Long COVID is a less talked-about aspect of the COVID-19 pandemic, yet its impact on society is already profound. Although this problem is still largely flying under the radar of the life sciences industry, a couple of first movers have already initiated clinical programs to address the condition. If more companies move into this space, long COVID may prove a catalyst for R&D in other related and underserved indications, like chronic fatigue syndrome.
Long COVID – also known as post-COVID-19 condition or post-acute sequalae of COVID-19 (PASC) – is a condition where a person fails to return to their baseline health after the initial acute phase of COVID-19 has passed. The list of associated symptoms is long with as many as 200 symptoms reported, the three most common being shortness of breath, cognitive dysfunction (also referred to as ‘brain fog’), and fatigue (reported in more than 50% of cases). The condition can be debilitating, causing physical incapacity due to severe fatigue, cardiac or respiratory dysfunction, neurological impairment, and psychological impacts.
“It has been estimated that a full quarter of people who contract the SARS-CoV-2 virus develop long COVID.”
It has been estimated that a full quarter of people who contract the SARS-CoV-2 virus develop long COVID, equating to tens of millions of people affected worldwide. Strangely, long COVID doesn’t seem to be restricted to the populations deemed most at risk for COVID-19 itself. In addition to the elderly or immunocompromised, the condition also occurs in those who are otherwise healthy and young, including patients who only had mild or no symptoms during the acute phase of their infection. Although children have a lower chance of developing long COVID, it still seems to affect 5-10% of those who contracted the corona virus, with longer-term implications for their health currently unknown. Initial statistics show that the proportion of people who have not fully recovered after 6-9 months ranges between 26-39%, creating an additional layer of complexity to the current global healthcare crisis.
Time to act
There’s clearly an urgent need for long COVID research and interventions – considering the large market and long-lasting nature of the condition, you would expect the life sciences industry to be highly motivated to develop targeted long COVID therapeutics. In reality, companies in this space have yet to receive government grants or VC investments.
Despite the lack of funding, a few first movers have publicly announced their entry into the field using repurposed drugs. US-based biotech Axcella is launching a Phase 2a clinical trial to evaluate its experimental drug AXA1125 in long COVID. Originally developed for Nonalcoholic Steatohepatitis (NASH), the company is hoping that AXA1125’s broad restorative effects on mitochondrial function and energetic efficiency can help long COVID patients experiencing exertional fatigue.
Mercaptor Discoveries is advancing its small molecule MD-012 towards clinical trials, targeting a protein involved in neuroinflammation and platelet aggregation – two things currently considered possible causes of the ‘brain fog’ experienced by many long COVID patients. Cryostem is also preparing an application for clinical trials addressing neurological dysfunction in long COVID, but using a stem cell therapy which the company is also testing on Post-Concussion Syndrome (PCS) to promote tissue regeneration.
“Diseases that share similar symptoms could serve as guiding stars for researchers.”
It may seem like a short list, but there have been many developmental roadblocks contributing to the scarcity of companies in this field so far. The medical definition of the condition was only made official by the WHO in October 2021, and we still have an incomplete understanding of the underlying pathophysiology and mechanisms of the condition, as well as a lack of biomarkers for clinical studies.
Progress is rapidly being made, however, with many research projects initiated this year to examine the disease mechanisms from different angles, including blood abnormality, immune dysregulation, and autoimmunity. The US government has provided the NIH with USD 1.15 billion in funding to study long COVID, and the UK’s NIHR has provided researchers with GBP 19.6 million to identify autoimmune antibodies, autoreactive T-cells, and biomarkers in long COVID patients. As these hurdles to progress are overcome, we expect more industry activity in this space.
Two birds with one stone
One of the crucial considerations in long COVID research and drug development is discriminating between true long COVID symptoms and those resulting from the acute disease itself. To crack the underlying mechanisms of the condition, we first need to exclude factors like long-term organ damage, the effects of an ICU-stay, and the mental distress brought on by the initial infection.
Diseases that share similar symptoms could serve as guiding stars for researchers. One example is chronic fatigue syndrome: also known as Myalgic Encephalomyelitis, this is a rare condition characterized by long-term, profound fatigue. As with long COVID, the cause of chronic fatigue syndrome is still unknown but is hypothesized to be triggered by a viral infection. Diagnosis and management of this syndrome may help determine the medical approach to long COVID.
Other areas under active investigation in relation to long COVID are immune dysregulation and autoimmunity. Notably, symptoms of autoimmune diseases such as multiple sclerosis also include neurological issues and fatigue. Acute infections with the mosquito-transmitted Chikungunya virus can also result in chronic autoimmune effects, including relapsing or persistent arthritis mimicking rheumatoid arthritis.
Long-term effects following acute viral infections – known as post-viral syndrome – have been documented in many other viruses, including the Epstein-Barr Virus (causing glandular fever, also known as mono), Cytomegalovirus, and even the original SARS-CoV. Altogether, there are many who may benefit from an influx of funding and innovation in the long COVID space, as new disease mechanisms and therapeutic avenues are uncovered which may be applicable in other conditions.
Opportunities for life sciences industry
With the end of COVID-19 nowhere in sight, and long COVID presenting a huge unmet medical need, we expect the few biotechs that have already entered the field to rapidly be joined by others. Progress in this space will not only affect long COVID, but also present opportunities for researchers and companies looking to tackle other conditions that share a common pathophysiology. Long COVID may serve as a catalyst to stimulate R&D and translational programs in fields such as chronic fatigue syndrome, providing new solutions for millions of patients.
