COVID-19 Coronavirus Containment Efforts

[PeroK]

https://www.statnews.com/2021/01/04...accines-upping-the-stakes-for-the-rest-of-us/

What's the opinion of the experts on here? Is this journalistic exaggeration, or are we risking everything by changing the double vaccination schedule?

 

[mfb]

We have seen that a single dose provides good protection - possibly as good as the two-dose protocol, at least for a while. The BioNTech/Pfizer graph is the most striking example of this. Even if it's not as good as two doses: Delaying the second dose means getting more people protected sooner. Two people with 60% protection are better than one with 80%.

Even rolling out the vaccine at all when there is so much transmission occurring is far from ideal, he said, suggesting it would have been safer to beat down the amount of virus in circulation before beginning the vaccine deployment.

That's a nice approach, but as we have seen that doesn't work well.

 

[atyy]

What's the opinion of the experts on here? Is this journalistic exaggeration, or are we risking everything by changing the double vaccination schedule?

The article has comments from a few other people, and there seem to be differing reasonable views, so I think it's not known for sure. There are other experts quoted in the article besides Paul Bieniasz.

BTW, when we go to Iwasaki's Twitter thread, we see she's concerned about the increased transmissibility of the UK variant. But although there is some evidence to support that, I think the increased transmissibility has not yet been solidly established, eg.Trevor Bedford comments "The @PHE_uk secondary attack rate analysis was not done on the matched cohort. There should be more stratification here. I'm sorry for the confusion. I'd take the 15% vs 10% secondary attack rate with a grain of salt for the moment.".

 

[Rive]

...are we risking everything by changing the double vaccination schedule?

The virus itself is known to cause only partial (? weak, maybe?) immunity: sometimes with very low antibody levels. Compared to - guess only! - 20% of the population having 'natural' unreliable immunity; 6% having artificial 60% immunity or 3% having 95% immunity... Well, the difference does not feels really dramatic.

I think the high number of copies (=> high number of mutations) racing to re-infest that 20% is a far more worse problem.

 

[PeroK]

The virus itself is known to cause only partial (? weak, maybe?) immunity: sometimes with very low antibody levels. Compared to - guess only! - 20% of the population having 'natural' unreliable immunity; 6% having artificial 60% immunity or 3% having 95% immunity... Well, the difference does not feels really dramatic.

I think the high number of copies (=> high number of mutations) racing to re-infest that 20% is a far more worse problem.

Sorry, I can't understand what you are saying here.

 

[mfb]

The virus itself is known to cause only partial (? weak, maybe?) immunity: sometimes with very low antibody levels.

It's good enough to protect almost everyone for at least ~9 months, because double infections are still incredibly rare. They do happen, but not at a level where they would be relevant for the pandemic. In particular, the protection from getting the disease itself is far better than 95% over the observable time range.

 

[Rive]

double infections ... do happen, but not at a level where they would be relevant for the pandemic.

Sorry, but you do not know that. There is no widespread random and regular PCR testing amongst the already infected.
The only thing actually known is that reinfections which are bad enough to be tested again are rare.

Sorry, I can't understand what you are saying here.

From the article:

if you wanted to make a vaccine-resistant strain, what you would do is to build a cohort of partially immunized individuals in the teeth of a highly prevalent viral infection

The virus itself known to be unreliable when it's about antibody levels after an infection. Compared to the virus (which is lacking any quality management standards, as it seems) the vaccine is actually far more reliable (again: it's about antibody levels).
So if somebody is worrying about new strains, then he should look for the growing number of already recovered patients first because at this point they are a far more 'beefy' population of interest for the virus (which were left to grew into a 'healthy' gene pool already, ready for some drifting to occur).

The situation is not good, but the vaccine and its usage is just a very minor part of it.

 

[Jarvis323]

Sorry, but you do not know that. There is no widespread random and regular PCR testing amongst the already infected.
The only thing actually known is that reinfections which are bad enough to be tested again are rare.From the article:

The virus itself known to be unreliable when it's about antibody levels after an infection. Compared to the virus (which is lacking any quality management standards, as it seems) the vaccine is actually far more reliable (again: it's about antibody levels).
So if somebody is worrying about new strains, then he should look for the growing number of already recovered patients first because at this point they are a far more 'beefy' population of interest for the virus (which were left to grew into a 'healthy' gene pool already, ready for some drifting to occur).

The situation is not good, but the vaccine and its usage is just a very minor part of it.

When I was studying the research on immunity months ago, it was thought that antibodies might not last long, but T-memory cell immunity was likely to be pretty reliable and long lasting. I haven't kept up on research since then, except that the vaccines were found to also trigger T-cell immunity. Does anyone know the current knowledge about this issue?

 

[atyy]

So if somebody is worrying about new strains, then he should look for the growing number of already recovered patients first because at this point they are a far more 'beefy' population of interest for the virus (which were left to grew into a 'healthy' gene pool already, ready for some drifting to occur).

It's probably on the time scale of a few years, if it's similar to other coronaviruses.

https://www.biorxiv.org/content/10.1101/2020.12.17.423313v1
A human Coronavirus evolves antigenically to escape antibody immunity
Rachel Eguia, Katharine H. D. Crawford, Terry Stevens-Ayers, Laurel Kelnhofer-Millevolte, Alexander L. Greninger, Janet A. Englund, Michael J. Boeckh, Jesse D. Bloom
Twitter summary by the authors

 

[Jarvis323]

I've been reading through this paper, which goes into depth about the issue.

What are the roles of antibodies versus a durable, high quality T-cell response in protective immunity against SARS-CoV-2?

These findings carry a potentially important message for SARS-CoV-2 vaccines. Most current vaccine candidates are focusing on spike protein as the immunizing antigen, but natural infection induces broad epitope coverage in T-cells. It will be essential to understand the relation between breadth, durability and quality of T-cell responses and resulting protective immunity with SARS-CoV-2 vaccines and natural infection.
...
It would be a public health and “trust-in-medicine” nightmare with potential repercussions for years - including a boost to anti-vaccine forces - if immune protection wears off or antibody-dependant enhancement develops and we face recurrent threats from COVID-19 among the immunized. Data correlating clinical outcomes with laboratory markers of cell-mediated immunity, not only with antibody responses, after vaccination or natural infection with SARS-CoV-2 or other betacoronviruses may prove critically valuable, particularly if protective immunity fades or new patterns of disease emerge.

https://www.sciencedirect.com/science/article/pii/S2590136220300231

Since T-cells give long lasting and cross-reactive protection, not dependent on the spike protein, I would guess that a good T-cell response would be important for minimizing risk of a mutation overcoming vaccine protection. We also already have spike protein mutations that occurred after the vaccines had been developed, so we don't know if the levels of antibody protection seen in trials will be the same against the new fast spreading variant. A population with waning antibody resistance primarily targeting the spike protein, but not good T-cell based protection, would probably be a bad recipe for adaptation. I'm not sure what is known about the effectiveness of vaccine induced T-cells immunity at this stage, except that it is triggered to some extent. The paper mentions some ways to measure T-cell effectiveness, and argues that antibody levels are a bad measure to look at. I also wonder how a second dose of the vaccine affects T-cell immunity.

Another issue I wish I understood more is antibody dependent enhancement.

Antibody-based drugs and vaccines against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) are being expedited through preclinical and clinical development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clinical safety risks related to ADE, resulting in failed vaccine trials. Here, we describe key ADE mechanisms and discuss mitigation strategies for SARS-CoV-2 vaccines and therapies in development. We also outline recently published data to evaluate the risks and opportunities for antibody-based protection against SARS-CoV-2.

https://www.nature.com/articles/s41564-020-00789-5

Is this something we've avoided, having successful trials, or something we need to keep worrying about down the line?

 

[mfb]

Sorry, but you do not know that. There is no widespread random and regular PCR testing amongst the already infected.
The only thing actually known is that reinfections which are bad enough to be tested again are rare.

Well, that is protection.
In addition plenty of people get tested as part of their job, so it's not like we wouldn't have any sample.

 

[Rive]

Well, that is protection.

Regarding the worries linked above it's just not good enough. No conclusive information about cold-like reinfections, while the 'no significant amount of reinfections' kind of responses are just too commonplace. That's just very bad kind of guesswork around an important issue.

...T-cells give long lasting and cross-reactive protection...

As far as I know that's around the field of 'colds'. While it does imply that you get - well: just a cold - it will not actually prevent you get that cold. So this kind of 'protection' would likely kind of allow the virus to coexist in the human population.
It would not be exactly a bad result and would mean a really important and rare chance to observe a virus going endemic, but still has some unclear implications, especially if there are worries about the virus 'learning' the immune system.

 

[mfb]

See the comment about people who get tested as part of their job.

We also know that at least the Moderna vaccine reduces both symptomatic and asymptomatic cases - even with their first dose. They studied that by testing people at the time of the second dose. See this earlier discussion.

 

[nsaspook]

The FDA statement on vaccine dosing.

https://www.fda.gov/news-events/pre...authorized-dosing-schedules-covid-19-vaccines

We have been following the discussions and news reports about reducing the number of doses, extending the length of time between doses, changing the dose (half-dose), or mixing and matching vaccines in order to immunize more people against COVID-19. These are all reasonable questions to consider and evaluate in clinical trials. However, at this time, suggesting changes to the FDA-authorized dosing or schedules of these vaccines is premature and not rooted solidly in the available evidence. Without appropriate data supporting such changes in vaccine administration, we run a significant risk of placing public health at risk, undermining the historic vaccination efforts to protect the population from COVID-19.
...
We know that some of these discussions about changing the dosing schedule or dose are based on a belief that changing the dose or dosing schedule can help get more vaccine to the public faster. However, making such changes that are not supported by adequate scientific evidence may ultimately be counterproductive to public health.

We have committed time and time again to make decisions based on data and science. Until vaccine manufacturers have data and science supporting a change, we continue to strongly recommend that health care providers follow the FDA-authorized dosing schedule for each COVID-19 vaccine.

 

[Ygggdrasil]

This is anecdotal evidence, but some food for thought with regard to discussions of re-infection and generating herd immunity to COVID-19 (through either infection or vaccination):

Researchers published a paper in Science, reporting that in the Brazilian city of Manaus, about 76% of the population had been exposed to COVID-19 by October (though some researchers question the methods). Regardless, the region experienced a huge surge of cases in April exposing a large fraction of the population to the virus. However, in recent weeks, hospitalizations in the city have risen surpass the levels than experienced during the April surge.

(source)

There could be a few (non-mutually exclusive) explanations for these observations. One could be that the researchers greatly overestimated prevalence of infection and the recent new surge reflects spread to new, virus-naïve populations. Alternatively, these data could suggest that immunity to the virus could wane quickly. If waning immunity is an issue, how long the immunity from vaccines last is a major issue to consider (and unfortunately we don't have much longer-term data on the vaccines). However, from what we know about immunology, a two dose vaccination regime would be expected to give longer term protection than a single dose regime. Especially when vaccinating high risk individuals, it would seem best to give them the best shot at long lasting immunity.

 

[Rive]

This is anecdotal evidence...

As I recall there was an article about the area of Bergamo (the most heavily affected area of Italy, with high estimated exposure rate at Spring) still having some (!) free beds in hospitals during the Autumn season.

But: with high exposure and the usual set of preventive measures I would expect them having only a few sporadic clusters and cases, but no actual pandemic (to just almost fill their hospitals).

Anyway, my point is not exactly that Covid works this way. My point is, that it has four human-endemic brothers which works this way (with two others unknown // not endemic), and so far there is no sufficient scientific care were shown for this possibility: while denying it is commonplace.

Just not good. We don't know.

 

[david2]

University of Miami leads groundbreaking trial for COVID-19 treatment

https://www.eurekalert.org/pub_releases/2021-01/uomm-uom010421.php

The paper describes findings from 24 patients hospitalized at University of Miami Tower or Jackson Memorial Hospital with COVID-19 who developed severe acute respiratory distress syndrome. Each received two infusions given days apart of either mesenchymal stem cells or placebo.

Researchers found the treatment was safe, with no infusion-related serious adverse events.


Patient survival at one month was 91% in the stem cell treated group versus 42% in the control group. Among patients younger than 85 years old, 100% of those treated with mesenchymal stem cells survived at one month.

 

[Jarvis323]

Another interesting article about vaccine immune response and adaptation.

If live attenuated vaccines are off the table, then how could other types of vaccines achieve long-lasting protection? According to Le Vert, the answer lies in aiming vaccines at antigens within the SARS-CoV-2 virus. His company, Osivax, is developing a vaccine candidate that consists of nanoparticles carrying copies of internal Covid-19 antigens.

“We believe that targeting internal antigens such as the nucleocapsid presents an advantage over surface antigens as they have a much lower mutation rate,” said Le Vert. He added that an immune T-cell response against these internal antigens could protect against both current and future strains of Covid-19.

https://www.labiotech.eu/medical/emergex-covid-19-vaccine/

Apparently, some argue there is still a risk of ADE after spike protein mutation.

“If these mutation trends persist and increase with the worldwide spread of the virus, we believe that the vaccines targeting the spike surface antigen might have limited efficacy.”

Furthermore, Le Vert pointed out that mutations in surface proteins on the SARS-CoV-2 virus could even cause some vaccines to exacerbate the infection. This can happen via a phenomenon known as antibody-dependent enhancement, where certain antibodies stick to the virus incorrectly and make it even better at infecting cells.

In a worst case scenario, the vaccines do more harm than good for people infected with a new variant. I hope that risk is low.

 

[mfb]

Based on the vaccination tracker: In the last week a few countries have vaccinated and reported data at a relatively constant rate. Assuming that rate won't decrease we can set lower bounds on vaccination rates.

* Israel gives 125,000 doses per day. Enough for 20% of the population per month. 16% already got a first dose in the last two weeks. If they can keep this rate they'll achieve herd immunity quickly (at least against everything the vaccine protects against).
* Germany administers 40,000 doses per day. This is enough for 600,000 people per month (with two doses), or ~0.8% of the population. Clearly not enough, this has to ramp up massively.
* The trend in the US isn't that linear but they give ~340,000 doses per day. That's 5 million people per month, or ~1.5% of the population. A factor 2 faster than Germany but still far below the needed rate.
* Canada gives 12,000 doses per day, enough for 0.5% of the population per month. Same here.
* Italy is ramping up vaccinations really quickly. We'll learn more in the next few days.
* Other countries report too infrequently or just started vaccinations, so we don't have a trend yet.

What Israel does cannot be done worldwide - the production capacity is not there. But it demonstrates that Israel has the capacity to get people vaccinated at a fast pace, while other countries still have to demonstrate that.

 

[Jarvis323]

More bad news.

Gottlieb cited experimental evidence from Bloom Lab, and explained 501.V2 does appear to partially escape prior immunity. It means that some of the antibodies people produce when they get infected with Covid, as well as the antibody drugs, may not be quite as effective.

“The new variant has mutated a part of the spike protein that our antibodies bind to, to try to clear the virus itself, so this is concerning,” Gottlieb said. “Now, the vaccine can become a backstop against these variants really getting more of a foothold here in the United States, but we need to quicken the pace of vaccination.”
...
“It really is a race against time trying to get more vaccine into people’s arms before these new variants become more prevalent here in the United States,” said Gottlieb.

https://www.cnbc.com/2021/01/05/sou...te-antibody-drugs-dr-scott-gottlieb-says.html

 

[TeethWhitener]

Re: SARS-CoV-2 immunity longevity, there's a new paper out in Science:
https://science.sciencemag.org/cont...scienceroundup&et_rid=34838822&et_cid=3620063
Science 04 Dec 2020:
Vol. 370, Issue 6521, pp. 1227-1230
Abstract
Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has caused a global pandemic with millions infected and more than 1 million fatalities. Questions regarding the robustness, functionality, and longevity of the antibody response to the virus remain unanswered. Here, on the basis of a dataset of 30,082 individuals screened at Mount Sinai Health System in New York City, we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust immunoglobulin G antibody responses against the viral spike protein. We also show that titers are relatively stable for at least a period of about 5 months and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggest that more than 90% of seroconverters make detectable neutralizing antibody responses. These titers remain relatively stable for several months after infection.

Edit: actually, Science Immunology has a ton of papers on immunity longevity this month:
https://immunology.sciencemag.org/c...scienceroundup&et_rid=34838822&et_cid=3620063

https://immunology.sciencemag.org/c...scienceroundup&et_rid=34838822&et_cid=3620063

https://immunology.sciencemag.org/c...scienceroundup&et_rid=34838822&et_cid=3620063

The consensus seems to be that about 90% of those known to have been infected with SARS-CoV-2 (even mildly/asymptomatically) show elevated antibody levels and production of B (memory) cells for several months after infection.

 

[Astronuc]

In the NY Times, "California has an oxygen shortage for patients as it sees a surge in Covid cases. Los Angeles County’s EMS agency issued guidelines for emergency workers to use the “minimum amount of oxygen necessary” to keep patients’ oxygen saturation level at or just above 90%."

Apparently, emergency medical technicians (EMTs) have been told not bring suspected COVID-19 patients to the some hospitals because there is no room. I think I heard a statistic that 1 or 4 persons in LA county are infected.

 

[mfb]

Total hospitalizations in the US are still increasing, reaching 130,000 now. The April and June peaks were only at 60,000.
Plot

The US has ~900,000 hospital beds overall (plus whatever was added in 2020), but most of them are filled with other patients, the regional distribution matters, and the number of beds with additional oxygen or other special requirements is much smaller.

 

[PeroK]

In the NY Times, "California has an oxygen shortage for patients as it sees a surge in Covid cases. Los Angeles County’s EMS agency issued guidelines for emergency workers to use the “minimum amount of oxygen necessary” to keep patients’ oxygen saturation level at or just above 90%."

Apparently, emergency medical technicians (EMTs) have been told not bring suspected COVID-19 patients to the some hospitals because there is no room. I think I heard a statistic that 1 or 4 persons in LA county are infected.

Where did it all go wrong, one wonders?

 

[AlexCaledin]

- the virus has waay too many spikes! - and the poor antibodies are supposed to bite all the spikes off... hard job, I should say.

 

[OmCheeto]

Where did it all go wrong, one wonders?

Indeed.
For quite a while I've been focusing on the worst cases, which are invariably, recently, small population locations.
It was quite an eye opener when I changed the filters this morning:

Population > 1 million​

Deaths/Million/Day > 18​

Scotland is included, as I heard the other day that they were going into full shutdown for the rest of the month. Which, from the shape of the graph, still has me confused.

 

[mfb]

Scotland is included, as I heard the other day that they were going into full shutdown for the rest of the month. Which, from the shape of the graph, still has me confused.

They don't want to end up like the other places.

If you only start shutting down things when it's bad then it's bad regularly.

 

[PeroK]

Scotland is included, as I heard the other day that they were going into full shutdown for the rest of the month. Which, from the shape of the graph, still has me confused.

You're from a country where the President would rather pretend that COVID doesn't exist, so I can see how you would be confused by a government that takes pro-active measures based on scientific modelling and epidemiology. I know that might be hard to accept, but it does happen!

 

[jim mcnamara]

Wade Fagen-Ulmschneider at illinois.edu has some very useful tools that facilitate visualizing several Covid-19 datasets (JHU, Worldometer, etc):
https://91-divoc.com/pages/covid-visualization/

I used it on Arizona data. Sigh. They currently lead the world in new cases per 100k population.

The site is worth considering when you want to explore some aspect.
"divoc-19" is "covid-19" reversed order of characters in case you didn't notice. Or care.

 

[Astronuc]

January 8, 2021 - States reported 2.1M tests, a record 310,080 new cases, 131,889 COVID-19 hospitalizations, and 3,777 deaths. The 7-day averages for cases, hospitalizations, and deaths are at record highs. From CovidTracking.com

Yesterday, there were CovidTracking reported 4,081deaths, a record for a single day.

The pandemic is far from over, there is essentially no containment, and folks are not getting proper treatment (as in Regeneron monoclonal antibody cocktail, remdesivir and dexamethasone).

Meanwhile - NY Time reports "False Reports of a New ‘U.S. Variant’ Came from White House Task Force"
https://www.nytimes.com/2021/01/08/health/US-variant-covid-false.html

Reports of a highly contagious new variant, published on Friday by multiple news outlets, were based on speculative statements made by Dr. Deborah Birx.

“Researchers at the Centers for Disease Control and Prevention are monitoring all emerging variants of the coronavirus, including in 5,700 samples collected in November and December,” according to Jason McDonald, a spokesman for the agency. “To date, neither researchers nor analysts at C.D.C. have seen the emergence of a particular variant in the United States,” he said.

Among the variants circulating in the U.S. are B.1.1.7, first identified in Britain and now driving a surge and overwhelming hospitals there. The variant has been spotted in a handful of states, but the C.D.C. estimates that it accounts for less than 0.5 percent of cases in the country so far.

Another variant circulating at low levels in the U.S., known as B 1.346, contains a deletion that may weaken vaccines’ potency. “But I have seen nothing on increased transmission,” said Michael Worobey, an evolutionary biologist at the University of Arizona who discovered that variant.

That variant has been in the United States for three months and also accounts for fewer than 0.5 percent of cases, so it is unlikely to be more contagious than other variants, according to a C.D.C. scientist who spoke on condition of anonymity because he was not authorized to speak about the matter.

All viruses evolve, and the Coronavirus is no different. “Based on scientific understanding of viruses, it is highly likely there are many variants evolving simultaneously across the globe,” Mr. McDonald, of the C.D.C., said. “However, it could take weeks or months to identify if there is a single variant of the virus that causes Covid-19 fueling the surge in the United States similar to the surge in the United Kingdom.”

Carl Zimmer contributed reporting from New Haven and Noah Weiland from Washington D.C.

 

[PeroK]

The figures from the UK show 91,000 excess deaths in 2020. There were 697,000 deaths last year, which is almost exactly 1% of the population. There were about 73,500 Covid deaths recorded by the end of 2020.

https://www.bbc.co.uk/news/uk-55631693

And we've had 8,500 Covid deaths already in the first eleven days of this year.

 

[mfb]

Hospitals find extra Pfizer/BioNTech doses.
The whole story is a bit bizarre. Some hospitals discard them - as if the sixth dose taken from the same bottle would suddenly be worse than the nominal first five. If the hospitals are worried about incorrect bottle contents then the obvious action would be to discard all the doses taken from that bottle.

Where Year Two of the Pandemic Will Take Us
A good (and very long) article about the current state and expectations for 2021.

Reported deaths will reach 2 million by the end of this week.

 

[fresh_42]

Who, who have been breaching the social distancing stand up, please!

https://www.sciencemag.org/news/2021/01/captive-gorillas-test-positive-coronavirus

 

[PeroK]

Lichfield Cathedral used as vaccination centre:

 

[Jarvis323]