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Research Summaries

Discover what the latest science from the RECOVER Initiative means for our ability to understand, diagnose, prevent, and treat Long COVID.

This page contains descriptions of findings from RECOVER research studies. These descriptions use plain language and a format that is easy to understand.

If you want to learn more about the scientific discoveries described here, you can also browse and search the complete list of RECOVER Publications.

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RECOVER researchers know that there is a lot of important information about COVID-19 and Long COVID in electronic health records (EHRs), especially in the notes that doctors write during care. The researchers used a computer tool called Natural Language Processing (NLP) to find signs and symptoms of different conditions. However, NLP doesn’t always work well, especially with new health problems like COVID-19 or Long COVID, which are always changing. To improve this, researchers created a new NLP system that could collect detailed information about Long COVID signs and symptoms from EHRs. After testing the system at other medical sites, they found it worked well across different locations. The study showed that the new NLP system could successfully find the information they were looking for about COVID-19 and Long COVID in EHRs. The NLP is now available to other researchers and is being used to collect information that can support additional studies on COVID-19 and Long COVID.

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Observational Pediatric Broad Symptoms Risk Factors

Gross, RS; Thaweethai, T; Kleinman, LC; et al., JAMA

This RECOVER study is one of the first of its kind to look at Long COVID symptoms in children across age groups. Researchers for this study also developed a new research tool to help identify children who were most likely to have Long COVID. The study asked about prolonged or long-lasting symptoms in both school-age children (ages 6 to 11 years old) and teenagers (ages 12 to 17 years old) and compared these symptoms between those with and without a history of COVID-19. The symptoms that were most likely to identify school-age children with Long COVID were trouble with memory or focusing, back or neck pain, stomach pain, headache, fears, refusing to go to school, skin rashes, trouble sleeping, nausea or vomiting, and lightheadedness or dizziness. The symptoms that were most likely to identify teenagers with Long COVID included change or loss of smell or taste, bone, muscle or joint pain, back or neck pain, feeling tired all day or after walking, having low energy, trouble with memory or focusing, headache, and lightheadedness or dizziness. These study findings show Long COVID symptoms can affect almost every organ system in the body. It also showed that while many of the symptoms between the two age groups were similar, there were differences. Understanding why these differences occur can help create future Long COVID treatments for children that are age-group specific. Read the Research Q&A

Short Summary
EHR Pediatric

Bose-Brill, S; Hirabayashi, K; Schwimmer, E; et al., Hospital Pediatrics

This RECOVER study looks at a medicine called nirmatrelvir/ritonavir, which is used to treat COVID-19 in teens and adults who are more likely to be hospitalized from COVID-19. Researchers wanted to understand why doctors might give this medicine to teens ages 12 to 17. They reviewed electronic health records (EHRs) from January 2022 to August 2023 to find which teens got this medicine after testing positive for COVID-19. Out of almost 21,000 teens with COVID-19, only 408 got the medicine within 5 days of diagnosis. The study found that teens with long-term health problems were 2.5 times more likely to get the medicine. Those with comorbidities (more than 1 ongoing health problem) were more likely to receive it. But most teens with 1 or more health problems did not receive this medication. This could be a reason why many teens with COVID-19 need to be hospitalized. The study also found that Hispanic or Latino kids were less likely to get the medicine compared to non-Hispanic, white kids. This study shows that kids with chronic health issues are more likely to get nirmatrelvir/ritonavir, but not many kids are getting this medicine overall.

Short Summary
EHR Adult Risk Factors

Hadley, E; Yoo, YJ; Patel, S; et al.; N3C and RECOVER consortia, Communications Medicine

This RECOVER study looks at how often people get COVID-19 more than once and if they develop Long COVID afterward. The study also looks at whether getting COVID-19 multiple times, also called a reinfection, is worse than the first time getting COVID-19. RECOVER researchers identified a reinfection when a person had a positive COVID-19 test at least 60 days after getting COVID-19 for the first time. They studied the health records of over 3 million patients in different ways to understand COVID-19 reinfections. By studying a large number of patients, the researchers were able to learn key details about COVID-19 reinfections. They found that about 6.9% of people got COVID-19 more than once. Most reinfections happened when the Omicron variant was spreading. Researchers found that Long COVID was more common in people who had COVID-19 for the first time compared to those who were reinfected. This finding suggests that protecting yourself from getting COVID-19 is the best way to prevent Long COVID. People who had a moderate or severe case of COVID-19 the first time were also more likely to get very sick again when they were reinfected. These people were often older and at higher risk of death.

Short Summary
EHR Adult Broad Symptoms Risk Factors

Zang, C; Hou, Y; Schenck, EJ; et al., Communications Medicine

Some people develop new conditions or symptoms after having COVID-19, called Long COVID. This can lead to ongoing health problems. Researchers still don’t fully understand why some people get Long COVID while others do not. In this RECOVER study, researchers wanted to learn what increases someone’s risk of developing Long COVID after getting COVID-19. Researchers studied the electronic health records of 2.1 million people from New York and Florida who either had or had not had COVID-19 between March 2020 and November 2021. Using this data, they created a new computational model (a computer program that imitates how something works in real life) to help identify the things that Long COVID patients had in common. The researchers looked at whether these shared factors increased their risk of developing Long COVID. The model found that the people who were more likely to develop Long COVID if they had severe COVID-19 the first time they got the virus, were underweight, or had other health problems, like cancer or liver disease. The results also show that computational models can help identify people who have a higher chance of developing different symptoms and types of Long COVID. This information is important because it can be used to help researchers find new ways to prevent, diagnose, and treat Long COVID.

Short Summary
EHR Pregnant Women Risk Factors

Bruno, AM; Zang, C; Xu, Z; et. al.RECOVER EHR CohortRECOVER Pregnancy Cohort, eClinicalMedicine

Little is known about Long COVID in pregnant women. This study looked at whether getting COVID-19 while pregnant might increase the chances of getting Long COVID. Researchers from the RECOVER Patient-Centered Clinical Research Network (PCORnet) checked health records from 19 health systems across the US. They studied women ages 18–49 years old who had a test showing that they had COVID-19 between March 2020 and February 2022, and looked at 83,915 women who were not pregnant and 5,397 who were. Women who got COVID-19 while pregnant were less likely to get Long COVID than those who weren’t pregnant. Pregnant women with COVID-19 were more likely to develop certain conditions related to Long COVID, like an abnormal heartbeat. But they had a lower risk of getting other conditions, like malaise (feeling unwell). Overall, pregnant women with COVID-19 had a lower chance of getting Long COVID in the 30 to 180 days after they first got sick.

The virus that causes COVID-19 can change over time, creating new virus types called variants. This study explored if problems related to Long COVID were different in people who got different variants of COVID-19. Researchers looked at medical records from 2 databases in New York and Florida. They compared people who had the original type of COVID-19 with those who had a variant called Delta, which was one of the main variants in 2021. The researchers found that some Long COVID conditions were more common in the people who had Delta. For example, some people who got the Delta variant developed clots in the blood vessels in their lungs. People who had Delta were also more likely to have stomach symptoms than people who got the original type of COVID-19. Based on these findings, the researchers concluded that Long COVID symptoms can be different depending on which variant of COVID-19 someone had.

Short Summary
Observational Pediatric

Gross, RS; Thaweethai, T; Rosenzweig, EB; et. al.RECOVER-Pediatric Consortium, PLOS ONE

Having COVID-19 can lead to new symptoms or symptoms that do not go away. This condition is called Long COVID. RECOVER researchers are working to answer questions about Long COVID in children. To do this, they are studying over 15,000 children and their caregivers in the US to understand how common Long COVID is in children and their caregivers; how the body changes when someone has Long COVID; what makes some people more likely to develop Long COVID, such as where a person lives and their age, race, and sex; and what happens in the body that might cause Long COVID. This paper is important because it can show other scientists how to do their own research on Long COVID in children.

The researchers and study team running the RECOVER-NEURO clinical trial published a paper detailing the study’s design. RECOVER-NEURO is looking at 3 possible treatments for cognitive dysfunction, or brain fog, symptoms related to Long COVID. The possible treatments, also called study interventions, are BrainHQ (an interactive online brain training program), PASC-Cognitive Recovery (an online goal management training program), and transcranial direct current stimulation (a safe, noninvasive form of brain stimulation). The research team is using a variety of assessments, including brain function tests and participant surveys, to determine if these study interventions reduce brain fog symptoms and help people function better.

People with brain fog may have trouble thinking clearly, remembering things, or focusing on tasks, which can severely affect their daily functioning and quality of life. Results from this study will help the Long COVID community learn if BrainHQ, PASC-Cognitive Recovery, and transcranial direct current stimulation can be used to treat cognitive dysfunction symptoms related to Long COVID.

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