Coronavirus Good News
Science and medical trial and error are keeping more patients alive.
By The WSJ Editorial Board
Updated June 7, 2020 9:40 pm ET
Research associate Sachi Johnson works at Sorrento Therapeutics where efforts are underway to develop an antibody, STI-1499, to help in prevention of the coronavirus disease in San Diego, May 2.
PHOTO: BING GUAN/REUTERS
Good news: A new study finds that the novel coronavirus has become less lethal over the past few months. While there’s no evidence that mutations are making the virus less deadly, treatments have improved enormously as scientists have learned more.
Doctors have observed that the coronavirus case-fatality rate seems to have decreased considerably since the early days of the pandemic. But a pre-publication study from Italian universities and local public-health authorities comparing the case-fatality rates in two provinces (Ferrara and Pescara) during March and April is the first to show this might be true.
After adjusting for age and comorbidities, the study found the overall death rate declined by some 40% from March to April with huge reductions in those over age 80 (from 36.3% to 16.1%), and subjects with hypertension (23% to 12.1%), diabetes (30.3% to 8.4%), cardiovascular disease (31.5% to 12.1%), COPD (29.7% to 11.4%) and renal disease (32.3% to 11.5%).
The study’s findings need to be confirmed by more studies of fatality rates over time in other places. But the researchers note that the decline in death rates is unlikely to be due to less crowded hospitals since infection rates were low in the two provinces and never exceeded the intensive care unit capacity. Hospital utilization could confound results in other hot spots.
They say their study confirms anecdotes from expert physicians that “the early administration of more tailored medications, is considerably improving the clinical course of COVID-19.” Doctors are using a cocktail of targeted therapies including repurposed HIV antivirals, anticoagulants and monoclonal antibodies like tocilizumab that lower inflammatory cytokine attacks on organs.
A European Journal of Internal Medicine study last month found that two of 62 patients receiving tocilizumab died compared to 11 of 23 in a group with similar characteristics. Randomized clinical trials are needed to draw solid conclusions about the efficacy of drug treatments, but they usually take months. So doctors have been experimenting and learning on the fly.
We now know, for instance, that deaths among severely ill patients often result from an overreactive immune response known as “cytokine storms” as well as systemic blood clots. The Food and Drug Administration this week approved a new blood test by Roche that measures levels of the inflammatory-causing protein interleukin-6 and can help predict patients at risk for cytokine storms. Using drugs to break up blood clots and calm down the immune system earlier can prevent severe cases from turning deadly.
Doctors have also observed that some patients with fatally low oxygen levels aren’t gasping for air or losing consciousness and their symptoms resemble altitude sickness—dizziness, nausea and headaches—more than pneumonia or acute respiratory distress. As a result they are using less intensive ventilation such as nasal cannulas and sleep-apnea machines.
Mechanical ventilators can cause long-term brain and respiratory damage as well as secondary infections. A study in the Journal of the American Medical Association has found that a shockingly high 80% of those between ages 18 and 65 who were placed on ventilators in New York City died while just 2.4% were discharged alive during the study period. More targeted therapeutics can reduce the need for ventilators.
The FDA last month approved Gilead’s antiviral remdesivir for emergency use after a phase-one trial found that the drug reduced recovery times in hospitalized patients on average to 11 days compared to 15 days for those in a control group. Remdesivir stops the virus from replicating, so it may be even more beneficial if administered earlier in the illness.
The treatment learning curve has been as steep as the infection curve. But even if there’s a second Covid-19 wave, it is likely to be less deadly than the first.
Regeneron, Sanofi to Test Arthritis Drug as Coronavirus Treatment
The drugmakers aim to begin testing within weeks exploring whether their rheumatoid-arthritis therapy could treat Covid-19 symptoms.
Dr. Leonard S. Schleifer, founder and chief executive of Regeneron, speaking during a meeting with the Coronavirus Task Force, attended by President Trump and Vice President Mike Pence at the White House in Washington, D.C., on March 2.
PHOTO: KEVIN DIETSCH/ZUMA PRESS
By Joseph Walker
Updated March 10, 2020 6:57 pm ET
Drugmakers Regeneron Pharmaceuticals Inc. and Sanofi SA are racing to launch clinical trials exploring whether their arthritis drug could treat symptoms of novel coronavirus infections.
The study preparations mark the latest effort in an emerging front in researchers’ hunt for
effective treatments for Covid-19, the respiratory disease caused by the novel coronavirus. In
the U.S., there aren’t any drugs or vaccines approved for the condition.
The research aims to see whether certain drugs already on the market to tackle immune
disorders like rheumatoid arthritis could help ease damage to the lungs and respiratory system caused by the immune system’s overreaction to the virus causing Covid-19.
The drugs wouldn’t treat the underlying virus. The Sanofi and Regeneron drug, called Kevzara, was approved by the Food and Drug Administration in 2017 to treat rheumatoid arthritis
“The goal would be in the next couple of weeks to have the trial up and running, and in weeks to months after that to have the data,” Regeneron Chief Scientific Officer George Yancopoulos said in an interview on Tuesday. Boosting the rationale for studying Kevzara’s effect on Covid-19 was a recent report by Chinese researchers that a similar-acting drug, Actemra from Roche Holding AG , had helped a small group of patients with severe or critical Covid-19 disease recover.
Several patients in the study “got out of death’s bed and walked out of the hospital” after receiving Actemra, Dr. Yancopoulos said. However, he cautioned that the study required repeating because it was small, not controlled and didn’t have defined parameters for success. Genentech, a Roche subsidiary, said it is exploring opportunities to conduct U.S. studies of Actemra in Covid-19 patients with pneumonia, said a company spokeswoman.
A study of the drug on Covid-19 was recently begun by the First People’s Hospital of University of Science and Technology of China, she said. Both Actemra and Kevzara block proteins called interleukin-6, or IL-6, that trigger the body’s immune and inflammatory response. Normally the response helps fight infections. If the immune system overreacts, however, it can attack healthy tissue and organs.
In some novel coronavirus patients, the immune response may be accelerating and damaging the lungs even after significantly diminishing the amount of virus in the body, said Naimish Patel, Sanofi’s head of global development for immunology and inflammation, in an interview.
Blocking IL-6 may put the brakes on the immune system and keep the body from attacking itself, he said. “Even though the virus is diminishing, it’s sending signals to the immune system to keep attacking,” said Dr. Patel.
“If there’s too much inflammation, you end up killing cells that aren’t infected and leading to more damage than you really need.” Symptoms associated with Covid-19 include fever, low oxygen levels in the blood and difficulty breathing.
One concern about deploying drugs that dampen the immune system is that patients could become more prone to infection, said Timothy Sheahan, assistant professor of epidemiology at the University of North Carolina, who conducts laboratory research into drugs for coronaviruses, including Gilead Sciences Inc.’s remdesivir.
Several drugmakers in addition to Gilead are looking for drugs aiming to cure novel coronavirus infections, while Sanofi and other companies are working on vaccines to prevent the infections. Regeneron is leading efforts to study Kevzara in the U.S. and is in talks with the FDA, New York state Health Commissioner Howard Zucker and hospitals designated to care for Covid-19 patients and could serve as research sites for the trial, Dr. Yancopoulos said.
The study would evaluate the drug only in patients with severe to critical disease. The company, based in Tarrytown, N.Y., is likely to kick off the trial in New York, he said.
The FDA didn’t immediately respond to requests for comment. Dr. Zucker didn’t immediately respond to a request for comment. Sanofi, based in Paris, is responsible for studying the drug in Covid-19 overseas and hopes to begin studies as soon as possible, perhaps in weeks, Dr. Patel said.
“Given the quickly evolving situation around Covid-19, we are working to leverage the knowledge of both companies in evaluating how Kevzara may be a potential treatment option for some patients,” a Sanofi spokeswoman said.
Regeneron and Sanofi co-developed Kevzara as part of a years long R&D collaboration. In December, the companies said that as part of a restructuring of the collaboration, Sanofi will take full ownership of the drug.
But the restructuring terms aren’t final yet and could change and the companies are actively discussing how the drug’s potential treating Covid-19 may factor into the completed pact, a Sanofi spokeswoman said. Dr. Yancopoulos said the companies jointly decided that Regeneron would lead the U.S. research program in Covid-19 “because it’s the right thing to do,” and they will figure out the details later.
Separately, Regeneron is developing new antibody drugs to kill the virus itself and aims to have the drugs ready to study in humans by the end of August, the company has said.
Blood thinners may help patients with severe Covid-19 infections, study finds
(CNN) Blood thinning drugs could help save some patients who are the most severely affected by the new coronavirus, doctors reported Wednesday.
The findings from a team at Mount Sinai Hospital could help with a troubling problem that has shocked and horrified doctors treating coronavirus patients around the world -- blood clots throughout the body that complicate an already hard-to-treat disease.
The team now says it is running experiments to see which anticoagulants may work best, and at which doses.
Covid-19 causes sudden strokes in young adults, doctors say
"The patients who received anticoagulants did better than those who didn't," Dr. Valentin Fuster, director of Mount Sinai Heart and physician-in-chief of The Mount Sinai Hospital, told CNN.
"This has implications already. People, I believe, should treat these patients with antithrombotics," he added.
The findings are not clear enough yet to make solid recommendations. The team noted that patients who were already severely ill were more likely to be given the blood thinners.
Fuster and colleagues looked at more than 2,700 patients treated at Mount Sinai in New York City, which has been hit hard by the coronavirus. Starting in March, some patients were given anti-clotting drugs based on bedside decisions made by doctors.
The team started taking a systematic look at whether the drugs made a difference. They did, especially for patients who were put on ventilators to help them breathe.
Doctors try to untangle why they're seeing 'unprecedented' blood clotting among Covid-19 patients
They found 29% of patients on ventilators who were given blood thinners died, compared to 63% of patients on ventilators who were not given blood thinners.
"Our findings suggest that systemic anticoagulants may be associated with improved outcomes among patients hospitalized with Covid-19," they wrote in their report, published in the Journal of the American College of Cardiology.
The researchers did not find that the patients who received blood thinners were significantly more likely to develop bleeding problems -- one of the risks of the drugs.
Different patients received different doses and different types of blood thinners, so it will be important to systematically study which combination of dose and drug works best, Fuster said.
'Clotting is a problem, without any question'
New Covid-19 crisis hits ICUs as more patients need dialysis
His team has started such a study and going forward will test varying doses of either the classic blood thinner heparin or one of the newer, oral anticoagulant drugs such as dabigatran, a direct thrombin inhibitor.
There's no doubt that blood clotting is a major factor in the deaths of patients with Covid-19, Fuster said.
"We have done 75 autopsies and clotting is a problem, without any question," he said.
"It starts with the lungs, followed by the kidneys, the heart and it ends up in the brain."
The consequences, he said, are devastating. "It is so dramatic for all of us. You feel that you can do very little except to sustain the life of the patient," Fuster said.
Fuster would also like to study whether blood thinners could help patients who are not sick enough to be hospitalized. Some hospitals have reported a troubling increase in strokes among people under age 50 who would normally not be at risk. Many of these patients have later been found to be infected with the coronavirus.
It's not yet clear why the virus is causing blood to clot, but increased clotting can be a side effect of the severe inflammation caused by some viral infections.