By Lambert Strether of Corrente
We’re hoisting this really informative comment by alert reader Biologist from Links yesterday. (I cleaned up the formatting a little). Biologist characterizes all his notes as “gloomy,” but I think there’s nothing wrong with a little realism after looking at the data; how else will we get through this? Whether or not the note on Vietnam is gloomy — they did, after all, hold deaths to 35 (thirty-five) in a nation of 100 million — depends on whether you think the State in this country can ultimately be as functional as Vietnam’s.
A few gloomy Covid notes, I think I posted one yesterday but it got lost in the ether.
New variants: The Brazilian and South-African ones are even more worrying than the UK one, as they seem to partly escape immunity. Like the UK one, these two variants contain the N501Y mutation in the Spike protein which probably contributes to its higher rates of transmission.
However, they also contain a new mutation E484K in Spike, which in a recent lab study was shown to strongly reduce neutralization by antibodies from plasma of donors that had recovered from Covid. With the caveats that sample size was small and there was a lot of variation between individuals, this is bad news. Why? Because it might mean that natural and vaccine-derived immunity against this variant could be lower or less long-lasting compared to the other virus variants. While this is still in the realm of (informed) speculation, it would mean that a) reinfection could be more likely or quicker, and b) vaccines might be less efficient or long-lasting.
Here is the non-peer-reviewed paper, and the author explaining:
Key results validate in neutralization assays. Mutations at E484 greatly reduce neutralization (>10 fold) by sera from some individuals (examples below). Unfortunately, the South African lineage has E484K, as do some other isolates from elsewhere. (6/n) pic.twitter.com/C3b7Xe8hH7
— Bloom Lab (@jbloom_lab) January 5, 2021
Not sure if it was the same study, but this mutation was identified in someone who was reinfected after 5 months:
1/?Concerning case of reinfection: healthy 45 year old was reinfected with the genetically distinct SARS-CoV-2 variant that harbors the E484K mutation – this is the variant that was recently reported to escape neutralizing antibodies 1/6? pic.twitter.com/h83eqc0sO8
— Dr. Ali Nouri (@AliNouriPhD) January 7, 2021
Note that the same mutations arising and rapidly spreading independently in several locations strongly suggests they have a selective advantage. The variants arose and spread in countries where the epidemic has been very severe (UK, Brazil, South Africa, new ones in USA), and there are indications that they arose in chronically infected immunocompromised patients that were treated with plasma. The reduced immune capacity of these patients kept the virus population alive, while the plasma provided strong selection to escape immunity. Basically, with the uncontrolled spread of this virus we’re providing it with lots and lots and lots of incubators to evolve. I am speculating here, but I wonder whether having a sizable population that’s been given just one vaccine dose might also increase selection pressure for escape variants.
Herd immunity is even harder to achieve than previously thought. Manaus was devastated in the first wave, in a mostly uncontrolled epidemic, but despite a whopping 76% of the population having been infected and mass death, herd immunity was not achieved:
“Buss et al. used data on the occurrence of SARS-CoV-2–specific antibodies (seroprevalence) in blood donors, adjusted for waning antibody responses over time, to calculate an estimated attack rate for COVID-19 of 66% in June, rising to 76% in October, in Manaus. (…) This attack rate resulted in a factor of 4.5 excess mortality in 2020 relative to previous years. The infection fatality rate was estimated to be between 0.17% and 0.28%, consistent with the population being predominantly young and at reduced risk of death from COVID-19. (…) Despite such a high proportion of the population being infected, transmission in Manaus has continued, even in the presence of nonpharmaceutical interventions (NPIs), with the effective reproduction rate R near 1.”
I strongly encourage you to read the very accessible write-up by Prof. Devi Sridhar and Dr. Deepti Gurdasani quoted above. The original technical article is here.
A lesson from Vietnam in how to do contact tracing and quarantining. From the CDC:
When 27 staff members in the catering company [of BMH hospital] tested positive for SARS-CoV-2, the entire BMH staff (7,664 persons) was put under quarantine. Contact tracing in the community resulted in an additional 52,239 persons being quarantined. After 3 weeks, the hospital outbreak was contained; no further spread occurred in the hospital.
?1/CDC Report on Vietnam's??Incredible Tracing/Quarantine Program: after outbreak in major Hanoi Hospital, entire 7,664-persons staff quarantined. Contact tracing in the community resulted in an additional 52,239 people being quarantined. After 3 weeks, outbreak was contained? pic.twitter.com/wzFiwAmmzE
— Dr. Ali Nouri (@AliNouriPhD) December 14, 2020
More on Vietnam from Global Asia:
Another effective containment strategy has been shutting down the border. A week after the first cases were confirmed, on Feb. 1, Vietnam declared a public health emergency and halted all flights to and from China. The flight ban gradually expanded to other virus-hit countries. By late March, the country had suspended all international flights. Since then, only Vietnamese nationals and some foreign experts and businessmen have been allowed in with strict conditions, including mandatory testing and a 14-day quarantine.
And quarantine actually means quarantine, none of that UK voluntary stuff that no-one adheres to:
All arrivals have to spend their quarantine at army-run camps or hospital facilities that are free of charge. Food expenses for foreign nationals are reportedly about double that of locals — the government is aware of diet differences and has made efforts to accommodate them by adding sausages and milk, thus increasing the cost.
Note that Vietnam – a poor country close to China with a population of almost 100 million – has had a total number of 35 (thirty-five) Covid deaths.
We’ll soon find out. Quebec is planning to give as many first doses as possible, and inject the second one 90 days after the first one. The recommended time frame is 21 to 28 days (depending on the vaccine) after the first injection, and Health Canada recommends not doing it later than 42 days.
How could it not increase selection pressure? Innovate or your lineage ends, right? But attributing volition to the virus looms.
My understanding about variants, it requires a large pool of infected patients for them to appear. If the vaccine roll-out is combined with rigorous NPI’s, my hope is that the pool will shrink and the variants decrease.
The vaccines are non-sterilizing in their current form. They will only generate enormous selective pressure in the direction of evolving new variants that escape them. Not only that, but because so far immune escape has been coupled to these things, those variants will be more contagious, and perhaps deadlier too.
It is VERY hard not to get depressed about all this…
And the notion that Team Blue can fix any of this is simply magical. Here we are almost a year in and we can’t make N95s in sufficient quantity, quarantine and contact tracing are jokes, ad infinitum.
Had to drive to get a script on Friday; an upscale bar and restaurant where you might spend an hour or two had a completely full parking lot. WTF? Thanks Andrew Cuomo!
And looking at the NYT or Reuters each day, reporting on the threat of these new strains is scant and always below the fold, if not a page 12 equivalent.
Thanks to NC we can be informed. Thank you.
No, no,no, do not become depressed, there are still lots of questions and there is a lot of speculation on what is going on. If one variant becomes more prevalent it could be for various reasons and not necessarily because it is more transmissible. Another thing to be said is that these variants have surged in places with relatively high incidence so transmission rates might be affected not directly by transmissibility but by, for instance, acquired immune resistance but this doesn’t need to mean higher infectivity or more severe disease by these variants. Nobody knows. In fact, even if serum prevalence studies are conducted, these are not good indicators of real incidence and, to say it in this way, ‘rate of naivety’ to Covid and its variants.
If anything I think these variants are the product of a pandemic that has already infected a significant fraction of the population and Covid is now ‘realising’ naivety has declined. The fact that different variants show common mutations might suggest convergence: there are not that many viable alternatives in the evolution of Covid and they converge in the same mutations that might have unexpected trade offs on other viral functions.
The new UK variant might not lead to higher mortality or severe disease, but the evidence that it is more transmissible is now getting stronger and stronger. More transmission under the same fatality rate means more death: https://twitter.com/EricTopol/status/1348739701243404289
The evidence for increased transmission of this variant so far is well summarised by this tweet I’m copying below:
Hi Biologist thanks for the links but note that even if in vitro binding to the receptor shows higher affinity this mustn’t be the reason that explains 2 totally or partially. It is not enough as a proof, as a single cause, or worse, as the single cause though it supports better transmissibility theoretically. Reason 1 has more explaining power for 4 and for this reason could explain 2, 6 and 7. Regarding 5 buff grains of salt everywhere!! and again 6 y 7 can have other explanations. Reason 2 can be explained as well as redundant 6 or 7 partially and/or totally by reasons other than the mutations themselves as well as by the mutations.
So, have already been all those variants compared in vitro and at the same time for receptor affinity? Do they behave similarly in this sense? That would give further support (or remove it).
Yep I agree evidence is not conclusive regarding mechanism. Your suggested experiment of binding affinity would certainly clarify things more.
Initially when they announced this new variant in UK I was rather skeptical because mutations crop up all the time, and there’s been no lack of exaggeration about supposedly horrible new mutants. Based on what I saw at the time as very flimsy evidence they locked down UK completely. But now more evidence is confirming that transmission is indeed higher so I think the new lockdown was prudent even if we don’t know the mechanism yet.
Thanks for your comments btw, always enjoy your input and expertise.
We have to bear in mind also that once you are not naive to a virus and if you had a decent immune response, the immune system has ways to deal with variants via memory cells and can with more ease select new antibodies to the newly arising variants (as long as these are not utterly different such as it could be the case with virus recombinants that combine pieces from different viruses). How this applies with vaccines is difficult to say but again these could still be somehow protective against immunologically different strains as long as these are not very, very different.
Regarding the origin of the new variant, it is speculated that all the mutations that characterise this variant arose in a single immunocompromised patient who was chronically infected for several months.
The reason is that there are 13 or so mutations, all of which had been seen individually before, but not in this combination. Despite lots of surveillance (genome sequencing), no ‘intermediate’ forms of this variant have been detected, which would have been expected if the mutations had arisen one by one in the general population.
To me, this suggests that the convalescent plasma treatment this individual received provided strong selection pressure on this virus to evolve within its host, and that the increased transmissibility is a by-product of this selection. Unfortunately for us a negative by-product.
Population-scale non-sterilizing vaccination will ratchet up the selective pressure orders of magnitude.
Guess what will emerge as a result of that..
well said. so much we still do not know.
IMO 10 years from now Sars Cov2 will have killed most of the people it is going to kill, with sporadic deaths in the frail and elderly thereafter. it will then be our 5th common CV. Vaccines or not. Vaccines will hopefully get us there with far fewer deaths
Is this the first opportunity that a medical community has had in human history, to analyze the progressive evolution of a coronavirus? As Darwinian as the results are, I find the subject of variants fascinating. There’s a little part of me that admires this virus. ‘Clever girl.’ You really have to give Mother Nature her due.
After reading about the Norway deaths in a Bloomberg article, my 96 year old father in law decided to cancel his vaccine shot at the VA hospital yesterday. He’ll wait for a month or so to see how things go and then revisit the decision. I had no opinion; he is a very smart and highly competent adult and can make his own medical and other choices. He doesn’t get out at all these days except for walks; he lives with us and has his own bathroom and is a compulsive hand washer and always has been; he never catches the numerous flus we catch. He is very healthy but very frail, so maybe this is the right choice; serious vaccine side effects could kill him. There have so far only been 113 cases (no deaths that I know of) in our zip code of over 15,000 people in Silicon valley. Of course I’m nervous about the new variants.
Curious: why have we seen NO reports of death in the elderly in the US?
Where are you getting your news? Numerous elder-care facilities have reported many deaths.
Trade offs. Something that I see as interesting from the Manaos story is that mortality rates could be diminishing and that might be the effect of ‘herd immunity’ rather than and/or earlier than noticeable reduction of disease incidence. I don’t know what are the differences between Sao Paulo and Manaos in age distribution but the mortality rate estimated in Manaos seems to be less than half compared with Sao Paulo’s estimate and such difference could well be related with the high incidence in Manaos. Re-infections might tend to be less deleterious as ‘herd immunity’, a term I dislike because it makes you take wrong assumptions when talking about respiratory viruses, is achieved. Immunity is always relative when talking about respiratory viruses, particularly infections in the upper respiratory tract.
I believe that Covid will in the future become endemic in humans and seasonal and less damaging with time. It will mostly cause common cold and the incidence of severe pneumonia will fall. How long will it take I don’t know, but if Manaos is in the fast track it would be very interesting to follow the course there. This might help figure out our future with Covid. Some of the most recently acquired Coronaviruses causing common cold can still cause severe pneumonia in a few subjects.
I don’t know what are the differences between Sao Paulo and Manaos in age distribution but the mortality rate estimated in Manaos seems to be less than half compared with Sao Paulo’s estimate and such difference could well be related with the high incidence in Manaos.
The population is much younger in Manaos. Correcting for age, infection fatality rates were similar between Manaos and Sao Paulo. No effect of ‘herd immunity’.
More details in full article https://science.sciencemag.org/content/371/6526/288
To tell the truth, if you go to supplement S2 figure (see page seven), it seems there are significant differences in mortality rates for the same group ages in both cities particularly for the elder cohorts. Though the differences reduced somehow in October. In any case it is quite possible that those June October results are not really comparable as it is quite possible that many more Covid deaths were unregistered in the first wave. The problem then is that we cannot see the real evolution of mortality because I assume June data is not good. May be when they have new data in April and next June we can say better.
As per the article, which is very good, you have to make strong assumptioms (as they admit) to consider their estimated incidences as valid so I take the conclusions with a grain of salt.
Thanks for pointing that out. Yes, mortality was ca 40-50% in Sao Paulo compared to Manaos higher for the >80 year olds, but I’m not convinced that’s enough to make average rates across the whole population differ so much as they did – more than double in Sao Paulo.
But you’re certainly right that data was sketchy in those early days. I would certainly not assume that other factors such as herd immunity are a better explanation until we have better data.
Sorry, to complete the picture. It is not only that deaths could be more under-represented in June, but also RT-PCR tests, possibly to the point of not being enough representative for the whole picture. Some differences between the cities could be due to differences in deployment of tests which might not have been equal. It seems to me there is a picture that Covid was less seriously treated in Manaos where the younger population possibly made it look less risky. Unfortunately the data is not good enough to assess the evolution of disease severity from the very beginning, IMO. My intuition is that the decline in mortality (and most probably morbidity) is probably more steep than what these figures reflect.
I’m far more concerned about moribity than mortality. The lung scans alone give me enough pause to NEVER want this crap, let alone the damages caused to other highly vascular systems in the body.
And I agree with the sediments re: the vaccine expressed above. We have an imperfect “vaccine” (that hasn’t been tested for immunity nor transmission, just severity limitation) being distributed via an inefficient / ineffective system and we’re (USA) no longer going to hold back the second doses resulting in imperfect administration. All the while, many of the people who get it will think they’re immune and become lax (or eliminate) their protective behavior…
All of this is external of the backdrop of the new varients. Much like our political discourse, I see this getting far worse before it starts to get any better :(
Be safe, my fellow humans.
Cemetery burials are higher during this second wave.
I watched The Hill last week because I was curious if knowledge of these new strains has impacted political calculations among the elite. Biden made a rather sensible speech about the new stimulus package recently.I was curious what motivated it, given his silence during the campaign. Unfortunately the answer seems to be no. The Hill’s conservative commentator, Saagar Enjeti, is convinced Biden will see huge gains politically this year because the economy will come roaring back when the entire population is vaccinated.
First, my understanding is we’re nowhere near on track to vaccinate the entire US population this year. Even if we get to 70%, based on the data from Manaus that’s not enough to stop the virus. Second, vaccinated people may still be able to spread the virus. I sense that once people are vaccinated, they’re going to immediately return to risky behavior regardless of the consequences for others. Imagine if there are lockdowns and vaccinated people ignore them en masse. Third, while we may see eye-popping numbers when economic activity picks up, I question whether the wider population will enjoy it. It looks like a third of small businesses are gone. Tens of millions have a huge debt overhang from rent they can’t pay. Sooner or later the eviction moratorium will expire and all of those people will be on the street. Fourth, if we see a spike in hospitalization and fatalities from these new strains, economic activity will crater again as a big chunk of the population chooses to stay home and others are forced to because of lockdowns. We’ll know if the new strains are going to have this impact within about 8 weeks. If we get a new wave, that will push out economic “recovery” another 4 months or so. The economy wouldn’t see big numeric gains until very close to the 2022 midterms. Too late for Democrats. Republicans aren’t going to lift a finger for someone else’s economy, and what happens when the stock market notices?
Does any of that spell good news for Biden…?
Contrary to Enjeti, the theme for 2021 may be “Operation Enduring Misery” rather than “good times are here again”. And 2024 looks like “interesting times” in the Chinese curse sort of way.
Things that could change my mind: (1) If we manage to do serious lockdowns this year and stop the virus in its tracks – no indication US elites have this capability, (2) If we do serious debt forgiveness by 2022 or so – elites are allergic to this, (3) If Democrats turn out to be serious about doing meaningful stimulus – also allergic, (4) If the virus goes away on its own (hospitalizations dramatically decrease for some reason) – within the realm of possibility.
1) The vaccine wasn’t tested to limit or prevent infection nor transmission, just symptom severity. And based on my reading, the medical community seems to assume that infection and transmission by vaccinated people will occur in not insignificant numbers.
2) With the eviction moratorium, there will be a non-insignificant number of people who have gotten back on their feet but are still behind on their rent. Like in 2008+ where people lived in their homes without paying their mortgage, I think we’ll see or are seeing a similar boost to spending being rerouted from rent to other activities thanks to the moratorium.
Based on number one alone, we’re not going to see a major bump. Mix in the variants and imperfect administration of the imperfect vaccine and it’s going to get worse IMHO. Saagar has been less upbeat in my opinion, but like you I disagree that good times will be here again in 2021.
The AstraZeneca one was. It has little effect on infection, only stops symptoms.
There is zero reason to think it will be any different with the RNA ones that were not tested for that.
“Even if we get to 70% . . .”
70 percent??? When you have surveys like this: https://jamanetwork.com/journals/jama/fullarticle/2774711? (sorry if this has already been posted)
“During November 25-December 8 (Table), the self-reported likelihood of getting COVID-19 vaccination was lower among women than men (51% vs 62%; aRR, 0.9 [95% CI, 0.8-0.9]) and Black vs White individuals (38% vs 59%; aRR, 0.7 [95% CI, 0.6-0.8]), and higher among adults aged 65 years and older vs those 18-49 years (69% vs 51%; aRR, 1.4 [95% CI, 1.3-1.5]) and those with at least a bachelor’s degree vs a high school education or less (70% vs 48%; aRR, 1.5 [95% CI, 1.3-1.6]).
Between April 1-14 and November 25-December 8, the percentage who stated they were somewhat or very likely to get vaccinated declined from 74% to 56% (difference: 18 percentage points [95% CI, 16-20]) (Figure). Significant declines over time in the likelihood of seeking vaccination were observed for both women and men and in all age, racial/ethnic, and educational subgroups.”
That’s a big drop in the percentage of people who are interested in being vaccinated. The numbers are from a little over a month ago; things can change of course. I’m noticing that people I know are very interested in finding out about how their friends who have been vaccinated have been doing, since it is hard to find articles on the topic, and the articles that one finds almost never have comment sections anymore. SF Gate seems to have just gotten rid of their comment section.
It’s much worse than that.
We have already seen the emergence of immunity evading mutants as a result of selective pressure, most likely due to plasma treatment.
Which is a monstrously stupid thing to ever try — plasma could only possibly help early in the infection, when you don’t have much of the virus in your system and when the hyperinflammation syndrome has not yet kicked in, not when patients are on their death bed, yet it is usually tried out of desperation precisely when it has zero effect.
And it has only been a relatively small number of patients treated with plasma — probably in the hundreds of thousands globally.
And here we are with these new variants.
From then on it only gets worse — it appears that resistance is evolving by outcompeting the antibodies, as the antibodies bind the exact same RBD residues as the receptor. The E484K+N501Y combination has 13X higher affinity for ACE2 than the regular virus does. Higher affinity means higher contagiousness.
Not just that, but the South African variant is very clearly deadlier than the regular strains — look at the stats from the second wave there and that becomes immediately clear.
But then have been able to find other variants in the lab with much higher affinity, and those are just another mutation away, we just haven’t seen them yet in the wild. And there is probably further evolutionary space to be explored after that.
Now we are launching a massive vaccination campaign with non-sterilizing vaccines, and many countries are not even going to give the second dose in order to give the first one to as many people as possible.
This is the most monumentally stupid thing one could do in this situation — we are only going to select for even more contagious and perhaps much deadlier too variants of the virus by doing that.
The only way out of this is elimination through quarantine, mass testing and isolation.
There is no other solution.
But nobody wants to hear that.
And as a result we are in for much worse in the future….
I’m pretty sure all of the out of work entrepreneurs will busily figuring out their next venture. New restaurants will open in time. In the mean time, the remaining ones will enjoy a windfall. All of that needs to wait for the epidemic to be knocked down.
More worrisome will be the collection of zombie firms, especially Fortune 500 zombie firms that don’t go quietly into the night, and just soak up market share for a long period before, finally, Finally, going under.
the UK recorded a total of 530,841 deaths from all causes in 2019, or about 1,454 a day…on January 13th, they reported 1,564 deaths from covid alone…
Do we yet have reliable recording/reporting of cause of death, i.e. the “died WITH covid” vs “died OF covid” that some sites have argued inflates #s? I have no opinion either way, just asking experts here if the reporting has normalized enough to interpret the latter figure. I agree that dying FROM covid can legitimately (to me anyway) be interpreted as premature demise of someone with a manageable but chronic condition (including general age fragility).
i know of no such data; they seem to have enough trouble reporting new cases and deaths in a timely manner…certainly most Covid deaths involve co-morbidities or age related fragility; not many otherwise healthy people die of Covid alone..
Here’s a problem I’m having with the numbers from China and Vietnam: can you really trust their statistics, given that they are completely one-party authoritarian states and command-based economies – especially given the extremely heavy hand of China’s Great Firewall? We’re now seeing reports that China is on a massive temporary hospital loadout due to recent increases of infections.
Even if Vietnam has 100 times as many deaths as they reported, it would still be only a few thousand.
With China, even if they had a few thousand more deaths than they report, considering they have a billion people, that would still be a success.
Its not as if either country could have tens of thousands of people getting sick and dying with covid without anybody noticing. I absolutely assume both countries are having more cases than they are reporting, but compared to the catastrophes happening on other continents, they’re clearly doing a fairly tight job.
China probably had 10 to 100 times as many deaths as it reported.
That does not mean that it did not control virus and that it would not have eliminated it had it not been for the continuous reintroduction from abroad.
Pretty much all of those deaths happened during the initial outbreak.
Vietnam’s numbers are reliable, and they are indeed doing a fantastic job at keeping it out.
People are grasping at straws with this suspicion — it is not actually that hard to control the pandemic, you just need to follow the rulebook, and the rulebook has been the same for centuries.
Just because the politicians and business elites in the West turned out to be mass murdering sociopaths who sacrificed millions at the altar of corporate profits, it does not means that it is not possible to solve the problem, quite the opposite.
Picked up some breakfast today in Trump country just outside Sacramento. Indoor diners and staff, no masks. Recall Newsom volunteer getting signatures. Even liberal friends and rationale centrists are succumbing to Covid fatigue. Meanwhile I’m in month ten of intermittent shortness of breath and exercise intolerance.
How was Roseville?
We’ve had quite the push back by local residents, though most still do comply outside of a number of local establishments that openly flout the restrictions (looking at you, Oliver).
FWIW, I’ve gotten nothing but praise when I wear my P95+ bubblegum pink filtered 3M Respirator from both the maskers and anti-maskers alike (“at least that one actually does something”).
I did my weekend shopping rounds in our very blue college town. Over the past 6 months people have become quite a bit less paranoid about being in eachother’s space. Everyone is masked up but people haven’t been operating like ninjas, trying to pick out a can of tomatoes without coming in contact with anyone. This weekend was noticeably different. It seemed like almost everyone was back to their early pandemic habits. Myself included. Mentioned this to my dad and he said he had noticed the same thing when he was out. I have the luxury of doing my shopping at off hours during the week, and I’m going back to doing that.
The undergrads will be returning to campus next week and it sounds like they will basically be in lockdown. The college has offered refunds of room and board to anyone who decides not to come back to campus. Sounds like they are trying to minimize the number of returnees.
Me thinks we’re heading to endemic. The only open questions are how many die along the way, how many disabled, and the associated healthcare costs until it evolves into common cold.
Questions for the immunologists here. Why have all of the SARS-CoV-2 vaccine candidates approved to date used the entire spike protein as the antigen? It seems like all of the thought has been directed toward clever ways to deliver the antigen (Pfizer, Moderna mRNA; Novavax recombinant nanoparticles), but very little if any thought has been put toward what ought to constitute the antigen. My guess is that the entire spike protein was chosen as antigen to make the vaccines resilient to mutations; or because the designers were in a rush; or a combination of both reasons.
I ask because I bookmarked the following paper last spring, and the issues it raises have been nagging at me ever since:
The authors state that they analyzed the spike protein, and found that it has 78.4% similarity to human-like epitopes, and thus only 21.6% non-human-like epitopes. Further, they state that they selected as antigen for their vaccine candidate only the non-human-like epitopes residing in the receptor binding domain (RBD), in the furin cleavage site, and in receptor binding sites outside of the main RBD.
Their reasoning for selecting as antigen only these epitopes was that “the immune system will be guided directly to the epitopes which are relevant to virus neutralization.” And further, since their vaccine presents only non-human-like epitopes, and only epitopes relevant to SARS-CoV-2’s methods of infectivity, the risks of: 1) autoimmune reactions (local or systemic toxicity) and 2) ineffective antibody formation (and even antibody-dependent enhancement (ADE) on subsequent exposure to the virus) are reduced with their vaccine candidate, vs. the conventionally-designed vaccines, which all present the entire spike protein as antigen.
What do the immunologists and other experts here make of these issues? How great is the risk with the conventional SARS-CoV-2 vaccines, which present the entire spike protein as antigen, of autoimmune reactions, or of ineffective antibody formation (or even ADE)?
These issues are the ones that are causing me the most to take a wait-and-see attitude to the vaccines that have been released to date, more than possible allergic reactions to their ingredients. And I do have a history of strong allergic reactions to certain things, but would be willing to take the chance if I see that the risk of autoimmune reactions, or of ineffective antibody formation, with the vaccines released to date is low. I’d appreciate thoughts from the experts in the audience.
First, the Spike protein must be the most immunogenic if properly presented in the vaccine and the one with best probabilities for neutralizing antibody production. As it is in the case with real virus infection.
If selecting only non-human epitopes you might end with poorly immunogenic vaccines if these are not stable enough or presented in not good enough forms that are highly immunogenic and at the same time elicit neutralizing antibodies. This requires a lot of previous work in animal models that are scant and requires longer time for development.
It could well be that second generation vaccines are much better but these arrive when they are less necessary than today while the first generation play their role now preventing many deaths.
In the beginning, but not now, I think the so called experts thought coronavirus would be like the Spanish flu which killed two of my Great Grandparents, one in Missouri and one in Sweden. A couple of waves, the susceptible would die off and the virus would become less lethal. Except coronavirus pandemic is one big wave with dips as it spread across the USA and the world and is becoming more contagious. The fifth common cold virus that kills is close to becoming endemic in the Americas. Life Expectancy in the US has taken a one year drop due to the virus.
This could continue and get worse, adding to the unrest.
The Biden Administration is in deep trouble already, but I really don’t believe they realize it. Democrats are still shell-shocked by the storming of the Capitol. Their hands are tied behind their backs by their corporate donors yet they still want to blame and ostracize the 71 million Trump dissidents.
So far there are only mRNA vaccines with an old fashion Johnson & Johnson vaccine not yet granted an emergency exemption in the USA. There are possible long term safety concerns for the novel vaccines. Herd Immunity will be impossible if half of the population won’t get jabbed. In an insurgency in the “no go” countryside, getting vaccinated will be impossible.
In lieu of a successful vaccine program, the only fall back is doing what Vietnam is doing. But Joe Biden is against free healthcare and forming a functional national public health system. A failed government will continue to fail until American civilization collapses. The only way to fixed this is to restore true democracy.
It is going to get worse.
The experts thought no such thing, that is just what was presented to the public to avoid panic.
That this is a SARS epidemic was known from the very beginning.
That SARS causes lifelong disability was well known long before SARS-2 came — up to half (depending on the cohort) of the people who survived the first SARS epidemic in 2003 never recovered and remained disabled more than a decade later. Those “long COVID” cases that are still showing no improvement 10 months later but are presented as somehow just waiting for their recovery? Well, they will keep waiting forever, there will be no recovery for a lot of them.
That there is no lasting immunity to coronaviruses was also well known long before COVID.
Already in late January everyone who knew this was another SARS virus had put those things together and understood that if this is not eliminated, it will be catastrophic in its impacts — it would sweep through the population every couple years in huge destructive waves, and progressively cripple those people that do not die with each successive reinfection. So far it has not even been that long — Iran has already seen three major waves, South America’s huge second wave is coming only 4-6 months after the first, etc.
Which is why China has treated it like airborne plague ever since it was understood what they were dealing with.
There is also another thing that was commonly understood by experts at the beginning — vaccine development was going to be hard based on difficult past experience. This was the sole bright spot — it turned out the RNA vaccines worked really well, much, much better than anyone expected. But they are not sterilizing vaccines, which means that by using them at a population scale we will only select for resistance to them and probably for much more contagious (and perhaps lethal too) variants. Vaccines should have been reserved for healthcare workers and the rest of society should have gone for elimination of the virus.
As to why “experts” did not properly warn the public about all that, that is a long story on its own, having to with conformism, cowardice, direct and indirect control by business interests, and many other pathologies of the modern academic and research enterprise.
Many thanks Lambert for highlighting these new data points.
I don’t want to be overly alarmist, as there is certainly the possibility that these new variants aren’t as bad as they seem, for instance that they won’t affect vaccines or immunity at all. This is certainly possible – we might get lucky.
The point is that we’re not certain about that at the moment, and if SarsCov2 has taught us anything, it’s that it’s very dangerous to assume that things won’t be as bad as they seem. So the question is: do we feel lucky?
Therefore I think it’s important to interpret early cues from fresh data, and map out what the potential consequences are even if their likelihood is not 100% (or even 10%). NC has been very very good at doing this since the beginning of the pandemic, even before Covid-19 had a name (not just Covid by the way, also the financial crisis, Brexit, etc).