In the absence of a common treatment for long COVID, researchers from around the world documented the best currently available therapies.
An international team of researchers has proposed a multimodal approach involving a mixture of physical and pharmacological interventions to treat post-acute infectious syndromes (PAIS), including the condition known as long COVID that affects survivors of SARS-CoV-2 infection, the virus that causes COVID-19.1,2
COVID-19 can cause long COVID in some patients. | Image credit: © CREATIVE WONDER | stock.adobe.com
The team sought to examine the optimal treatment strategy for PAIS, which affects not only survivors of COVID-19 but those of influenza and acute infections such as Ebola and polio. Symptoms across these conditions, regardless of the precipitating condition, are consistent and overlap, “indicating the potential contribution of a shared etiopathogenesis,” the team wrote.1
Through a systemic review of registered trials for treatment of PAIS, the team sorted through a variety of therapies, including pharmacotherapies, rehabilitative approaches and other methods like psychotherapy. Though they cautioned that not one treatment can be used for all patients, they discussed multiple forms of treatments that had a positive effect on patients with long COVID.1
Metformin, a first-line drug in the treatment of type 2 diabetes mellitus, was found to be a pharmaceutic treatment that had a positive effect on long COVID. A safe and affordable treatment, metformin is a powerful suppressor of chronic inflammatory responses in macrophages. By reducing levels of inflammatory markers seen in acute and chronic inflammation, the drug was hypothesized to be helpful in the treatment of long COVID.1,4
Specific studies were cited by way of a targeted machine analysis to back up its effectiveness. A double-blind trial in which adults with overweight or obesity and SARS-CoV-2 infection took metformin for 2 weeks found that they were less likely than those who took a placebo to report a diagnosis of long COVID.1
Low-dose naltrexone (LDN), an oral μ-opioid receptor antagonist, is another treatment that showed promise in the systemic review. LDN is FDA approved to treat opioid and alcohol dependence; through the formation of endogenous opioids, the immune system is modulated, and the proliferation of B and T cells is inhibited.1
LDN’s anti-inflammatory effects have led to its use in treating diseases like multiple sclerosis and fibromyalgia. In one recent test assessing LDN as a treatment for long COVID, it demonstrated a positive effect on clinical symptoms and patient-reported measures of fatigue, according to the investigators. The drug’s immune modulating and pain reducing effects make it an ideal candidate to pair with metformin.1
Physical therapies were also discussed by the team, making this a truly multimodal approach. One such treatment, extracorporeal apheresis can enhance blood viscosity, thereby reducing oxidative stress and mitigating inflammation. In one study, the treatment led to significant improvement in long COVID symptoms in 70% of patients.1
In addition, transcutaneous electrical nerve stimulation, an alternative strategy for non-transponders of pharmacotherapy, was discussed, though the exact mechanism of how the process works is not fully understood.1
“We've learned that post-viral syndromes are incredibly complex, with no single cause or cure,” Steenblock said in a news release. “Our research suggests that by combining different treatment modalities, we might be able to reset the body's systems and provide relief to those suffering from these debilitating conditions."2
1. A multimodal approach to treating long COVID and other post-acute infectious syndrome was revealed by a team of researchers.
2. The approach centers on both pharmacotherapies and rehabilitative therapies.
3. By emphasizing an approach from many different angles, patients with a variety of manifestations of long COVID can be treated.
This new study comes as investigations in long COVID continue and advancements are made in treatment. This month, the FDA granted an investigational new drug application to BioVie for bezisterim, an insulin sensitizer with anti-inflammatory properties, for the treatment of long COVID. This correlates with Steenblock et al.’s study and others finding that metformin, a treatment for diabetes, had positive effects on long COVID development.3,4
"What's particularly exciting about this approach is its potential to address the wide range of symptoms seen in PAIS," Milo A Puhan, co-author of the study, said in the news release. "From fatigue and brain fog to cardiovascular issues, we're looking at a treatment strategy that could tackle multiple aspects of these conditions simultaneously."2
Despite the current availability of potential treatments, there is still no common and effective therapy for PAIS. There is a major lack of comprehensive, prospective studies, making it difficult for the investigators to draw conclusions about a treatment’s efficacy and effects.1
“To develop a clinical scoring system for PAIS, multicenter studies involving a larger patient cohort, inclusive of those who have not responded to treatment, will be imperative,” the study authors concluded. “A comprehensive approach is needed to address global health disparities while also encouraging specialists to combine well-established treatments with potentially lesser-known therapies to achieve optimal results.”1
