Skip to main content
Top
Published in: Italian Journal of Pediatrics 1/2024

Open Access 01-12-2024 | Long-COVID Syndrome | Research

Long-term effects of SARS-CoV-2 infection in hospitalized children: findings from an Italian single-center study

Published in: Italian Journal of Pediatrics | Issue 1/2024

Login to get access

Abstract

Background

Limited evidence exists regarding the association between COVID-19 and Long COVID manifestations in children, particularly concerning variants of concern (VOCs). We aimed to characterize a cohort of pediatric patients hospitalized with confirmed acute SARS-CoV-2 and monitor them for Long COVID symptoms. Additionally, it seeks to explore any potential correlations between VOCs and clinical symptoms.

Methods

We conducted a prospective study involving children hospitalized from November 2021 to March 2023, with confirmed acute SARS-CoV-2 infection. A telephone survey was conducted at 3-6-12 months after discharge.

Results

We included 167 patients (77 F/90 M). Upon hospital admission, 95.5% of patients presented as symptomatic. Regarding patients for whom it was feasible to determine the SARS-CoV-2 variant (n = 51), the Delta variant was identified in 11 children (21.6%) and Omicron variant in the remaining 40 patients (78.4%: 27.5% BA.1 variant; 15% BA.2 variant; 57.5% BA.5 variant). 19 patients (16.5%) reported experiencing at least one symptom indicative of Long COVID (weight loss 31.6%, inappetence 26.3%, chronic cough 21.1%, fatigue 21.1%, and sleep disturbances, wheezing, abdominal pain and mood disorders 15.8%). In only 4 patients with Long COVID we could identified a specific SARS-CoV-2 variant (3 Omicron: 2 BA.1 and 1 BA.2; 1 Delta).

Conclusions

this study underscores that long COVID is a significant concern in the pediatric population. Our data reinforce the importance of continuously monitoring the impact of long-COVID in infants, children, and adolescents. A follow-up following SARS-CoV-2 infection is therefore advisable, with symptom investigation tailored to the patient’s age.
Appendix
Available only for authorised users
Literature
1.
go back to reference WHO. A Clinical Case Definition of Post COVID-19 Condition by a Delphi Consensus 2021. WHO. A Clinical Case Definition of Post COVID-19 Condition by a Delphi Consensus 2021.
2.
go back to reference Dennis A, Wamil M, Alberts J, Oben J, Cuthbertson DJ, Wootton D, Crooks M, Gabbay M, Brady M, Hishmeh L, Attree E, Heightman M, Banerjee R, Banerjee A, COVERSCAN study investigators. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study. BMJ Open. 2021;11(3):e048391. https://doi.org/10.1136/bmjopen-2020-048391.CrossRefPubMed Dennis A, Wamil M, Alberts J, Oben J, Cuthbertson DJ, Wootton D, Crooks M, Gabbay M, Brady M, Hishmeh L, Attree E, Heightman M, Banerjee R, Banerjee A, COVERSCAN study investigators. Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a prospective, community-based study. BMJ Open. 2021;11(3):e048391. https://​doi.​org/​10.​1136/​bmjopen-2020-048391.CrossRefPubMed
3.
go back to reference Zhang P, Li J, Liu H, Han N, Ju J, Kou Y, Chen L, Jiang M, Pan F, Zheng Y, Gao Z, Jiang B. (2020). Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study. Bone Res. 2020;8:8. https://doi.org/10.1038/s41413-020-0084-5. Erratum in: Bone Res. 21;8:34. Zhang P, Li J, Liu H, Han N, Ju J, Kou Y, Chen L, Jiang M, Pan F, Zheng Y, Gao Z, Jiang B. (2020). Long-term bone and lung consequences associated with hospital-acquired severe acute respiratory syndrome: a 15-year follow-up from a prospective cohort study. Bone Res. 2020;8:8. https://​doi.​org/​10.​1038/​s41413-020-0084-5. Erratum in: Bone Res. 21;8:34.
5.
go back to reference Heiss R, Tan L, Schmidt S, Regensburger AP, Ewert F, Mammadova D, Buehler A, Vogel-Claussen J, Voskrebenzev A, Rauh M, Rompel O, Nagel AM, Lévy S, Bickelhaupt S, May MS, Uder M, Metzler M, Trollmann R, Woelfle J, Wagner AL, Knieling F. Pulmonary Dysfunction after Pediatric COVID-19. Radiology. 2023;306(3):e221250. https://doi.org/10.1148/radiol.221250.CrossRefPubMed Heiss R, Tan L, Schmidt S, Regensburger AP, Ewert F, Mammadova D, Buehler A, Vogel-Claussen J, Voskrebenzev A, Rauh M, Rompel O, Nagel AM, Lévy S, Bickelhaupt S, May MS, Uder M, Metzler M, Trollmann R, Woelfle J, Wagner AL, Knieling F. Pulmonary Dysfunction after Pediatric COVID-19. Radiology. 2023;306(3):e221250. https://​doi.​org/​10.​1148/​radiol.​221250.CrossRefPubMed
7.
go back to reference Matschke J, Lütgehetmann M, Hagel C, Sperhake JP, Schröder AS, Edler C, Mushumba H, Fitzek A, Allweiss L, Dandri M, Dottermusch M, Heinemann A, Pfefferle S, Schwabenland M, Sumner Magruder D, Bonn S, Prinz M, Gerloff C, Püschel K, Krasemann S, Aepfelbacher M, Glatzel M. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol. 2020;19(11):919–29. https://doi.org/10.1016/S1474-4422(20)30308-2.CrossRefPubMedPubMedCentral Matschke J, Lütgehetmann M, Hagel C, Sperhake JP, Schröder AS, Edler C, Mushumba H, Fitzek A, Allweiss L, Dandri M, Dottermusch M, Heinemann A, Pfefferle S, Schwabenland M, Sumner Magruder D, Bonn S, Prinz M, Gerloff C, Püschel K, Krasemann S, Aepfelbacher M, Glatzel M. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol. 2020;19(11):919–29. https://​doi.​org/​10.​1016/​S1474-4422(20)30308-2.CrossRefPubMedPubMedCentral
9.
go back to reference Raman B, Cassar MP, Tunnicliffe EM, Filippini N, Griffanti L, Alfaro-Almagro F, Okell T, Sheerin F, Xie C, Mahmod M, Mózes FE, Lewandowski AJ, Ohuma EO, Holdsworth D, Lamlum H, Woodman MJ, Krasopoulos C, Mills R, McConnell FAK, Wang C, Arthofer C, Lange FJ, Andersson J, Jenkinson M, Antoniades C, Channon KM, Shanmuganathan M, Ferreira VM, Piechnik SK, Klenerman P, Brightling C, Talbot NP, Petousi N, Rahman NM, Ho LP, Saunders K, Geddes JR, Harrison PJ, Pattinson K, Rowland MJ, Angus BJ, Gleeson F, Pavlides M, Koychev I, Miller KL, Mackay C, Jezzard P, Smith SM, Neubauer S. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine. 2021;31:100683. https://doi.org/10.1016/j.eclinm.2020.100683.CrossRefPubMedPubMedCentral Raman B, Cassar MP, Tunnicliffe EM, Filippini N, Griffanti L, Alfaro-Almagro F, Okell T, Sheerin F, Xie C, Mahmod M, Mózes FE, Lewandowski AJ, Ohuma EO, Holdsworth D, Lamlum H, Woodman MJ, Krasopoulos C, Mills R, McConnell FAK, Wang C, Arthofer C, Lange FJ, Andersson J, Jenkinson M, Antoniades C, Channon KM, Shanmuganathan M, Ferreira VM, Piechnik SK, Klenerman P, Brightling C, Talbot NP, Petousi N, Rahman NM, Ho LP, Saunders K, Geddes JR, Harrison PJ, Pattinson K, Rowland MJ, Angus BJ, Gleeson F, Pavlides M, Koychev I, Miller KL, Mackay C, Jezzard P, Smith SM, Neubauer S. Medium-term effects of SARS-CoV-2 infection on multiple vital organs, exercise capacity, cognition, quality of life and mental health, post-hospital discharge. EClinicalMedicine. 2021;31:100683. https://​doi.​org/​10.​1016/​j.​eclinm.​2020.​100683.CrossRefPubMedPubMedCentral
10.
go back to reference Yong SJ. (2021). Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 202;53(10):737–754. Yong SJ. (2021). Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis (Lond). 202;53(10):737–754.
11.
go back to reference Karlsson AC, Humbert M, Buggert M. The known unknowns of T cell immunity to COVID. Sci Immunol. 2020;5(53):19.CrossRef Karlsson AC, Humbert M, Buggert M. The known unknowns of T cell immunity to COVID. Sci Immunol. 2020;5(53):19.CrossRef
12.
go back to reference Hirotsu Y, Maejima M, Shibusawa M, Amemiya K, Nagakubo Y, Hosaka K, Sueki H, Hayakawa M, Mochizuki H, Tsutsui T, Kakizaki Y, Miyashita Y, Omata M. Analysis of a persistent viral shedding patient infected with SARS-CoV-2 by RT-qPCR, FilmArray Respiratory Panel v2.1, and antigen detection. J Infect Chemother. 2021;27(2):406–9. https://doi.org/10.1016/j.jiac.2020.10.026.CrossRefPubMed Hirotsu Y, Maejima M, Shibusawa M, Amemiya K, Nagakubo Y, Hosaka K, Sueki H, Hayakawa M, Mochizuki H, Tsutsui T, Kakizaki Y, Miyashita Y, Omata M. Analysis of a persistent viral shedding patient infected with SARS-CoV-2 by RT-qPCR, FilmArray Respiratory Panel v2.1, and antigen detection. J Infect Chemother. 2021;27(2):406–9. https://​doi.​org/​10.​1016/​j.​jiac.​2020.​10.​026.CrossRefPubMed
16.
go back to reference Cojocaru M, Cojocaru IM, Silosi I, et al. Manifestations of systemic lupus erythematosus. Maedica (Bucur). 2011;6(4):330–6.PubMed Cojocaru M, Cojocaru IM, Silosi I, et al. Manifestations of systemic lupus erythematosus. Maedica (Bucur). 2011;6(4):330–6.PubMed
19.
go back to reference Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, Chan V, Ling L, Joynt G, Hui DS, Chow KM, Ng SSS, Li TC, Ng RW, Yip TC, Wong GL, Chan FK, Wong CK, Chan PK, Ng SC. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70(4):698–706. https://doi.org/10.1136/gutjnl-2020-323020.CrossRefPubMed Yeoh YK, Zuo T, Lui GC, Zhang F, Liu Q, Li AY, Chung AC, Cheung CP, Tso EY, Fung KS, Chan V, Ling L, Joynt G, Hui DS, Chow KM, Ng SSS, Li TC, Ng RW, Yip TC, Wong GL, Chan FK, Wong CK, Chan PK, Ng SC. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021;70(4):698–706. https://​doi.​org/​10.​1136/​gutjnl-2020-323020.CrossRefPubMed
20.
go back to reference Howard-Jones AR, Burgner DP, Crawford NW, Goeman E, Gray PE, Hsu P, Kuek S, McMullan BJ, Tosif S, Wurzel D, Bowen AC, Danchin M, Koirala A, Sharma K, Yeoh DK, Britton PN. COVID-19 in children. II: Pathogenesis, disease spectrum and management. J Paediatr Child Health. 2022;58(1):46–53. https://doi.org/10.1111/jpc.15811.CrossRefPubMed Howard-Jones AR, Burgner DP, Crawford NW, Goeman E, Gray PE, Hsu P, Kuek S, McMullan BJ, Tosif S, Wurzel D, Bowen AC, Danchin M, Koirala A, Sharma K, Yeoh DK, Britton PN. COVID-19 in children. II: Pathogenesis, disease spectrum and management. J Paediatr Child Health. 2022;58(1):46–53. https://​doi.​org/​10.​1111/​jpc.​15811.CrossRefPubMed
24.
go back to reference Wanga V, Gerdes ME, Shi DS, Choudhary R, Dulski TM, Hsu S, Idubor OI, Webber BJ, Wendel AM, Agathis NT, Anderson K, Boyles T, Chiu SK, Click ES, Da Silva J, Dupont H, Evans M, Gold JAW, Haston J, Logan P, Maloney SA, Martinez M, Natarajan P, BMBS1, Spicer KB, Swancutt M, Stevens VA, Brown J, Chandra G, Light M, Barr FE, Snowden J, Kociolek LK, McHugh M, Wessel D, Simpson JN, Gorman KC, Breslin KA, DeBiasi RL, Thompson A, Kline MW, Boom JA, Singh IR, Dowlin M, Wietecha M, Schweitzer B, Morris SB, Koumans EH, Ko JY, Kimball AA, Siegel DA. (2021). Characteristics and Clinical Outcomes of Children and Adolescents Aged < 18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021. MMWR Morb Mortal Wkly Rep. 70(5152):1766–1772. https://doi.org/10.15585/mmwr.mm705152a3. Erratum in: MMWR Morb Mortal Wkly Rep. 2022;71(5):185. Wanga V, Gerdes ME, Shi DS, Choudhary R, Dulski TM, Hsu S, Idubor OI, Webber BJ, Wendel AM, Agathis NT, Anderson K, Boyles T, Chiu SK, Click ES, Da Silva J, Dupont H, Evans M, Gold JAW, Haston J, Logan P, Maloney SA, Martinez M, Natarajan P, BMBS1, Spicer KB, Swancutt M, Stevens VA, Brown J, Chandra G, Light M, Barr FE, Snowden J, Kociolek LK, McHugh M, Wessel D, Simpson JN, Gorman KC, Breslin KA, DeBiasi RL, Thompson A, Kline MW, Boom JA, Singh IR, Dowlin M, Wietecha M, Schweitzer B, Morris SB, Koumans EH, Ko JY, Kimball AA, Siegel DA. (2021). Characteristics and Clinical Outcomes of Children and Adolescents Aged < 18 Years Hospitalized with COVID-19 - Six Hospitals, United States, July-August 2021. MMWR Morb Mortal Wkly Rep. 70(5152):1766–1772. https://​doi.​org/​10.​15585/​mmwr.​mm705152a3. Erratum in: MMWR Morb Mortal Wkly Rep. 2022;71(5):185.
25.
go back to reference Delahoy MJ, Ujamaa D, Whitaker M, O’Halloran A, Anglin O, Burns E, Cummings C, Holstein R, Kambhampati AK, Milucky J, Patel K, Pham H, Taylor CA, Chai SJ, Reingold A, Alden NB, Kawasaki B, Meek J, Yousey-Hindes K, Anderson EJ, Openo KP, Teno K, Weigel A, Kim S, Leegwater L, Bye E, Como-Sabetti K, Ropp S, Rudin D, Muse A, Spina N, Bennett NM, Popham K, Billing LM, Shiltz E, Sutton M, Thomas A, Schaffner W, Talbot HK, Crossland MT, McCaffrey K, Hall AJ, Fry AM, McMorrow M, Reed C, Garg S, Havers FP, COVID-NET Surveillance Team; COVID-NET Surveillance Team. Hospitalizations Associated with COVID-19 among children and adolescents - COVID-NET, 14 States, March 1, 2020-August 14, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(36):1255–60. https://doi.org/10.15585/mmwr.mm7036e2.CrossRefPubMedPubMedCentral Delahoy MJ, Ujamaa D, Whitaker M, O’Halloran A, Anglin O, Burns E, Cummings C, Holstein R, Kambhampati AK, Milucky J, Patel K, Pham H, Taylor CA, Chai SJ, Reingold A, Alden NB, Kawasaki B, Meek J, Yousey-Hindes K, Anderson EJ, Openo KP, Teno K, Weigel A, Kim S, Leegwater L, Bye E, Como-Sabetti K, Ropp S, Rudin D, Muse A, Spina N, Bennett NM, Popham K, Billing LM, Shiltz E, Sutton M, Thomas A, Schaffner W, Talbot HK, Crossland MT, McCaffrey K, Hall AJ, Fry AM, McMorrow M, Reed C, Garg S, Havers FP, COVID-NET Surveillance Team; COVID-NET Surveillance Team. Hospitalizations Associated with COVID-19 among children and adolescents - COVID-NET, 14 States, March 1, 2020-August 14, 2021. MMWR Morb Mortal Wkly Rep. 2021;70(36):1255–60. https://​doi.​org/​10.​15585/​mmwr.​mm7036e2.CrossRefPubMedPubMedCentral
26.
go back to reference Bloise S, Isoldi S, Marcellino A, De Luca E, Dilillo A, Mallardo S, Martucci V, Sanseviero M, Del Giudice E, Iorfida D, Leone R, Testa A, Frasacco B, Gizzone P, Proietti Ciolli C, Sinceri A, Zuliani F, Zanardi E, Gambarotto A, Lisa Grandinetti A, Ventriglia F, Lubrano R. (2022). Clinical picture and long-term symptoms of SARS-CoV-2 infection in an Italian pediatric population. Ital J Pediatr. 2022 48(1):79. https://doi.org/10.1186/s13052-022-01270-1. Bloise S, Isoldi S, Marcellino A, De Luca E, Dilillo A, Mallardo S, Martucci V, Sanseviero M, Del Giudice E, Iorfida D, Leone R, Testa A, Frasacco B, Gizzone P, Proietti Ciolli C, Sinceri A, Zuliani F, Zanardi E, Gambarotto A, Lisa Grandinetti A, Ventriglia F, Lubrano R. (2022). Clinical picture and long-term symptoms of SARS-CoV-2 infection in an Italian pediatric population. Ital J Pediatr. 2022 48(1):79. https://​doi.​org/​10.​1186/​s13052-022-01270-1.
28.
29.
go back to reference Jacobson KB, Rao M, Bonilla H, Subramanian A, Hack I, Madrigal M, et al. Patients with uncomplicated COVID-19 have long-term persistent symptoms and functional impairment similar to patients with severe COVID-19: a cautionary tale during a global pandemic. Clin Infect Dis. 2021;73:e826–9.CrossRefPubMed Jacobson KB, Rao M, Bonilla H, Subramanian A, Hack I, Madrigal M, et al. Patients with uncomplicated COVID-19 have long-term persistent symptoms and functional impairment similar to patients with severe COVID-19: a cautionary tale during a global pandemic. Clin Infect Dis. 2021;73:e826–9.CrossRefPubMed
30.
go back to reference Molteni E, Sudre CH, Canas LS, Bhopal SS, Hughes RC, Antonelli M, Murray B, Kläser K, Kerfoot E, Chen L, Deng J, Hu C, Selvachandran S, Read K, Capdevila Pujol J, Hammers A, Spector TD, Ourselin S, Steves CJ, Modat M, Absoud M, Duncan EL. (2021). Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc Health. 5(10):708–718. https://doi.org/10.1016/S2352-4642(21)00198-X. Epub 2021 Aug 3. Erratum in: Lancet Child Adolesc Health. 2021. Molteni E, Sudre CH, Canas LS, Bhopal SS, Hughes RC, Antonelli M, Murray B, Kläser K, Kerfoot E, Chen L, Deng J, Hu C, Selvachandran S, Read K, Capdevila Pujol J, Hammers A, Spector TD, Ourselin S, Steves CJ, Modat M, Absoud M, Duncan EL. (2021). Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2. Lancet Child Adolesc Health. 5(10):708–718. https://​doi.​org/​10.​1016/​S2352-4642(21)00198-X. Epub 2021 Aug 3. Erratum in: Lancet Child Adolesc Health. 2021.
31.
go back to reference Meherali S, Punjani N, Louie-Poon S, Abdul Rahim K, Das JK, Salam RA, Lassi ZS. Mental Health of children and adolescents amidst COVID-19 and Past Pandemics: a Rapid systematic review (2021). Int J Environ Res Public Health 18(7):3432. https://doi.org/10.3390/ijerph18073432. Meherali S, Punjani N, Louie-Poon S, Abdul Rahim K, Das JK, Salam RA, Lassi ZS. Mental Health of children and adolescents amidst COVID-19 and Past Pandemics: a Rapid systematic review (2021). Int J Environ Res Public Health 18(7):3432. https://​doi.​org/​10.​3390/​ijerph18073432.
33.
go back to reference Sandmann FG, Tessier E, Lacy J, Kall M, Van Leeuwen E, Charlett A et al. Long-term health-related quality of life in non-hospitalized coronavirus disease 2019 (COVID-19) cases with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in England: longitudinal analysis and cross-sectional comparison with controls (2022). Clin Infect Dis 75(1):e962–73. Sandmann FG, Tessier E, Lacy J, Kall M, Van Leeuwen E, Charlett A et al. Long-term health-related quality of life in non-hospitalized coronavirus disease 2019 (COVID-19) cases with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in England: longitudinal analysis and cross-sectional comparison with controls (2022). Clin Infect Dis 75(1):e962–73.
35.
go back to reference Kritikos A, Caruana G, Lazor-Blanchet C, Currat M, Chiche JD, Vollenweider P, Bart PA, Opota O, Greub G. Comparison of nasopharyngeal and saliva swab nucleic acid amplification and Rapid Antigen Testing to detect Omicron SARS-CoV-2 variant of concern: a prospective clinical trial (OMICRON). MicrobiolSpectr. 2022;10(6):e0392322. https://doi.org/10.1128/spectrum.03923-22.CrossRef Kritikos A, Caruana G, Lazor-Blanchet C, Currat M, Chiche JD, Vollenweider P, Bart PA, Opota O, Greub G. Comparison of nasopharyngeal and saliva swab nucleic acid amplification and Rapid Antigen Testing to detect Omicron SARS-CoV-2 variant of concern: a prospective clinical trial (OMICRON). MicrobiolSpectr. 2022;10(6):e0392322. https://​doi.​org/​10.​1128/​spectrum.​03923-22.CrossRef
Metadata
Title
Long-term effects of SARS-CoV-2 infection in hospitalized children: findings from an Italian single-center study
Publication date
01-12-2024
Published in
Italian Journal of Pediatrics / Issue 1/2024
Electronic ISSN: 1824-7288
DOI
https://doi.org/10.1186/s13052-024-01596-y

Other articles of this Issue 1/2024

Italian Journal of Pediatrics 1/2024 Go to the issue