J Biol Regul Homeost Agents. 2020 May-Jun;34(3):767-773. doi: 10.23812/EDITORIAL-RONCONI-E-59.



SARS-CoV-2, which induces COVID-19, causes Kawasaki-like disease in children: role of pro-inflammatory and anti-inflammatory cytokines.

Ronconi G1, Teté G2, Kritas SK3, Gallenga CE4, Caraffa A5, Ross R6, Conti P7.

Author information

1 Clinica dei Pazienti del Territorio, Fondazione Policlinico Gemelli, Rome, Italy.
2 Specialization School in Oral Surgery, Vita-Salute San Raffaele University, Milan, Italy.
3 Department of Microbiology and Infectious Diseases, School of Veterinary Medicine, Aristotle University of Thessaloniki, Macedonia, Greece.
4 Department of Biomedical Sciences and Specialist Surgery, Section of Ophthalmology, University of Ferrara, Ferrara, Italy.
5 School of Pharmacy, University of Camerino, Camerino, Italy.
6 University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
7 Postgraduate Medical School, University of Chieti, Chieti, Italy.


Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2) caused a global pandemic coronavirus disease 2019 (COVID-19). In humans, SARS-CoV-2 infection leads to acute respiratory distress syndrome which presents edema, hemorrhage, intra-alveolar fibrin deposition, and vascular changes characterized by thrombus formation, micro-angiopathy and thrombosis. These clinical signs are mediated by pro-inflammatory cytokines. In recent studies it has been noted that COVID-19 pandemic can affect patients of all ages, including children (even if less severely) who were initially thought to be immune. Kawasaki disease is an autoimmune acute febrile inflammatory condition, which primarily affects young children. The disease can present immunodeficiency with the inability of the immune system to fight inflammatory pathogens and leads to fever, rash, alterations of the mucous membranes, conjunctiva infection, pharyngeal erythema, adenopathy, and inflammation. In the COVID-19 period, virus infection aggravates the condition of Kawasaki disease, but it has also been noted that children affected by SARS-V-2 may develop a disease similar to Kawasaki’s illness. However, it is uncertain whether the virus alone can give Kawasaki disease-like forms. As in COVID-19, Kawasaki disease and its similar forms are mediated by pro-inflammatory cytokines produced by innate immunity cells such as macrophages and mast cells (MCs). In light of the above, it is therefore pertinent to think that by blocking pro-inflammatory cytokines with new anti-inflammatory cytokines, such as IL-37 and IL-38, it is possible to alleviate the symptoms of the disease and have a new available therapeutic tool. However, since Kawasaki and Kawasaki-like diseases present immunodeficiency, treatment with anti-inflammatory/immunosuppressant molecules must be applied very carefully.

Acute severe respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged in Wuhan City, Hubei Province, China, and caused a global pandemic coronavirus disease 2019 (COVID-19), officially declared early in 2020 by the World Health Organization (WHO). In humans, SARS-CoV-2 infection leads to respiratory syndrome ranging from light to severe to fatal pneumonia (1). Histologically, acute respiratory distress syndrome presents edema, hemorrhage and intra-alveolar fibrin deposition. In addition, COVID-19 causes vascular changes characterized by alveolar damage with fibrin thrombus formation, microangiopathy and thrombosis (2). All these clinical signs are mediated by the pro-inflammatory cytokines that provoke the so-called “cytokine storm”. Protective measures against the novel SARS-CoV-2 have not been sufficient to guarantee the lack of infection in many patients and healthcare professionals (for example, approximately one doctor’s death occurred in every 5,000) who died after being affected by COVID-19 (3). Most of the deaths were older men with previous illnesses, while women were less affected (4). The current, diagnostic gold standard of COVID-19 is carried out mostly through the transcription-polymerase chain reaction (RT-PCR) laboratory method, a molecular diagnostic research of SARS-CoV-2 RNA, although these methods are not totally error-free (5). The analysis is carried out through sputum or collection of the nasopharynx samples.

In recent studies it has been noted that the coronavirus pandemic (COVID-19) can affect patients of all ages, including children, who were initially thought to be immune, even if they have fewer symptoms and the disease is less severe (Table I). Furthermore, pregnant women affected by COVID-19 can have a preterm birth. The incubation time of the virus varies widely between individuals and can range from a minimum of 2 days to a maximum of 25 days. Veena G. Jones, et al. in an interesting article (in press), describes the case of a 6-month-old infant diagnosed with Kawasaki disease (KD), who was suffering from COVID-19 (6). This is the first case where it is shown that even children are not immune from this terrible and deadly infection. The young patient presented the classic clinical symptoms of COVID-19, including fever and systemic inflammation. Moreover, children affected by COVID-19 can present other signs including flu, mycoplasma, cough, nasopharyngeal secretions, pharyngitis, nasal congestion, runny nose, tachypnea, wheezing, diarrhea, fatigue, vomiting, and headache (Table I); but they can also be positive for the SARS-CoV-2 and be asymptomatic (7).


COVID-19, Kawasaki, SARS-CoV-2, anti-inflammatory, cytokines, immunity, immunodeficiency, inflammation, virus

Publication type

  • Editorial

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