 in pregnant women is essentially a non-starter—largely due in fault to the fact that clinicians have no observed understanding of how currently regulated mRNA vaccines interact in the key patient group.

The group was largely excluded, or not at all recruited, for assessment in global, real-world trials which eventually generated the first available COVID-19 vaccines. That said, clinical history would indicate a likelihood of safety for expecting mothers and their newborns.

In the second segment of an interview with 

, Eric Forman, MD, of the Columbia University Fertility Center, discussed why mRNA vaccines—limited in assessment among pregnant women—is theorized to be safe for the population.

“In general, we recommend avoiding live, attenuated vaccines, mostly from a theoretical concern due to the immunosuppressed state of pregnant women,” Forman said. “But even there, there are registries of women who inadvertently gotten MMR before realizing they were pregnant, and the safety was very good.”

As Forman noted, the significant transmissibility and effect of COVID-19, along with the makeup of vaccines, would lead to belief that the patient, her fetus and placenta would be safe. But supporting data is still lacking.

As such, Forman suggested pregnant be considered up-front in future COVID-19 vaccine trials.

“I don’t know if you’d have big enough numbers, but it would have been a start,” he said. “The pregnant state is different from the non-pregnant state, and it shouldn’t be excluded from studies.”

Videos

Current trial evidence is severely lacking for the at-risk group, but does clinical history suggest safety?

Navigating COVID-19 Vaccines with Pregnant Women

A new study showed vaccine hesitancy may be highly prevalent among patients undergoing fertility treatment.

In data from a survey-based assessment conducted by the Columbia University Fertility Center and published in 

investigators reported that 58% of 284 patients to receive fertility treatment in the last year stated they would either not receive currently available 

Though the rate is fairly similar to the current general population’s feelings on COVID-19 vaccines, perception was far worse among those further along the fertility care process.

Just 17.3% of patients who were either pregnant or planning to conceive within the next month said they would get the vaccine. Another 90% of patients on fertility treatment said they would not change their treatment plan due vaccination.

, study coauthor Eric Forman, MD, discussed the survey’s findings, and helped to rationalize the concerns of his patients—particularly those already pregnant.

“Pregnant women were not included in the trials to develop vaccines,” Forman said. “We don’t have a lot of data. We know a lot of vaccines are not safe in pregnancy, and are not recommended in pregnancy.”

Adversely, Forman also noted the risk pregnant women may face in viral infection, given they’re considered immunosuppressed. Though understanding of how COVID-19 affects pregnant women is still not perfected, the lack of representation in vaccine trials negates rationale for vaccination.

“We have a high-risk population and they know less than the general population about safety,” he explained.

Forman also touched on other elements influencing fertility and pregnant patients’ current vaccine concerns, including unfounded social media rumors, and the unknowns of messenger RNA (mRNA) vaccines.

An interview on new survey data suggesting a majority of fertility and pregnant patients are not interested in the currently available vaccines.

Fertility Patients Express Concern Over COVID-19 Vaccines

Though this is a matter that—as explained to 

by Adam S. Lauring, MD, PhD—was anticipated with an uncontrolled pandemic virus, it is still going to require an improvement in monitoring and prevention measures immediately.

, Lauring, a professor in the Division of Infectious Diseases at the University of Michigan, and author of a recently published 

viewpoint on genetic SARS-CoV-2 variants, discussed the need for vital means of surveillance right now: SARS-CoV-2 testing, sequencing, and contact tracing.

“They’re somewhat unglamorous but that’s really the key to control,” he said. “Until we have vaccines in the arms of a large percentage of our population, these are the tools we’re going to need to deploy better.”

Lauring highlighted his team’s current work in improved sequence-based surveillance, a strategy which he hopes allows them to more efficiently target control measures, including contact tracing, depending on the variant spread.

He stressed that, though the newest variants do not appear to be more lethal, their greater susceptibility of spread may mean increased cases—and, as such, more critical and fatal cases.

The ability to mitigate or prevent emerging variant spread may also influence the possibility of the virus becoming a constant or seasonal threat.

“It’s certainly possible that this could just become one of the viruses people get sick with every year,” Lauring said. “Nut the hope is we have the vaccines, and we get enough immunity out there that it hasn’t been as bad as it’s been in the last year.”

The ability to monitor, mitigate, and prevent new variant spread could influence the odds of majority immunity.

How COVID-19 Variants Could Change Timelines

 cases continue to rise in early 2021, discussion around the pandemic virus has shifted to the emergence and tracking of differing variants, borne out of mutation.

The most significant of recently observed variants—the so-called B.1.1.7. variant, initially traced from southeast England—has spread internationally at a rapid pace. It is anticipated by experts that it is a much more transmissible form of the virus, and could eventually become the dominant variant in the world.

Though this news come as an alarm—and puts even greater stress on the rollout of available vaccine doses in the coming weeks—it’s nothing surprising to investigators.

Adam S. Lauring, MD, PhD, a professor in the Division of Infectious Diseases at the University of Michigan, and author of a recently published 

viewpoint on genetic SARS-CoV-2 variants, explained the newly discussed variants have been long-developing and essentially inevitable.

“We may see another variant become the dominant strain,” he said. “That’s a lot of what virus evolution is. It’s just something that we’re going to keep seeing, and the work for scientists is to figure which ones are concerning and why.”

Lauring also highlighted the B.1.1.7. variant, a result of numerous mutations which has allowed for greater transmissibility and the potential for the variant to become globally dominant.

Among the practices necessary to address the new COVID-19 threats are increased sequencing and an improvement of social distance strategies.

“It’s important to put the concern in the right place,” Lauring explained. “The more immediate concern is: if this virus is spreading more rapidly, then it’s going to be harder to control period, with our current practices.”

More transmissible variants are emerging quickly. An expert explains why it's expected, but concerning.

New COVID-19 Variants: What Do They Mean?

Acute respiratory distress syndrome (ARDS) can be brought on by COVID-19 and without any approved medication to treat it, patients can be put on a ventilator.

Cleveland, Ohio-based Athersys has developed its MultiStem cell therapy and is studying it for COVID-19 related ARDS. MultiStem is a regenerative candidate in clinical development that has shown the ability to promote tissue repair and healing in a variety of ways, such as through the production of therapeutic factors in response to signals of inflammation and tissue damage.

The therapy was recently given a Regenerative Medicine Advanced Therapy designation from the U.S. Food and Drug Administration (FDA) for ARDS. This allows sponsors to work closely with the FDA and receive their guidance on expediting development of their products.

Prior to this designation, Athersys had completed research exploring MultiStem for the treatment of pulmonary distress and recently completed an exploratory Phase 1/2 clinical trial for the treatment of ARDS.

They reported encouraging data from the study, and decided to also explore treatment for COVID-19.

As such, the company has initiated a phase 2/3 clinical trial evaluating MultiStem for the treatment of COVID-19 induced ARDS, which is now enrolling patients. The primary efficacy endpoint for the randomized, double-blind, placebo-controlled study will compare the number of ventilator-free days through day 28 among MultiStem and placebo treatment groups. 


Secondary objectives of the study are to evaluate 60-day all-cause mortality, time in the intensive care unit, pulmonary function, tolerability, and quality of life among survivors through one-year of follow-up. 

Athersys CEO Gil Van Bokkelen, PhD, and CFO Ivor Macleod, MBA, CPA about the investigative therapy and the company.

Athersys has developed its MultiStem cell therapy for COVID-19 Acute respiratory distress syndrome (ARDS). Athersys CEO Gil Van Bokkelen, PhD, and CFO Ivor Macleod, recently spoke to Contagion providing background on the company and their MultiStem therapy.

Stem Cell Therapy for ARDS

An optimist may look at the difficulties surrounding vaccine hesitancy in the US and consider that, given the public’s investment of time and research into understanding 

, the eventual vaccine for the pandemic may be met with more acceptance than previous prophylaxes.

The outcome is a not certain one, but is one that clinicians like Bridget Calhoun, DrPH, MMS, would obviously hope for.

In the final segment of an interview with 

, Calhoun, Associate Dean for Academic Affairs and Research, and Chair and Associate Professor at Rangos School of Health Sciences at Duquesne University, discussed the need for people to learn parameters of vaccine development to better embrace the products.

She discussed how she and her peers are at benefit of being able to trust the development system implicitly, having seen the science that drives vaccines, knowing the oversight that’s required of any regulated product, and participating in the very clinical scrutinization of vaccines.

Calhoun also discussed the likelihood of COVID-19 vaccine risk-stratified prioritization, a strategy which will likely upset those who are not at significant risk of COVID-19 severity nor mortality, but would nonetheless want a vaccination as soon as possible. She noted how a similar situation during a flu vaccine shortage a decade ago led to such criticism.

Regardless of vaccination status in 2021 and beyond, people will still have a role of community protection to play for those at risk.

“There are some people who just can’t get the vaccine, whether they have had adverse reactions to vaccines in the past, or they have demonstrated an allergy to one of the components of the vaccine,” Calhoun said. “We have to be mindful of those folks, too.”

In consideration of the idea that the pandemic may lead to greater knowledge and adoption of preventive health measures.

Does COVID-19 Make a Better Case for Vaccines?

Just last week, the US Food and Drug Administration (FDA) launched an independent investigation into the safety data currently available for 

The adenovirus-based vaccine, being investigated by the company and the University of Oxford in phase 2/3 international trials, is among the leading candidates for potential FDA regulation and marketing for the prevention of the virus, pending late-stage efficacy and safety findings.

However, this new independent safety investigation is a continued stop from reports of a serious adverse event in a UK-based participant last month, and could greatly influence the FDA’s decision on marketing approval once an application is submitted.

Or, does this investigation serve another purpose?

, Bridget Calhoun, DrPH, MMS, Associate Dean for Academic Affairs and Research, and Chair and Associate Professor at Rangos School of Health Sciences at Duquesne University, discussed the appropriateness of the FDA’s decision to hit pause on the US-based trial arm for AZD1222—especially at a time of heightened scrutiny surrounding rapidly-progressing COVID-19 vaccine trials.

“Particularly in our democracy, we put a lot of faith in our national organizations,” Calhoun said. “So they have to be spot-on. They have to have reputable, responsible folks who are going to look at the data and make data-driven decisions based on the safety and efficacy of these vaccines.”

Calhoun added that public willingness and interest in a COVID-19 vaccine—a major factor in adopting a safe level of COVID-19 immunity—may be influenced by assuredness in vaccine research.

“And the way that we convince the general public to do that, and show them that it is in fact beneficial, is to know that it was scrutinized at every level,” she said.

Perspective on the ongoing independent safety reviews for one of the more promising vaccine candidates.

What to Make of the AstraZeneca COVID-19 Vaccine Trial Stalls

In recent months, convalescent plasma for the treatment of 

 has seen its share of news and public debate within the medical science community and beyond. 

In August, clinicians at Houston Methodist 

that transfusing critically ill COVID-19 patients with high antibody plasma early in their illness—within 72 hours after hospitalization proving most effective&mdash;reduced the mortality rate.

They transfused 316 patients, and a preliminary analysis showed a significant reduction (P = 0.047) in mortality within 28 days, specifically in patients transfused with an anti-spike protein receptor binding domain titer of ≥1:1350 within 72 hours of their admission with plasma.

Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 non-transfused control COVID-19 patients.

During that same month, the US Food and Drug Administration (FDA) 

 an Emergency Use Authorization (EUA) for convalescent plasma in treating COVID-19. However, the FDA came under scrutiny when the agency reported a 35% lesser mortality rate for patients taking convalescent plasma. FDA Commissioner Steve Hahn, MD, took responsibility for the information and walked back the statistic after there was an outcry from the medical community.

Historically, convalescent plasma has been used for infectious disease treatment for over 100 years, and there are ongoing trials right now looking at the therapy for COVID-19. In late September, the National Institutes of Health (NIH) decided to expand 2 existing trials. These are randomized, placebo-controlled clinical trials to evaluate further convalescent plasma for hospitalized COVID-19 patients.

"The evidence on convalescent plasma as a treatment for severe cases of COVID-19 is promising but incomplete. We need to carry out rigorous randomized control clinical trials to determine how this therapy can improve outcomes," said Francis Collins, MD, PhD, director, NIH. "While the world waits for an effective vaccine, it is vital that we simultaneously expand the options for available treatments for those currently suffering from the worst effects of this disease."

The trials are receiving $48 million in support through Operation Warp Speed. Within NIH is the National Center for Advancing Translational Sciences (NCATS), and they will oversee the grant awards through its Clinical and Translational Science Awards (CTSA) Program research network. The CTSA's Trial Innovation Network (TIN) will play a key role in working to add study sites and enroll patients, including those from communities disproportionately affected by COVID-19.

Christopher Austin, MD, director, NCATS, says the center was developed to solve the problem of getting devices, diagnostics, and therapies to patients. They are involved in the “scientific and operational” aspects of translational research.

 recently about the organization’s mission and the specifics of the 2 expanded trials for convalescent plasma.

Within NIH is the National Center for Advancing Translational Sciences (NCATS) and they will oversee the grant awards. Christopher Austin, MD, director, NCATS, discusses the specifics of the 2 trials being expanded.
 

NIH: Expanding Trials for Convalescent Plasma

Guidance from the US Centers for Disease Control and Prevention (CDC) came under scrutiny last month when reports showed dissent between federal leadership-pushed language on 

 transmission and testing parameters, and the members of the CDC who emphasized science-informed measures.

What eventually manifested was a series of amended and removed guidances on the CDC’s website, the most recent of which weighed in on the topic of SARS-CoV-2 aerosol versus droplet transmission risk debate.

Last week, Anthony Fauci, MD, director of the National Institutes of Allergy and Infectious Diseases (NIAID), 

, a respiratory health podcast series from sister publication 

 and the American Lung Association (ALA).

On the topic of the CDC’s varying messages, Fauci admitted he wasn’t sure of where the agency stood.

“I just know it is likely that there is some degree of aerosol transmission,” he said. “I don’t know to what extent it is responsible for transmissions.”

Fauci also provided perspective on the current state of transmission risk in community gatherings including college campuses, suggesting a strategy of minimal-risk infection management that would allow for classes and programs to continue (mostly) unaffected.

 “The perfect scenario would be that if a college had the capability, when a student got infected—and students will get infected&mdash;they had the capability of putting them on a separate floor of a dorm, or in a completely separate dorm, where they could comfortably recover, because most of the time they’re going to be very sick,” he said.

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Fauci also shares suggestions for college campus to mitigate community-based spread while classes continue.

Anthony Fauci, MD: How SARS-CoV-2 Is Most Likely Spread

As leading vaccine developers continue to collect phase 3 data for 

 candidates, focus is beginning to turn from clinical effectiveness and safety toward vaccine prioritization and distribution.

How will the first regulated COVID-19 vaccines be managed and distributed?

, Lorne Clancey, senior director of temperature and environmental monitoring solutions at CenTrak, discussed an interesting facet of COVID-19 vaccine strategies: required storage temperatures for leading candidates.

“Some are going to require extreme cold—ultra-low temperatures, as a matter in fact, about minus-80 (Fahrenheit),” he said. “They have to be kept at this temperature to provide the necessary inoculation strength it has to deliver.”

Promising vaccines including the quartet of mRNA-based candidates from Pfizer and BioNTech would require dry ice use for storage and transportation, and space- and energy-consuming ultra-low units in hospitals and physician’s offices.

More is riding on the scientific community’s ability to cater to these specific needs than is discussed relative to the clinical data of the vaccines themselves.

“If the vaccine is compromised because of temperature, it’s not going to deliver the anticipated outcome, and that would basically mean the patient would have to come back and get it again,” Clancey said.

A discussion with an expert on the particularities of the vaccines, which vary in temperature climate requirements and dosages.