In recent months a coronavirus (which triggers the COVID-19 disease) has repeatedly been suspected to be the cause of severe inflammatory disease in children. The results of an English case-control study with 58 hospitalized children who met the criteria of PIMS-TS (Pediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 infection), and of acute respiratory syndrome when infected with SARS-CoV-2, suggest a new type of inflammatory syndrome after COVID-19 infection that differs from the Kawasaki syndrome known to the medical community.1
In the present case-control study, infection with SARS-CoV-2 was detected in 78% of the children. Each of these children showed fever, as well as nonspecific symptoms consisting of abdominal pain (53%), vomiting (45%), and diarrhea (52%). About half of the children developed exanthema (52%), conjunctivitis (45%), and shock symptoms (50%). Only in 22% of these children the symptoms fit the diagnostic criteria of Kawasaki syndrome. 14% of the children suffered cardiac complications in the form of dilatations and aneurysms of the coronary arteries.1
Clinically and serologically no particular differences had been detected between the children who tested positive for SARS-CoV-2 and the virus-negative children. All hospitalized children showed elevated inflammation levels. These included elevated levels of CRP, neutrophil lymphocytes, and serum ferritin. Elevated troponin concentrations could be measured in about 70% of the children. An elevated concentration of the B-type natriuretic peptide was even found in 83% of the children.1
A comparison of the affected children in this study with children with Kawasaki syndrome from other studies revealed some important differences: The children in the current study had been older overall than the children with Kawasaki syndrome. 80% of the children with Kawasaki's syndrome are younger than 5 years. Compared to the children with Kawasaki's syndrome, the hospitalized children showed a higher number of neutrophil lymphocytes, a higher concentration of CRP, and a significantly more pronounced lymphopenia and anemia. Fibrinogen and troponin concentrations also exceeded those otherwise known in children with Kawasaki's syndrome. PIMS-TS differs from known childhood inflammatory diseases: Kawasaki syndrome, Kawasaki shock syndrome, and toxic shock syndrome. It raises many questions about its pathogenesis, diagnostic criteria, and prevention.1
Kawasaki syndrome is present when 4 symptoms occur in addition to a 5-day fever. These include exanthema, enanthema, conjunctivitis, cervical lymphadenopathy, and swelling of the hands or feet. The swelling of the lymph nodes in the neck is unilateral and is more than 1.5 cm in diameter. In the chronic stage, swelling of the extremities can be accompanied by scaling of the skin in the 2nd to 3rd week. Conjunctivitis is usually bilateral. Children often have varnished lips and a strawberry tongue. If less than 4 of these criteria are added to the 5-day fever, it is called an incomplete Kawasaki syndrome. The fever often lies above 40°C. The reduction of fever is often difficult with the Kawasaki syndrome. Serologically, the Kawasaki syndrome shows an increased CRP value, an accelerated blood sedimentation rate, a leukocytosis with a left shift, a thrombocytosis, an increase in cardiac markers (troponin I, BNP, NT-proBNP) and liver values. Some of these symptoms may be absent in infants.2
A Kawasaki shock syndrome is characterized by arterial hypotension of (more than 20% compared to baseline) or underperfusion. In children with Kawasaki shock syndrome, vasoactive substances are often used (54%). The laboratory parameters indicate a significantly stronger inflammatory response compared to Kawasaki's syndrome: The CRP is higher and the hemoglobin level lower. Consumption coagulopathy with thrombocytopenia may even occur. Heart function is also more severely affected in children with Kawasaki shock syndrome.3
Diagnostic criteria for streptococcal TSS include isolation of group A streptococci, arterial hypotension, liver damage, coagulopathy, necrotizing fasciitis, generalized exanthema, acute respiratory syndrome, or kidney failure. In childhood, TSS is rarely more likely to occur. Most STSS patients are between 20 and 50 years old. Burns and viral infections are the major risk factors for STSS.4 In adult patients, mortality is 30-80%. If children are affected by STSS, 5-8% of these children die.5,6
References:
1. Whittaker E. et al. (2020). Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 2020; doi: 10.1001/jama.2020.10369.
2. Sk2-Leitlinie 2019. DGPK. (In German only).
3. Kanegaye J.T. et al. (2009). W Recognition of a Kawasaki disease shock syndrome. Pediatrics. 2009;123(5):e783-e789. doi:10.1542/peds.2008-1871
4. Hufnagel M. et al. Pädiatrie. Toxisches Schocksyndrom. Springer Medizin. (In German only).
5. Strom M. A. et al. (2017). Prevalence, comorbidities, and mortality of toxic shock syndrome in children and adults in the USA. Microbiol Immunol. 2017;61(11):463-473.
6. Chuang Y.Y. et al. (2005). Toxic shock syndrome in children: epidemiology, pathogenesis, and management. Paediatr Drugs. 2005;7(1):11-25.