Covid-19 News

Boris Johnson, bless his heart, has proposed setting up research institutes to produce new vaccines in 100 days, in case another virus emerges. I do not admire Johnson, but that seems like a great idea. Just what the world needs! A much more virulent virus might emerge, that could quickly kill millions of people. An emergency 100-day vaccine development schedule might save millions of lives. We can all hunker down in deep shut-downs with canned food and social distancing for 100 days. We can't do that for a year, obviously. This institute would have to be coupled with vaccine factory production lines maintained and ready, whether we need them or not.

If Johnson pulls this off he will be one of the UK's greatest Prime Ministers, whatever else he does. I think Biden would be inclined to go along with this plan.

See:

https://www.politico.eu/articl…cines-ahead-of-g7-summit/

Quote from JedRothwell

The UK variant is a frightening problem, but not because the two vaccines now in use cannot deal with it.

The UK variant was never a frightening problem. It was only (miss-) used by politicians to suppress the people and shed them in to vaccination.

The UK variant can better infect younger people. So it, in total, has a slightly larger reservoir that also is much more mobile than the old reservoir that currently dries out. This looks on first sight like an increase in numbers and also can be seen in most countries statistics e.g. Switzerland where it did cause a small uptick and a delay in falling number by about 4 weeks. As said overall it changes nothing to the dynamics.

The UK variant also never was a problem with all known vaccines.

The RSA mutation & the BRA mutation are a real problem where e.g. the Pfizer vaccine looses up to 75% of its protective power. We will soon know more as Israel is testing it for us. In Israel the Pfizer vaccine efficiency did fall by more than 3% in one week and the true picture we will have after end of lockdown.

So far the J&J vaccine is more or less guaranteed to help against the RSA strain. That's the reason why RSA ordered it!

It also looks like Pfizer, Moderna are ready with updates and want to bring them on the market - without any study - what is a criminal act against humanity. There is absolute no emergency situation. People that still own a brain an know how to use it did buy their personal ivermectin.

Advantage: The ones that once got CoV-19 can avoid further lockdowns. The vaccinated certainly not except in some countries with a criminal government like Israel. Vaccinated people can carry the virus 4x less in average and also within 15% (UK data) of the Pfizer vaccinated the protection fails.

Quote from Wyttenbach

The UK variant was never a frightening problem. It was only (miss-) used by politicians to suppress the people and shed them in to vaccination.

Nothing frightens you, because you are God, you know everything, and you can read men's hearts and minds. Lucky you! Also you have conspiracy theories to explain everything, including what I had for breakfast.

M. Osterholm et. al at CIDRAP think we should delay the second dose. Their technical paper is here:

https://www.cidrap.umn.edu/sit…d19-viewpoint-report7.pdf

CNN summarized it in somewhat easier language:

A new report out Tuesday warns that a more transmissible variant of coronavirus threatens to start a renewed surge of infections in March, and suggests the US speed up vaccination by skipping second doses for now.

People over 65 should go to the front of the line, since they are by far the most vulnerable to severe disease and death, Epidemiologist Michael Osterholm and colleagues at the Center for Infectious Disease Research and Policy at the University of Minnesota recommended.

They call on the US Food and Drug Administration and the US Centers for Disease Control and Prevention to quickly assemble advisers to help change vaccination guidelines to get more vulnerable people vaccinated more quickly, before the B.1.1.7 variant of the virus, first seen in the UK, causes more spread.

“If the US experiences a surge similar to that seen in the UK, one could expect to see unprecedented healthcare demand of 175,000 to 193,000 hospitalizations per day — far surpassing the US peak of 132,474 individuals hospitalized with COVID-19 set in early January,” the report reads. Right now, just over 55,000 people are currently hospitalized for Covid-19 in the US, according to the Covid Tracking Project.

“To maintain healthcare capacity during a B.1.1.7 surge, we have a time-limited period to strategically target vaccination to those at highest risk of hospitalization and death before the surge arrives," it adds.

Quote from JedRothwell

People over 65 should go to the front of the line, since they are by far the most vulnerable to severe disease and death,

Exactly: Here 97% of all death are older than 65!

Here the latest UK report : https://assets.publishing.serv…t_February_2021_FINAL.pdf

Here the study: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3790399

The endpoint was a bit early so 85% is 7 days after second shot. This might go up to the current accepted value of 89..90%.

Quote from JedRothwell

“If the US experiences a surge similar to that seen in the UK, one could expect to see unprecedented healthcare demand of 175,000 to 193,000 hospitalizations per day

This is absolute nonsense for the UK strain as the younger are not the risk group!

Here something about the war behind the scene : https://healthpolicy-watch.new…d-manufacturing-concerns/

Russian hackers atacked EMA. Nothing spectacular, but certainly some people will make missues of it.

Here a link for a summary how state terror about free speech is increasing among USA

https://childrenshealthdefense…s-vaccine-misinformation/

Read the sublinks! One citation:

Reuters reported that Biden, concerned that “fear about taking the vaccine has emerged as a major impediment” to his administration’s pandemic plan, wants help from the social media moguls to keep “misinformation” from going viral.

Of course daddy cool (Biden) knows all the misinformation...

Recurrent coronavirus diseases 19 (COVID‐19): A different presentation from the first episode

https://onlinelibrary.wiley.com/doi/full/10.1002/ccr3.3967

DISCUSSION

While our knowledge regarding the risk factors for COVID‐19 recurrence and other associated parameters is evolving, data are pointing out to the temporary immunity of anti–SARS‐CoV‐2 antibodies in unvaccinated individuals6 and the emergence of viral escape mutants as potential mechanisms for recurrent cases.7 Our case developed a reinfection with SARS‐CoV‐2 after an initial episode of severe disease and a 2‐month disease‐free interval. The second episode was significantly milder requiring no inpatient medical care but relatively different in presentation from the initial episode. In a surveillance study at the Oxford University Hospitals in the United Kingdom, Lumley et al measured anti‐spike and anti‐nucleocapsid IgG antibodies in 12 541 healthcare workers and followed them for a period of 31 weeks.6 The authors found that out of 1265 seropositive cases, 88 had developed seroconversion during the follow‐up period. On the other hand, 223 seronegative subjects developed a positive PCR test (1.09 per 10 000 days at risk) of whom 44.84% were asymptomatic and 51.6% were symptomatic. This was significantly different from the only 2 seropositive cases, who became PCR‐positive during the follow‐up period (0.13 per 10 000 days at risk). While the anti–SARS‐CoV‐2 antibodies rendered, on average, an immunity against reinfection for a duration of 6 months, our case report along with others raises questions about the generalizability of such a short‐term protection.4, 5 However, none of these case reports have monitored the evolution of neutralizing antibodies or their titers against SARS‐CoV‐2 from the initial infection to the time of reinfection.

A genomic analysis of SARS‐CoV‐2 at two different times from a 25‐year‐old man from Washoe, Nevada, revealed genetically significant differences between the two species.4 Unlike our patients, the second episode was more severe in terms of clinical symptomatology. Further case reports have also shown a declining antibody titer to coincide the reinfection with SARS‐CoV‐2.2, 3, 8 The case report from Hong Kong showed that an initial mild infection with SARS‐CoV‐2 did not produce any effective neutralizing antibody, which 5 months later, although completely asymptomatic, resulted in reinfection with the virus.2 Another case report from the Netherlands showed a more severe presentation of COVID‐19 recurrence compared with the index episode.3 Although the latter patient was immunocompromised due to a recent B‐cell–depleting chemotherapy for Waldenström's macroglobulinemia, an effective innate immunity or T‐cell response might have acted as a savior. The same path can be imagined for the case report from Hong Kong in whom no effective neutralizing antibody was detected in either of the episodes. Unfortunately, our current laboratory setting did not permit measuring anti–SARS‐CoV‐2 serum antibody titers from the index infection to the recurrence of COVID‐19, nor did it allow the genomic analysis of the causative agents in these two different episodes.

The time interval between the initial infection with SARS‐CoV‐2 and the second episode has been variably reported in the literature.3-5, 8 While the duration of immunity rendered by anti‐spike or anti‐nucleocapsid IgG antibodies has been shown to be for a minimum of 6 months, a systematic review of the reported cases of reinfection with SARS‐CoV‐2 has estimated this interval to be 35.4 days.5 The review has also found that a younger age and a longer time to become PCR‐negative are significantly associated with a higher risk of reinfection with SARS‐CoV‐2, while a severe disease might play a protective role.

Our case report supports the growing doubt about a lasting immunity against SARS‐CoV‐2. Although our patient presented differently in the second episode from the initial one, the clinical manifestation was clinically less severe. The time from initial infection to the recurrent episode was above the average time, which is reported in the literature. However, we could not examine the evolution of neutralizing antibody over this time interval as the titer was not measured in our case. While the current endeavors in global vaccination against SARS‐CoV‐2 are ongoing, clinicians should remain alert about variation in individuals' response to the infection and the potential risk of reinfection despite receiving the vaccine. This is especially important when we are reading the news about the emerging new variants of the SARS‐CoV‐2, which seem to be more contagious.

Quote from Fm1

our case report supports the growing doubt about a lasting immunity against SARS‐CoV‐2.

One more fear & bash paper: Reinfections are very rare. Some estimate at most 1/10000 of the cases. Why is re-infection scaring? The only problems so far are reported among people that once had a very soft infection and afterwards get a high dose. But this has nothing to do with a re-infection as it in fact it is the first infection.

Please be aware, that all of us, already multiple times, were in contact with CoV-19 but with very low doses. So testing the optimal day you will find anti bodies a few weeks later none.

If you had CoV-19 with real symptoms, then you certainly can only get a re-infection by one of the strongly mutated version from RSA/BRA!

Two potent SARS-CoV-2 neutralizing antibodies effective against B.1.351 and B.1.1.7 variants

https://www.news-medical.net/n…51-and-B117-variants.aspx

Understanding antibody binding complexes

Using SARS-CoV-2 spike protein complexes with antibody 1-57, the team reconstructed the structure at a resolution of 3.42 Å (roughly three ten-billionths of a meter). They identified a single conformation with three antigen-binding fragments per trimer. Each fragment was bound to an RBD in the down configuration

The primary interaction of the RBD to the antibody was via the CDR H3, forming disulfide bonds, hydrophobic interactions, and hydrogen bonds. Of the mutations in the UK and South African variants, only E484K of the South African strain was close to the binding site of 1-57. Structural modeling revealed a lysine residue was geometrically compatible with 1-57 binding.

For the 2-7 antibody, cryoEM analysis revealed three fragments bound to a single spike, with two bound to the RBD in the up configuration and one to the RBD in the down configuration. The interactions with the RBD were predominantly with the residues 438-451 and 495-502. CDR H2 formed several salt bridges and hydrogen bonds. In the UK and South African mutations, antibodies 2-7 only bound near N501.

The antibodies 1-57 and 2-7 used heavy chain genes and were not frequent in the SARS-CoV-2 specific group of antibodies. This suggests antibodies that are genetically similar to 1-57 and 2-7 may not be common in the human response to the virus.

Parts of the virus that are frequently a target of antibodies may cause the virus to develop evasion mechanisms. Using previously reported structures of antibody-RBD complexes, the authors found that epitopes of the antibodies 1-57 and 2-7 are targeted less often. These epitopes are also on regions that are not important for binding to the angiotensin-converting enzyme (ACE2) or for neutralizing antibody escape.

Although the antibodies 1-57 and 2-7 were not affected by the RBD mutations on the UK and South African variants, other RBD mutations can affect them. For example, mutations at positions 452 and 494 may affect 1-57 binding and mutation at position 439 may affect 2-7 binding. However, more research needs to be done to understand this further.

SARS-CoV-2 infection drives a glycan switch of peripheral T cells at diagnosis

https://www.medrxiv.org/conten…101/2021.02.17.21251918v1

Results

SARS-CoV-2 infected individuals display decreased β1,6-GlcNAc branched and α2,6-sialic acid N-glycans on peripheral T cells at diagnosis

Taking into consideration the fact that it is still unclear the underlying mechanisms that explain a differential inter-individual clinical presentation of COVID-19 at diagnosis, we herein characterized the glycosylation profile of T cells from patients’ peripheral blood. A lectin-based flow cytometry of the T cell populations was performed to evaluate glycosylation profiles. We started by analysing the levels of expression of ß1,6-GlcNAc branched N-glycan structures, known to have a major impact on the regulation of T cell activity and function(13, 16, 26), using the L-PHA lectin. Our results demonstrated that, overall, T cells from infected (IF) subjects have a decrease in branched N-glycan structures, particularly on CD8+ and γδ T cells, when compared to non-infected (non-IF) ones (Figure 1A, top and bottom left panel). Moreover, T cells from asymptomatic patients have lower levels of ß1,6-GlcNAc branched N-glycans, that gradually tend to increase along disease severity (Figure 1A, right). Notably, CD8+ T cells display a significant decrease in the levels of expression of complex branched N-glycans in asymptomatic and mild disease patients, when compared to non-IF individuals

A vitamn D deficenccy

Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging

https://www.medrxiv.org/conten…2.17.21251918v1.full-text

Discussion

Our results demonstrated for the first time that SARS-CoV-2 infection imposes a glycosylation reprogramming of adaptive immune cells suggesting a specific glycan switch of T cells that may define their ability to successfully deal with infection. We identified a specific glycosylation signature of circulating T cells that is associated with their activity and function, distinguishing infected patients from non-infected individuals. Our results also suggest that the glycan switch imprinted in circulating T cells could be mediated by a serum extracellular factor(s), occurring just after SARS-CoV-2 infection (Supplemental Figure 2). In fact, previous evidences from others and us demonstrated that the deficiency in branched N-glycan structures on T cells imposes a hyper-reactive phenotype with decreased threshold of T cell activation and increased T cell activity(13, 28). We herein propose that the immune response against SARS-CoV-2 infection appears to be influenced by the glycosylation profile of circulating T cells which defines their effective functions. In fact, a pronounced deficiency of complex branched and sialylated glycans on CD8+ and γδ T cells were observed in asymptomatic COVID-19 patients. This dynamic and plastic glycoimmune modulation (“Glyco-Immune Alert” mechanism) may constitute a novel mechanism of host-response, that contributes to further understand the immunological differences among infected individuals(36).

Furthermore, we also showed another glycan-based mechanism of host response to SARS-CoV-2 driven by the upregulation of the viral’s glycans recognizing receptor DC-SIGN in monocytes, with prognostic application when detected at diagnosis.

This study unlocks the identification of a specific glycosignature of T cells as well as a prognostic biomarker in COVID-19. Further studies are needed to explore the mechanistic impact of the T cell glycan switch in infection and along disease course. Moreover, it is fundamental to identify the critical serological factor(s) that instructs this T cells glyco-reprogramming, as a potential new biomarker and therapeutic target. Our study was conducted during the first wave of COVID-19 (March-July 2020) having a limitation in terms of sample size, indicating the need to validate these promising observations in larger and well-characterized multicentric cohorts as well as analysing the impact of other SARS-CoV-2 variants in T cells glycan switch.

These new evidences in COVID-19 pave the way to the identification of a specific blood glycosignature able to stratify patients at diagnosis according with their risk to evolve to worsen disease. This will certainly contribute to improve vaccination strategy and patients risk stratification, optimizing an effective allocation and management of health care resources such as ventilators and intensive care facilities.

B cells continue to work against SARS-CoV-2 months after infection, but do not recognize mutant

https://www.eurekalert.org/pub…021-02/aaft-bcc022321.php

A new analysis of B cells and more than 1,000 different monoclonal antibodies from 8 patients with COVID-19 shows that, contrary to previous hypotheses, protective B cell responses to the SARS-CoV-2 spike protein remain stable and continue to evolve over a 5-month period, many months after the initial period of active viral replication. However, a large proportion of the neutralizing antibodies generated from these long-lasting B cells did not efficiently recognize various emerging SARS-CoV-2 variants from Brazil and South Africa. These results - from an academia-industry collaboration - will help inform the design of future COVID-19 vaccines that work to constrain viral evolution and stimulate better neutralizing antibody and B cell responses against emerging SARS-CoV-2 variants. Mrunal Sakharkar and colleagues profiled spike protein-specific B cell and antibody responses in 8 patients with mild and severe COVID-19 over five months. Consistent with previous findings, they observed a significant decline in neutralizing antibody levels in the blood over time; however, levels of spike protein-specific memory B cells remained stable or even increased during the same time frame. As well, over the course of 120 days, monoclonal antibodies isolated from these B cells underwent increased somatic hypermutation, binding affinity, and neutralization potency - all signs of persistent B cell activity. The researchers also observed cross-neutralizing B cell populations, but these comprised just a small fraction of the B cell repertoire and were not prominent in the neutralizing response to SARS-CoV-2. Rather, a large proportion of the neutralizing antibody response only targeted conserved epitopes shared between SARS-CoV-2 and SARS-CoV and did not efficiently recognize emerging SARS-CoV-2 variants from Brazil and South Africa that harbor mutations at amino acid positions 417 and 484 of the spike protein. Thus, the authors suggest careful monitoring of circulating SARS-CoV-2 variants for variability in these protein sites to determine how these mutations impact vaccine-induced immunity.

Experts worry variant-fueled surge of Covid-19 could be weeks away but cases will likely fall again by summer

https://amp.cnn.com/cnn/2021/0…irus-wednesday/index.html

CNN)Coronavirus infections across the US are still on the way down and more Americans are getting their vaccinations -- but variants could cause complications in the coming weeks.

Several experts predicted Tuesday the highly contagious B.1.1.7 variant that was first detected in the UK is likely to fuel another surge of cases in just a matter of weeks.

"It could result in more of a wave in, say, April or May than we would have expected otherwise," Trevor Bedford of the University of Washington and the Fred Hutchinson Cancer Research Center, said during a briefing sponsored by the center. "But I still do suspect that things will be brought under control in the summer, and there will be very little virus circulating.

The predicted surge is why many experts have highlighted the need to double down on safety measures like face masks, social distancing and avoiding crowded areas. Helping to lower cases will also give the virus less of a chance to spread further and mutate, experts have said.

Vaccinating as many people as possible will also be a big help in slowing any more surges -- but Dr. Josh Schiffer, an infectious diseases specialist at Fred Hutchinson, said the new, infectious variants make it "difficult to prevent a fourth wave altogether."

To speed up vaccinations, one report suggests the US should consider skipping second doses for now. People over 65 should go to the front of the line since they're by far the most vulnerable to severe disease and death, according to a recommendation from Mike Osterholm and his colleagues at the University of Minnesota's Center for Infectious Disease Research and Policy.

Quote from Fm1

To speed up vaccinations, one report suggests the US should consider skipping second doses for now.

This seems like a good idea. They are doing this in the UK. On the other hand, the three manufacturers (including J&J) say they are ramping up production and they will have 120 million doses by the end of March. So maybe this is not necessary? Not in the U.S., anyway, although it might be a good idea to ship millions of doses to Canada and the Third World.

There are reportedly more than enough doctors and nurses to administer 5 million doses per day, or more. Drug stores administer millions of doses of flu vaccine per day in September.

Quote from Alan Smith

The friends and family of the 120,00 UK covid corpses might not agree with your point of view.

You misuse the data. We had a larger peek than UK already without the UK mutation. So its really a made up a problem. I explained the details in earlier posts.

You should deliver fact based answers!

mast cell activation and covid part 1

Quote from Alan Smith

That's real enough for me.

It was about variants that are dangerous. E.g. RSA/BRA/California are of concern not UK1.1.7.1...

Alan wrote this in response to the statement: "The UK variant was never a frightening problem."

Quote from Alan Smith

The friends and family of the 120,00 UK covid corpses might not agree with your point of view.

I think he means the COVID is frightening in all forms, both the original and the UK variant. I guess the UK variant is even more frightening.

Fortunately, it seems the present vaccines are effective against it. If they are not, a new formula can be devised and tested quickly with the mRNA vaccines. In the U.S. the FDA says it would not even require a new set of safety tests. I guess that means it would be very similar. That's remarkable. In the worst case, everyone would have to undergo a third round of vaccinations. A booster to the booster. People who never got the first one should be protected from all variants with a revised vaccine. That's my understanding from mass media reports.

I hope the J&J vaccine works against the UK variant. Supposedly, they are going to allow the J&J starting on February 27. Unfortunately, J&J has only a few million manufactured and stockpiled. They say they will have 20 million by the end of March.

This situation with not enough vaccines now but a flood of vaccines in a month or two reminds of World War II. UK and U.S. arms production began to increase in 1939, but there was not enough of anything through 1940 and 1941. Finally, in 1942, U.S. production capabilities began to tell, and there was enough to send to the UK, Russia, and to supply U.S. forces. Then in 1943, 44 and 45, mountains of supplies were finally available. Too much, in some ways. Thousands of airplanes ended up unused, and were scrapped. Freeman Dyson described the building of factories and cranking up production: "you can have anything you want, in two years."

With a pandemic, you know how many vaccines you need. You can plan for it. In a war, you never know how many airplanes and tanks are needed. During WWII a member of Congress said to a general: "We seem to be manufacturing huge numbers of tanks and sending them to Europe. Are we making too many?" The general replied, "better a thousand too many than one not enough."

New California coronavirus variant is spreading really fast, study says

https://www.latimes.com/scienc…ansmissible-and-dangerous

A coronavirus variant that probably emerged in May and surged to become the dominant strain in California not only spreads more readily than its predecessors but also evades antibodies generated by COVID-19 vaccines or prior infection and is associated with severe illness and death, researchers said.

In a study that helps explain the state’s dramatic holiday surge in COVID-19 cases and deaths — and portends further trouble ahead — scientists at UC San Francisco said the cluster of mutations that characterizes the homegrown strain should mark it as a “variant of concern” on par with those from the United Kingdom, South Africa and Brazil.

Californians, along with the rest of the country, have been bracing for an onslaught of the more transmissible strain from the U.K. known as B.1.1.7. But they should know that a rival strain that is probably just as worrisome has already settled in, and will probably account for 90% of the state’s infections by the end of next month, said Dr. Charles Chiu, an infectious diseases researcher and physician at UCSF.

“The devil is already here,” said Chiu, who led a team of geneticists, epidemiologists, statisticians and other scientists in a wide-ranging analysis of the new variant, which they call B.1.427/B.1.429. “I wish it were different. But the science is the science.”