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May 2020

What If A Vaccine Becomes Available?

There has been a lot of talk about “herd-immunity” to this coronavirus. The hope is that this will enable a return to more normal, less cautious times. Sweden has tried to achieve “natural” herd immunity by sacrificing many of its citizens to a nasty pathogen. Their approach is rather experimental; almost like a clinical trial in which the subjects are never given full disclosure of risks vs benefits and never have the chance to volunteer or decline to participate. The Swedish government declared by fiat that all its population would be guinea pigs. It hasn’t gone well there. Stay tuned for a soon-to-come blog on the Swedish experiment.

As I have written before in these pages, with a new pathogen it is not at all guaranteed that herd immunity will be effective or beneficial. It remains to be seen. Given that, it seems unethical to expose people to a potentially deadly pathogen in order to achieve something that is uncertain. This highlights the value of vaccines. Simply stated, a vaccine is a way to trick the body into thinking it has a virus infection without undergoing the risk of actually encountering the virus. That way, we can try to develop herd immunity at low health risk. If a vaccine can effectively stimulate a protective immune response, without risking viral disease, that is the ethical way to try to achieve herd immunity. The Milken Institute tracker now lists 145 candidate vaccines under development around the world.

In this blogger’s opinion, there is a pretty good chance that an effective and safe vaccine will be found and made available to not only protect individuals, but also to potentially protect the entire population for years to come by achieving herd immunity. However, finding that vaccine is just the first hurdle in developing herd immunity; getting the vax to sufficient numbers of people is the second hurdle. There already is a small, but nasty and persistent anti-vaccine strain in the US and European populations. I am concerned that this will prove to be a major impediment for using a vaccine to achieve herd immunity. A recent poll supports this concern.

A recent Associated Press-NORC Center for Public Affairs Research poll shows that only about half of Americans would get a CoV-2 vaccine if available. A population needs about 70% to carry protective immunity in order for herd immunity to be effective. Among those who said that they would not get vaccinated, 70% said that they were worried about vaccine safety. This is despite the demonstrable fact that vaccines have proven extremely safe, especially when compared to the risks of the diseases they prevent.

40% of the non-vaxers also said that they were concerned about catching COVID-19 from the vaccine. That statistic reveals how lack of information and emotion informs many health decisions in lay people. Catching the virus from the vaccine is impossible. Most of the lead vaccines in development do not even use the CoV-2 virus. They take pieces of the virus that researchers believe can tickle the immune system, and put them into inert or crippled vectors that are not infectious. They can enter human cells, but cannot exit. They do not spread. Many of the vaccines under development don’t even use an inert or crippled vector. Some are just using potential immune-provoking genetic elements without the rest of the virus or its genome. Fear of being infected with a virus from a vaccine is unwarranted.

Bottom line: There is a Great Race around the world to develop a CoV-2 vaccine and it probably will be successful. But, fear of the vaccine that is greater than fear of the disease will, sadly, minimize the immediate impact of the vaccine.

Misleading Headlines About the Hydroxyquinoline Trials

Today, several news sources are running with headlines that the WHO has stopped testing hydroxychloroquine. That is misleading. There are several arms to the WHO trials and they are pausing ONE of them due to what is called, interim stopping rules that can be triggered by what is called an interim data analysis.

Interim data analysis is when, at specific points of a clinical trial, an independent panel not involved in the research unblinds the research data in order to assess whether the study is progressing as planned and that study measures will be met. This interim analysis also looks for unanticipated side effects that occur too often. If this interim data analysis raises alarms the independent panel can halt the trial for further data analysis and discussion. Specific criteria that would trigger such pauses are required to be built into any clinical study in order to protect study subjects from undue harm. Sometimes studies are shut down early simply because the data show that investigators will not be able to recruit sufficient numbers of study participants and it would be unethical to continue exposing subjects to experimental therapies if the study will not be able to reach any definitive conclusion.

Apparently, in this case, the study arm treating advanced COVID-19 patients is being paused so that the independent panel can further assess whether the drug is causing an unacceptable incidence of cardiovascular events. Preliminary statements suggest that that could be happening, but we won't know for sure until the unblinded data are more thoroughly examined. It is quite possible that there are unacceptable side effects on this cohort of patients.

HOWEVER, other arms of the study on patients without advanced disease and prophylactic studies of uninfected patients will continue. Despite the cryptic and misleading headlines, trials of hydroxychloroquine continue as of this writing. In other words.....

...we will see.

Oxford Vaccine Study Rolls Back Expectations

About two weeks ago, I posted an update on the >100 coronavirus candidates under development around the world. I said that perhaps the lead vaccine was being developed by vaccinologists at Oxford University in the UK. They are aggressively recruiting test subjects for a Phase II/Phase III trial and predicted that they had about an 80% chance of having an effective vaccine by the Fall. Along with this high expectation, the pharma giant, AstraZeneca is already producing hundreds of millions of vaccine doses that will be ready immediately after the vax is approved.

However, I cautioned that as the pandemic winds down in many EU countries and in North America, it could be hard to vaccinate sufficient numbers of people who then catch the virus in order to test the vax's efficacy.

Because of the decline in infection rate in the UK, Oxford researchers have rolled back the expected chance of success of the vaccine to 50%. This is not to say that the vax would be ineffective, but there might not be enough infected subjects on which to test the vaccine.

It is a race against the virus disappearing. The outcome of the race could be affected if a second wave hits England or if the researchers arrange to undertake international trials, say in India or Brazil where the virus is not slowing.

We will see.

Grim US Statistics

The statistics for COVID deaths in the US are sobering as we approach 100,000 dead in four months.

  • COVID is now the third leading cause of death in the US, trailing only cancer and heart disease.
  • All deaths in the US are up about 30% since late March according to the National Center for Health Statistics.
  • NCHS data also show a huge spike in the weekly death average for 2020 beginning late March through early April compared to the weekly average for the same time period 2017-2019.
  • Between 2000-2018 deaths from flu AND pneumonia combined averaged 57,000 annually. NCHS and Johns Hopkins University data show that between February-May 24, 2020, COVID-19 deaths have almost reached 100,000 in the US.

And all of that is WITH isolation measures.

A Question for Readers About the Coronavirus Vaccine

A few days ago, I posted a COVID Vaccine Updateon the race to develop a vaccine for this coronavirus and a few days later, posted on what seems to be the most promising lead vaccine. At that time, 125 vaccines were under development. Today, according to the Milken Tracker, that number is 141.

It seems that the lead vax candidate is a highly novel RNA vaccine that is being developed by Oxford University scientists. As I earlier pointed out, the pharma company, AstraZeneca has already begun the highly risky production of this unproven vax in case it proves effective. If it doesn’t, or if another of the other 140 vaccines under development proves to be better, this effort will be for naught. As I said, “we will see.”

I have a question for blog readers. The Oxford investigators and AstraZeneca claim that they could have an effective and clinically tested vaccine as early as October. Even if they don’t meet that goal, there are several other vaccine candidates nipping on their heels. Some of these companies claim that their vaccines could be ready by the end of the year.

My question is this: if one of these vaccines shows sufficient safety and efficacy to gain expedited approval by the FDA, would you take it?

Would you line up to get one of these vaccines if the FDA says that they are safe and effective?

Please put your short answers in the comments section below. Just say yes” “no” or “not sure.”

Comments explaining your “vote” would be appreciated if you want to share them.

Note: in order to comment you have to sign your name (first name alone is fine, or even a pseudonym is ok). You also have to provide an email address, but rest assured that this is just so that Typepad can determine that you are legitimate and not a spammer. I never learn who comments unless they want to share their real name. My contract with Typepad states that they do not harvest any identifiable data from blog commenters. Your privacy is safe.

Where Did This Coronavirus Come From?

Inquiring minds, of both honest and conspiratorial sets, have been pondering, speculating, and even authoritatively announcing the origin of the CoV-2 virus that is causing this pandemic. Some say it has a natural origin, others say it came from a lab, either accidentally or on purpose. Some say that the lab of origin is in Wuhan and others say it came from a US military lab and neither provide much evidence for their allegations. What do we believe?

At first, based on previous experience with SARS and MERS, people immediately pointed to bats with some animal intermediate as the source of the human infection. From that, the Wuhan wet market became immediately suspect for being ground zero. Then the silliness began. China shut down release of much information on its testing to find ground zero. Trump, Secretary of State Mike Pompeo and no shortage of shrill conspiracy fans pointed to the fact that Wuhan has an Institute for Virology where labs study coronaviruses; therefore, they announced it had to have come from that lab, either by design or by incompetence. The Chinese unhelpfully, and with just as little evidence and as much shrillness, countered that the virus was introduced to Wuhan by the US military. Other, more irrational tin-hatters claim that Bill Gates created this so he could develop a vaccine with which he can surreptitiously inject us with a microchip thereby turning us all into Stepford Wives or Manchurian Candidates. I even saw a video of an MD who claimed that there is no virus. Rather, he authoritatively asserted that the COVID-19 malaise comes from toxins excreted by our cells in response to 5G technology. It has all been great show, but I don’t know whether to laugh at or fear my fellow travelers who so willingly buy such bunk.

Maybe there are a few of us left who like to look at facts and evidence before reaching conclusions. This post is for you. All others can go back to their tinfoil hat channels.

Some backstory:

Early on, in January, as news about the virus began emerging, China began pointing to animals at the Wuhan market, probably a pangolin or scaly anteater (a delicacy in China) as the likely source of the virus. After a while that story began to break down as they found infected people in Wuhan who had no contact with the market and a large scale surveillance of coronaviruses in pangolins concluded that these animals are not the source of the human virus. Then the Chinese stopped releasing information to the world, while simultaneously totally isolating and Hubei province where Wuhan is found  from all outsiders. US reporters were kicked out of China. Meanwhile, the virus had already escaped and was rapidly racing around the world.

Recently the Wall Street Journal published an expose of what went on in Wuhan during the first few days of the outbreak. In the middle of the night on December 31st, before anyone outside China knew there was a coronavirus on the loose, Wuhan officials began disinfecting its wet market. Officials collected biological samples from the stalls, goods and animals. China’s CDC said that a team from Beijing arrived on Jan. 1 and collected 585 “environment” samples from a garbage truck, drains and sewers in the market. They reported that 33 of the environmental samples tested positive for the virus. 14 of the positive samples were from the area of the market where wildlife was traded.  

Four months later, however, China inexplicably has yet to release data on the animal samples they collected from the Wuhan market. Why? A UN body charged with coordinating research into the origins of the virus has been denied entry by China. The EcoHealth Alliance, a nonprofit organization based in New York, has studied coronaviruses in China for 15 years and helped establish that the SARS virus originated in bats then jumped to humans via an intermediate civet in a market in Southern China. But the Alliance’s partners in China also have been unable to investigate anything about this virus. Why?

Clearly, the virus passed through the market, but how did it get there? Its origin remains unknown and shrouded in mystery, which only fuels speculation.

The virus:

It is well known that bats are an important reservoir for coronaviruses. About 500 different coronaviruses have been isolated from bats around the world. Other animals also carry the virus. In fact there are about 7 (including SARS, MERS and CoV-2) that can be found in humans.

A virus isolated from a species of bat found in Southern China and not found in the Wuhan area has 96% genetic sequence identity to CoV-2. This suggests that this bat carried an ancestor of the Wuhan virus, but how did it make its way to Wuhan where that species of bat is not found? It is eminently plausible that an animal in Southern China picked up the virus, was trapped and shipped to Wuhan. It also is possible that this didn’t happen.

Did the virus come from a lab?

Scientists from around the world who have examined the sequence of CoV-2 are convinced that it has a natural origin. They say it lacks telltale signs that certain sequences were purposefully cut out of the RNA backbone and replaced with other engineered sequences. And as viruses replicate, they make random, infrequent errors in copying the millions of bases in their genomes and these mistakes are passed on to daughter viruses that go on to replicate. These small genome mistakes provide a sort of fingerprint from which forensic analyses can be done and the molecular sleuths all seem to agree that the fingerprints do not point to a guilty verdict. The scientific consensus is almost unanimous in rejecting that the virus was engineered by humans. In a letter to Nature in March, a team in California led by microbiology professor Kristian Andersen said “the genetic data irrefutably shows that [Covid-19] is not derived from any previously used virus backbone” – in other words spliced sections from another known virus.

However, a team of Australian scientists, led by Nikolai Petrovsky, very recently described evidence that the novel coronavirus has an unexpectedly high affinity for receptors on human cells. A virus from another animal would be expected to have primarily adapted to that species and not to have undergone changes that make it more infectious in a different species. From this they jumped to the conclusion that the virus could have been specifically designed by humans to penetrate human cells. This is not based on any experimental data, but on computer models that predict the virus’ ability to bind to receptors in humans and other animals. While this observation is not what one would expect for a naturally evolved virus, it remains eminently possible that the virus really did evolve this human preference by happenstance in other species. Most viruses do tend to prefer the species they are found in, but there are myriad molecular and biological reasons why they sometimes do jump across species. And this virus has shown an unusual propensity to move between species. The genetic sequence that encodes for the region of the viral spike protein that binds to cell receptors is also  known to be the most mutable part of the coronavirus genome, which makes it less surprising that it could spontaneously mutate in animals to a form that could more easily infect other species.

Therefore, in this blogger’s opinion, this computer simulation does little to answer the question regarding the origin of the virus. In the absence of more direct data proving it was engineered, and the reality that the molecular sequence shows no “fingerprint” of such engineering, it remains premature to claim that it was created in the lab.

In a recent interview, Francis Collins, Director of NIH, explained that If you wanted to design a virus weapon, you would not design this one because it looks like viruses we already know about. It is not very novel in its genome sequence. Genome analysis comparing this virus to all of the 500 or so known coronaviruses shows more compelling evidence that nature was the bioterrorist that created it and that its creation has been going on naturally for a long time.

Peter Forster, an archaeological research fellow at Cambridge University, co-invented phylogenetic algorithms that have, since the 1990s, become standard software for mining genetic data to reconstruct evolutionary trees, or networks. His team applied the software to genome samples of the earliest coronavirus sequences from China.  In the Proceedings of the National Academy of Sciences, Forster reported finding three main strains of the virus that he labeled A, B and C. His research determined that A was the founding variant because it was the version most similar to the ancestral Cov-2 found in bats from Southern China.  He also discovered that the A strain wasn't the predominant type in Wuhan. Of 23 Wuhan samples, only three were type A, the rest were type B, a version that was derived from A and that is identified by two point mutations that distinguish it from type A. In other parts of China type A was the predominant strain. In other words, it appears that the type A founding strain frequently appeared in other parts of China very early after it was first found in Wuhan in December. Forster’s research adds to the confusion of the virus origin since it seems possible that the virus could have been introduced into humans in a number of places in China, not necessarily Wuhan. This suggests, but does not prove, that the virus might not have even originated in Wuhan.

The Wuhan Institute of Virology:

The Wuhan Institute of Virology is a world class coronavirus research facility and many have speculated that the virus could have escaped the lab by accident. They point to a Washington Post article from 2018 that reported that US Embassy officials who visited the WIV had  concerns over the security of the lab. However, James Le Duc, the head of the Galveston National Laboratory in the US, the biggest active biocontainment facility on a US academic campus, poured cold water on that suggestion. He also visited and toured the lab and stated that it has safety and quality measures comparable to the best Western labs. Other Western scientists who have visited the lab also believe that an accidental release was “implausible” and highly rate the facility. One of the major responsibilities of the lab is to isolate coronaviruses from bats from all corners of China. They then sequence the viral genomes and post the sequences into a repository that is freely available to any researcher around the world. The genome sequence of the current virus does not match the sequence of coronaviruses posted in the library suggesting, but not proving, that they never worked on it.

Of course, it is possible that Wuhan lab researchers simply have not reported all of their research to the public, but until specific evidence of that omission is presented, that just remains an unproven possibility.

Bottom line:

It seems clear that the ancestral virus came from a bat, but there is little certainty about what happened after that. At this point, the only thing certain about the virus is its uncertainty.

Coronavirus in rural areas

Today it was reported that the Navajo Nation surpassed New York for the highest CoV-2 infection rate in the US. The Navajo Nation is a highly rural, impoverished population of <200,000 people spanning parts of Arizona, New Mexico and Utah. They have an infection rate of >2300 per 100,000 people. For comparison, New York has an infection rate of ~1800 per 100,000 according to data from Johns Hopkins University.

The press and policy makers are correct to note that this is another example of health disparities seen by minority groups in the US. This is an important issue that transcends this coronavirus and has long been recognized and discussed to death. Yet the problem persists.

I won’t add to that discussion here. Rather, I want to point out how these data also illuminate another concern specific to this coronavirus and to the calls to begin returning the country to normal.

It is quite understandable that New York City, with its extremely high population density and being a world center for global travel, would be hard hit by the virus. NYC accounts for almost half of the COVID-19 deaths in the US. Meanwhile, rural areas in New York and across the country are often very lightly hit with the virus. That makes sense. In those rural areas people are automatically socially distanced by living far apart, reducing viral spread. So, why not relax stay-at-home restrictions in these lightly populated areas that have been only minimally affected by the virus? Why not let them go back to work, bars, bingo and bowling leagues?

Doesn’t it make sense to not make everyone equally share the pain when they don’t equally share the risk?

At this point, we come back to the Navajo Nation. Despite being a rural, low density population that has one of the strictest stay-at-home orders in the country, they are being disproportionately hammered by the virus. This humble blogger submits that the experience of the Navajo Nation should provide a cautionary note to those who think that great swaths of rural America that mostly have not been hard hit with the virus are largely immune to the pandemic. The Navajo Nation shows that even these remote parts of the country can indeed be devastated by the virus. If we open up similar areas around the country, will the virus also devastate them like it has the Navajos?

What is the right choice? Do we keep the country under wraps to prevent spread of the virus, but at great economic expense? Or, do we open things up and keep our fingers crossed that the virus won’t roar back and cause even more economic and medical damage even in relatively untouched parts of the country? I don’t know the answer to this question. I am a simple scientist who is very glad that I don’t have to make this decision. I just want to make sure that the bio-health risks are known. I will leave the economic risk considerations to experts in those fields. Together, we can hopefully present policy makers with a complete picture of the issues on which they can base intelligent decisions.


A very novel vaccine candidate shows early promise

Six days ago, I posted a summary of the international efforts to develop a vaccine to CoV-2. At that time, the Milken Institute tracker listed 125 vaccines under development around the world. Yesterday, they listed 133. The effort is intense and growing. Will any of these work? We will see.

Over the weekend, a Cambridge, Massachusetts biotech company, Moderna, that is developing a highly novel CoV-2 vax candidate in partnership with NIH, announced positive results in early stage testing of a vaccine that does not use the standard inactivated or “crippled” virus. This experimental vaccine uses only part of the RNA from the virus that encodes a protein that the immune system can see. This sort of “gene” vaccine has never been used before, but it proved to be safe in a few dozen test subjects who were followed over several weeks. In eight of these subjects, it also seemed to generate antibodies that blocked, or neutralized, the virus so that it was less likely to infect new cells in a petri dish.

Based on these results, Moderna is now undertaking a larger Phase II clinical trial involving a few hundred test subjects. Plans are also underway to begin Phase III trials on a few thousand subjects beginning in July to test the ability of the vaccine to actually protect people from getting COVID-19. Since only a few dozen subjects have received the vax at this point, that schedule seems overly ambitious. Details are not available as to where the trials will be undertaken, which could affect their ability to recruit sufficient numbers of subjects who will likely be exposed to the virus and provide a good test of its effectiveness. But time is of the essence. We will see.

This announcement also comes just days after one of the company’s directors, Moncef Slaoui, stepped away from the company to become the chief scientist for the US Warp Speed initiative to quickly find an effective vaccine against CoV-2. Slaoui retains stock in Moderna worth about $10 million, which raises significant questions of financial conflict of interest. On this point too, we will see.

While it is encouraging that the antibodies that are elicited by the virus seem to neutralize the virus in a lab petri dish, it remains to be determined whether this provides effective protection in a two legged petri dish that is a human. We also need to know the level of neutralizing antibodies that are produced by the vax. Emerging evidence shows that many patients who become infected with the virus and later recover do not show an antibody titer high enough to be protective against subsequent infection. This might be the reason for recurring anecdotes from China, South Korea and the US aircraft carrier, Roosevelt, of previously infected patients acquiring the infection again. On this point, like many others regarding the behavior of CoV-2 and the disease, uncertainty is the only certain thing at this time. We will see.

Moderna’s vaccine uses part of the viral RNA genome that encodes the surface spike protein that gives the virus its halo appearance and that binds to cell receptors in a person’s lungs and other tissues. The vaccine directly delivers this RNA coding sequence into human cells, which then make and express the spike protein, thereby tricking the immune system into responding to what it thinks is an infection. The cells will make the viral spike protein for a short while and then the RNA is degraded, it won’t last a long time. No other viral genes or structures are used in this vaccine, so nothing is “live” that is infectious or that needs to be crippled or inactivated. The idea is that this is a way to narrowly direct the immune response to a very specific viral protein. This approach has not been used before, but several of the organizations around the world are trying this sort of approach where you try to vaccinate with a gene rather than with a crippled or inactivated virus.

We will see.

Some Myths About the Coronavirus and Disease


Young people do not get sick.

A mid-March analysis from the CDC found that more than half of the nearly 2,500 Americans who had been hospitalized with COVID-19 at that point were younger than 55. And while the rate of hospitalizations for COVID-19 is higher in adults 65 and older, it’s still significant in people under 65.

You are immune if you have been infected.

That is not yet clear, though we have a lot of optimism that will be true.

In the case of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) — two other illnesses caused by coronaviruses — infected survivors develop an immune response that can last for months to years.  However, the virus’s close cousin that causes about 30% of common colds is a bit different since people get colds over and over. That throws a bit of cold water on the optimism.

Also, there are recurring, anecdotal reports of people being re-infected a second time with CoV-2, but we don’t know if these are legitimate re-infections or whether the sensitive RT-PCR test for the virus is just picking up residual viral RNA rather than live virus. Interestingly, the viral receptor, called ACE-2, is found at high levels in the testes. Testes are “immune privileged” sites, meaning any immunity a guy would have against the virus, would probably not clear this potential viral reservoir. Maybe that is responsible for some positive virus tests that look like someone has been re-infected.

Bottom line is we don’t really know how protective our immune response is to this particular virus. We also do not know whether, if protected, how long that protection lasts—a few months? Years? Lifetime? Stay tuned.

You can’t catch it from your pets.

There is no evidence that the virus spreads from pets to people, but there also is no evidence that it does not. It is pretty clear that humans picked this virus up from an animal and that humans have given it back to pet dogs and cats. The virus seems to easily pass between different species, so there is a good chance that you can get it from domestic animals (see: Pets: An Unexpected Reservoir for CoV-2?). Some health experts have recommended social isolation for your pets, keeping them from other people as well as from other animals. If someone in your household becomes infected with the virus, it could also be wise to keep that person separate from pets as well as other people.

Ibuprofen makes COVID-19 worse.

That myth was spread via a flood of news reports in March, which claimed that nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen could exacerbate the disease. That has been debunked by several experts, the FDA and NIH. Over-the-counter pain relievers like ibuprofen or acetaminophen are recommended for the general pain and fever that often accompanies COVID-19.

Injecting disinfectants or aquarium cleaner can treat the infection. 

Get real!  No.They.Do.Not!

Insects and ticks can transmit the virus.

While there are ample data proving that other viruses and pathogens are transmitted by biting bugs, there is no evidence that this or other coronaviruses are transmitted this way. Nevertheless, when outdoors, it is always wise to protect yourself from insect-transmitted pathogens like Zika virus, Lyme disease and others. Therefore, if you protect yourself from these, you should be covered if insects are ever shown to transmit coronaviruses.