Research Summaries

The researchers leading the RECOVER-VITAL clinical trial published a paper describing the study’s design in the journal Clinical Trials. RECOVER-VITAL tested 2 different treatment durations of nirmatrelvir/ritonavir, an antiviral medication commonly used to treat mild to moderate COVID-19. The trial evaluated whether the antiviral could improve Long COVID symptoms including brain fog, dizziness, fast heart rate, fatigue, and low energy. Researchers believe these symptoms may be caused by viral persistence, which occurs when the virus that causes COVID-19 remains in the body and disrupts organs or the immune system.

The design paper outlines how the trial was organized and conducted to produce accurate results. The authors describe how the protocol was developed, as well as the development of the primary and secondary outcomes. The authors also describe the study’s broader goals: advancing understanding of Long COVID symptoms, strengthening clinical trial design, and evaluating potential treatments at a time when limited evidence was available.

The researchers leading the RECOVER-AUTONOMIC clinical trials recently published a paper describing the study’s design. The trial was a multicenter, randomized, double-blinded, placebo-controlled, platform trial employing a flexible, adaptive design. The trial tested 3 possible interventions, or study treatments, for postural orthostatic tachycardia syndrome (POTS), an autonomic nervous system disorder that can develop in some people with Long COVID. These study treatments included intravenous immunoglobulin (IVIG), ivabradine, and coordinated non-drug care.

The design paper includes details on the development of the study protocol and determination of the outcomes studied. Results from RECOVER-AUTONOMIC will be shared in the coming months.

This RECOVER study looked at whether social determinants of health (SDOH) affect the risk of children developing Long COVID after having COVID-19. SDOH are the conditions in the places where people live, learn, work, and play that can affect health, such as safety or access to food, education, and healthcare. Researchers looked at survey data from more than 4,500 children. The surveys included questions about family income, access to food, school life, and how children are treated by others. The study found that children whose families struggled to pay for basic needs, like housing and food, were much more likely to have Long COVID. However, children in families who always had access to food, even if they struggled to pay for other things, were less likely to have Long COVID. This study also found that children who felt they were treated worse than others or parents who did not have enough support from friends and family had a higher chance of Long COVID. This RECOVER study is important because it shows that access to food and a supportive community may play a key role in protecting children from developing Long COVID.

This RECOVER paper combined research findings, patient experiences, and possible explanations about how the body works to understand how different germs and health factors might play a role in Long COVID. Researchers looked at how having a viral, bacterial, or fungal infection before, during, or after COVID-19 might make someone more likely to develop Long COVID. The combined information suggests that these infections can confuse the immune system, making it attack healthy cells or cause problems to the body’s organs. For example, the stress of fighting SARS-CoV-2, the virus that causes COVID-19, might “wake up” old viruses that were dormant (asleep or inactive) in the body, which can make a person sicker or more likely to develop Long COVID. This paper is important because it shows that Long COVID is complex and may involve different germs that change the body’s responses to infection. By learning more about these connections, researchers hope to find better ways to test for and treat Long COVID in everyone.

In this RECOVER study, researchers wanted to find out how Long COVID symptoms change over 15 months. To do this, researchers studied 3,659 adults who had COVID-19 before joining the RECOVER study or while they were enrolled. Researchers found that Long COVID does not look the same in everyone. Instead, people’s Long COVID symptoms usually fell into 1 of 8 different patterns over time. While most people felt better after recovering from COVID-19, about 1 in 20 participants had symptoms of Long COVID that lasted throughout the entire study. About 3 in 25 participants with Long COVID had symptoms that came and went. Other participants did not have Long COVID symptoms early on but started having health problems many months after having COVID-19. These findings show that doctors should continue monitoring patients for a long time after they have COVID-19 because their symptoms can stay, come and go, or start several months after getting sick. Understanding these patterns will help researchers find better ways to prevent and treat Long COVID in different groups of people.

The RECOVER-NEURO Cognitive Dysfunction (BrainHQ, PASC-CoRE, & tDCS) clinical trial tested 3 non-drug treatments to see if they improved thinking, focus, and memory for people with Long COVID. The 3 treatments included:

1. An interactive online brain training program called BrainHQ.
2. A virtually delivered, small group cognitive rehabilitation program called PASC-Cognitive Recovery or PASC-CoRE.
3. 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.

This RECOVER study tested a new way to identify Long COVID in children. Researchers created a special computer-based tool, called a computable phenotype (CP), that scans electronic health records (EHRs) for specific codes and symptoms linked to Long COVID. To test the CP, researchers scanned records for nearly 340,000 children who had COVID-19. Doctors then checked a smaller group of 651 children’s records to see how well it worked. The study showed that the CP was able to successfully find that a child had Long COVID. But it sometimes marked symptoms that fit in with health problems someone had before getting COVID-19 (pre-existing conditions), so it wasn’t clear if those symptoms were due to COVID-19. When the researchers updated the CP to pay closer attention to pre-existing conditions, it became more accurate at identifying Long COVID from EHRs. This study is important because it provides a faster and more consistent way for researchers to identify Long COVID in large groups of children. This tool can help doctors give better care to children with Long COVID.

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.