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We read with interest the article by Pouletty et al,1 in which the authors describe a multicentre compilation of patients with Kawasaki disease (KD) in France, associated with the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Other colleagues in Europe and USA have recently reported similar experiences.2–5
We report a prospective case series of paediatric patients that fulfilled clinical diagnostic criteria of KD during the SARS-CoV-2 pandemic in a paediatric referral centre in Barcelona, Spain. KD was defined according to the 2017 criteria of the American Heart Association.6 Assessment of SARS-CoV-2 infection was made by means of quantitative real-time PCR assay (GeneFinder COVID-19 Plus, Elitech; Puteaux, France) in nasopharyngeal samples; stools were tested in patients with diarrhoea. SARS-CoV-2 IgG qualitative determination (SARS-CoV-2 IgG chemiluminescent microparticle immunoassay; Abbot, Chicago, Illinois) was performed during admission. Statistical analyses were performed using SPSS V.25 (IBM). Informed consent was obtained from parents or legal guardians, as was informed assent in patients aged >12 years.
From March 23 to May 14, twelve previously healthy patients with KD were admitted to our institution (table 1). The yearly number of patients with KD diagnosed in our centre is around 10–12. Prior to diagnosis, several patients reported gastrointestinal symptoms (10/12, 83.3%; vomiting, diarrhoea and abdominal pain) and neurological symptoms (5/12, 41.6%; irritability, headache, decreased consciousness and febrile seizures). Only patient 10 was referred with respiratory symptoms (cough) and had an abnormal chest X-ray showing pneumonia at presentation. Lymphopenia and thrombocytopenia were observed at diagnosis in eight and five patients, respectively. Inflammatory markers (C-reactive protein, ferritin, erythrocyte sedimentation rate and procalcitonin) were elevated in most patients, as were N-terminal pro-brain natriuretic peptide levels (median (range): 2930 (178–7994) ng/L).7
At or during admission, 6/12 (50%) patients showed microbiological and/or serological evidence of SARS-CoV-2 infection. As compared with children in whom SARS-CoV-2 infection was not demonstrated, the former had statistically significant lower platelet counts, and higher levels of inflammatory markers (C-reactive protein, procalcitonin and ferritin) and N-terminal pro-brain natriuretic peptide at diagnosis (table 2).
Ultrasound or clinical signs of cardiac involvement were noted at admission only in patient 8 (left and right coronary aneurysm, +4.7 and +4.8 Z-score). Coronary aneurysms were observed later in two further patients: on day 14 in patient 1 (left coronary aneurysm, 4.2 Z-score) and on day 12 in patient 10 (left coronary aneurysm, +3.6 Z-score). Patient 10 was a toddler who developed decreased consciousness, hypotension and clinical signs of hypoperfusion consistent with KD shock syndrome on day 3 of fever. Transfer to the paediatric intensive care unit was required and vasoactive support (for 48 hours) and non-invasive mechanical ventilation (for 3 days) were implemented, together with intravenous immunoglobulins (IVIG), methylprednisolone, hydroxychloroquine and azithromycin.
All patients were treated within 10 days of symptoms onset; only patient 12, with a self-limited incomplete KD, did not receive any immunomodulatory treatment. Median (range) duration of admission was 4 (2–12) days and all patients were discharged without incidents. Follow-up is ongoing in all cases.
We describe a higher than expected incidence of KD within a very short time frame (7 weeks) in Catalonia, compared with a historical series,8 with half of the cases being associated with SARS-CoV-2 infection, in line with the experience of other authors.2–5 Surprisingly, SARS-CoV-2-related KD cases were not reported in China, where the pandemic began and where the incidence of KD (40.9–55.1 per 100 000 children <5 years) is higher than in European countries.9
KD seems to be caused by a complex interaction between genetic and immunity factors, triggered by infections.6 10 Several pathogens have been found to be involved in the pathogenesis of KD, including coronaviruses.11 As compared with ‘classical’ KD, SARS-CoV-2-related KD cases differ in several clinical characteristics: patients are older2–5; present more often with respiratory, gastrointestinal or neurological symptoms3; and develop a more severe disease in terms of cardiovascular involvement.3–5 The incidence of coronary aneurysms in KD treated with IVIG ranges from 4% to 6%,12 as compared with 25% in our series. Also, higher rates of leucopenia, lymphopenia and thrombocytopenia, as well as increased inflammation, have been reported.1 3–5 Interestingly, in our series, significant differences in these lab values were observed between patients with and those without confirmed SARS-CoV-2 infection. While preliminary, these differences point at an association between SARS-CoV-2 infection and the pathogenesis of KD, beyond the temporal sequence.
Given the lack of evidence-based treatments for COVID-19, we treated the patients in our series according to available KD treatment guidelines,6 mainly IVIG (n=10) and steroids (n=6). Outcomes were good in all cases. We did not need to use other immunomodulatory drugs, such as anakinra or infliximab, as other authors have reported doing.2–5
Our study is limited by low numbers, the short follow-up period and its observational design. Nevertheless, our series is in line with recent observational data that describe an association between SARS-CoV-2 infection and a paediatric inflammatory multisystem syndrome that shares a number of clinical and analytical features with KD in children. Further studies are needed to confirm the more pronounced inflammatory response we observed in those cases in which a SARS-CoV-2 infection was demonstrated.
Patient consent for publication
This study was approved by the Hospital Sant Joan de Déu local ethics committee (Ref: PI-77-20).
AN-J and JA contributed equally.
Contributors RP, IJ, VF, CF, JJGG, ANJ and JA designed the study. RP, ACI, MRB, SR, MFDS, LM, CL, IC, LL, JSM, JMM, JSdT and VF collected the clinical data. MM, CE and CMA supervised the microbiological studies. RP, ANJ and JA analysed the data and wrote the paper. All authors have reviewed and approved the version submitted for publication.
Funding This work was supported by 'Subvencions per a la Intensificació de Facultatius Especialistes' (Departament de Salut de la Generalitat de Catalunya, Programa PERIS 2016-2020) (SLT008/18/00193) to ANJ.
Competing interests CF has received funds for speaking at symposia organised on behalf of Gilead Sciences. JA has received grants, personal fees and non-financial support from Sobi; grants and personal fees from Novartis; grants from Roche; grants, personal fees and non-financial support from Pfizer; grants and personal fees from BMS; grants from Lilly; grants from Novimmune; grants and personal fees from Gebro; and grants, personal fees and non-financial support from AbbVie, outside the submitted work.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; internally peer reviewed.