COVID-19 and the emergence of a Kawasaki-like inflammatory condition
The current pandemic has had an impact on all aspects of society: healthcare, economy, education, and most certainly the rare disease community. COVID-19 has affected rare diseases in multiple dimensions ranging from their prevalence to the course of treatment availability. This article will be viewing the Multi-System Inflammatory Disorder, through the lens of this pandemic, and assessing its implications for patients living with a related rare disease: Kawasaki Disease (KD).
Kawasaki disease (KD) is an acute illness that primarily affects infants and young children. It is characterized by prolonged fever, skin rash, swollen lymph nodes, conjunctivitis, and redness of the lips, mouth, tongue, palms, and soles. The symptoms are associated with abnormal activation of the immune system that makes it attack small blood vessels in the body; however, the trigger to this response remains a mystery. A variation in the ITPKC gene seems to be associated with an increased risk of KD.1 The ITPKC gene is responsible for making an enzyme that helps limit the production of T cells, which are involved in producing the body’s immune and inflammatory response. Variations associated with KD may interfere with the body’s ability to limit T cell production, which leads to some of the symptoms characteristic of the disorder1.
“The first known case of this disorder associated with COVID-19 was reported in late April when a six month old was screened for and received treatment for Kawasaki Disease, but also tested positive for COVID-19.”
Beyond genetic predisposition, risk factors for KD have remained a mystery1. However, the current pandemic could offer some additional insight on the matter. The COVID-19 pandemic has seen a flare in the number of children diagnosed with a Kawasaki-like disease: the Multi-System Inflammatory Disorder. The first known case of this disorder associated with COVID-19 was reported in late April when a six month old was screened for and received treatment for Kawasaki Disease, but also tested positive for COVID-192. This opens up the question of a potential link between viral infections, such as SARS-CoV 2, and the presentation of KD. This claim is worth investigating since up to 42% of patients diagnosed with KD also tested positive for a viral respiratory illness a month prior to the diagnosis3. Some studies have suggested that the disorder could be caused by a RNA virus that initially results in an asymptomatic infection followed by inflammatory symptoms in genetically predisposed children4
Currently, while a causative relationship between COVID-19 and Multi-System inflammatory disorder cannot be declared, the epidemic peak of COVID-19 is seen to have a correlation with Multi-System Inflammatory Disorder cases 5. Data suggests a delay of 2 to 4 weeks between COVID-19 infections and the onset of the inflammatory disorder, suggesting that the immune responses acquired to COVID-19 could be a part of the mechanism triggering inflammatory symptoms5. However, the relationship between COVID-19 infections and the Multi-System Inflammatory Disorder brings many unanswered questions regarding why the Multi-System inflammatory disorder is not prevalent in countries like Japan and China that have experienced significant COVID-19 case loads as well6. Thus, more research is needed to identify the causative mechanism of this novel inflammatory disorder. Doing so could also answer some questions regarding the causes of KD.
While the similarities between KD and Multi-System Inflammatory Disorder can offer direction for research on KD, it is important to note that KD and the multi-system inflammatory disorder carry some key differences. The main difference between the Multi-System Inflammatory Disorder and the rare disease KD is that Pediatric Multi-System Inflammatory Syndrome predominantly affects teenagers whereas KD more commonly presents in children less than 5 years old. In addition, Multi-System inflammatory disorder has shown greater reports of abdominal pains and GI inflammations compared to prototypical cases of KD5. There have also been observable differences in the clinical markers of these two conditions which could be key in making an accurate diagnosis followed by appropriate treatment. For instance, low white blood cell counts and high levels of ventricular natriuretic peptide, an indication of cardiac failure, are reported features seen with Multi-System Inflammatory Disorder, but not KD. Despite these differences, the current characterization of the disorder is very broad and can also be used to describe KD6. This complicates the ability to distinguish between the two disorders, and provide the appropriate diagnosis and treatment.
This seemingly COVID-19 induced Kawasaki-like syndrome has received growing attention, because timely diagnosis and treatment is crucial. Since some children get sick rapidly, they are usually cared for in pediatric and cardiac intensive care units and are treated by a multidisciplinary team with infectious disease, rheumatology, and cardiology specialists7. Giving consideration to the resources some severe cases might need, it makes sense to start monitoring patients early. The growing attention towards Multi-System Inflammatory disorder could also warrant greater investments and publicity about rare diseases like Kawasaki Disease.
Currently available treatments for the multi-system inflammatory disorder mainly include anticoagulants, IV immunoglobulin, IL-1 or IL-6 blockade, and corticosteroids. Some children only require supportive care rather than the medications7. As evidenced, the treatment and monitoring of the progress of this disorder requires health care resources and facilities. However, one consequence of the pandemic is that due to public health measures, many parents now hesitate to seek in-person consultations, which is reflected in a reduction of emergency room visits, and hospitalization due to other critical illnesses, including rare diseases such as KD8
“The information gathered surrounding the multisystem inflammatory disorder and momentum consequently generated towards KD could also be used to further rare disease infrastructure and research.”
This trend can be concerning in the case of KD patients because when left untreated, the risks of coronary artery aneurysms increase to 25%8. On a broader level, the pandemic has had a substantial impact on the health care services that rare disease patients can access. The results of a survey conducted by Canadian Organization of Rare Diseases (CORD) in April suggest that 50% of respondents have experienced difficulties accessing health care due to delays or cancellations in surgeries, blood work, and dialysis9. Given existing strains in the health care systems posed by the pandemic, it has become harder for the rare disease community to access services. Thus, when tackling a disease whose numbers grow with the pandemic, it becomes important for policy makers to think about resources needed and strategies to ensure that necessary health services, testing, and treatment are available.
The emergence of the SARS-CoV2 virus posed many challenges to the scientific community, and many questions regarding the virus remain unanswered. These include questions surrounding the cause, characteristics, and classification of the Multi-system inflammatory disorder. More research is specifically needed to create a case definition for the Multi system inflammatory disorder that allows for a timely diagnosis and prevents mislabeling the disorder as similar conditions like Kawasaki Disease. While we have a long way to go in achieving comprehensive research on the Multi-System Inflammatory disorder and KD, the research that has already been conducted can help parents, physicians, and policy makers make informed decisions regarding a child’s treatment and the structure of the systems needed to fight other rare diseases as well. The information gathered surrounding the multi-system inflammatory disorder and momentum consequently generated towards KD could also be used to further rare disease infrastructure and research.
Oviya Ananthakrishnan
Works Cited:
1.Kawasaki Disease. Genetics Home Reference. https://ghr.nlm.nih.gov/condition/kawasaki-disease#definition. Published July 7, 2020. Accessed May 14, 2020
2.Phend C. Kawasaki Disease From COVID-19 in Kids: How Common?. MedPage Today. https://www.medpagetoday.com/infectiousdisease/covid19/86393. Published May 8, 2020. Accessed May 14, 2020.
3.Jones VG, Mills M, Suarez D, et al. COVID-19 and Kawasaki disease: novel virus and novel case. Hosp Pediatrics. 2020; doi: 10.1542/hpeds.2020-0123
4.Rowley AH, Shulman ST. The Epidemiology and Pathogenesis of Kawasaki Disease. Front Pediatr. 2018;6:374. Published 2018 Dec 11. doi:10.3389/fped.2018.00374
5.Morand A, Urbina D, Fabre A. COVID-19 and Kawasaki Like Disease: The Known-Known, the Unknown-Known and the Unknown-Unknown. Preprints. 2020. doi: 10.20944/preprints202005.0160.v1. Accessed May 14, 2020
6.Rowley AH. Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children. Nat Rev Immunol. 2020. https://doi.org/10.1038/s41577-020-0367-5
7.Fliesler N. COVID-19 and a serious inflammatory syndrome in children: Unpacking recent warnings. Discoveries. https://discoveries.childrenshospital.org/covid-19-inflammatory-syndrome-children/. Published May 8, 2020. Accessed May 14, 2020.
8.Harahsheh AS, Dahdah N, Newburger JW, et al. Missed or delayed diagnosis of Kawasaki disease during the 2019 novel coronavirus disease (COVID-19) pandemic. J Pediatr. 2020;222:261-262. doi:10.1016/j.jpeds.2020.04.052
9.COVID-19 Impact on Rare Disease Patients: Letter to Ministers of Health & Responses. Canadian Organization for Rare Disorders. http://www.raredisorders.ca/covid-19-impact-on-rare-disease-patients/. Published April 28, 2020. Accessed May 14, 2020
Cite This Article:
Ananthakrishnan O, Chharawala V, Charron B, Kozak A, Vinokurtseva A. COVID-19 and the emergence of a Kawasaki-like inflammatory condition. Illustrated by F. Choudary. Rare Disease Review. November 2020. DOI:10.13140/RG.2.2.22485.24801 .
