COVID-19 - Facts and Information Only Topic

[Hapless Bills Fan]

On 5/16/2020 at 9:12 AM, Hapless Bills Fan said:

I think upthread there are links to several other companies with monoclonal antibody therapies they’re trialing or getting ready to trial for Covid-19.  I’ll look later and link this in.  Edit: here it is:

Article on the earlier report of antibody

https://www.10tv.com/article/pandemic-scientist-says-his-team-has-discovered-potential-cure-covid-19-2020-mar

 

Time for a brief update here.  Since I’m a lazy scut, will link to Derek Lowe’s blog update from June, then loop in and add a couple things later

.

[Hapless Bills Fan]

Interview with Epidemiologist Larry Brilliant. 

This is one of the epidemiologists who crafted the strategy to do something mankind has never done - eradicate an entire virus, Smallpox.  He Da Man amoung epidemiologists.

 

He goes a bit into how he feels we could bring our covid-19 epidemic in America back into control

 

https://www.wired.com/story/larry-brilliant-on-how-well-are-we-fighting-covid-19/?utm_source=pocket-newtab

 

Scroll down to "Speaking of ending the curse, how do we get out of this mess?" for his take on a path forward (but you really should read the entire interview to get a sense for the guy.  He's very down-to-earth - practical.

 

Imma link to this post over in the discussion thread to encourage discussion

[Hapless Bills Fan]

Interesting interview with Pfizer CEO Albert Bourla. 

 

If he were Moderna (press release and word of mouth, no actual published data) I wouldn't link an interview, but Pfizer/BioNTech have actually published data from their Phase I and II clinical trials, including showing neutralizing antibody data from all participants.

 

https://time.com/5864690/pfizer-vaccine-coronavirus/
 

Pfizer is starting manufacture pre-approval:
"You’ve invested more than $1 billion in this. What if the FDA rejects the vaccine?

We will just have to write it off and call it a day. We will throw it away. It’s only money we’re going to lose."

 

 

 

[PromoTheRobot]

Florida trending the wrong way.

 

https://www.politico.com/states/florida/story/2020/07/12/florida-reports-15k-new-cases-smashing-national-record-1299981

[Hapless Bills Fan]

JHU study on RT-PCR false negative rate.  Data have been made publicly available and will be added to as additional data are collected.

 

Key findings:

1) false negative rate lowest 8 days post infection (3 days after symptom onset), but still 20%

2) at symptom onset (average 5 days post infection) false negative rate 38%

3) in the first 4 days post infection, 67% negative rate (in people who eventually develop symptom and test positive)

 

Key quote:

"We are using these tests to rule out COVID-19, and basing decisions about what steps we take to prevent onward transmission, such as selection of personal protective equipment for health care workers," says Kucirka. "As we develop strategies to reopen services, businesses and other venues that rely on testing and contact tracing, it is important to understand the limitations of these tests."

 

 

[Hapless Bills Fan]

2 minutes ago, spartacus said:

so how is the PCR test essentially fool proof for all positive results - even those with no symptoms

but basically a coin flip when it genrates a negative result even for sick people with obvious symptoms

 

Good question.  It has to do with how the test works.  The solution to be tested, containing (or not containing) the extracted viral RNA is heated to denature it, then cooled so that 2 sets of primers to RNA unique to the virus can bind -“anneal”.  The annealing temperature is chosen so that the primers can bind only where they have a complete or nearly complete match to the viral RNA sequence.  Otherwise they fall off.  The enzyme that amplifies the RNA then goes to work.  The cycle is repeated a number of times - 45x in the CDC test.  But if the extracted viral RNA is not there, the primers have nothing to bind to, the enzyme can’t go to work, and the amplification won’t take place.  So unless the technician really f’s it up (and a lot of this is done robotically) it’s very hard to get a false positive.  (And there are negative controls in each plate, so the most usual ways to f’ up has the negative controls fail and you know something is wrong).

 

On the other hand, as something WEO said implied, there are lots of ways to get a false negative.  The sample collection swab can not go deep enough to hit the right place and collect enough virus, or if it’s a saliva sample the stabilizing solution doesn’t do its thing.  The sample can be stored improperly or for too long a time.  But most probable, the concentration of virus may be below the limit of detection at the sampled location - maybe it’s hanging out in the lungs, or the GI tract instead of the nasopharynx, or maybe the patient’s immune system is beating it down with a club.

 

I was thinking what a good analogy would be, and I came up with growing plants in sterilized soil in a greenhouse.  It’s easy to get a “false negative” where the seeds don’t grow even though you planted them.  Maybe the seeds were too old to germinate well, or were planted too deep, or not deep enough.  Maybe the soil tray wasn’t treated properly - allowed to dry out.  But it’s not easy to get a false positive in a sterilized growing tray in a greenhouse - no seeds => no plants

 

 

[DrDawkinstein]

Not sure what is appropriate for this thread, so Hap, move/delete is necessary. But a couple of articles from today...

 

Coronavirus immunity can start to fade away within weeks, according to a new study which puts a 'nail in the coffin' in the idea of herd immunity

 

Two months after infection, COVID-19 symptoms persist

 

Neither are great news for the "Just let all the players get it" crowd.

[Edit: here's the link to the "persistent symptoms" study.  Most common symptoms: fatigue, and dyspnea (shortness of breath).  Most of the patients in the study were diagnosed with pneumonia, so that makes a lot of sense.  On the other hand the "fade away within weeks" thing doesn't really mean what they say it means.  Serum antibody levels are not the be-all and end-all of adaptive immunity.]

[PetermansRedemption]

1 hour ago, DrDawkinstein said:

Not sure what is appropriate for this thread, so Hap, move/delete is necessary. But a couple of articles from today...

 

Coronavirus immunity can start to fade away within weeks, according to a new study which puts a 'nail in the coffin' in the idea of herd immunity

 

Two months after infection, COVID-19 symptoms persist

 

Neither are great news for the "Just let all the players get it" crowd.

@Hapless Bills Fan, do you have any insight on what this means for a vaccine? Are makers able to somehow get around rapidly deteriorating antibodies?

[Hapless Bills Fan]

1 hour ago, PetermansRedemption said:

@Hapless Bills Fan, do you have any insight on what this means for a vaccine? Are makers able to somehow get around rapidly deteriorating antibodies?

 

Sure. Well at least, I'll take a crack at it.  An immunologist I ain't and I keep hoping we have one here who will "out" him or her self, but I've got a couple threads by actual immunologists and stuff.

 

Upthread I posted a link to a decent overview of immune response with a little picture and all

Unroll of Twitter thread referenced in that article
Here's a link to another Twitter thread with a bunch of sketches about immune response that ID the key players
Unroll of the same thread: https://threadreaderapp.com/thread/1278357445023109121.html

 

Here's a link to the article referenced by Lowe

 

My TL;DR best guess response: we measure antibodies to look for immunity because they're easy to measure.  But they're only part of the adaptive immune response, and (quite probably) for covid-19, not the most important part.  Adaptive mucosal immune response and T-cell response may play a larger role and be more important for covid-19 infection as T-cells eliminate virus-infected cells.   Makes sense right - the virus has to get through the mucosal layer to bind to ACE2 and get into the cells it infects in the lungs (or gut, or whereever), and then once it subverts the cell to become a little virus factory, its goal is to bud and burst and release a bunch of virus to repeat the cycle.  If your immune system is doing a great job of nipping that process in the bud (ha!  see what I did there?), you never have enough virus rolling around in your bloodstream to get your B-cells all worked up about making lotsa antibodies.  Doesn't mean they can't, but why bother?  Your immune system is just like anything else, doesn't want to work any harder than it must.  So you make antibodies while you're fighting the infection, then you quit, and within a few weeks the ones you made get cleared. 

Often, the presence of antibodies and their persistence are correlated to other forms of adaptive immune response such as T-cell response and memory B-cell response (B-cells make antibodies; memory B-cells hang out for decades and hand out instructions "how to make THESE antibodies").  Here's a paper in Cell which actually looked at T-cell response and antibodies in covid+ patients.  But they're not always correlated, or another way to put it would be just because you aren't still putting out antibodies, doesn't mean you don't have the fly swatter (rest of adaptive immune response) ready to hand.

 

For example, a study found that while 90% of people with a positive RT-PCR test had antibodies a few weeks later, 40% of asymptomatically infected people went negative (for antibodies) during their convalescence.  That probably doesn't mean that their immune systems are ill-equipped to deal with a repeat challenge of covid-19 viral infection - to the contrary, their immune systems Did There Job the first time like a fly swatter and swatted that virus like a buuuugggg so why wouldn't they keep up the good work?  The fly-swatter just didn't involve heavy IgG response so no reason to keep making 'em.

 

For an effective, lasting immune response to be elicited by a vaccine, we need to elicit the entire spectrum of adaptive immunity, not just antibody response.

[Hapless Bills Fan]

I think this belongs here, but please respect the request to discuss in the discussion thread

 

NY State DOH report on covid-19 deaths in nursing homes. 

 

It is exculpatory and concludes that the 6,500 covid-19 positive patients sent to nursing homes in NYS were not the driver of infection, but rather community-acquired infection of up to 1 in 4 staff members

 

Actual report: https://health.ny.gov/press/releases/2020/docs/nh_factors_report.pdf

Article about it: https://www.news10.com/news/ny-capitol-news/new-report-out-from-nys-doh-on-coronavirus-in-nursing-homes/

 

 

 

 

[HappyDays]

The Governor of Missouri weighs in on hersd immunity. I recommend everyone click and read this entire thread. These are sobering numbers.

 

 

[Edit: it's a good find, @HappyDays, but Tate Reeves is the Governor of Mississippi.  The Governor of Missouri is Mike Parson (R), who was recently quoted defending his unmasked public appearances by saying "if YOU want to wear a Dang Mask, wear a Dang Mask"  "You don’t need government to tell you to wear a dang mask,” Parson said to a cheering and largely maskless crowd over the weekend. His campaign posted pictures online of a maskless Parson interacting with the public.  Meanwhile MO covid cases be like, 1020 new positives today!

Meanwhile, the official Missouri DHSS figures reportedly feature about a 7,000 positive test backlog.  In addition, in most of MO, test results are taking 7-11 days to be returned.]

 

[SlimShady'sSpaceForce]

During a press conference on Monday afternoon the Director for the Centers of Disease Control and Prevention, Dr. Robert Redfield, continued with the theme of pleading with Americans to put on a mask to stymie the spread of COVID-19. He said that, if everyone complied with said pleading, then "over the next six weeks we could drive [the virus] into the ground."

 

 

 

 

 

[spartacus]

this test is now being used in hospitals

accuracy is barely above a coin flip

who knows where else it is now being used to speed up the process

 

https://www.medicalnewstoday.com/articles/covid-19-antigen-test-could-give-quick-results-but-is-not-foolproof

[Edit: here's a paper https://www.frontiersin.org/articles/10.3389/fmed.2020.00225/full.  It seems to be a lateral flow immunoassay, as discussed here.

There are two parts to 'accuracy': sensitivity (if the patient has the disease, is it positive?) and specificity (if the patient doesn't have the disease, is it negative?). 

 

It appears the test is not giving false positives. 

 

That means it's actually potentially useful to clinicians and as a screening tool.  Let's say you're screening 800 workers at a Tyson Chicken plant in Joplin MO.

Assuming the test is not in short supply, you test everyone using it.  Let's say 200 are positive.  You still have to take and send 600 samples for RT-PCR, but you've just reduced the burden on your RT-PCR throughput by 25%, and you can tell those 200 people right away "we know you are positive, please isolate and we'll need to screen the people you're in close contact with." 

 

Similar thing for a patient in the ER who has symptoms that might be covid-19.  You test for covid-19 right then and there.  If the covid-19 test is positive, you admit them or give them home-care instructions accordingly.  If it's not, you take a swab and send it for RT-PCR.  Could potentially cut the burden on hospital labs by 50%.

 

But to be useful in taking the burden off RT-PCR throughput and reagents, it needs to be used in a consistent and coordinated fashion, with a clear decision chart - not "ok, you tested positive with this test but we'll send your sample for RT-PCR to confirm" ]

[Hapless Bills Fan]

Website with interesting covid-19 maps I have not seen elsewhere:

 

https://www.dartmouthatlas.org/covid-19/

 

1) map of covid-19 active cases by "hospital referral regions" - this is an interesting idea as hospital referral regions may be larger or smaller than counties.  Looking this way may give a better idea whether a system is close to overwhelmed

2) average daily growth rate of covid-19 cases over the last 7 days.  helps to see where cases are growing rapidly

3) map of at-risk populations (defined as >65 with 2 or more chronic conditions)

 

 

 

 

 

 

[Mr Info]

Moderna early vaccine results reported this morning in CNBC article summarizing NEJM publication late yesterday...all great news.

https://www.cnbc.com/2020/07/14/moderna-says-its-coronavirus-vaccine-trial-produced-robust-immune-response-in-all-patients.html

 

• Moderna's potential vaccine to prevent Covid-19 produced neutralizing antibodies in all 45 patients in its early stage human trial, according to newly released data.
• The findings provide more promising data that the vaccine may give some protection against the coronavirus.

Moderna's shares soared after the company said its potential vaccine to prevent Covid-19 produced a "robust" immune response in all 45 patients in its early stage human trial, according to newly released data published Tuesday evening in the peer-reviewed New England Journal of Medicine.

 

All 45 patients produced neutralizing antibodies, which scientists believe is important for building immunity and provided more promising data that the vaccine may give some protection against the coronavirus. In the trial, each participant received a 25, 100 or 250 microgram dose, with 15 people in each dose group. Participants received two doses of the potential vaccine.

After two vaccinations, the vaccine elicited a "robust" immune response in all participants in all dose cohorts, Moderna said. The company said the levels of neutralizing antibodies in patients in the high dose group were fourfold higher than in recovered Covid-19 patients. 
 

"These Phase 1 data demonstrate that vaccination with mRNA-1273 elicits a robust immune response across all dose levels and clearly support the choice of 100 µg in a prime and boost regimen as the optimal dose for the Phase 3 study," Moderna's chief medical officer, Tal Zaks, said in a statement. "We look forward to beginning our Phase 3 study of mRNA-1273 this month to demonstrate our vaccine's ability to significantly reduce the risk of COVID-19 disease."

In May, the company had released preliminary information from its early stage trial, but it lacked all of its data and it hadn't been peer-reviewed yet.

Moderna said the vaccine was generally well tolerated, but more than half of the participants reported mild or moderate symptoms such as fatigue, muscle aches or pain at the injection site.
 

Evaluation of the durability of immune responses is ongoing, Moderna said, and participants will be followed for one year after the second vaccination.

The effort by Moderna is one of several working on a potential vaccine for Covid-19, which has infected more than 13 million people and killed at least 573,200 across the globe as of Tuesday, according to data compiled by Johns Hopkins University. More than 100 vaccines are under development globally, according to the World Health Organization.

Earlier Tuesday, Moderna announced it would begin its late-stage trial for its vaccine on July 27. The trial will enroll 30,000 participants across 87 locations, according to ClinicalTrials.gov. Participants in the experimental arm will receive a 100 microgram dose of the potential vaccine on the first day and another 29 days later. Some patients will also receive a placebo.

Moderna's experimental vaccine contains genetic material called messenger RNA, or mRNA. The mRNA is a genetic code that tells cells what to build — in this case, an antigen that may induce an immune response to the virus. It became the first candidate to enter a phase 1 human trial in March.

Scientists are still learning about key aspects of the virus, including how immune systems respond once a person is exposed. The answers, they say, may have important implications for vaccine development, including how quickly it can be deployed to the public.

The U.S. is aiming to deliver 300 million doses of a vaccine for Covid-19 by early 2021. 

[Edit: here's the NEJM article, finally.  https://www.nejm.org/doi/full/10.1056/NEJMoa2022483?query=featured_home

A key figure for neutralizing antibodies:

 

Edited July 15, 2020 by Hapless Bills Fan
add link to NEJM article, change link to actual article

[shoshin]

Nationwide map of cases by county. Pretty great overview map. 

 

https://globalepidemics.org/key-metrics-for-covid-suppression/

 

Can't paste the entire image due to size but here's a peak. 

 

[shoshin]

Deaths all causes vs history. Just stumbled on this. We have talked about wanting to see this. I would not put a ton of faith in the last few bars because the CDC provisional deaths counts can take weeks to sort into categories and be confirmed:

 

Provisional death counts are weighted to account for incomplete data. However, data for the most recent week(s) are still likely to be incomplete. Weights are based on completeness of provisional data in prior years, but the timeliness of data may have changed in 2020 relative to prior years, so the resulting weighted estimates may be too high in some jurisdictions and too low in others. As more information about the accuracy of the weighted estimates is obtained, further refinements to the weights may be made, which will impact the estimates. Any changes to the methods or weighting algorithm will be noted in the Technical Notes when they occur. More detail about the methods, weighting, data, and limitations can be found in the Technical Notes.

 

 

https://www.cdc.gov/nchs/nvss/vsrr/covid19/excess_deaths.htm

[shoshin]

The country one looks OK...the state ones depending on the state look better and worse:

 

 

 

 

 

 

[SlimShady'sSpaceForce]

 

I feel sorry for the locals, or more specifically, the ones that care.  

 

Georgia Gov. Brian Kemp (R) is prohibiting local municipalities across the state from mandating that masks be worn in public to mitigate the spread of the coronavirus.

 

 

https://www.npr.org/sections/coronavirus-live-updates/2020/07/16/891718516/georgias-governor-issues-order-rescinding-local-mask-mandates

 

2 days old  v 

 

 

 

 

 

[Hapless Bills Fan]

I confirmed legit with another source.  Has not been released to the public, WTF, why?
 

https://publicintegrity.org/health/coronavirus-and-inequality/exclusive-white-house-document-shows-18-states-in-coronavirus-red-zone-covid-19/