Emergence of a Deadly Coronavirus

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It would be good to create a separate thread for the biology of COVID-19 but Alex probably needs to create a science discussion forum first.

There are thought to be 3 distinct genetic strains of COVID-19. Researchers at Cambridge University have discovered that the coronavirus mutated into three distinct strains as it spread across the globe. They traced the origins of the epidemic by analyzing 160 genomes from human patients and found that the strain in Wuhan mutated from an earlier version.

As i mentioned before (and nobody commented) the US government (Mike Pence) has now reignited the theory that earliest version of the virus escaped (released?) from the Wuhan laboratory. The ease with which this virus has spread into the human populations remains a highly suspicious aspect of COVID-19, one which is not so easily dismissed.

NEWS FLASH!

Australia:
Wastewater analysis used to detect outbreaks of COVID-19.

https://www.statnews.com/2020/04/16/ear ... -150595041

I expect much of the shelter-in-place (quarantine) will be lifted in the next few days in the U.S. It will not happen all at once. Some states that are heavily infected will take a bit longer. With that said, I would like to interject some thoughts.

It is my impression that mass transit (buses, trains, subways) pose a significant risk for infection. Compare infections in New York City with Los Angeles. Therefore it is very important for those using this type of transportation to take some additional precautions when using this transportation during the late fall/winter/early spring times when humidity levels fall below 40% relative humidity.

What type of extra precautions? I would recommend that you wear an N95 masks or greater or the best is a RespoKare AntiViral Mask. These masks will protect your mouth and nose from breathing in viruses, and bacterial infections. They may be out of stock at the moment but they will be back on store shelves soon and the prices will become reasonable again. It is your life on the line, protect it. These mask are reusable when used intermittently. I have worn my N95 for over two months.

The mask should be sanitized after you return home. There are sanitizer boxes under $100 that will treat the mask with UVC light and ozone that will destroy any viruses on the mask. The one I bought has an 8 minute decontamination cycle.

I also recommend that you carry a small bottle of hand sanitizer gel with you. This you can apply several times during the day to eliminate any virus that you hands pick up during transit.

Kizzmekia Corbett has been leading a team of scientists working around the clock at the National Institutes of Health (NIH) for an experimental vaccine against the coronavirus. Earlier this month, her team had a breakthrough. Her team has already begun first-stage clinical trials of a vaccine. The COVID-19 trials began in Seattle in March, and according to Dr. Anthony Fauci, in “record speed” -- just two months. The vaccine could be ready for patients by early to mid-2021, if effective.

Not so long ago, scientists would have had to grow the virus itself to create a vaccine. The NIH is using a new method that skips that step. Researchers instead copy the section of the virus’ genetic code that contains the instructions for cells to create the spike protein and let the body become a mini-factory.

Corbett’s team had a head start. Because they’d spent years trying to develop a vaccine against MERS, a cousin of the new virus, they knew how to make spike proteins stable enough for immunization, and sent that key ingredient to Moderna Inc. to brew up doses.

Source: 'Brilliant' scientist, 34, cheered for helping lead coronavirus vaccine trials

https://www.biospace.com/article/gilead-shutters-covid-19-trial-in-china-stocks-drop-3-percent-/

Gilead Suspends a Remdesivir COVID-19 Trial in China
Published: Apr 15, 2020
By Mark Terry
Clinical Trial Stop

Alert for whichever way the wind might be blowing, many investors have jumped on the news that Gilead Sciences suspended one of its clinical trials of remdesivir for COVID-19 in China. The company is running at least five clinical trials for its experimental antiviral drug remdesivir against COVID-19. Readouts for at least one or two of them will occur this month. Meanwhile, more than 1,800 patients have been treated using the drug on an individual compassionate use basis so far. They recently published data in the New England Journal of Medicine on 53 of those patients suggesting promising results.

But company shares dropped 3% this morning after the company indicated it had suspended one of the trials in China. Gilead said that the Phase III trial for mild to moderate patients had been ended because of lack of patients to enroll.

According to a note by RBC analyst Brian Abrahams, the company is continuing studies in severely affected patients, and pulling data from the halted trial. He wrote, “Key upcoming readouts for the drug remain the Gilead-sponsored studies in severe (late April, though lack of a control arm may limit interpretability) and moderate (May) COVID-19 patients. NIAID’s remdesivir data may also come as early as May.”

Abrahams interprets all this to suggest limited efficacy of the drug, writing, “We continue to believe that while remdesivir showed a promising signal of activity in the recent open label compassionate use published data, the fact that no data has been revealed from the truncated severe study in China—the only randomized study thus far—despite today’s update also indicated it had enrolled a reasonably robust number of patients (n=237), suggests any benefits observed were likely inconclusive and maintains our view that the likelihood of remdesivir demonstrating substantial activity remains at best 50/50.”

The limited data on the 53 patients receiving the drug on compassionate use basis had no controls and, as a result, made it difficult to draw any definitive conclusions. The study of the 53 patients in the U.S., Europe and Canada who required respiratory support showed that about two-thirds benefited from the drug. About half of the patients received mechanical ventilation and four were on a heart-lung by-pass machine. Eight patients were excluded from analysis, one because of a dosing error and seven because there was no information available on how they did.

All the patients received remdesivir for up to 10 days. Over 18 days, 68% showed improvement, with 17 of the 30 patients on ventilators able to be taken off the devices. Almost half of patients were discharged, while 13% died. Mortality was highest in patients receiving ventilation, with 18% dying.

Gilead was quick to point out that the study has limitations. It is running two Phase III trials of remdesivir, the SIMPLE trials, in countries with high prevalence of COVID-19. Data from the SIMPLE trial in patients with severe COVID-19 are expected sometime this month. Data from the SIMPLE trial in patients with moderate disease are expected in May. It is also supporting several trials led by other groups, including two in Hubei Province, China. A trial in China in patients with severe disease was terminated early because of low enrollment. The data is still pending. A China study in mild-to-moderate disease is ongoing. A global trial led by the U.S. National Institute of Allergy and Infectious Diseases (NIAID) continues to enroll patients. Data is expected in May. Other studies based on a master protocol by the World Health Organization have also started patient enrollment worldwide.

Researchers doubt this recent study data is anything more than suggestive, if that.

“The data from this paper are almost uninterpretable,” Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine, told Bloomberg. “There is some evidence suggesting efficacy, but we simply do not know what would have happened to these patients had they not been given the drug.”

Remdesivir is a broad-spectrum antiviral originally developed to treat Ebola, but was ineffective. In preclinical work conducted at the University of North Carolina and Vanderbilt University before the pandemic, it had shown promise against a wide range of viruses, including coronaviruses. In Ebola it had been found to be safe but ineffective. But the data acquired in those trials helped move it to more advanced trials in COVID-19.

Another analyst, Hartaj Singh of Oppenheimer, is a bit less pessimistic, but he too expressed concern that the compassionate use study had no controls. He wrote, “We view these results as purely directional.” The trials discussed are “highly unorthodox in how quickly they are being conducted, and how many corners are being cut in the interests of getting results quickly,” reported Yahoo Finance. Singh added, the trial “was provided in the U.S., the EU, Canada, and Japan, likely with varying clinical protocols,” depending on which medical institution or system was involved.

Of course, the analysts have the job of evaluating the drug’s effectiveness on how it might affect the company’s stock price and giving investors recommendations. Gilead already manufactured 1.5 million vials of the drug that it was treating patients with it for free.

Alan Carr, an analyst with Needham, indicated that Gilead is only now “evaluating options for pricing strategy for subsequent batches if the drug is found to be helpful for COVID-19.”

Even if the drug is only slightly helpful, there will likely be huge demand. But in the midst of a global pandemic, it’s unlikely to become any sort of a profit center for Gilead.

A Florida man battling COVID-19 came out of a medically induced coma on Easter Sunday -- days after receiving plasma donated by someone who had recovered from the virus, according to a local report.

A few days after that, Michael Kevin Rathel was taken off the ventilator and breathing on his own, Fox 35 reported.

"We are in a very different place than we were 24 hours ago," his wife, Stacie, told the outlet Wednesday, after speaking to her husband over FaceTime. "He was even cracking jokes with the nurses. So I thought, OK yeah, he’s back."

Doctors at Orlando Health initially put him on a ventilator and into the medically induced coma on April 4, according to the report. He received plasma therapy four days later.

“The donor had the proper blood type to allow his plasma to be given to Kevin. Things lined up the way we could have hoped for," said Dr. George Ralls, vice president of quality and clinical transformation for Orlando Health.

The Food and Drug Administration (FDA) approved the plasma treatment on March 24, and officials at the hospital said it can be administered on a case-by-case basis.

Blood centers and hospitals around the country are calling for people who have recovered from the coronavirus to donate their plasma to help treat critically ill patients.

Source: Florida coronavirus patient emerges from coma on Easter after plasma treatment, report says

As firemonkey noted:

The experimental COVID-19 treatment remdesivir is showing promise in a Chicago clinical trial, according to the health news site STAT.

STAT reported that patients in the trial experienced rapid recoveries from fever and respiratory symptoms. Nearly all patients were discharged in less than a week, it said.

Some 125 people with COVID-19 -- 113 with severe symptoms -- were recruited by the University of Chicago Medicine into the two Gilead Phase 3 clinical trials, according to STAT. Kathleen Mullane, the University of Chicago infectious disease specialist overseeing the remdesivir studies, said that most of the patients had already been discharged and only two had perished.

Source: Experimental coronavirus drug remdesivir shows promise in Chicago trial, report says

With the exception of hot spots like New York, shutdowns should start lifting by April 30th to May 7th in most US states and most countries.

It is going to take way too long to develop a vaccine in terms of a continuing shutdown.

Also a vaccine is probably not going to be entirely effective. Influenza vaccines are well established, but that did not keep 80,000 in the US and 650,000 worldwide from dying of it in 2018.

In the meantime it seems an effective treatment is the best hope for saving lives and keeping hospitals from being overloaded. It does not seem that covid19 will continue being much of a danger if severe symptoms can be knocked out. That in combination with the vast majority of cases not needing any treatment whatsoever.

I wonder how long remsedivir takes to manufacture and when the test results on moderate to mild covid patients come out.

Sounds like a heck of a better option than hooking up so many people to ventilators the very act of which, regardless of illness or reason, gives them about a 50/50 chance of survival. When people hear "We'll need to use a ventilator" many think of it as just shy of a death sentence.

Trump can’t make states lift their shutdowns. I hope the west coast stays united against his stupidity. My local cases have remained steady and if we reopen itLl flare up. We don’t have enough tests.

As of now Washington's stay-at-home order is extended until May 4.

How long do you want everything shutdown?

Covid19 continues to be considerably way behind influenza in number of cases and number of deaths.