Are Monoclonal Antibodies the Future of Long COVID Treatments?

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Four years have passed since the start of the COVID-19 pandemic. While lockdowns and vaccine jabs may now be a distant memory for the majority who lived through those first years, a minority are still experiencing the effects of the virus every day. These are the people with long COVID, a broad term to describe the debilitating, often perplexing symptoms that can persist after a SARS-CoV-2 infection. Sufferers have been diagnosed with atrial fibrillation, cardiac arrest, anemia, diabetes, fatigue, acute gastritis, myalgia, memory problems and peripheral neuropathy, among other dozens of other maladies. According to one comprehensive study published in Nature last year, just over 30% of these sequalae remained "significant" in non-hospitalized patients for two years.

Despite the persistence of these symptoms - and the misery they can inflict - treatments haven't exactly been forthcoming. The bulk of long COVID research carried out over the past four years has attempted to understand the health issue, not cure it. These kinds of characterization studies have at least been fruitful, though, bearing a new leading explanation of what may be causing long COVID: viral reservoirs.

The theory goes that parts of the virus may have hidden themselves away in patients' tissues, prompting an ongoing immune response. One study published in PLOS Pathogens in 2022 found that long COVID patients had 100 times the levels of SARS-CoV-2-specific T cells normally seen in people who recovered from the virus - one of the many findings that supports the viral reservoir hypothesis.

So, based on this theory, is there any specific treatment that could finally rid patients of their lingering COVID? Quite possibly, according to one group of researchers, but it may need to be provided to patients ASAP, as time is running out…

Monoclonal antibodies and COVID-19

Back in 2021, some of Dr. Paul Pepe's long COVID patients started coming to him with desperate pleas; they had been reinfected with the virus and were terrified of losing any health progress they had made with their condition since first becoming infected in 2020. Luckily, by late 2021, Pepe, of Dallas, Texas, had something to offer them: monoclonal antibodies.

By that time, a variety of COVID antibody solutions had been developed by several pharmaceutical companies as a precautionary tool to prevent serious illness in vulnerable patients with an active infection. The solutions' synthetic proteins act like human antibodies, sticking to the virus' spike protein and neutralizing it before it can wreak its damage.

After prescribing three of his long COVID patients with an antibody cocktail of casirivimab and imdevimab (known commercially as Regeneron™), Pepe was relieved to hear that his patients' infections hadn't worsened their long COVID symptoms. And that wasn't the only good news; Pepe was somewhat astounded to learn the patients' symptoms had disappeared altogether. One 43-year-old woman had been plagued with fatigue, joint pain and palpitations since her first COVID infection in January 2021; 5 days after receiving the Regeneron cocktail, all her symptoms had vanished.

"Dr. Pepe called me up almost two years ago saying that he'd had this experience using COVID monoclonal antibodies in long COVID patients that had got reinfected," Dr. Nancy Klimas, director of Nova Southeastern University's Institute for Neuro-Immune Medicine, told Technology Networks. "And they when [he] treated them for their second infection with the antibodies, he had these outcomes that were surprising, and seemed to be curative in the patients."

The explanation goes that, if remnants of SARS-Cov-2 really are clinging to the intestinal tract and other corners of patients' bodies, then an infusion of monoclonal antibodies could finally flush out the virus.

"[Let's say the virus] went into a compartment somewhere and is smoldering, [creating] a long-term persistent infection - this is the hypothesis for this kind of treatment, because then your immune system could find it, and the antibody could find it, bind to it and clear it," Klimas added.

As the director of Nova Southeastern University's Institute for Neuro-Immune Medicine, Florida, Klimas has been at the forefront of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) research for decades. Given the similarities between the often-maligned illness and long COVID - debilitating fatigue, memory problems, etc. - she recently turned her attention to leading new studies into treating the latter, including one study to replicate Pepe's findings. There's just one major issue.

Best before 2022

Unfortunately, the evolution of COVID-19 has outmoded the very infusions that could treat the first wave of patients damaged by the virus. Stocks of these initial monoclonal antibodies still exist, but their expiry dates are getting nearer.

"It won't be hard to recruit 20 people into the study, because everybody wants this stuff," said Klimas. "The real big problem is the drugs themselves; they're old."

"The first cases were done during alpha, beta and delta variants [of COVID-19]. And the monoclonal antibodies that we had at the time were designed for those variants, and they work right for those variants. They don't work very well for Omicron. In fact, the US Food and Drug Administration (FDA) pulled them because they don't work on the current variants. So right now, they're on hold at the FDA," Klimas added.

"The bamlanivimab monoclonal [made by Eli Lilly, AbCellera and Junshi Biosciences] has an expiration date next summer, so I can get this study done using their drug," she added. "Regeneron was the drug that we reported on [in Pepe's original trial], and I would love to be doing that one. But they have an expired label. So, we're talking to them to see if there's a way to be able to get a unexpired drug there. They've been nice."

Having been supplied with the bamlanivimab monoclonal mixture, Klimas intends to start her trial this April. There's a long path ahead, and even if the drug again proves efficacious, there's currently no guarantee it will be reproduced by its manufacturer to meet long COVID patient demand. Nonetheless, Klimas says the prospect of the antibodies are so good, there's still reason to have hope.

"I'm very excited about the potential for monoclonal antibodies to work and I'm glad that we're going to be able to try it," she said. "I do think some of the sickest people I've seen are the people that had COVID-19 from 2020 and 2021, when there was no vaccine to protect you and the variants were wicked bad. They do tend to be this sickest end of the spectrum of long COVID. So it's great if we come up with a therapy for the sickest folks, and the longest term ill."

"This is a group of people that often feel helpless because they've been sick long enough," she added. "It's just hard to hold on to hope every single day when you feel really, really bad every single day. It's really important to do the studies and find the answers."

About the interviewee

Dr. Nancy Klimas is the director of the Institute for Neuro-Immune Medicine at Nova Southeastern University. She has 40 years of professional experience researching myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), Gulf War illness (GWI), fibromyalgia, and most recently Long COVID.

Dr. Klimas was speaking to Leo Bear-McGuinness, a Science Writer for Technology Networks.