Six Years In: The Future of Long COVID (Part 3 of 3)
What's Being Tested, What's Coming, and What You Can Do Now
Welcome to a Special Edition of Waves of Evidence. Normally, this is a monthly research roundup where I break down and rate key Long COVID studies through the lens of a physical therapist specializing in Long COVID rehabilitation. However, I will be doing something a little different this month. The month of March happens to be Long COVID Awareness Month. Today’s piece is the final piece of a three-part series in honor of Long COVID Awareness Month. If you missed Part 1 or Part 2, click the links to read them.
Today, we look ahead to the future of Long COVID. I will be covering what is being tested right now and where things are heading.
What’s Being Tested Right Now
Six years ago, there weren’t any clinical trials specifically targeting Long COVID. There wasn’t even a research infrastructure. Today, a PubMed search of “Long COVID” yields over 4,400 research studies. Although, there are more studies than this when using additional names for Long COVID like PASC. At this stage, one of the largest initiatives to solve Long COVID is the NIH’s RECOVER initiative, which stands for Researching COVID to Enhance Recovery. The NIH received $1.15 billion to research Long COVID, and it stands to be one of the largest federally funded investments for a new condition in U.S. history. Since RECOVER’s launch in 2021, the core mission has focused on two things. One: why some people develop long-term symptoms after Sars-Cov-2 while others completely recover and two: figure out how to prevent and treat it….(here is where I insert that the #1 way to prevent having Long COVID is to never get COVID in the first place, but that is another topic for another day).
To be clear, the first few years of RECOVER wasn’t testing treatments at all. It was building the scientific foundation by collecting millions of datapoints to understand the foundation of Long COVID. You can’t design a good trial if you don’t know what you’re treating. That groundwork is what made the treatment phase possible. Between 2023 and 2025, RECOVERY moved into its first round of clinical trials for treatment, organized into five different categories. In total, there are 8 clinical trials exploring 13 different interventions. The five categories were created to target a different symptom cluster identified as most burdensome by patients:
The Five Categories of NIH RECOVER’s Initiative
RECOVER-VITAL: Aimed to study viral persistence and answer the question about whether paxlovid can help treat Long COVID.
RECOVER-NEURO: Aimed to study possible treatments for brain fog. Three interventions were studied including Brain HQ (an interactive online brain training program), BrainHQ + PASC CORE (training in strategies to manage mental tiredness), and Transcranial Direct Current Stimulation (brain stimulation via electrical current).
RECOVER-AUTONOMIC: Aimed to study treatments for those impacted by symptoms like dizziness, fast heart rate, or other changes in automatic body functions. There are 2 different interventions being studied including the medication Ivabradine (aka Corlanor) and Gamunex-C (a form of intravenous immunoglobulin or IVIG).
RECOVER-ENERGIZE: Aimed to study treatments for exercise intolerance and post-exertional malaise. This has 2 different interventions. One is personalized cardiopulmonary rehabilitation and tailored exercise for people without post-exertional malaise. The other is for people with post-exertional malaise who will be participating in a structured pacing program with a pacing coach.
RECOVER-SLEEP: Aimed to study treatments for sleep disturbance in Long COVID. There are two treatments being studied. They will study the effects of the medication for modafinil/Solriamfetol for those who have hypersomnia and sleep too much. They will also study the effects of Melatonin and light therapy to help regulate sleep-wake patterns.
At this point, RECOVER-NEURO is the only arm that has published results and to no surprise here, none of the three interventions were proven effective. Every group, including the two control groups, showed modest improvement over time, meaning no single intervention outperformed another. This is the phenotype problem playing out in real time. Brain fog isn’t one thing. Someone whose cognitive symptoms stem from serotonin disruption is not going to respond the same way as someone whose brain fog is rooted in autonomic dysfunction or viral persistence. Lumping them together and studying them this way was destined to yield average results. That being said, this isn’t a failure. It’s groundwork. The rest of the original RECOVER trials aren’t expected to release results until sometime in 2026 or 2027, and you know I will be all over it when they do.
The Next Phase of NIH RECOVER: What’s Next
The NIH RECOVER initiative is now officially in its RECOVER-TLC (treating Long COVID) phase with four interventions chosen for its first round of trials.
The four interventions are:
Baricitinib: a JAK inhibitor that blocks a specific inflammatory pathway to reduce inflammation in autoimmune and inflammatory diseases. Other JAK inhibitors such as Rinvoq are commonly used for rheumatoid arthritis, atopic dermatitis, and ulcerative colitis. This is meant to target persistent inflammation and immune dysregulation, and this study is currently enrolling.
Low-dose naltrexone: Naltrexone is historically a drug used to treat alcohol and opioid addiction by blocking the euphoria experienced with these substances. It’s a non-addictive opioid blocker at higher doses, but at lower doses (hence the name LOW DOSE naltrexone) under 4.5mg, it operates differently on the system. It acts to reduce inflammatory neurotoxins, boosts the production of endorphins and improves the immune response. While there are research studies already proving the safety and efficacy of LDN in Long COVID, but no randomized control studies to date. This study is a randomized control trial, and enrollment for this trial is expected to open to people ages 6-25 years old in summer 2026.
GLP-1 receptor agonist: This is the same class of drugs behind medications like Ozempic, which are known for weight loss. Glucagon-like-1 peptides have also been shown to directly influence immune cells like macrophages and lymphocytes, which results in the reduction of pro-inflammatory cytokines like TNF-ɑ, IL-6, and IL-1𝛽. All three of these are known to be elevated in Long COVID and contribute to chronic inflammation, so in theory this should help. By reducing inflammation and oxidative stress, GLP-1s also have the potential to restore endothelial function. This study is expected to enroll in summer of 2026.
Stellate ganglion nerve block: this study is still in protocol development. The 2 week public commentary period just ended March 8th, 2026. The aim of this study is to evaluate the effects of performing a medical procedure in which a physician injects an anesthetic in the stellate ganglion, which is a bundle of nerves located at the bottom of the neck. This bundle is part of the sympathetic nervous system. Numbing it temporarily disrupts the signals to hopefully reduce any sympathetic dominance. It is used in complex regional pain syndromes and PTSD. In this case, it will be used to examine its effect on the autonomic nervous system in Long COVID. Similar to the studies on LDN, there aren’t any randomized control trials on this to date. All we have are cohort studies and case studies. In one cohort study, it claimed that 86% of the 41 patients reported a reduction in Long COVID symptoms. It will be interesting to see what the protocol is that they develop as there is the question of receiving a block on one side versus both sides, and how long the block lasts. I think that is the most important piece of information we need to know. This one is definitely a ‘to be continued’.
The Trials are Running. The Clock Is Ticking
We are now in a unique position where we aren’t waiting for the science to begin, we are waiting for the results. And I will be honest with you. I am holding a mix of skepticism and cautious optimism about what those results will show.
Let’s start with the skepticism.
