The Playground

I wonder if good old Rossi can think of a solution-break up the NUCLEAR WEAPONS to fuel his E-CATS!

Dr Richard* perhaps not

Circular Reasoning: Severely Disabled Man Vaccinated Over Parents Wishes So he Can Participate in Outdoor Activities

Circular Reasoning: Severely Disabled Man Vaccinated Over Parents Wishes So he Can Participate in Outdoor Activities

A February 4 report from the British Medical Journal has raised disturbing questions about the ethics of the COVID-19 regime in the UK, a Western

trialsitenews.com

A February 4 report from the British Medical Journal has raised disturbing questions about the ethics of the COVID-19 regime in the UK, a Western Democracy. In the case of a young man who lacks the capacity to make health decisions, a court ruled he “must be vaccinated against SARS-CoV-2, despite his parents’ fears that the vaccine could seriously harm or even kill him.” Known legally as “DC,” the 20-year-old man lives in a care home in England at which he is the sole unvaccinated resident. DC has “schizencephaly, microcephaly, cerebral palsy, curvature of the spine, dystonia, intermittent stridor, and pseudomonas of the lungs.” DC weighs as much as a small child and generally needs to be hospitalized several times a year for lung illness.

Judge Simon Burrows noted that DC’s “highly intelligent” parents, who don’t, in general, oppose vaccines, had a logical and rational basis for their objection to COVID-19 vaccination. The young man’s dad is a professional risk evaluator, and he did a massive amount of research on mRNA vaccines. He is particularly concerned about a history of blood clots in the family. Yet Borrows said that the risks of the vaccination did not outweigh the benefits. And the main “benefit” cited is not even a medical benefit: the court’s main justification for this action was that it would be a positive in DC’s life, as unvaccinated, “he was not allowed to attend outdoor events and had to be isolated in his room for 10 days after home visits.”

TrialSite suggests that such judiciary moves, encroaching on the lives of individual families and their preferences, represent an overreach of the British judiciary. Political fallout is expected.

Study finds previous COVID-19 infection, but not vaccination, improves performance of antibodies

Study finds previous COVID-19 infection, but not vaccination, improves performance of antibodies

New research to be presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022, Lisbon, 23-26 April) shows that,…

medicalxpress.com

New research to be presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022, Lisbon, 23-26 April) shows that, although over time the number of SARS-CoV-2 antibodies falls in both previously infected and vaccinated patients, the performance of antibodies improves only after previous infection (and not vaccination). This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated.

The study, by Dr. Carmit Cohen of the Sheba Medical Center, Ramat Gan, Israel, and colleagues, also found that, contrary to expectations, previously infected patients with obesity had a higher and more sustained immune response than overweight and normal weight range patients.

While protection against re-infection lasts for a long time in SARS-CoV-2 recovered patients, breakthrough infections are increasingly common six months after vaccination. In this study the authors analyzed the humoral (antibody-induced) immune response in COVID-19 recovered but unvaccinated individuals for up to a year and compared it with those who had received two doses of the Pfizer vaccine (but no previous infection) over eight months.

The study recruited previously infected-unvaccinated and double-vaccinated-never infected individuals from 25 March 2020 to 25 of November 2020 and closed in April 2021, just before the delta variant arrived in Israel. Those previously infected in this study had been infected by the original and alpha variants (and some cases of beta) of SARS-CoV-2, although it is not known which variant for each patient as the laboratory only gained the ability to sequence variants long after the study began.

The researchers followed-up of 130 patients diagnosed with SARS-COV-2 using PCR testing. These patients had not been vaccinated and remained unvaccinated during the study. None of these patients were reinfected across the study period. Data were collected on acute (during infection and immediately after) as well as long term (after 6 weeks) symptoms. They compared anti-spike protein IgG and neutralizing antibodies of these 130 recovered patients to 402 age and body mass index (BMI), matched individuals who were double-vaccinated with the Pfizer vaccine but who had never had COVID-19. These double-vaccinated patients also remained uninfected across the study period; however, evidence had begun to emerge in Israel at this time (the second quarter of 2021) that double-vaccinated, never infected healthcare workers were experiencing 'breakthrough' infections at around six months after their second dose, whereas previously infected individuals that had not been vaccinated were not being reinfected. This study aimed to explore why.

The avidity index (simply expressed as the quality of antibody performance) was compared at one and six months for sub-cohorts composed of 16 people who had recovered from COVID-19 and 22 never-infected individuals who had been double vaccinated. For recovered patients, questionnaires concerning symptoms including long COVID were also collected.

The researchers found that the numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group. The avidity (antibody performance quality) index was higher in vaccinated individuals than in recovered patients initially. However, up to six months avidity did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients and potentially protected them from reinfection.

Interestingly, and against expectations, the level (titers) of antibodies in recovered patients with a body mass index of 30 or higher (in the obese range) was higher at all time points when compared with those with a BMI under 30 (normal weight to overweight range), suggesting people with obesity who had been previously infected were better protected against future infection than those who were overweight or normal weight and had been previously infected.

Of all recovered patients, 42 (36%) experienced long COVID symptoms including mental health (5%), neurological (9%), cardiovascular (5%) and respiratory (31%) manifestations.

The authors conclude: "While the number of antibodies decrease with time in both COVID-19 recovered (but never vaccinated) patients and vaccinated (but never infected) individuals, the quality of antibodies increases following infection but not after vaccination. People with obesity have a significantly higher and sustained antibody-induced immune response following infection. These results provide specific characteristics of the immune response that may explain the differential protection against COVID-19 in previously infected compared with only-vaccinated individuals."

Now that most people in Israel are vaccinated, it has become much more difficult to do any new study of never-vaccinated individuals.

This team of researchers is now following a cohort of people recovered from the delta variant (specifically focused on families) and also a separate cohort recovered from the omicron variant. In these newer studies, they are examining both the humoral and innate immune responses (different parts of the immune system).

Dr. Cohen adds: "With the omicron variant vaccinated individuals are better protected from severe disease, yet the fourth vaccine dose, now given to many people over 60 years old and those who are immunocompromised, does not appear to be protective against infection with the omicron variant. I think that the most interesting people to follow up now are those who have recovered from the earlier variants and have then been re-infected by, and recovered from, infection with the omicron variant. Hypothetically, these individuals should have very high antibody performance against most variants."

COVID lockdown study shows government used pandemic as 'excuse' to 'overreach' authority: small biz owners

One business owner called for 'controls' to avoid future government-imposed lockdowns

COVID lockdown study shows government used pandemic as 'excuse' to 'overreach' authority: small biz owners | Fox Business

Small business owners are expressing frustration after a new study shows that lockdowns had little effect on public health outcomes in the early days of the coronavirus pandemic.

A study conducted by Johns Hopkins University shows that lockdowns during the spring of 2020, when the coronavirus pandemic began, only reduced COVID-19 deaths by 0.2% in the U.S. and Europe.

The study, conducted by Johns Hopkins University economics professor Steve Hanke, Lund University economics professor Lars Jonung and special advisor at Copenhagen's Center for Political Studies Jonas Herby, says a meta-analysis shows that lockdowns had major economic consequences, but little public health effects.

"While this meta-analysis concludes that lockdowns have had little to no public health effects, they have imposed enormous economic and social costs where they have been adopted," the study states

Joseph Tota, founder and chief executive officer for Tapville, which has restaurants across the country and specializes in self-pour and service technology for craft beer, wine and cider, told FOX Business the lockdowns were "frustrating," given the new study showing their ineffectiveness.

"I think it's frustrating, and I think, you know, the government officials who made the decisions to do lockdowns — particularly in certain states — I think, you know, they kind of owe it to businesses that they impacted with those decisions," Tota said.

Tota said he had to close his business during periods of the pandemic and had to temporarily lay off some employees because there were no customers. He said that a "significant" amount of money was lost during the pandemic, adding that there needs to be controls put in place so another government shutdown of businesses doesn't happen again.

The government and the executive branch overreached their authority and kind of used the pandemic as kind of an excuse to do that," Tota said. "But I think there needs to be more in the future controls so this doesn't happen again."

Tina Van Curen, owner of Autobooks-Aerobooks, a bookstore in Burbank, California, focused on cars, motorcycles and airplanes told FOX Business the Johns Hopkins University study is "completely logical," and said that lockdowns are pointless.

"The whole idea of the lockdown is completely senseless. I mean, all they've done is destroy a lot of businesses and threw a lot of people out of work," Van Curen said.

She said that there "should have been a lot of consideration" that went into the decision of forcing businesses to shut down in the beginning of the pandemic.

Van Curen added that even though pandemic restrictions are being lifted, it's too late for many small businesses, and said that the California legislature should have taken more action to curb Gov. Gavin Newsom's pandemic orders.

"We had a legislature who was supposed to make laws, and they haven't even opened their mouth, especially in California. They've just been hiding," Van Curen said.

what do kids think of mask mandates?

Quote from Fm1

Interestingly, and against expectations, the level (titers) of antibodies in recovered patients with a body mass index of 30 or higher (in the obese range) was higher at all time points when compared with those with a BMI under 30 (normal weight to overweight range), suggesting people with obesity who had been previously infected were better protected against future infection than those who were overweight or normal weight and had been previously infected.

Not against expectations.

• We know COVID is more severe (on average) for obese people
• We know that survivor's immunity is stronger for survivors who have a more severe illness. TANSTAAFL

That is not weird Mafia-prompted propaganda from a faux-expert (which i've never claimed to be). It is remembering stuff posted here from real experts - and anyway it is pretty obvious common sense!

No scientific merit

Sock puppet alarm. What a pathetic and pityful self-praise.

Quote

2022-02-12 08:52 Charlotte

Dear Dr Andrea Rossi,

it is very moving to read the theoretical paper

http://www.researchgate.net/pu…nge_particle_interactions

and immediately after the reading to watch the video of the SKLep presentation ( Youtube Video Ecat SKLep Presentation December 9 2021 ).

It seems you can touch with hands the theory becoming reality.

Thank you for the immense work of you and your great team,

Charlotte

2022-02-12 10:31 Andrea Rossi

Charlotte:

Thank you for your attention to the work of our Team,

Warm Regards,

A.R.

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Quote from RobertBryant

I’m still pissed at myself that I took the 2nd shot but I did ask medical “professionals” though

Only fools kill themselves with CoV-19 or a CoV-19 gene therapy...

Some historic documents:: 6 months phase III study results -- more or less unusable as after unblinding all got RNA crap treatment.

Moderna:: https://www.nejm.org/doi/pdf/1…2113017?articleTools=true

Table with details :: https://www.nejm.org/doi/suppl…ejmoa2113017_appendix.pdf

Pfizer:: Fake study compared to Moderna's details :: https://www.medrxiv.org/conten…07.28.21261159v1.full.pdf

Overall not a single death has been prevented among study participants ... as the groups have been healthy and mostly young people...

So based on fake studies half the world has been "vaccinated" or better said did enjoy multiple gene-tech immune stimulation cancer chemo treatment...But people can't await real cancer for having it again...

Quote from Wyttenbach

So based on fake studies half the world has been "vaccinated"

I'm off this antivaxxer navel gazing competition mostly - but just to inject some reality:

Compare delta deaths in the UK before vaccination (high) and after vaccination (low). Or look at any of the statistics on naive (no previous infection) COVID mortality.

You can argue at the margins about how many teenagers are killed. Like that healthy martial arts girl from Portsmouth who died from COVID - in fact from pericarditis -n or maybe myocarditis - induced by a COVID infection on the day she was due to get vaccinated. You can't argue that the UK has been able to open up keeping threat to health service in bounds due to vaccination.

That is, you can argue it, but normal people would not.

Hungarian Researchers Find Unique SARS-CoV-2 Variant in Soil Sample—Data Point Supporting Lab-Leak Theory of COVID-19?

Hungarian Researchers Find Unique SARS-CoV-2 Variant in Soil Sample—Data Point Supporting Lab-Leak Theory of COVID-19?

Where did SARS-CoV-2 originate? The result of a natural zoonotic process, a lab leak, or some other explanation? TrialSite suggests there is no absolute

trialsitenews.com

Where did SARS-CoV-2 originate? The result of a natural zoonotic process, a lab leak, or some other explanation? TrialSite suggests there is no absolute proof of cause but past entries suggest the lab leak theory is possible. Now a couple of studies produce more data pointing to the possibility of a lab leak. Based on an analysis of soil samples, Hungarian scientists point to traces of pathogen that could possibly support the lab leak theory. While studying DNA samples in soil in Antarctica, the study authors detected traces of a unique coronavirus variant from Chinese samples. More specifically, the scientists, based in Hungary, were conducting research with the Antarctica-based material originally from Shanghai’s Sangon Biotech. They found genetic material from animals associated with Chinese labs suggesting the virus could have been studied in a Chinese lab. Noteworthy, public access to the Sangon Bio data was revoked after the Hungarian researchers uploaded their preprint identifying the COVID-19 ancestor.

According to the Hungarian scientists from Eötvös Loránd University and the University of Veterinary Medicine, traces of the early version of the pathogen could have been studied in a Chinese lab. But does this point to or raise the probability of a lab leak theory?

The researchers leveraged advanced sequencing techniques to examine a large set of samples in the international public sequence archives such as the International Nucleotide Sequence Database Collaboration. The study team hypothesized that “gold mines” of sequences archives could possibly include “genome fragments from early human SARS-CoV-2 cases or from the hypothesized originator zoonotic host.”

Examining the metagenomic profiles of samples of the earliest known cases of the pandemic for SARS-CoV-2 genetic sequence traces, the team found several samples and report the results of their analysis in the recent still to be reviewed study.

Uploaded to Research Square, this study hasn’t been peer reviewed and, consequently, cannot be viewed as evidence. Led by Istvan Csabai at Eötvös Loránd University, the study team tapped into a large public sequencing data vault’s samples collected earlier than the earliest known cases of the pandemic speculating if they might contain traces of SARS-CoV-2.

Undertaking a bioinformatic analysis of “a metagenome sample set collected from soil on King George Island, Antarctica,” the study team’s sample collection originate from December 24, 2018, to January 23, 2019.

Findings

Interestingly, the Hungarian scientists uncovered that the soil contained “sequence fragments matching the SARS-CoV-2 reference genome with altogether more than half-million nucleotides, covering the complete genome on average 17x.”

Conducting an initial phylogeny analysis, the team authored that this “places the sample close to the known earliest cases.” This suggests “the high sequence coverage rules out chance alignments from other species, but possible laboratory contamination cannot be excluded.”

They researchers from Hungary found “a unique combination of mutations, unseen in other samples, so whatever its origin, it can add important piece of information to the puzzle of the ongoing pandemic.”

The authors report that the soil sample analysis suggests coronavirus may have not transferred via a zoonotic process, the common mainstream explanation, yet there is no proof to date.

The mainstream press has for the most part ignored this obscure but interesting study. For example, the UK’s DailyMail reported a summary of the findings. Professor Jesse Bloom, operating out of the Seattle, Washington-based Fred Hutchinson Cancer Research Center, apparently verified the study in a test confirming the samples in fact contain the virus. However, Bloom went on the record that the “ultimate implications remain unclear.”

Writing for DailyMail, Health Reporter Luke Andrews recounted the chain of events associated with the soil samples, including:

Step Date Series of Events

1 January 2019 Soil samples collected King George Island, Antarctica

2 December 2019 In China at Sangon Biotech in Shanghai DNA extracted from the soil sample

3 November 2019 Three workers at Wuhan Institute of Virology hospitalized with COVID-19 like symptoms

4 December 2019 At Sango Biotech, an error on testing equipment—possibly due to barcode error—contaminates the sample with DNA from monkeys and hamsters commonly used in lab experiments. It’s now known that WIV sent Sangon Biotech material for analysis

5 Late 2019 The monkey and hamster DNA contains a rare mutation of COVID-19. Most experts suspect the origin to be the original virus. While the Hungarian scientists suspect the trace elements ae an ancestor of COVID-19, one that could “bridge the gap between bat-based coronavirus and the first Wuhan strain.

6 December, 2019 COVID-19 cases start to be identified by WIV.

7 January, 2022 Interestingly public access to the Sangon Bio data is revoked after Hungarian researchers upload their preprint identifying the COVID-19 ancestor.

Some Concern

Luke Andrews was able to elicit a quote from a top virologist at Warwick University, Professor Lawrence Young who supports the natural origin theory (meaning the pathogen somehow jumped from an animal to a human—like the previous coronaviruses origins—yet declared publicly the findings were “very, very intriguing and very, very suspicious.”

While by no means definitive proof that SARS-CoV-2 was engineered in a lab the data suggests Chinese scientists were conducting experiments associated with coronavirus early on during the pandemic

Meanwhile professor Young continued: “The two things that really stand out for me are there are these three key mutations bringing the bat COVID closer to the first Wuhan strain. It is very, very suspicious [and could be] a signature of the ancestral SARS-CoV-2.”

Other Pointers to Lab Activity?

Also, DailyMail reports that the Antarctic samples included DNA from Chinese hamsters as well as green monkeys, which professor Young pointed out could point to a situation where Chinese virologist may have been growing the pathogen in animal cells.

On the other hand, the soil could have originated from the first COVID-19 patients reported in China back in December 2019.

Eotvos Lorand University

Based in Budapest, this public research university called Eötvös Lorand University was founded hundreds of years ago in 1635. Also, knowns as ELTE, this is one of the largest and most prestigious institutions of higher education in the nation’s largest city. The academic medical center is affiliated with 5 Nobel laureates as well as winners of the Wolf Prize, Fulkerson Prize and Abel Prize.

Funding

The study was funded by the EU Horizon 2020 program (multiple grants), while the authors are grateful for access to the GISAID database and all labs that contributed to SARS-CoV-2 sequence data.

Lead Research/Investigator

István Csabai, Eötvös Loránd University

Krisztián Papp, Eötvös Loránd University

Dávid Visontai, Eötvös Loránd University

József Stéger, Eötvös Loránd University

Norbert Solymosi, University of Veterinary Medicine

Source

·

https://www.researchsquare.com/article/rs-1330800/latest.pdf

·

Quote from THHuxleynew

Compare delta deaths in the UK before vaccination (high) and after vaccination (low).

I only compare CoV-19 treating India/Japan etc.. and other countries with FM/R/B killing governments.

I know you are proud to work for the masters of killers hosting institution the Oxford University...

Quote from THHuxleynew

but just to inject some reality:

BMJ questions Pfizer vaccine trials

Facebook questions BMJ

When FB becomes Minitrue,,

Quote from Dr Richard*

No new developments...

Only postmortems

"Corporations like Pfizer should never have been put in charge of a global vaccination rollout,

because it was inevitable they would make life-and-death decisions based on what’s in the short-term interest of their shareholders.

We need to dismantle the monopolies that have handed these financialised beasts such power, and instead invest in a new network of research institutes and medical factories around the world that can actually serve the public."

Putting big pharma in charge of global vaccine rollout was a big mistake | Nick Dearden

Covid has made it clear: the likes of Pfizer, in thrall to shareholders, only really care about their huge profits, says the director of Global Justice Now

www.theguardian.com

erectile dysfunction was OK for Pfizer but not a pandemic..

“Freedom Convoy” Goes International

"Freedom Convoy" Goes International

The Canadian “Freedom Convoy” of truckers now appears to be a worldwide form of protest. In France, a “Convoi de la Liberte” (Freedom Convoy) has started

trialsitenews.com

California Democrat Legislators Propose COVID-19 Vaccination Mandate: All Employers & Stiff Financial Fines for Non-Compliance

The Canadian “Freedom Convoy” of truckers now appears to be a worldwide form of protest. In France, a “Convoi de la Liberte” (Freedom Convoy) has started driving from the south of France toward Paris. Protesters are demonstrating against France and Europe’s vaccine pass, which prevents the unvaccinated from attending theaters, movie houses, and eating in restaurants. The French convoy plans to drive on from Paris to Brussels, the capital of Belgium and the headquarters of many European Union institutions. These protests are not new to France. The country had anti-pass and mandate protests in several cities, even though only 8% of the French population remains unvaccinated. The Convoi de la Liberte started in the southern city of Nice with many protesters stocking up on food and were given detailed maps of Paris by the organizers.

Paris police have vowed not to allow the drivers to enter the capital. Drivers from other cities in France are expected to join the motorcade, which includes trucks, cars, and motorcycles all protesting COVID-19 restrictions. Protesters who are caught by the police receive a two-year prison sentence, a fine of 4500 Euros ($5100), and a three-year ban from driving.

The French protest is a copy of the Canadian Freedom Convoy which appears to be effective. The premier of Ontario has declared a state of emergency as the capital city of Ottawa is about to enter its third weekend of the trucker blockade. The Canadian protest extends beyond the capital to other parts of the country and has shut down thoroughfares to the United States blocking highways and bridges threatening the flow of goods and trade between the two countries. What started as a protest targeting vaccination requirements of truckers traveling between the North American neighbors has turned into a demand for Prime Minister Justin Trudeau to resign. The Canadian government is now threatening fines of up to $75,000 and a year in prison if the protest continues. Also, while trucker donations were usurped by GoFundMe, they moved to seize another funding site. Media reports that the Ontario Superior Court of Justice issued an order stopping access to the funds at the Christian-oriented “GiveSendGo website.

The Canadian protest may spread south. A planned “American Freedom Convoy” could start as early as Super Bowl Sunday with plans to possibly disrupt the big game. The U.S. Department of Homeland Security has issued a warning the protest could “severely disrupt transportation, federal government, and law enforcement operations through gridlock and potential counter-protests”.

Facebook has shut down several groups supporting the demonstration. The American truckers have plans to start with the Super Bowl or perhaps by early March in Los Angeles and then drive across the country and arrive in Washington D.C. in time for President Joe Biden’s State of the Union address.

Other reports of truck-driven protests now surface in other nations—from Austria in Europe to Australia in Oceania. For example, in Austria, the government issued a ban on vehicular-based protests as hundreds of vehicles were to converge in downtown Vienna. The government in that German-speaking country plans to enforce prohibitions of this class of protest based on the environmental commotion (e.g., noise pollution) such an event could cause.

In the meantime, major marches continue in Australia, this time in Canberra, the nation’s capital. While the protestors are pegged as “antivaxxers,” it appears that the biggest focal point centers on the mandates and restrictions on freedoms.

In the meantime, just a few days ago on Thursday, clashes between protestors and police on the grounds of the country’s parliament led to dozens of arrests. Marchers had seized the legislature for three days with activists repeating a Maori chant “hold the line” as scuffles with the line police intensified; the police were charged with breaking up the protest contingent.

In New Zealand, protestors are standing against vaccine requirements against a range of professions including teachers, frontline health workers, police and the military.

Though this is not the first of international protests against COVID-19 decrees, it seems as if the “Freedom Convoys” have been the most effective demonstration, to this point, against mandates. For example, possibly due to the mounting social pressure, some provinces back in Canada are planning on dropping the mandates such as Saskatchewan Premier Scott Moe who announced this past Tuesday that by Valentines Day (February 14th), the province will remove all vaccination requirements. But other locales remain resolute that they’ll take a more guarded, incremental approach.

Mask Mandates Didn’t Make Much of a Difference Anyway

The policies clearly didn’t stop omicron. Let’s focus on tactics that have worked better.

https://www.bloomberg.com/opinion/articles/2022-02-11/did-mask-mandates-work-the-data-is-in-and-the-answer-is-no

States across the U.S. have dropped their mask mandates this week, worrying Americans who think they’re still needed and cheering people who are ready to go “back to normal.” Both groups need to take a deep breath: Dropping mask mandates isn’t the same thing as ignoring Covid-19.

Masks have been the most visible part of America’s pandemic response, but one of the least consequential. The fact that 500,000 people worldwide died during the omicron surge means it’s time to change tactics, and focus on what went wrong that led to so many hospitalizations and deaths.

Mask mandates are predicated on the effectiveness of “universal masking” in which everyone wears a mask to keep case numbers lower. One of the leaders in proposing universal masking, Monica Gandhi of UCSF, has unfairly been accused of being an anti-masker for talking about the limitations of her own strategy and the much greater importance of vaccination campaigns.

But there’s no avoiding it: The benefits of universal masking have been difficult to quantify. One controlled study in Bangladesh showed a small but statistically significant benefit — among people who consistently used masks, 7.6% got symptomatic infections compared to 8.6% in the control group. Other studies have been inconclusive.

It is intuitive that a barrier ought to prevent germs from being emitted into the air. But if that’s true, why isn’t there more evidence for the benefits of masking two years into the pandemic? Experts associated with The Center for Infectious Disease Research and Policy (CIDRAP) at the University of Minnesota have laid out a more complex analysis: Given the current understanding that the virus is transmitted in fine aerosol particles, it’s likely an infectious dose could easily get through and around loose-fitting cloth or surgical masks.

Many experts say only N95 respirators or similar devices are truly effective at stopping this virus — and some, such as the CIDRAP head Michael Osterholm, have been going public urging people to put less faith in cloth masks and adopt respirators such as N95s. He does not advocate universal N95 use in schools, however, where children are unlikely to be able to wear them consistently or correctly.

Most of the people who were only wearing masks because of the mandate were donning the less effective masks. Those concerned enough to get an N95 aren’t going to stop because it’s not required. Future policies should focus on helping people understand their risks and making sure everyone who wants a supply of N95 masks can get one.

The most visible change will be in stores, and these are not the most dangerous venues. Much riskier are crowded bars or private gatherings where people were already removing their masks to eat and shouting to be heard. Several studies have shown that the louder someone talks, the more particles they expel. Other studies show prolonged exposure to others indoors is much riskier than fleeting exposures.

All those factors may explain why the states with mask mandates haven’t fared significantly better than the 35 states that didn’t impose them during the omicron wave. Rhode Island, where I live, has had a mask mandate since mid-December; nonetheless, we saw our January surge rise far higher than any other state. There’s little evidence that mask mandates are the primary reason the pandemic waves eventually fall — though much of the outrage over lifting mandates is based on that assumption. Many experts acknowledge that the rise and fall of waves is a bit of a mystery, as epidemiologist Sam Scarpino explained to me on my podcast.

What is clear is that states with high vaccination rates have fewer hospitalizations and deaths, and that booster shots are essential for anyone over the age of 65 or at high risk of severe disease.

Megan Ranney, an emergency medicine physician and a dean at the Brown University School of Public Health, says most of her hospitalized patients were unvaccinated or they live in multi-generational homes and got the disease from younger family members who skipped the shots. She sees no problem with the idea of lifting mask mandates when the stress on hospitals has eased.

It’s absolutely appropriate to relax mask mandates as cases drop below a threshold, particularly in areas with high vaccination and particularly once hospitals are not in crisis mode,” she says. She would have liked to see some states wait a bit longer, though, and says lifting mandates in schools should depend on both case counts coming down and vaccination rates among students getting above 85%. (Vaccination rates are currently at 23% for kids ages five to 11 and 57% for kids 12 to 17.)

In other countries, mask mandates have been imposed and lifted with little or no rancor. Last week I talked to Michael Bang Petersen, a political scientist and psychologist who has been directing a research project on pandemic behavior at Aarhus University in Denmark. There, remarkably, all restrictions were lifted this month with little controversy.

Some of that is due to good communication and trust. “We can see that a clear majority of the population feel that they actually getting clear information from the authorities,” he said.

And Danish authorities have a realistic goal — not minimizing all cases or eliminating the virus but preventing the healthcare system from breaking down. “I think if we look at how it is that the Danish public thinks about coronavirus, they don't think of it as an individual threat … they think of it as a societal threat,” he said.

Americans are not selfish — we think about protecting society too — but we’re deeply divided about what our obligations should be. One way we might ease our tensions is by putting the role of mask mandates in perspective

Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein

Plasticity in structure and assembly of SARS-CoV-2 nucleocapsid protein

Worldwide SARS-CoV-2 sequencing efforts track emerging mutations in its spike protein, as well as characteristic mutations in other viral proteins. Besides…

www.biorxiv.org

Abstract

Worldwide SARS-CoV-2 sequencing efforts track emerging mutations in its spike protein, as well as characteristic mutations in other viral proteins. Besides their epidemiological importance, the observed SARS-CoV-2 sequences present an ensemble of viable protein variants, and thereby a source of information on viral protein structure and function. Charting the mutational landscape of the nucleocapsid (N) protein that facilitates viral assembly, we observe variability exceeding that of the spike protein, with more than 86% of residues that can be substituted, on average by 3-4 different amino acids. However, mutations exhibit an uneven distribution that tracks known structural features but also reveals highly protected stretches of unknown function. One of these conserved regions is in the central disordered linker proximal to the N-G215C mutation that has become dominant in the Delta variant, outcompeting G215 variants without further spike or N-protein substitutions. Structural models suggest that the G215C mutation stabilizes conserved transient helices in the disordered linker serving as protein-protein interaction interfaces. Comparing Delta variant N-protein to its ancestral version in biophysical experiments, we find a significantly more compact and less disordered structure. N-G215C exhibits substantially stronger self-association, shifting the unliganded protein from a dimeric to a tetrameric oligomeric state, which leads to enhanced co-assembly with nucleic acids. This suggests that the sequence variability of N-protein is mirrored by high plasticity of N-protein biophysical properties, which we hypothesize can be exploited by SARS-CoV-2 to achieve greater efficiency of viral assembly, and thereby enhanced infectivity.

Discussion

The worldwide sequencing effort has led to the assembly of an unprecedented database of viable SARS-CoV-2 variants, alone for N-protein describing ∼25,000 different species as of November 2021. In the present work we have combined an analysis of the amino acid variability of SARS-CoV-2 N-protein with biophysical experiments of select mutants, and found remarkable plasticity on all levels of organization. Plasticity has been hypothesized to be a unique feature of RNA virus proteins, which have more loosely packed cores and an abundance of intrinsically disordered regions that confer high degrees of flexibility for adaptation and tolerance to mutations (25). In the present case of the SARS-CoV-2 N-protein, more than 86% of positions in the amino acid sequence are subject to variation, on average by 3-4 different amino acids, about half of which score low on a physicochemical similarity scale. We observed substitutions at many positions thought to be critical due to their conservation across related coronaviruses, or their constitution of phosphorylation and protein interaction sites, are found to be viable. Our data show that the single mutation G215C causes significantly altered secondary structure; gross differences in hydrodynamic shape indicate altered subunit arrangements; and strongly enhanced protein-protein interactions modulate the formation of quaternary structure. More extended studies are required to elucidate the expected impact of mutations in N-protein, for example, on host protein interactions, interactions with other viral proteins, and on phase boundaries for condensation and nucleic acid coassembly. This plasticity poses significant challenges to identify the essential functions and mechanisms that may serve as therapeutic targets in N-protein.

Earlier examinations of emerging mutations in N proteins (6, 14, 61–63), going back to June 2020, were necessarily more limited in scope, and while sufficient to examine hot spots and identify key replacements such as R203K/G204R (6, 10, 14, 64), it was not yet possible to draw conclusions from a survey of the entire mutational landscape. Due to the orders of magnitude larger coverage that has become available through the global genomic epidemiology efforts since then, we believe that the observed data now approaches the limits of possible mutations for functioning N-protein, and therefore reflects its biophysical properties.

The study of the constraints in the mutational landscape appears very useful to complement structural biophysical tools, particularly to examine intrinsically disordered regions. These generally are permissive for a wide range of amino acid substitutions and, in fact, harbor three of the four persistent N-protein mutations characteristic of the Delta variant, and all of the Omicron mutations in N-protein. However, the mutational landscape of N-protein reveals several islands within these regions that are highly protected and therefore appear to have critical functions.

One of these is in the central linker adjacent to the G215 position, where the G215C mutation has quickly outcompeted all other variants in 2021 after its appearance alongside only ORF1ab and ORF7b mutations in the Delta variant. NMR and molecular dynamics studies have reported distinct α-helical propensity flanking position 215 in the SR-rich region (63) and in the leucine-rich region (38). The latter was proposed by Cubuk et al. to provide interfaces for oligomerization. Most recently, NMR experiments showed formation of an α-helix 219-230 when in complex with nsp3a, which binds to N-protein competitively with RNA (65). In the present work, we found this region highly protected against mutation. We propose that these helices may be essential for higher-order assembly of N-protein and are either stabilized or exposed in the emerging G215C mutant. Indeed, our simulations show a stable helix spanning residues G215-S235 exhibiting an extended hydrophobic surface on one side. Mutation to C215 repositions the downstream sequence relative to the helix, which renders the hydrophobic surface more accessible for protein-protein interactions.

The potential introduction of disulfide bonds in the N:G215C mutant stabilizing dimer-dimer crosslinks in the linker region would constitute an even more drastic change in the assembly pathway. It is uncertain, however, whether these disulfide bonds are formed in vivo. Disulfide bonds are absent in nucleocapsid proteins of related betacoronaviruses, but assist oligomerization of nucleocapsid proteins of other RNA viruses at least transiently (66, 67). However, even without disulfide bonds, we found a 200-fold enhancement of dimer-dimer self-association in N:G215C, accompanied by augmented co-assembly with NA, which we hypothesize profoundly alters the co-assembly kinetics of ribonucleoprotein particles. This may contribute to the clinical phenotype of strongly increased viral load and infectivity of the Delta variant, and the overwhelming dominance of the 21J Delta clade relative to the 21I Delta clade despite the lack of additional changes in the spike protein.

After writing of this manuscript, the 21J Delta variant of SARS-CoV-2 has been replaced by the Omicron variant as the worldwide dominant variant. Interestingly, the latter has none of the N-protein mutations defining for the Delta variant, but it exhibits deletions and new mutations that may impact viral fitness, in addition to the characteristic spike protein mutations. While this development does not impact our conclusions on the mutational landscape of N-protein and its relation to its biophysical properties and assembly functions, it will be interesting to examine to which extent Omicron will explore, on a global population level, a similar N-protein sequence space as Delta and prior variants.