Proven ways to boost Covid-19 vaccination: mandates plus nudges

 The United States is approaching a plateau in vaccination rates at a perilous moment as the highly transmissible Delta variant has become the dominant strain.

People are throwing away their masks and going to restaurants, movies, and traveling as they did in the time before the coronavirus pandemic emerged. New Covid-19 cases have doubled during the last three weeks, with the vast preponderance of hospitalizations and deaths among people who have not been vaccinated. Slightly more than 48% of the population is fully vaccinated, and nearly half of unvaccinated Americans say they won’t get the jab. Some states in the South and Midwest have vaccinated less than 40% of their populations.

It’s time to get serious about vaccination. If we have a checkerboard of communities across America without adequate uptake of Covid-19 vaccines, we will never stem the pandemic.

Evidence-based tools can make us all safer and more secure by making vaccination the default choice in Americans’ everyday lives — in schools, businesses, and hospitals.

The case for vaccine mandates

Let’s begin with vaccine mandates. Writing in STAT, Ezekiel Emanuel and colleagues made the case for mandates in health care settings. There is strong evidence that mandates achieve high immunization coverage in a variety of settings. Influenza vaccination coverage is highest (94.4%) among health workers where vaccination is required.

School entry requirements dramatically boosted and maintained high levels of childhood vaccinations. Colleges and universities have a history of mandating certain jabs such as hepatitis B and meningococcal vaccines. Currently, nearly 600 colleges and universities have announced Covid-19 vaccine requirements. On July 19, a federal judge upheld Indiana University’s vaccine mandate, ruling that it served a valid public health interest. Requiring vaccinations in post-secondary education can help reach young adults who are among the most resistant to Covid-19 vaccinations.

Mandating vaccination as a condition for returning to the workplace would make it the norm, becoming a key setting for expanding vaccine coverage nationally. In fact, many surveys demonstrate an overwhelming majority of Americans support employer requirements for vaccination as a condition to return to work.

Three simple steps would boost vaccine coverage. First, the Food and Drug Administration should grant Covid-19 vaccines a biologics license. States, businesses, and universities would be more inclined to require vaccines that were fully approved than those being administered under emergency use authorization. Many individuals who think the vaccine is “experimental” would be encouraged to get the jab if the FDA granted full approval.

The case is overwhelming, and the FDA shouldn’t wait much longer.

Second, once Covid-19 vaccines are fully approved for all school-age children, the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices should consider recommending their inclusion as a prerequisite for in-person instruction.

Third, the Biden administration should encourage reliable and secure “proof of vaccination” systems. The CDC could fund and offer technical guidance to states, schools, and businesses for the development of trusted systems to confidentially authenticate vaccine status.

Beyond mandates: a ‘nudge’

We understand that vaccine mandates have become a political third rail. There are less restrictive ways to achieve high vaccination coverage. Nudges — ways to influence people’s choices without forbidding any option — are proven to work. One kind of nudge is what we call routine offering. That is, everyone in a given setting — whether it’s a school, workplace, or hospital — is scheduled to receive a Covid-19 vaccine. Most people would get the jab if their peers were all being vaccinated. People could opt out, but not easily. They would have to undergo a process, such as attending a vaccine education session or simply filling out a declaration saying why they won’t get vaccinated. States that have more detailed exemption processes for parental exemptions achieve significantly higher rates of childhood vaccinations. The same dynamic would be effective for Covid-19 vaccines by placing a small burden on those who choose to remain unvaccinated.

Here’s another nudge that’s proven to work. If an employer or college, for example, required unvaccinated members of their community to take safety precautions, which were enforced, most people would not want to undertake the burdens. Those who opt out would have to always use a mask indoors, distance themselves from their peers, and undergo routine testing once or twice every week. Those safety measures are fully justified, but most would want to get back to normal and would just get the jab. Unvaccinated individuals would also not want to be singled out as different from their peers.

Behavioral science research shows the power of nudges to make the healthier and safer choice easier and the risky choice harder. Nudges also operate by showing vaccine-hesitant individuals that their peers are getting the jab. Vaccinations would become routine and expected. They would become a gateway to all the things we value from learning and working to going to the movies, dining in restaurants, attending sporting events, and traveling.

Today, remaining unvaccinated is too casual a choice given its dangers. Refusing to be vaccinated poses major threats to others, especially vulnerable individuals who have weak immune systems or children who can’t be vaccinated. It also prevents our nation from achieving the level of herd immunity to protect everyone from the dangers of Covid-19 and the new variants rampaging through the country.

We need to make being vaccinated the easier default choice. If we do that, watch how quickly we will achieve, and far exceed, President Biden’s goal of 70% of the adult population getting at least one dose. Then we can really celebrate freedom from the coronavirus.

Lawrence O. Gostin is a professor global health law at Georgetown University Law Center where he directs the O’Neill Institute and the World Health Organization Collaborating Center on National and Global Health Law. Scott C. Ratzan is a physician, distinguished lecturer at CUNY Graduate School of Public Health, and executive director of Business Partners to CONVINCE, a global network of employers that promote vaccine literacy and encourage Covid-19 vaccination among employees, suppliers, and customers.

https://www.statnews.com/2021/07/22/proven-ways-to-boost-covid-19-vaccination-mandates-plus-nudges/

How concerned should we be about breakthrough coronavirus infections?

 In the past week, you may have heard about Olympic athletes who are fully vaccinated getting positive Covid tests or people in Provincetown, Mass., or Texas Democrats or the New York Yankees. These are called breakthrough infections, and they’re causing a lot of anxiety about whether the vaccines hold up against the hyper-transmissible Delta variant.

But how concerning are they? And as cases are surging across the country, how much do they matter as a metric of the pandemic when we have a vaccine to protect against severe disease?

STAT spoke with Céline Gounder, a clinical assistant professor of medicine and infectious disease at NYU’s Grossman School of Medicine, host of the “EPIDEMIC” podcast, member of the Biden-Harris Transition Covid-19 Advisory Board, and a member of the class of people we are calling pandemic celebrities.

Dr. Gounder, how concerned are you about these instances of breakthrough infections in people who are fully vaccinated?

I think we really need to better define what we mean by breakthrough infections. That’s really a catch-all for people who might have an infection with no, or very mild, symptoms, all the way to somebody who might end up in the ICU, or even dead. What concerns me is breakthrough disease — people who have significant symptoms, who are struggling to breathe, who are ending up in the hospital, and we really haven’t seen breakthrough disease with the vaccines.

We’ve seen a lot of criticism in recent weeks about the way the CDC is handling the release of data and tracking of these breakthrough infections. Do you think their actions have been sufficient or is there more information that you think we need to have from from federal regulators?

I really think we should be tracking breakthrough infections. And here’s why. Those people who are still getting infected despite being vaccinated, they may not get sick, but it is possible that they could transmit the infection on to others. And so that’s something we still don’t really have a handle on. There is some evidence from the sports leagues, where they do a lot of testing, that some of these people may, in fact, be contagious. And so that is concerning.

The second reason that we really want to be tracking breakthrough infections is for what we call genomic surveillance, which is where we look at new variants that are starting to emerge and what do those look like? You’re more likely to find new emerging variants among people who have breakthrough infections. We’re sort of flying blind with respect to that, because we’re not assessing those breakthrough infections.

All this talk about breakthrough infections or breakthrough disease has also raised the issue of boosters, whether Americans will be required to go back and get reinjected with Covid vaccine. What are your thoughts on that?

First of all, booster is really not the right terminology here. I think the problem with boosters is when people hear that word, they’re like, oh, well, it’s going to be like a flu shot. I’m going to need to get a shot every year. The way I would frame this is much more like, say, a blood pressure medicine that your doctor prescribes you — where you start at one dose and they might adjust the dose over time. Just because we are still figuring out the best dosage regimen for the Covid vaccine does not mean that the vaccines don’t work, and does not mean you’re going to need a yearly Covid shot.

That’s really interesting. Where do you fall on the J&J vaccine and the current information we have about it? There’s so much anxiety because it’s just one dose. There are people who got J&J who are feeling not fully vaccinated with one shot. What do you think?

So first of all, the CDC is looking at this. In fact, the CDC’s ACIP, which is a group of people who advise the CDC on their vaccination guidelines, is meeting today as we speak to evaluate whether additional doses of vaccine should be given, specifically in this case for people who have immunosuppression. But I anticipate they will be looking at other categories of patients as well.

With respect to the J&J vaccine, I think it’s really important for people to understand that this is a very good vaccine. This is why we thought that one dose would be sufficient. Now, what we’re learning is that, particularly against some of these new variants, that one dose of J&J may not be enough. And I think what you will see over the next month or two are recommendations, at least for some subsets of people who got J&J, that they do get an additional dose of vaccine. The other thing that we’re seeing is when you mix and match different types of vaccine, so say J&J, which is very similar to the AstraZeneca vaccine. If you mix and match that with one of the many vaccines like Pfizer or Moderna, you actually get an even better immune response. So I do think you’re going to see more mixing and matching in the future as well.

So sort of a separate matter: We’ve seen cases on the rise across the United States. And as you mentioned, there’s this important differentiation between what might be a positive test versus what might be symptomatic disease or something more serious. And we know that vaccines are effective at limiting severe disease. But at the same time, cases are going up. How should we look at this when we have a relatively high vaccination rate and a lot of available vaccine for anyone who might want it? How should we perceive these rising case counts? How worried should we be, you know, vis-a-vis last year when there were no vaccines?

We are seeing this decoupling between cases and hospitalizations and deaths. So what we mean by decoupling is we’re seeing the cases shoot up more steeply than we are seeing hospitalizations and deaths shoot up. That said, it remains to be seen whether that decoupling holds because we’re still early in our own surge with Delta. And unfortunately, there are parts of the country that really have very low vaccination rates. And we don’t know how much some of these breakthrough infections among vaccinated people might then be contributing to onward transmission and circulation of the virus among unvaccinated people. So that’s really a black box at this time.

It seems like the rise in case counts has also resurrected the whole mask debate and whether we need to be wearing masks. Do we need to think about going back to wearing them?

So this is a really good question. Many local municipalities are looking at this question right now. I was on a call with several New York City public officials yesterday where they were asking for my advice on this question. I think, unfortunately, with the rise of Delta, which is about a thousand times more infectious than the original strains of the virus, we really do need to think about layering protections. And so what are those layers? Vaccination. But some of the other layers that we should consider would be masking indoors when you’re outside of your household bubble, optimizing ventilation in the home — just opening your window works really well. It works even better than many of those units that you can buy to filter the air. I think people really underestimate the power of opening windows. And finally, socializing outdoors as much as possible to minimize your risk. Those would be the things that I think we do need to be thinking about. At the beginning of the pandemic, the CDC said that a close contact was somebody that you’re indoors with unmasked for 15 minutes or more. The equivalent of that with the Delta variant is not 15 minutes, it’s one second.

Does the indoor/outdoor difference in protection still hold? Let’s say, somebody is worried about their unvaccinated child playing in the playground. Is it OK if they’re not wearing a mask?

The way to think about your exposure is dose times time. So your dose is a reflection of how much virus the person is carrying, but it’s also diluted in the air around them. So if you’re indoors, there’s not a lot of air dilution unless you’re opening up windows and doing that sort of thing. When you’re outdoors, it’s almost infinitely diluted. And so outdoors, your risk is really low. I think the only places that would concern me outdoors is if you’re packed in together with people, say, at an outdoor concert or in an outdoor sports sporting event. But in general, outdoors is really pretty safe.

That is reassuring. How are you looking at where the pandemic goes from here? There were a lot of stories a couple of months ago thinking about how does this pandemic end. But we’re in a fourth surge now. And of course, many countries don’t have access to the vaccine yet. How much longer is this going to go on?

Well, remember, pandemic means around the world, so across multiple continents. So if you’re asking, you know, when is the pandemic going to be over? It’s going to be years before this is over. I think what really worries me as somebody who, for the better part of my career, worked in HIV and tuberculosis, those are pandemics. You’re looking at about 3 million or so people dying from TB a year. A similar number of people dying from HIV per year. And that’s something that’s been going on for decades. And so I think this is going to become another disease of the poor and marginalized as the pandemic continues to evolve.

https://www.statnews.com/2021/07/23/how-concerned-should-we-be-about-breakthrough-coronavirus-infections-one-expert-weighs-in/

Case Mounts for COVID Vaccine Boosters in Kidney Transplant Recipients

 Kidney transplant recipients who didn't mount an antibody response to two COVID-19 vaccine doses might benefit from a third jab, a new study suggested.

In kidney transplant patients with no response following their second dose of the Moderna vaccine, 49% of those who received a third shot saw a serologic response -- defined as antibody levels greater than 50 AU/mL -- after a median 28 days (median antibody titers of responders 586 AU/mL), reported Sophie Caillard, MD, PhD, of Strasbourg University Hospital in France, and colleagues.

However, this still left 51% of kidney transplant patients without a response, the group explained in a JAMA research letter.

"The findings in this large group of kidney transplant recipients are in accordance with other studies of solid organ transplant recipients," the researchers pointed out, adding that "the use of a third dose of vaccine may be considered in organ transplant recipients."

However, some kidney transplant patients were more likely to mount a response following a third shot than others.

Specifically, patients who had a weak response after the second dose were more likely to develop an antibody response versus those without an antibody response at all (81.3% vs 27.4%, respectively; mean adjusted difference of antibody titers 894.89 AU/mL, 95% CI 377.41-1,410.37, P=0.001).

Additionally, those taking tacrolimus, mycophenolate, and steroids for immunosuppression were less likely to develop antibodies than those treated with other regimens (35% vs 63%, respectively; mean adjusted difference of antibody titers -697.28 AU/mL, 95% CI -1,193.00 to -201.56, P=0.006).

Of note, there weren't any serious adverse events reported after the third dose.

The study looked at kidney transplant recipients at the outpatient Kidney Transplantation Department of Strasbourg University Hospital from January 20 to June 3. All had a negative history of COVID-19 and SARS-CoV-2 anti-spike IgG levels less than 50 AU/mL. The majority were men, with a median age of 58, and the median time from transplantation was about 5 years.

Most had a deceased kidney donor (77%), and more than half were on tacrolimus plus mycophenolate mofetil/mycophenolic acid and steroids as their immunosuppression maintenance therapy.

One month after receiving their second Moderna dose, 159 kidney transplant patients failed to mount an antibody response. Of this group, 60% had no response at all (titers less than 6.8 AU/mL), and about 40% showed a weak response that still fell under the positivity limit (titers 6.8-49.9 AU/mL).

The standard 100-μg Moderna vaccine dose was administered about 51 days after the second dose.

Response to this booster was measured using Abbott's ARCHITECT IgG II Quant test. According to the manufacturer's label, titers greater than 50 AU/mL were considered positive and correlated with in vitro neutralization of SARS-CoV-2.

"The possibility that patients developed cellular immunity capable of conferring protection against severe disease was not assessed," Caillard's group wrote. "However, the occurrence of severe COVID-19 in some vaccinated transplant recipients may suggest a lack of immunity."

Detailed B-cell and T-cell analyses were not performed, which was a study limitation, they noted.

Disclosures

Caillard and co-authors reported relationships with Astellas, Novartis, Sanofi, Bristol Myers Squibb, Sandoz, Fresenius Medical Care, and Chiesi.

Primary Source

JAMA

Source Reference: Benotmane I, et al "Antibody response after a third dose of the mRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients with minimal serologic response to 2 doses" JAMA 2021; DOI: 10.1001/jama.2021.12339.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/93740

Aclaris target upped to $32 from $27 by Jefferies

 Maintains Buy

https://finviz.com/quote.ashx?t=ACRS

Protagenic Updates Timeline for Trial Enrollment

 Protagenic Therapeutics, Inc. (Nasdaq: PTIX) a biopharmaceutical company focused on developing therapies to treat stress-related neurologic disorders, today announced that upon reviewing its investigational new drug (IND) application filed on June 29th, the U.S. Food and Drug Administration (FDA) has requested that Protagenic provide clinical sites with ready-to-inject clinical vials rather than providing site pharmacies with drug substance to be formulated locally. Implementing this FDA guidance will have the added benefit of Protagenic’s control of the formulation of the final drug product. Protagenic is immediately implementing this required change. As a result of this development, the company expects to refile its IND and commence patient enrollment in the 4th quarter of 2021.

https://finance.yahoo.com/news/protagenic-therapeutics-updates-timeline-commencement-202100878.html

Incyte gets Complete Response Letter in carcinoma trial

 Incyte Corporation (Nasdaq:INCY) today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding its Biologics License Application (BLA) for retifanlimab, an intravenous PD-1 inhibitor, for the treatment of adult patients with locally advanced or metastatic squamous cell carcinoma of the anal canal (SCAC) who have progressed on, or who are intolerant of, platinum-based chemotherapy.

The complete response letter states that the FDA cannot approve the application in its present form. Consistent with the Oncologic Drugs Advisory Committee recommendation on June 24, 2021, the FDA determined that additional data are needed to demonstrate the clinical benefit of retifanlimab for the treatment of patients with advanced or metastatic SCAC. Incyte is reviewing the letter and will discuss next steps with the FDA.

“Patients with SCAC who have progressed after first-line chemotherapy currently do not have approved treatment options,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “While we are not surprised with the FDA decision given the ODAC recommendation, we are disappointed. We remain committed to advancing science to find solutions for patients with unmet medical needs, and we will ensure close coordination with the FDA in order to address feedback and determine next steps for the review of retifanlimab.”

The BLA submission was based on data from the Phase 2 POD1UM-202 trial evaluating retifanlimab in previously treated patients with locally advanced or metastatic SCAC who have progressed on, or were ineligible for or intolerant of, platinum-based chemotherapy.

https://www.businesswire.com/news/home/20210723005449/en/Incyte-Provides-Regulatory-Update-on-Retifanlimab-for-the-Treatment-of-Certain-Patients-with-Squamous-Cell-Carcinoma-of-the-Anal-Canal-SCAC

Tonix stops enrolling Phase 3 fibromyalgia trial after interim analysis

 RALLY Study Will Stop Enrolling New Participants Following Recommendation from an Interim Analysis Indicating Inadequate Separation from Placebo at Week-14 in the First 50% of Participants, Based on the Original Targeted Study Size

Company Plans to Unblind and Report Topline Results in the Fourth Quarter of 2021 Following Completion of Study for Currently Enrolled Participants

RALLY Study Follows Announcement in December 2020 of Positive Results from First Phase 3 Study, RELIEF, of TNX-102 SL 5.6 mg for the Management of Fibromyalgia

https://www.globenewswire.com/news-release/2021/07/23/2268197/0/en/Tonix-Pharmaceuticals-Announces-Outcome-of-Interim-Analysis-of-Phase-3-RALLY-Study-of-TNX-102-SL-for-the-Management-of-Fibromyalgia.html