Doctors Express Hope By Turning To Limited Treatments For Coronaviruses

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Now, for the first time since a wave of patients flooded their emergency rooms in March, Pascual and others on the front lines express a feeling that they say they have not felt for a long time – gleams of hope. They say they have designed an admittedly limited and imperfect toolkit of drugs and therapies that many believe give today’s patients a better chance of survival than those who only came a few weeks ago.

To be clear, these are not proven therapies to kill or stop the virus. They range from protocols for diagnosing and treating dangerous, but sometimes invisible, respiratory problems, which can be an early warning of covid-19 in some people, to efforts to reduce the severity or duration of the disease. At this point, these are still experimental approaches by doctors who are desperately looking for ways to help the seriously ill and throw anything they can think of about the problem.

The menu of treatment options, tried individually and increasingly in combination, includes blood plasma from survivors of Covid-19, a rich source of antibodies that can help neutralize the virus; drugs to suppress the body’s own immune response, which some believe goes into hyperdrive as it tries to fight an invader; blood thinners, which reduce the risk of deadly clots; and third, antivirals, such as remdesivir, the drug Gilead Sciences, which recently received approval for emergency use from the Food and Drug Administration.

Randomized clinical trials are needed to confirm early anecdotal evidence, with results likely within months. But doctors say they believe they see positive results from these and other things they have learned by trial and error in the past 10 weeks.

“Things have changed almost completely, going from knowing nothing at all to rumors from Milan, Seoul and Wuhan – to say, ‘Well, it’s something we know we can do,'” said Pascual .

The World Health Organization also issued a note of optimism on Tuesday, saying it sees “potentially positive data” in four or five treatments for coronaviruses and has planned additional studies to make recommendations. “We have certain treatments that seem to be the subject of very early studies limiting the severity or duration of the disease,” said spokeswoman Margaret Harris.

While doctors are still far from having a complete picture of the virus and its effects, “it is a different world today,” said David Reich, cardiac anesthesiologist and president of Mount Sinai Hospital in New York. .

A flood of small discoveries

Medicine as a field is evolving slowly. But during the pandemic, the months were reduced to days, decades to weeks. The knowledge accumulated over the past two months is not due to a single eureka moment but rather to a constant flow of small discoveries.

Yogen Kanthi, assistant professor of cardiology at the University of Michigan, said the medical community has “a much better idea of ​​who are the major contributors to death and is moving to the next phase of trying more targeted treatments.” “

As doctors began to think of Covid-19 as a disease that causes clotting and inflammation problems, he says, research has turned in new directions.

“Is there a drug that will do all of this?” My gut tells me it’s more of a combination of things, “he said.

Kanthi and colleagues in rheumatology who focus on immune problems launch study to examine various combinations of anti-inflammatory drugs and blood thinners to find out if they work best together, as well as their timing, dosage and mix optimal.

Some other drugs that have shown promise include the heartburn drug that contains the active ingredient Pepcid. A study of 1,536 patients found that those who took it were more likely to survive, but the researchers warned that this could only be a coincidence.

A study published last week in The Lancet found that a combination of three antiviral drugs – used separately to treat HIV, hepatitis C and multiple sclerosis – appeared to speed healing in some patients.

Although the status of some drugs has been high, many others – including those with toxic effects that could have hurt patients – have been largely excluded. This includes the use of hydroxychloroquine – the antimalarial drug touted by President Trump and administered to patients with coronavirus in many medical centers, even by doctors skeptical of the evidence but who had nothing else to offer .

“Curveballs”

In February, warnings about covid-19 from the Centers for Disease Control and Prevention described a “pneumonia-like” disease making its way around the world. The health agency has highlighted three symptoms: fever, cough and shortness of breath. These first communications, used as part of the test criteria and as the basis for hospital preparations, reflected what was known at the time but sent the whole medical response wrong.

Pascual recalled that when the five Penn Medicine hospitals prepared for a flare-up, they focused on the lungs. The fans were lined up in neat rows. Additional personnel were called in to train in emergency treatment of respiratory complications.

But as the intensive care units were filling up with covid-19 patients, the startled doctors began to see dysfunction in other organs: the kidneys. Liver. Intestines. Skin. Even the brain. Pascual called them “curve balls”, and there were many.

The same goes for medical centers in other parts of the United States.

In New York, Reich was touring the hospital as his load of patients accelerated, and an intensive care doctor grabbed him in the hallway to tell him how strange it was that the tubes of the devices kidney blockage. A few days later, he heard from a lung specialist who saw an unusual pattern of high levels of carbon dioxide in the patients, even after giving them large amounts of oxygen. Then a neurosurgeon called about unusual clots in patients in their 30s and 40s.

About 200 miles north, at Brigham and Women’s Hospital in Boston, Mandeep Mehra, medical director of the heart center, and colleagues discussed what he called “an interesting dichotomy with this infection.”

The vast majority, about 80 to 85 percent, of people appear to be fighting without hospitalization while 15 to 20 percent fall very ill.

“The main question is who are these people and how can we predict them,” said Mehra. “Very clearly, some facts have started to emerge, namely that this disease is not just a virus disease. Something else special happens to the human body where it creates a deregulated response. ”

Improvisations

Some of the ways doctors can save more lives involve simple changes to the protocols that have been destroyed and reinvented to reflect the peculiarities of a new disease.

One of the most important is to diagnose dangerous but often hidden lung problems.

Many doctors, nurses and paramedics have described being disturbed by patients with life-threatening illnesses but with no obvious signs of breathing difficulties. Patients with “silent hypoxia” may have alarming oxygen levels but will not experience shortness of breath. The problem results in pneumonia when the lungs are not getting enough oxygen but the carbon dioxide is still being expelled. Many of these patients were initially dismissed by primary care physicians as having mild cases – until their bodies were so hungry for oxygen that they lost consciousness and died. Now doctors advise anyone suspected of having Covid-19 to use finger-clip oximeters to assess the oxygen saturation of their blood, and staff at some nursing homes regularly use them to monitor their residents.

Doctors have also improvised new approaches to increase respiratory support, including the way respirators are used.

One of the main conclusions is that a simple procedure of turning patients to the side or stomach in a process called “pronation” could bring some people’s oxygen levels back to normal. Doctors said they believed it saved a number of patients from being placed on a ventilator. Once people put on the respirators, complications can arise and it takes a lot more medicine and more staff to keep them alive.

Many hospitals have also revised the time, concentration, and flow of oxygen they use in patients, and some vow to shift the time they put patients on a ventilator – whether earlier or later than they never could have in the past – made a difference.

Doctors also said that they realized that some patients were suffering from respiratory distress because their throat was inflamed and causing problems with the ventilation tubes. This has been easily resolved with steroids that reduce swelling.

An article published by Mehra in the New England Journal of Medicine showed that ACE inhibitors, a drug used by millions of Americans to control blood pressure, but which has been stopped in many hospital patients due to fears that it could worsen their illness, seemed safe when used. on these patients, at least.

Other discoveries have been more somber.

A number of centers have started to see unsafe heart rate readings in patients who were on hydroxychloroquine and who subsequently died. Many of these patients were seriously ill with multiple affected organs, so the exact cause of death was unclear. But doctors were worried enough to give up using the drug weeks before a study by the Veteran’s Administration showed a higher risk of death, and the Food and Drug Administration warned against using it on 30 April.

Meanwhile, test results for various drugs followed one another quickly: an HIV drug by AbbVie showed no improvement in a clinical trial of 199 patients. An arthritis medication from Regeneron and Sanofi has produced equally disappointing results.

Some theorize that the early failures of certain drugs that target an overactive inflammatory response may be due to the fact that these drugs tend to suppress only one of a broad category of cytokines, or proteins important in cell signaling. “It was like playing with a mole,” said Kanthi of the University of Michigan. “You block a cytokine, then another appears. “

One of the challenges of therapies for covid-19, said Pascual, is that the ravages caused by the virus seem to last a long time – in some patients, two, three, or even six weeks. Severely ill patients may need many different treatments during this time to stay alive – blood pressure medication for the heart, dialysis for their kidneys, respirators for breathing. If they can be held steady for this time until doctors can remove the stand from the machines, he said, more patients may stand a chance.

“What is reassuring is that this virus, like others, eventually dies out,” said Pascual. “In the end, it’s a waiting game. “

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