NIH-funded Project Wants to Identify Children at Risk for MIS-C From COVID-19

Part of a CDC inforgraphic on MIS-C based on reports from U.S. cases March-May 2020.[2] The full inforgraphic can be found at https://www.cdc.gov/coronavirus/2019-ncov/covid-data/infographic-mis-c.html #COVID19

Part of a CDC inforgraphic on MIS-C based on reports from U.S. cases March-May 2020.[2] The full inforgraphic can be found at https://www.cdc.gov/coronavirus/2019-ncov/covid-data/infographic-mis-c.html

August 7, 2020 — The National Institutes of Health (NIH) announced research funding to encourage the development of approaches that identify children at high risk for developing Multisystem Inflammatory Syndrome in Children (MIS-C), thought to be a severe complication of COVID-19 (SARS-CoV-2). Up to $20 million will be awarded to successful research proposals over four years.

Most children exposed to or infected with SARS-CoV-2, the virus that causes COVID-19, develop only a mild form of the illness. However, others go on to develop MIS-C, a severe, sometimes fatal, inflammation of organs and tissues, including the heart, lungs, kidneys, brain, skin and eyes. The new effort seeks to encourage studies of genetic, immune, viral, environmental, and other factors that influence how severe a case of COVID-19 will be and the chances of developing to MIS-C.

“We urgently need methods to distinguish children at high risk for MIS-C from those unlikely to experience major ill effects from the virus, so that we can develop early interventions to improve their outcomes, ” said Diana W. Bianchi, M.D., director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The NICHD-led project, called Predicting Viral-Associated Inflammatory Disease Severity in Children with Laboratory Diagnostics and Artificial Intelligence (PreVAIL kIds), is part of NIH’s Rapid Acceleration of Diagnostics (RADx) initiative to speed innovation in the development, commercialization, and implementation of technologies for COVID-19 testing. PreVAIL kIds aims to encourage development of cutting-edge approaches for understanding the underlying factors influencing the spectrum of conditions that may occur in children and youth infected with the SARS-CoV-2 virus. These range from no symptoms at all to fever and cough, abdominal pain and diarrhea, and inflammation of the coronary arteries. The goal of the initiative is to understand the range of symptoms of COVID-19 and the factors leading to MIS-C.

Studies funded through PreVAIL kIds will evaluate genes and other biomarkers in COVID-19 pediatric cases, as well as examine how the virus interacts with its host and how the immune system responds. Researchers will rely on artificial intelligence and machine learning to sort and categorize the data they acquire to understand the disease patterns they uncover.

Other NIH components providing funding for PreVAIL kIds are the NIH Office of the Director; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute on Drug Abuse; National Institute of Minority Health and Health Disparities; and Fogarty International Center.

Below is more more information on MIS-C from recent peer-review journal reports:

Multisystem Inflammatory Syndrome in U.S. Children and Adolescents

A report July 23 in the New England Journal of Medicine looked at 186 patients with MIS-C in 26 states were hospitalized after April 16, 2020.[1] Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).

Part of a CDC inforgraphic on MIS-C based on reports from U.S. cases March-May 2020.[2] The full inforgraphic can be found at https://www.cdc.gov/coronavirus/2019-ncov/covid-data/infographic-mis-c.html

Part of a CDC inforgraphic on MIS-C based on reports from U.S. cases March-May 2020.[2] The full inforgraphic can be found at https://www.cdc.gov/coronavirus/2019-ncov/covid-data/infographic-mis-c.html

Multisystem Inflammatory Syndrome in Children in New York State

Another report on cases from New York State offered more statics from about 100 pediatric patients.[3] As of May 10, 2020, a total of 191 potential cases were reported to the New York State Department of Health. Of 95 patients with confirmed MIS-C and 4 with suspected MIS-C, 31 patients (31%) were 0-5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days.

MIS-C Report in an Adult

NYU Langone Health in New York City reported a 45-year-old Hispanic man presented to its emergency room with a Kawasaki-like multisystem inflammatory syndrome, similar to what has been reported in children with MIS-C.[4] He did not have any past medical history and presented to the emergency department with six days of fever, sore throat, diarrhea, bilateral lower extremity pain, conjunctivitis, and diffuse exanthem (widespread rash) after having cared for his wife with SARS-CoV-2 infection two weeks earlier. The patient denied respiratory symptoms on presentation, although his respiratory rate was elevated (25–33 breaths per min), and he had not taken any medications before symptom onset. A SARS-CoV-2-specific RT-PCR was positive, and chest X-ray showed diffuse interstitial haziness typical of COVID-19. Vital signs throughout admission were notable for persistent fever despite antipyretics (maximum temperature 39·4°C), hypotension (systolic blood pressure 80–90 mm Hg), tachycardia with episodes of atrial fibrillation with rapid ventricular response, and minimal oxygen requirements (1–2 L/min by nasal cannula). Physical examination revealed bilateral, non-exudative conjunctival injection, tender left neck swelling with palpable lymphadenopathy, periorbital oedema with overlying erythema, lip cheilitis, and targetoid erythematous papules and plaques with central duskiness involving the back, palms, neck, scalp, anterior trunk, and upper thighs.