USA: The RECOVER Initiative - Long Covid research

Reminder that this starts in 1.5 hours.

 

They presented findings from two large observational studies of Paxlovid use during acute COVID, using a "Target Trial Emulation" methodology, which is an attempt to emulate an RCT as much as possible using observational data. They use statistical methods such as "Inverse Probability of Treatment Weighting" to control for as many possible confounders as possible.

PCORnet (see thread for study)
For the PCORnet study, they studied 497,499 patients. Paxlovid treatment was required to be within 5 days of infection.

159,659 high risk received treatment
5,597 low risk received treatment
272,048 high risk did not receive treatment
35,874 low risk did not receive treatment
​

When looking at incidence of long COVID over 180 days after infection, they found that about 3 fewer people developed long COVID per 100 people that were infected when taking Paxlovid. The hazard ratio was 0.88. (12% less likely to develop long COVID). Also found decreased incidence of hospitalization greater than 30 days after infection and decreased mortality with Paxlovid use.

They looked at the effect of Paxlovid on specific long COVID symptoms in various categories (neurologic, skin, pulmonary, etc). The hazard ratio is significantly less than 1 in almost every category (Paxlovid associated with decreased risk of LC). The two exceptions that were not significant were associations with hair loss and with receiving the long COVID diagnostic code U09.9.

They also looked separately at high risk and low risk patients. High risk means older age (≥ 50), smoker, or underlying conditions such as cancer or diabetes. There was a significant association of Paxlovid with decreased LC in high risk, but not low risk patients. When splitting by factors such as specific condition or age in the high risk population, the hazard ratios are still almost consistently significant when grouping based on these factors.

N3C (see thread for study)
This study on the N3C cohort also found decreased risk of long COVID with Paxlovid use. 1 fewer person per 366 infected when treated with Paxlovid [about 0.27 per 100 when comparing to 2.99 per 100 in PCORnet cohort].

There was a lower risk of long COVID when looking at the overall definition (RR=0.94, 95% CI: 0.92-0.97). When splitting by symptom clusters, there was significant decrease for cognitive phenotype (RR=0.86, 95% CI: 0.81-0.91) and fatigue/malaise phenotype (RR=0.92, 95% CI: 0.88-0.96), but not respiratory phenotype (RR=1.03, 95% CI: 0.97-1.09).

Also corroborated previously published findings about Paxlovid reducing risk of hospitalization and death.

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The findings were fairly close for relative risk between the cohorts showing a modest reduction in risk of long COVID in those who take Paxlovid during acute COVID infection, specifically in high risk patients.

The differences in absolute risk reduction were likely due to the different definitions used for long COVID. About 30% of people developed LC using rule-based PCORnet definition, versus only about 5% using machine learning-based N3C definition.

Edit: Fixed typo in relative risk value for fatigue/malaise phenotype.

 

Nature: "Identifying commonalities and differences between EHR representations of PASC and ME/CFS in the RECOVER EHR cohort"

 

Recording available

4/14/25, RECOVER Initiative: 'Effectiveness of Paxlovid in Protecting Against Long COVID: EHR Insights'

Speakers:
Dr. Fei Wang, Cornell University
Dr. Rainu Kaushal, Cornell University
Alexander (Sandy) Preiss, RTI
Dr. Abhishek Bhatia, University of North Carolina
Hannah Mandel, NYU Langone Health

 

May 13 RECOVER webinar: 'Understanding metformin use and Long COVID and ME/CFS following COVID-19 infection: Insights from two studies'

 

1/30/25 - Univ. of Alabama Birmingham (UAB), Dept. of Pathology: 'Benson secures RECOVER grant to study effects of Long COVID'

'The grant will fund $158,000 per year and will run through April 2026.'

'Paul Benson, M.D., Professor and Autopsy Section Head in the Department of Pathology's Division of Anatomic Pathology, was awarded a Researching COVID to Enhance Recovery (RECOVER) grant from the National Institutes of Health for his project, titled, "A Multi-site Pathology Study of Post-Acute Sequelae of SARS-CoV-2 Infection'

"We believe the RECOVER tissue pathology (autopsy) study will inform Long COVID research and treatment options for years to come," Benson said.

'Autopsies will be performed to address the pathophysiology of the potential long-term effects of SARS-CoV-2 infection on human health'

 

Weren't all those RECOVER grants cancelled by the new administration?

 

RECOVER affiliated grants were restored following patient advocacy.

I can’t speak for non-RECOVER grants though.

 

That's good news! Is the programme still giving out new grants?

 

R3 Seminar Recap: Effectiveness of Paxlovid in Protecting Against Long COVID: EHR Insights

'Mr. Bhatia noted that the results from the two studies are complementary and reach a consensus that Paxlovid can help reduce the risk of Long COVID. Both studies are currently in pre-print, which means they are publicly available online while the results continue to be peer-reviewed by other researchers to confirm accuracy and scientific rigor. Mr. Bhatia also recommended that future research should account for the wide range of symptoms associated with Long COVID and explore tailored treatments for different symptoms.

Studies that analyze EHR data do have limitations, Dr. Wang explained. For example, structured EHR data may be incomplete, and researchers do not have a way to determine whether people actually took Paxlovid after being prescribed the medication. However, EHR studies allow researchers to examine large groups of people from all walks of life, meaning that results will be relevant for a wide range of people.'

 

Join RECOVER for the next R3 Seminar, Understanding Metformin Use and Long COVID and ME/CFS following COVID-19 Infection: Insights from Two Studies, to be held Tuesday, May 13, 2025, at 12:00-1:30 pm ET.

RECOVER investigators will present findings about the association between metformin use and the incidence of Long COVID using the EHR-based cohort study. The speakers will also present findings about the incidence and prevalence of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) following COVID-19 infection using the adult observational cohort study.

Panelists for the seminar include:

• Steve Johnson, University of Minnesota
• Carolyn Bramante, University of Minnesota
• Suzanne Vernon, Bateman Home Center
• Yu Chen, NYU Langone Health

 

5/8/25, 'ACP Long COVID Interest Group - Dr. Linda Geng (Stanford)'

Geng: "RECOVER Initiative has some of the biggest platform trials and different trials for different phenotypes right now and then there should be another hopefully, to launch soon, the second phase of the trials called RECOVER-TLC or Treating Long COVID. I'm excited to see hopefully what agents will be chosen for that next round of trials. And then currently and previously, part of the original phrase of the clinical trials under RECOVER, we were running trials testing for example, transcranial stimulation, as well brain HQ and other interventions for brain fog. There's a trial we're running right now testing Ivabradine and other sites are testing potentially IVIG for the POTS phenotype, there's another trial running right now for exercise intolerance and sleep, so there's lots of trials underway. And I know there's nationally trials testing other anti-inflammatory agents and of course there's tons of trials that are registered, so this is definitely not comprehensive by any means, but I think the big categories that I'm really interested to see are those anti-inflammatory agents, immune modulators, potentially neurological agents, cardiovascular agents as as well as again non-pharmacologic strategies and possibly combining some of these therapies may be also the ultimate answer."

 

Just sharing from RECOVER webinar today. I'm sure recording will be up shortly

Text: 'Appreciate Dr. Vernon answering my Q&A question'

https://twitter.com/user/status/1922340468202840552

 

Daily Herald [Chicago]: '‘I’m still battling this’: Endeavor Health recruiting patients for long-COVID studies'

'Endeavor Health, formerly NorthShore University HealthSystem, has been part of multiple long-COVID studies conducted through Researching COVID to Enhance Recovery, or RECOVER, a nationwide research program established by the National Institutes of Health.'

'Shah expects some answers “very soon.”

“The only way I can explain it is like you feel like you hit a brick wall, because all of a sudden you need to lay down,” the Buffalo Grove woman said.

'“It could be brain fog and all these neurologic-type issues. It could be cardiopulmonary issues related to exercise intolerance.'

“You probably know someone that has had long COVID, really, if it’s 8% of the population, 20 million people,” Shah said. “..there are these cases where…they just can’t function anymore, and they’re not getting better …"

“the sooner we have answers,” she said, “the sooner we can all move on with our lives.”

 

5/15/25, Stanford Medicine: 'The Engine of Innovation: Ten Years of SCCR at Stanford Medicine'

'SCCR has played a key role in the NIH RECOVER initiative, one of the largest studies of Long COVID in the nation. With more than 1,000 participants enrolled at Stanford and SHC Tri-Valley, the team is leading several intervention sub-studies exploring treatments for brain fog, autonomic dysfunction, and post-exertional malaise.'

 

Global Autoimmune Institute: 'Data Confirms Long COVID Can Mirror ME/CFS'

'A major new study from the NIH RECOVER Initiative confirms what patients have reported for years: Long COVID and Myalgic Encephalomyelitis (ME/CFS) can look remarkably similar'