The more often someone is infected with COVID, the more likely they are to develop "long COVID," according to a new pediatric study. Young people and children infected with the COVID virus for a second time were twice as likely to develop long COVID than their peers who were infected just once. Long COVID from the second infection coincided with higher risks for heart disease, damaged kidneys, cognitive issues, and more, according to analysis published today in The Lancet Infectious Diseases from researchers at the Perelman School of Medicine at the University of Pennsylvania.
"Many had hoped reinfections of COVID would be milder or carry less long-term risk, but we found increased risks for a broad range of conditions, challenging the assumptions many had that children bounce back quickly," said first author Bingyu Zhang, MS, an Applied Mathematics & Computational Science PhD student in the Penn Computing, Inference and Learning (PennCIL) lab. "Our findings should inform clinical decision-making, support vaccine uptake, and guide how resources are allocated to monitor and care for COVID patients."
Analysis of data from roughly 407,000 patients across 40 pediatric hospitals, showed that among patients with just one documented COVID infection, there was a population-level rate of 904 cases of long COVID per million people every six months. But when the researchers crunched the numbers for those who experienced a second COVID infection, the rate more than doubled to 1,884 cases per million.
Filling the knowledge gap: spotlighting some of the youngest patients
Most work examining long COVID (also called post-acute sequelae of SARS-CoV-2 infection [PASC]) focuses on adults, so the Penn researchers wanted to learn more about how young people, especially those under 21 years of age, respond to infection and experience long-term effects. And while the study focused on the omicron wave, the predominant virus strain between late 2021 and early 2022, that version of the virus—along with its subvariants—still remains a strong presence, infecting and reinfecting young people today.
"The results of this study further support one of the strongest reasons I give patients, families and physicians about getting vaccinated: More vaccines should lead to fewer infections, which should lead to less long COVID," said co-author Ravi Jhaveri, MD, head of Pediatric Infectious Diseases at Ann & Robert H. Lurie Children's Hospital of Chicago.
Potential risk for potentially deadly conditions
The researchers examined the specific risk that a second infection posed for a variety of known conditions and symptoms that have been associated with long COVID by examining health records dating to the omicron wave. The records were studied for a documented diagnosis of long COVID, and then the researchers analyzed the records for updates covering a period of roughly one to six months after.
Pediatric patients who had COVID twice were more than 3.5 times as likely to develop myocarditis, a swelling of heart muscle that can weaken the heart and be life threatening. After that, the next greatest risk to pediatric patients after a second COVID infection was a doubling of their chance of developing blood clots.
In addition, the risks of developing severely damaged kidneys, abnormal heartbeats, heart disease, and severe fatigue all were significantly more likely with a second COVID infection.
"Studying the public health consequences of COVID, including long COVID, helps us identify what children may be more vulnerable to after infection and direct support to them, such as allocating public health resources to monitor and manage long-term effects," said co-author Jeffrey Morris, PhD, director of Biostatistics.
The indispensable value of a well-funded broad look
This analysis was part of the National Institutes of Health (NIH)-funded RECOVER initiative, which was established to investigate COVID's long-term effects. The project pooled data from health facilities and patients across the United States to provide an in-depth look at how the virus could continue to affect people for years to come.
"The level of coordination, data sharing, and analysis requires massive infrastructure and sustained support," said senior author Yong Chen, PhD, a professor of Biostatistics and the director of PennCIL. "Without this investment, we wouldn't have had access to such a large and diverse pediatric population, nor the capacity to rigorously evaluate long COVID in a way that is applicable across many different levels of care."
Moving forward, the team plans to track data on pediatric patients that span longer periods of time, examine whether newer COVID variants change the risk patterns, and explore specific strategies that might help prevent severe long-term effects.
They also hope to identify which categories of patients might be most vulnerable to long COVID and its associated conditions so families and clinicians can better protect them from the lasting impact of reinfections.
This work was supported in part by the National Institutes of Health (OT2HL161847, U01TR003709, U24MH136069, RF1AG077820, R01AG073435, R56AG074604, R01LM013519).
