Long Covid-19 affects as many as one in five people who previously had an acute Covid-19 infection. But a constellation of distinct symptoms—ranging from breathing problems to brain fog—makes designing clinical trials a steep challenge.
The solution will be finding common symptom denominators based on a deeper understanding of long Covid-19’s underlying pathogenesis, explains Dr Anthony Fauci, Chief Medical Advisor to the US President, at a National Press Foundation Q&A attended by Clinical Trials Arena. “Endpoints absolutely have to be standardised,” he says.
Currently, the largest common denominators of Covid-19 symptoms appear to be exercise-induced exhaustion and fatigue, Fauci notes. Symptoms with a greater variation include temperature dysregulation, dysautonomia, sleep disturbances, and mental cognitive problems, also known as brain fog, he adds.
However, Fauci notes the field still lacks an adequate understanding of long Covid-19’s underlying mechanisms: “We’re very much swimming in the dark until we get more information.”
Mixed results in long Covid-19 clinical trials
In an effort to better understand long Covid-19, the National Institute of Health (NIH) recently launched the 700-patient observational RECOVERY trial (NCT05292274). Over the course of two years, the study tracks four primary endpoints: presence of inflammation, fibrosis, thrombosis, and necrosis.
“We’re collecting large cohorts of people to try and find some clinical and laboratory common denominators and then pursue a pathogenic mechanism,” Fauci says of RECOVERY. “Once you get a pathogenic mechanism, then you could start thinking about treatment. Otherwise, there’s no guidepost on what to treat.”
Meanwhile, drug developers are taking aim at long Covid-19 treatments with a slate of clinical trials targeting a variety of symptom profiles. So far, the completed trial results have been mixed.
Earlier this month, PureTech announced its long Covid-19 candidate LYT-100 failed a Phase II trial targeting respiratory complications. One month prior, AIM ImmunoTech announced positive results in a Phase III long Covid-19 trial treating fatigue. But most long Covid-19 trials are still ongoing, including a Humanetics trial for long-term pulmonary damage that recently expanded.
As drug developers search for long Covid-19 solutions, drug repurposing has emerged as a common strategy. Earlier this year, Tonix Pharmaceuticals told Clinical Trials Arena about plans for a Phase II trial testing its fibromyalgia asset. This trial and others follow a similar trend of drug repurposing in acute Covid-19 antiviral studies.
As Covid-19 shifts from its pandemic peak to a new endemic stage, the growing unmet need for long Covid-19 treatments looms large.
Misinformation in the age of Covid-19
Throughout the press briefing, Fauci was most animated when addressing questions about the bevy of misinformation surrounding Covid-19 in the US. “I’ve never seen anything of the magnitude of the deliberate misinformation, disinformation, and conspiracy theories that we’re seeing with Covid-19,” Fauci tells around 20 reporters at the briefing. “It is truly unprecedented to the highest extent.”
Fauci admits this is a difficult problem to solve, adding that the best possible solution is to flood the system with correct information. At times, this has come at a great political cost, Fauci says, pointing to the times former US President Donald Trump publicly attacked him.
Reflecting on his public perception and legacy, Fauci says there is a big dichotomy: “For a great proportion of the population, I’ve become symbolic of truth and integrity and telling things as they are. And for another portion of the population, I’ve been public enemy number one.”