-2 infection.
CYPs: children and younger persons
Fig. 1(b). Prevalence of common symptoms persistent beyond 3, 4 and 6 months in children and younger persons (CYPs) with prior SARS-CoV-2 infection.
CYPs: children and younger persons
Predictive factors for Long COVID
Table 3 summarises the analysis of the relationships between specific factors and development of Long COVID in CYPs. Male gender was significantly associated with higher odds of Long COVID in cases in univariate analysis and remained so after adjustments in multivariate analysis (OR 1.71, 95% CI 1.04–2.83 and OR 1.69, 95% CI 1.01–2.81, respectively). All other factors, including age, ethnicity, housing type, any comorbidity, number of symptoms during acute infection and COVID-19 hospitalisation, were not found to be significantly associated with Long COVID for CYPs in our study. Although not statistically significant, cases who were vaccinated had lower odds of Long COVID (adjusted OR 0.65, 95% CI 0.34–1.25) compared to cases who were unvaccinated, and cases of older age had higher odds of Long COVID compared to those of younger age (adjusted OR 1.78, 95% CI 0.94–3.37).
To our knowledge, this is the first study from Asia documenting Long COVID in CYPs. CYPs with COVID-19 infection in a multi-ethnic paediatric population in Singapore had a more than 2-fold increase in the odds of developing Long COVID. The prevalence of Long COVID was 16.8% at 3 months but this dropped to 8.7% at 6 months post-infection. Persistent cough, nasal congestion or runny nose, and fatigue were the most common symptoms reported in CYPs with Long COVID. After adjusting for potential confounders, male gender was found to be predictive of developing Long COVID in CYPs. Vaccinated CYPs were less likely to progress to Long COVID but the difference was not statistically significant.
The reported prevalence of Long COVID in CYPs ranges widely from 2% to 67%11,14,15 due to differences in Long COVID definitions and study methodologies. Our reported rate of 16.8% is lower than studies of persistent symptoms in CYPs 3 months post SARS-CoV-2 infection which have reported prevalence of 23–67%.13,15 Due to the widespread availability and recommended use of ART kits in Singapore,16 the infection status of our survey population was highly verified. Almost all CYPs with prior SARS-CoV-2 infection in our study cohort had infection during the period of omicron variant dominance, and vast majority experienced mild or asymptomatic COVID-19 infection, with only 3.8% reporting hospitalisation for acute infection. This is representative of the disease course of acute COVID-19 infection in children.17
Persistent cough, nasal congestion or runny nose, and fatigue were the most common symptoms reported in CYPs with Long COVID in our cohort. Our rates were similar to published studies where the proportion of Long COVID with persistent cough and nasal congestion or rhinorrhoea were 7.0%18 and 7.5%,11 respectively. Loss of taste and smell were common symptoms (6–29%) of Long COVID in earlier studies involving CYP with infections during the period of delta variant dominance.11,19,20 Only 1 case (0.2%) each was reported in our study and this is in-keeping with the different symptomatology of infections caused by different SARS-CoV-2 variants.21,22
Meta-analysis of Long COVID studies involving CYPs have also reported high prevalence of sleep disorders, cognitive difficulties and headaches.11,20 In our study, prevalence of persistent insomnia, hypersomnia, headache, loss of concentration and memory problems were higher in CYPs with COVID-19 after 3 months but these were not statistically significant compared to controls, possibly due to our smaller study sample size. Fatigue has been reported to affect 21–76% of CYPs with Long COVID,14,18,19,23,24 higher than CYPs of our cohort (3%). These differences may be explained in part by differing study populations and social restrictions in place in various countries during the COVID-19 pandemic, and different tools used to measure cognitive and functional changes used in different studies. Nevertheless, cognitive and functional difficulties in CYPs should be furthered explored in future studies.
Notably, both cases and controls reported prevalence of various symptoms surveyed in this study which persisted beyond 3 months, including fatigue, headache, insomnia and poor appetite. This is similar to observations in Long COVID studies involving both adult25,26 and paediatric populations,15,19,27 suggesting that symptoms are unlikely to be exclusive due to the specific consequence of SARS-CoV-2 infection. The pandemic and control measures used to limit its spread, such as school closures, social isolation and home-based learning, would have had a significant impact on the well-being of CYPs. It is clear that many CYPs experienced a range of physical and functional changes during the COVID-19 pandemic that warrant further investigation and intervention.
After adjusting for potential confounders, male gender was found to be predictive of developing Long COVID in CYPs in our study. Studies in paediatric populations have contrasting results with regard to the association of gender and risk of Long COVID.13,15,28,29 More studies in CYPs are needed to confirm the association between gender and Long COVID.
Studies in adults have shown a protective effect of vaccination against Long COVID.30 Our study found that CYPs who were vaccinated were less likely to have Long COVID in both univariable analysis (crude OR 0.89, 95% CI 0.54–1.49) and multivariable analysis after adjustment for potential confounders (adjusted OR 0.65, 95% CI 0.34–1.25). However, the association did not meet statistical significance, similar to a study by Morello et al. which reported reduced risk of Long COVID in vaccinated children (OR 0.60, 95% CI 0.33–1.11).12 Further studies are required to study the protective effect of 3 or more doses of COVID-19 vaccines on Long COVID in children, as the third dose is introduced to greater numbers of CYPs.
This study has limitations, including the cross-sectional nature of the questionnaire. Data on symptoms and testing were retrospective and hence, prone to recall bias. Persons who had persistent symptoms might also be more likely to respond to the survey. Our use of controls mitigated these factors, but may not have fully eliminated them. As it was an internet-based survey, there could have been selection bias, favouring those with internet access. Self-reported symptoms can also be biased by age since younger children are not able to express their emotional and functional status adequately compared to older children.
It was also possible that infections were missed in controls. However, the strict legally-enforced contact tracing and testing systems in place with easily accessible ART and PCR testing in Singapore reduced the likelihood of such false negative misclassification. Even after the end of legal enforcement in April 2022, ART testing with self-isolation continued to be recommended as a national policy for individuals with symptoms of respiratory tract infection, and implemented in all healthcare settings, educational settings and offices. There was a risk of false-positives tested by ART alone without confirmation with PCR. However, ART kits have been shown to perform well with high sensitivity and specificity for the diagnosis of COVID-19.31 We adjusted for known potential confounders of gender, ethnicity, medical history, or type of residence (socioeconomic status), but may have missed unknown confounders.
In conclusion, we found that approximately 1 in 6 CYPs in Singapore developed Long COVID with persistence of 1 or more symptoms after 3 months post-infection. Reassuringly, about half will recover by 6 months with prevalence falling to about 1 in 11. Commonly reported Long COVID symptoms included cough, nasal congestion and fatigue. Vaccination could potentially be protective against Long COVID in CYPs, but the findings did not reach statistical significance. More research is needed to identify risk factors for the development of Long COVID in CYPs.
Conflict of interest (including financial disclosure)
The authors have no conflict of interest to disclose.
The study was supported by the Tan Cheng Lim (TCL) Research and Education Grant (PAEDSACP-TCL/2022/RES/002), awarded by the Paediatrics Academic and Clinical Programme, SingHealth-Duke NUS.
Role of funder/sponsor
The funder had no role in the design and conduct of the study.
- United Nations International Children’s Emergency Fund. Child mortality and COVID-19, March 2023. https://data.unicef.org/topic/child-survival/covid-19. Accessed 29 June 2023.
- World Health Organization. Post COVID-19 condition (Long COVID), 7 December 2022. https://www.who.int/europe/news-room/fact-sheets/item/post-covid-19-condition. Accessed 29 June 2023.
- Stephenson T, Allin B, Nugawela MD, et al. Long COVID (post-COVID-19 condition) in children: a modified Delphi process. Arch Dis Child 2022;107:674-80.
- Department of Statistics, Singapore. Population and population structure. https://www.singstat.gov.sg/find-data/search-by-theme/population/population-and-population-structure/latest-data. Accessed 29 June 2023.
- The Straits Times. Singapore confirms first case of Wuhan virus; second case likely, 23 January 2020. https://www.straitstimes.com/singapore/health/singapore-confirms-first-case-of-wuhan-virus. Accessed 29 June 2023.
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