Big picture, these findings are bad for EVERYBODY, but ESPECIALLY for those still clinging to the fantasy of "natural immunity."

The takeaway? It's unclear if ANYONE has strong immunity to COVID infection!

Here's a deep analysis thread, written for a general audience!

1/many Published July 26, 2024 in Nature Medicine: "SARS-CoV-2 correlates of protection from infection against variants of concern"  Abstract: "Serum neutralizing antibodies (nAbs) induced by vaccination have been linked to protection against symptomatic and severe COVID-19. However, much less is known about the efficacy of nAbs in preventing the acquisition of infection, especially in the context of natural immunity and against SARS-CoV-2 immune-escape variants. Here we conducted mediation analysis to assess serum nAbs induced by prior SARS-CoV-2 infections as potential correlates ...
The paper is fairly complex, but the takeaways are pretty straightforward, so I'll start with the highlights!

Method is robust, data collection was EXTENSIVE: It's a longitudinal study (follows the same individuals over time) with regular nasal swabs and blood draws!

2/ Figure 1: "Timing of cohort sample collections with respect to SARS-CoV-2 variants’ circulations in the two study sites. a, Timing of the blood draws with respect to the SARS-CoV-2 epidemic waves in the rural site (Agincourt) of the PHIRST-C cohort. The bar plot represents the weekly incidence (per 100,000 population) of SARS-CoV-2 cases from routine surveillance data collected from the Ehlanzeni district in the Mpumalanga province (where rural participants reside). The shaded areas represent the timing of the serum sample collections for the ten blood draws. Each curve within the shad...
Because they have blood draws from just before each wave, it's the perfect data to examine the immunity conferred by prior infections.

Because South Africa had a low vaccination rate at the beginning of Omicron, this is also great data for examining natural immunity!

3/ [Note: The 1st wave (Alpha) is referred to as D614G throughout the paper. The 4th wave (Omicron) is referred to as Omicron.]  "This high-intensity sampling scheme allowed us to reconstruct the cohort participants’ SARS-CoV-2 infection histories with high fidelity, and to monitor infection-induced antibody responses over time. Blood samples collected immediately before Delta and Omicron waves offered a unique opportunity to investigate serum immune marker levels in close proximity to the next SARS-CoV-2 exposure. Furthermore, vaccine-derived immunity remained low at the onset of the Omi...
This study is also an important contribution to the overall body of knowledge, because much of what we know of SARS-CoV-2 antibody dynamics comes from vaccine studies. In comparison, much less is known about the dynamics of serum antibodies in natural infections.

4/ "There has been substantial progress in defining serum neutralizing or binding antibodies to the spike protein as CoPs for COVID-19 vaccines, although most of these data are derived from early randomized controlled trials focused on peak immune responses shortly after vaccination and measured against symptomatic disease caused by the ancestral strain, with updated data on variants.  In comparison, less is known about serum CoPs for infection-induced immunity, and protection against acquisition of subclinical infections."
Now, there's one thing to keep in mind before we continue: This study looks at serum antibodies in unvaccinated people. We already know that the mRNA vaccines induce less-robust mucosal (airway lining) immunity, but a stronger serum (blood) antibody response,...

5/ "CoPs may differ for immunity induced by infection versus vaccination: SARS-CoV-2 infections tend to induce more robust mucosal immunity despite lower serum antibody responses than intramuscularly delivered mRNA vaccines, as shown in a mouse model26 , and mucosal immunity may play a more important role in reducing risk of infection and transmission than systemic immunity."
...which means that for all the results we see here, vaccinated people will likely have much higher serum antibodies, but less-robust mucosal immunity.

As we go, consider what this flipped pattern implies for the ability of the vaccines to PREVENT transmission/infection!

6/
As for the potential for immunity acquired via infection, the rapid evolution of SARS-CoV-2 has consistently meant that more recent variants are more transmissible, even with equivalent levels of antibodies in the blood.

Of course, the antibodies also decline over time!

7/ "Moreover, CoPs need to be interpreted in the context of viral evolution: in the pre-Omicron era, SARS-CoV-2 variants of concern emerged independently from one another, with the Alpha, Beta, Gamma, Delta and Omicron variants exhibiting distinct phenotypic characteristics. The Omicron variant stands out due to substantial genetic divergence from earlier strains and marked immune-evasion capabilities against antibody neutralization. Equivalent antibody titers may not provide equivalent levels of protection against ancestral strains compared to more transmissible and immune-evasive varian...
See, this is actually a follow-up to their previous study that DID find "immunity conferred by prior infection reduced the risk of reinfection," BEFORE the Omicron wave began.

Will this pattern of infections conferring immunity continue for Omicron?

[Spoiler: Hell no.]

8/ "We analyzed data from the multi-year PHIRST-C cohort study, covering the first four waves of SARS-CoV-2 infections including the Delta (3rd) and Omicron (4th) waves. The study included a rural and an urban site in two provinces of South Africa. Households with more than two members and where at least 75% of members consented to participate were eligible. A total of 1,200 individuals from 222 randomly selected and eligible households among the two study sites were longitudinally followed from June 2020 through April 2022. ... We previously reconstructed the detailed SARS-CoV-2 infectio...
During the Delta wave, 34% of the cohort was infected:

- 42% of those WITHOUT prior infection were infected
- 17% of those WITH prior infection were infected

This indicates that, up until that point, prior infection did confer SOME (but not full) immunity to infection.

9/ "SARS-CoV-2 infections during the Delta wave were inferred based on the anti-nucleocapsid antibody level of two pre-Delta and one post-Delta wave serum samples, as previously described31 . We focused on households with no more than six infected household members during this wave, due to computational constraints of the transmission model (Methods). Among the 797 subgroup participants, 34% (273/797) were infected during the Delta wave, with attack rates of 42% (229/544) and 17% (44/253) for naive and previously infected participants, respectively."
But even at that point, issues with the cross-neutralization were starting to show. Those infected with Beta variants had lower detectable levels of neutralizing antibodies against the Alpha variant, because the antigens mismatched!

10/ "To evaluate the potential impact of antibody waning, we also measured the peak nAb level for each participant (defined as the highest D614G nAb titer among the first five blood draws). ... Notably, 28% (32/113) and 58% (81/140) of individuals previously infected with D614G and Beta exhibited D614G nAb titers below the detection threshold at BD5, respectively (Extended Data Table 1). The proportion below the detection threshold was higher for individuals previously infected with the Beta variant than the D614G variant, given the Beta variant has eight amino acid differences in the spik...
Things changed A LOT when Omicron entered the picture.

During the Omicron wave, 67% of the cohort was infected:

- 77% of those WITHOUT prior infection were infected
- 61% of those WITH prior infection were infected

So like... what immunity?

11/ "Similarly, for the Omicron wave, we focused on a subgroup of 535 participants from 184 households who had only one prior SARS-CoV-2 infection (vaccinated and repeatedly infected individuals were excluded from the analysis) or remained naive just before the Omicron wave. Prior SARS-CoV-2 infection was ascertained in a similar fashion as for the Delta wave (that is, positivity by anti-nucleocapsid assay and/or rRT–PCR for the time period spanning the first eight blood draws). Infections during the Omicron wave were inferred based on the anti-nucleocapsid antibody level of two pre-Omicro...
Boiling it down:

- Between the Alpha and Delta waves, there was a **1.47-fold reduction** in neutralizing antibody levels due to waning.
- Between the Alpha and Omicron waves, there was a **4.01-fold reduction** "attributed to the immune-evasive properties of Omicron."

12/ "Fig. 2 | D614G and BA.1 nAb titers for the Delta wave and the Omicron wave analysis.  a, For the Delta wave subgroup, the distribution of the peak D614G nAb titer up to BD5 (light blue dots) and the D614G nAb titer at BD5 (dark blue dots), among individuals who had one prior SARS-CoV-2 infection before BD5. Each dot represents one individual, with two measurements of the same individual connected through a gray line. GMFC, geometric mean fold change from peak D614G titer to that at BD5; r, Pearson correlation coefficient.  e, For the Omicron wave subgroup, the distribution of D614G nA...
That was the actual data analysis portion of the study. They used the same data to build a model that can be used to understand how prior infection protects against reinfection! (simplified explanation in alt text)

13/ "We conducted mediation analyses in a household transmission modeling framework to investigate how nAb titers against SARS-CoV-2 variants at the onset of a SARS-CoV-2 wave mediate the risk of infection during the corresponding epidemic wave. Specifically, ... we introduced SARS-CoV-2 transmission probabilities as causal parameters, representing either the risk of acquiring infection from the general community or the per-contact transmission risk within the household. Transmission probabilities were dependent on an individual’s prior infection history, the level of preexisting nAb titer...
Prior infection reduced risk of reinfection by 61% in the Delta wave, but only by 37% in the Omicron wave.

Prior antibodies were responsible for 37% of the protective effect in the Delta wave, while they were responsible for 11% in the Omicron wave.

14/ Summary of the above excerpts:  Immunity derived from prior infection, during the Delta wave:  - Reduced the risk of contracting an infection by 61% - For every 10-fold increase in antibodies, the risk of infection decreased by 40% - Protection from the Alpha antibodies accounted for 37% of the overall protection derived from prior infection.  Immunity derived from prior infection, during the Omicron wave:  - Reduced the risk of contracting an infection by 37% - For every 10-fold increase in antibodies, the risk of infection decreased by 28% - Protection from antibodies that could actually ...
More importantly, there is a MASSIVE difference in the risk of passing on Delta or Omicron reinfections to other members of your household:

Delta: 78% less likely to pass on a reinfection than a primary infection
Omicron: No differences between primary and reinfection!

15/ Delta wave: Reinfected individuals were 78% less likely to transmit SARS-CoV-2 to others in their household compared to primary infections  Omicron wave: Reinfected individuals were (trending toward) more likely to transmit SARS-CoV-2 to others  ---  "...individuals reinfected with the Delta variant were 78% (95% CI: 24-94%) less likely to transmit the infection to other household members.... This finding suggested that even in cases where prior immunity is not sufficient to block reinfection with the Delta variant, infection-induced immunity still offered sizable mitigation against on...
Simply:
- "[When] prior immunity is not sufficient to block reinfection with the Delta variant, infection-induced immunity [reduces] transmission."
- "Omicron not only evades prior immunity's protection against acquisition of infection but also [allows] onward transmission."

16/ "a, Causal diagram of the Delta wave mediation analysis showing the hypothesized relationship between prior immunity (induced by prior SARS-CoV-2 infection) and SARS-CoV-2 infection (outcome of interest) during the Delta wave. ... The direct effect represents protection operating through immune mechanisms other than the mediators of interest. We hypothesized that the direct effect could wane over time since the initial immune exposure. ... Furthermore, cohort participants may experience heterogeneous levels of SARS-CoV-2 exposure due to different intensity SARS-CoV-2 transmission in th...
The important parts:
1. Direct protection of prior infection is reduced by half every 4 months.
2. Direct protection (not nAb) is responsible for 89% of Omicron protection.
3. In total, risk of onward transmission of Omicron is "reduced" by -17% if it's a reinfection.

17/ 1. Waning of direct effects: "Protection through the direct effect, waned over time, with waning half-life of 121 (72–242) days," which means that the effect of this pathway is reduced by half every four months. 2. How much the direct effects contribute to protection from reinfection with Omicron: "Contribute to 89% (88-91%) of the total protection" 3. "No evidence that prior immunity reduces reinfection's onward transmission risk: -17% (-110-35%)"
So while prior infections did, at one point, have a protective effect against further SARS-Cov-2 infection, that hasn't been true since the beginning of the Omicron wave. The mutations just escape the immune system too well.

18/ "Discussion  In this cohort of unvaccinated individuals, we found that nAb titers immediately before the onset of the Delta wave (that is, D614G nAb level at BD5) correlated with protection against Delta wave infections. Moreover, we demonstrated that nAb titers lost over time due to waning (that is, AnAb") were not associated with protection, aligning with the expectation that waning of nAbs in serum corresponds to waning of clinical protection. For the Omicron wave subgroup, we further investigated the impact of immune escape against protection mediated through nAbs. We found th...
There is a tiny bit a good news, however! This finding shows that, although acquired immunity seems to primarily operate at mucosal sites, the neutralizing antibodies are adequate for monitoring how well vaccines match the variants in circulation.

19/ "The identification of variant-neutralizing antibodies derived from infection induced immunity as CoPs against infections for both Delta and Omicron variants aligns with findings from studies on variant-specific correlates for vaccineinduced or hybrid immunity. Considering that antibody-mediated protection against acquisition of infection likely operates at the mucosal site rather than in serum, it is interesting that serum antibody levels can anticipate protection. In a recent analysis of the data from the COVE trial, Zhang et. al. further demonstrated that boosting of nAb titers agai...
When it comes down to it, Omicron is a tricky little shit. Prior infection with Omicron seems to *barely* prevent reinfection with other variants of Omicron, which means you can theoretically get it over and over and over and over and over.

And if you recall,...

20/ "In comparison, nAbs mediate about two-thirds of the mRNA-1273 vaccine efficacy. For the Omicron wave subgroup, Omicron BA.1 nAbs are estimated to mediate only 11% of protection, which was substantially lower than that observed for the Delta wave and vaccine-induced immunity. This low percentage of protection mediated by nAbs for the Omicron wave could be attributed to the highly immune-evasive nature of Omicron against neutralizing activity. Omicron effectively rendered a substantial proportion of serum D614G nAbs nonfunctional against Omicron. The large proportion of overall protecti...
The vaccines induce a much stronger serum neutralizing antibody response than they do a mucosal immune response. So not only has nobody ever actually said that the vaccines can *prevent infection*, but it's looking like in the Omicron era, they can't!

21/
You should still get updated vaccinations! Serum antibodies do have SOME effect, and the vaccines definitely do seem to have an impact in preventing severe COVID. Additionally, Novavax may induce a more broadly neutralizing antibody response than the mRNA vaccines!

22/
But it also means that we can't rely on our immune systems to stop the spread of COVID. The Omicron variants are just too immune-evasive for that anymore. Until we have next gen vaccines, we need other tools to prevent the transmission of Omicron!

23/
You know what the virus CAN'T evade? Electrostatically charged fibers.

An N95 respirator is engineered to filter airborne particulate. SARS-CoV-2 is airborne particulate.

Wear a respirator to protect yourself and others. It's really THAT simple.

24/
It's a solid paper, and IMO it shows how we can't vaccinate (or "hybrid immunity") our way out of a problem that has SPECIFICLLY adapted to evade our immune systems! WHY ISN'T THAT OBVIOUS!?

Source:

My annotated copy:

25/25nature.com/articles/s4159…
dropbox.com/scl/fi/g1ffj3f…
The answer is *conceptually* very simple, but difficult to do in the real world! We need next-gen vaccines which:

1. Elicit robust mucosal immunity
2. Targets antigens OTHER than the S protein

The spike is easy to target, but CHANGES more easily!

26/25
Additionally, things like soluble ACE2 receptors may complement vaccines:

For example, if a nasal spray containing soluble ACE2 receptors could bind to the virus before it ever touches a cell, it could have significant prophylactic effect!

27/25 sciencedirect.com/science/articl…

From Antiviral Research, Volume 227, July 2024: "SARS-CoV-2 evolution has increased resistance to monoclonal antibodies and first-generation COVID-19 vaccines: Is there a future therapeutic role for soluble ACE2 receptors for COVID-19?"  doi: 10.1016/j.antiviral.2024.105894
Article Highlights  • After intense study the correlates of protective immunity to SARS-CoV-2 are now better understood.  • Although several COVID-19 vaccines have received full authorization for use, they do not prevent breakthrough infection although disease severity is mitigated in fully-immunized individuals.  • There is a dearth effective antiviral therapeutics for SARS-CoV-2: Repurposing existing drugs for COVID-19 has been disappointing. While effective, Paxlovid is beyond the reach of most low- and middle-income countries.  • A recent in vitro study showed that the ancestral Wuhan a...
Vaccines elicit an immune response that is meant to target a very specific antigen protein, but lots of little changes can make the antigen presentation change—even if the receptor is uses stays the same!

Soluble ACE receptors would be, essentially, decoys!

28/25
Definitely not a dumb question! I only ever imply it, but YES, we are still in the Omicron era!

All of the BA*, BQ*, XBB*, EG*, HK*, and JN* variants are Omicron.

Oddly enough, the BA.2 family actually seems to be making a comeback this year!

29/25

Omicron was the majority of circulating SARS-CoV-2 variants beginning around December 2021.  Oddly enough, the dominant clade from early 2022 (BA.2) is making a comeback this year, and currently accounts for 19% of variants in circulation.  All of the BA*, BQ*, XBB*, EG*, HK*, and JN* variants belong to the Omicron lineage.
Well, this is fucking hilarious!

Someone quoted this to say I don't know what I'm talking about because... I apparently think intramuscular vaccination prevents transmission?... in a thread where I point out that it absolutely doesn't

Try reading for once in your life!

30/25 A coder and writer that doesn't understand basic anatomy nor mucosal immunity.  Why masks don't work: [some made-up nonsense that misses the point]  Why intramuscular injections don't work: [a point made in this very thread about mucosal immunity]

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More from @NickAnderegg

Feb 1
Many people are asking for recommendations about what storage media to buy, so here's a buying guide from an experienced data hoarder (me)

The MOST IMPORTANT thing to know is that SOLID-STATE MEDIA IS NOT DURABLE. Flash drives, SSDs, SD cards, etc. are NOT long-term storage.

1/
That's not to say that it's impossible to use solid-state media for long-term storage. It's just that anything with durability guarantees gets prohibitively expensive quickly. Spinning hard drives—as well as DVDs and Blu-ray discs!—are your friend.

2/
- The way data is stored in solid-state media makes it much more susceptible to bit rot than other media.
- In a spinning hard drive, the moving parts are the most common point of failure.
- When you burn a DVD, that shit is fairly permanent.

3/
Read 42 tweets
Jan 9
I wish people would understand that insurance underwriters have armies of actuaries calculating risks, and if an insurance company drops you, it's because things have changed in such a way that insuring you will take more out of the financial pool than you're putting in

1/
It sucks, but it's a direct result of the fact that humans are widely inhabiting locations that are rapidly becoming impossible to inhabit safely. If you can't find insurance for your home, it means there's a high likelihood you'll need to move soon anyway.

2/
You get insurance so that you can replace all of your stuff in the event of a disaster. When the insurance company effectively says "the risk of disaster is so high that insuring you would almost certainly cause us to lose a lot of money," it ALSO means your life is in danger

3/
Read 7 tweets
Jan 5
So here’s the thing about some of the subtle neuro damage related to SARS-CoV-2 infection that I think a lot of people miss: some of the known deficits are correlated with things like impulsiveness and poor emotional control, so we might expect to see deficits there are well

1/
Consider how impatient people seem to be on the road in the last couple years relative to the 2010s, and I think we have a perfect example of where this is LIKELY already manifesting.

2/
This impact is particularly insidious for the person experiencing it, because poor impulse control, by definition, doesn’t really come on gradually. My biggest concern is how interactions under these circumstances will play out if this impact continues to become more common

3/
Read 15 tweets
Jan 3
Let's review some major points in the Nukit controversy, since some people are unclear:

- Someone criticized someone's use of Nukit lanterns.
- Nukit attacked the critic because, as noted, this is how they market
- Nukit now demands "mediation" with the community (how??)

1/ @marigoldglitter: "these tools should be used for people who must be in public despite the dangers, not for white men who want to eat in restaurants and maintain the status quo. if this is what you're gonna use these for, give them to a disabled person who can't go to the doctor b/c of risk."  Nukit: ""White man" in this case is buying those products from non-white small businesses who are focused on providing the community with effective, tested mitigations at far, far lower costs than anyone else."  OP: "Like why are you coming at me with this aggressive...
Nukit: "If you are in the US, and would like to purchase Far-UVC products, we cannot help you at this time. We tried to resolve the issues there, but the US COVID-Aware community was uninterested in mediation or intercession. As a result of that disinterest, a great deal of harm was done. When stock is finished, we will not be selling our products to the Us anymore. If you are in the US and want Nukit products, would like 333 million Americans, many disabled or immune compromised, to be able to access the most affordable Far-UVC on the market, kindly address the people who made it unsa...
So let's look at this a bit more critically. Here is the "evidence" Nukit provided that the didn't say anything racist. First of all, these aren't the comments in question, but it's worth a look anyway.

2/ Ok, I get that "evidence," "citations," and "personal accountability" are going to be called racist, but since people insist on just spewing lie after lie without any pushback- here's what actually happened. @marigoldglitter- a white woman attacked a Nukit customer who was supporting us by showing our products. This is something we rely on to fund research and donations. If our customers do not do this, that money goes to paid advertising. So yes, attacking our customers is attacking our company and directly harming marginalized folks who receive our products. ...
Seems to be framed this way because Nukit knows it's not an adequate explanation, so they're acting like anyone who criticizes them is in the wrong.  ---  A bigoted comment is a bigoted comment, even if it's not directed at someone who might be personally offended. Of course, Nukit didn't include the comments people actually call racist!  ---  Nukit is explicitly saying here that they view any criticism as an "attack," because criticisms can potentially hurt their business goals. Fundamentally, Nukit is angry that this usage of their products are being criticized.  ---  After Nuki...
Let's be clear about what happened here: Someone lamented the unequal access to protective measures and criticized someone who seems to be using a certain device to *maintain the status quo*, and the manufacturer of the device found it unacceptable.

3/
Read 16 tweets
Oct 9, 2024
NEW STUDY! This exploratory study identifies a SPECIFIC PHENOTYPE OF LONG COVID that appears related to NEUROMUSCULAR DISTURBANCE rather than lung damage—and they've termed it Complex Ventilatory Dysfunction!

Breakdown of the paper (thread written for a general audience!)...

1/ Published Oct 7, 2024: "A new phenotype of patients with post-COVID-19 condition is characterised by a pattern of complex ventilatory dysfunction, neuromuscular disturbance and fatigue symptoms"  Abstract:  Background Patients with post-COVID-19 condition frequently suffer from chronic dyspnoea. The causes and mechanism for dyspnoea in these patients without evidence of structural lung disease are unclear.  ...  Results ... A pattern of reduced forced vital capacity (FVC), but normal total lung capacity (TLC), termed complex ventilatory dysfunction ... was observed and occurred mo...
Broadly speaking, there are two groups of acute covid outcomes involving dyspnea (shortness of breath) as a long-term symptom:

- Severe cases that may have physical lung damage
- "Mild" cases that now have ME/CFS-like features, but who have no evidence of lung damage!

2/ "Current evidence suggests that cellular damage, a robust innate immune response with inflammatory cytokine production and a procoagulant state induced by SARS-CoV-2 infection are factors potentially contributing to post-COVID-19 sequelae such as dyspnoea, fatigue, and cognitive and mental disturbances... Dyspnoea has been well characterised as a major clinical symptom of post-COVID condition after severe and critical COVID-19 and is correlated with impaired lung function in terms of pulmonary restriction, and with reduced diffusion capacity as a possible consequence of pulmonary remod...
In this study, they explored this distinction further and identified a distinct subset of patients with a pattern of breathing abnormality that they have termed complex ventilatory dysfunction (CVD).

So how did they arrive at this conclusion? Let's dig in!

3/16 "We hypothesise that patients suffering from post-COVID-19 condition who have fatigue and exertional intolerance also have a reduction in respiratory muscle strength, causing a dysfunctional breathing pattern which is distinct from typical pulmonary sequelae after COVID-19 such as obstruction, restriction or impaired diffusion capacity. Based on clinical observations, we describe a new breathing abnormality termed complex ventilatory dysfunction (CVD), defined as total lung capacity (TLC) - forced vital capacity (FVC) >10% predicted value and absence of restriction (TLC ≥ lower limit o...
Read 16 tweets
Sep 22, 2024
NEW STUDY! It VERY thoroughly supports the hypothesis that SARS-CoV-2 emerged as a zoonotic spillover event in the Huanan Seafood Wholesale Market—using multiple methods!

Breakdown of the paper (written for a general audience!)...

1/many (but it's worth it, I promise!) Published Sep 19, 2024 in Cell: "Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic"  Highlights: - Common ancestor of SARS-CoV-2 linked to Huanan market matches the global common ancestor - Wildlife mitochondrial DNA identified in samples from stalls positive for SARS-CoV-2  Abstract:  "... 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...
This paper reanalyzes the same data from the April 2023 paper in Nature that cast doubt on the Huanan Market hypothesis (pictured).

In the new paper published in Cell this week, another group conducted far more detailed (and statistically sound) analyses!

2/
Original paper that analyzed this same data: "Surveillance ofSARS-CoV-2 at the Huanan Seafood Market"  "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, emerged in December 2019. Its origins remain uncertain. It has been reported that a number of the early human cases of coronavirus disease 2019 had a history of contact with the Huanan Seafood Market...."
"...It should be noted that the selection of shops for sampling was biased because shops selling wildlife as well as shops linked to early cases were prioritized for sampling. The origin of the virus cannot be determined from the analyses available so far. Although gene barcode analysis of animal species in the study suggested that Myotis, Nyctereutes and Melogale-species that have been recognized as potential host species of sarbecoviruses-were present at the market, these barcodes were mostly detected within the SARS-CoV-2 RT-qPCR-negative samples from the environment. It remains pos...
This new paper starts by reviewing the evidence supporting the Huanan Market hypothesis, and some of the details are FASCINATING!

To begin with, of the 174 COVID cases identified with an onset of December 2019, 32% had a link to the Huanan Market.

In a city of 12 million.

3/ "INTRODUCTION Many of the earliest known cases of COVID-19 worked at or visited the Huanan Seafood Wholesale Market ("Huanan market") in the city of Wuhan, a link first made by clinicians at different hospitals throughout the city. Retrospective review of early COVID-19 cases identified 174 patients with onset in December 2019, 32% of whom had an ascertained link to this location, within a city of over 12 million."
Read 24 tweets

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