The graph lines look like mountains erupting unexpectedly from a plain. The peaks represent the heart rates of two young adults with long COVID-19 during just 10 minutes of standing.

In daily life, the extreme increase in heart rate (to 129 beats per minute or more) translates to a cross-country athlete who suddenly can’t stand through a game of cornhole, or a teenage karate instructor who becomes homebound, or an A student who struggles to write or string thoughts together.

“Long COVID-19 is something you wouldn’t wish on your worst enemies,” says Peter Rowe, director of the Johns Hopkins Children's Center Chronic Fatigue Syndrome and Related Disorders Program. “It is profoundly impairing.”

One of the few consolations in the COVID-19 pandemic has been the virus’ lesser grip on children. But children and teens can still suffer the chronic fatigue effects of long COVID-19 and complications like multisystem inflammatory syndrome in children (MIS-C). The Johns Hopkins Children’s Center is working to pin down and mitigate the effects of COVID-19 on children and young people.

Over the past two years, thanks to the generosity of donors, Rowe’s clinic has been able to expand the number of young patients who can be seen. Renee Swope began work as the clinic’s nurse in May 2020, and adolescent medicine physician Camille Broussard is due to join the team this summer.

“Dr. Robinson’s arrival will allow us to expand the clinical and research activities of the program,” says Rowe, “and we will be looking for additional philanthropic support to allow us to bring on an additional physician with special expertise in autonomic nervous system disorders.”

The clinic’s work has only become more urgent as COVID-19 drives a new flood of cases.

Rowe has been working on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) research and treatment for close to 30 years. Patients with persistent COVID-19 symptoms six months post-onset look so similar to pre-pandemic ME/CFS patients that they may be suffering from the same syndrome, he says. One striking similarity is orthostatic intolerance, or symptoms — such as fatigue, lightheadedness, headaches, difficulty processing thoughts, breathlessness and more — brought on by standing upright for brief periods. These symptoms are either caused by the reduction of blood flow to the brain or the body reacting with adrenaline and other chemicals to that decreased blood flow.

Long COVID-19 is only one of the virus’ complications that affects children. A subset of kids infected with COVID-19 develop dangerous inflammatory symptoms, thought early in the pandemic to be Kawasaki disease, which causes swelling in the walls of blood vessels. But the symptoms — high fever, rash and swelling — are shared with another condition: MIS-C. And critically, the monitoring and treatments can be different. Patients with MIS-C are prone to developing heart issues and going into shock, while patients with Kawasaki disease are more at risk of coronary artery aneurysms.

Cedric Manlhiot, who recently joined the Division of Pediatric Cardiology as the director of the Cardiovascular Analytic Intelligence Initiative, is working on an algorithm to help doctors sort patients into MIS-C or Kawasaki categories. Manlhiot’s algorithm, currently in the research stage, would use information gathered from labs and physician assessments to provide the likelihood of the condition being MIS-C or Kawasaki — something the doctor could take into account when making a diagnosis. Eventually, the number of times doctors agree with or disagree with the finding would be used to measure success of the algorithm, along with the time to diagnosis and treatment.

Neither disease has a definitive diagnostic test, so distinguishing between the two is a matter of looking at the overall clinical picture and making a call.

“Kawasaki has been around for 50 years now, and it’s been really well described, but there are still a number of kids who are misdiagnosed, and those kids are at a high risk of complications,” Manlhiot says. “The problem with these patients is the wrong diagnosis, but also the delayed diagnosis — the longer you wait before starting therapy, the worse the risk is.”

The algorithm and related software platform could someday be used to help sort patients along the entire spectrum of difficult-to-diagnose syndromes associated with fever, rash and inflammation, Manlhiot says.

If the pandemic has a silver lining, it’s the possible therapies, solutions and realizations arising from the sudden, urgent needs of COVID-19 cases.

“With the intensity of the focus on this problem and new ideas coming into the field, the hope is that there will be some discoveries that help the previous patients, as well as the ones who are just now getting ill,” Rowe says.