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Sharing our progress toward recovery

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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Research Summary
Clinical Trial Adult Broad Symptoms Potential Treatments

Knopman, DS; Koltai, D; Laskowitz, D; et al., JAMA Neurology

The RECOVER-NEURO Cognitive Dysfunction (BrainHQ, PASC-CoRE, & tDCS) clinical trial tested three non-drug treatments to see if they improved thinking, focus, and memory for people with Long COVID. The three treatments included:

  • An interactive online brain training program called BrainHQ.
  • A virtually delivered, small group cognitive rehabilitation program called PASC-Cognitive Recovery or PASC-CoRE.
  • A cap that provided a non-invasive form of brain stimulation via electrical current called transcranial direct current stimulation or tDCS.

A unique aspect of RECOVER-NEURO was its decentralized design, enabling 328 adults across 22 U.S. sites to participate in this research despite living with Long COVID symptoms. The participants completed most study activities remotely during a 10-week study period. Some participants were assigned to a treatment group and received one of the three active treatments (BrainHQ, PASC-CoRE plus BrainHQ, or tDCS-active plus BrainHQ). Other participants were assigned to a comparison group and received either the BrainHQ active comparator or tDCS-comparator plus BrainHQ. Researchers found that all of the treatment groups and comparison groups reported similar results in their improvement in thinking, focus, and memory. All participants reported some improvement over time and many said they felt better overall after they completed their assigned treatment, even though no one treatment outperformed other groups, including the comparison groups.

Short Summary
EHR Adult Risk Factors

Vekaria, V; Thiruvalluru, RK; Verzani, Z; et al., JAMA Network Open

In this RECOVER study, researchers wanted to find out if adults with a serious mental illness (SMI)—like major depression, schizophrenia, or bipolar disorder—were more likely to develop Long COVID. To do this, researchers looked at the electronic health records (EHRs) of more than 1.6 million adults across the US. They found that adults with an SMI had a higher chance of developing Long COVID than adults without an SMI. This may be because SMIs can cause stress and problems with a person’s immune system, which could make them more likely to develop long-lasting symptoms after having COVID-19. Among adults with an SMI, higher rates of Long COVID were seen in older people, non-Hispanic Black and Hispanic people, people with public health insurance, people with other long-term illnesses like heart disease or diabetes, and people who were hospitalized after they got COVID-19 for the first time. This study is important because it shows that healthcare teams should look at SMIs in addition to other risk factors to help prevent and treat Long COVID. 

Short Summary
Observational Pediatric Vaccination

Thaweethai, T; Gross, RS; Pant, DB; et al., Vaccine

This RECOVER study looked at whether the COVID-19 vaccine could help protect teenagers ages 12–17 from developing Long COVID. Researchers studied 1,231 teenagers enrolled in RECOVER who had confirmed COVID-19. Some were vaccinated before they got COVID-19 (724 teenagers), and some were not (507 teenagers). Researchers made sure the 2 groups were similar in terms of sex, date when they got COVID-19, and when they joined the study to make comparisons fair. They found that teenagers who were vaccinated in the 6 months before getting COVID-19 for the first time were about one-third less likely to get Long COVID. This study is important because it shows that COVID-19 vaccines, which were previously found to prevent getting COVID-19, can also protect against developing Long COVID in young people.

Short Summary
Observational Pregnant Women Risk Factors Viral Variants

Metz, TD; Reeder, HT; Clifton, RG; et al., Obstetrics & Gynecology

This RECOVER study looked at whether pregnant women who had the Omicron type of COVID-19 were more likely to have Long COVID than women who were not pregnant when they had the Omicron type of COVID-19. Researchers studied the symptom surveys and study visits of more than 2,400 RECOVER pregnancy participants, ages 18–45, to see if being pregnant while having COVID-19 impacted the risk of developing Long COVID. They found that about 10.2% of the participants who had COVID-19 while pregnant later got Long COVID, compared with 10.6% of the those who were not pregnant at the time of infection. This suggests that there was no real difference in the chance of getting Long COVID based on whether someone was pregnant or not when they got COVID-19. This study is important because it helps researchers better understand the risk of developing COVID-19 based on whether or not someone is pregnant.

In this RECOVER study, researchers wanted to find out if natural language processing (NLP) could be used to identify Long COVID symptoms in children. NLP is a tool that can help find details in electronic health records (EHRs) beyond what is usually looked at in EHRs, such as diagnosis or billing codes (known as standard EHR data). Researchers used an NLP tool to look for 25 signs of Long COVID in children: 21 symptoms (like pain or extreme tiredness) and 4 types of daily life challenges (such as trouble with school). They compared children who had been diagnosed with Long COVID to those who had COVID-19 but did not develop Long COVID. The NLP tool analyzed more than 48,000 doctors’ notes within the EHRs of more than 10,000 children across 12 hospitals. Researchers found that the NLP tool identified almost all 25 symptoms much more often in the children who had Long COVID. The NLP tool also often identified patients’ symptoms that were not recognized when researchers only looked at standard EHR data. The study shows that using NLP to read EHR notes can help researchers better understand the symptoms and daily challenges that children with Long COVID experience when compared to looking only at codes and medication lists. This supports the idea that NLP should be used when doing scientific studies that need to identify children with Long COVID.

Video
Observational Adult Broad Symptoms Risk Factors

Fain, MJ; Horne, BD; Horwitz, LI; et al., Journal of the American Geriatrics Society

This RECOVER study looked at how Long COVID symptoms change as people get older and how often those changes happen. Researchers compared younger adults (ages 18–59) and older adults (age 60 and older) who did and did not have COVID-19. They found that Long COVID was most common in people ages 40–59, and less common in those ages 70 and older. Among the participants ages 70 and older, symptoms like fatigue, pain, and hearing problems were less helpful in identifying Long COVID because they were also common in older people who had never had COVID-19. Instead, symptoms of Long COVID in older adults were more likely to include problems with smell and taste as well as stomach issues. This finding is important because it helps doctors know what to look for when diagnosing and treating Long COVID in older patients.

Video
Observational Adult Broad Symptoms

Horwitz, LI; Becker, JH; Huang, W; et al., JAMA Network Open

This RECOVER study looked at how sense of smell changed over time in people who had COVID-19. Researchers gave a “scratch-and-sniff” test to a large group of people about 2 years after they had COVID-19. This test, called the University of Pennsylvania Identification Test (UPSIT), checks whether people can smell certain odors. The study found that 8 out of 10 people who felt that they had lost or had changes in smell after having COVID-19 were in fact not able to smell the odors normally. Even two-thirds of the people who thought their sense of smell was completely normal had a weaker sense of smell than they realized. These findings show that a weaker sense of smell can be a common and lasting problem after COVID-19. Because changes in smell have been linked to memory and thinking problems in other conditions, this could mean that people with changes in smell from COVID-19 could be at risk for thinking and memory issues. Doctors should use special smell tests to point out smell loss that patients may not notice to help them understand their condition and its risks, like not being able to smell smoke or spoiled food.

In this RECOVER study, researchers wanted to update a smart computer program, called a machine learning pipeline, to better identify people with Long COVID. In 2021, the first version of the program, called LCM 1, was created to identify people with or likely to have Long COVID. LCM 1 depended on people having a COVID-19 diagnosis date in their electronic health records (EHR). This meant LCM 1 could miss people who may have taken a COVID-19 test at home. LCM 1 also did not look at information about whether people got COVID-19 more than once. To improve the program and create a new version called LCM 2, researchers used more than 5 million EHRs from a large set of data called the National COVID Cohort Collaborative (N3C). They taught the program to look at a person’s health information over many years, not just starting from their first recorded COVID-19 diagnosis. Researchers found that LCM 2 was very accurate. They used it to estimate that about 1 in 10 people in the database who had COVID-19 went on to develop Long COVID. This study is important because it shows that older machine learning models, like LCM 1, can be updated to keep up with the way an illness is tracked and diagnosed over time. This can help other researchers improve their machine learning models to produce more accurate findings.

Short Summary
EHR Adult New-onset and Pre-existing Conditions Risk Factors

Anzalone, AJ; Krichevsky, S; Yoo, YJ; et al., Clinical Journal of the American Society of Nephrology

In this RECOVER study, researchers wanted to understand the connection between Long COVID and chronic kidney disease (CKD) in adults who had COVID-19. CKD is long-term, permanent damage to the kidneys. Researchers looked at the electronic health records (EHRs) of more than 2 million adults across 59 health systems in the US to see if people with CKD were more likely to develop Long COVID. The study found that, compared to people without CKD, those who had even mild cases of CKD were more likely to get Long COVID after COVID-19. Researchers also found that, compared to adults who did not get Long COVID, those who developed Long COVID and had healthy kidneys before getting COVID-19 were more likely to develop new CKD or have worsened kidney function within a year. These findings show how Long COVID and kidney disease can affect each other and highlight how important it is for doctors to monitor people’s kidney health after they get COVID-19.

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