COVID-19
Read Time: 4 mins

Long Coronavirus Disease 2019 in Children

Published Online: September 20th 2022 touchREVIEWS in Infectious Diseases. 2022;1(1):Online ahead of journal publication
Authors: Katelyn Krivchenia
Quick Links:
Abstract
Article
Article Information
Abstract:
Overview

Katelyn Krivchenia

Katelyn Krivchenia, MD, is a paediatric pulmonologist at Nationwide Children’s Hospital and an assistant professor of paediatrics at The Ohio State University College of Medicine. She is director of the Interstitial and Rare Lung Disease Program as well as director of the Infant Cystic Fibrosis and Newborn Screening Program. Dr Krivchenia has been managing paediatric patients with long coronavirus disease 2019 since the creation of her institution’s Pediatric Pulmonary Post-COVID clinic in early 2021.

Article:

It has now been over 2 years since the start of the coronavirus disease 2019 (COVID-19) pandemic, and millions of cases have been reported worldwide. It is increasingly being recognized that many individuals suffer from debilitating symptoms for months after the acute phase of the disease. This has been termed long COVID and is a heterogeneous condition comprising a range of symptoms, for which a number of definitions exist.1,2 To date, most research on long COVID has focused on adults. However, long COVID is also prevalent among paediatric populations.

In an expert interview, Dr Katelyn Krivchenia discusses the incidence, risk factors and severity of long COVID in children.

Q. What studies have investigated long COVID in children, and what are their limitations?

Most of the clinical research addressing long COVID in paediatrics has been descriptive in nature, with attempts to define its prevalence and describe signs and symptoms experienced after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Study results have relied mostly on self-reported symptoms by the patient or guardian, often through surveys by phone or in person. The lack of clarity surrounding the definition of long COVID has made it a challenging entity to study, with very few (if any) truly objective measures available for its diagnosis or monitoring. Current suggested definitions include signs or symptoms developing and persisting for more than 4 weeks1 or more than 12 weeks2 following COVID-19 that cannot be otherwise explained.

Q. What have study data taught us about the incidence, risk factors and severity of long COVID in children?

A recent meta-analysis evaluating more than 80,000 children and adolescents across 12 countries found that 25.2% of children under the age of 18 reported one or more symptoms more than 4 weeks following SARS-CoV-2 infection.3 Whilst more than 40 signs and symptoms were identified, the most commonly reported manifestations were mood symptoms, fatigue, sleep disorders, headache and respiratory symptoms.3 An Italian study of over 600 children aged 16 years or younger suggested that having symptomatic COVID-19 increased the likelihood of developing long COVID symptoms compared with children who were asymptomatic.4 Additionally, increasing age in this cohort of patients also increased the likelihood of long COVID symptoms, particularly those related to neurologic and psychiatric symptoms and fatigue. Respiratory symptoms were more common in children younger than 5 years.4 The Italian study suggested that children with pre-existing medical conditions did not seem to be at an increased risk of developing long COVID, and, in fact, the presence of immunodeficiency has been associated with a decreased incidence of long COVID symptoms.4,5

Q. What different manifestations of long COVID have been reported in children?

Mood symptoms, including symptoms of depression and anxiety, are commonly reported by children with long COVID. Children or their guardians may also report difficulties with cognitive function and task completion during school or daily household tasks, which are sometimes termed ‘brain fog’. Fatigue is frequently reported and sometimes difficult to separate from mood symptoms or its association with reports of impaired sleep or exertional dyspnoea.

The most common respiratory symptoms reported by paediatric patients include exertional dyspnoea, cough and exercise intolerance.6 Lung function testing in patients with long COVID may show evidence of airway obstruction (15%) or bronchodilator responsiveness (28–30%), while plethysmography and diffusion capacity are generally normal in these patients.7 Evaluating for paroxysmal vocal fold movement disorder may also be warranted, as this has been reported in both the paediatric and adult population.

Symptoms of dysautonomia, including orthostatic hypotension, positional orthostatic tachycardia syndrome and orthostatic symptoms not meeting the criteria for these diagnoses, are commonly reported. This has raised the concern of the possible overlap of long COVID with myalgic encephalomyelitis/chronic fatigue syndrome.8

Q. How can we distinguish the long-term symptoms caused by SARS-CoV-2 infection from pandemic-related symptoms?

Studies using age-matched negative controls may help us distinguish the symptoms of long COVID from those related to the pandemic. Reported symptoms of depression and anxiety in children and adolescents are higher than in pre-pandemic conditions worldwide.9 Whilst many posit that mood symptoms of long COVID are due to pandemic-related isolation, research in young adults has found significantly higher objective scores of depression and anxiety symptoms in patients post-COVID-19 compared with their non-infected peers, even after controlling for days of social distancing, amount of social interaction and number of significant life changes during the pandemic.10 Additionally, patients with a history of COVID-19 had a significant decrease in executive functioning during computer-based testing compared with their non-infected peers.10

A large cohort study from the Public Health England database of more than 50,000 patients revealed that adolescents were significantly more likely to experience fatigue, dyspnoea, chest pain, headaches, difficulty with attention and muscle pains 3 months after SARS-CoV-2 infection when compared with their age-matched, SARS-CoV-2-negative peers.11 While pandemic-related isolation has likely had an impact on the physical conditioning of children worldwide, it does not account for the persistence in patients with long COVID now years out from the initial lockdown.

Q. What questions remain unanswered regarding long COVID in children?

There is obviously much to learn about the cause of long COVID symptoms and how best to treat them. Researchers have proposed a persistent viral antigen presence triggering a dysregulated immune response resulting in low-grade inflammation and multi-organ involvement as a major cause of long COVID sequelae.12 Other potential contributing mechanisms include virus-specific damage to various organ systems and, for adult patients, sequelae of post-intensive care.13

Once the underlying mechanisms of long COVID are better understood, studies addressing effective and safe therapies should move forward, including those with a focus on paediatric patients. Quantifying disease severity in this group of children is difficult and has not been adequately explored. For many patients, persistent symptoms result in missed school, poor academic performance, inability to participate in prior extracurricular activities and a fundamental change in daily life. Further work to quantify this burden in the paediatric space is required.

Article Information:
Disclosure

Katelyn Krivchenia has no financial or non-financial relationships or activities to declare in relation to this article.

Compliance With Ethics

This article is an opinion piece and does not report on new clinical data, or any studies with human or animal subjects performed by the author.

Review Process

This is an expert interview and as such has not undergone the journal’s standard peer review process.

Authorship

The named author meets the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, takes responsibility for the integrity of the work as a whole, and has given final approval for the version to be published.

Correspondence

Katelyn Krivchenia, Section of Pulmonary Medicine, Nationwide Children’s Hospital, Columbus, OH 43210, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA. E: katelyn.krivchenia@nationwidechildrens.org

Support

No funding was received in the publication of this article.

Access

This article is freely accessible at touchINFECTIOUSDISEASES.com. © Touch Medical Media 2022

Acknowledgements

Medical writing support was provided by Katrina Mountfort of Touch Medical Media and funded by Touch Medical Media.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analysed during the writing of this article.

References

  1. Datta SD, Talwar A, Lee JT. A proposed framework and timeline of the spectrum of disease due to SARS-CoV-2 infection: Illness beyond acute infection and public health implications. JAMA. 2022;324:2251–2.
  2. Soriano JB, Murthy S, Marshall JC. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis.2022;22:e102–7.
  3. Lopez-Leon S, Wegman-Ostrosky T, Ayuzo del Valle NC, et al. Long-COVID in children and adolescents: A systematic review and meta-analysis. Sci Rep. 2022;12:9950.
  4. Trapani G, Verlato G, Bertino E, et al. Long COVID-19 in children: An Italian cohort study. Ital J Pediatr. 2022;48:83.
  5. Kuczborska K, Buda P, Ksiazyk J. Long-COVID in immunocompromised children.Eur J Pediatr. 2022;181:3501–9.
  6. Leftin Dobkin SC, Collaco JM, McGrath-Morrow SA, et al. Protracted respiratory findings in children post-SARS-CoV-2 infection. Pediatr Pulmonol. 2021;56:3682–7.
  7. Palacios S, Krivchenia K, Eisner M, et al. Long-term pulmonary sequelae in adolescents post-SARS-CoV-2 infection. Pediatr Pulmonol. doi: 10.1002/ppul.26059.
  8. Morrow AK, Malone LA, Kokorelis C, et al. Long-term COVID 19 sequelae in adolescents: The overlap with orthostatic intolerance and ME/CFS. Curr Pediatr Rep. 2022;10:31–44.
  9. Racine N, McArthur Bam Cooke JE, et al. Global prevalence of depressive and anxiety symptoms in children and adolescents during COVID-19: A meta-analysis. JAMA Pediatr.2021;175:1142–50.
  10. Lamontagne S, Winters M, Pizzgalli D, et al. Post-acute sequelae of COVID-19: Evidence of mood & cognitive impairment. Brain Behav Immun Health. 2021;17:100347.
  11. Stephenson T, Pinto Pereira S, Shafran R, et al. Physical and mental health 3 months after SARS-CoV-2 infection (long COVID) among adolescents in England (CLoCk): A national matched cohort study. Lancet Child Adolesc Health. 2022;6:230–9.
  12. Buonsenso D, Piazza M, Boner A, et al. Long COVID: A proposed hypothesis-driven model of viral persistence for the pathophysiology of the syndrome. Allergy Asthma Proc. 2022;43:187–93.
  13. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27:601–15.

Further Resources

Share this Article
Related Content In COVID-19
  • Copied to clipboard!
    accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Sponsored Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72