The nerdy amounts of pandemic detail thread

[elbows]

I havent read this yet but I will:

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

A multinational Delphi consensus to end the COVID-19 public health threat - Nature

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

www.nature.com

 

[2hats]

(Tübingen) An immunological study points to post-primary-series doses typically only buying immunocompetents a boost in circulating antibodies. Though persons dosed only on the original short-interval primary series would likely also benefit from the longer interval to boosting (6+ months) in terms of affinity/avidity/breadth, reduced risk of pathogenicity - which long interval hybrids already possess. So, for those with adequate affinity maturation, a booster likely largely only provides for some degrees of infection reduction and thus some (lesser) degrees of reduction in long covid risk. T-cell responses remained stable following the primary series (conservation of key cross-variant T-cell epitopes); suggesting efficacy to disease is likely maintained. The situation obviously can be different for the immuno-dysfunctional/compromised.

Booster vaccination led to a significant increase of anti-spike IgG responses, which showed a marked decline 6 month after complete vaccination. In contrast, T-cell responses remained stable over time following complete vaccination with no significant effect of booster vaccination on T-cell responses and cross-recognition of Omicron BA.1 and BA.2 mutations.This suggested that booster vaccination is of particular relevance for the amelioration of antibody response. Together, our work shows that different vaccination regimens induce broad and long-lasting spike-specific CD4+ and CD8+ T-cell immunity to SARS-CoV-2.

In summary, the booster vaccination led to a significant increase of anti-spike IgG responses which show a marked decline 6 month after complete vaccination. In contrast anti-spike T-cell responses remained stable over time following complete vaccination with no significant effect of booster vaccination on total intensity and frequency of T-cell responses and on cross-recognition of Omicron BA.1 and BA.2 mutations within the spike protein.

DOI:10.1126/sciimmunol.add3899.

 

[HAL9000]

Start at 24 minutes 30 seconds,

A study of viruses infecting bats, 2015 to 2019 in China, so they've not found the origin of covid 19 but they might have found a close relative, 5 to 10 years away from SARS‑CoV‑2.
The other point, there were other viruses that have the potential to jump and infect humans.

Science In Action - COVID spreads in China - BBC Sounds

COVID spreads in China

www.bbc.co.uk

Individual bat viromes reveal the co-infection, spillover and emergence risk of potential zoonotic viruses

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased...

www.biorxiv.org

Fig. 4 | The virus-sharing network of bats. (A) The virus-sharing network reveals connectivity among viromes of different bat taxa. Viruses of concern and putative cross-species transmissions are shown in different colours. Two network modules (subnets) were detected with a network betweenness-based criterion and are visualised by coloured areas. (B, C) The relationship between the number of shared viruses with phylogenetic (B) or geographic distance (C) between pairs of host individuals. Phylogenetic distance is calculated as the sum of phylogenetic tree branch length between a pair of hosts, and the tree was estimated with nucleotide sequences of the COI gene employing a maximum likelihood method. The line and blue area is the estimated partial effect and standard error of phylogenetic or geographic distance by Poisson regression.

 

[elbows]

Some parts of the UK establishment have not waited for the public inquiries before issuing technical advice for future pandemics to their successors. This came out on December 1st but I only just noticed.

I havent read it yet, I'll probably skim through it shortly but will probably resist talking about most of the details until sometime in the new year:

Technical report on the COVID-19 pandemic in the UK

A technical report for future UK Chief Medical Officers, Government Chief Scientific Advisers, National Medical Directors and public health leaders in a pandemic.

www.gov.uk

This is a technical report for our successors on some of the scientific, public health and clinical aspects of the COVID-19 pandemic in the 4 nations of the UK. This is from the UK Chief Medical Officers (CMOs), Government Chief Scientific Adviser (GCSA), UK deputy CMOs (DCMOs) most closely engaged in the COVID-19 response, NHS England National Medical Director, and the UK Health Security Agency (UKHSA) Chief Executive.

This is written for a specific audience: future CMOs, GCSAs, National Medical Directors and UK public health leaders facing a new pandemic or major epidemic in the UK and who were not part of the public health response COVID-19 pandemic. It is of necessity technical.

Ongoing public inquiries will give the definitive narrative of the COVID-19 pandemic to date, including policy decisions taken and why. This report does not cover that ground. It does however cover relevant issues on science and public health that might be useful in the future.

 

[2hats]

(HKU) A study of SARS-CoV-2 respiratory samples with different viral lineages to determine the patterns of within-host mutational diversity under different conditions, including vaccine-breakthrough infections. The highest diversity was found in unvaccinated individuals (alpha, delta and omicron samples) and the lowest in hybrid immunes.

In unvaccinated individuals, variant of Concern (VOC) Alpha, Delta, and Omicron respiratory samples were found to have higher within-host diversity.

The study results also hints at the effect of adequate maturation on curbing within-host mutational diversity:

Overall, 2-dose Comirnaty vaccination seemingly amplifies the within-host mutations in Delta virus samples, but 3-dose Comirnaty vaccination reduces the within-host mutations in Omicron samples.

This research suggests that vaccination limits the emergence of new viral variants (likely, aside from the non-immunocompetent, the unvaccinated are probably the other chief group of drivers of new variant selection pressure).
DOI:10.1038/s41467-023-37468-y.

 

[2hats]

(UCSF) A nice, indeed fairly thorough study into asymptomatic infection and HLA genetics. The authors demonstrate that T cell cross-reactivity of high-affinity public T cell receptors in HLA-B*15:01 individuals, arising from some pattern of previous exposure to OC43-CoV and/or HKU1-CoV, provides the basis for explaining some apparent pre-existing immunity and thus for some individuals in that cohort being asymptomatic on exposure to SARS-CoV-2 (recall: somewhere around 20% of cases originally appeared to be asymptomatic).
DOI: 10.1038/s41586-023-06331-x.

This study only looked at 4 epitopes (and found one, NQK-Q8, that was key, being sufficiently 'near-common' with the aforementioned 'common cold' CoV), but there are probably quite a few (maybe many) others. Perhaps if 'non-HLA-B*15:01' people can make a similar response to this epitope (as the HLA-B*15:01 do) it would make a good target (possibly could be one of several) for a universal CoV vaccine (it is well preserved as it is a key structural protein). Or, at the very least, this work provides clues as to where to look for potential targets for such a vaccine.

 

[existentialist]

(UCSF) A nice (and fairly thorough) study into asymptomatic infection and HLA genetics. The authors demonstrate that T cell cross-reactivity of high-affinity public T cell receptors in HLA-B*15:01 individuals, arising from some pattern of previous exposure to OC43-CoV and/or HKU1-CoV, provides the basis for explaining some apparent pre-existing immunity and thus for some individuals in that cohort being asymptomatic on exposure to SARS-CoV-2 (recall: somewhere around 20% of cases originally appeared to be asymptomatic).
DOI: 10.1038/s41586-023-06331-x.

This study only looked at 4 epitopes (and found one, NQK-Q8, that was key, being sufficiently 'near-common' with the aforementioned 'common cold' CoV), but there are probably quite a few (maybe many) others. Perhaps if 'non-HLA-B*15:01' people can make a similar response to this epitope (as the HLA-B*15:01 do) it would make a good target (possibly could be one of several) for a universal CoV vaccine (it is well preserved as it is a key structural protein). Or, at the very least, this work provides clues as to where to look for potential targets for such a vaccine.

As someone who either remains uninfected, or at least only had an asymptomatic infection, this stuff is interesting to me.

 

[2hats]

It's interesting. Diverse HLA polymorphism provides for an evolutionary "survival strategy" (at the population level, not the individual), whereby, at the very least, a small percentage of the population will always survive in the face of any pathogen (note: so that's a different small percentage each time - each individual will be immune to a different subset of potential pathogens, no one will be immune to all - immunity to one usually predisposes that individual to potential susceptibility to other maladies).

 

[yield]

bump

Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic
Cell. Volume 187, Issue 19p5468-5482.e11September 19, 2024

Summary
Zoonotic spillovers of viruses have occurred through the animal trade worldwide. The start of the COVID-19 pandemic was traced epidemiologically to the Huanan Seafood Wholesale Market.

Here, we analyze environmental qPCR and sequencing data collected in the Huanan market in early 2020. We demonstrate that market-linked severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic diversity is consistent with market emergence and find increased SARS-CoV-2 positivity near and within a wildlife stall.

We identify wildlife DNA in all SARS-CoV-2-positive samples from this stall, including species such as civets, bamboo rats, and raccoon dogs, previously identified as possible intermediate hosts. We also detect animal viruses that infect raccoon dogs, civets, and bamboo rats.

Combining metagenomic and phylogenetic approaches, we recover genotypes of market animals and compare them with those from farms and other markets. This analysis provides the genetic basis for a shortlist of potential intermediate hosts of SARS-CoV-2 to prioritize for serological and viral sampling.

Much too technical for me tbh. Thought elbows, 2hats or others might find it interesting

 

[elbows]

bump

Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic
Cell. Volume 187, Issue 19p5468-5482.e11September 19, 2024




Much too technical for me tbh. Thought elbows, 2hats or others might find it interesting

Thanks. I'd only heard of the study via mainstream news reporting. And the nature of that reporting means I usually end up having my mind dragged into the whole 'proof or origins' angle. And what usually happens then is that I end up trying to unpick whether 'definitive proof' is actually on display. Unable to perform that analysis on my own, I end up reliant on any remaining diversity of opinion from the expert community, and any caveats they are able to highlight that I would miss on my own.

In this case, the latter part of a BBC article helps me:

Covid origins: Genetic ghosts suggest pandemic started in market

A team of scientists say it is "beyond reasonable doubt" the Covid pandemic started with infected animals.

www.bbc.co.uk

Prof Andersen said: "To many this seems like the most likely scenario - 'the lab is right there, of course it was the lab, are you stupid?'. I totally get that argument."

However, he says there is now plenty of data that "really points to the market as the true early epicentre" and "even locations within that market".

Identifying the animals that could have been the source of the pandemic does provide clues to where scientists could look for further evidence of an animal origin.

However, because farms destroyed their animals in the early days of Covid it means there may no longer be any evidence left to find.

"In all likelihood, we missed our chance," says Prof Worobey.

Prof Alice Hughes, from the University of Hong Kong, who was not involved in the analysis, said it was a “good study”.

“[But] without swabs from the actual animals in the market, which were not collected, we cannot obtain any higher certainty."

Prof James Wood, the co-director of Cambridge Infectious Diseases, said the study provided “very strong evidence” of the pandemic starting in wildlife stalls at the market. However, he said it could not be definitive because the samples were collected after the market closed, and the pandemic probably started weeks earlier.

Even before this particular study was highlighted and framed in the usual way, I had doubts about getting to the bottom of the matter because subsequent studies dont tend to have brand new data, they have new analysis of existing data, and cannot in themselves hope to eliminate all the gaps and weaknesses in that data. And if the wrong assumptions about outbreak timing are involved, then you can easily reach the wrong conclusions. This means that I usually default into a skeptical position when headlines that attempt to sound definitive appear, and find myself more inclined to agree with those who point out any weaknesses.

But if I am content not to try to use such studies to really prove the origin, then there is still much they can offer in terms of our understanding of zoonotic risks. If we are serious about reducing the chances of another pandemic then we dont actually need to know which transmission vector happened to be involved in the last one, instead focus on improving our understanding and reducing risk across ALL the potential transmission pathways. And so I welcome any study that might help illuminate the detail of which intermediate animal hosts could be involved, and what genetic fingerprints it may be possible to discover via genomic analysis of the evolution of a particular virus.

And at least when it comes to direct animal vectors that didnt go via a lab, such studies and findings may actually proceed without ending up shrouded in secrecy, negative bias or an unwillingness to explore that direction. Unlike some of the other possibilities which are more likely to end up obscured by murk due to the 'sensitivities' involved. Those sensitivities range from government stuff of both the diplomatic and secret weapons etc research varieties, but also sensitivities that are present within some expert communities. Because some of the implications of lab lapses have implications for their own careers, their own ability to carry out the sort of lab research they would like to do in future, and indeed their own sense of being on the right side of history, always being only a force for good, their professions image etc etc. Such stuff can lead to bias, and then of course someone like me might think they were detecting that bias whenever a bunch of scientists try to tell us that a study has a conclusion that really counts as being 'beyond reasonable doubt'. Of course, I may be making mistakes of my own by having my own bias detection radar set to too sensitive a level when aimed in this direction.