Search This Blog

Wednesday, March 31, 2021

Germany and Canada restrict AZ vaccine over blood clot fears

 Germany and Canada have both slapped restrictions on the AstraZeneca vaccine, recommending its use only in older patients, because of concerns over a link with blood clots.

The moves come after the country’s medicines regulator found 31 cases of a rare type of blood clot known as cerebral venous sinus thrombosis (CVST) in people who had received the vaccine produced by AZ.

The decision to restrict use of the shot in under-60s comes from Germany’s independent vaccine committee known as STIKO made the decision based on available data about the blood clotting events.

The decision runs counter to central guidance from the European Medicines Agency’s safety committee, which earlier this month said the AZ vaccine was safe and effective following a thorough review including incidences of CVST.

It is also a reversal of a previous position, where German authorities said that the AZ vaccine should not be used in patients in over 65, because of the smaller number of older patients in the first trials of the shot.

According to STIKO the side effect occurred four to 16 days after vaccination and was predominantly seen in people under 60 years of age.

The committee will address the issue of whether younger people who have already received a first dose of the AZ vaccine.

Germany’s Paul Ehrlich Institute said that within the 31 cases of CVST, there were 19 cases of thrombocytopenia.

Of those nine cases of thrombocytopenia, nine of the people affected died.

All but two of the 31 cases involved women aged 20 to 63 while two men affected were 36 and 57 years old, the institute said.

The decision had a knock-on effect: Canada’s National Advisory Committee on Immunization (NACI) also suspended vaccinations in those aged under-55s in updated guidance published earlier this week.

Several provinces have now suspended use of the vaccine for anyone below the age of 55 while Health Canada, the country’s central regulator, assesses the risk.

https://pharmaphorum.com/news/germany-and-canada-restrict-az-vaccine-again-over-blood-clot-fears/

Data Suggest Vaccinated Individuals Don't Carry Virus or Get Sick: CDC

 As COVID-19 cases continue to decline and vaccinations rise, people that have been fully vaccinated are wondering if they could still get the virus and if they can spread it.

“This pandemic, everything is so new, everything is constantly changing constantly evolving,” said teacher Angela Dancheva. 

The San Jose resident is fully vaccinated and not quite sure what to think about information that comes out of the Centers for Disease Control and Prevention (CDC).

“They are always changing,” said hospitality worker Yvonne Duarte. “The only thing I can say is just be informed do the best that you can.”

Their reaction comes after hearing this statement from CDC Director Dr. Rochelle Walensky.

“Our data from the CDC today suggests that vaccinated people don’t carry the virus, don’t get sick and that it’s not just in clinical trials, but it’s also in real world data,” said Walensky.

The director is referring to a new study of nearly 4,000 frontline workers, some vaccinated and some not. They tested themselves weekly for COVID-19 infections between December and March.

Among fully vaccinated people in the study, there were only three COVID-19 infections detected.

Unvaccinated participants logged 161 covid cases, scientific evidence experts say proves fully-vaccinated people are protected in two ways.

“Essentially vaccines block you from getting and giving the virus,” said UCSF Infectious Disease Specialist Dr. Monica Gandhi, adding this new information is significant.

“You can feel safe as a vaccinated person going indoor dining, going to a gym, going to the movies, going to places you did not feel safe before,” said Ghandi.

You can feel safe, she said, without being reckless.

“Now they can rewrite guidelines and say vaccinated people can be around unvaccinated people even without masks and distancing,” said Ghandi. “Not out in public because we don’t know who is vaccinated and who is not,  still going to maintain masks and distancing until everyone who wants to get a vaccine can get it.”

https://www.nbcbayarea.com/news/coronavirus/vaccinated-individuals-dont-carry-virus-or-get-sick-cdc/2506677/

Blood Clots and the AZ Vaccine, Revisited

By Derek Lowe

Once again, what’s going on with vascular events and the AZ/Oxford vaccine? I last wrote about this situation a couple of weeks ago, and it’s taken some real turns since then. At that point several EU countries had suspended dosing, but over the next week several began administering the vaccine again after the European Medicines Agency recommended it, in some cases with advisories about which age groups should be targeted.

But there’s more to the story, it seems. Here’s an excellent writeup at Science (open access) by Kai Kupferschmidt and Gretchen Vogel.   A possible concern is what’s being called vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) by Andreas Greinacher at Univ. Griefswald. This is a blood clotting syndrome that’s similar to what’s observed with the (already known) syndrome of heparin-induced thrombocytopenia. That problem, first over 40 years ago, is a paradoxical effect that occurs in a few people of administering heparin for blood clotting problems and actually making the situation worse. The mechanism for HIT is apparently the generation of antibodies to the complex of heparin bound to platelet factor 4 (PF4) protein. That binding sets off further inappropriate platelet activation, and that’s why the free platelet count drops (the “thrombocytopenia” part) as new clots form and existing blood clots become larger and more dangerous. You’d be used to someone presenting with thrombocytopenia to be at risk for bleeding disorders, not suffering from too many blood clots, but HIT is coming around from the other direction.

Greinacher’s team showed that patients who developed clotting disorders after vaccination showed the anti-heparin/PF4 antibodies, as in HIT, but it looks like these also bind to PF4 even when it’s not complexed to heparin. It’s possible that this happens (at least partially) via the adenovirus vector binding to platelets, but the details aren’t clear. There apparently is a subset of “classic” HIT cases who have shown this atypical PF4-alone antibody binding, so it’s a phenomenon that can happen without vaccination. The question, though, is whether vaccination is making it more likely, and whether there are particular populations who are more at risk.

Kupferschmidt passed on more information from Germany’s Paul-Ehrlich Institute just this morning. 2.7 million people have received the AZ/Oxford vaccine there, and 31 patients have been identified with cerebral venous thrombosis. Not all of those are HIT or VIPIT, though, because only 19 of the 31 had thrombocytopenia. There have been nine deaths, and as always, key questions are how many cases one would expect in the population that’s been dosed so far. Earlier this month, the figures were 1.7 million vaccinated and 7  cases of CVT, and the institute said that they would have expected about one case as normal background. The EMA, when they came out recommending the vaccine earlier this month, noted that figuring these background rates is not easy. But they found that if there is indeed an imbalance, it’s most noticeable in the younger age cohort and not in the older. The PEI mentioned today that of the 31 cases they have analyzed, 29 of them have been women, which certainly seems significant as well.

The UK experience with this vaccine has apparently shown no overall increase in thrombotic events – if anything, the vaccinated cohort has been slightly lower in that regard than the general population. But if there is an increased risk in people under 50, especially women, that’s actionable, as they say, even if the risk is very small (as it certainly appears to be). Other vaccines need to be available so that the doses can be aimed better. It’s also worth remembering that HIT (and presumably VIPIT, if it does turn out to be a real subset) can be treated with non-heparin anti-clotting drugs and/or by immunoglobin infusions, so the attempts by the EMA and others to raise awareness among physicians of this side effect are well worth it.

This is all happening against a background of increased infection in many European countries, of course. A worry is that some people will decide not to get vaccinated at all after hearing about these side effects, and regions where most of the available vaccine is the AZ/Oxford one may well see people deciding to wait for a different one, if that’s a possibility. If such things noticeably affect the number of people getting vaccinated, they could easily end up killing off more people in general than any of the vascular side effects will. But it’ll be in different groups – if the information we have now holds up, then younger women would be at small-but-greater-than-others risk of side effects, but the pandemic fatalities would probably be more in older men. A grim thing to be totaling up – more on this as we get more information.

https://blogs.sciencemag.org/pipeline/archives/2021/03/30/blood-clots-and-the-az-vaccine-revisited

Blood from critically ill COVID-19 patients contains antibodies that contribute to clotting

 A McMaster University-led study has teased out the reason for blood clots caused by COVID-19, a serious potential complication of the virus.

Blood from critically ill COVID-19 patients contains antibodies that can contribute to clotting, says Ishac Nazy, associate professor of medicine and director of the McMaster Platelet Immunology Laboratory. These antibodies form immune complexes that activate platelets, the cells that lead to  clotformation. Some blood-thinner medications can block these immune complexes and potentially reduce clots.

"By discovering the mechanism, we can inform doctors on the use of blood-thinners, known as anticoagulants, that can stop the clotting in COVID-19 patients," said Nazy, whose findings have been published in the Journal of Thrombosis and Haemostasis.

Nazy said his laboratory suddenly saw an increase in patients with blood clots at the onset of the pandemic in Canada in early 2020, as COVID-19 began spreading worldwide.

At first, Nazy and his colleagues thought these patients had heparin-induced thrombocytopenia (HIT), a clotting condition that can occur in patients given heparin, ironically an anticoagulant medication.

However, these patients tested negative for HIT, despite being at medium to high-risk of the condition. Instead, these critically-ill patients were positive for COVID-19, which can also cause life-threatening blood clots.

Of the 10 patient blood samples tested by Nazy, six had platelet-activating immune complexes when their  were tested in the lab. These  were not found in eight recovered COVID‐19 patients or pre-pandemic patient samples.

Nazy said this discovery gives  better insight into the underlying mechanisms of COVID-19 and potential future therapies to combat .

This is increasingly important with the recent information regarding the clotting complication in a few patients who have received the AstraZeneca vaccine in several European countries. The mechanisms of clotting could potentially be similar in response to the infection by the virus or by the vaccines.

More information: Ishac Nazy et al. Platelet‐activating immune complexes identified in critically ill COVID‐19 patients suspected of heparin‐induced thrombocytopenia, Journal of Thrombosis and Haemostasis (2021). DOI: 10.1111/jth.15283

https://medicalxpress.com/news/2021-03-blood-critically-ill-covid-patients.html

Closer look urged at sunlight's efficacy in inactivating SARS-CoV-2 virus

 A year ago scientists everywhere were scrambling to get their minds around the SARS-CoV-2, a novel coronavirus that caused the pandemic from which we are only now beginning to emerge. The world clung to every new development, every bit of science that could provide clues to managing life in the presence of this mysterious killer.

Many science-backed COVID-19 management concepts remain unchanged to this day: handwashing with soap and warm water disrupts the virus' lipid membrane. Social distancing can attenuate the virus's spread, ideally keeping it out of a host until it degrades. Other notions, such as droplet contact being the primary mode of transmission, were modified when emerging evidence showed that under certain conditions, the virus could remain suspended in air for extended periods of time.

In a letter in the Journal of Infectious Diseases, a team of researchers from UC Santa Barbara, Oregon State University, University of Manchester and ETH Zurich examines another of SARS-CoV-2's well known characteristics—its vulnerability to sunlight. Their conclusion? It might take more than UV-B rays to explain sunlight inactivation of SARS-CoV-2.

The idea that an additional mechanism might be in play came when the team compared data from a July 2020 study that reported rapid sunlight inactivation of SARS-CoV-2 in a lab setting, with a theory of coronavirus inactivation by  that was published just a month earlier.

"The theory assumes that inactivation works by having UV-B hit the RNA of the virus, damaging it," said UC Santa Barbara mechanical engineering professor and lead author Paolo Luzzatto-Fegiz. Judging from the discrepancies between the experimental results and the predictions of the theoretical model, however, the research team felt that RNA inactivation by UV-B "might not be the whole story."

According to the letter, the experiments demonstrated virus inactivation times of about 10-20 minutes—much faster than predicted by the theory.

"The theory predicts that inactivation should happen an order of magnitude slower," Luzzatto-Fegiz said. In the experiments, viruses in simulated saliva and exposed to UV-B lamps were inactivated more than eight times faster than would have been predicted by the theory, while those cultured in a complete growth medium before exposure to UV-B were inactivated more than three times faster than expected. To make the math of the theory fit the data, according to the letter, SARS-CoV-2 would have to exceed the highest UV-B sensitivity of any currently known virus.

Or, Luzzato-Fegiz and colleagues reasoned, there could be another mechanism at play aside from RNA inactivation by UV-B rays. For instance, UV-A, another, less energetic component of sunlight might be playing a more active role than previously thought.

"People think of UV-A as not having much of an effect, but it might be interacting with some of the molecules in the medium," he said. Those reactive intermediate molecules in turn could be interacting with the virus, hastening inactivation. It's a concept familiar to those who work in  and other environmental science fields.

"So, scientists don't yet know what's going on," Luzzatto-Fegiz said; "Our analysis points to the need for additional experiments to separately test the effects of specific light wavelengths and medium composition."

Results of such experiments might provide clues into new ways of managing the virus with widely available and accessible UV-A and UV-B radiation. While UV-C radiation is proved effective against SARS-CoV-2, this wavelength does not reach the earth's surface and must be manufactured. Although UV-C is presently used in air filtration and in other settings, its short wavelengths and  also makes UV-C the most damaging form of UV radiation, limiting its practical application and raising other safety concerns.

"UV-C is great for hospitals," said co-author Julie McMurry. "But in other environments—for instance kitchens or subways—UV-C would interact with the particulates to produce harmful ozone." While no single intervention will eliminate risk, this research would provide one further tool to reduce exposure, thus slowing transmission and improving health outcomes.

Co-author and UCSB mechanical engineering professor Yangying Zhu added that UV-A turning out to be capable of inactivating the  could be very advantageous: there are now widely available inexpensive LED bulbs that are many times stronger than natural sunlight, which could accelerate inactivation times. UV-A could potentially be used far more broadly to augment air filtration systems at relatively low risk for human health, especially in high-risk settings such as hospitals and public transportation, but the specifics of each setting warrant consideration, said co-author Fernando Temprano-Coleto.


Explore further

Electrochemical oxidation to inactivate SARS-CoV-2

More information: Paolo Luzzatto-Fegiz et al. UVB Radiation Alone May Not Explain Sunlight Inactivation of SARS-CoV-2, The Journal of Infectious Diseases (2021). DOI: 10.1093/infdis/jiab070
https://medicalxpress.com/news/2021-03-urge-closer-sunlight-efficacy-inactivating.html

Sanofi Discloses 7% Stake in Lava Therapeutics

 


  1.   

  Names of Reporting Persons

 

  SANOFI

  2. 

  Check the Appropriate Box if a Member of a Group (See Instructions)

  (a)  ☐        (b)  ☐

 

  3. 

  SEC Use Only

 

  4. 

  Citizenship or Place of Organization

 

  The Republic of France

Number of

Shares

 Beneficially 

Owned by

Each

Reporting

Person

With

  5.    

  Sole Voting Power

 

  1,919,455 shares

  6.  

  Shared Voting Power

 

  0 share

  7.  

  Sole Dispositive Power

 

  1,919,455 shares

  8.  

  Shared Dispositive Power

 

  0 share

  9.   

  Aggregate Amount Beneficially Owned by Each Reporting Person

 

  1,919,455 shares

10. 

  Check if the Aggregate Amount in Row (9) Excludes Certain Shares (See Instructions)

 

  ☐

11. 

  Percent of Class Represented by Amount in Row (9)

 

7.0%

12. 

  Type of Reporting Person (See Instructions)

 

  CO

 

2


Item 1.
  (a)  Name of Issuer
LAVA Therapeutics N.V.
  (b)  Address of Issuer’s Principal Executive Offices
Yalelaan 60, 3584 CM Utrecht, The Netherlands
Item 2.
  (a)  Name of Person Filing
Sanofi
  (b)  Address of Principal Business Office or, if none, Residence
54 Rue La Boétie, 75008 Paris (France)
  (c)  Citizenship
The Republic of France
  (d)  Title of Class of Securities
Common Shares, €0.12 par value
  (e)  CUSIP Number
N51517105
Item 3.  If this statement is filed pursuant to §§240.13d-1(b) or 240.13d-2(b) or (c), check whether the person filing is a:
  (a)    Broker or dealer registered under section 15 of the Act (15 U.S.C. 78o);
  (b)    Bank as defined in section 3(a)(6) of the Act (15 U.S.C. 78c);
  (c)    Insurance company as defined in section 3(a)(19) of the Act (15 U.S.C. 78c);
  (d)    Investment company registered under section 8 of the Investment Company Act of 1940 (15 U.S.C. 80a-8);
  (e)    An investment adviser in accordance with §240.13d-1(b)(1)(ii)(E);
  (f)    An employee benefit plan or endowment fund in accordance with §240.13d-1(b)(1)(ii)(F);
  (g)    A parent holding company or control person in accordance with §240.13d-1(b)(1)(ii)(G);
  (h)    A savings association as defined in Section 3(b) of the Federal Deposit Insurance Act (12 U.S.C. 1813);
  (i)    A church plan that is excluded from the definition of an investment company under section 3(c)(14) of the Investment Company Act of 1940 (15 U.S.C. 80a-3);
  (j)    non-U.S. institution in accordance with § 240.13d–1(b)(1)(ii)(J);

 

  

(k)

  

  

Group, in accordance with § 240.13d–1(b)(1)(ii)(K). If filing as a non-U.S. institution in accordance with

§ 240.13d–1(b)(1)(ii)(J), please specify the type of institution:____________________________

 

3



Item 4.  Ownership
Provide the following information regarding the aggregate number and percentage of the class of securities of the issuer identified in Item 1.
  (a)  

Amount beneficially owned:

1,919,455 shares

  (b)  

Percent of class:

7.0%

  (c)  Number of shares as to which the person has:
    (i)  

Sole power to vote or to direct the vote

1,919,455 shares

    (ii)  

Shared power to vote or to direct the vote

0 share

    (iii)  

Sole power to dispose or to direct the disposition of

1,919,455 shares

    (iv)  

Shared power to dispose or to direct the disposition of

0 share


https://www.streetinsider.com/SEC+Filings/Form+SC+13G+LAVA+Therapeutics+NV+Filed+by%3A+Sanofi/18203652.html

Biden $2T infrastructure plan: 5 notes for healthcare leaders

 The White House on March 31 unveiled an approximately $2 trillion jobs and infrastructure plan that includes expanding access to long-term care services and other healthcare-related measures. 

The proposal, called the American Jobs Plan, targets aging highways and bridges, as well as climate change, the nation's digital infrastructure and home care. 

Here are five notes about the plan for healthcare leaders.

1. President Joe Biden's proposal provides $18 billion for upgrading veterans hospitals and clinics. 

2. The plan includes $400 billion to expand access to home- or community-based care for older Americans and disabled people under Medicaid. According to USA Today, this would involve aid to Americans to obtain long-term services and support, as well as increasing wages for essential home care workers who currently earn about $12 per hour.

3. The White House said President Biden's administration also wants to extend the long-standing Money Follows the Person program under Medicaid. The program, in part, aims to boost use of home and community-based services and reduce use of nursing homes and other institutionally based services.

4. President Biden's plan is partly paid for by increasing the corporate tax rate and global minimum tax, according to The Washington Post. The plan increases the corporate tax rate from 21 percent to 28 percent and the global minimum tax for U.S. multinational corporations from about 13 percent to 21 percent.

5. Republicans and business groups have criticized President Biden's plans for corporate tax increases because they contend it will hurt competition among American companies, according to The New York Times

https://www.beckershospitalreview.com/hospital-management-administration/biden-s-2-trillion-infrastructure-plan-5-notes-for-healthcare-leaders.html