Developing the Covid-19 vaccine

[Herainestold]

So why is COVID-19 more severe in POC and BAME individuals? Do we know?

The question to be asked is "Why do people of colour have worse health outcomes across the board than whites?" This problem is not covid specific

The obvious answer, which I agree with, is white supremacy. However there may be Covid specific aspects of which we are only dimly aware.

[Bird on a Fire]

Vitamin D might be relevant as well. Maybe.

But yes, as JQH says, part of it is just that covid is yet another way that racism kills people.

[jdc]

The vaccine doesn't reproduce but the immune system thingies do.

My understanding is that the mRNA vaccine does reproduce. It's more like a conventional attenuated vaccine than an inactivated one: first it subverts the body into producing millions of blank newspaper articles labelled "Daily Mail", then over the next two or three weeks the immune system learns to destroy anything carrying that logo. After that, if exposed to real Mail articles, the immune response will be to turn on the shredder.

A virus gets a host cell to make more copies of the virus which can then infect other host cells.

I think the mRNA vaccine particles each get into a host cell where the mRNA gets the host cell to make spike proteins, which then can't go on to infect other cells.

The viral-vector ones just use a virus to get the mRNA into a host cell to make spike proteins but again then viral vector itself doesn't reproduce in humans for some reason. AstraZeneca uses a chimp adenovirus for example.

Genetically modified innit: 'weakened adenovirus... genetically changed so that it is impossible for it to grow in humans'

[shpalman]

[img alt="that Johnson & Johnson graph which looks like a penis"[/img]

Hahaaa! is funny because Johnson also means penis in some idioms.

[Herainestold]

This is the kind of thing I am thinking about. Does it apply to vaccines as well?

Different races have been found to react differently to certain medical treatments, in part based on an individual’s genetic ancestry. Those genetic health risks are being studied by Dr. Timothy Thornton, a professor, the associate chair of education, and the graduate program director in the department of biostatistics at the University of Washington School of Public Health.

Essentially, Dr. Thornton explains that the same genetics behind one’s race can also determine how somebody may react to certain medical treatments.

“We’re finding that not only do we see differences in a lot of clinical outcomes by race or ethnicity, but there are a number of examples where we’re seeing differences in how individuals respond to treatment based on race as well,” he said.

https://mynorthwest.com/2656687/uw-thor ... treatment/

[tom p]

This is the kind of thing I am thinking about. Does it apply to vaccines as well?

Different races have been found to react differently to certain medical treatments, in part based on an individual’s genetic ancestry. Those genetic health risks are being studied by Dr. Timothy Thornton, a professor, the associate chair of education, and the graduate program director in the department of biostatistics at the University of Washington School of Public Health.

Essentially, Dr. Thornton explains that the same genetics behind one’s race can also determine how somebody may react to certain medical treatments.

“We’re finding that not only do we see differences in a lot of clinical outcomes by race or ethnicity, but there are a number of examples where we’re seeing differences in how individuals respond to treatment based on race as well,” he said.

https://mynorthwest.com/2656687/uw-thor ... treatment/

I have never seen any evidence of this applying to vaccines. That's not to say it doesn't; but I don't know of anything saying it does.
I've also not seen evidence of this in immune suppressant therapies either, which do the opposite to vaccines, but on the same system in the body.
And the good thing with vaccinating a population is that even if it were, say, 90% effective in a caucasian population and 75% effective in a west african population, in Europe & the US, all people of west african origin would be adequately protected anyway.
Also, as others have noted, thanks to Bolsonaro being a c.nt, there were lots of Brazilians tested, and Brazil is a very ethnically diverse country, so the overall is based on people from multiple ancestral geographies.

[shpalman]

Well, some AstraZeneca doses have arrived in Nigeria so we'll see if it works, but it has been noted that the covid situation in most of Africa, apart from South Africa, hasn't been anything like as bad as that in Europe for some reason. Which would point to racism/inequality creating problems in Europe rather than any inherent difference in physiology.

[Woodchopper]

Which would point to racism/inequality creating problems in Europe rather than any inherent difference in physiology.

One inherent difference in physiology is the average age of the populations - which is 18.4 in Nigeria and 40.5 in the UK. Its also suggested that people living in slum conditions already have more pre-existing immunity due to high exposure to infectious diseases. Which would also be a physiological difference, though perhaps not an inherent one.

[shpalman]

Which would point to racism/inequality creating problems in Europe rather than any inherent difference in physiology.

One inherent difference in physiology is the average age of the populations - which is 18.4 in Nigeria and 40.5 in the UK. Its also suggested that people living in slum conditions already have more pre-existing immunity due to high exposure to infectious diseases. Which would also be a physiological difference, though perhaps not an inherent one.

Well Nigeria had 4.5 million people at age 65 or over in 2006 so probably a few more by now; Italy something like 14 million now (was about 12 million in 2010).

Nigeria: 157,671 confirmed cases of COVID-19 and 1,951 deaths. CFR 1.2%.

Italy: 2,999,119 cases and 98,974 deaths. CFR 3.3%.

So maybe that seems about right for the scaling of the CFR at least, but not the massive difference in absolute numbers of deaths, assuming there isn't an order of magnitude of under-reporting. (I'm not even considering what it would look like if you scaled the Italian population of 60 million up to the 200 million of Nigeria).

This thing about average ages often comes up, and I tried to discuss it before (see my post about life expectancy at 65). In Nigeria's case the lower average age seems to come from a population boom which hasn't had time to grow old yet, rather than people dying sooner. I'm not even going to bother quoting "life expectancy at birth".

[Herainestold]

Another physiological difference between Italy and Nigeria is levels of obesity, which is a possible risk factor.

[Woodchopper]

Which would point to racism/inequality creating problems in Europe rather than any inherent difference in physiology.

One inherent difference in physiology is the average age of the populations - which is 18.4 in Nigeria and 40.5 in the UK. Its also suggested that people living in slum conditions already have more pre-existing immunity due to high exposure to infectious diseases. Which would also be a physiological difference, though perhaps not an inherent one.

Well Nigeria had 4.5 million people at age 65 or over in 2006 so probably a few more by now; Italy something like 14 million now (was about 12 million in 2010).

Nigeria: 157,671 confirmed cases of COVID-19 and 1,951 deaths. CFR 1.2%.

Italy: 2,999,119 cases and 98,974 deaths. CFR 3.3%.

So maybe that seems about right for the scaling of the CFR at least, but not the massive difference in absolute numbers of deaths, assuming there isn't an order of magnitude of under-reporting. (I'm not even considering what it would look like if you scaled the Italian population of 60 million up to the 200 million of Nigeria).

This thing about average ages often comes up, and I tried to discuss it before (see my post about life expectancy at 65). In Nigeria's case the lower average age seems to come from a population boom which hasn't had time to grow old yet, rather than people dying sooner. I'm not even going to bother quoting "life expectancy at birth".

As far as I remember from the research on school children they are less contagious than adults. So a much younger population might have fewer infections. Add to that the benefits from climate and spending lots of time out doors or in well ventilated areas.

There are only two options though. Either there is massive under reporting of mortality and serious illness, or there is something about being a Nigerian (either physiological or environmental) that means that far fewer people are dying.

[jdc]

assuming there isn't an order of magnitude of under-reporting

Speaking of which: https://www.nytimes.com/2021/01/02/worl ... rting.html

The United Nations Statistics Division collects vital statistics from around the world. In North and most of South America, Europe and Oceania, it says at least 90 percent of deaths are registered. In Asia, coverage is patchier.

But for most African countries, the United Nations has no death data at all.

In 2017, only 10 percent of deaths were registered in Nigeria, by far Africa’s biggest country by population — down from 13.5 percent a decade before. In other African countries, like Niger, the percentage is even lower.

Mr. Agunbiade, the Lagos registrar, fills out a table each month tallying what caused the deaths he registered, if known. There are about a dozen categories to choose from. Old age. Malaria. Maternal mortality.

There is no Covid-19 column, though he said sometimes he crossed out the AIDS / H.I.V. column and put Covid.

researchers have just declared that there was a huge, hidden outbreak in the capital of Sudan. In the absence of a good death registration system, they used a molecular and serological survey and an online one distributed on Facebook, where people reported their symptoms and whether they’d had a test. The researchers calculated that Covid-19 killed 16,000 more people than the 477 deaths confirmed by mid-November in Khartoum, which has a population roughly the size of Wisconsin’s.

Imperial report on Sudan here: https://www.imperial.ac.uk/mrc-global-i ... -39-sudan/

Between April and September 2020, we estimate that 2% (sensitivity range 2% - 5%) of deaths due to COVID-19 were reported in official reported mortality numbers.

We estimate there were 16,090 (95% CI: 14,300 - 17,990) undetected COVID-19 deaths up to 20 November.

[Woodchopper]

Thanks for that jdc.

So it looks like there could be massive under reporting. The Covid deaths should be included in overall mortality. But excess mortality estimates may not be reliable either.

[Herainestold]

Thanks for that jdc.

So it looks like there could be massive under reporting. The Covid deaths should be included in overall mortality. But excess mortality estimates may not be reliable either.

So we just don't know how bad covid is in Africa, but we know it is worse than we thought.

[Woodchopper]

Here’s a new study from Denmark on how older people have a higher viral load and so are more likely to transmit the virus: https://www.medrxiv.org/content/10.1101 ... 21252608v1

So having a young population would seem to reduce transmission.

[Woodchopper]

So why is COVID-19 more severe in POC and BAME individuals? Do we know?

You can find some answers here: https://assets.publishing.service.gov.u ... r_2020.pdf

In short, severity is affected by their jobs, housing, members of the household and health conditions before they contracted COVID-19. But those factors don't explain all the disparities.

Long article here, was open access for me: https://www.ft.com/content/0e63541a-8b6 ... 91bf44a492

“Early on, it was all ‘we’re in this together’ and ‘the virus doesn’t discriminate’. But then it emerged that it did,” says Jason Strelitz, Newham’s director of public health. “Certain populations were not only more likely to become infected and suffer the worst impacts from the virus but also the adverse impacts of trying to control the pandemic and the economic consequences.”

[shpalman]

EMA says AstraZeneca vaccine can be used during blood clot investigation

The EMA said 30 cases of “thromboembolic events” or blood clots had been reported among 5 million people who had received the jab in Europe so far.

[raven]

Doesn't Covid itself cause clotting?

I've been wondering... I read something a while ago about Covid interefering with the bradykinin system by perhaps blocking lots of ACE2 receptors at once. So if the vaccine works by generating a lot of spike protein for you to react to, would that spike protein foul up the ACE2 receptors too, & is that how we get some of the flu-ey/nauseous side effects to vaccination? (I have no idea if that is possible, but it seems plausible.)

[JQH]

EMA says AstraZeneca vaccine can be used during blood clot investigation

The EMA said 30 cases of “thromboembolic events” or blood clots had been reported among 5 million people who had received the jab in Europe so far.

How many would have developed blood clots any way?

[shpalman]

EMA says AstraZeneca vaccine can be used during blood clot investigation

The EMA said 30 cases of “thromboembolic events” or blood clots had been reported among 5 million people who had received the jab in Europe so far.

How many would have developed blood clots any way?

AZ of course says that this number isn't more than you would expect just in general.

In the Italy rollout thread I mention 2-3 events in relatively young healthy males which seem to have their onsets within hours after receiving the AZ dose from a particular batch in Sicily, but bear in mind that there are half a million doses in that batch in Italy alone (although I wouldn't know how many doses have been given from it alreaady).

Maybe you'd expect 1 in 20,000 males of age around 50 to die each day from natural causes but I wouldn't know if sudden onset of a “thromboembolic event” in someone with no history (?) of it counts as a natural cause.

[shpalman]

Thailand delays Oxford vaccine rollout amid blood clot reports

[tom p]

EMA says AstraZeneca vaccine can be used during blood clot investigation

The EMA said 30 cases of “thromboembolic events” or blood clots had been reported among 5 million people who had received the jab in Europe so far.

How many would have developed blood clots any way?

Unsurprisingly, that was the first question the EMA asked themselves.
The EMA is funding university-run studies looking at observed vs expected for all kinds of possible reactions, with room to add in other events, all obviously stratified as you would expect.
These vaccines are going to be the best-studied-by-regulators medicines ever.

[Herainestold]

EMA says AstraZeneca vaccine can be used during blood clot investigation

How many would have developed blood clots any way?

Unsurprisingly, that was the first question the EMA asked themselves.
The EMA is funding university-run studies looking at observed vs expected for all kinds of possible reactions, with room to add in other events, all obviously stratified as you would expect.
These vaccines are going to be the best-studied-by-regulators medicines ever.

Good to hear.

[basementer]

EMA says AstraZeneca vaccine can be used during blood clot investigation

The EMA said 30 cases of “thromboembolic events” or blood clots had been reported among 5 million people who had received the jab in Europe so far.

How many would have developed blood clots any way?

I did a quick search. I found venous thromboembolism rates estimated as "142 to over 300 per 100,000 person-years" so a finger in the air guess is, those five million people being 50 * 100,000, they generate almost 100,000 person-years per week elapsed, so assuming (cagily) an average time since jab of two to three weeks, the lower bound is 280 to 420 such events. If I'm a whole order of magnitude out, 30 in 5 million still looks like noise not signal.
https://www.ncbi.nlm.nih.gov/pmc/articl ... 2C%2099%5D.

[Woodchopper]

Immunity to SARS-CoV-2 variants of concern

Although much debated, many researchers have the sense that people with a neutralizing antibody IC50 (half maximal inhibitory concentration) greater than ∼1/100 serum dilution would likely be safe from infection, or at least from symptomatic infection. Given that these are highly potent vaccines that often induce neutralizing antibody responses with IC50 of at least 1/1000, there is hopefully a reasonable safety margin before reduced recognition of variants means that effective protection is lost (see the figure). Ultimately, the best defense against emergence of further variants of concern is a rapid, global, vaccination campaign—in concert with other public health measures to block transmission. A virus that cannot transmit and infect others has no chance to mutate.

https://science.sciencemag.org/content/ ... /1103.full