The COVID-19 pandemic has swept across the globe at an alarming pace, claiming more than 127,000 lives in the UK alone at the time of writing . From early in the pandemic, children appeared to be more resilient to SARS-CoV-2 (the virus that causes COVID-19) compared with adults. Most infected children tended to experience only mild symptoms, if any at all, and admissions to intensive care units (ICUs) and deaths were rare .
However, during the first wave of the pandemic in the spring of 2020, reports emerged from UK paediatric ICUs of a small number of otherwise healthy children being admitted with a rare multisystem hyperinflammatory syndrome . As the pandemic progressed, children presenting with similar symptoms were seen elsewhere in Europe and in America [4, 5]. The majority of these children tested negative for COVID-19 at the time of hospitalisation but showed evidence of prior exposure, either through contact with a confirmed case or through a positive antibody test, indicating previous infection.
This unexplained syndrome showed some clinical similarities with other inflammatory illnesses, such as Kawasaki disease and toxic shock syndrome. However, it was subsequently defined as a separate condition, referred to as paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) in the UK and multisystem inflammatory syndrome in children (MIS-C) internationally [4–6].
What is PIMS-TS?
The Royal College of Paediatrics and Child Health defines PIMS-TS as a child presenting with persistent fever and inflammation, with single or multi-organ dysfunction. Other microbial causes must be excluded, and SARS-Cov-2 infection may be positive or negative . This definition differs slightly from that applied to MIS-C by the Centers for Disease Control and Prevention in the USA, which also requires a positive result for a SARS-CoV-2 infection or antibody test, or exposure to COVID-19 during the four weeks preceding the onset of symptoms .
What are the signs and symptoms of PIMS-TS?
Patients with PIMS-TS commonly present with persistent fever, severe gastrointestinal disturbances and myocarditis (inflammation of the heart muscle) [3,7]. Other symptoms may include a rash, fatigue, headaches and vomiting, and some patients may experience acute kidney injury [8, 9].
Unlike Kawasaki disease, which tends to affect children under the age of five years, children with PIMS-TS are generally of school age. A high proportion of patients are male and usually do not have any major underlying health conditions . Another prominent finding is that children from ethnic minority backgrounds are over-represented in cases of PIMS-TS, with 28% and 47% of a UK cohort of patients with PIMS-TS being of Asian or Afro-Caribbean descent, respectively . These data may indicate a genetic predisposition to PIMS-TS, or rather reflect the disproportionate impact the pandemic is having on ethnic minority communities.
What causes PIMS-TS?
The hyperinflammatory state seen in children with PIMS-TS points towards a potential cause being an overactive host immune response to a pathogen. The relationship between spikes in cases of COVID-19 and PIMS-TS, combined with the delayed onset of PIMS-TS symptoms in patients who are often negative for the SARS-CoV-2 infection but show evidence of prior exposure, supports the theory that PIMS-TS is not caused by the infection itself but is instead a post-infection response .
How is PIMS-TS diagnosed and managed?
No specific diagnostic tests for PIMS-TS exist. Diagnosis is largely based on symptom presentation, blood tests and other medical investigations (e.g., echocardiogram, electrocardiogram and ultrasound) .
Many children diagnosed with PIMS-TS are admitted to ICUs and treated with inotropic agents (drugs that alter the force of cardiac contractions) to treat cardiac instability . Others require mechanical ventilation and extracorporeal membrane oxygenation . Patients should be managed by a multidisciplinary team comprising paediatric cardiologists, immunologists, rheumatologists and critical care specialists [5, 11]. There is a lack of data regarding treatment; however, current therapies include anti-inflammatory agents (such as intravenous immunoglobulins and corticosteroids) and biologics targeting specific inflammatory cytokines .
The rapidly evolving nature of the COVID-19 pandemic constantly presents new questions and challenges, with PIMS-TS being just one example of this. We are quickly learning more about this novel syndrome as more data become available, but many questions remain. For example: What are the risk factors for PIMS-TS? What are the long-term impacts for patients with PIMS-TS? How can clinicians most effectively treat PIMS-TS? Research addressing some of these questions is ongoing, which will improve not only the timely identification of children with PIMS-TS but also the treatment that they receive.
1. John Hopkins University & Medicine. Coronavirus resource center. Available at: https://coronavirus.jhu.edu/map.html. Accessed April 2021.
2. Zimmermann P and Curtis N. COVID-19 in children, pregnancy and neonates: A review of epidemiologic and clinical features. Pediatr Infect Dis J 2020; 39 (6): 469–477.
3. Riphagen S, Gomez X, Gonzalez-Martinez C et al. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020; 395 (10237): 1607–1608.
4. Centers for Disease Control and Prevention. Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). Available at: https://emergency.cdc.gov/han/2020/han00432.asp. Accessed April 2021.
5. Harwood R, Allin B, Jones CE et al. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): Results of a national Delphi process. Lancet Child Adolesc Health 2021; 5 (2): 133–141.
6. Royal College of Paediatrics and Child Health. Guidance: Paediatric multisystem inflammatory syndrome temporally associated with COVID-19. Available at: https://www.rcpch.ac.uk/sites/default/files/2020-05/COVID-19-Paediatric-multisystem-%20inflammatory%20syndrome-20200501.pdf. Accessed April 2021.
7. Jiang L, Tang K, Levin M et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis 2020; 20 (11): e276–e288.
8. Great Ormond Street Hospital for Children. Paediatric inflammatory multisystem syndrome. Available at: https://www.gosh.nhs.uk/conditions-and-treatments/conditions-we-treat/paediatric-inflammatory-multisystem-syndrome-pims/. Accessed April 2021.
9. Ahmed M, Advani S, Moreira A et al. Multisystem inflammatory syndrome in children: A systematic review. EClinicalMedicine 2020; 26: 100527.
10. Davies P, Evans C, Kanthimathinathan HK et al. Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: A multicentre observational study. Lancet Child Adolesc Health 2020; 4 (9): 669–677.
11. White M, Tiesman B, Handforth J et al. Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS): The Evelina Experience. Arch Dis Child 2020; 105 (11): 1025–1027.