Do Vaccines Help COVID Long-Haulers?

 Some people suffering from long COVID have found significant symptom relief after the first dose of their COVID-19 vaccine, though the jury's still out as to whether that's the case for the majority of so-called long-haulers.

Last week, New York Times editorial board member Mara Gay tweeted that she felt significantly better after her first vaccine dose.

She acknowledged that her report was both "anecdotal and early," but that many other long COVID survivors had described a similar experience.

Several commenters responded to Gay that they, too, had significant symptom relief after their first dose, including Sharon MacMillan, MD, an ob/gyn in Massachusetts, who said she's been symptom-free for 6 weeks after her vaccine.

There are no definitive data on what percentage of long COVID patients may experience such relief, how long it lasts, or even if the effect is real. But the scientific community has indeed taken an interest, and some have even suggested the possibility of prospective studies.

The Data

Hannah Davis, co-chief of Patient-Led Research for COVID-19, said her organization is currently working on a survey to study the phenomenon.

"While there have been anecdotes of this happening, they generally seem to be in the minority so far," Davis told MedPage Today.

She pointed to a video report by U.K. film producer and long COVID patient Gez Medinger on results of an informal survey of long COVID patients from various Facebook groups and the Body Politic Slack group, another organization that has been tracking COVID long-haulers.

Medinger's survey had 473 responses -- 80% from the U.K. and 15% from the U.S.; 86% women -- and he had the help of a statistician when analyzing his results. The majority of patients received Pfizer's vaccine (60%), followed by AstraZeneca (30%) and Moderna (9%).

One week after their first dose, 9% of patients said their long COVID symptoms had improved, and by 2 weeks, 16% said their symptoms were much better.

Among all people who had their vaccine 2 weeks ago or longer, 27% said their long COVID symptoms are slightly better, while just 14% said their symptoms were slightly worse. About 5% felt completely back to normal and only 3.8% felt much worse than previously.

"Taking the vaccine is more likely to completely resolve your symptoms than it is to make you feel much worse," Medinger said. "It's almost twice as likely to make you feel slightly better than slightly worse."

He cautioned that a limitation of the survey is that there's no comparison group, so it's impossible to say whether people may have started to feel better on their own, without the vaccine.

Experts have indeed proposed the idea of a prospective study to see the impact of the vaccine on long-haulers. Akiko Iwasaki, PhD, of Yale University, tweeted that such a trial may be difficult, but is worth considering, given that it could potentially confirm vaccination as a therapy for long COVID.

Iwasaki tweeted out Medinger's video, saying that "while the numbers are still small in some groups, there are encouraging signs," and presented hypotheses on how vaccines may improve long COVID.

The Immunology

In June, Iwasaki proposed three potential mechanisms for long COVID: a persistent viral reservoir; viral fragments or remnants that drive inflammation; or an autoimmune response induced by the infection. Many papers have since provided support for all three theories, she said, noting that they're not mutually exclusive.

It could be that vaccine-induced T-cell and antibody responses can eliminate the viral reservoir or the viral fragments/remnants, or that the vaccine somehow diverts autoimmune cells, she tweeted.

Vaccines could also help by stimulating the innate immune response, she said. That transient inflammation may divert leukocytes causing long COVID. But if that is indeed the case, she warned, any benefit from vaccines wouldn't be sustained long-term.

Other experts agreed that studying the impact of vaccines on this population would be worthwhile.

Elisa Perego, a research associate at University College London, who coined the phrase "long COVID," agreed that there's a need for "appropriate data collection and clinical trials."

"We also need to verify whether any improvement -- if such improvements are indeed recorded and linked to vaccination -- is permanent or not," Perego added. "Data on the effects of vaccination on long COVID ... could help [us] understand whether people living with long COVID should have fast access to vaccines, among other target groups like those with pre-existing conditions or the elderly."

"It's a fascinating observation," Stanley Weiss, MD, an infectious disease specialist and epidemiologist at Rutgers New Jersey Medical School, told MedPage Today. "The way you progress in science and medicine, is that you take observations from astute observers and pursue them with scientific rigor."

https://www.medpagetoday.com/special-reports/exclusives/91476

How Do COVID-19 Vaccines Compare?

 

While direct comparisons can't be made because head-to-head trials don't exist, people are questioning how the three COVID-19 vaccines authorized in the U.S. stack up.

Below are the key characteristics of each of those vaccines. This list will be updated as additional vaccines become available.

Company: Pfizer/BioNTech

Vaccine Name: BNT162b2

Mechanism of Action: mRNA vaccine

Dosing Schedule: Two doses, 21 days apart (30 μg/dose)

Efficacy: 95% at least 7 days after dose 2

Illness was defined as having a confirmed positive COVID-19 test and at least one of the following symptoms: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting.

Trial Participants: 43,548 people age 16 and up

Side Effects: Most common were fatigue and headache after both doses, with both being more prominent after the second dose. These were milder for participants over 55 compared with those age 16 to 55. In this latter group, the rates of fatigue and headache were 59% and 52%, respectively, after dose 2.

Storage: Ultra-cold freezer required, -112ºF to -76ºF (-80ºC to -60ºC) for up to 6 months; FDA recently agreed to allow storage of frozen, undiluted vials at standard pharmacy freezer temperatures between -13ºF and 5ºF for up to 2 weeks.

Variants: No clinical data; lab studies have shown that the South African (B.1.351) variant may reduce antibody titers by two-thirds. Pfizer is studying a third "booster" dose of the original vaccine against this variant, as well as evaluating a variant-specific vaccine with a modified mRNA sequence.

Number of Doses Contracted by the U.S.: 300 million

-- -

Company: Moderna

Vaccine Name: mRNA-1273

Mechanism of Action: mRNA vaccine

Dosing Schedule: Two doses, 28 days apart (100 μg/dose)

Efficacy: 94.1% at least 14 days after dose 2

Illness was defined as having a confirmed positive COVID-19 test and at least two of the following symptoms: fever, chills, myalgia, headache, sore throat, new olfactory or taste disorder; or at least one respiratory sign or symptom including cough, shortness of breath, or clinical or radiographic evidence of pneumonia.

Trial Participants: 30,420 people age 18 and up

Side Effects: Overall systemic adverse events including fever, chills, headache, and myalgia were recorded in 60% of participants after the first dose and in 80% of participants after the second dose.

Storage: Frozen between -13ºF to 5ºF (-25ºC to -15ºC); can be stored refrigerated from 36ºF to 46ºF (2ºC to 8ºC) for up to 30 days prior to first use.

Variants: No clinical data; lab studies found no significant impact on neutralizing antibodies with the U.K. variant (B.1.1.7) but a six-fold reduction in neutralizing antibodies with the South African variant (B.1.351). Moderna plans to test a variant-specific booster candidate, a multivalent booster candidate, and a third dose of the original vaccine at 50 μg.

Number of Doses Contracted by the U.S.: 300 million

-- -

Company: Johnson & Johnson/Janssen

Vaccine Name: Ad26.COV2.S

Mechanism of Action: Adenovirus vector vaccine

Dosing Schedule: One dose (two-dose regimen under evaluation)

Efficacy: 72% in the U.S. and 66% globally against moderate-to-severe disease; 85% effective against severe disease, 28 days after a single dose

Moderate illness was defined as a confirmed positive COVID-19 test plus one more of the following: evidence of pneumonia, deep vein thrombosis, shortness of breath or abnormal blood oxygen saturation above 93%, abnormal respiratory rate (≥20); or two or more systemic symptoms suggestive of COVID-19. Severe illness was defined as a confirmed positive COVID-19 test plus one or more of the following: signs consistent with severe systemic illness, admission to an intensive care unit, respiratory failure, shock, organ failure, or death.

Trial Participants: 43,783 people age 18 and up

Side Effects: Most common systemic reactions were headache (39%), fatigue (38%), myalgia (33%), nausea (14%), and fever (9%).

Storage: Stable for 2 years at -4ºF (-20ºC) but can be stored for at least 3 months at typical refrigeration temperatures of 36ºF to 46ºF (2ºC to 8ºC).

Variants: 57% efficacy in South Africa; 66% efficacy in South America (Brazil was among the countries studied, but there were no sequenced cases of the P.1 variant)

Number of Doses Contracted by the U.S.: 100 million

https://www.medpagetoday.com/special-reports/exclusives/91489

Indian vaccine giant SII warns of supply hit from U.S. raw materials export ban

 

A temporary U.S. ban on exports of critical raw materials could limit the production of coronavirus vaccines by companies such as the Serum Institute of India (SII), its chief executive said in a World Bank panel discussion https://www.worldbank.org/en/events/2020/12/14/7th-south-asia-economic-policy-network-conference-on-vaccinating-south-asia on Thursday.

SII, the world's biggest vaccine maker, has licensed the AstraZeneca/Oxford University product and will soon start bulk-manufacturing the Novavax shot.

"There are a lot of bags, filters and critical items that manufacturers need," Adar Poonawalla said. "The Novavax vaccine, which we are a major manufacturer of, needs these items from the U.S."

He said the recent invocation of the U.S. Defence Production Act to preserve vaccine raw materials for its own companies went against the global goal of sharing vaccines equitably.

The White House said this week it had used the act to help drugmaker Merck & Co produce Johnson & Johnson's COVID-19 vaccine.

"This really needs to be looked at because if they are talking about building capacity all over the world, the sharing of these critical raw materials, which just can't be replaced in a matter of six months or a year, is going to become a critical limiting factor," Poonawalla said.

India's Biological E has tied up with J&J to potentially contract manufacture up to 600 million doses of its vaccine per year. They have signed an initial deal but production volumes have not been agreed upon.

https://www.marketscreener.com/quote/stock/ASTRAZENECA-PLC-4000930/news/AstraZeneca-nbsp-Indian-vaccine-giant-SII-warns-of-supply-hit-from-U-S-raw-materials-export-ban-32614382/

Boston Scientific’s next targets

 With the purchase of Lumenis’s surgical laser business for $1.1bn on Wednesday and a $925m pounce on the cardiac monitoring group Preventice in January, Boston Scientific is very much following its plan to acquire high-growth companies to dig itself out of the hole Covid-19 put it in. 

And it is sticking to the script in another way. Preventice and Lumenis both had prior agreements with their buyer, chiming with Boston’s stated preference for acquiring companies with which it has a pre-existing relationship. A look at the groups in which Boston has recently invested, then, might give a clue towards its future purchases. 

Acquiring a company having first invested in it a common occurrence in medtech, but Boston is unusual in pursuing this as a defined strategy – almost as a particularly thorough form of due diligence.

Over the past three years Boston has bought four companies with which it was already, in some way, involved. Its partnership with Lumenis dates back more than 20 years (March medtech merger madness, March 4, 2021).

Boston had minority stakes in Preventice and the heart valve repair specialist Milipede before buying them, and had backed stent maker Veniti via its corporate VC arm.

Companies Boston has acquired after partnering or investing, 2018-21
Company	Focus	Date acquired	Acquisition value ($m)	Prior relationship
Surgical laser business of Lumenis	Surgery	Mar 3, 2021	1,070	Distribution partnership since 2002
Preventice	Patient monitoring	Jan 21, 2021	925	Has invested since 2015; has equity stake of approx 22%
Milipede	Cardiology	Jan 29, 2019	450	Took minority stake in 2018
Veniti	Cardiology	Aug 31, 2018	160	Participated in $25m series D in 2016
Source: EvaluateMedTech.

Boston has made it clear that it will remain keen on M&A throughout 2021 and probably beyond. A glance at its recent investments might offer an idea of its priorities.

The clearest signal is surely the option it took in September to acquire Farapulse. This private group is developing a device, Farapulse PFA, to ablate cardiac tissue to treat atrial fibrillation. Unlike current cardiac ablation devices, which scar heart muscle using either radiofrequency energy or extreme temperatures, Farapulse’s tech uses electrical fields. The company maintains that this allows greater precision than existing techniques. 

The system is in a pivotal US trial, Advent, in which 900 patients will be randomly assigned to either Farapulse PFA or, in the control group, radiofrequency or thermal ablation. According to clinicaltrials.gov, data could emerge by mid-2023; perhaps at that point Boston might pull the trigger. 

Boston's investments, 2018-21
Company	Focus	Date	Type of investment	Investment ($m)
Farapulse	Cardiac ablation	Sep 21, 2020	Option to acquire	Undisclosed
Saluda Medical	Neuromodulation	Jun 28, 2019	Undisclosed VC	75.0
Intervene	Cardiology	Jun 25, 2019	Series B	15.0
Francis Medical	Urological cancer	Dec 13, 2018	Series A	18.0
Source: EvaluateMedTech.

The recipients of Boston’s three most recent venture investments might be on the menu too. Corporate VCs often cluster together in syndicates, but Boston was the only strategic involved in the three rounds listed above, so no other medtechs have marked out the same territory. 

Of course, this does not make the acquisitions of Saluda, Intervene and Francis by Boston Scientific inevitable. In February 2017 Corindus Vascular Robotics closed a $45m private investment in public equity deal in which both Boston and Philips took part. Two years later Corindus was bought by Siemens Healthineers – and neither Healthineers nor its precursor, Siemens, had ever invested in the group. 

https://www.evaluate.com/vantage/articles/news/deals/boston-scientifics-next-move

How the different Covid vaccines will handle new variants

 New more contagious variants of the coronavirus are being investigated in the United States, raising questions about whether the Covid vaccines currently in use will provide protection against mutations.

There are multiple more contagious variants emerging around the globe, in the United Kingdom, South Africa and Brazil. In the U.S., variants from New York City and California have been identified.

So far, studies suggest that the vaccines currently in use can recognize the emerging variants — but they don’t provide as much protection against these new strains. The variant from South Africa, for example, reduced Pfizer-BioNTech’s antibody protection by two-thirds, according to a February study. Moderna’s neutralizing antibodies dropped six-fold with the South Africa variant.

(There are several reasons the antibodies generated after receiving a vaccine might recognize a variant but not fight it as well. Antibodies protect you by attaching to each individual spike protein on the surface of the coronavirus, which prevents it from infecting your cell. If a variant produces many times more virus, the antibodies may not be able to attach to all those virus pieces as precisely or efficiently.)

But boosters and new versions of vaccines that target the variants are already being explored.

The three vaccines that have been authorized by the Food and Drug Administration for emergency use from Moderna, Pfizer-BioNTech and Johnson & Johnson work in different ways, and therefore have different approaches to handling variants. Here’s what we know:

Moderna

Moderna is testing using a third dose of its existing vaccine, as well as using a booster shot that targets the South Africa variant. (It sent samples to the National Institutes of Health for clinical trials on Feb. 24.)

Moderna’s CEO Stephane Bancel said that the company “is committed to making as many updates to our vaccine as necessary until the pandemic is under control,” in a press release Feb. 24.

Moderna’s vaccine uses messenger RNA or “mRNA” technology to deliver genetic material to cells with instructions for how to make a non-infectious piece of the coronavirus’ spike protein. The immune system recognizes the copies of the spike protein and creates antibodies against it. If a fully vaccinated person is exposed to the actual virus in the future, the body can recall how to trigger an immune response and create antibodies that fight the virus.

The boosters for new variants use the same technology as Moderna’s original Covid vaccine. Bancel has said that it’s essentially a matter of “copying and pasting” the new mutations into the vaccine. Dr. Kizzmekia Corbett, who led the team responsible for Moderna’s vaccine, calls this approach “plug and play.”

It could take months for the clinical data to be ready to review, and even longer for the boosters to be approved, produced and ready to be administered.

Moderna’s president Stephen Hoge told Scientific American that if the variants start to dominate infections in the coming months, the company is prepared to “figure out when we switch and how.” Hoge did not comment on when the booster would be available.

Pfizer-BioNTech

Pfizer-BioNTech is also testing a third booster shot of its vaccine (which is an mRNA vaccine) on people who were fully vaccinated in the Phase 1 study. Participants will get their third dose six to 12 months after they were fully vaccinated, according to a release.

In addition, the company is discussing a clinical trial for “a variant-specific vaccine” that’s a reconstructed version of its original vaccine using the strain from South Africa, according to a release.

“We think our vaccine is robustly active against all strains,” Pfizer Chief Scientific Officer Mikael Dolsten said in an interview Feb. 25. In the future, it’s “a reasonable possibility” that people would need to get regular booster shots, Dolsten said. Or, the companies may need to change the strains every few years to adapt, he said.

Like Moderna, Pfizer’s mRNA vaccine is fairly adaptable.

“The flexibility of our proprietary mRNA vaccine platform allows us to technically develop booster vaccines within weeks, if needed,” Ugur Sahin, CEO and co-founder of BioNTech, said in a release.

“This regulatory pathway is already established for other infectious diseases like influenza. We take these steps in order to ensure a long-term immunity against the virus and its variants.”

Johnson & Johnson

The newest vaccine to gain emergency use authorization from the Food and Drug Administration had a 72% efficacy rate for preventing moderate illness in the U.S. But in South Africa, where a highly contagious mutation of the virus is the primary variant, the effectiveness was 64% effective at preventing moderate to severe or critical Covid, according to FDA data. In Brazil, the vaccine was 66% effective.

(Experts say that it’s worth noting that Johnson & Johnson’s trials took place when the new variants had already become the dominant strains in South Africa and Brazil, while Moderna’s and Pfizer’s trials took place before that happened.)

Johnson & Johnson’s single-dose vaccine uses an adenovirus, a virus that causes the common cold, as a messenger to deliver instructions to the body’s cells.

Johnson & Johnson CEO Alex Gorsky said that the company is well-positioned to adapt the vaccine for variants, and is working on developing software that will “help address some of these new and emerging variants,” during an interview with CNBC’s “Squawk Box” March 1. He did not explain how the software would work.

“We’re quite confident based upon the clinical data that we already have with our vaccine that we’re going to see a very robust response, but we’re simultaneously doing the exact same thing [as other companies working on variants],” Gorsky said.

Novavax

Although Novavax’s Covid two-shot vaccine is not yet approved in the U.S., the company expects that it will get FDA approval by May.

Data from the U.K. trial in January shows that the vaccine was more than 89% effective in protecting against Covid and 85.6% effective against the U.K. variant. But the Novavax vaccine was less than 50% effective on the South African strain.

Novavax is working on a third booster that could be tested in April, a spokesperson for the company told Scientific American.

Novavax is a two-dose “protein subunit vaccine,” meaning it contains harmless pieces of the surface spike protein that directly trigger the immune system. So, essentially, scientists can add different strains to the existing vaccine as variants emerge.

Novavax CEO Stanley Erck told NPR that the Covid vaccines can be tweaked “very easily,” similar to how a flu vaccine is tweaked each year to fit the prominent strains.

It could even end up being a “bivalent vaccine,” which is a vaccine that protects against several strains of a virus. “So we’ll use the original Wuhan strain and the South African strain [to tweak the vaccine] and test it in humans probably in the second quarter of this year,” Erck told NPR.

https://www.cnbc.com/2021/03/05/how-the-different-covid-vaccines-will-handle-variants.html

Abivax stops phase 2b/3 miR-AGE Covid-19 trial due to lack of efficacy

 Abivax (Euronext Paris: FR0012333284 - ABVX), a clinical-stage biotechnology company modulating the immune system to develop novel treatments for inflammatory diseases, viral diseases and cancer, announces today that it is halting the miR-AGE phase 2b/3 clinical trial in high-risk Covid-19 patients after the independent Data Safety and Monitoring Board (DSMB) recommendation for lack of efficacy.

The multinational miR-AGE ABX464 phase 2b/3 clinical trial (ABX464-401), has already recruited 500 high-risk Covid-19 patients out of the planned 1,034 and has been declared "Research National Priority" by the French government in December 2020. The study has a robust randomized, double-blind and placebo-controlled design to test whether ABX464 could prevent the development of severe Covid-19 disease in the participants. The DSMB recommendation is based on a planned, interim analysis evaluating data of 305 high-risk Covid-19 patients who completed the study period. The comparison of the data generated in the patient group treated with ABX464 versus the placebo group, did not show a difference in the rate of severe disease between the placebo group and the ABX464 group. Importantly, ABX464 was well tolerated and safe in these high-risk Covid-19 patients.

Eric Cua, M.D., infectious disease specialist at the University Hospital Center (CHU) of Nice and principal coordinator of the miR-AGE trial in France, said: The very well designed and conducted miR-AGE study aimed at preventing severe acute disease characterized by hyperinflammation and cytokine storm. Thanks to the robust study design, we can rely on the outcome of the interim analysis that showed the futility of the trial. The analysis also confirms the good safety of ABX464. The low rate of severe disease in this high-risk population was unexpected, however, it is good news about the prognosis of high risk Covid-19 patients with the current standard of care and with emerging variants."

https://www.pharmiweb.com/press-release/2021-03-05/abivax-follows-dsmb-recommendation-to-stop-the-phase-2b3-mir-age-covid-19-clinical-trial-due-to-lac

EU regulator advises on use of Lilly's COVID-19 antibody cocktail

 Europe's medicines regulator said on Friday Eli Lilly and Co's antibody drug combination can be used to treat COVID-19 patients who do not require oxygen support and are at high risk of progressing to severe illness.

The recommendation can now be used as guidance in individual European nations on the possible use of the combination of bamlanivimab and etesevimab, before a broader approval is given, the European Medicines Agency (EMA) said. (https://bit.ly/3kMpkZr)

The medicines in the cocktail, given via a drip, belong to a class of drugs known as monoclonal antibodies, which are synthetically manufactured copies of infection-fighting proteins produced naturally by the human body.

The EMA said while results indicated the combination reduced the amount of virus present in the back of the nose and throat, there was some uncertainty around the benefits of using bamlanivimab alone. However, the regulator did not rule out the monotherapy as a possible option.

"In terms of safety, most side effects reported were mild or moderate; however, reactions related to the infusion (including allergic reactions) are likely and should be monitored for," the EMA said.

The results also indicated that the combination and monotherapy led to fewer coronavirus-related medical visits.

The combination was granted U.S. emergency use authorisation last month after a late-stage trial showed the therapies together helped cut the risk of hospitalisation and death in COVID-19 patients by 70%.

The EMA's advice on Lilly's therapy follows similar guidance on Regeneron Pharmaceuticals Inc's antibody treatment last month. The European regulator is currently reviewing a COVID-19 antibody drug from South Korea's Celltrion.

https://finance.yahoo.com/news/1-eu-regulator-advises-lillys-172954536.html