Researchers say that after more than two-years and a nearly $1.2 billion investment, they have come up with 12 symptoms that reliably classify people as having long Covid. This is a working definition which should speed research into this disabling disorder.
The study was published in the medical journal JAMA on Thursday. It is the first of many studies that have been conducted by the National Institutes of Health as part of their RECOVER initiative. RECOVER stands for Researching Copid to Enhance Recover.
The cohort is one of five arms within RECOVER. It was launched in September of 2021. Nearly half a billion dollar award - a significant chunk of RECOVER's budget - went to the Grossman School for Medicine at New York University.
The RECOVER initiative, with its huge budget and scope, has been a great relief to people who have long Covid. Some of them are too ill even to get out of bed or a wheelchair for a long time.
Census data suggest that 6% (or 100 million) of US adults with Covid experience new symptoms or persistent symptoms years after their initial infection. Scientists have called this phenomenon postacute sequelae or PASC. People with PASC and long Covid have reported more than 200 symptoms.
Patients have expressed their dismay at what they perceive as the lack of urgency from the federal government, as deadlines to start clinical trials testing potential treatments have been pushed back. They say that the focus is on observational studies such as this one which attempt to characterize a disease they believe has already been well defined - through decades of research into post-viral diseases.
NIH organizers still defend their decision to invest into this definition. They say it is crucial to finding effective treatment.
The adult cohort is 'going to be the most diverse, largest cohort of Covid patients in the world that are deeply characterised', said Dr. Gary Gibbons, Director of the National Heart, Lung, and Blood Institute.
The new criteria was welcomed by doctors who treat patients with Covid, but were not part of the study.
I know we are all eager to find answers. We all want evidence-based recommendations for therapeutic interventions, said Dr. Daniel Griffin of Columbia University, an infectious diseases specialist.
"But we do understand the challenges here. This is a brand new disease. This is a brand new phenomenon. Before we waste resources on bad trials and rush into the field, we must first understand what we are studying. Griffin stated that we need to know the target group.
Lack of biomarkers, which doctors can measure or test to determine if someone has long Covid, has stymied the search for treatments.
Doctors often use clinical scales for diagnosing diseases such as lupus in cases where a biomarker unique to the disease has not been identified.
We have a lot of diseases that we can't test for with a blood test. In those cases, there are a number of symptoms. We look for those who have the symptoms that we've identified,' explained Dr. Leora HORWITZ, professor at the Departments of Population Health and Medicine of NYU and a lead investigator in the new study.
Long Covid is defined by the World Health Organization and US Centers for Disease Control and Prevention as any symptoms, signs or conditions that persist or develop following a Covid-19 infected.
Horwitz says that although this definition is flexible and allows people to have a variety of symptoms, it is not useful for research.
She said, 'We have to define something concrete and identify a group of individuals who we believe are suffering from this condition.' We can then study these people and learn what's going on inside their bodies.
Researchers asked almost 10,000 adults, some of whom had already been infected with Covid and others who hadn't, based upon antibody testing, to answer detailed questions regarding 44 symptoms that affected all parts of the human body. The list was then narrowed down to 37 symptoms that were experienced by more than 2.5% individuals.
Then, each symptom was given a score. Twelve symptoms received a score of one or higher.
- Postexertional Malaise or a worsening in health after mental or physically active activity
Changes in sexual capacity or desire
Change in taste or smell
The symptoms are weighted based on how likely they are for them to occur in those with long-term Covid as compared to those without. For example, a loss of taste or smell was given eight points because it's very rare in people without Covid. Dizziness is given a score of one.
Covid was defined as a long Covid for people who scored 12 or more on their entire list of symptoms.
Horwitz explained that the goal is to identify those symptoms which are most distinctive. It doesn't necessarily mean they're most common, most severe, most burdensome or most important for patients. This does not mean anything. This just means that these are the ones which are collectively more likely to occur in people who had Covid compared to those who didn't.
Researchers found that when they applied the criteria across the entire group they are following for their study, it identified about 23% who had been previously infected. Only 4% of the people who hadn't been infected were flagged. This makes it unlikely that a person who scored 12 on the scale is a false negative - meaning that they screened positive but didn't have it.
The researchers were also able to find out some interesting things about the participants. People were more likely than not to have Long Covid if infected prior to the arrival of Omicron: about 35% of those infected pre Omicron met the Long Covid definition, compared with 10% of participants infected by Omicron subvariants.
However, researchers said this doesn't necessarily mean that 1 in 3 Covid cases before Omicron was introduced resulted in long Covid. They believe that people who signed up for the study before November 2021 were likely infected because they still had health problems and were motivated to find answers.
Long Covid is more common among participants who first became infected with Omicron. This finding validates earlier studies that used health records.
If people were hospitalized for their infection, they were more likely than not to develop long Covid. They were less likely to get it if vaccinated.
"This is something anyone can do. To be vaccinated, and to be boost as boosters are released. She said that it was one of the only proactive things people could do to lower their risk of getting long Covid.
Researchers also discovered that the condition long Covid is distinct from myalgic fatigue syndrome/chronic encephalitis (ME/CFS), which can follow a virus illness.
Horwitz stated that while most of the people who met the ME/CFS definition also met the long Covid definition, the opposite wasn't always true. Only 10% to 20% of people who met the long Covid definition also met the ME/CFS definition, meaning that it's a subset but not exactly the same.
Researchers said that certain symptoms appeared to cluster together, and defined subgroups of Covid patients. The researchers found that people with a loss of taste or smell did not have as many symptoms, which indicates a milder condition. The second group reported mostly postexertional fatigue, gastrointestinal problems and malaise but not any trouble with memory or thinking. Third subset reported mainly postexertional fatigue, brain fog and malaise. The fourth group, the most severely affected, had multiple symptoms, and reported most commonly fatigue, dizziness and brain fog.
This may be a limitation in the scale, and is one of the main reasons why it must continue to improve. Robert Gross and Vincent Lo Re III of the Perlman School of Medicine at the University of Pennsylvania, who wrote an editorial that was published with the study, are co-authors.
They wrote that 'anyone who has a high level of functioning, despite a loss of smell and taste, should be considered to have the same entity.
There are other limitations to the study. The study hasn't yet reached its full enrollment and information could change as more people enter the analysis.
Participants can also sign up themselves, so the weight may fall more on those who are motivated by ongoing health issues.
The study participants' race and ethnicity is representative of the US population, with about 15% being Black and 16% Hispanic or Latino. However, there is a gender imbalance. Nearly three quarters of the participants are women. Only 5% of the participants are from rural areas. It may not reflect the experiences of rural people or men.
The Covid scale is not applicable to children, as they will have their own Covid long scale.
Researchers say this is a first attempt at a scale that may one day be used for diagnosing people with Covid.
Daniel Lewis, long-time Covid patient, and advocate, says that the definition is still in need of improvement. He also worries that doctors may rush to implement it.
Lewis, who has spent most of his life in an electric wheelchair or bed since a Covid infection ten months ago, said: "I don't want anyone to use this as a diagnosis."
He believes that the first definition leaves out too many people.
Doctors are reading it and trying to determine if they have patients with long Covid. He said, 'I don't believe this is a great way to do it.