This video was originally published on sister publication HCPLive.

Right now, the Advisory Committee on Immunization Practices (ACIP) is convening an emergency meeting to discuss

 that recently led to thrombotic events in 6 women administered the Johnson & Johnson COVID-19 vaccine in the US.

The committee, meeting following the federal pause of Johnson & Johnson vaccine distribution by the US Food and Drug Administration (FDA), is addressing the matter of cerebral venous thrombosis risk among women aged 18-49 vaccinated with the one-shot prophylaxis.

But what is this concerning side effect—and what is its link to both COVID-19 and adenovirus-based vaccines designed to prevent the pandemic virus?

, Maja Zaric, MD, interventional cardiologist and assistant professor at Zucker Medical School, discussed the risk of thrombotic events now observed in a pair of adenovirus-based COVID-19 vaccines: that from Johnson & Johnson, as well as AstraZeneca.

Per Zaric, the chimpanzee-based adenovirus vector is made inactive, made unable to replicate, and is therefore doses in “large amounts” to vaccinated persons.

“Each vaccine carries somewhere over 50 billion particles,” Zaric explained. “This is a massive amount of adenovirus that has to be injected because it doesn’t replicate in order to achieve the effectiveness.”

What’s being observed in affected patients is the development of PF4 factor antibodies, which inhibits platelet development—a pathology similar to heparin-induced thrombosis (HIT).

“What happens is there is an abrupt cascade of clotting activated in the venous system that is not typically seen in COVID patients, but broader in the vaccine reaction,” Zaric explained.

This commonly occurs in the patient’s brain or cut systems. Symptoms have occurred up to 2 weeks following vaccination—far beyond the standard local site and symptomatic reactions anticipated with COVID-19 vaccines—and include headache, blurry vision, swelling, high temperatures, and shortness of breath.”

Mortality risk with cerebral venous thrombosis is up to 25%, Zaric said.

“The condition rapidly develops and consumes large amounts of coagulation factors and platelets, therefore causing simultaneous clotting,” she explained. “It can be treated early on, when diagnosed."

“We’re just starting to pick and recognize these cases in the US,” Zaric added. “I would be alert on those folks who get the vaccination over the next 2-3 weeks.”

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An interventional cardiologist discusses the observed cases of cerebral venous thrombosis in women administered the Johnson & Johnson COVID-19 vaccine.

Understanding Links Between COVID-19, Vaccines, and Thrombosis

Tomorrow, the Advisory Committee on Immunization Practices (ACIP) will convene an emergency meeting to discuss

 reported among 6 women administered the Johnson & Johnson COVID-19 vaccine in the US.

The committee, in conjunction with the US Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), is tasked with weighing the benefits of the emergency-authorized adenovirus vaccine product from Johnson & Johnson versus the newly observed risks: a half-dozen cases of cerebral venous thrombosis among women aged 18-49 years old.

Whatever their decision, it will likely be reflective of not only unique patient population risks with the vaccine, but the current state of US COVID-19 vaccination rollout—a trend which provides federal agencies the luxury of selectivity.

 on the day of the Johnson & Johnson news, Carlos del Rio, MD, executive associate deanof the Emory School of Medicine & Grady Health System, discussed the benefit of the US more greatly distributing and administering mRNA vaccines from Pfizer-BioNTech and Moderna, particularly as it relates to the Johnson & Johnson vaccine pause.

“I think we have enough vaccines to vaccinate everybody with either Moderna or Pfizer,” del Rio said. “If the decision here in the US is to not use Johnson & Johnson or AstraZeneca, I think we will be fine. I’m more worried about the rest of the world.”

As del Rio noted, the Johnson & Johnson product could currently be better served in the global effort to mitigate COVID-19—particularly in at-need countries, where the benefit of the vaccine versus the pandemic greatly outweighs the newly observed and very rare risk.

“I’m 62,” del Rio said. “If I was scheduled to get a COVID-19 vaccine today and it was Johnson & Johnson, I would still get it. I have a much higher risk of getting and dying from COVID at my age than I do of getting any complications from the vaccine.”

In anticipating federal decision on the availability of the vaccine in the US, del Rio looked to how other agencies responded to similar blood clot-related issues reported with the AstraZeneca vaccine.

“I would not be surprised if the regulators here in the US do something similar to what they did in Europe: say that this vaccine should not be used with people under the age of 50 or 60, then keep this adenovirus vaccine for older populations, where the risk is lower,” he said.

Carlos del Rio, MD, discusses the United States' pandemic situation in assessing the blood clot events observed in 6 Johnson & Johnson vaccine recipients.

What Does the Johnson & Johnson COVID-19 Vaccine Pause Mean?

, the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) stopped administration of the Johnson & Johnson 

 at federal sites and launched investigation of 6 US cases of cerebral venous thrombosis among women aged 18-49 given the one-shot vaccine.

The decision, which also called on states to withhold available doses of the vaccine previously given Emergency Use Authorization (EUA) by the FDA, proceeded the reported death of 1 affected woman, and the critical condition of another.

The news also comes at a time when COVID-19 cases are fluctuating state-by-state, while first doses have been administered to half of all US adults in pursuit of majority immunity rates.

FDA and CDC investigators from the Advisory Committee on Immunization Practices (ACIP) will convene in an emergency meeting on the matter this Wednesday, in order to discern whether the company’s EUA should continue as-is or become altered.

The news, at face value, is ultimately disappointing. But there’s more context to discuss beyond the vaccine pause.

, editor-in-chief Jason Gallagher, PharmD, clinical professor at the Temple University College of Pharmacy, shared his perspective into the impact the pause may have on US COVID-19 vaccine rollout goals.

“As disappointing as it is, it is the system working: picking up these adverse effects, investigating them and pausing the administration of the vaccine while we figure it out,” Gallagher said. “It’s not just like it’s been approved and we ignore what happens.”

Gallagher also shared his anticipation into what will be decided in the ACIP meeting, in terms of possible alteration to the Johnson & Johnson EUA, or a planed resumption of administration after federal assessment has concluded.

On the matters of why Ad26.COV2.S is now the second adenovirus-based COVID-19 vaccine linked to thrombotic event risk after the AstraZeneca product last year, Gallagher discussed the possibility of limiting heparin prescription to such vaccinated persons, as well as a supposed link to oral contraceptives and vaccinated persons’ risk of thrombotic events.

Lastly, Gallagher provided advice for clinicians and caregivers likely fielding new concerns today from persons already vaccinated with Johnson & Johnson, who may not have perspective on the absolute risks versus benefits.

“No matter what, even if there’s 10 times as many cases, it’s still something very uncommon—so uncommon that it wouldn’t show up in vaccine trials of 40-50,000 people,” he explained. “We’ve got a long way to go before the vaccine is not worth it.”

Jason Gallagher, PharmD, adds context behind the FDA and CDC's decision to pause and review blood clotting events in 6 women given the company's COVID-19 vaccine.

The Johnson & Johnson COVID-19 Vaccine Pause: What You Need to Know

As of this week, the United States has provided at least 1 

 dose to one-third of its entire population.

The effort to vaccinate the entire adult population kicks into another gear this month, as the country begins to expand access to include all interested parties, and the Biden administration makes good on its guarantee of available doses for all adults by May 2021.

But vaccine buy-in, even into the fourth and fifth month of rollout, is a crucial conversation toward achieving majority vaccination rates.

In a second segment from his interview with 

, Kevin Grumbach, MD, professor of Family Community Medicine at the UCSF School of Medicine, discussed the matter of COVID-19 vaccine reluctance—and its differentiation from the much smaller and more obstinate anti-vaccination movement.

“One of the strongest reasons it was associated with people saying that they have a reluctance with getting vaccinated was the speed of the approval process,” Grumbach said. “I don’t interpret that as they’re dead-set against it. They’re in the “wait and see” group.”

Grumbach argued a hesitant perspective is “understandable” given the circumstances of the approval process, and that experts need to encourage continued dialogue with such individuals while providing them reliable sources of information.

In discussing the hesitancy among minority and ethnically diverse communities, Grumbach stressed there needs to be an acknowledgement of the country’s history with racism and its role in medical practice—and understand that it’s a vital part of the vaccine decision-making process for many people.

Lastly, he stressed the need for more accommodating vaccination strategies and resources as more doses become available for a greater rate of people. Current vaccination sites require amenities that are often taken for granted, such as internet access and a car.

“We have to be much more diversified and not just think there’s this one method of making a big, grand drive-in site,” he said. “Those need to be coupled with a lot of ones that are much more community-based and locally accessible.”

An expert stresses the need to consider individuals' worry over information—and even their history with systemic biases.

Solutions to COVID-19 Vaccine Hesistancy

A new research letter highlighting a San Francisco-based survey study highlighted concerning disparities in racial and ethnic likelihood of interest in getting a COVID-19 vaccine.

, which come at a time when COVID-related inequity has been well-defined among differing races and ethnic groups in the US, highlight the historical systemic issue of healthcare inequality among patients.

Investigators reported that Asian and multiracial individuals, and those of other races were more similar to Black and Latinx individuals than White individuals in their likeliness of getting a COVID-19 vaccine.

As people of color and their respective US communities have faced disproportionate burden of the pandemic, inequities in vaccination, investigators wrote, would compound these disparities.

 interview regarding these findings, study author Kevin Grumbach, MD, of the Department of Family and Community Medicine at University of California San Francisco, discussed the implication of results at a time when vaccination rollout is peaking in the US, and new cases are again steadily increasing.

“There’s been a really good framework to say we should really talk about our trustworthiness,” Grumbach said. “Have we earned the trust, as people in public health, biomedical research, and healthcare, particularly with communities that have been subject to oppression and even in exploitation in certain biomedical activities?”

Vaccine access and new cases are both increasing. An expert discusses earning trust in at-risk communities.

Building COVID-19 Vaccine Trust is a Two-Way Street

Today, March 24, marks World TB Day, the date reflecting Dr. Robert Koch’s discovery of 

In recognition of the annual medical holiday, our sister publication 

 between American Lung Association (ALA) Al Rizzo, MD, and Philip LoBue, MD, Director of Tuberculosis Elimination at the US Centers for Disease Control and Prevention (CDC) National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.

Among their topics of discussion on the history and current state of 

 in the US was the actual treatment of the respiratory infection.

As LoBue noted, the disparity of tuberculosis treatment strategy depends on its status in a patient: latent, or active. Latent TB generally requires 1-2 therapies for a shorter period of time, prescribed in 3 different regimens:

3 months of once-weekly isoniazid (INH) plus rifampin (RIF)

3 months of daily combination INH and RIF

“Those are all very effective—probably more than 90% effective,” LoBue explained.

Active disease, meanwhile, is more difficult to treat and requires more complicated regimens. Treatment will generally run 6-9 months, LoBue said, and include any of 4 therapies:

Among the most promising developments in TB care is the hopeful reduction of active tuberculosis care, from 6 to 4 months, with the addition of moxifloxacin.

In the meantime, however, LoBue stressed the significance of state-set care teams and at-risk patients adhering to what’s understood to benefit either form of tuberculosis—in order to avoid a worse form of the disease.

“If all the doses of medication are not taken correctly, not only is there a good chance that the person will fail their treatment and not get better, but it puts them at great risk to develop drug-resistant TB, which is much more difficult to treat,” he said.

Lungcast is a monthly podcast series from HCPLive and the ALA. Listen to the full episode here:

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To mark World TB Day, a pair of experts break down the currently defined regimens for latent and active tuberculosis—and what may still come.

Tuberculosis Treatment Strategies in the US

comprehensive assessment from the Serum Statens Institut in Denmark

 that showed last week that COVID-19 reinfection risk was about 0.65% in its population last year, is the means by which the team was able to compile its data.

In the second segment of an interview with 

, study author Daniela Michlmayr, PhD, emphasized the value of Denmark’s emphasized COVID-19 testing strategy—a priority similar to other smaller countries that have fared better during the pandemic.

Michlmayr and colleagues were able to assess approximately 4 million PCR test results from COVID-19—equivalent to two thirds of Denmark’s population.

“Denmark has a really good testing strategy,” Michlmayr said. “In our study, we were also able to capture asymptomatic or mild cases. Often you’re not able to catch them in your cohorts—or what’s been published has only focused on healthcare workers.”

She went on to highlight her country’s avoidance of limitations and costs to testing access—decisions which have already contributed toward breakthrough research from herself and colleagues.

“I think Denmark has done a really good job compared to other nationals when compared to other nations when it comes to testing strategies,” Michlmayr said. “And it just shows that if you put that in place, we’re really able to learn a lot.”

Turning back to the matters of COVID-19 reinfection and achieved population immunity—whether it be by acquired protection and/or vaccination—Michlmayr highlighted her team’s past comparative research into previous outbreaks to understand how long safety could be assured from the current COVID-19 virus.

“It will be a hot topic for awhile, I suppose,” she said. “But our studies from MERS and SARS suggest that maybe it could be 1-2 years that we could hope to have immunity for.”

The small country's emphasis on accessible testing provided more up-to-date tracking, and opportunity for research into reinfection risk.

Learning from Denmark During COVID-19

 from the Statens Serum Institut in Denmark last week reported nationwide PCR test result-based findings showing that 

 reinfection was prevalent in just 0.65% of the country’s population through 2020.

, would suggest that previously infected COVID-19 patients are likely to have a protection from reinfection at least through 6 months after testing positive.

That said, more research is being considered, and investigators additionally found stipulations among age groups.

on her team’s findings, study author Daniela Michlmayr, PhD, explained the inspiration for the assessment that was made possible by an impressive 4 million data-logged PCR test results from Denmark—approximately two-thirds of the country’s population.

Michlmayr also discussed currently ongoing genome sequencing assessments with the same available national database, to help better inform their new interpretation of improved protection from COVID-19 reinfection.

Most importantly, Michlmayr discussed the unique age-stratified findings from the newly-published research, which shows that elderly patients fared worse than the younger population’s approximate 80% overall protection from COVID-19 reinfection.

“We found really alarming results that among the elderly, everybody who is 65 and beyond, actually had a reduced protection—only 50%, approximately,” she said. “That alarmed us, personally, and motivated us to conduct these studies.”

An interview on perspectives learned from a nationwide PCR test database assessment.

Reduced SARS-CoV-2 Reinfection Risk Among the Denmark Population

 Makeshift COVID-19 data-sharing networks


 Interpreting SARS-CoV-2 sequence changes


The communication networks connecting major US laboratories conducting 

 sequencing may not be any greater than a Slack channel established by the US Centers for Disease Control and Prevention (CDC).

But it’s proven to be more than enough for teams including Cooper, Kamil, and Domman, a trio of microbiology investigators

 into a lineage B.1.2 variant with a Spike protein Q677P substitute in a growing proportion of cases in the South and Southwest regions earlier this year.

, the team discussed the intricacies of SARS-CoV-2 sequencing and reporting—a matter which, given the urgent nature of the COVID-19 pandemic, conflicted against the scientific instincts of raised patience and scrutiny. Kamil and colleagues faced such conflict when observing the prevalent lineage.

“It’s so easy to get stuck in the hyper-cautious, ‘Wait, we need more proof’,” Kamil said. “It’s such a balance in science where you don’t want to want to be irresponsible but you also don’t want to sit on a story that’s real.”

For reference, Kamil discussed the caution placed around D614G mutation, nicknamed ‘Doug,’ by the scientific community in the late spring of 2020.

“We were all kind of too cautious about Doug,” Kamil explained. “It now is 98% of all the viruses in the world. It became a signal in June, and it probably popped up in maybe April or March—and it probably occurred first maybe February, January, or December (2019). It came from almost nothing to overtake all the population.”

But the opportunity to observe and share virus evolution first-hand is almost unprecedented in the modern history of sequencing, regardless of the means by which it’s being collected.

“I think it’s really valuable for everyone to know how quickly we were able to put this data together because of data-sharing, and because of scientific networks that we basically put together ad hoc,” Cooper said

It does speak to the benefit of improved resourcing for such monitoring—for COVID-19 and beyond.

“Sequencing is cheaper than it has ever been,” Kamil said. “Why are we not sequencing more? We have not updated our public health surveillance on any respiratory pathogens.”

How observed changes in SARS-CoV-2 lineage have warranted heightened priority, and why sequencing deserves better resourcing beyond the pandemic.

SARS-CoV-2 Sequence Reporting: Changing Mindsets


Professor, Microbiology and Molecular Genetics
University of Pittsburgh


Associate Professor, Microbiology and Immunology
LSU Health Shreveport


Assistant Professor, Center for Global Health
University of New Mexico

, data from a team of nationwide investigators found a SARS-CoV-2 a variant first observed on October 23, 2020, had come to represent more than 27% and 11% of all sequenced pandemic virus genomes in Louisiana and New Mexico by mid-January.

The lineage B.1.2 variant carries a Q677P substitution in the Spike protein (S) and had been linked to 499 viral sequences as of February 3.

The uncovered variant has led to the makeshift team of microbiology investigators continuing assessment into the increasing prominent strain’s proteolytic processing, cell tropism, and cell transmissibility.

Their efforts also highlight the benefit of cross-country genomic surveillance during COVID-19—a practice which the US, in relation to other major countries, has lacked in since the beginning of the pandemic.

In fact, as the investigators explain in the video above, the variant’s mutation was first observed in New Mexico. Domman observed through a shared data and communication platform that Kamil’s team was reporting the same variant in Louisiana.

They began to collaborate on their research around the time that Cooper’s team in Pittsburgh began to observe a similar S substitution in variants, almost to the day.

“Within 2 days, we knew for sure there was more to the study than 1 lineage that Jeremy and Daryl had discovered,” Cooper explained.

While interpretation of the mutations’ function and influence on the virus’ transmission is still not fully formed, the discovery speaks to the value of bolstered surveillance and data-sharing—at regional, national, and global levels.

“One of the things we’d like to highlight is that open source and sharing data in real time has been absolutely fundamental to this entire effort globally, in terms of linking up scientists to understand how the virus is changing and transmitting through the globe and even locally,” Domman said.

A team of cross-country investigators discuss their coordinated tracking of a new variant in the US earlier this year.