MOLECULAR DIAGNOSTICS: INFLAMMATORY SYNDROME AND COVID-19


response. Researchers have shown that the immune systems of patients with severe MIS tend to have a specific phenotype.7 That phenotype is marked by increased and persistent immunoglobulin G (IgG) antibodies, a reduced white blood cell count, reduced neutrophil count, reduced total T cell count, and increased CD8+ T cell activation. CD8+ T cells are activated as part of the body’s antiviral response and are re- sponsible for “killing” the viruses. The spe- cific superantigen8


that triggers this height-


ened immune response is still unknown. Some researchers have suggested that components of the infamous SARS-CoV-2 spike protein might trigger the response, while others suspect unknown secondary microbes or opportunistic microbes (ones that typically might not cause disease but become pathogenic secondary to another infection), might be the culprit. Another theory traces MIS symptoms to SARS-CoV-2 related antigens leaking from the intestines and into the blood- stream. A recent study found that MIS-C patients exhibit detectable virus within their stool several weeks after initial infection. Researchers suspect that the release of a protein called zonulin makes the gut “leaky” and, thus, allows the an- tigens to escape the intestines and into the bloodstream.9 While these studies offer some insight


into why MIS may happen following COVID-19 infection or exposure, there is still a lot to learn.


How is MIS diagnosed?


Because the symptoms are non-specific, diagnostic criteria for MIS still varies from one institution to the next. Nonetheless, an American College of Rheumatology guideline10


states that if an individual


has had a recent SARS-CoV-2 infection or exposure and reports an extended fever, skin rash, gastrointestinal symp- toms, and conjunctivitis, it is likely they’re experiencing MIS. Physicians evaluate these symptoms


while considering other possible infec- tions and other inflammatory diseases. Diagnostic studies might also include imaging and blood tests to study anti- bodies and blood cell counts. An echo- cardiogram might be used to study and diagnose heart dysfunction.


How is MIS treated? Currently, there is little evidence that one optimal treatment works for treating MIS. Nonetheless, treatment of MIS can be


divided into two broad strategies: • multi-system supportive care • anti-inflammatory therapies.


34 JANUARY 2022 MLO-ONLINE.COM


MIS patients can present or develop complications in various systems. Thus, a multidisciplinary team of healthcare providers might be managing a case. Physicians may manage MIS patients using immune-modulatory therapy such as intravenous immune globulin (IVIG) and glucocorticoids.11


So far, these two


treatments have been widely used to treat MIS with success.


Curbing MIS Like COVID-19, there is still so much to discover about MIS in adults and children alike. Yes, the condition is rare, but there is very little to predict who might develop the syndrome beyond a prior or current positive COVID-19 test. And because it affects multiple organs with irregularity, it is more important than ever to work at slowing or preventing the spread of the virus.


During the thick of the COVID-19 pandemic and as the world reopened, widespread routine testing was critical for slowing the spread of the virus. The prevalence of free testing in many com- munities and accessible at-home testing measures can still help individuals self- quarantine or get COVID-19 treatment early. At a community level, detection of COVID-19 waves, through testing, can concurrently warn of an impending increase in MIS cases. At the individual- case level, knowledge of your COVID-19 status can help doctors determine if they should be looking for symptoms of MIS so it can be treated early. Community surveillance using waste-


water testing is helping cities catch large outbreaks early. All these tools have helped communities and countries to blunt the severity of the pandemic. In doing this, we can also curb the incidence of MIS. Collectively, the tools listed above have also helped to identify MIS and its relationship to COVID-19 and illuminated parallel cyclic patterns in COVID-19 and MIS cases. In conclusion, though vaccination has dramatically improved the course of the pandemic, continued vigilance is important. MIS can be a severe, even life-threatening, condition, but like the broader pandemic, this syndrome can be prevented with broad testing and informed policy decisions that minimize virus spread.


REFERENCES


1. Information for healthcare providers about multisystem inflammatory syndrome in chil- dren (MIS-C). cdc.gov. Updated May 20, 2021. Accessed November 1, 2021. https://www.cdc. gov/mis/mis-c/hcp/index.html


2. Patel P, DeCuir J, Abrams J, Campbell AP, Godfred- Cato S, Belay ED. Clinical characteristics of multi- system inflammatory syndrome in adults: a system- atic review. JAMA Netw Open. 2021;4(9):e2126456. doi:10.1001/jamanetworkopen.2021.26456.


3. Centers for Disease Control and Prevention. Health Department-Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States. https://covid.cdc.gov/covid-data- tracker/#mis-national-surveillance. Updated November 1, 2021. Accessed December 2, 2021.


4. Morris SB, Schwartz NG, Patel P, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection — United Kingdom and United States, March–August, 2020. MMWR. 2020; 69(40);1450-1456. doi:http://dx.doi. org/10.15585/mmwr.mm6940e1.


5. World Health Organization. Multisystem inflammatory syndrome in children and adoles- cents temporally related to COVID-19. https:// www.who.int/news-room/commentaries/detail/ multisystem-inflammatory-syndrome-in-children- and-adolescents-with-covid-19. Published May 15, 2020. Accessed December 1, 2021.


6. Feldstein LR, Rose EB, Horwitz SM, et al. Mul- tisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334-346. doi:10.1056/NEJMoa2021680.


7. Son MBF, Friedman K. COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clini- cal features, evaluation, and diagnosis. UpToDate. Updated April 2, 2021. Accessed November 1, 2021. https://www.uptodate.com/contents/covid-19-mul- tisystem-inflammatory-syndrome-in-children-mis- c-clinical-features-evaluation-and-diagnosis


8. Noval Rivas M, Porritt RA, Cheng MH, Bahar I, Arditi M. COVID-19-associated multisystem inflammatory syndrome in children (MIS-C): A novel disease that mimics toxic shock syndrome-the superantigen hypothesis. J Allergy Clin Immunol. 2021;147(1):57-59. doi:10.1016/j.jaci.2020.10.008


9.Yonker LM, Gilboa T, Ogata AF, et al. Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier. J Clin Invest. 2021;131(14):e149633. doi:10.1172/JCI149633


10. Henderson LA, Canna SW, Friedman KG, et al. American College of Rheumatology clinical guidance for multisystem inflammatory syndrome in children associated with SARS-CoV-2 and hyperinflammation in pediatric COVID-19: Version 2. Arthritis Rheumatol. 2021;73(4):e13-e29. doi:10.1002/ art.41616.


11. American Academy of Pediatrics. Multisystem inflammatory syndrome in children (MIS-C) interim guidance. aap.org. Updated October 2, 2021. Accessed November 1, 2021. https://www.aap.org/ en/pages/2019-novel-coronavirus-covid-19-infec- tions/clinical-guidance/multisystem-inflammatory- syndrome-in-children-mis-c-interim-guidance/


Bruno Larida, MS, MBA, is Vice President of Marketing at Seegene Technologies. He brings more than 25-years of experience in the diagnostics industry, with knowledge in corporate management and global strategic


marketing, expertise in product development, sales, and regulatory affairs.


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