Wait goes on for effective long Covid treatments

While Covid-19 rapidly emptied cities and shut industries, long Covid has been more stealthy.

Yet its impact in the past two years has been huge: a study last month showed the condition is so widespread that the “healthy life years” lost across the population surpassed those lost to cancer or heart disease.

Long Covid took 80 healthy life years per 1,000 residents — a preferred way of measuring quality of life — in the first two years post-infection, compared with 50 for cancer and 52 for heart disease, according to researchers at Washington University School of Medicine and the Veterans Affairs St Louis healthcare system.

Ziyad Al-Aly, study co-author and epidemiologist at Washington University, says it shows a “staggeringly high burden” and pointed out that, unlike cancer and heart disease, there is no treatment for long Covid. “It appears that the effects of long Covid for many will not only impact such patients and their quality of life, but potentially will contribute to a decline in life expectancy and also may impact labour participation, economic productivity, and societal wellbeing,” he says.

The number of sufferers — estimated conservatively at 65mn worldwide — suggests it is a public health emergency. As at the start of Covid-19, clinicians are far from understanding how to treat the disease. But, unlike the beginning of the pandemic, few are being funded to find new options quickly.

While widely known as long Covid, the World Health Organization describes it as “post-Covid-19 condition”, and defines it as usually occurring at least three months after the initial infection and with symptoms that last for at least two months. Common symptoms include fatigue, shortness of breath, and cognitive dysfunction, often called “brain fog”. But patients also suffer from a far wider range of symptoms and scientists have discovered many potential mechanisms behind the condition. Sufferers can have heart problems, diabetes and disorders of the nervous system.

Researchers have found radiological abnormalities in the brain, heart, and lungs; microclots that suggest an inflammatory response; and evidence that there could be reservoirs of the virus in some patients, according to a paper in July in Nature Reviews Immunology. Another recent journal article examined how the virus could disturb the function of people’s mitochondria, the energy factories inside cells.

While long Covid is clearly complex, some patients and scientists are frustrated with the time it is taking to catalogue the problems, before moving on to find treatments. Todd Davenport, a physical therapy professor at the University of the Pacific, says one problem is that there are not enough specialists in the “previously unloved [field of] post-infectious diseases”, such as chronic disease syndrome, so new researchers have flooded in: “Folks who have been active in other areas of biomedical research and are sort of picking up post-infectious illnesses on the fly.”

Despite the long list of potential mechanisms, there are no tests for long Covid. But a recent paper using data from the UK’s post-hospitalisation Covid-19 study found blood tests taken when a patient was in hospital with the infection could help predict if they would later suffer from cognitive problems as part of long Covid.

Eric Topol, a cardiologist who co-authored a paper on the condition in Nature Reviews Microbiology, says diagnostics are important for creating treatments, as they allow recovery to be measured. “We don’t have a biomarker, a convenient lab assay to track it in individuals, and that holds us back,” he says. Researchers are looking at using scans to detect microclots, ECG to identify heart problems, and MRI scans to examine breathing dynamics.

Trials to find treatments have been slow to get off the ground. Scientists are prioritising finding existing drugs to repurpose, in the hope that this could be quicker than starting from scratch. Those drugs include diabetes drug metformin, antihistamines usually used for allergies, and the anti-gout drug colchicine. Naltrexone, used to treat alcohol and opioid use disorders, is being studied at a lower dose as it has also been given for chronic fatigue syndrome.

However, the studies are often too small to reach a solid conclusion. And many of the drugs are off-patent, so their makers are unlikely to invest in trials. Researchers have relied on funding from bodies such as the US National Institutes of Health (NIH) and the UK’s National Institute for Health and Care Research. Now, the money is drying up.

Diana Güthe, founder of patient group Survivor Corps, says the NIH’s research has been “a day late and a dollar short” and it “is only interested in characterising long Covid, they are not interested in solving long Covid, not interested in creating treatments and therapeutics.” The NIH says it is a “high priority to rapidly advance from fully understanding [the condition] towards the testing of treatment candidates for long Covid”.

Meanwhile, patients are experimenting with unproven drugs on themselves or falling into the hands of charlatans offering often costly cures. Topol says efforts should be made to recruit 100,000 patients online and set up digital trials. “Three and a half years into this we still have so little to show for the work on treatment,” he says. “We shouldn’t give up: it is too important.”