COVID-19 Research, Drug trials and Pathophysiology

Thank you so much for your expert opinion and guidance, and believe me, I know you aren't 'prescribing medicine' at all. If I even think I'm 'coming down' with something unusual at all, I'll be onto our family doctor in a heartbeat. I didn't want to, but with reluctance (because of the price involved), my wife and I became members of a 'Concierge' medical practice organized by the primary care physician we've both been seeing for over 25 years already. I'd have very immediate access to him, and I promise I would not be one who 'self-medicates'. Again, thank you for your great willingness to help us all understand this virus' 'brave new world'....

 

Trials to test combination of Oxford and Sputnik vaccines
https://www.bbc.com/news/health-55273907

AstraZeneca coronavirus vaccine approved for use in UK
https://www.bbc.com/news/health-55280671

get the idea?

 

I find it odd the Russia is struggling with the epidemic seeing as they claimed they had the Sputnik vaccine in August??

 

Probably are having the same problems with anti-vaxers and anti-maskers as we have. No vaccine will work if it takes too long to persuade enough people to have the vaccine

 

PROBLEM what's the PROBLEM ?
If you've have had your Vaccine - & you believe that it works, then you must believe yourself
to be IMMUNE. - It either works or it does NOT ! - so why in HELL are you disturbed about
a bunch of supposedly suicidal, Tinfoil Hat Nut Jobs who refuse your Goddamn Vaccines ?

& why have the anti-vaxers & antimaskers come, to so distrust the CRAP that "so called" authorized
governance has been feeding them? Because they have now lost their Jobs and are now in the process
...................................................................................................................................................... of losing their Homes - Mayhap ?
.....................................................................................................................................................

 

Did the Coronavirus Escape From a Lab?

Nicholson Baker, New York Magazine

What happened was fairly simple, I’ve come to believe. It was an accident. A virus spent some time in a laboratory, and eventually it got out. SARS-CoV-2, the virus that causes COVID-19, began its existence inside a bat, then it learned how to infect people in a claustrophobic mine shaft, and then it was made more infectious in one or more laboratories, perhaps as part of a scientist’s well-intentioned but risky effort to create a broad-spectrum vaccine. SARS-2 was not designed as a biological weapon. But it was, I think, designed. Many thoughtful people dismiss this notion, and they may be right. They sincerely believe that the coronavirus arose naturally, “zoonotically,” from animals, without having been previously studied, or hybridized, or sluiced through cell cultures, or otherwise worked on by trained professionals. They hold that a bat, carrying a coronavirus, infected some other creature, perhaps a pangolin, and that the pangolin may have already been sick with a different coronavirus disease, and out of the conjunction and commingling of those two diseases within the pangolin, a new disease, highly infectious to humans, evolved. Or they hypothesize that two coronaviruses recombined in a bat, and this new virus spread to other bats, and then the bats infected a person directly — in a rural setting, perhaps — and that this person caused a simmering undetected outbreak of respiratory disease, which over a period of months or years evolved to become virulent and highly transmissible but was not noticed until it appeared in Wuhan.

There is no direct evidence for these zoonotic possibilities, just as there is no direct evidence for an experimental mishap — no written confession, no incriminating notebook, no official accident report. Certainty craves detail, and detail requires an investigation. It has been a full year, 80 million people have been infected, and, surprisingly, no public investigation has taken place. We still know very little about the origins of this disease.

Nevertheless, I think it’s worth offering some historical context for our yearlong medical nightmare. We need to hear from the people who for years have contended that certain types of virus experimentation might lead to a disastrous pandemic like this one. And we need to stop hunting for new exotic diseases in the wild, shipping them back to laboratories, and hot-wiring their genomes to prove how dangerous to human life they might become. . . .

 

Good measured article, calling for some learning.

 

New findings suggest that monoclonal antibodies used to treat could improve severe COVID-19 outcomes, including risk for death.

Given within 24 hours of critical illness, tocilizumab (Actemra) was associated with a median of 10 days free of respiratory and cardiovascular support up to day 21, the primary outcome. Similarly, sarilumab (Kevzara) was linked to a median of 11 days. In contrast, the usual care control group experienced zero such days in the hospital.

It's the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP).

https://www.medrxiv.org/content/10.1101/2021.01.07.21249390v1

 

I'd take the word of actual virologists instead of that of lay journalists who says "I think it's what happened" and "I've come to believe."

It's good that your interesting article has the real thing, though:

"Vincent Racaniello, a professor at Columbia and a co-host of a podcast called This Week in Virology, said on February 9 that the idea of an accident in Wuhan was “complete bunk.” The coronavirus was 96 percent similar to a bat virus found in 2013, Racaniello said. “It’s not a man-made virus. It wasn’t released from a lab.”

Plus, fortunately the article also quotes other virologists saying the same thing, and over here I've posted a couple of times a couple of virology articles detailing the issue.

By the way, the idea that this originated in a city with a BSL-4 lab which is how so many people get tempted to think that it came from there, has been questioned already, with a lung cancer study in Italy that froze serum samples being retrospectively looked at, with numerous cases being found in those samples of antibodies specific against the SARS-CoV-2 (could be cross-reactivity, but unlikely, to this degree) as far back as September 2019, three full months before the first superspreader event in Wuhan. We don't even know if this virus truly first surfaced in Wuhan or was just brought back there by tourists or something. 23 Italians in September, and 27 in October!

Here is the "evidence" the proponents of the man-made and/or lab accident angle basically say: "Hey, Wuhan has a Virology BSL-4 lab! Hey, there was a superspreader event in a Wuhan wet market that started the [I'd add, VISIBLE phase of the] pandemic! THEREFORE it's man-made or a lab accident!!!! Oh those evil Chinese from the Wuhan lab!!! They unleashed it!!!"

I wonder how they managed to unleash it in Italy three months prior and thousands of miles away. Here is the Italian study:

https://journals.sagepub.com/doi/full/10.1177/0300891620974755

 

The selective quotations game is open to all.

". . . I asked Jonathan A. King, a molecular biologist and biosafety advocate from MIT, whether he’d thought lab accident when he first heard about the epidemic. “Absolutely, absolutely,” King answered. Other scientists he knew were concerned as well. But scientists, he said, in general were cautious about speaking out. There were “very intense, very subtle pressures” on them not to push on issues of laboratory biohazards. Collecting lots of bat viruses, and passaging those viruses repeatedly through cell cultures, and making bat-human viral hybrids, King believes, “generates new threats and desperately needs to be reined in.”

“All possibilities should be on the table, including a lab leak,” a scientist from the NIH, Philip Murphy — chief of the Laboratory of Molecular Immunology — wrote me recently. Nikolai Petrovsky, a professor of endocrinology at Flinders University College of Medicine in Adelaide, Australia, said in an email, “There are indeed many unexplained features of this virus that are hard if not impossible to explain based on a completely natural origin.” Richard Ebright, a molecular biologist at Rutgers University, wrote that he’d been concerned for some years about the Wuhan laboratory and about the work being done there to create “chimeric” (i.e., hybrid) SARS-related bat coronaviruses “with enhanced human infectivity.” Ebright said, “In this context, the news of a novel coronavirus in Wuhan ***screamed*** lab release.”. . . . "

 

Well, as you may have noticed, none of these are virologists. A professor of endocrinology??? What the hell does he know about it??? These people are not talking from the standpoint of the genomic sequencing of the virus, and its phylogenetic analysis to compare it to other coronaviruses, like in this article (a real virology one):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159086/

I find it extremely likely that the good professor of endocrinology Nikolai Petrovsky wouldn't even be able to understand the article above, so his statement about the "unexplained features" is laughable. Which ones? I'd love to hear him detail them.

And in my previous post I didn't just go by the article you have linked to; I added a scientific paper to it as well. So, I'm not playing the game of selective quotes. I simply said that in your article, when REAL virologists spoke about it, they stated quite the opposite of what the journalist is implying (unsurprising, given the virology facts). I'm simply favoring the expertise of virologists over the opinion of lay journalists AND actually, scientists from other fields, who may issue a lot of opinions when interviewed by a journalist but actually, sorry, don't know what they are saying. They should stay on their lanes.

Anyway, let's put it this way: I don't for a second believe in this virus being man-made, manipulated, or escaped from a lab, and for good reason. If you do, be my guest, but you won't change my mind on this (as it is based on undeniable virology facts rather than speculation), therefore we might just want to agree to disagree. As such, I don't find that it is productive to engage in a long discussion about this. I've done it in other threads, and I have no further appetite for it at this time. If you have any interest in what I had to say about it earlier on, you can do an advanced search and you'll find my posts. If not, that's fine, too. This is the last of my posts on this issue, at this time. Cheers.

 

As you wish. I'm not an advocate for any answer to the question of virus origin. I merely note that the question remains open and there is good faith disagreement. See you downstream.

 

How long is it going to take for everyone to be vaccinated?

 

Everyone, where? In the United States? If the Johnson & Johnson shows good efficacy (phase 3 results are expected anytime) and is approved (could happen in about 4 weeks) there will be a substantive boost in our ability to vaccinate the population, given that we pre-ordered 100 million doses from them, and it's a one-shot vaccine that doesn't require freezers. Assuming that J&J gets approved, I'd imagine that we'll have all the adult population (these vaccines are not approved for people younger than 16-1 - or actually, those who don't decline the vaccines - inoculated by late summer or early fall. If we don't get a boost from J&J (say, their efficacy is lousy and they don't get approved) it will take longer.

In the world? Well, that's much harder. Maybe two more years? Could be even longer in certain places.

 

@CenterField
Cheeky ask, but as you are a doctor can I ask at what point would you consider the risk of serious illness reduced enough to re-open the economy. Everyone extremely vulnerable and everyone aged over????

 

I guess there isn't much we can do but pray and mean it.

 

The economy is largely reopened. I understand that there are no lockdown orders anywhere; California cancelled the last one. North Carolina has a curfew order I think from 11 PM to 5 AM and it's never been enforced, it's toothless. All other states have no lockdowns. I don't understand why people complain of lockdowns so much; they aren't happening since May for 49 states; California didn't have them either for months since May, then they restarted one for part of the state and now they stopped that, too.

Now, there are phased specific orders for specific businesses such as, in my state, 30% capacity for indoor dining in restaurants. Interestingly enough, now that both my wife and I have achieved the theoretical immunity peak one week after the second dose of the Pfizer vaccine, I asked her if she'd risk going to a restaurant this Saturday. She said she'll think about it; she is afraid.

Anyway, just in preparation for the possibility, I looked up the restaurants in my area (a very touristic, very foodie city). Usually, when we wanted to dine out on Saturday we had to book with more advance. OK, two days earlier... I looked at Opentable, it's wide open. There are lots of slots everywhere.

So, the idea that these businesses are suffering because of governmental decrees is a bit off, I think. They are suffering because people are afraid. Even the existing authorized capacity is not being met. So, movie theaters are open in my area... nobody is going. Even though a lot of people (unreasonably) traveled for Christmas, it was still only one third of the number pre-pandemic.

I've always said, what kills the economy is a pandemic out of control, frightening the population and decreasing consumer confidence, rather than a lockdown that only lasted for 3 to 5 weeks (depending on the state; 6 of them never had it) 9 months ago.

I see a lot of whining about lockdowns... and no lockdowns to be seen.

Now, this said, what do we currently have? A dip in new cases by 30% over the last two weeks, and a dip in hospitalizations, if I'm not mistaken, of 12%. That's great. Deaths haven't dipped but they are a delayed indicator.

Now, is this something that we'd take as a green flag to go back to full economic activity pre-pandemic? First of all, this reprieve may be temporary. Remember, the B.1.1.7 more contagious strain is supposed to become dominant by March. Numbers will probably go up again. So it's not yet the time to get over-confident. Also, the dip may be just the passing of the Christmas surge. We'll see.

Vaccines will help. The goal is to get 240 million eligible Americans vaccinated by the end of the Summer. This, added to the natural infection, might be enough to get us to the herd immunity threshold and slow down new cases to a trickle. Some models say that if we continue to vaccinate 1.5 million people per day, by late May we might see a very significant drop in new infections. So I'm hopeful for that, especially if we get a boost from the Janssen vaccine; phase 3 results are expected next week so with the usual 3-week delay for application and application review by the FDA and CDC, by the end of February we may have a third vaccine, and it is one that doesn't require freezer, and doesn't require a second dose. J&J promised to deliver 100 million doses by the end of June, if their product is approved.

Now, the above supposes that we won't see a catastrophic new strain that will completely escape the vaccines. I think it is unlikely that this will happen in short notice like this. For now, the B.1.1.7 (UK) strain seems to be fully covered by the existing vaccines. The B.1.135 (South Africa) less so but still with sufficient coverage. The P.1 (Brazil) is still being studied; we don't know yet; we do know that two well-documented cases of re-infection with the P.1 were found in Brazil in two patients that had Covid-19 before, with the then regular strain, so that is not very hopeful in terms of the strain's ability to escape natural antibodies. Do realize that vaccine-induced antibodies are actually better than natural antibodies so it doesn't necessarily spell disaster.

Your question is complex. The answer depends on four factors: 1. Availability of vaccines. 2. Acceptance of vaccines by the population. 3. Ability of the system to get the vaccines into people's arms. 4. Effectiveness of the vaccines against new strains.

If the answer to all four factors is favorable, I'd say that we'll be largely in much better shape by the end of the summer. If one or more of these factors go wrong, especially #4, then we're in for more trouble. I'm sorry to be unable to give you a more precise answer, but it is impossible to know since the answer depends on factors that are still uncertain.

--------

Oh, re-reading, you're focusing on vulnerable populations. There a few caveats. I wouldn't change the approach above, due to this distinction. People keep saying, "herd immunity, just protect the vulnerable" and that's a mistake, for various reasons:

1. There are too many vulnerable. Just hypertension alone, hits 100,000 Americans. 40% of our population is obese. Add millions more with many other conditions. I'd say that probably half of our adult population is susceptible one way or the other. And then, trying to protect these but encouraging the non-susceptible ones to roam about, will just bring the virus to the susceptible ones.

2. There's been some notions that the new strains, especially the P.1 (which has already been found in America) may be more virulent in younger people. Still to be confirmed, but this might change the equation on vulnerability.

3. People talk of vulnerability thinking of the death toll, but Covid-19 is much trickier than that. It's potential to inflict damage is not just linked to deaths. It is estimated that at least 10%, more likely 20% of people of all ages including those without underlying medical conditions may recover from an acute bout of Covid-19 but with some significant morbidity even if the mortality is low. This means, people won't die, but may come out of it with annoying and partially disabling organ damage, such as permanent lung fibrosis, heart inflammation, cognitive and other neuropsychiatric problems, renal and liver issues, chronic fatigue, etc. So, younger and healthier people should ALSO try to avoid catching Covid-19; they may have more consequences than they realize. Of course, there are some 40% of people who don't even have symptoms and come out fine. But not everybody. So prudence is recommended.

 

And accept the vaccine, when one's turn comes. And social distance and wear masks (actually two of them, it's the new recommendation once the new strains take over; one on top of the other).

 

A scathing new documentary from HBO alleges a Chinese coverup on the coronavirus
By Steven Zeitchik

 

Oh I have no doubt they tried to cover it up.

 

Something like that.

 

@centrefield.
Hi. Thank you for you very comprehensive answer.
I am in the UK and we appear to be dealing with the situation very differently to you. We are in complete lock down with only essential shops open, no restaurants or pubs, only allowed to meet 1 other person outside for exercise.
My own business has been shut for 11 months now at a cost to myself of $1.8m.
Anyway aside from some very interesting stuff (Thank you). Your answer turned into an explanation of how fast you could get everyone vaccinated, rather than which people would need to be vaccinated.
I guess to you the cost to the economy is worth less than even one life lost.
For me I am trying to balance the cost in ruined lives (from the economic effect) against the cost in years of life lost and who they are lost to.

 

We still have to stick to the rules as well.

 

I forgot what business you are in.

To me getting the teachers vaccinated is the important one to the economy.
I don't know about the UK, but here the teachers aren't keen on going back to in person teaching.
This is keeping a lot of people out of the workforce.
The assumption is the teachers can get the kids to follow the rules and some modifications are made to the schools.

 

Yes same thing here, though evidence is that no more teachers have become ill than any other group.
There is a lot of misinformation about how children can spread/catch the virus.
1, in the UK "Children" are lumped into one group aged 1 to 18, even though they react completely differently aged 10 and 18
2, Children can pass on the virus, is very different to children DO pass on the virus in any significant way.
3, Children can die from the virus, but we are never given the percentage, or the underlying conditions of those few who have.