Researchers at Washington University School of Medicine in St. Louis have found in a preliminary study that the drug fluvoxamine seems to prevent some of the most serious complications of COVID-19 patients and make hospitalization and the need for supplemental oxygen less likely.
In an innovative twist to research during the pandemic, the study, involving 152 patients infected with SAR-CoV-2, the virus that causes COVID-19, was conducted remotely. When a symptomatic patient tested positive and enrolled in the study, research staff delivered the medication or inactive placebo to them, along with thermometers, automatic blood pressure monitors and fingertip oxygen sensors.
For two weeks, subjects took either the antidepressant drug or placebo sugar pills while having daily interactions with members of the research team via phone or computer. That allowed patients to report on their symptoms, oxygen levels and other vital signs. If patients suffered shortness of breath or were hospitalized for pneumonia, or their oxygen saturation levels fell below 92 percent, their conditions were considered to have deteriorated.
After 15 days, none of the 80 patients who had received the drug experienced serious clinical deterioration. Meanwhile, six or 8.3 percent of the 72 patients given placebo became seriously ill, with four requiring hospitalization.
"There are several ways this drug might work to help COVID-19 patients, but we think it most likely may be interacting with the sigma-1 receptor to reduce the production of inflammatory molecules," said senior author Angela M Reiersen, an associate professor of psychiatry. "Past research has demonstrated that fluvoxamine can reduce inflammation in animal models of sepsis, and it may be doing something similar in our patients."
Reiersen said the drug's effects on inflammation could prevent the immune system from mounting an overwhelming response, which is thought to occur in some COVID-19 patients who seem to improve after a few days of illness and then worsen. Many of those patients end up hospitalized, and some die.
In the next few weeks, the researchers will begin a larger study, using mobile and internet technology to conduct clinical trials throughout the United States.
Fluvoxamine is used commonly to treat obsessive-compulsive disorder (OCD), social anxiety disorder and depression. It is in a class of drugs known as selective serotonin-reuptake inhibitors (SSRIs), but unlike other SSRIs, fluvoxamine interacts strongly with a protein called the sigma-1 receptor. That receptor also helps regulate the body's inflammatory response.
The study was published online Thursday in the Journal of the American Medical Association.
Even though it’s known as a respiratory virus, doctors believe the coronavirus can directly infect the heart muscle and cause other problems leading to heart damage.
In some people, as COVID-19 decreases lung function, it may deprive the heart of adequate oxygen. Sometimes it causes an overwhelming inflammatory reaction that taxes the heart as the body tries to fight off the infection.
The virus can also invade blood vessels or cause inflammation within them, leading to blood clots that can cause heart attacks.
Clots throughout the body have been found in many COVID-19 patients. That has led some doctors to try blood thinners, although there is no consensus on that treatment.
Dr. Sean Pinney of the University of Chicago says people with heart disease are most at risk for virus-related damage to the heart. But heart complications also have been found in COVID-19 patients with no known previous disease.
A recent review in the Journal of the American College of Cardiology notes that evidence of heart involvement has been found in at least 25% of hospitalized coronavirus patients. At some centers, the rate is 30% or higher. And some studies have found elevated enzyme levels and other signs suggesting heart damage even in patients with milder disease. It is not known whether that damage is permanent.
One small study found evidence of the virus in the hearts of COVID-19 patients who died from pneumonia. Another, using heart imaging, found inflammation of the heart muscle in four college athletes who had recovered from mild COVID-19 infections. There were no images available from before the athletes got sick, and therefore no way to know if they had pre-existing heart problems.
Dr. Tom Maddox, an American College of Cardiology board member, says it’s unclear if the virus can cause a normal heart to become dysfunctional.
“There’s still so much we don’t know,” Maddox said.
Chinese and German researchers, in a recently-published study, have suggested that Shufeng Jiedu capsules, a patented herbal drug composed of eight medicinal plants, might be "a promising herbal therapy for moderate COVID-19."
The scientific paper was published online on Oct. 22 by Phytomedicine, a monthly peer-reviewed medical journal.
The research team included Xia Lu of Shanghai Public Health Clinical Center affiliated to Fudan University, Shi Yujing of the China Academy of Chinese Medical Sciences, Su Jie of Shanghai Tech University, and Thomas Friedemann of HanseMerkur Center for Traditional Chinese Medicine at the University Medical Center in Germany.
There is currently no confirmed cure or vaccine for COVID-19. But the use of Traditional Chinese Herbal Medicine (TCM) to combat COVID-19 got international attention because it was regularly used during the pandemic, the authors said in the study.
TCM was used successfully for the treatment of SARS in 2003 and influenza A (H1N1) in 2009, they said.
Shufeng Jiedu capsules, consisting of eight medicinal plants, are recognized for the treatment of different viral respiratory infectious diseases based on their antiviral, anti-inflammatory and immunomodulatory activities against acute lung injury, the authors said.
The antiviral and anti-inflammatory properties of Shufeng Jiedu capsules were confirmed by the mouse model. The decreased inflammatory factors in the lung tissue of coronavirus-infected mice can be explained by attenuation of pro-inflammatory pathways by bioactive compounds of the capsules, they said.
Network analysis showed that 11 inflammation and immunomodulation-related pathways were influenced by bioactive compounds of the capsules, they said.
The authors had investigated data from a clinical pragmatic empirical study of patients diagnosed with COVID-19 to assess the clinical effectiveness of the capsules and to determine the optimal time to initiate treatment, according to the study.
Clinical data showed that Shufeng Jiedu capsules, added to standard antiviral therapy, significantly reduced the clinical recovery time of COVID-19 and fatigue as well as cough days, compared to standard antiviral therapy alone.
The herbal therapy was significantly more effective when used within the first eight days after the onset of COVID-19 symptoms, the authors said.
"Clinical data provided some promising evidence that the capsules might shorten the symptomatic course of COVID-19 in patients with mild and moderate symptoms. The results indicated that it is beneficial to administer the capsules immediately from the onset of the first symptoms," the authors said.
However, a large-scale randomized, double-blinded and placebo-controlled clinical trial is necessary to confirm the effect of this real-world study of Shufeng Jiedu capsules for the treatment of COVID-19 patients, they added.
A thick quilt of smog lingered over the Indian capital and its suburbs on Friday, fed by smoke from raging agricultural fires that health experts worry could worsen the city’s fight against the coronavirus.
Air pollution in parts of New Delhi have climbed to levels around nine times what the World Health Organization considers safe, turning grey winter skies into a putrid yellow and shrouding national monuments. Levels of the most dangerous particles, called PM 2.5, climbed to around 250 micrograms per cubic meter, which is considered hazardous to breathe, according to the state-run System of Air Quality Weather Forecasting and Research.
The throat-burning smoke regularly turns the city of 20 million people into the world’s most polluted at this time of the year.
This year’s haze, however, comes as New Delhi battles a new surge in coronavirus infections, and health experts fear that if the air quality continues to worsen, then people with chronic medical conditions could become more vulnerable.
“We are already registering more infections after the air quality started to deteriorate. I fear things will only get worse from here on,” said Arvind Kumar, a chest surgeon in New Delhi.
India has reported the second most coronavirus infections in the world after the United States, with more than 8.4 million confirmed cases and nearly 125,000 deaths. The number of new daily infections reported across the country has slowed since mid-September, but New Delhi has recently seen a new surge.
On Thursday, the national capital recorded nearly 6,700 new COVID-19 cases, the second-highest single-day spike since the pandemic began. The surge comes ahead of the country’s festival season, when people normally gather in large numbers.
With fears growing about rising infections, New Delhi chief minister Arvind Kejriwal on Thursday banned firecrackers from being used this month during Diwali, the Hindu festival of light.
“The corona situation is worsening because of pollution,” he said.
Xiao Wu, a researcher at Harvard University, said emerging research suggests that pollution exposure could increase the severity of coronavirus infections.
“The relationship of long-term air pollution and COVID-19 indicate adverse health impacts that make people prone to the infection,” Wu said.
He said extended exposure to severely polluted air can cause chronic lung inflammation which could leave people more vulnerable to the coronavirus.
The link between air pollution and worsening COVID-19 cases remains mostly theoretical at the moment. But several researchers have said that in addition to factors such as mask wearing, social distancing, population density and temperature, dirty air should also be considered a key element in coronavirus outbreaks.
Recently, India’s National Centre for Disease Control said New Delhi is likely to report around 15,000 new COVID-19 cases a day in the winter, in part because of the prevalence of respiratory illnesses during the season resulting from toxic air.
New Delhi’s air pollution woes aren’t new.
Every winter season, air pollution levels in the capital soar to dangerous levels and dark yellow haze blankets the city for months. What makes things worse is the burning of crop debris on farms in neighboring states, which sends up huge clouds of smoke that drift toward New Delhi.
The New Delhi government has been doing more this year to fight air pollution by setting up a war room to track hot spots, using huge anti-smog guns that spray high pressure mist to help dust particles settle, and reducing smoke caused by agricultural burning.
But many say it is not doing enough.
“Our government only wakes up at the time of emergency. We don’t want a quick-fix solution,” said Bhavreen Kandhari, a New Delhi environmentalist.
One of the biggest drug decisions in decades is looming as U.S. regulators consider whether to approve the first medicine that’s claimed to slow mental decline from Alzheimer’s disease, the most common form of dementia.
A panel of outside experts meets Friday to advise the Food and Drug Administration on aducanumab, a drug from Cambridge, Massachusetts-based Biogen Inc. and Japan’s Eisai Co. FDA doesn’t always follow the panel’s advice but usually does and has until March to decide.
The drug does not cure or reverse Alzheimer’s; the claim is that it modestly slows the rate of decline.
The evidence is murky: The companies stopped two studies last year when the drug didn’t seem to work, then did an about-face and said additional results suggest it was effective in one study at a high dose. Results still have not been published.
An FDA staff report released Wednesday gave a generally glowing view, saying the positive study might be “exceptionally persuasive.” But an FDA statistician noted flaws and inconsistencies in the results and potential safety issues.
The drug is expected to be very expensive and “could bankrupt our health care system” while giving patients false hope, the consumer group Public Citizen warned.
More than 5 million people in the United States and many more worldwide have Alzheimer’s. Current drugs only temporarily ease symptoms and the last one was approved nearly two decades ago.
The FDA evaluation focuses on safety and effectiveness. But advocates for approval, including the Alzheimer’s Association, are pushing to make need part of the decision.
“There is a dire and drastic need” to help people impacted “by the crushing realities” of the disease, the association wrote to the FDA. The association got $450,000 from Biogen and Eisai last year, less than 1% of its total revenue.
Others say the need for a drug has no bearing on whether it works or is safe.
“This is a difficult decision. I think it’s going to be contentious no matter how it falls out,” said Dr. Howard Fillit, chief science officer of the Alzheimer’s Drug Discovery Foundation, who consults for Biogen.
ABOUT THE DRUG
Aducanumab (pronounced “add-yoo-CAN-yoo-mab”) aims to help clear harmful clumps of a protein called beta-amyloid from the brain. Other experimental drugs have done that but it made no difference in patients’ ability to think, care for themselves or live independently.
It’s a biotech medicine made from living cells, and such drugs are very expensive. No price estimate has been announced for the drug, which is given through an IV once a month. Fillit notes that Biogen drugs for other diseases cost $3,500 a month, plus fees for each infusion.
If aducanumab is approved, it’s expected to be covered by Medicare, the government plan for seniors. The FDA and Medicare are barred from considering cost when reviewing a new drug or treatment.
Even qualifying for the drug could be expensive. It’s only been tested in people with mild dementia from Alzheimer’s or a less severe condition called mild cognitive impairment. To verify a diagnosis has required brain scans that cost $5,000 or more. Insurers including Medicare don’t cover the scans because their benefits are unclear, but that could change if a scan becomes a gateway to treatment.
Historically, the FDA often required two studies showing safety and effectiveness, but in recent years has relaxed that standard.
Each of the two aducanumab studies enrolled about 1,650 people and were stopped roughly halfway through when it seemed the drug wasn’t working. Biogen says that later results show one study was positive at the highest dose; the second study was clearly negative. The company says an analysis from both studies on people who got the highest dose for the longest time shows benefit.
But there are many questions about the validity of such analyses. Another complication: the studies were changed after they were underway to let some people get a higher dose. And the placebo group in the positive study worsened more than the one in the negative study did, which could help explain why aducanumab appeared better by comparison in that one.
The FDA review largely dismissed safety concerns, including swelling in the brain that occurred in as many as one-third of patients, often leading to discontinuation of the drug.
The FDA should require a third study to test the drug in ideal conditions and get a clear answer, said the Mayo Clinic’s Dr. David Knopman. He’s on the FDA advisory panel but won’t vote on aducanumab because he helped lead one study. He and other doctors published a journal report earlier this week arguing against approval.
WHAT IT WOULD MEAN FOR PATIENTS
Any benefit from the drug “is relatively small,” said Dr. Eliezer Masliah, neuroscience chief at the U.S. National Institute on Aging.
In the positive study, the drug modestly slowed the rate of mental decline -- a difference of only 0.39 on an 18-point score of thinking skills. How much that means in terms of being able to live independently, recognize family members or remember things is unclear.
Drugs that remove amyloid may have to be combined with medicines that do other things in the brain, and used early enough before damage occurs, to do much good, Masliah said.
If the drug is approved, the American Academy of Neurology urged the FDA to not make it a broad authorization, which could expose many patients to a medicine that might harm rather than help, and could “overwhelm the health care system.”