Bhasha Mewar has had it in the past. Over the past two years, Mewar has spent nearly all of her life savings going to a lot of different doctors to try and tame her chronic symptoms. She has taken a lot of drugs, some of which were prescribed for reasons she didn't understand.

He always told Mewar that she needed to exercise when she visited her lung doctor. She said she couldn't walk to the bathroom.

There are millions of people living with long COVID, a complex and sometimes disabling syndrome that can linger for months or years after an acute disease. Doctors and people with the condition are left to play whack-a-mole with its many symptoms. Sometimes people with the syndrome turn to self-medication. At least 26 randomized clinical trials of long-COVID therapies are under way, but many are too small or lack the necessary control groups to give clear results. Danny Altmann is an immunologist at Imperial College London.

Researchers are looking at the pathology that underlies COVID. Key trials could yield results for drugs that target the immune system, blood clot or fragments of the coronaviruses. Altmann is still hopeful. There is a lot of funding out there for the right things. Something is going to make a difference.

Chart showing number of long covid drug trials.

The source is Airfinity.

Complex condition

There is uncertainty about the root cause of the condition. Researchers hope that insight into which hypotheses are correct will help them develop therapies. The immune system is being stimulated by the remnants of the disease. The infections can cause damage to the body long after the initial illness. There are hints that COVID-19 could cause blood clot. It is1-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-6556 is1-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-65561-6556

Many researchers think that long COVID can have more than one cause. The ideas suggest a route to relief. Antiviral drugs may be able to eliminate the persistence of the disease. The immune system could be quenched by drugs. Micro-clots could be dissolved by powerful anti-coagulant.

Although evidence is gradually accumulating in support of each of these possibilities, their links to long COVID are still tenuous enough to stop some investigators from launching clinical trials. The hypotheses are getting better. They are not cast Iron.

Martin Landray is an epidemiologist at the University of Oxford. A promising treatment could be ruled useless in a clinical trial if it was given to the wrong people.

There is no list of symptoms that can be used to enroll participants or sort them into different groups. More than 200 symptoms have been associated with the syndrome, and many are hard to measure, such as fatigue and brain fog. Mewar keeps a library of photographs of the medicines she has tried in order to keep track of her treatments. They would stay here a week and then leave.

Landray is an architect of a large UK trial of treatments for COVID-19. The trial found that low doses of dexamethasone reduced deaths from severe COVID-19 by one third. Landray has received requests from people with long COVID to engineer a similar effort. He says he hasn't been involved in the space. The science seems to be too young.

A trickle of trials

Some researchers are moving forward. There are several trials trying to tame the immune system. Colchicine is used to treat gout and is often prescribed to people with long Covid. Steroids and other immunosuppressants, such as sirolimus, which is used to prevent organ rejection after a transplant, are being used in other trials. According to Hannah Davis, who lives in New York City, small trials and anecdotal reports suggest that antihistamines provide a Band-Aid solution. Davis is a co- founder of the Patient-Led Research Collaborative. It would be great to know that it is helping.

An experimental drug called RSLV-132 is being investigated by a rheumatologist in Seattle. The drug is intended to removeRNA from the blood, which is thought to promote inflammation. In small trials, the company has found some success with its drug in reducing fatigue in people with Sjgren's Syndrome.

A patient lying on a hospital bed with sensors attached to his chest at a long COVID clinic

A doctor looks at a patient at a long-COVID clinic. A credit is given to Amir Cohen.

Extreme fatigue, muscle weakness and memory problems are some of the symptoms that other approaches aim to manage. The University of Toronto's Roger McIntyre is conducting a trial to find out if a drug that has been shown to boost cognitive function can be used to treat long-term COVID.

The cardiovascular system is still being impacted by COVID-19. Some studies have shown that inflammation in the lining of blood vessels could cause the formation of small blood vessels in the lung. A clinical trial is planned to test a cocktail of drugs that target the clotting process. Two people who had been waiting for the trial became emotional when she presented her plans to them.

Duncan doesn't want to reveal which drugs have been chosen out of fear that people will try to buy them on the internet and treat themselves. She says that these are people who are very sick and desperate for help. The drugs increase your risk of bleeding and need to be monitored very carefully.

Some people with chronic illnesses have been taking care of themselves. A triple-drug therapy that was tested in a small trial of 24 people with long COVID has been replicated by some. The trial has not yet been published in a peer-reviewed journal. Davis says that others have traveled to clinics that will perform apheresis, a procedure that filters the blood with the aim of removing clotting agents that can cause inflammation. She says that these people have paid thousands of dollars for a procedure that is not proven to work.

Future hopes

There are some drugs that are not being tested in trials. There are several antivirals used. Some researchers think these drugs could ease the symptoms of long COVID, too, as evidence grows that a linger of the SARS-CoV-2 could cause the problem.

At the end of last year, the US Food and Drug Administration approved two new antivirals, one of which was made in New Jersey. Since the beginning of the Pandemic, remdesivir has been used to treat COVID-19.

There are no studies looking at whether these antivirals could help with long-COVID symptoms.

Researchers will continue to follow clinical- trial participants for six months after treatment with Paxlovid and Lagevrio. People with long Covid are being tested to see if they have remdesivar. As data pile up on how common and long- lasting COVID can be, pharmaceutical companies might be persuaded to launch more studies. According to the UK Office for National Statistics, more than one million people in the United Kingdom reported symptoms three months after being exposed to an infectious disease. Over three hundred thousand people had been experiencing symptoms for at least 2 years.

After the numbers were released, a pharmaceutical company agreed to sponsor a trial of an antiviral drug that Strain had proposed be tested, but he won't say which one. He says that it took a while for the companies to be ready to invest. Drugs are expensive.

A woman suffering from long COVID looks inside a cupboard filled with medications to treat her symptoms

A woman goes through the pills and supplements she takes to manage her symptoms of depression, anxiety, and brain fog. The Washington Post's Carolyn Van Houten was credited.

According to Akiko Iwasaki, an immunologist at Yale University in New, each of these trials could help researchers to better understand the causes of long COVID, as well as how to treat it. She says that this is a chance to learn more about the disease and not just find a cure.

Large-scale, well-designed trials can be difficult for individual investigators to set up. She says that we can't just have one site doing one thing. There needs to be a coordinated effort.

Most of the money dedicated to long-COVID research in the United States and UK has gone to finding treatments. He feels like there hasn't been enough will from the top.

Larger trials are getting ready to begin, but have yet to enroll participants. The United States has a large study called RECOVER that focuses mostly on long COVID. There was a call for proposals for trials that would test interventions for treatment or prevention.

The trial called STIMULATE-ICP began to enroll participants this summer. The first-round candidates for the trial are the anti-Inflammatory Colchicine, two antihistamines, and an anticlotting drug. Further proof of concept trials of other agents could be added to a later phase of the trial. One study found that two doses of an adenoviral-vector vaccine was associated with a 9% reduction in the odds of long COVID in people who were exposed to the coronaviruses before beingvaccinated.

Patchwork treatments

Doctors and people with long COVID will continue to experiment with combinations of drugs and therapies until the results of these trials are in. Kathy Raven, an infectious-diseasegenomicist at the University of Cambridge, UK, has received a lot of treatment that consists of management techniques, such as setting alarms to help her remember to take her medicine, and guidance. She was told recently that she will be discharged from the clinic with no change to her condition.

Other physicians are using their previous experience to treat the same conditions. Taslim Uddin is a rehabilitation specialist who treats people with long-term weakness in their muscles after being bitten by a mosquito. Post-exertional malaise is a condition in which debilitated muscles are rehabilitated without worsening their function. He says that most people who he has treated respond well to similar therapy, but there are some who remain seriously ill.

Some physicians are concerned about the risk of harm from long-COVID treatments. The deputy director of the Disease Control and Prevention Center at the National Center for Global Health and Medicine in Tokyo says that some doctors are using epipharyngeal abrasive therapy, in which the throat is scratched with cotton swabs soaked in zinc chloride He says the goal is to decrease inflammation at a key site of coronaviruses. Some physicians claim to have achieved promising results in small trials. I don't think it's evidence based and it's not good for patients. Randomized controlled trials are needed. He doesn't know of any randomized controlled trials for this in Japan.

Mewar has encountered doctors who push him to exercise more graded exercise therapy is still advocated by some physicians. Some people with post-viral illnesses, such as chronic fatigue syndrome, have found graded exercise therapy to make their symptoms worse. Duncan doesn't think graded exercise therapy should be available.

Mewar doesn't want to follow the scientific literature or put her faith in doctors. She knows that if she exerts herself, her symptoms will come back to life.

She takes a mixture of vitamins from online accounts and is researching traditional Indian medicines for her symptoms. She stopped trying to explain what she was talking about. I try to take care of my body.

Nature 608 and 258- 260.