SARS‐CoV‐2 causes Kawasaki‐like disease in children: Cases reported in Pakistan

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), causing coronavirus disease (COVID), has spread promptly globally. ¹ , ² In adults, COVID‐19 shows classic symptoms that range from severe interstitial pneumonia to hyperactivation of the inflammatory cascade. ³ In children, respiratory involvement is mild and has a nonthreatening course, with almost no mortalities. ⁴ Recently, many cases of post‐COVID inflammatory syndrome are being reported in Karachi, Lahore, and Islamabad/Rawalpindi, Pakistan. ⁴ It is also known as Kawasaki‐like multisystem inflammatory, ⁵ it named because of some similar symptoms with the other rare childhood conditions Kawasaki disease such as skin rash, lymphadenopathy, strawberry tongue, and elevated inflammatory biomarkers. ⁶ The association between COVID‐19 and Kawasaki‐like multisystem inflammatory syndrome in children (MIS‐C) is not well understood. ⁶ The incidence of post‐COVID inflammatory syndrome is 1 of 1000 children affected by COVID‐19. ⁷ In the present case report, we present a rare and unique manifestation of COVID‐19‐related Kawasaki symptoms in Pakistani children.

As per news report, eight cases of Kawasaki‐like multisystem inflammatory syndrome that are associated with COVID‐19, have been reported in children between the ages of 5 to 15 years at Children Hospital, Lahore. ⁵ All the affected children have been tested positive for coronavirus antibodies. They either have been recovered from COVID‐19 or have been around someone with COVID‐19. Children presented with this condition are very ill and show signs and symptoms of inflammation in many internal organs, such as the intestines, heart, lungs, and kidneys. Thus, overlapping with toxic shock syndrome and Kawasaki disease shock syndrome are presented. ⁵ News reports are also proposed that fever (for more than 3 days), stomach ache, vomiting, diarrhea, red eyes, and rashes on the trunk are the most common presenting complains. A few of the children are presented with a low blood pressure, cold hands, and feet suggestive of shock. ⁵ Among them one or two develop inflamed red spots on mouth and tongue while only a few have swollen glands in the neck. It has also been reported that due to inflamed blood vessels, blood carrying capacity of vessels have significantly reduced. Post‐COVID‐19 syndrome puts a strain on the heart and compromises its ability therefore children with heart involvement require mechanical ventilation. ⁵ Though the condition has gotten better with medical care with intravenous immunoglobulin (IVIG), steroids, and high dose aspirin. Supportive treatment and assisted ventilation are required for the heart and lungs stabilization. ⁵

Kawasaki‐like MIS‐C with combination of COVID‐19 syndrome overlaps the typical symptoms of Kawasaki disease. ⁸ Outside Pakistan, the very first case of Kawasaki‐like multisystem inflammatory was reported on 26 April 2020, in the United Kingdom. ⁹ A COVID‐19 recovered child presented with a severe inflammatory syndrome that has some common features as in Kawasaki disease. ⁹ Further, eight cases were reported with the complaint of persistent fever, hypotension, and multiorgan (cardiac, gastrointestinal, renal, hematologic, dermatologic, and neurologic) involvement, and all of them have elevated inflammatory markers. ¹⁰ Respiratory symptoms were mild or not present in all cases. ¹⁰ , ¹¹ Over time, more similar cases have been reported by authorities of different countries whereas children are being presented with the severe inflammatory syndrome and also have a laboratory‐confirmed case of COVID‐19 or an epidemiological link to the COVID‐19 case. ¹ Three cases of Kawasaki‐like multisystem inflammatory syndrome in teenagers of Afro‐Caribbean and Asian ethnic background have been reported. ¹² In correspondence to our case, all three patients presented with fever, conjunctivitis, and gastrointestinal symptoms  ¹² They were also tested positive for SARS‐CoV‐2 immunoglobulin G with elevated inflammatory markers. Their labs result indicate low platelet count, prolonged prothrombin time, and activated partial thromboplastin time. ¹² In this study two out of three patients have been tested positive for group A streptococcal infection and Epstein‐Barr virus viremia at the time of presentation. ¹² The treatment for all post‐COVID syndrome cases remain constant, all patient received corticosteroid therapy and IVIG infusions. ¹² Another case with a similar presentation has been reported in a 54‐year‐old patient. In contrast to our study where Kawasaki‐like multisystem inflammatory syndrome present among children and adolescents. ¹³ Here, the main presenting complaint was bilateral blurry vision and rashes after 2 weeks of COVID‐19 infection whereas, in our study, only one or two patient develop inflamed red spots on mouth and tongue. ¹³ However, the pathophysiology of how SARS‐CoV‐2 causes Kawasaki‐like MIS‐C is unknown but it is hypothesized that COVID‐19 infection causes abundant inflammation and children with Kawasaki‐like multisystem inflammatory syndrome demonstrate a storm of inflammation in their body. ⁶

The Centers for Disease Control and Prevention (CDC) has recommended the MIS‐C diagnostic criteria. ¹⁴ They proposed that all health care providers should report the suspected case to their territorial health department if they found as (a) an individual with less than 21 years presenting with fever (≥38.0°C for ≥24 hours or subjective report of fever lasting ≥24 hours), (b) laboratory evidence of inflammation (elevated C‐reactive protein, erythrocyte sedimentation rate, fibrinogen, procalcitonin, d‐dimer, ferritin, lactic acid dehydrogenase, interleukin 6, raised neutrophils, low lymphocytes, and low albumin), (c) with multisystem (≥2) organ involvement (eg, cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic, or neurological etc) (d) with no alternate possible diagnosis, and (e) positive for current or recent COVID‐19 infection. ¹⁴ These children should be evaluated for Kawasaki‐like MIS‐C and prompt management is required. For the parents, CDC has also recommended that any child who has been recovered from the COVID‐19 or has been around someone with COVID‐19 if develop symptoms such as persistent fever, abdominal pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes should be assessed for Kawasaki‐like multisystem inflammatory syndrome or if they develop breathing difficulty, chest pain, altered mental status, bluish lips/face should seek emergency care. ¹⁵

The best way to prevent MIS‐C is to control the interaction of children with infected or suspected COVID‐19 patients. And should follow all the precautionary measures such as repeatedly washing hands for at least 20 seconds, avoid people who are sick, 6 ft distance between the child and other individuals outside, wear a mask, regularly clean, and disinfect the high touch surfaces on daily basis. ¹⁶ COVID‐19 positive child parents should be advice by the physicians regarding the symptoms and immediate appointment with doctor. There is immense need of awareness of this complication in community to look after their children and to follow WHO preventative measure.