Next Article in Journal
Effects of Exergaming on Morphological Variables, Biochemical Parameters, and Blood Pressure in Children and Adolescents with Overweight/Obesity: A Systematic Review with Meta-Analysis of Randomized Controlled Trials
Previous Article in Journal
Motor Learning Deficits in a Neonatal Mouse Model of Hypoxic-Ischemic Injury
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Children
Volume 12
Issue 1
10.3390/children12010028
children-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Adolescents with Persistent Symptoms Following Acute SARS-CoV-2 Infection (Long-COVID): Symptom Profile, Clustering and Follow-Up Symptom Evaluation

by
Marco Floridia
1,*,
Danilo Buonsenso
2,
Laura Macculi
3,
Liliana Elena Weimer
1,
Marina Giuliano
1,
Flavia Pricci
4,
Leila Bianchi
5,
Domenico Maurizio Toraldo
6,
Graziano Onder
3,7 and
The ISS Long-COVID Study Group
†
1
National Center for Global Health, Istituto Superiore di Sanità, 00161 Rome, Italy
2
Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00136 Rome, Italy
3
Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00136 Rome, Italy
4
Department of Cardiovascular, Endocrine-Metabolic Diseases and Ageing, Istituto Superiore di Sanità, 00161 Rome, Italy
5
Infectious Diseases Unit, Meyer Children’s Hospital IRCCS, 50139 Florence, Italy
6
Cardiorespiratory Rehabilitation Unit, Department of Rehabilitation, “V. Fazzi” Hospital, 73100 Lecce, Italy
7
Office of the President, Istituto Superiore di Sanità, 00161 Rome, Italy
*
Author to whom correspondence should be addressed.
†
Membership of the ISS Long-COVID Study Group is provided in the Acknowledgments.
Children 2025, 12(1), 28; https://doi.org/10.3390/children12010028
Submission received: 13 November 2024 / Revised: 23 December 2024 / Accepted: 26 December 2024 / Published: 27 December 2024
(This article belongs to the Section Global Pediatric Health)
Browse Figures
Versions Notes

Abstract

:
Background: Few studies have evaluated long-COVID in adolescents. Methods: Cohort study. Demographics, clinical data, and the presence of 30 symptoms were collected with a modified WHO form. Mean values were compared by Student’s t test and proportions by the chi-square test or Fisher test, with trends over time analysed using the chi-square test for trend. Potential risk factors independently associated with persisting symptoms were evaluated in a multivariable logistic regression model. Clustering of cases was analysed by two-step automatic clustering. Results: A total of 97 adolescents aged 12–17 (54.6% females, 45.4% males) were evaluated. After a mean interval of 96 days (SD 52) from acute infection, the mean number of symptoms (2.8 overall) was higher for pre-Omicron (3.2 vs. 2.5 in Omicron, p = 0.046) and moderate/severe acute infections (4.2 vs. 2.7 in mild, p = 0.023). Fatigue (62.9%) and dyspnea (43.3%) were the most common symptoms, followed by headache (28.9%), thoracic pain (22.7%), diarrhea (20.6%), palpitations/tachycardia (17.5%), articular pain (15.5%), difficult concentration (14.4%), muscle pain (12.4%), taste reduction (8.2%), smell reduction (8.2%), fever (6.2%), and skin disorders (5.2%). The symptom profile was similar in males and females but showed significant differences from that observed in concurrently followed adults. After a mean interval of 340 days from infection, 45.3% still presented symptoms, with persistence associated with higher number of initial symptoms. Two clusters were defined that differed in the phase of acute infection and the number and profile of symptoms. Conclusions: Long-COVID manifestations in adolescents may differ from those observed in adults. Polisymptomaticity may predict long-term persistence.

1. Introduction

The long-term sequelae of COVID-19 infection are increasingly recognised as a significant cause of morbidity and disability worldwide [1,2,3]. The UK National Institute for Health and Care Excellence (NICE) defines ‘Long-COVID’ as any symptom persistence beyond four weeks [4], in concordance with the definition of the US Department of Health and Human Services (DHHS) and the Centers for Diseases Control and Prevention (CDC) [5]. The WHO has defined post COVID-19 condition/long COVID as the continuation or development of new symptoms three months after the initial SARS-CoV-2 infection [6], and subsequently issued a separate clinical case definition for children and adolescents [7], acknowledging that symptoms in children and adolescents are non-specific and can occur with other infections and illnesses, complicating the diagnosis. Such difficulties, together with the variable definitions used in clinical studies, have led to a wide array of the prevalence of paediatric long-COVID in the scientific literature. In some studies, prevalence has peaked with frequencies of 20% or higher [8,9,10,11,12,13]. More recent studies have suggested lower rates, with 1–5% of children and adolescents affected [10,14]. The prevalence of individual symptoms is also ill-defined and similarly variable [15,16]; only a few studies have compared the symptom profiles in contemporary enrolled adults and paediatric populations [17]. Finally, the vast majority of the studies conducted in younger individuals have evaluated mixed populations of children and adolescents, who may, however, differ significantly in several aspects.
With the aim to contribute information on this issue, we used data from a multicentre national cohort to define the clinical characteristics of adolescent patients accessing care for long-COVID in specialised centres, the profile of symptoms reported, their persistence during follow-up, and the possible clustering of cases.

2. Materials and Methods

The present clinical study is part of the larger project “Analysis and strategies for responding to the long-term effects of the COVID-19 infection (Long-COVID)”, funded by the National Centre for Disease Prevention and Control (CCM) of the Italian Ministry of Health. Within this project, before the current study, a national survey was conducted to identify centres providing care to individuals with long-COVID [18].
The project, patient information sheet, and consent form were approved by the Italian National Ethics Committee (AOO-ISS—19/04/2022–0015066 Class: PRE BIO CE 01.00). Written informed consent was required for patient inclusion. This study started in January 2023 and was closed in March 2024, with data extracted on 2 April 2024. Data were entered by medical staff in participating centres using an online dedicated platform with two levels of authentication that included one-time passwords. For data collection, a shortened version of the Post COVID-19 CRF from the WHO Global Clinical Platform for COVID-19 was used, that included demographics, comorbidities, severity, and timing of acute COVID, subjective functional status after infection, plus 30 different symptoms and the presence of 34 specific clinical diagnoses [19]. Adolescents underwent two clinical evaluations using the above form for data collection, with the first evaluation conducted at least four weeks after acute infection (recommended: between 3 and 6 months) and the second (follow up) after at least three months from first visit (recommended: 6–12 months from acute infection).
Inclusion criteria were age between 12 and 17 years, known date of acute SARS-CoV-2 infection, and at least one symptom persisting for more than four weeks after acute infection. Severity of acute SARS-CoV-2 disease was defined as mild, moderate, severe, or critical according to the WHO grading [19]. Respiratory assistance was categorised as none, low, or high flow oxygen, continuous positive airway pressure (CPAP), mechanical ventilation, and extracorporeal membrane oxygenation (ECMO). The phase of the pandemic was categorised as pre-Omicron or Omicron according to the occurrence of date of acute infection before or after 23 December 2021 [20]. The prevalence of symptoms was compared with that observed among adult patients contemporarily enrolled in the same project [21].
Data were summarised as a proportion, for categorical variables, and as a mean with standard deviation, for quantitative variables. Mean values were compared by Student’s t test and proportions by the chi-square test or Fisher test in contingency tables. Trends over time in proportions were analysed using the chi-square test for trend.
Clustering of cases was performed with the two-step automatic clustering method, which considered all symptoms with an observed frequency of at least 5% plus the following five clinical and demographic variables: sex, presence of comorbidities, phase of the pandemic (Omicron vs. pre-Omicron), number of symptoms, and WHO grade of severity of acute disease (mild vs. moderate/severe), with the final number of clusters automatically selected according to the quality of the model provided by the Schwarz Bayesian information criterion.
Potential risk factors independently associated with persisting symptoms at second evaluation were evaluated in a multivariable logistic regression model that included age, sex, number of symptoms at first evaluation, phase of acute disease (Omicron vs. pre-Omicron), presence of comorbidities, and severity of acute disease (mild vs. moderate/severe) as independent variables. All analyses were performed using the SPSS software, version 27.0 (IBM Corp., 2017, Armonk, NY, USA).

3. Results

3.1. Clinical Characteristics of Adolescent Patients Accessing Care for Long-COVID

The study population included 97 adolescent patients aged 12–17 years (53 females, 44 males), evaluated at three clinical centres after a mean interval from acute infection of 96.5 days (SD 52). Their general characteristics are shown in Table 1. No significant differences were observed between males and females in terms of age, vaccination status, epidemic phase of acute infection, or severity of acute infection (mild in 90.7% of cases). Only three cases were hospitalised during acute infection and none required respiratory assistance. Eight adolescents (8.2%) had relevant comorbidities (three had asthma, five had other conditions) (Table 1).

3.2. Complications Related to Acute SARS-CoV-2 Infection

Nine patients (9.3%) following acute SARS-CoV-2 infection were diagnosed with new conditions that were considered related to COVID: pericarditis (2), low blood pressure (1), pancreatitis (1), sleep disturbances (1), anxiety, depression, psychosis, post-traumatic stress disorder (1), polyneuropathy (1), fasciculations (1), and asthma (1). Most of these conditions occurred in the first few weeks after acute infection and all resulted to be resolved at follow up evaluation.

3.3. Profile of Symptoms Reported and Variables Associated with Symptoms

The mean number of symptoms reported by the entire adolescent population was 2.8 (SD 1.8), with no significant differences by sex (3.0 in females vs. 2.7 in males, p = 0.526), vaccination status (2.8 in vaccinated vs. 2.9 in unvaccinated, p = 0.658) or presence of comorbidities (2.5 with comorbidities vs. 2.9 without comorbidities, p = 0.563), but with significant differences by pandemic phase (3.2 for pre-Omicron vs. 2.5 for Omicron, p = 0.046) and by severity of acute disease (4.2 in patients with moderate or severe acute disease compared to 2.7 in those with mild acute disease, p = 0.023).
The observed symptom profile included 23 different symptoms. None of the adolescent reported as persistent symptoms paresthesia, weight loss, disorders of equilibrium or gait, hearing disturbances, pharyngodynia, chilblains, delirium, or hallucinations. The prevalence of the 13 symptoms more commonly reported (at least five per cent of cases) were compared by sex, phase of the pandemic, presence of comorbidities, and severity of the acute disease. No significant differences were observed by sex (Supplementary Table S1). With respect to the phase of the pandemic, fatigue was significantly more common among adolescents infected during the Omicron phase compared to those infected during the pre-Omicron phase, (72.5% vs. 52.2%, p = 0.038). An opposite trend approaching statistical significance was observed for dyspnea and thoracic pain that were more common among those infected during the pre-Omicron phase compared to the Omicron phase (52.2% vs. 35.3% for dyspnea, p = 0.094, and 30.4% vs. 15.7% for thoracic pain, p = 0.083). With respect to comorbidities, fatigue was significantly more common among the adolescents without comorbidities (66.3% vs. 25.0% in those with comorbidities, p = 0.049), while thoracic pain was significantly more common among those with previous comorbidities (62.5% compared to 19.1% in those without comorbidities, p = 0.014) (Table 2).
Finally, with respect to severity of acute disease, palpitations/tachycardia were significantly more common among adolescents with more severe acute disease (50.0% for moderate or severe acute disease compared to 14.8% for mild disease, p = 0.031), with a similar trend approaching statistical significance for muscular pain (37.5% vs. 10.2%, p = 0.059), fever (25.0% vs. 4.5%, p = 0.077), articular pain (37.5% vs. 13.6%, p = 0.107), and thoracic pain (50.0% vs. 19.3%, p = 0.066) (Table 2).
Overall, the symptom profile was markedly different from that observed in 1297 adults contemporarily enrolled in the same project, with twelve symptoms showing significant differences between the two age groups: headache, thoracic pain, diarrhea, and fever were significantly more frequent in adolescents; while memory loss, sleep disturbances, depressed mood, cough, anxiety, weight loss, paresthesias, and gait/equilibrium disturbances were significantly more common in adults (Figure 1 and Supplementary Table S2).

3.4. Clustering of Cases

The cluster analysis automatically selected three- and two-cluster models as solutions with adequate statistical quality. Given the low number of cases, the two-cluster solution was preferred. The results are presented in Table 3. The two clusters were similar with respect to sex and presence of comorbidities, but cluster 1 was characterised by a lower prevalence of the more recent (Omicron) acute infection and by a higher overall number of symptoms that translated to a higher prevalence of most of the individual symptoms evaluated (Table 3).

3.5. Diagnostic Tests

The clinical evaluation and the diagnosis of new conditions was accompanied by a variety of instrumental tests that most commonly included chest ultrasonography (42, 43.3%), heart ultrasonography (17, 17.5%), electrocardiogram (9, 9.3%), cardiopulmonary exercise testing (9, 9.3%), Holter electrocardiography (9, 9.3%), and chest X-ray (5, 5.2%). The complete list of the instrumental tests performed is reported in Supplementary Table S3.

3.6. Symptom Persistence During Follow Up

Ninety-five adolescents (97.9%) following first clinical long-COVID evaluation had a follow-up evaluation, performed after a mean interval from the first evaluation of 248 days (SD 94) and after a mean interval from acute infection of 340 days (SD 94). At this timepoint, 43 adolescents (45.3%) still presented with persistent symptoms. In this population of adolescents who remained symptomatic, the mean number of persistent symptoms decreased significantly from 3.3 (SD 1.9) to 2.1 (SD 1.3) (p < 0.001). No patients increased their symptom number compared to first evaluation. Seven symptoms (anxiety, depressed mood, sleeping disturbances, visual disturbances, loss of appetite, skin disorders, and menstrual disorders) that were present at the first evaluation in one or more of the adolescents were not reported at the second evaluation. The follow up rates of the most common initial symptoms and their proportional reduction compared to the first evaluation are reported in Figure 2.
The proportion of adolescents free of symptoms at the second evaluation was inversely correlated to the number of initial symptoms, with a significant decrease at the increasing of initial symptoms (68.0% in those with one symptom, 64.3% with two symptoms, 58.3% with three symptoms, 35.7% with four symptoms, 33.3% with five symptoms, and 42.9% with 6 symptoms) (p = 0.025, chi square for trend for the inverse correlation).
Finally, we assessed the potential risk factors independently associated with persisting symptoms at the second evaluation, considering age, sex, number of symptoms at first evaluation, phase of acute disease (Omicron vs. pre-Omicron), presence of comorbidities, and severity of acute disease (mild vs. moderate/severe) as independent variables. In the corresponding multivariable logistic regression model, only the number of symptoms at the first evaluation was significantly associated with persisting symptoms (adjusted odds ratio per each additional symptom reported: 1.354, 95%CI 1.022–1.794, p = 0.035). The full results of the multivariable logistic regression model are shown in Supplementary Table S4.

4. Discussion

The present study characterised a population of 97 adolescents accessing care for persistent symptoms following SARS-CoV-2 infection. The mean number of symptoms did not show differences by sex or vaccination status but was significantly higher for infections that occurred in the pre-Omicron phase and for patients with the more severe acute disease. This finding is consistent with several studies that have linked the presence and persistence of post-COVID conditions to a more severe acute disease, possibly driven by the more virulent variants circulating in the earlier phases of the pandemic [8,17].
Fatigue (62.9%) and dyspnea (43.3%) were the most commonly observed symptoms. Such rates are consistent with those that we observed in contemporarily enrolled adults (55.9% and 47.2%, respectively) [21]. Fatigue is consistently reported by several studies as the most common long-COVID manifestation in children and adolescents [12,13,15,16], and has been recognised as a predominant factor affecting quality of life in paediatric long-COVID [22]. It has also been included as a critical outcome in the Core Outcome measurement set produced by the International PC-COS Children Consensus [23] and as a key symptom in the WHO consensus on Post-COVID clinical case definition in children and adolescents [7]. In our study, its prevalence reduced three-fold during follow up, and no cases of its most severe form, represented by chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME), were diagnosed. Despite these favourable findings, fatigue remained, even after a longer follow up, the most common persistent symptom, with a final prevalence in our case series of roughly 20% that deserves clinical attention, particularly because this symptom appeared to be significantly more common among adolescents more recently infected, suggesting a current clinical relevance of this finding.
Dyspnea was the second most frequent symptom. The prevalence rates reported for this symptom in published studies of paediatric and adolescent individuals are highly variable, with some studies reporting it as a key symptom [11,16,17], while other studies found it to be much less frequent compared to other manifestations [9,12,13,15]. Although such differences may be explained by variable definitions, settings, and populations, persistent dyspnea might also reflect a more severe involvement of the respiratory system in acute SARS-CoV-2 disease, possibly due to the more aggressive variants circulating during the early pandemic [8,24]. Consistent with this assumption, in our cluster analysis, all cases of dyspnea aggregated in cluster one, predominantly composed by adolescents infected during the pre-Omicron phase, and no cases were present in cluster 2, where almost all individuals were infected during the Omicron phase.
Headache, thoracic pain, and diarrhea were also frequent symptoms, affecting more than 20% of cases. These three symptoms were much less frequent in the adult population concurrently studied (6.4%, 9.4%, and 3.5%, respectively), and characterised together with fever (6.2% vs. 1.5% in adults), the specific symptom profile of adolescents, confirming the different clinical phenotypes of long-COVID already described by systematic reviews, multicentre studies, and consensus statements [7,11]. Based on these findings, we suggest that, in the evaluation of adolescents for long-COVID, in addition to fatigue, dyspnea, palpitations, difficult concentration, articular or muscle pain, smell or taste changes that are equally common in young and older age, particular attention should be paid to these symptoms that appear to be more frequent in younger patients and that can significantly affect quality of life and daily living [7].
The cluster analysis indirectly confirmed the association between pre-Omicron infection and a higher number of symptoms (3.5 vs. 1.5 in clusters with pre-Omicron and Omicron predominance, respectively). Although the results for individual symptoms, as already discussed, were particularly striking for dyspnea, that was present only in cluster one, most of the other symptoms were significantly more frequent in cluster one, with the exception of fatigue, headache, and fever, that were more frequent, although not significantly, in cluster two. Overall, these findings suggest that the acute infections occurred during the Omicron phase, while generally milder, may translate in a different long-COVID phenotype, possibly through distinct pathogenetic pathways that should be explored. In general, the few studies that have evaluated the clinical phenotypes of long-COVID in children and adolescents have provided inconsistent results [25,26,27]. Further research on this issue is needed.
The diagnostic tests that accompanied the clinical evaluation were most commonly directed to respiratory and cardiac morbidities. In this regard, some centres are offering advanced diagnostics for these patients to measure and monitor fatigue and inappropriate tachycardia syndromes, like cardiopulmonary exercise testing and 24-h ECG with measurement of heart rate variability [28]. Following acute infection, roughly ten per cent of adolescents had COVID-19 related clinical conditions diagnosed, usually in the first few weeks after acute infection, and all such conditions were no more present during follow up, providing reassurance on their reversibility.
The follow up evaluation showed that, after a mean interval of eight months from initial visit and at one year from acute infection, more than half of the adolescents who were previously symptomatic were symptom-free. Moreover, among those who remained symptomatic, the mean number of symptoms decreased significantly. Such findings are consistent with other studies that showed improvement in recovery rates at the increase of follow up [8,16]. Despite such reassuring findings, a significant proportion of adolescents remained symptomatic at one year from acute infection, and a longer follow up is essential to better define the long-term trajectories of symptoms. The association between persistence and the initial number of symptoms, confirmed in a multivariable analysis that was adjusted for age, sex, phase, and severity of acute disease, indicates that initial polysymptomaticity should be considered a risk factor for longer persistence.
The strengths of the present study include the evaluation of a population strictly characterised by precise age limits, while other studies have usually included mixed populations of children and adolescents, who may differ in several aspects. We also were able to show that the symptom profile of adolescents presents some significant differences with that of adults who were concurrently evaluated with the same instrument. The use of a WHO instrument may also allow comparisons with other international studies. We were also able to evaluate, together with a large number of symptoms, several demographic and clinical characteristics, such as comorbidities, severity of acute disease, and phase of the pandemic, assessing their potential role on the number and type of symptoms.
In terms of study limitations, our study was based on patients accessing care for long-COVID symptoms and did not allow any estimate of the prevalence of this condition. Having focused on patients evaluated in specialised centres, we also may have selected cases characterised by greater severity or complexity. We also did not evaluate psychosocial factors, measures of familiar well-being, quality of life, or impact on daily life and on educational attendance and performance, that would have usefully complemented the data collected [22,23,29].
Our data also do not allow for any conclusions about the possible role of vaccination in preventing long-COVID; this has been analysed by some authors, with variable results [15,30,31,32]. In our study, the proportion of adolescents vaccinated before infection was low. This might indirectly suggest a protective effect of vaccination in preventing long-COVID, but specifically designed prospective studies are needed to address this issue. With respect to symptoms, our instrument did not include some of the symptoms that were highlighted by the WHO consensus, issued in February 2023, while our study was already ongoing [7]. Finally, the identification of possible predictors of the persistence of individual symptoms was limited by the size of the sample studied.

5. Conclusions

In conclusion, this study characterised the symptom profile of a population only composed of adolescents that accessed care for persistent symptoms following SARS-CoV-2 infection. The findings indicate that, although the main symptoms, represented by fatigue and dyspnea, are common to adolescent and adult individuals, headache, thoracic pain, diarrhea, and fever are significantly more common in adolescents, defining a specific long-COVID phenotype for this age group. The phase of the pandemic, possibly through earlier variants determining increased disease severity, influenced the number and the type of symptoms. More than half of the previously symptomatic adolescents were symptom-free at one year, with a better outcome than those who had fewer initial symptoms. The above findings, contributing to a further definition of the possible manifestations of this condition and of its clinical correlates in adolescents, may be of interest for paediatricians, epidemiologists, and public health officers and could provide the basis for future clinical studies.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/children12010028/s1, Table S1: Symptom prevalence by sex; Table S2: Symptom profile in contemporarily enrolled adolescent and adults; Table S3: Instrumental tests performed; Table S4: Multivariable analysis of factors associated with persisting symptoms during follow-up.

Author Contributions

M.F. was responsible for data acquisition, directly accessed and verified the underlying data reported in the manuscript and performed the analyses. M.F. drafted the manuscript. Full data were available to all authors. M.F., M.G. and G.O. contributed to the conception and design of this study. D.B., L.M., L.E.W., F.P., L.B., D.M.T. and The ISS Long-COVID Study Group contributed to the data acquisition. All authors contributed to the interpretation of results and review of the manuscript for intellectual content. All authors have read and agreed to the published version of the manuscript.

Funding

The present study is part of the project “Analysis and strategies of response to the long-term effects of COVID-19 infection (Long-COVID)” funded by the National Center for Disease Prevention and Control of the Italian Ministry of Health in 2021 (Grant I85F21003410005) and approved by the Ethics Committee of the ISS (ref. PRE BIO CE 01.00 0015066, 2022). The study sponsor had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication. No honorarium, grant, or other form of payment were given to anyone to produce the manuscript.

Institutional Review Board Statement

The project, patient information sheet, and consent form were approved by the Italian National Ethics Committee (AOO-ISS—19/04/2022–0015066 Class: PRE BIO CE 01.00, approved on 19 April 2022). Written informed consent was required for patient inclusion.

Informed Consent Statement

Informed consent was obtained from all subjects involved in this study.

Data Availability Statement

The study data can be made available upon reasonable request. Ethics Committee consultation may be necessary in order to obtain permission to share. Requests to access the datasets should be directed to marco.floridia@iss.it.

Acknowledgments

We thank Fabio Galati, IT services, Istituto Superiore di Sanità, Rome, Italy, for implementing the online platform used for data collection and for data management and extraction; Tiziana Grisetti and Katia Salomone, Istituto Superiore di Sanità, Rome, Italy, for administrative support; Cosimo Polizzi, Istituto Superiore di Sanità, Rome, Italy, for data management during all the study. The ISS Long-COVID Study Group: Graziano Onder, Marco Floridia, Marina Giuliano, Tiziana Grisetti, Flavia Pricci, Tiziana Grassi, Dorina Tiple, Marika Villa, Liliana Elena Weimer, Cecilia Damiano, Cosimo Polizzi, Fabio Galati (Istituto Superiore di Sanità, Rome, Italy); Maria Rosa Ciardi, Patrizia Pasculli (Dipartimento di Sanità Pubblica e Malattie Infettive, Università La Sapienza, Roma); Piergiuseppe Agostoni, Francesca Colazzo, Irene Mattavelli, Elisabetta Salvioni (Centro Cardiologico Fondazione Monzino, Milano e Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano); Paolo Palange, Daniela Pellegrino, Marco Bezzio, Federica Olmati, Arianna Sanna, Arianna Schifano, Dario Angelone, Antonio Fabozzi (Dipartimento di Sanità Pubblica e Malattie Infettive, Università La Sapienza, Roma); Patrizia Rovere Querini, Simona Santoro, Anna Fumagalli, Aurora Merolla, Valentina Canti, Maria Pia Ruggiero, Marco Messina, Marina Biganzoli (U.O. Medicina Generale ad Indirizzo Specialistico e della Continuità Assistenziale, IRCCS Ospedale S. Raffaele, Milano); Danilo Buonsenso (Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma); Silvia Zucco, Alice Ianniello (ASL Città di Torino, Ospedale Amedeo di Savoia, Torino); Matteo Tosato, Vincenzo Galluzzo, Laura Macculi (Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Roma); Aldo Lo Forte, Valeria Maria Bottaro (USL Toscana Centro, Ospedale S. Giovanni di Dio Torregalli, Firenze); Paolo Bonfanti, Luca Bonaffini, Anna Spolti, Nicola Squillace (Unità di Malattie Infettive, Fondazione IRCCS San Gerardo dei Tintori, Monza); Donato Lacedonia, Terence Campanino (AOU OORR Foggia Pneumologia, Dipartimento di Scienze Mediche e Chirurgiche, Università di Foggia); Emanuela Barisione, Teresita Aloè, Elena Tagliabue (IRCCS Ospedale Policlinico San Martino, Genova); Stefano Figliozzi, Federica Testerini (Ospedale di Ricerca IRCCS Humanitas, Rozzano); Paola Andreozzi, Marzia Miglionico, Antonia Barbitta, Chiara Cenciarelli (Unità di Medicina Predittiva, Azienda Ospedaliero Universitaria Policlinico Umberto I and Dipartimento di Medicina Interna, Scienze Endocrino-Metaboliche e Malattie Infettive Università La Sapienza, Roma); Gianluca Pagnanelli, Giuseppe Piccinni (Istituto Dermopatico dell’Immacolata—IDI IRCCS—Roma); Paola Gnerre, Eugenia Monaco, Sandra Buscaglia, Antonella Visconti (ASL Liguria 2, Medicina Interna, Ospedale S. Paolo, Savona); Kwelusukila Loso (Ospedale di Manduria, ASL TA); Giuseppe Pio Martino, Giuseppina Bitti, Laura Postacchini, Antonella Cognigni (U.O.C. Medicina Interna, Ospedale “A. Murri”, Fermo); Maria Antonietta di Rosolini, Sergio Mavilla (UOSD di Malattie Infettive, PO Giovanni Paolo II, Ragusa); Domenico Maurizio Toraldo (Polo Riabilitativo, Plesso di S. Cesario, Ospedale di Lecce); Guido Vagheggini, Giulio Bardi, Giuseppa Levantino (Azienda USL Toscana Nord Ovest); Cristina Stefan (IRCCS Eugenio Medea, Polo Scientifico Veneto, Pieve di Soligo); Gianfranco Parati, Elisa Perger, Enrico Gianfranceschi, Francesca Pozzoli (IRCCS Istituto Auxologico Italiano, Università di Milano Bicocca, Milano); Pasqualina De Leo, Sara Grignolo (ASL Liguria 2, Struttura Complessa Malattie Infettive, Ospedale S. Paolo, Savona); Caterina Monari (AOU Unicam Vanvitelli, Napoli); Leila Bianchi, Luisa Galli (Azienda Ospedaliero-Universitaria Meyer, Firenze); Lorenzo Surace, Elisabetta Falbo (Centro Medicina del Viaggiatore e delle Migrazioni, Dipartimento di Prevenzione PO Lamezia Terme, ASP Catanzaro); Silvia Boni (S.C. Malattie Infettive, EO Ospedali Galliera, Genova); Claudia Battello (Azienda Sanitaria Universitaria Friuli Centrale, Medicina Latisana, PO Palmanova,); Caterina Baghiris (SC Pneumologia ASL Friuli Occidentale, Pordenone); Gaetano Serviddio (UOC di Epatologia, AOU OO RR, Foggia).

Conflicts of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be considered as a potential conflict of interest. The funders had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

References

  1. World Health Organization (WHO). COVID-19 Epidemiological Update. Edition 167, 17 May 2024. Available online: https://www.who.int/publications/m/item/covid-19-epidemiological-update-edition-167 (accessed on 3 September 2024).
  2. Ramos, S.C.; Maldonado, J.E.; Vandeplas, A.; Ványolós, I. European Commission Directorate-General for Economic and Financial Affairs. Long COVID: A Tentative Assessment of Its Impact on Labour Market Participation and Potential Economic Effects in the EU. Available online: https://economy-finance.ec.europa.eu/publications/long-covid-tentative-assessment-its-impact-labour-market-participation-and-potential-economic_en (accessed on 3 September 2024).
  3. European Center for Disease Prevention and Control (ECDC). Prevalence of Post COVID-19 Condition Symptoms: A Systematic Review and Meta-Analysis of Cohort Study Data, Stratified by Recruitment Setting. 27 October 2022. Available online: https://www.ecdc.europa.eu/sites/default/files/documents/Prevalence-post-COVID-19-condition-symptoms.pdf (accessed on 3 September 2024).
  4. National Institute for Health and Care Excellence (NICE). NICE Guideline, No. 188, 2020 Dec 18: COVID-19 Rapid Gguideline: Managing the Long-Term Effects of COVID-19. Available online: https://www.nice.org.uk/guidance/ng188 (accessed on 25 December 2024).
  5. Centers for Diseases Control and Prevention (CDC). Long COVID or Post-COVID Conditions. Updated 14 March 2024. Available online: https://www.covid.gov/be-informed/longcovid/about#term (accessed on 3 September 2024).
  6. World Health Organization (WHO). Post COVID-19 Condition (Long COVID). 7 December 2022. Available online: https://www.who.int/europe/news-room/fact-sheets/item/post-covid-19-condition (accessed on 3 September 2024).
  7. World Health Organization (WHO). A Clinical Case Definition for Post COVID-19 Condition in Children and Adolescents by Expert Consensus, 16 February 2023. Available online: https://www.who.int/publications/i/item/WHO-2019-nCoV-Post-COVID-19-condition-CA-Clinical-case-definition-2023-1 (accessed on 3 September 2024).
  8. Rao, S.; Gross, R.S.; Mohandas, S.; Stein, C.R.; Case, A.; Dreyer, B.; Pajor, N.M.; Bunnell, H.T.; Warburton, D.; Berg, E.; et al. Postacute Sequelae of SARS-CoV-2 in Children. Pediatrics 2024, 153, e2023062570. [Google Scholar] [CrossRef] [PubMed]
  9. Schiavo, M.; Di Filippo, P.; Porreca, A.; Prezioso, G.; Orlandi, G.; Rossi, N.; Chiarelli, F.; Attanasi, M. Potential Predictors of Long COVID in Italian Children: A Cross-Sectional Survey. Children 2024, 11, 221. [Google Scholar] [CrossRef] [PubMed]
  10. Johnston, R.; Sonnappa, S.; Goddings, A.-L.; Whittaker, E.; Segal, T.Y. A review of post COVID syndrome pathophysiology, clinical presentation and management in children and young people. Paediatr. Respir. Rev. 2024; in press. [Google Scholar] [CrossRef] [PubMed]
  11. Behnood, S.; Newlands, F.; O’mahoney, L.; Ghahfarokhi, M.H.; Muhid, M.Z.; Dudley, J.; Stephenson, T.; Ladhani, S.N.; Bennett, S.; Viner, R.M.; et al. Persistent symptoms are associated with long term effects of COVID-19 among children and young people: Results from a systematic review and meta-analysis of controlled studies. PLoS ONE 2023, 18, e0293600. [Google Scholar] [CrossRef]
  12. Pellegrino, R.; Chiappini, E.; Licari, A.; Galli, L.; Marseglia, G.L. Prevalence and clinical presentation of long COVID in children: A systematic review. Eur. J. Pediatr. 2022, 181, 3995–4009. [Google Scholar] [CrossRef] [PubMed]
  13. Toepfner, N.; Brinkmann, F.; Augustin, S.; Stojanov, S.; Behrends, U. Long COVID in pediatrics—epidemiology, diagnosis, and management. Eur. J. Pediatr. 2024, 183, 1543–1553. [Google Scholar] [CrossRef] [PubMed]
  14. Vahratian, A.; Adjaye-Gbewonyo, D.; Lin, J.M.S.; Saydah, S. Long COVID in Children: United States, 2022. NCHS Data Brief 2023, 479, 1–6. [Google Scholar]
  15. Zhang, J.; Kuang, T.; Liu, X. Advances in researches on long coronavirus disease in children: A narrative review. Transl. Pediatr. 2024, 13, 318–328. [Google Scholar] [CrossRef]
  16. Alizadeh, A.H.; Nurchis, M.C.; Garlasco, J.; Mara, A.; Pascucci, D.; Damiani, G.; Gianino, M.M. Pediatric post COVID-19 condition: An umbrella review of the most common symptoms and associated factors. Eur. J. Public Health 2024, 34, 517–523. [Google Scholar] [CrossRef] [PubMed]
  17. Zhang, Y.; Romieu-Hernandez, A.; Boehmer, T.K.; Azziz-Baumgartner, E.; Carton, T.W.; Gundlapalli, A.V.; Fearrington, J.; Nagavedu, K.; Dea, K.; Moyneur, E.; et al. Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults. BMC Infect. Dis. 2024, 24, 181. [Google Scholar] [CrossRef]
  18. Floridia, M.; Grassi, T.; Giuliano, M.; Tiple, D.; Pricci, F.; Villa, M.; Silenzi, A.; Onder, G. Characteristics of Long-COVID Care Centers in Italy. A National Survey of 124 Clinical Sites. Front. Public Health 2022, 10, 975527. [Google Scholar] [CrossRef]
  19. Post COVID-19 CRF from the WHO Global Clinical Platform for COVID-19. Available online: https://www.who.int/publications/i/item/global-covid-19-clinical-platform-case-report-form-(crf)-for-post-covid-conditions-(post-covid-19-crf-) (accessed on 3 September 2024).
  20. Castriotta, L.; Onder, G.; Rosolen, V.; Beorchia, Y.; Fanizza, C.; Bellini, B.; Floridia, M.; Giuliano, M.; Silenzi, A.; Pricci, F.; et al. Examining potential Long COVID effects through utilization of healthcare resources: A retrospective, population-based, matched cohort study comparing individuals with and without prior SARS-CoV-2 infection. Eur. J. Public Health 2024, 34, 592–599. [Google Scholar] [CrossRef] [PubMed]
  21. Floridia, M.; Giuliano, M.; Weimer, L.E.; Ciardi, M.R.; Agostoni, P.; Palange, P.; Querini, P.R.; Zucco, S.; Tosato, M.; Forte, A.L.; et al. Symptom profile, case and symptom clustering, clinical and demographic characteristics of a multicentre cohort of 1297 patients evaluated for Long-COVID. BMC Med. 2024, 22, 532. [Google Scholar] [CrossRef]
  22. Chen, E.Y.B.; Morrow, A.K.; Malone, L.A. Exploring the Influence of Pre-Existing Conditions and Infection Factors on Pediatric Long COVID Symptoms and Quality of Life. Am. J. Phys. Med. Rehabil. 2024, 103, 567–574. [Google Scholar] [CrossRef]
  23. Seylanova, N.; Chernyavskaya, A.; Degtyareva, N.; Mursalova, A.; Ajam, A.; Xiao, L.; Aktulaeva, K.; Roshchin, P.; Bobkova, P.; Aiyegbusi, O.L.; et al. Core outcome measurement set for research and clinical practice in post-COVID-19 condition (long COVID) in children and young people: An international Delphi consensus study “PC-COS Children”. Eur. Respir. J. 2024, 63, 2301761. [Google Scholar] [CrossRef] [PubMed]
  24. Zhu, Y.; Almeida, F.J.; Baillie, J.K.; Bowen, A.C.; Britton, P.N.; Brizuela, M.E.; Buonsenso, D.; Burgner, D.; Chew, K.Y.; Chokephaibulkit, K.; et al. International Pediatric COVID-19 Severity Over the Course of the Pandemic. JAMA Pediatr. 2023, 177, 1073–1084. [Google Scholar] [CrossRef] [PubMed]
  25. Noij, L.C.E.; Blankestijn, J.M.; Lap, C.R.; van Houten, M.A.; Biesbroek, G.; der Zee, A.-H.M.-V.; Abdel-Aziz, M.I.; van Goudoever, J.B.; Alsem, M.W.; Brackel, C.L.H.; et al. Clinical-based phenotypes in children with pediatric post-COVID-19 condition. World J. Pediatr. 2024, 20, 682–691. [Google Scholar] [CrossRef]
  26. Weakley, K.E.M.; Schikler, A.M.; Green, J.V.; Blatt, D.B.; Barton, S.M.M.; Statler, V.A.M.; Feygin, Y.; Marshall, G.S. Clinical Features and Follow-up of Referred Children and Young People with Long COVID. Pediatr. Infect. Dis. J. 2023, 42, 1093–1099. [Google Scholar] [CrossRef] [PubMed]
  27. Palacios, S.; Krivchenia, K.; Eisner, M.; Young, B.; Ramilo, O.; Mejias, A.; Lee, S.; Kopp, B.T. Long-term pulmonary sequelae in adolescents post-SARS-CoV-2 infection. Pediatr. Pulmonol. 2022, 57, 2455–2463. [Google Scholar] [CrossRef]
  28. Buonsenso, D.; Morello, R.; De Rose, C.; Spera, F.; Baldi, F. Long-term outcome of a child with postcovid condition: Role of cardiopulmonary exercise testing and 24-h Holter ECG to monitor treatment response and recovery. Pediatr. Pulmonol. 2023, 58, 2944–2946. [Google Scholar] [CrossRef] [PubMed]
  29. Buonsenso, D.; Camporesi, A.; Morello, R.; De Rose, C.; Fracasso, M.; Valentini, P. Paediatric long COVID studies should focus on clinical evaluations that examine the impact on daily life not just self-reported symptoms. Acta Paediatr. 2024, 113, 778–780. [Google Scholar] [CrossRef]
  30. Gutfreund, M.C.; Kobayashi, T.; Callado, G.Y.; Pardo, I.; Hsieh, M.K.; Lin, V.; Perencevich, E.N.; Salinas, J.L.; Edmond, M.B.; Mendonça, E.; et al. The effectiveness of the COVID-19 vaccines in the prevention of post-COVID conditions in children and adolescents: A systematic literature review and meta-analysis. Antimicrob. Steward. Health Epidemiol. 2024, 4, e54. [Google Scholar] [CrossRef] [PubMed]
  31. Man, M.A.; Rosca, D.; Bratosin, F.; Fira-Mladinescu, O.; Ilie, A.C.; Burtic, S.-R.; Fildan, A.P.; Fizedean, C.M.; Jianu, A.M.; Negrean, R.A.; et al. Impact of Pre-Infection COVID-19 Vaccination on the Incidence and Severity of Post-COVID Syndrome: A Systematic Review and Meta-Analysis. Vaccines 2024, 12, 189. [Google Scholar] [CrossRef]
  32. Razzaghi, H.; Forrest, C.B.; Hirabayashi, K.; Wu, Q.; Allen, A.J.; Rao, S.; Chen, Y.; Bunnell, H.T.; Chrischilles, E.A.; Cowell, L.G.; et al. Vaccine Effectiveness Against Long COVID in Children. Pediatrics 2024, 153, e2023064446. [Google Scholar] [CrossRef]
Children 12 00028 g001
Figure 1. Prevalence of persisting symptoms in contemporarily enrolled adults and adolescents.
Figure 1. Prevalence of persisting symptoms in contemporarily enrolled adults and adolescents.
Children 12 00028 g001
Children 12 00028 g002
Figure 2. Follow up prevalence and relative reduction of the symptoms most commonly reported at first evaluation.
Figure 2. Follow up prevalence and relative reduction of the symptoms most commonly reported at first evaluation.
Children 12 00028 g002
Table 1. Population characteristics.
Table 1. Population characteristics.
AllFemaleMalep
Sex: (n, %)97 (100%)53 (54.6%)44 (45.4%)
Age (years, mean, SD)13.5 (1.5)13.4 (1.5)13.6 (1.6)0.502
Comorbidities (n, %)8 (8.2%)4 (7.5%)4 (9.1%)0.783
 Asthma330
 Tourette syndrome, anxiety101
 Obesity, pituitary hypoplasia, metabolic syndrome, anxiety101
 Hashimoto thyroiditis101
 Epilepsy101
 Trisomy 21110
Vaccinated before infection * 40 (43.0%)21 (42.0%)19 (44.2%)0.832
Not vaccinated53 (57.0%)29 (58.0%)24 (55.8%)
Acute infection pandemic phase: Pre-Omicron46 (47.4%)25 (47.2%)21 (47.7%)0.956
               Omicron51 (52.6%)28 (52.8%)23 (52.3%)
Hospitalised during acute phase (n: 96):3 (3.1%)1 (1.9%)2 (4.5%)0.462
Admitted to intensive care unit:000
WHO COVID severity grade:    Mild88 (90.7%)49 (92.5%)39 (88.6%)0.482
               Moderate7 (7.2%)3 (5.7%)4 (9.1%)
               Severe1 (1.0%)0 (0%)1 (2.3%)
               Critical000
               Unknown1 (1.0%)1 (1.9%)0 (0%)
Respiratory assistance:       None96 (99.0%)52 (98.1%)44 (100%)0.360
               Unknown1 (1.0%)1 (1.9%)0 (0%)
SD: standard deviation; * N with known vaccination status = 93. Vaccinated: any dose.
Table 2. Symptom prevalence by phase of the pandemic, presence of comorbidities and severity of acute disease.
Table 2. Symptom prevalence by phase of the pandemic, presence of comorbidities and severity of acute disease.
Phase of PandemicComorbiditiesSeverity of Acute Disease
All
(n: 97)		Omicron (n: 51)Pre-Omicron
(n: 46)		p ValueYes
(n: 8)		No
(n: 89)		p ValueMild
(n: 88)		Moderate/Severe
(n: 8)		p Value
Fatigue (n, %)61 (62.9%)37 (72.5)24 (52.2)0.0382 (25.0)59 (66.3)0.04954 (61.4)6 (75.0)0.706
Dyspnea (n, %)42 (43.3%)18 (35.3)24 (52.2)0.0944 (50.0)38 (42.7)0.72437 (42.0)5 (62.5)0.292
Headache (n, %)28 (28.9%)16 (31.4)12 (26.1)0.5662 (25.0)26 (29.2)1.00025 (28.4)3 (37.5)0.688
Thoracic pain (n, %)22 (22.7%)8 (15.7)14 (30.4)0.0835 (62.5)17 (19.1)0.01417 (19.3)4 (50.0)0.066
Diarrhea (n, %)20 (20.6%)8 (15.7)12 (26.1)0.2061 (12.5)19 (21.3)1.00019 (21.6)1 (12.5)1.000
Palpitations, tachycardia (n, %)17 (17.5%)8 (15.7)9 (19.6)0.6161 (12.5)16 (18.0)1.00013 (14.8)4 (50.0)0.031
Joint pain or swelling (n, %)15 (15.5%)7 (13.7)8 17.4)0.6181 (12.5)14 (15.7)1.00012 (13.6)3 (37.5)0.107
Difficult concentration (n, %)14 (14.4%)6 (11.8)8 (17.4)0.4311 (12.5)13 (14.6)1.00013 (14.8)1 (12.5)1.000
Muscle pain (n, %)12 (12.4%)5 (9.8)7 (15.2)0.4190 (0)12 (13.5)0.5909 (10.2)3 (37.5)0.059
Taste reduction (n, %)8 (8.2%)2 (3.9)6 (13.0)0.1450 (0)8 (9.0)1.0008 (9.1)0 (0)1.000
Smell reduction (n, %)8 (8.2%)2 (3.9)6 (13.0)0.1451 (12.5)7 (7.9)0.5118 (9.1)0 (0)1.000
Fever (n, %)6 (6.2%)1 (2.2)5 (9.8)0.2081 (12.5)5 (5.6)0.4124 (4.5)2 (25.0)0.077
Skin disorders, alopecia (n, %)5 (5.2%)3 (5.9)2 (4.3)1.0001 (12.5)4 (4.5)0.3565 (5.7)0 (0)1.000
Other less frequently reported symptoms included brain fog (4 cases), loss of appetite (4 cases), memory loss (3 cases), sleep disturbances (2 cases), menstrual disorders (1 case), visual disturbances (1 case), nausea or vomiting (1 case), depressed mood (1 case), cough (1 case), and anxiety (1 case).
Table 3. Case clustering by clinical and demographic variables and symptoms reported.
Table 3. Case clustering by clinical and demographic variables and symptoms reported.
Cluster 1Cluster 2p
N (96)6432
Female (n, %)38 (59.4)14 (43.8)0.148
Omicron phase of the pandemic (n, %)22 (34.4)28 (87.5)<0.001
Presence of comorbidities (n, %)5 (7.8)3 (9.4)1.000
Acute infection moderate or severe (n, %)7 (10.9)1 (3.1)0.262
Number of symptoms reported (mean, SD)3.5 (1.8)1.5 (0.8)<0.001
Fatigue (n, %)38 (59.4)22 (68.8)0.371
Dyspnea (n, %)42 (65.6)0 (0)<0.001
Headache (n, %)16 (25.0)12 (37.5)0.204
Thoracic pain (n, %)18 (28.1)3 (9.4)0.040
Diarrhea (n, %)19 (29.7)1 (3.1)0.003
Palpitations, tachycardia (n, %)15 (23.4)2 (6.3)0.047
Joint pain or swelling (n, %)15 (23.4)0 (0)0.002
Difficult concentration (n, %)13 (20.3)1 (3.1)0.030
Muscle pain (n, %)12 (18.8)0 (0)0.007
Taste reduction (n, %)8 (12.5)0 (0)0.049
Smell reduction (n, %)8 (12.5)0 (0)0.049
Fever (n, %)2 (3.1)4 (12.5)0.093
Skin disorders, alopecia (n, %)4 (6.3)1 (3.1)0.662
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Floridia, M.; Buonsenso, D.; Macculi, L.; Weimer, L.E.; Giuliano, M.; Pricci, F.; Bianchi, L.; Toraldo, D.M.; Onder, G.; The ISS Long-COVID Study Group. Adolescents with Persistent Symptoms Following Acute SARS-CoV-2 Infection (Long-COVID): Symptom Profile, Clustering and Follow-Up Symptom Evaluation. Children 2025, 12, 28. https://doi.org/10.3390/children12010028

AMA Style

Floridia M, Buonsenso D, Macculi L, Weimer LE, Giuliano M, Pricci F, Bianchi L, Toraldo DM, Onder G, The ISS Long-COVID Study Group. Adolescents with Persistent Symptoms Following Acute SARS-CoV-2 Infection (Long-COVID): Symptom Profile, Clustering and Follow-Up Symptom Evaluation. Children. 2025; 12(1):28. https://doi.org/10.3390/children12010028

Chicago/Turabian Style

Floridia, Marco, Danilo Buonsenso, Laura Macculi, Liliana Elena Weimer, Marina Giuliano, Flavia Pricci, Leila Bianchi, Domenico Maurizio Toraldo, Graziano Onder, and The ISS Long-COVID Study Group. 2025. "Adolescents with Persistent Symptoms Following Acute SARS-CoV-2 Infection (Long-COVID): Symptom Profile, Clustering and Follow-Up Symptom Evaluation" Children 12, no. 1: 28. https://doi.org/10.3390/children12010028

APA Style

Floridia, M., Buonsenso, D., Macculi, L., Weimer, L. E., Giuliano, M., Pricci, F., Bianchi, L., Toraldo, D. M., Onder, G., & The ISS Long-COVID Study Group. (2025). Adolescents with Persistent Symptoms Following Acute SARS-CoV-2 Infection (Long-COVID): Symptom Profile, Clustering and Follow-Up Symptom Evaluation. Children, 12(1), 28. https://doi.org/10.3390/children12010028

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop