All things CoronaVirus

[Typical Lax Dad]

guys, all the action is over on the princeton lacrosse forum.

make haste.

It’s a mislabeled Hopkins thread!

[tech37]

I disagree with your almost immediate dismissal of Paxlovid before it has even been put to work and data can be reviewed. Your pessimistic POV may end up being correct but I certainly hope not. [/color][/b]

I'm not dismissing ANY drug. I'm with you----I hope they're wonderful, and have said so in the past. I have NO interest in any more of my fellow Americans dying.

But what I'm trying to tell you East Coast lot that things are different out this way. So when Old Salt links John Madden quotes as if I'm not working with these people on a daily basis--------truck drivers, orchardists, farmers, etc.------it tells me that he's forgotten where I live, and what I do for a living.

I"m now up to five dead. Five rural colleagues and/or friends.....dead from stubbornness. They didn't die from Covid, IMHO. They died from a mixture of social media and stubbornness. That's why I brought up Reagan, btw-----every one of these wonderful, hardcore, salt of the Earth conservatives are the people who run blood drives in their rural towns. Baked goods for HS trips. And 20+ years ago? They would have been out there, running a vaccine drive for their community.

Would've been six dead if my brother's best friend from HS didn't make it out of ICU around Thanksgiving. Staunch anti-vaxxer. Whole family is unvaxxed----five kids, all of them dependent on dad to put food on the table. Did he consider them when making his silly choices? F no. And, of course, he took the full range of treatments/advice the doctor had on hand when he arrived near-dead. Could he tell you what was in the drugs and treatments he received? Did he "do his research" on this care he received? F no. Hypocrisy that nearly killed him.

So yep------I'm angry, frustrated, tired, and freaking sad. And yep, it may come across as condescension....but when someone acts like a child, instead of the rational adult that you've known for years? You owe it to them to tell them they're not making any sense, and are acting like irresponsible children.

a fan, I'm sorry to hear this pandemic has become personal for you. That does add perspective.

And I'm sorry if this stuff gets me grumpy to others here....don't have too many outlets. I know everyone here has followed their Doc's orders when it comes to vaccines. I have no quarrel with anyone here.
Well, since you're replying to me and just to be accurate, I didn't follow any doctor's orders when I decided, all things considered, that vaxx would be best for me.

If I may, I'd like to add some personal perspective but from a more selfish angle (as in, looking out for #1). A while ago, you and I went back and forth re my doctor visit in Oct. I was trying to get an idea of what advice/decisions I could expect from him should I come down with Covid. When I asked about monoclonals, he said I would qualify based on age but based on my physical results (no brag, just fact ), I probably wouldn't be sick enough to qualify. I guess he thought he was making me feel better Seriously though, where would that leave me? I want treatment options to go home and wait this sh!t out with. Paxlovid is something I would hope to have as an option. Sans Pax, I would take Ivermectin and/or Fluvoxamine, based upon the years they've been utilized (I fully realize it would be off-label) and their safety records. Re the Merck pill, I would not feel very confident based on what I've read/heard.

I would love to see those options and more available for everyone, but as you know, charity begins at home.

Yes. I and I agree that these avenues need to be explored. I just wish that the availability of these treatments weren't leading to some folks choosing to not get vaccinated.....
I doubt that has anything to do with not getting vaccinated, they wouldn't anyway... just IMO.

[CU88]

https://yourlocalepidemiologist.substac ... dium=email


Here come the antivirals

Katelyn Jetelina
Dec 31

As epidemiologists, “primary prevention” is our main goal—reduce morbidity and mortality by preventing large populations from getting disease altogether. Vaccines are our best (but not only) tool to prevent severe disease from SARS-CoV-2. But even if someone gets the vaccine, there is still a small chance they could end up in the hospital. (This is especially true for those over 65 years or with comorbidities). Some immunocompromised vaccinated people are also not protected. And of course millions are not vaccinated. So, if someone gets severe disease, how can we help them?

One viable option is antiviral drugs. This is a class of prescription medications that can fight a virus once someone is infected. There are many mechanisms through which antivirals can potentially help. As depicted in the figure below, once the virus enters the human body, it searches for a host cell. Then the virus’s life cycle begins: 1) entry into our cells; 2) replication within our cells; 3) assembly; and 4) escape to go infect other cells. Scientists try to create antivirals to disrupt any one of these steps.


Jones et al. Viral and host heterogeneity and their effects on the viral life cycle. Nat Rev Microbiol 19, 272–282 (2021)
For example, oseltamivir (Tamiflu), the antiviral for the influenza, disrupts the last stage: it stops the virus from dissolving its way out so it can’t go infect others. This helps people recover from the flu 1 or 2 days earlier. But, antivirals are really difficult for scientists to make for a myriad of reasons (see my previous post here). This is why it’s taken so long to get an evidence-based antiviral, compared to, for example, vaccines, of which we now have 19 authorized and 9 approved worldwide.

Thankfully, the science for SARS-CoV-2 antivirals is finally coming through. In the past week, the FDA has authorized two for use in the United States. And this is a big deal.

Here’s what they are, what they do specifically, and pros/cons of each.

Paxlovid

This antiviral was created by Pfizer and is the most promising option so far. This treatment combines three pills that must be taken twice a day for five days. Two of the three pills are Paxlovid and the other pill is Ritonavir—a low dose HIV drug that will help the Paxlovid drug remain active in the body longer.

Paxlovid’s main mechanism is to slow down viral replication. (Stage 2 in the figure above). It does this by inhibiting one of the virus’s tools—called an enzyme—that it uses to replicate itself.

After Pfizer developed this drug, it went through randomized control trials just like vaccines do. Pfizer’s Phase III randomized clinical trial (called EPIC-HR) had 2,246 participants with a confirmed COVID19 infection that were randomized to get a five-day course of Paxlovid or a five-day course of a placebo. For this trial, all participants had to be “high risk:” unvaccinated with at least one high risk characteristic, like over the age of 65 or a comorbidity. The participants were followed for 28 days after entering the trial to see if they were hospitalized or died from COVID19. What did scientists find?

There was an 88% reduction in hospitalization and death among the Paxlovid group compared to placebo. Which is really high! Specifically,

Paxlovid group: 5 of 697 (0.7%) participants were hospitalized. None died.

Placebo group: 44 of 682 (6.5%) were hospitalized. Nine died.

Importantly, efficacy was similar whether the treatment was given within three or five days of symptom onset: 89% efficacy in the first three days and 88% efficacy in the first five days.

This was a huge win, because antivirals only work if given early. In the “real world,” this is difficult because it means the patient needs to realize their symptoms (which takes a few days), get tested (which is really hard right now), go to the doctor to get a prescription, and then start treatment. All of this needs to happen within a small window. The bigger that window, the better.

After receiving the full results, the FDA quickly authorized Paxlovid. They did this without convening their external scientific committee board for a review of the evidence. To me, this is a sign that the results were solid and/or an indication of the dire need for a highly effective antiviral in the wake of Omicron.

It was also very reassuring to see an independent study (i.e. science not conducted by Pfizer) come out this week confirming Pfizer’s results. The scientific group also found that this drug works against Omicron. We hypothesized that it would, because Omicron’s mutations don’t target the process mentioned above, but this is great news nonetheless. The figure below shows the effectiveness of the pill series (called Nirmatrelvir; orange lines) did not change in light of various variants of concern.


Pfizer also has two other concurrent studies using this drug:

EPIC-SR: This clinical trial evaluates the efficacy of Paxlovid among 662 people that were not considered high risk. Preliminary data showed that 2 of 333 (0.6%) patients who received Paxlovid were hospitalized compared to 8 of 329 (2.4%) who received the placebo. Unfortunately, the 0.6% isn’t statistically different than 2.4%, which means the drug isn’t too much help for non-high risk groups. But only 45% of the data is in thus far; we will see if the scale tips as more data comes in.

Concurrently, Pfizer is evaluating if, and by how much, Paxlovid blocks transmission in households. We should expect results in the first half of 2022.

And while this is all great news, the big concern is supply. Pfizer only manufactured enough pills for 65,000 people this month. When divided by 50 states, the availability gets smaller and smaller. For example, in DC—the place hardest hit with Omicron right now—there is only enough supply for 120 people. Antivirals are difficult to manufacture, so supply will ramp up slowly. Pfizer said they will have enough for 300,000 Americans by the end of February and, eventually, 120 million courses in 2022. The antiviral’s promise is also dependent on affordability and the assumption that individuals can get it in a timely manner (symptoms, test, doctor’s appointment, prescription), which is becoming more and more difficult across the country right now. There’s no doubt this antiviral will help down the road, but the promise for right now is limited.

Molnupiravir

The second antiviral drug that was authorized this week was created by Merck and and Ridgeback Biotherapeutics. It, too, is a pill series: four capsules twice a day for five days early in infection.

Molnupiravir works differently from Paxlovid, in that it does not directly slow down the replication or copying process. Instead, the drug interferes and inserts numerous mutations when the virus is replicating. As a result, the copied virus is weaker and the immune system is able to clear it much more quickly.


(FDA Molnupiravir Background Package Here)
Merck’s clinical trial (called the MOVe-OUT study) had 1,433 participants with confirmed COVID19 infection that were randomized to receive a drug or placebo series between May and October 2021. After the placebo or series, the participants were followed for 29 days to see if they were hospitalized or died. This cohort of participants will also continue to be followed until their late-follow up visit at 7 months. What did Merck find? Well, this data story is fascinating:

When Merck originally submitted their FDA application they announced promising interim results: 50% reduction in hospitalization and death.

Molnupiravir group: 7.3% (28 out of 385 people) were hospitalized. No deaths were reported.

Placebo group: 14.1% (53 out of 377 people) were either hospitalized or died. Eight deaths were reported.

Importantly this analysis was only among 762 participants from May to July 2021. Once Merck analyzed data from the second half of the study in August and early October (646 additional people), they only found only a 3% reduction in hospitalization and death. This was a shocking difference. (I’m giving them the benefit of the doubt that this was truly a weird data phenomenon, rather than purposeful and deceitful).

So, pooled together (50% efficacy from first half and 3% efficacy from second half), Molnupiravir had an overall 30% reduction in hospitalization and death compared to the placebo. Results are shown below, from Merck’s presentation to the FDA.


Merck Presentation at FDA Here
On November 30, 2021, the FDA’s external scientific advisory board met to discuss Merck’s authorization application. There were two streams of significant reservations during the discussion:

Modest efficacy: There was disappointment voiced around Molnupiravir’s modest effectiveness. The advisory board also had a lot of questions for Merck about the drastic effectiveness difference (50% to 3%). Merck didn’t have an answer for them.

Possible dangers: There was also a lot of interesting discussion about theoretical dangers. The drug works by causing of a lot of mutations in the virus (making it weaker and allowing the immune system to clear it). However, there is a risk that the virus mutates a lot but isn’t cleared. Thus, there is the theoretical danger that the drug could drive viral evolution. There is also the opportunity for the drug to change a person’s DNA. While no data has supported this, data has found this happens with pregnant rats. Some voting members voiced theoretical concerns that the drug could lead to cancer-causing mutations down the road.

This interesting discussion resulted in the external scientific committee narrowly voting to authorize this medication in a 13-10 vote. It took the FDA an abnormally long time to then take the advisory board’s vote to authorization. I was actually very surprised that the FDA ended up authorizing; I didn’t think this would happen.

Bottom line: While it may take a few months for supply, an antiviral like Paxlovid will be a game changer. I’m incredibly excited to see the science’s progression, as we can use all the help we can get in this pandemic.

Love, YLE

[youthathletics]

Interesting clip from Fauci, this is exactly what we were seeing back in 2020, where they were counting covid deaths if you were killed by a shark: https://www.instagram.com/p/CYIfOKnq-4W/

Then there is this.....

It's as if asymptomatic individuals can not spread the virus Not testing at the end of 5 days is shortsighted.

As Bart mentioned yesterday this is getting so convoluted. Here Fauci makes the assumption that the prevalence is Omicron, but the CDC walked that back last week and confirmed Delta is still a real and present danger.

[Kismet]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

[tech37]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

Or... would be completely out of the loop.

Happy New Year Kismet

[youthathletics]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

Or... Fauci would be completely out of the loop.

Happy New Year Kismet

Almost makes you miss those the daily press briefings, where they would all huddle up in one room, then speak....well, almost . But then again, it's all on the states now. What is clear to me, is that the Peter Principle is applicable with this administration...much like the last.

Happy New Year Tech, Kismet, and to my fellow FL Brethren.

[tech37]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

Or... Fauci would be completely out of the loop.

Happy New Year Kismet

Almost makes you miss those the daily press briefings, where they would all huddle up in one room, then speak....well, almost . But then again, it's all on the states now. What is clear to me, is that the Peter Principle is applicable with this administration...much like the last.

Happy New Year Tech, Kismet, and to my fellow FL Brethren.

Thanks! Best to you and your family youth

[DMac]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

My HO is in agreement with your HO. Too many people listening to their every word of stuff every minute too and completely immersing themselves in the subject driving themselves and everyone around them nuts. Meanwhile many a friendship has been broken and some families are imploding while the wedge is driven in deeper and deeper. It aint good folks. JFTR, I haven't listened to one word of any of them, haven't watched any (not an exaggeration) news in probably six months or so now. Highly recommend it. I click on a few links here and catch some stuff on YouTube now and then, that's in touch enough for me.
Happy New Year to everyone of you too. Well, except for ggait. Was going to send him a personal note but couldn't afford the postage from Mouth Breather, Dumbforkistan to 1 Highhorse Lane, Arroganceville. Oh well, he'll get the message anyway.

[Typical Lax Dad]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

My HO is in agreement with your HO. Too many people listening to their every word of stuff every minute too and completely immersing themselves in the subject driving themselves and everyone around them nuts. Meanwhile many a friendship has been broken and some families are imploding while the wedge is driven in deeper and deeper. It aint good folks. JFTR, I haven't listened to one word of any of them, haven't watched any (not an exaggeration) news in probably six months or so now. Highly recommend it. I click on a few links here and catch some stuff on YouTube now and then, that's in touch enough for me.
Happy New Year to everyone of you too. Well, except for ggait. Was going to send him a personal note but couldn't afford the postage from Mouth Breather, Dumbforkistan to 1 Highhorse Lane, Arroganceville. Oh well, he'll get the message anyway.

+1 on TV news. I limit it to local news. Haven’t watched a news entertainment show in over a year.

[Kismet]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

My HO is in agreement with your HO. Too many people listening to their every word of stuff every minute too and completely immersing themselves in the subject driving themselves and everyone around them nuts. Meanwhile many a friendship has been broken and some families are imploding while the wedge is driven in deeper and deeper. It aint good folks. JFTR, I haven't listened to one word of any of them, haven't watched any (not an exaggeration) news in probably six months or so now. Highly recommend it. I click on a few links here and catch some stuff on YouTube now and then, that's in touch enough for me.
Happy New Year to everyone of you too. Well, except for ggait. Was going to send him a personal note but couldn't afford the postage from Mouth Breather, Dumbforkistan to 1 Highhorse Lane, Arroganceville. Oh well, he'll get the message anyway.

regardless of opinions - all of us might want to consider thinking about a fan and ggait in Colorado and hope they don't live up in Boulder County where 500 homes (and an additional 300 other structures) went up in flames yesterday and overnight in the blink of an eye.

[Typical Lax Dad]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

My HO is in agreement with your HO. Too many people listening to their every word of stuff every minute too and completely immersing themselves in the subject driving themselves and everyone around them nuts. Meanwhile many a friendship has been broken and some families are imploding while the wedge is driven in deeper and deeper. It aint good folks. JFTR, I haven't listened to one word of any of them, haven't watched any (not an exaggeration) news in probably six months or so now. Highly recommend it. I click on a few links here and catch some stuff on YouTube now and then, that's in touch enough for me.
Happy New Year to everyone of you too. Well, except for ggait. Was going to send him a personal note but couldn't afford the postage from Mouth Breather, Dumbforkistan to 1 Highhorse Lane, Arroganceville. Oh well, he'll get the message anyway.

regardless of opinions - all of us might want to consider thinking about a fan and ggait in Colorado and hope they don't live up in Boulder Country where 500 homes (and an additional 300 other structures) went up in flames yesterday and overnight in the blink of an eye.

Hope that everyone is safe.

[DMac]

Yup, count me in on that, sincerely hoping the best for all. Just awful and scary.
I'll take the #1 city for snowfall over these places that catch fire any day. Damn.

[youthathletics]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

My HO is in agreement with your HO. Too many people listening to their every word of stuff every minute too and completely immersing themselves in the subject driving themselves and everyone around them nuts. Meanwhile many a friendship has been broken and some families are imploding while the wedge is driven in deeper and deeper. It aint good folks. JFTR, I haven't listened to one word of any of them, haven't watched any (not an exaggeration) news in probably six months or so now. Highly recommend it. I click on a few links here and catch some stuff on YouTube now and then, that's in touch enough for me.
Happy New Year to everyone of you too. Well, except for ggait. Was going to send him a personal note but couldn't afford the postage from Mouth Breather, Dumbforkistan to 1 Highhorse Lane, Arroganceville. Oh well, he'll get the message anyway.

regardless of opinions - all of us might want to consider thinking about a fan and ggait in Colorado and hope they don't live up in Boulder County where 500 homes (and an additional 300 other structures) went up in flames yesterday and overnight in the blink of an eye.

My goodness....just catching up on this. Seems to have been the result of power lines during 110 mph winds. https://www.cnn.com/us/live-news/colora ... index.html

[a fan]

IMHO too many people, talking too often, thus confusing almost everybody

By now, you'd think that Fauci and CDC would be talking and coordinating statements....but both are on TV all the time saying stuff all the time.

My HO is in agreement with your HO. Too many people listening to their every word of stuff every minute too and completely immersing themselves in the subject driving themselves and everyone around them nuts. Meanwhile many a friendship has been broken and some families are imploding while the wedge is driven in deeper and deeper. It aint good folks. JFTR, I haven't listened to one word of any of them, haven't watched any (not an exaggeration) news in probably six months or so now. Highly recommend it. I click on a few links here and catch some stuff on YouTube now and then, that's in touch enough for me.
Happy New Year to everyone of you too. Well, except for ggait. Was going to send him a personal note but couldn't afford the postage from Mouth Breather, Dumbforkistan to 1 Highhorse Lane, Arroganceville. Oh well, he'll get the message anyway.

regardless of opinions - all of us might want to consider thinking about a fan and ggait in Colorado and hope they don't live up in Boulder County where 500 homes (and an additional 300 other structures) went up in flames yesterday and overnight in the blink of an eye.

My goodness....just catching up on this. Seems to have been the result of power lines during 110 mph winds. https://www.cnn.com/us/live-news/colora ... index.html

Thanks for thinking of us, guys. This was miles to the NorthWest of us....we're fine.

It was NUTS. 100mph winds. And we haven't had snow (water) yet in Denver Metro. So football fields worth of brush went up in seconds.

Have a few acquaintances that lost everything.

[a fan]

Yes. I and I agree that these avenues need to be explored. I just wish that the availability of these treatments weren't leading to some folks choosing to not get vaccinated.....
I doubt that has anything to do with not getting vaccinated, they wouldn't anyway... just IMO.

[/quote]The folks I keep mentioning discuss the therapeutics all the time.....as in "I'll be fine if I get Covid because treatment is available".

It bolsters their anti-vaxx position.

This is anecdotal, obviously, and may not apply to many or even most. Happy New Year to you and your family!

[tech37]

Yes. I and I agree that these avenues need to be explored. I just wish that the availability of these treatments weren't leading to some folks choosing to not get vaccinated.....
I doubt that has anything to do with not getting vaccinated, they wouldn't anyway... just IMO.

The folks I keep mentioning discuss the therapeutics all the time.....as in "I'll be fine if I get Covid because treatment is available".

It bolsters their anti-vaxx position.

This is anecdotal, obviously, and may not apply to many or even most. Happy New Year to you and your family!
[/quote]
Thanks a fan, you as well. Glad to hear you're out of harm's way.

[ggait]

Thanks for the kind thoughts.

I did have to evacuate but my house and neighborhood are fine.

My old house and neighborhood (about a mile away) were completely destroyed. Nothing left standing but the chimneys. Several friends lost everything. And others are fine, but the house next door a total loss. Amazingly, zero casualties.

Wild fires during Christmas week. Beyond crazy.

2021 going out with a bang.

[seacoaster]

Thanks for the kind thoughts.

I did have to evacuate but my house and neighborhood are fine.

My old house and neighborhood (about a mile away) were completely destroyed. Nothing left standing but the chimneys. Several friends lost everything. And others are fine, but the house next door a total loss. Amazingly, zero casualties.

Wild fires during Christmas week. Beyond crazy.

2021 going out with a bang.

Good to know you guys are safe. Hope folks can turn the page on this year with some optimism. HNY.

[SCLaxAttack]

Glad to hear our fanlax Coloradans are safe, but sorry for others.

It's off the subject, but the Colorado news reminded me of the sticker shock I had when I got my next twelve month's home insurance bill a few weeks ago. Prepare yourselves. The combination of construction costs, home appreciation, and this past year's natural disasters are going to make your home insurance go through the roof. This was the first year since moving to NC four years ago that my county didn't experience a tropical storm or hurricane, and my bill still increased 52%!