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Member since: Sun Feb 14, 2016, 07:36 PM
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Substantial Differences in SARS-CoV-2 Ab Responses Elicited by Natural Infection and mRNA Vaccine

This is really, really good news. It was difficult choosing only a few paragraphs to quote, so I encourage you to follow the link to read more, if only the "Discussion" section.

What it says, though, is that mRNA vaccine immunity appears to be superior to natural immunity--for various reasons they describe (some included below).

https://www.biorxiv.org/content/10.1101/2021.04.15.440089v1.full.pdf+html

In this study, we compared antibody responses induced by SARS-CoV-2 natural exposure with the responses induced by the mRNA vaccines.

(snip)

mRNA vaccines induce higher Ab levels and greater Ab breadth than natural exposure to infection and differences were particularly notable against the RBD domain. ... (snip) ...The virus uses the spike RBD domain that binds to the ACE2 receptor on respiratory cells to enter and infect them. Vaccinated individuals had significantly elevated Ab levels against RBD domain segments, supporting the protective immunity induced by this vaccine as previously published. To account for this difference between natural exposure and the vaccine, the virus may have evolved to conceal the RBD epitope to evade immune recognition. The mRNA vaccine produces a protein conformation that better exposes the RBD epitope to the immune system.

In addition to inducing increased Ab levels again SARS-CoV-2 RBD, the mRNA vaccine induced cross-reactive responses against SARS spike and SARS RBD. Conversely, natural exposure did not induce a cross-reactive response against the SARS spike and SARS RBD. The weak anti-RBD response induced by natural exposure may provide a mechanism for new variants to enter the population. This result can be interpreted based on immune selection pressure. Importantly, the mRNA vaccine induces a marked cross-reactive response against SARS spike, indicating that the mRNA vaccine adopts a conformation that presents cross-reactive epitopes to the immune system. This effect of the mRNA vaccine to induce cross-reactivity against diverse CoV strains is encouraging, providing further evidence that it may be effective against emerging virus variants.

(snip)

These results may also have relevance for both the dose response hypothesis and with regard to herd immunity. Several authors have suggested that disease outcomes may be related to the dose inoculum, with individuals being exposed to inocula with higher virus loads potentially having more severe disease outcomes. [9] While the currently used vaccines in this setting do not rely on viral materials, they do offer a glimpse into controlled high level exposure to proteins that are specific to SARS-CoV-2. Our results show that individuals who have been vaccinated mount higher across-the-board antibody responses than those who have been exposed to variable viral inocula (i.e. through natural exposure). Second, the variable antibody responses among the pre-vaccine population may also indicate that immune responses to natural infections are not as strong as those among individuals who have been vaccinated. This could also indicate that immunity from naturally acquired infections is not as strong as that acquired from vaccination, with potential relevance for reaching and maintaining herd immunity. We should not assume that previously infected individuals are immune or that they cannot transmit the virus.


ETA: adding the standard disclaimer for all pre-print articles posted on bioRxiv
bioRxiv is receiving many new papers on coronavirus SARS-CoV-2. A reminder: these are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information.

Nature: Engineered bat virus stirs debate over risky research

Engineered bat virus stirs debate over risky research

Lab-made coronavirus related to SARS can infect human cells.

https://www.nature.com/news/engineered-bat-virus-stirs-debate-over-risky-research-%201.18787

An experiment that created a hybrid version of a bat coronavirus — one related to the virus that causes SARS (severe acute respiratory syndrome) — has triggered renewed debate over whether engineering lab variants of viruses with possible pandemic potential is worth the risks.

In an article published in Nature Medicine1 on 9 November, scientists investigated a virus called SHC014, which is found in horseshoe bats in China. The researchers created a chimaeric virus, made up of a surface protein of SHC014 and the backbone of a SARS virus that had been adapted to grow in mice and to mimic human disease. The chimaera infected human airway cells — proving that the surface protein of SHC014 has the necessary structure to bind to a key receptor on the cells and to infect them. It also caused disease in mice, but did not kill them.

Although almost all coronaviruses isolated from bats have not been able to bind to the key human receptor, SHC014 is not the first that can do so. In 2013, researchers reported this ability for the first time in a different coronavirus isolated from the same bat population2.

The whole article is worth reading at the link, but this is the paragraph I'd like to discuss:

Studies testing hybrid viruses in human cell culture and animal models are limited in what they can say about the threat posed by a wild virus, Daszak agrees. But he argues that they can help indicate which pathogens should be prioritized for further research attention.

The general topic is gain-of-function (GOF) research, which is controversial, and about which I, personally, remain ambivalent.

But this article highlights and clearly illustrates what one viewpoint postulates: that GOF research is mostly academic (while being highly risky).

The proof is that the paper being referenced (A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence https://www.nature.com/articles/nm.3985) is a study of a group of viruses collected at the same time, and from the same location as the virus RaTG13, which is the bat coronavirus that, to date, is the closest known relative to SARS-CoV-2, causative agent of Covid-19.

To be clear: RaTG13 was (at least partially in 2016; fully by 2018) sequenced at the same time, so was known about and published (in 2016, as sample "4991" in Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft https://link.springer.com/article/10.1007/s12250-016-3713-9 ).

If it sounds like a detective case where the serial killer is apprehended by police, taken in for questioning, and is then released (:cough:Ted Bundy:cough: ), it's because it is the scientific equivalent.

After the current pandemic outbreak, when queried about why RaTG13 did not undergo further analysis and experimentation, the researchers said that RaTG13 (basically, paraphrasing) "wasn't interesting enough." Here's what that paper says about RaTG13 aka RaBtCoV/4991:

Only two sequences detected in this study were homologous to betacoronaviruses. One of them (RaBtCoV/4991) was detected in a R. affinis sample and was related to SL-CoV. The conserved 440-bp RdRp fragment of RaBt-CoV/4991 had 89% nt identity and 95% aa identity with SL-CoV Rs672 (Yuan et al., 2010). In the phylogenetic tree, RaBtCoV/4991 showed more divergence from human SARS-CoV than other bat SL-CoVs and could be considered as a new strain of this virus lineage (Figure 2).

RaTG13 was in the sights, the crosshairs, but then shelved as being "not interesting enough." That they characterized it as a potential "new strain" and also failed to pursue studying it, strikes me as odd.

Yes, hindsight is 20/20. But the whole point of GOF research is the be able to predict and prepare for that unforeseen future pandemic. If it fails--and let's be honest, short of them having had the actual SARS-CoV-2 virus in their sampling population, this was damned close!--then we must question the value of such research vis a vis risk vs. reward.

Of course, another view could be that this research failed to predict this pandemic because there wasn't enough being invested in GOF work. I suspect that will be the prevailing conclusion, and that tons more money will be spent expanding that focus, with hundreds more BSL3/4 labs being built worldwide.

Are we prepared for that?

BTW, the article in the title of this OP is from 2015.

No, I am not certain of that at all

In fact, I am fairly confident that the virus has a natural evolution and that transmission was zoonotic.

But what intrigues me is the cover-up. When someone goes to great lengths to obscure something, there's a reason.

When I received my scientific training, one of the most valuable tips I learned was to design experiments as though you were trying to *disprove* your favored hypothesis. To approach your studies as a contrarian--because your peer reviewers will most certainly be doing so. It's the best way to try to ensure a balanced perspective, to fight against our natural inclination towards confirmation bias.

So that partly explains my approach to this. The other part, as I described above, is my observation of odd behaviors on the part of the CCP regarding this question on origins. That set off major alarms for me.

In terms of the Nature citation issue: nobody will ever convince me that it was trivial. Even for a "rushed" paper. Especially because of the surrounding circumstances: it was Shi's own prior work that deserved the cite. One thing I can absolutely guarantee you: no scientist, especially when writing a paper for Nature, omits an opportunity to cite their own published work. Go ahead and ask any/every scientist you know if that is a fair statement. Not to mention that the piece of data in question (RaTG13 sequence) was the central, pivotal piece of data proving the paper's thesis: that the newly discovered infectious agent was a bat coronavirus. Why not mention that you know this because your lab collected that specimin back in 2013 inside of a mineshaft where, just months prior, six workers contracted a mysterious respiratory disease--that would kill three of them--and that you partially sequenced that specimin and published about it in 2016? I mean, that is the normal way for a scientist to report a finding.

Below is the Addendum, published a full nine months later. See for yourself. There's nothing relevent in there that wasn't known in Feb 2020, and the critical citation I'm so concerned with is right there, too--Ge et al (2016). Why the nine month delay? Aren't you even a little bit curious?

Published: 17 November 2020

Addendum: A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou, Xing-Lou Yang, […]Zheng-Li Shi
Nature volume 588, pageE6(2020)

Here we provide further information about the bat SARS-related coronavirus (SARSr-CoV) strain RaTG13 reported in our Article. Between 1 July and 1 October 2012, we received 13 serum samples collected from 4 patients (one of whom was deceased) who showed severe respiratory disease. These patients had visited a mine cave in Tongguan town, Mojiang County, Yunnan Province, China, to clean bat faeces in order to mine copper before being admitted to the First Affiliated Hospital of Kunming Medical University on 26–27 April 2012. The samples we received were collected by the hospital staff in June, July, August and September 2012. To investigate the cause of the respiratory disease, we tested the samples using PCR methods developed in our laboratory targeting the RNA-dependent RNA polymerases (RdRp) of Ebola virus, Nipah virus and bat SARSr-CoV Rp3, and all of the samples were negative for the presence of these viruses. We also tested the serum samples for the presence of antibodies against the nucleocapsid proteins of these three viruses, and none of the samples gave a positive result. Recently, we retested the samples with our validated enzyme-linked immunosorbent assay (ELISA) against the SARS coronavirus 2 (SARS-CoV-2) nucleocapsid protein—which has greater than 90% amino acid sequence identity with bat SARSr-CoV Rp3—and confirmed that these patients were not infected by SARS-CoV-2.

We suspected that the patients had been infected by an unknown virus. Therefore, we and other groups sampled animals including bats, rats and musk shrews in or around the cave, and found some alphacoronaviruses1 and paramyxoviruses2. Between 2012 and 2015, our group sampled bats once or twice a year in this cave and collected a total of 1,322 samples. From these samples, we detected 293 highly diverse coronaviruses, of which 284 were designated alphacoronaviruses and 9 were designated betacoronaviruses on the basis of partial RdRp sequences. All of the nine betacoronaviruses are SARSr-CoVs, one of which (sample ID4991; renamed RaTG13 in our Article to reflect the bat species, the location and the sampling year) was described in a 2016 publication1. The partial RdRp sequence (370 bp) of ID4991 was deposited in GenBank in 2016 under accession number KP876546. All of the identified bat SARSr-CoVs are distantly related to SARS-CoV based on partial RdRp sequences. In 2018, as the next-generation sequencing technology and capability in our laboratory had improved, we performed further sequencing of these bat viruses and obtained almost the full-length genome sequence (without the 5′ and 3′ ends) of RaTG13. In 2020, we compared the sequence of SARS-CoV-2 with our unpublished bat coronavirus sequences and found that it shared a 96.2% identity with RaTG13.

References
1.
Ge, X. Y. et al. Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft. Virol. Sin. 31, 31–40 (2016).

Cnet: How the coronavirus origin story is being rewritten by a guerrilla Twitter group

This isn't going away. Please read the full article.

https://www.cnet.com/google-amp/news/how-the-coronavirus-origin-story-is-being-rewritten-by-a-guerrilla-twitter-group/

After a lot of trial and error, the Seeker stumbled upon exactly what he was looking for: a master's thesis written by a Chinese doctor. The document contained an account of six cases of "severe pneumonia caused by unknown viruses" in workers who had been cleaning an abandoned copper mine in Yunnan, China, in 2012. The patients' symptoms seemed eerily similar to those of COVID-19. Three of the patients, it said, died from the mystery illness.

The Yunnan mine and its resident bats, the Seeker knew, had been sampled by researchers at the Wuhan Institute of Virology. He'd uncovered a missing puzzle piece: an association between the closest known relative of the coronavirus and research conducted at the institute in Wuhan, China.

(snip)

Part of the problem is that the origins story has become entangled in geopolitics and conspiracy. Bad actors have seized upon the lab leak theory for political gain, sometimes attempting to shift the blame for catastrophic failures in managing the pandemic. Instead of remaining a scientific debate, the origin story morphed into a political one. For instance, in March 2020, US President Donald Trump and Secretary of State Mike Pompeo began propagating the idea that SARS-CoV-2 may have leaked from a Wuhan lab. The lab leak became intertwined with Trump, foreign policy and the right. Deigin says Trump weighing in "poisoned" the discussion.

How the Chinese Govt Fabricates Social Media Posts for Strategic Distraction, not Engaged Argument

https://gking.harvard.edu/50C

Gary King, Jennifer Pan, and Margaret E. Roberts. 2017. “How the Chinese Government Fabricates Social Media Posts for Strategic Distraction, not Engaged Argument.” American Political Science Review, 111, 3, Pp. 484-501.

The Chinese government has long been suspected of hiring as many as 2,000,000 people to surreptitiously insert huge numbers of pseudonymous and other deceptive writings into the stream of real social media posts, as if they were the genuine opinions of ordinary people. Many academics, and most journalists and activists, claim that these so-called ``50c party'' posts vociferously argue for the government's side in political and policy debates. As we show, this is also true of the vast majority of posts openly accused on social media of being 50c. Yet, almost no systematic empirical evidence exists for this claim, or, more importantly, for the Chinese regime's strategic objective in pursuing this activity. In the first large scale empirical analysis of this operation, we show how to identify the secretive authors of these posts, the posts written by them, and their content. We estimate that the government fabricates and posts about 448 million social media comments a year. In contrast to prior claims, we show that the Chinese regime's strategy is to avoid arguing with skeptics of the party and the government, and to not even discuss controversial issues. We show that the goal of this massive secretive operation is instead to distract the public and change the subject, as most of the these posts involve cheerleading for China, the revolutionary history of the Communist Party, or other symbols of the regime. We discuss how these results fit with what is known about the Chinese censorship program, and suggest how they may change our broader theoretical understanding of ``common knowledge'' and information control in authoritarian regimes.

The Covid dissidents taking on China

https://unherd.com/2021/04/the-covid-dissidents-taking-on-china/

Feng Zijian played a central role in the World Health Organisation’s inquiry into the origins of Covid-19. The Chinese epidemiologist was one of the team leaders who briefed diplomats on the findings, which fell suspiciously in line with Beijing’s version of events. Feng explained how the carefully vetted team had concluded that the virus was most likely to be a natural disease that spilled over from bats to humans, although it could have been imported on frozen food. The chance of a leak from a Chinese laboratory was dismissed as “extremely unlikely”.

The Chinese-controlled results sparked global accusations of a whitewash and further corroded confidence in the WHO. Few experts give much credibility to claims the pandemic was imported on a packet of chilled pork or slab of frozen pangolin sold at a market. And demands are growing for the leak hypothesis to be taken more seriously. Wuhan, after all, is the major research centre for bat coronaviruses in Asia, where there are secretive labs, known biosafety concerns and high-risk experiments being conducted.

It has now emerged that Feng, deputy head of China’s Centre for Disease Control and Prevention (CDC) and an expert on emergency health responses, performed an even more sinister role as the pandemic played out. He was one of four names copied on a CDC memo sent out in February 2020 ordering China’s scientists not to share any data, documents or specimens relating to the epidemic and to “prioritise the interests of the country”. The memo warned that anyone violating the request would be “dealt with severely in accordance with discipline, laws and regulations” — a threat to be taken seriously in a country ruled by fear.

Much, much more at link above.

Trevor Bedford thread about Covid variants (Tw)

My question: what is the significance of the quiescent 10 months? Is that typical?

https://twitter.com/trvrb/status/1349774271095062528

FBI #107-AFO: Do you know this guy? (Tw)

https://twitter.com/SeditionHunters/status/1382081731835129857

Meet the Censored: The U.S. Right to Know

This story is about how, after a Google algorithm update, the website of U.S. Right to Know (USRTK) experienced a 60% drop in traffic--for no discernable reason--and how they were left scrambling to try to guess the reason. Was it due to the controversial nature of their content? Or was it just typical search engine optimization (SEO) issues?

https://taibbi.substack.com/p/meet-the-censored-the-us-right-to?r=ep9dv&utm_campaign=post&utm_medium=web&utm_source=copy

USRTK, whose reporting is mostly based on public document searches, is an organization that inspires strong opinions. They inhabit a corner of the media universe focusing on who pays for what kind of research, and to what result, around topics like food additives and Genetically Modified Organisms. The material can get very personal, and thanks to headlines like “The misleading and deceitful ways of Dr. Kevin Folta,” they’re not generally in the friend-making business.

Moreover, agencies like USRTK are particularly vulnerable in the age of algorithmic moderation, as computers don’t easily distinguish between conspiracy theory and legitimate reporting that runs counter to present accepted narratives. Any organization that swims in those waters and isn’t attached to a big name now has to keep looking over its shoulder. If such an organization does end up suspended, deleted, or de-ranked, as USRTK later would be, it has to wonder: was it something we wrote?

(snip)

U.S. Right to Know is basically ad-free. It doesn’t aggregate, but instead publishes original reporting based mainly on public documents. It’s the opposite of a click-chasing SEO-oriented site that is “attempting to guess what might rank well.” It doesn’t have shocking or sensational headlines — in fact, it barely had an engagement strategy. Its work is referenced by peer-reviewed medical journals and established outlets like the New York Times.

More at link above.

Nature: SARS-CoV-2 evolution during treatment of chronic infection

Well this is a cautionary tale, if not completely expected. Variants/mutants have a selective advantage while under pressure from treatment with convalescent plasma.

Published: 05 February 2021
SARS-CoV-2 evolution during treatment of chronic infection

Abstract
The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for virus infection through the engagement of the human ACE2 protein1 and is a major antibody target. Here we show that chronic infection with SARS-CoV-2 leads to viral evolution and reduced sensitivity to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequencing. There was little change in the overall structure of the viral population after two courses of remdesivir during the first 57 days. However, after convalescent plasma therapy, we observed large, dynamic shifts in the viral population, with the emergence of a dominant viral strain that contained a substitution (D796H) in the S2 subunit and a deletion (ΔH69/ΔV70) in the S1 N-terminal domain of the spike protein. As passively transferred serum antibodies diminished, viruses with the escape genotype were reduced in frequency, before returning during a final, unsuccessful course of convalescent plasma treatment. In vitro, the spike double mutant bearing both ΔH69/ΔV70 and D796H conferred modestly decreased sensitivity to convalescent plasma, while maintaining infectivity levels that were similar to the wild-type virus.The spike substitution mutant D796H appeared to be the main contributor to the decreased susceptibility to neutralizing antibodies, but this mutation resulted in an infectivity defect. The spike deletion mutant ΔH69/ΔV70 had a twofold higher level of infectivity than wild-type SARS-CoV-2, possibly compensating for the reduced infectivity of the D796H mutation. These data reveal strong selection on SARS-CoV-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals.
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