Abstract
Background
Long COVID-19 syndrome is a complex of symptoms that occurs after the acute SARS-CoV-2 infection, in the absence of other possible diagnoses. Studies on Long COVID-19 in pediatric population are scanty and heterogeneous in design, inclusion criteria, outcomes, and follow-up time. The objective of the present study is to assess the prevalence of Long COVID-19 syndrome in a cohort of Italian pediatric primary care patients, observed for a period of time of 8 to 36 weeks from healing. Prevalence was also assessed in a cohort of pediatric patients hospitalized during acute infection.
Methods
Data concerning 629 primary care patients with previous acute SARS-CoV-2 infection were collected by a questionnaire filled in by Primary Care Pediatrician (PCP). The questionnaire was administrated to patients by 18 PCPs based in 8 different Italian regions from June to August 2021. Data concerning 60 hospitalized patients were also collected by consultation of clinical documents.
Results
Cumulative incidence of Long COVID-19 resulted to be 24.3% in primary care patients and 58% in hospitalized patients. The most frequently reported symptoms were abnormal fatigue (7%), neurological (6.8%), and respiratory disorders (6%) for the primary care cohort. Hospitalized patients displayed more frequently psychological symptoms (36.7%), cardiac involvement (23.3%), and respiratory disorders (18.3%). No difference was observed in cumulative incidence in males and females in both cohorts. Previous diseases did not influence the probability to develop Long COVID-19. The prevalence of Long COVID-19 was 46.5% in children who were symptomatic during acute infection and 11.5% in asymptomatic ones. Children aged 0 to 5 years had a greater risk to develop respiratory symptoms, while adolescents (aged 11–16 years) had a greater risk to develop neurological and psychological Long COVID-19 symptoms.
Conclusions
Our study demonstrates that Long COVID-19 is a reality in pediatric age and could involve even patients with mild or no acute symptoms. The results stress the importance of monitoring primary care pediatric patients after acute COVID-19 infection and the relevance of vaccination programs in pediatric population, also in order to avoid the consequences of Long COVID-19 syndrome.
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Background
Despite more than 10,000 Articles are available nowadays on Pub Med on the Long COVID-19 issue, data and interpretations about this clinical condition are still not clear, especially in pediatric age.
The World Health Organization estimates that approximately 25% of adult patients with COVID-19 infection may develop persistent symptoms [1]. An Italian study shows that persistence of at least 2 symptoms after acute infection is evident in 32% of patients, and of at least 3 symptoms in 55% [2]; a Chinese study, on the other hand, observes the presence of Long COVID-19 in 76% of patients after 6 months from the detection of the infection [12]: in our cohort, prevalence goes from 11.5% in asymptomatic children to 46.5% in children with symptomatic infection, to 58% in hospitalized children.
Being symptomatic during the SARS-CoV-2 infection increased six folds the risk of having at least one symptom of long COVID-19, particularly respiratory, neurological, and psychological symptoms. This requires the PCP to monitor all patients who have had COVID-19, especially the symptomatic ones during the acute phase, but also the asymptomatic ones. Knowing that putative explanations for these Long COVID-19 symptoms include viral protein persistence in epithelial reservoirs, persistence of low-level inflammation, mitochondrial dysfunction, and virus-induced dysautonomia, it seems plausible that symptomatic children develop more frequently Long COVID-19 syndrome, as they typically experience a more virulent infection [13].
Long COVID-19 is far more frequent in hospitalized patients, but curiously abnormal fatigue has major prevalence in children who did not need hospitalization. This data contrasts with other studies reporting fatigue as the major symptom of Long COVID-19 after discharge [14, 15]. This data could be due to the accuracy of the detection of symptoms made directly by the pediatrician in the interview with the parents or during the clinical visit.
Generally, children recruited in primary care developed less severe Long COVID-19 symptoms (fatigue, upper respiratory system symptoms), while hospitalized children showed high prevalence of cardiac involvement (~ 22%) and above all psychological symptoms (~ 37%): anxiety, fear in social relationships, depression, insomnia, and concentration difficulties.
According to the data available in literature, children aged 11–16 years have a greater risk of develo** Long-COVID-19 symptoms, such as fatigue, anosmia, ageusia than the younger ones, aged 0–5 years [14, 16]. However, this data could be unreliable as a consequence of the difficulty in the assessment of these symptoms in younger children. The frequency of respiratory disorders related to long COVID-19, instead, decreases with age. Younger children should be carefully monitored, because they could be more susceptible of severe respiratory complications.
In our study, gender and pre-existing diseases do not affect the occurrence of long COVID-19; also children without comorbidities can have a severe course for long COVD-19 symptoms.
The limitation of our study is that it relies on forms retrospectively filled by the PCP according to parents’ reported symptoms. Anyway, we believe that the information is reliable because PCPs in Italy have a very close relationship with the children’s families and the data have been carefully collected.
Conclusion
For many months after the breakout of the pandemic, parents’ worries about their children’s symptoms were minimized, often labelled as “psychological issues” [15, 17]. Our study demonstrates that Long COVID-19 is a reality in pediatric age and could involve even patients with mild or no acute symptoms. The prevalence of Long COVID-19 is higher in symptomatic children, with no difference between males and females. Symptoms of Long COVID-19 are less severe in children assisted in primary care than in children hospitalized during acute illness. Our study provides useful information that stress the importance of monitoring primary care patients after acute COVID-19 infection, in particular younger children for respiratory symptoms and older children for psychological symptoms or fatigue.
Moreover, our results stress the importance of vaccination programs in pediatric population, also in order to avoid the consequences of Long COVID-19 syndrome.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- SARS-CoV-2:
-
Severe Acute Respiratory Syndrome CoronaVirus 2
- COVID-19:
-
CoronaVirus Disease 2019
- PCP:
-
Primary Care Pediatrician
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Acknowledgements
We sincerely thank the Primary Care Pediatrician Research Group for the pivotal contribution to our study.
For the of Primary Care Pediatrician Research Group: Al Jamal O, Casti T, Zanino L, Sottemano S, Careddu D, Bembo V, Franchi G, Muià CC, Macrì F Tiozzo V, Camilli S, Meleleo D, Lombardi Mistura L, Romeo L, Brazzoduro V, Soldato G, Lanza C, Piasenti C, Ragnatela G, Minchilli G.
Funding
The study has been pursued with no sources of funding to declare.
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Authors and Affiliations
Contributions
EB, VF, GT and GV have made substantial contributions to conception and design of the study, interpretation of data, and revising the manuscript critically for important intellectual content; GM and RV, have made substantial contributions to conception and design of the study, acquisition of data and analysis, interpretation of data, and drafting the manuscript; AS and AD have made substantial contributions to acquisition of data and analysis, and drafting the manuscript. All authors have given the final approval of the version to be published.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
The present study was approved by the Regional Ethics Committee of Liguria on the 16th of June 2021 with protocol number 419/2021—id 11611. Written informed consent was obtained from all parents and/or legal guardian of enrolled children. All the methods were carried out in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments.
Consent for publication
Informed consent was obtained from all patients’ parents.
Competing interests
The authors declare that they have no competing interests.
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Supplementary Information
Additional file 1:
Supplementary Table 1. Cumulative incidence of Long COVID-19 symptoms and signs, as a function of age, in hospitalized children. Supplementary Figure 1a-1b. Cumulative incidence of Long COVID-19 symptoms in the hospitalized patients, as a function of previous diseases. Supplementary Table 2. Independent effect of setting, gender, age, and symptoms during SARS-CoV-2 infection on the Long COVID-19 symptoms.
Appendix
Appendix
Questionnaire
Questions indicated with * had a mandatory answer
QUESTIONS FOR PRIMARY CARE PEDIATRICIAN |
Total number of patients assisted* |
How many patients underwent nasopharyngeal swab for COVID-19 diagnosis since the breakout of the pandemic until today? |
How many patients were positive to COVID-19? |
QUESTIONS FOR PATIENT’S PARENTS |
Age of the patient:* 1yrs 2 yrs 3 yrs 4 yrs 5 yrs 6 yrs 7 yrs 8 yrs 9 yrs 10 yrs 11 yrs 12 yrs 13 yrs 14 yrs 15 yrs 16 yrs |
Sex*: Female Male |
The child has tested negative from COVID-19* |
For a month |
For two or three month |
For four or five month |
For more than six month |
Does the child suffer from chronic pathologies*? YES NO If YES, specify………………… |
After COVID-19 acute infection, Has the child suffered more freqently from respiratory disorders*? YES NO |
If YES, specifiy among the reported*: |
Tonsillitis YES NO Othitis YES NO Pharingitis and/or Tracheitis YES NO Bronchitis or Pulmonary Disorders YES NO |
After COVID-19 acute infection, Has the child suffered more freqently from gastrointestinal disorders*? YES NO |
If YES, specifiy among the reported*: |
Diarrhea YES NO Vomit YES NO Abdominal colics YES NO |
After COVID-19 acute infection, Has the child reported other symptoms*? |
If YES, specifiy among the reported*: |
Anxiety and fear of social relationships YES NO |
Depression YES NO |
Learning disabilities YES NO |
Eating disorders YES NO |
Cephalalgy YES NO |
Insomnia. YES NO |
Palpitations YES NO |
Joint and muscolar pain YES NO |
Abnormal fatigue YES NO |
Cutaneous disorders YES NO |
Loss of hair YES NO |
Loss of taste YES NO |
Loss of smell. YES NO |
Other symptoms YES NO If YES specify ………………………………………………………. |
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Trapani, G., Verlato, G., Bertino, E. et al. Long COVID-19 in children: an Italian cohort study. Ital J Pediatr 48, 83 (2022). https://doi.org/10.1186/s13052-022-01282-x
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DOI: https://doi.org/10.1186/s13052-022-01282-x