, 2025-04-21 06:30:00
The Centers for Disease Control and Prevention confirmed its first US case of COVID-19 in early 2020, and 8 months later the World Health Organization described a post-viral condition called long COVID. Since then, millions of Americans, around 8% of those with acute COVID, have also been identified as having long COVID. And to make matters worse, on March 24, the Office of Long Covid Research and Practice within the Department of Health and Human Services was shuttered, leaving scientists concerned for the future of research.
As scientists have gained a broader understanding of the nature of long COVID, they and other health experts hope to make strides in treating this debilitating condition.
Despite the progress that has been made in helping doctors recognize symptoms tied to long COVID, no standard diagnostic tests or treatments have been identified. With a broader understanding of monoclonal antibodies, combination antiviral therapies, viral reservoirs, and disease phenotypes, experts predict 2025 could be the year better ways to diagnose and treat this vexing condition will emerge.
“We need to be laser focused on clinical trials so that we arrive at more precise treatments sooner rather than later,” said Ziyad Al-Aly, MD, senior clinical epidemiologist at Washington University in St. Louis, St. Louis, Missouri.
Here are some of the most exciting predictions for the coming year.
#1 More Focused, Improved Treatments
In 2024, scientists gained a deeper understanding of the mechanism of long COVID and how it causes serious disease in patients. Several mechanisms can cause the condition, and some of them may overlap. The cause of long COVID are viral reservoirs — leftover viral fragments which remain in the blood or in the tissue of the body after the acute phase of the infection. Symptoms persist because patients are never able to fully eradicate the infection.
Other research has shown that the virus changes the makeup of the microbiome in the gut, which, in turn, causes symptoms. Another mechanism for disease is the virus’ impact on the mitochondria, the energy powerhouse of the cell.
With a better understanding of long COVID’s causes, researchers are looking at potential treatments that target those underlying mechanisms. For example, over the next year, researchers will be looking at targeting viral reservoirs in the body using a combination of antivirals and monoclonal antibodies.
#2 A Major Step Forward for Monoclonal Antibodies
For researchers and patient advocates alike, the promise of monoclonal antibodies for the treatment of long COVID holds a lot of hope in the coming year. The treatment involves cloning white blood cells and then using them to target the viral reservoirs that activate the immune system and cause long COVID symptoms.
“This is one of the most exciting potential treatments for patients,” said Charlie McCone, 35, a patient advocate from San Francisco who has had long COVID for the past 4 years.
A small study published in the January 2024 issue of The American Journal of Emergency Medicine found full remission of long COVID symptoms within a week of receiving an infusion of monoclonal antibodies.
Researchers and clinicians are anxiously awaiting the results of a large-scale clinical trial at the University of California San Francisco, where participants are receiving a SARS-CoV-2 monoclonal antibody or a placebo to see whether long COVID symptoms are alleviated postinfusion. The hope is that for some patients, monoclonal antibodies could spell relief of their symptoms in the coming year.
#3 More Antiviral Combo Therapies
Initially, researchers found that Paxlovid was ineffective for the treatment of long COVID. Then another study came out which found that when it was taken for longer periods of time, for some patients, it did alleviate symptoms, especially brain fog and fatigue. As a result, a number of researchers think there may still be promise in Paxlovid. But it’s more likely that it will require a combination of antivirals taken for longer periods of time to finally get at the virus that’s hidden deep in the body’s blood and tissue.
With viruses like HIV, for example, it takes a much longer duration on antivirals before the medications are able to clear the virus from the body. And the thought is that it might be similar to SARS-CoV-2.
“I think it will take high doses and combinations of antivirals to get at these viral reservoirs,” said David Putrino, the Nash Family Director of the Cohen Center for Recovery from Complex Chronic Illness, New York City, and a national leader in the treatment of long COVID.
The combination may be different for each patient, based on how much and where the virus is hiding in the body. For example, if the viral reservoir is hiding in a certain type of tissue, it might be harder to reach than if it’s in the blood, said Putrino.
#4 Precision Medicine Based on Phenotype
It’s been well established by researchers and clinicians that long COVID is more accurately an umbrella term for a condition that has various phenotypes or subtypes of disease.
A June 2024 study published in The Journal of Infectious Diseases identified various groups based on a cluster of symptoms. For example, sensory symptoms like a loss of taste and smell, fatigue symptoms related to extreme physical fatigue and brain fog, and cardiovascular or respiratory symptoms.
In 2025, the hope is that researchers will design studies that include patients grouped with a similar cluster of symptoms, resulting in treatments that work on a specific disease phenotype. “We desperately need to see a shift away from the mindset of thinking this is just one disease,” said Putrino.
#5 Understanding Why New Strains Are Milder Than Earlier Ones
It’s amazing to think that long COVID has been going on for nearly half a decade and some patients that got it in the beginning are still very much struggling with serious symptoms. McCone, who has had the condition for 4 years, still struggles day to day. He can only work a few hours a day and depends financially on his partner to stay afloat.
But the good news is that some research is showing that the first strains of COVID-19 and earlier variants like Delta seemed to produce more severe forms of long COVID than the later strains.
“We know for sure that the new cases are milder than the earlier strains,” said Grace McComsey, MD, who leads a long COVID center funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. “However, we’re still seeing some new cases of long COVID that are serious.” She added that we have a lot of leads, but in many ways, we still have more questions than answers.
McComsey, Al-Aly, McCone, and Putrino all separately addressed the elephant in the room: Huge potential cuts to funding at the National Institutes of Health as a result of the Trump Administration and how they might impact long COVID research.
“I would be lying if I didn’t say that I was extremely concerned,” said Al-Aly.
