Clinical Manifestation of Children with Kawasaki Disease during the COVID-19 Pandemic in Iran:  A Case Series 

Samiyeh Kazemi1, Zahra Fotokian2, Mohammad Hasan Nadimi dafrazi3, Khatereh Shiroudbakhshi4 and Fatemeh Larijani5.

1 Reproductive and sexual health, Clinical Research Development Unit, Ramsar Imam Sajjad Hospital, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran.
2 Nursing Care Research Center, Health Research Institute, Babol University of Medical Sciences, Ramsar, Iran.
3 Department of Cardiology, Ramsar Campus, Mazandaran University of medical sciences, Ramsar, Iran.
4 Department of Pediatrics, Ramsar Campus, Mazandaran University of medical sciences, Ramsar, Iran.
5 Master of Geriatric Nursing, Clinical Research Development Unit, Ramsar Imam Sajjad Hospital, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran.

Correspondence to: Fatemeh Larijani. Master of Geriatric Nursing, Clinical Research Development Unit, Ramsar Imam Sajjad Hospital, Ramsar Campus, Mazandaran University of Medical Sciences, Ramsar, Iran. E-mail: fatemeh.larijani72@gmail.com 
Published: March 01, 2025
Received: December 18, 2024
Accepted: February 08, 2025
Mediterr J Hematol Infect Dis 2025, 17(1): e2025017 DOI 10.4084/MJHID.2025.017

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

To the editor

Kawasaki disease is a rare disease, but it is one of the most common childhood vasculitis,[1-2] with approximately 85% of affected children being under 5 years of age and the most common age of onset being 18 to 24 months.[1] The diagnostic criteria for Kawasaki disease established by the American Heart Association include ≥5 days of fever, oral mucosal changes, bilateral no exudative conjunctivitis, eczematous rash, peeling of the hands and feet, and cervical lymphadenopathy. Apart from hyperthermia, at least four of the five main clinical features are required for a complete form of Kawasaki disease and fewer than four for an incomplete form of Kawasaki disease.[2-4] Coronavirus infection in children and rarely in infants is associated with acute respiratory syndrome.[1-3] The COVID-19 pandemic has brought Kawasaki disease into the spotlight in both overt and covert forms. The overt form is the most common primary vasculitis in children,[4] primarily affecting medium-sized and small arteries. The covert form, on the other hand, is multisystem inflammatory syndrome in children (MIS-C), a rare but severe disease that affects children 2 to 6 weeks after infection with SARS-CoV-19 and was initially mistaken for Kawasaki disease.[4-5] However, there has been an increase in the incidence of Kawasaki-like disease among children with COVID-19, either concomitantly or after resolution of symptoms.[7] Although the etiology of Kawasaki is unclear, a role for a viral and infectious agent has been suggested.[1-3] In a systematic review by Mardi et al. (2021) in Iran, the incidence of Kawasaki-like syndrome increased significantly during the COVID-19 pandemic.[8] Other studies have also shown that the COVID-19 pandemic has increased the incidence of Kawasaki-like syndrome.[3-4] Given that the manifestations of Kawasaki disease overlap with acute infectious diseases such as COVID-19, timely recognition of clinical manifestations and timely treatment in children with Kawasaki manifestations are essential to prevent acute and chronic complications in children such as cardiac, pulmonary, and renal complications. We conducted a retrospective study to evaluate the demographic, clinical, and laboratory characteristics of 10 children with Kawasaki disease during the COVID-19 pandemic in a government hospital in Mazandaran province (northern Iran) from February 2020 to May 2023. We collected medical records of all children with Kawasaki disease or Kawasaki-like disease admitted to the hospital using the Kawasaki-specific code in the discharge records in the Health Information System (HIS). We also collected information on demographic characteristics, clinical symptoms, laboratory findings, radiological findings, cardiac examination results, and disease diagnosis (initial, in-hospital, and final). The inclusion criteria for the study included children aged 0-16 years who had typical and atypical symptoms of Kawasaki disease. Half of the children (50%) were boys (Table 1). Fever was observed in all patients; 1 (10%) patient required intensive care and gastrointestinal symptoms were observed in more than three-quarters of patients (Table 2). Pericarditis was observed in only 1 (10%) patients. X-ray, CT-scan, and LP results were positive in only 1 (10%) patient. The duration of hospitalization was 3.8 days (Table 1).
Complete Kawasaki disease was diagnosed in 6 patients (60%) and its incomplete form in 4 patients (40%) by the opinion of pediatric and cardiovascular specialists (Table 2).
Table 1 Table 1. Characteristics of patients with Kawasaki disease or Kawasaki-like disease.

Table 2 Table 2. Diagnosis strategies.
None of the patients developed coronary aneurysms, dilatations, or myocarditis. Pericardial effusion was seen in one patient (10%). Kawasaki disease has a wide range of clinical signs and symptoms.[6-9] The most common presenting symptoms are high fever, rash, conjunctivitis, lymphadenopathy, and strawberry tongue.[7,10] In addition, gastrointestinal manifestations of fever lasting more than 5 days have been suggested as a predictor of coronary artery involvement. In a study by Jafari et al. (2023) in Iran, the results of multivariate regression analysis showed that the duration of fever until diagnosis (fever more than 5 days) was a predictor of coronary artery involvement.[10] In the present study, more than three-quarters of children had a fever for more than 5 days, and coronary artery involvement was observed in one-quarter of children. Seven children (70%) had positive CRP. The study conducted by Li et al. (2024) also confirmed that a nomogram can effectively predict the risk of coronary artery lesions using CRP, IL-6, ESR, HDL, ox-HDL, etc. These findings suggest that when hospital laboratory resources are limited, standard detection indices such as HDL, ox-HDL, and ESR can be used to forecast the level of oxidative stress and inflammation-associated targets in coronary artery lesions associated with Kawasaki disease.[11] Although cardiac manifestations were less observed in the present study, gastrointestinal symptoms were reported in almost 100% of children. Early diagnosis and timely treatment when gastrointestinal symptoms are observed are recommended.[4]
Kawasaki disease lacks a definitive association with any single agent, and several infectious triggers, such as rhinovirus, Para influenza virus, respiratory syncytial virus, adenovirus,[10] human coronavirus,[6] and novel coronavirus, are known. However, some studies have ruled out the association of human coronavirus with Kawasaki disease.[10] At the same time, a study by Feldstein et al. (2020) in the U.S. reported Kawasaki-like disease during the COVID-19 epidemic.[2] Therefore, it is still unclear whether the diagnosis of COVID-19 in children with Kawasaki-related symptoms should be treated with a diagnosis of Kawasaki disease or whether a new separate diagnosis of COVID-19 infection is required. There is a need to differentiate coincidental COVID-19 infection with Kawasaki disease from Kawasaki disease caused by COVID-19. This article will help to understand and address the Kawasaki-like manifestations of pediatric COVID-19 infection, especially in intensive care units, and its possible complications. It will also help to make timely and appropriate decisions about its treatment and management. Based on the results of the present study, the manifestations of Kawasaki disease overlap with acute infectious diseases such as COVID-19, so timely identification and treatment of children with Kawasaki manifestations is essential to prevent acute and chronic cardiac, pulmonary, and renal complications. Therefore, the preparation of standard guidelines for screening and early identification of children with symptoms of acute inflammatory diseases (MISC, COVID-19, and KD) seems necessary.

References   

  1. Sharma C, Ganigara M, Galeotti C, Burns J, Berganza FM, Hayes DA, et al. Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison. Nat Rev Rheumatol 2021; 17:731-48 https://doi.org/10.1038/s41584-021-00709-9 PMid:34716418 PMCid:PMC8554518 
  2. Feldstein LR, Rose EB, Horwitz SM, Collins JP, Newhams MM, Son MBF, et al. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020; 383:334-46. https://doi.org/10.1056/NEJMoa2021680 PMid:32598831 PMCid:PMC7346765
  3. Belhadjer Z, Meot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children in the context of global SARS-CoV-2 pandemic. Circulation. 2020; 142:429-436. https://doi.org/10.1161/CIRCULATIONAHA.120.048360 PMid:32418446 
  4. Jones VG, Mills M, Suarez D, et al.: COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatr. 2020, 10:537-540. 10.1542/hpeds.2020-0123. https://doi.org/10.1542/hpeds.2020-0123 PMid:32265235
  5. Freeman AF, Shulman ST: Kawasaki disease: American Heart Association guidelines summary. Am Fam Physician. 2006, 74:1141-1148. 
  6. Toubiana J, Poirault C, Corsia A, et al. Outbreak of Kawasaki disease in children during COVID-19 pandemic: a prospective observational study in Paris, France. medRxiv. 2020; doi: 2020.05.10.20097394. https://doi.org/10.1101/2020.05.10.20097394 
  7. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 2020; 395:1771-8. https://doi.org/10.1016/S0140-6736(20)31103-X PMid:32410760 
  8. Mardi, Parham, et al. Characteristics of children with Kawasaki disease-like signs in COVID-19 pandemic: a systematic review. Frontiers in pediatrics, 2021, 9: 625377. https://doi.org/10.3389/fped.2021.625377 PMid:33816398 PMCid:PMC8012548
  9. Kwak JH, Lee SY, Choi JW, the Korean Society of Kawasaki Disease. Clinical features, diagnosis, and outcomes of multisystem inflammatory syndrome in children associated with coronavirus disease 2019. Clin Exp Pediatr 2021; 64:68-75. https://doi.org/10.3345/cep.2020.01900 PMid:33445833 PMCid:PMC7873390
  10. Sarouei MJ, Kamali M, Charati FG, Shahbaznejad L, Hajialibeig A, Razavi-Amoli SK, & et al. Epidemiological and Clinical Characteristics of Kawasaki Disease in Journal Mazandaran Univ Med Sci 2022; 32 (212): 97-106 (Persian).
  11. Li Y., Lan S., Zhang H. Expression of oxidative stress and inflammatory indicators for coronary artery disease in Kawasaki disease. Mediterr J Hematol Infect Dis 2024, 16(1): e2024052. https://doi.org/10.4084/MJHID.2024.052 PMid:38984102 PMCid:PMC11232689