Hydroxychloroquine lowers COVID-19 death rate – Henry Ford Health study

A Henry Ford Health System study shows the controversial anti-malaria drug hydroxychloroquine helps lower the death rate of COVID-19 patients, the Detroit-based health system said Thursday.

Officials with the Michigan health system said the study found the drug “significantly” decreased the death rate of patients involved in the analysis.

The study analyzed 2,541 patients hospitalized among the system’s six hospitals between March 10 and May 2 and found 13% of those treated with hydroxychloroquine died while 26% of those who did not receive the drug died.

Among all patients in the study, there was an overall in-hospital mortality rate of 18%, and many who died had underlying conditions that put them at greater risk, according to Henry Ford Health System. Globally, the mortality rate for hospitalized patients is between 10% and 30%, and it’s 58% among those in the intensive care unit or on a ventilator.

“As doctors and scientists, we look to the data for insight,” said Steven Kalkanis, CEO of the Henry Ford Medical Group. “And the data here is clear that there was a benefit to using the drug as a treatment for sick, hospitalized patients.”

The study, published in the International Society of Infectious Disease, found patients did not suffer heart-related side effects from the drug.

Patients with a median age of 64 were among those analyzed, with 51% men and 56% African American. Roughly 82% of the patients began receiving hydroxychloroquine within 24 hours and 91% within 48 hours, a factor Dr. Marcus Zervos identified as a potential key to the medication’s success.

“We attribute our findings that differ from other studies to early treatment, and part of a combination of interventions that were done in supportive care of patients, including careful cardiac monitoring,” said Zervos, division head of infectious disease for the health system who conducted the study with epidemiologist Dr. Samia Arshad.

Other studies, Zervos noted, included different populations or were not peer-reviewed.

“Our dosing also differed from other studies not showing a benefit of the drug,” he said. “We also found that using steroids early in the infection associated with a reduction in mortality.”

But Zervos cautioned against extrapolating the results for treatment outside hospital settings and without further study.

Lynn Sutfin, spokeswoman for the Michigan Department of Health and Human Services, respond to the study Thursday by noting “prescribers have a responsibility to apply the best standards of care and use their clinical judgment when prescribing and dispensing hydroxychloroquine or any other drugs to treat patients with legitimate medical conditions.”

The study found about 20% of patients treated with a combination of hydroxychloroquine and azithromycin died and 22% who were treated with azithromycin alone compared with the 26% of patients who died after not being treated with either medication.

Henry Ford Health has been working on multiple clinical trials of hydroxychloroquine, including one that is testing whether the drug can prevent COVID-19 infections in first responders who work with coronavirus patients. The first responder clinical trial was trumpeted by Trump administration officials early in the pandemic.

Many health care institutions, including the World Health Organization, suspended clinical trials of the drug touted by President Donald Trump after a faulty study was published in the British medical journal The Lancet on May 22. The WHO restarted the trials in June.

The study is vital, Zervos said, as medical workers prepare for a possible second wave of the virus and there is plenty of research that still needs to be conducted to solidify an effective treatment.

Still, use of the malaria drug became highly controversial.

Doctors at Michigan Medicine, the University of Michigan’s health system, remain steadfast in their decision not to use hydroxychloroquine on coronavirus patients, which they stopped using in mid-March after their own early tracking of the treatment found little benefit to patients with some serious side effects.

Michigan’s largest system of hospitals, Southfield-based Beaumont Health, also stopped using the decades-old anti-malarial drug as a coronavirus treatment after deciding it was ineffective.

St. Joseph Mercy health system has also backed away from the treatment. The system has St. Joseph hospitals in Ann Arbor, Chelsea, Howell, Livonia and Pontiac, as well as the Mercy Health hospitals in Grand Rapids, Muskegon and Shelby.

Heidi Pillen, director of pharmacy at Beaumont Health, confirmed on Thursday that the health system is not using hydroxychloroquine to treat COVID-19 patients.

A recent United Kingdom study evaluating hydroxychloroquine in hospitalized patients with coronavirus was stopped after preliminary analysis found it didn’t have any benefit. About 26% of patients in the trial using the drug died, compared with about 24% receiving the usual care, according to the Oxford University study.

But doctors at Detroit Medical Center’s Sinai-Grace told The Detroit News in April, when the hospital was overloaded with senior COVID patients, that they were giving the drug to anyone they could.

https://www.detroitnews.com/story/news/local/michigan/2020/07/02/michigan-henry-ford-health-study-finds-hydroxychloroquine-lowers-covid-19-death-rate/5365090002/

Mutation on the novel coronavirus has come to dominate the globe

Flashback to mid-March: the novel coronavirus had reached San Diego, California. Few people could get tested, and even less was known about how the virus mutated as it spread from person to person.

Scientists now know that two variants of the novel coronavirus (SARS-CoV-2) were circulating at that time. The variants, called G614 and D614, had just a small difference in their “spike” protein–the viral machinery that coronaviruses use to enter host cells.

In a new study, an international team of scientists show that the G version of the virus has come to dominate cases around the world. They report that this mutation does not make the virus more deadly, but it does help the virus copy itself, resulting in a higher viral load, or “titer,” in patients.

The new study, led by scientists at Duke University, Los Alamos National Laboratory and La Jolla Institute (LJI) was published July 2, 2020 in Cell.

“We are focused on the human immune response because LJI is the headquarters for the Coronavirus Immunotherapy Consortium (CoVIC), a global collaboration to understand and advance antibody treatments against the virus,” says LJI Professor Erica Ollmann Saphire, Ph.D., who leads the Gates Foundation-supported CoVIC.

Saphire explains that viruses regularly acquire mutations to help them “escape” antibodies made by the human immune system. When a virus acquires many of these individual changes, it “drifts” away from the original virus. Researchers call this phenomenon “antigenic drift.” Antigenic drift is part of the reason you need a new flu shot each year.

It is extremely important for researchers to track antigenic drift as they design vaccines and therapeutics for COVID-19.

For the study, Saphire collaborated with Bette Korber, Ph.D., a fellow at Los Alamos National Laboratory (LANL), who serves as senior author of the study. Korber and her colleagues at LANL have developed tools to track mutations around the world. In the new study, their tracking showed that while the G and D viruses both spread widely around the world, the G virus was “fixed” as the dominant variant by mid-March.

Meanwhile, Saphire and co-author David Montefiore, Ph.D., of Duke University Medical Center, led research into the immune response to these variants. They determined that viruses carrying spike with the G mutation grew two to three times more efficiently, leading to a higher titer.

Saphire and her colleagues then used samples from six San Diego residents to test how human antibodies neutralized the D and G viruses. Would the fast-growing G virus be harder to fight?

Their experiments showed that the human immune response could neutralize the new G virus as well or better than the original D virus. This meant the immune system didn’t need to produce more antibodies or better antibodies against the G virus, even though this variant was more successful at spreading. This finding was in line with what doctors saw in COVID-19 patients.

“The clinical data in this paper from the University of Sheffield showed that even though patients with the new G virus carried more copies of the virus than patients infected with D, there wasn’t a corresponding increase in the severity of illness,” says Saphire.

Korber adds, “These findings suggest that the newer form of the virus may be even more readily transmitted than the original form–whether or not that conclusion is ultimately confirmed, it highlights the value of what were already good ideas: to wear masks and to maintain social distancing.”

Saphire says the novel coronavirus could be successful precisely because many patients do only get a mild version, or no symptoms at all.

“The virus doesn’t ‘want’ to be more lethal. It ‘wants’ to be more transmissible,” Saphire explains. “A virus ‘wants’ you to help it spread copies of itself. It ‘wants’ you to go to work and school and social gatherings and transmit it to new hosts. Of course, a virus is inanimate–it doesn’t ‘want’ anything. But a surviving virus is one that disseminates further and more efficiently. A virus that kills its host rapidly doesn’t go as far–think of cases of Ebola. A virus that lets its host go about their business will disseminate better–like with the common cold.”

So while the G mutation doesn’t make cases more severe, a different mutation might. “We’ll be keeping an eye on it,” says Saphire.

###

The study, titled, “Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus” was supported by the Medical Research Council (MRC) part of UK Research & Innovation (UKRI); the National Institute of Health Research (NIHR); Genome Research Limited, operating as the Wellcome Sanger Institute; a Wellcome Trust Intermediate Clinical Fellowship (110058/Z/15/Z); CoVIC, INV-006133 of the COVID-19 Therapeutics Accelerator, supported by the Bill and Melinda Gates Foundation, Mastercard, Wellcome; private philanthropic support, as well as the Overton family; a FastGrant, from Emergent Ventures, in aid of COVID-19 research; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Interagency Agreement No. AAI12007-001-00000.

Additional study authors included W.M. Fischer, S. Gnanakaran, H. Yoon, J. Theiler, W. Abfalterer, N. Hengartner, E.E. Giorgi, T. Bhattacharya, B. Foley, K.M. Hastie, M.D. Parker, D.G. Partridge, C.M. Evans, T.M. Freeman, T.I. de Silva, C. McDanal, L.G. Perez, H. Tang, A. Moon-Walker, S.P. Whelan and C.C. LaBranche.

DOI: 10.1016/j.cell.2020.06.043

https://www.eurekalert.org/pub_releases/2020-07/ljif-ham070220.php

New, more infectious strain of COVID-19 now dominates global cases of virus

Researchers have shown that a variation in the viral genome of Covid-19 improved its ability to infect human cells and helped it become the dominant strain circulating around the world today.

The study, published today in the journal Cell, shows the variation is more infectious in cell cultures under laboratory conditions. The variant, named ‘D614G’, makes a small but effective change in the ‘spike’ glycoprotein that protrudes from the surface of the virus, which it uses to enter and infect human cells.

The D614G variant of Covid-19 quickly took over as the dominant strain soon after it first appeared, with geographic samples showing a significant shift in viral population from the original, to the new strain of the virus.

Researchers from the Los Alamos National Laboratory in New Mexico and Duke University in North Carolina, partnered with the University of Sheffield’s Covid-19 Genomics UK research group to analyse genome samples published on GISAID, an international resource for sharing genome sequences among researchers worldwide.

Dr Thushan de Silva, Senior Clinical Lecturer in Infectious Diseases at the University of Sheffield, led analysis of data from Sheffield. He said: “We have been sequencing SARS-CoV-2 strains in Sheffield since early in the pandemic and this allowed us to partner with our collaborators to show this mutation had become dominant in circulating strains. The full peer-reviewed study published today confirms this, and also that the new D614G genome mutation variant is also more infectious under laboratory conditions.

“Data provided by our team in Sheffield suggested that the new strain was associated with higher viral loads in the upper respiratory tract of patients with Covid-19, meaning the virus’s ability to infect people could be increased.

“Fortunately at this stage, it does not seem that viruses with D614G cause more severe disease.”

Dr Bette Korber, from the Los Alamos National Laboratory in New Mexico, was the lead author of the study. She said: “It is possible to track SARS-CoV-2 (Covid-19) evolution globally because researchers worldwide are rapidly making their viral sequence data available through the GISAID viral sequence database. Currently tens of thousands of sequences are available through this project, and this enabled us to identify the emergence of a variant that has rapidly become the globally dominant form.”

New supporting experiments, more extensive sequencing and clinical data, and improved statistical models have been published today in full at Cell, however the researchers are keen to stress that further laboratory analysis in live cells needs to be done to determine the full implications of the mutation.

“It’s remarkable to me,” commented Dr Will Fischer, from Los Alamos National Laboratory and an author on the study. “That this increase in infectivity was detected by careful observation of sequence data alone, and that our experimental colleagues could confirm it with live virus in such a short time.”

###

-Access the full paper ‘Tracking SARS-CoV-2 Spike mutations: evidence for increased infectivity of D614G’ in the journal Cell

– The research was uploaded to bioRxiv in April, and was accessed over 200,00 times by researchers around the world, a record for the preprint site.

– GISAID, the Global Initiative for Sharing All Influenza Data, established a COVID-19 database early in the epidemic for sharing outbreak sequences among researchers worldwide.

– The research was supported by the Medical Research Council (MRC); the National Institute of Health Research (NIHR); Genome Research Limited, operating as the Wellcome Sanger Institute; CoVIC, INV-006133 of the COVID-19 Therapeutics Accelerator, supported by the Bill and Melinda Gates Foundation, Mastercard, Wellcome; private philanthropic support, as well as the Overton family; a FastGrant, from Emergent Ventures, in aid of COVID-19 research; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Interagency Agreement No. AAI12007-001-00000, and the Los Alamos National Laboratory Directed Research and Development program.

https://www.eurekalert.org/pub_releases/2020-07/uos-nmi070220.php

As Cases Jump, Are We Better Prepared for COVID?

People are hitting the beaches. Stores and restaurants are reopening. Baseball is back (at least spring training).

Yet just as life seems to be returning to something more normal, there’s also worrisome news.

There are record numbers of COVID-19 cases in the U.S., with several states in the South and West driving the resurgence. Texas has closed its bars, California has closed its restaurants in some counties, and some beaches in Florida are closed.

Officials of all political stripes are encouraging people to wear masks, if not mandating it.

Has the country made progress in containing this disease?

“As we see new cases rising ― and we’re tracking them very carefully ― there may be a tendency among the American people to think that we are back to that place that we were 2 months ago, that we’re in a time of great losses and great hardship on the American people,” Vice President Mike Pence said last week at the first briefing in 2 months of the White House task force on the pandemic. “The reality is we’re in a much better place.”

Richard Besser, MD, president and CEO of the Robert Wood Johnson Foundation and a former CDC acting director, says there’s been improvement in some crucial areas.

For example, more hospitals have personal protective equipment (PPE) for front-line employees, he says, although many hospitals say they’re still woefully short. More testing is available. Doctors understand more about the virus and treatment.

But, on the whole, “We’re in worse shape than we were 2 to 3 months ago,” Besser says.

Many health experts agree, and some governors have paused or rolled back their state’s efforts to reopen the economy. As more of their residents get sick, states are again trying to keep them at home more, knowing that business restrictions could bring political heat from constituents eager to work and resume other normal activities.

“We are not even beginning to be over this,” says Anne Schuchat, MD, the CDC’s principal deputy director, offering a summary of expert opinion.

So where exactly do we stand? Here’s a look at new case numbers, death rates, hospitalizations, and more.

On Death Rates, Hospitals, and Medication

The number of people dying each day has slowed, Pence said. People are getting diagnosed earlier, hospitals are sharing treatment information, and some drugs are helping recovery.

“We can still take some comfort in the fact that fatalities are declining,” Pence said, pointing out that last week, there were 2 days when fewer than 300 Americans died, down from a peak of more than 2,500.

But death rates typically lag behind diagnoses, experts say, so an increase in deaths could be coming soon. More younger people have begun testing positive. Their death rate is lower, but they are able to infect others, including more vulnerable people with whom they come in contact.

Hospitals might be, in some ways, better prepared ― certainly, at least, now experienced ― in dealing with the coronavirus than they were a few months ago.

But many report they’re at or approaching a crisis point with COVID-19 patients and available ICU beds. On June 29, 33 states were at 80% or greater capacity of their ICUs and beds, according to CovidExitStrategy.org. That’s up from 23 on May 28.

In Los Angeles, health officials say the city’s hospital beds could reach capacity in a few weeks.

And experts say contact tracing and testing capacity still lag.

Medication is helping somewhat. A trial sponsored by the National Institutes of Health found that the drug remdesivir cut recovery time by an average of 4 days. It did not improve the death rate. In the United Kingdom, a trial found that dexamethasone ― a cheap, common steroid ― can save the lives of people seriously ill with COVID-19.

The cost of remdesivir will be more than $3,000 per treatment course for Americans who have private insurance, and about $2,300 for those who have government-sponsored insurance, its manufacturer, Gilead Sciences, and the U.S. Department of Health and Human Services say.

Results Are “Tip of the Iceberg,” Former CDC Chief Says

More Americans are being tested than in April, and public health officials say that’s a good thing.

“To one extent or another, the volume of new cases coming in is a reflection of a great success in expanding testing across the country,” Pence said.

But it’s not so simple, according to statistics and health experts.

“As a doctor, a scientist, an epidemiologist, I can tell you with 100% certainty that in most states where you’re seeing an increase, it is a real increase,” says Tom Frieden, MD, a former CDC director. “It is not more tests. It is more spread of the virus. … The numbers you’re seeing are just a tip of the iceberg of even more spread.”

Some states are seeing higher percentages of positive tests, not just higher numbers of positive tests. “That’s explosive spread of coronavirus,” Frieden says.

Anthony Fauci, MD, the country’s top expert on infectious diseases, told a Senate hearing June 30 that the country could go from “now having 40-plus thousand new cases a day … to up to 100,000 a day if this does not turn around.”

The CDC now says the number of Americans who have been infected could be 10 times higher than those revealed by testing ― because relatively few people have been tested at all.

“The window is closing” for the country to control the pandemic, the administration’s top health official, Health and Human Services Secretary Alex Azar, said 2 days after Pence’s comments.

“This is a very, very serious situation,” he said.

What Slowing the “Reopenings” Means

New cases hit a record June 26, breaking the mark set just the day before, numbers from Johns Hopkins University reveal. The country’s daily average of new cases was also higher than ever. And more than 30 states saw their own numbers rising, as well.

That caused states including California, Arizona, Texas, and Florida to halt or lessen their efforts to reopen the economy. It again brought into sharp focus the struggle to balance economic freedom with public health, a problem faced by governments at all levels, health care experts, business leaders, and ordinary Americans. After the devastating effects of the initial shutdowns ― lost businesses, high unemployment, lower consumer spending, and more ― the country saw economic improvement as more people returned to work.

Los Angeles officials were not prepared for the surge in cases. Mayor Eric Garcetti said after Pence’s comments that the next 2 weeks would be a “second big test” to see if the state can “keep people living and to keep livelihoods.”

Other examples of governors forced to reinstate restrictions on business, knowing they would face political backlash from some businesses, voters, and local governments desperate for revenue:

• In Texas, bars are closed.
• So are some Florida beaches, ahead of the Independence Day holiday.
• Arizona closed bars, gyms, theaters, and more, with the governor citing “brutal” case numbers that he expects to continue to rise.
• New York, New Jersey, and Connecticut are requiring visitors from 16 states with rising coronavirus case numbers to quarantine for 2 weeks before they’re allowed to visit.

“These increases (in new cases) are in many places,” Schuchat says. “It’s so many geographic areas. We’re clearly not at a point where there’s so little virus being spread that it’s going to be easy to snuff out.”

The Way Forward

Besser says that at first, the country had a shared sense of purpose and a belief that individual actions can have an effect on the pandemic. But since then, political pressure and a desire to get back to working and socializing have clouded the mission.

“We’re seeing consequences of that now,” he says, also noting that Black people, Hispanics, and many “essential” workers are still suffering and dying disproportionately.

“Pretending that the virus is going away is not a very successful strategy,” Besser says, calling for continued commitment to masks, hand-washing, and social distancing, plus testing, tracing, and isolating patients.

“To sustainably reopen the economy, we need to follow the path being laid out by public health,” he says. That means, among other things, seeing 2-week declines in cases and hospitalizations, and ensuring hospitals can handle COVID-19 needs as well as non-pandemic care.

“We can successfully contain and control this,” Besser says. “The big question is will we.”

https://www.medscape.com/viewarticle/933333#vp_1

Protective equipment makers rise after statewide Texas mask mandate

Makers of masks and personal protective equipment are unsurprisingly higher after a mandate from Texas Gov. Greg Abbott for Texans to wear masks when outdoors.

After hours: Alpha Pro Tech (NYSEMKT:APT) is up 3.3%; Allied Healthcare Products (NASDAQ:AHPI) is up 3.8%; and Lakeland Industries (NASDAQ:LAKE) is up 2.3%.

Meanwhile, anti-infection specialist NovaBay Pharmaceuticals (NYSEMKT:NBY) is up 6.5% postmarket.

https://seekingalpha.com/news/3588507-protective-equipment-makers-rise-after-statewide-texas-mask-mandate

Immmunomedics up after setting clinical update for Monday

Immunomedics (NASDAQ:IMMU) is up 3.4% after hours following notice it’s holding a conference call/webcast to offer a clinical update.

The company’s set its call for Monday, July 6 at 8 a.m. ET.

The webcast will be on its investor relations page.

https://seekingalpha.com/news/3588506-immmunomedicsplus-3_4-after-setting-clinical-update-for-monday

Texas governor issues statewide order to wear masks

Texas Gov. Greg Abbott – a proponent of a relatively early reopening of the state’s economy – has now issued an executive order for Texans to wear masks in public spaces.

That comes alongside skyrocketing COVID-19 case numbers in the state.

Texans will be required to wear a face covering over their nose and mouth in counties with 20-plus positive cases, covering all but the most rural areas.

Abbott also issued a proclamation giving mayors and county judges the ability to restrict some outdoor gatherings of more than 10 people, and making it mandatory that (with certain exceptions) people can’t congregate in groups larger than 10 and must maintain social distancing.

The move is a sharp reversal of his earlier stance, when he prevent Texas city mayors from enacting mask requirements

Exemptions to the public mask order abound – those free from the requirement include children younger than 10; people eating or drinking, or seated in a restaurant to eat or drink; outdoor exercisers; those driving alone or with their household members; anyone in a pool or body of water; most anyone at a polling place; and anyone providing or obtaining access to religious worship.

https://seekingalpha.com/news/3588471-texas-governor-issues-statewide-order-to-wear-masks-updated