Rollback of pandemic protections to test Medicaid managed care organizations

 Millions of Americans are at risk of losing health coverage when pandemic-era protections are peeled back. Yet one-third of those estimated to lose coverage — nearly 3 million adults — may still have access to subsidized coverage through the Affordable Care Act marketplace.      

The impending rollback will test the strategies of insurers who have made offering marketplace plans a key piece of their business model to insure low-income Americans.

The question is whether insurers will be able to shift Medicaid members who lose coverage to subsidized marketplace plans.

The link between Medicaid and the marketplace “will soon be put to a real-world test when millions face the loss of their coverage,” according to a recent report from the Robert Wood Johnson Foundation. 

In 67% of counties, insurers already provide both Medicaid and marketplace plans, according to an RWJF researcher.

From a public health perspective, insurers offering both Medicaid and marketplace plans are expected to fill an important role. 

“They’re absolutely critical players in mitigating the potential loss of coverage that is likely to occur,” said Sabrina Corlette, co-director of the Center on Health Insurance Reforms at Georgetown University. 

The federal government has barred states from kicking members off Medicaid during the COVID-19 pandemic to ensure Americans didn’t lose access to coverage. Insurance executives are preparing for redeterminations, a process for determining whether a member is still eligible for Medicaid coverage, to begin this year.

States will need to conduct audits for about 80 million people on the program when the public health emergency ends, according to one estimate.  

Still, stakeholders have voiced concerns about how difficult it is to conduct redeterminations and warned an influential advisory board in January that it’s not as simple as flipping a switch. 

Another estimate shows that as many as 15 million people could lose Medicaid coverage as a result of the eligibility audits. Of the 8.7 million adults expected to lose coverage, as many as one-third could qualify for subsidized marketplace coverage, a report from the Urban Institute found.

For issuers like Centene and Molina, selling marketplace plans is a way to piggyback off their core Medicaid business by leveraging the same provider networks and offering members a familiar experience. 

“It’s a residual market for people that are no longer eligible for Medicaid but still need subsidies to afford health care,” Molina CEO Joe Zubretsky said in April on a call with investors.

Zubretsky said when states resume eligibility checks it should validate the company’s marketplace strategy.

“It’s going to be the proof point that if we can … transfer them into a marketplace product and enjoy their membership for another year or two then its position in the portfolio is validated,” Zubretsky said.

Prior to the arrival of the marketplace in 2014, Medicaid insurers typically did not compete with private insurers like UnitedHealthcare in offering traditional commercial coverage. Instead, Medicaid insurers focused on contracting with state governments to provide coverage to the state’s low-income residents enrolled in Medicaid, according to a previous Urban Institute report.    

Together, Centene and Molina cover nearly 20 million Medicaid enrollees, according to recent first quarter enrollment figures. Nearly 87 million were enrolled nationwide in Medicaid and CHIP as of January, according to figures from federal regulators, and Medicaid remains the largest business line by membership for both Centene and Molina.

Enrollees frequently churn on and off Medicaid, and they lose eligibility — and regain it — as their income fluctuates. Medicaid insurers view the marketplace as a way to maintain members who become ineligible for Medicaid coverage.

Insurers like Centene and Molina overlap their Medicaid and marketplace plan footprints in an effort to catch those who might transition.

“For some plans, most notably Centene, there is a high degree of overlap between their Medicaid and Marketplace participation, while for others like Anthem and United Health Group there is far less,” RWJF found.

There is less evidence about how frequently members move between Medicaid and marketplace plans, RWJF said. 

“We are doing a study of churn now — so far it seems like there is less churn than we thought especially from Medicaid to Marketplace which is why people are worried about the PHE,” RWJF Senior Policy Adviser Katherine Hempstead told Healthcare Dive. 

It’s also unclear whether certain plans want to see an influx of Medicaid to marketplace members above a certain threshold. Earlier this year, Molina said it wanted to trim its marketplace membership after ballooning enrollment lead to adverse selection, picking up sicker members that cut into profitability.   

“Plans may have mixed emotions about gaining their Medicaid members in the Marketplace as the PHE unwinds. To the extent that they think the marketplace is getting selected against, this could dim their enthusiasm,” Hempstead said. 

As the public health emergency expires, it will be important to proactively reach out to members to help lessen potential coverage losses, experts have said.

Federal regulators are urging states and insurers to work closely with one another time to mitigate potential coverage losses.

In a statement, Centene said, “In the coming months, we will continue to work with our state and federal partners to understand the most current eligibility status of beneficiaries, while helping our members retain or obtain critical health insurance coverage.”

https://www.healthcaredive.com/news/rollback-pandemic-protections-test-medicaid-managed-care/624106/

Toward ceramics tailored for optimized bone self-repair

 Your chance of breaking a bone sometime within the next year is nearly 4%. If you're unlucky enough to need a bone replacement, it'll probably be based on a metal part. Unfortunately, metal parts are sometimes toxic over time, and will not help your original bone regrow. Calcium phosphate ceramics -- substitutes for the bone mineral hydroxyapatite -- are in principle an ideal alternative to conventional metals because bone can eventually replace the ceramic and regrow. However, applications of such ceramics in medical settings have been limited by insufficient control over the rate of absorption and replacement by bone after implantation.

Now, in a study recently published in Science and Technology of Advanced Materials, researchers from TMDU and collaborating partners have studied the effect of the carbon chain length of a phosphate ester ceramic containing calcium ion on the rate of its transformation into hydroxyapatite mediated by alkaline phosphatase which presents in our bones. This work will help move bone regeneration research from laboratories to medical use.

"Medical professionals have long sought a means of healing bone fractures without using implanted medical devices, but the underlying science that can make this dream a reality isn't yet fully elaborated," explains lead author Taishi Yokoi. "Our careful analysis of the effect of the ceramic's ester alkyl chain length on hydroxyapatite formation, in a simulated body fluid, may help develop a novel bone-replacement biomaterial."

The researchers report two main findings. First, most of the studied ceramics underwent chemical transformations into particulate or fibrous hydroxyapatite within a few days. Second, smaller alkyl groups facilitated faster chemical reactions than larger alkyl groups. Because the rate-limiting step of hydroxyapatite formation is dissolution of the ceramic, the greater solubility imparted by smaller alkyl groups sped up production of hydroxyapatite. Such knowledge gives a means of tailoring the speed of bone regrowth.

"We now have specific chemical knowledge on how to tailor the rate of hydroxyapatite growth from calcium phosphate ceramics," says Yokoi. "We expect that this knowledge will be useful for bench researchers and medical practitioners to more effectively collaborate on tailoring bone reformation rates under medically relevant conditions." The results of this study are important for healing bone fractures after surgery. By using chemical insights to optimize the rate of bone reformation after implantation of calcium phosphate ceramics, patient outcomes will improve, and returns to the hospital years later for further repairs will be minimized.

Story Source:

Materials provided by Tokyo Medical and Dental University. Note: Content may be edited for style and length.

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Journal Reference:

1. Taishi Yokoi, Akiyoshi Mio, Jin Nakamura, Ayae Sugawara-Narutaki, Masakazu Kawashita, Chikara Ohtsuki. Transformation behaviour of salts composed of calcium ions and phosphate esters with different linear alkyl chain structures in a simulated body fluid modified with alkaline phosphatase. Science and Technology of Advanced Materials, 2022; 23 (1): 341 DOI: 10.1080/14686996.2022.2074801

https://www.sciencedaily.com/releases/2022/06/220603124824.htm

Why ketamine is a speedster antidepressant

 Ketamine is the speedster of antidepressants, working within hours compared to more common antidepressants that can take several weeks. But ketamine can only be given for a limited amount of time because of its many side effects.

Now, a new Northwestern Medicine study identifies for the first time exactly how ketamine works so quickly, and how it might be adapted for use as a drug without the side effects.

The study in mice shows ketamine works as a rapid antidepressant by increasing the activity of the very small number of newborn neurons, which are part of an ongoing neurogenesis in the brain.

New neurons are always being made at a slow rate. It's been known that increasing the number of neurons leads to behavioral changes. Other antidepressants work by increasing the rate of neurogenesis, in other words, increasing the number of neurons. But this takes weeks to happen.

By contrast, ketamine produces behavioral changes simply by increasing the activity of the existing new neurons. This can happen immediately when the cells are activated by ketamine.

"We narrowed down the population of cells to a small window that is involved," said lead study author Dr. John Kessler, a professor of neurology at Northwestern University Feinberg School of Medicine and the Ken and Ruth Davee Professor of Stem Cell Biology. "That's important because when you give ketamine to patients now, it affects multiple regions of the brain and causes a lot of adverse side effects. But since we now know exactly which cells we want to target, we can design drugs to focus only on those cells."

The side effects of ketamine include blurred or double vision, nausea, vomiting, insomnia, drowsiness and addiction.

The study was published recently in Nature Communications.

Goal to develop faster-working antidepressant

"The goal is to develop an antidepressant that doesn't take three to four weeks to work because people don't do well during that period of time," Kessler said. "If you are badly depressed and start taking your drug and nothing is happening, that is depressing in itself. To have something that works right away would make a huge difference."

Newborn neurons act like a match to ignite activity in neurons

"We prove neurogenesis is responsible for the behavioral effects of ketamine," Kessler said. "The reason is these newborn neurons form synapses (connections) that activate the other cells in the hippocampus. This small population of cells acts like a match, starting a fire that ignites a bunch of activity in a lot of other cells that produce the behavioral effects."

"However, it has not been understood that the same behavioral changes can be accomplished by increasing the activity of the new neurons without increasing the rate at which they are born," Kessler said. "This obviously is a much more rapid effect."

For the study, Northwestern scientists created a mouse in which only the very small population of newborn neurons had a receptor that allowed these cells to be silenced or activated by a drug that did not affect any other cells in the brain. Scientists showed if they silenced the activity of these cells, ketamine didn't work anymore. But if they used the drug to activate this population of cells, the results mirrored those of ketamine. This showed conclusively that it is the activity of these cells that is responsible for the effects of ketamine, Kessler said.

This work was supported by grants F30MH124269, K99MH125016 and R01 MH114923 from the National Institute of Mental Health and T32GM008152 from the National Institute of General Medicine, all of the National Institutes of Health, and the Davee Foundation.

Story Source:

Materials provided by Northwestern University. Original written by Marla Paul. Note: Content may be edited for style and length.

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Journal Reference:

1. Radhika Rawat, Elif Tunc-Ozcan, Tammy L. McGuire, Chian-Yu Peng, John A. Kessler. Ketamine activates adult-born immature granule neurons to rapidly alleviate depression-like behaviors in mice. Nature Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-30386-5

https://www.sciencedaily.com/releases/2022/06/220601142833.htm

Best Practices for Managing Patients With Long COVID

 As patients continue to experience post-acute sequelae of SARS-CoV-2, or long COVID, a panel of experts discussed the best practices and approaches for managing this condition's many and varied symptoms.

The panel, made up of members of the American College of Physicians, also published their guidance in the Annals of Internal Medicine.

One primary area of concern with long COVID is that the condition is not clearly defined yet, said H. Clifford Lane, MD, of the National Institute of Allergy and Infectious Diseases.

"I think there's a great need to get some uniformity" in the definition for long COVID, Lane noted. "It is a diagnosis of exclusion, and you don't want to use that as an excuse to not then look for something else."

The panelists agreed that it is important to know what to look for and how to approach patients with potential long COVID.

A common presentation is complaints of fatigue or cognitive deficiencies, such as difficulty concentrating or memory loss. These symptoms require careful monitoring, said Lindsay Lief, MD, director of the Weill Cornell Post-ICU Recovery Clinic in New York City.

"The key is finding cognitive psychologists or occupational therapists in your area who are accessible and that is really the limiting factor," she noted. "There can be improvement and there can be coping mechanisms that are taught."

Lief suggested regular imaging for patients with pulmonary concerns until they are presenting as normal or stable, especially patients who were previously hospitalized with COVID-19. It is also important to continue testing patients for any potential cardiac or vascular causes of those symptoms, she added.

Of note, some patients may present with specific concerns about long COVID even though they never tested positive for acute COVID-19 infection. Understanding the patient's history of illness and vaccination status is crucial to taking the next steps, said Carlos del Rio, MD, of Emory University School of Medicine in Atlanta.

If a patient is unsure of previous infection, it would be appropriate to test for SARS-CoV-2 antibody levels to confirm COVID-19 infection. The next steps would be liver, thyroid, and pulmonary function testing, as well as chest x-ray, and even an echocardiogram, if deemed necessary.

In addition to this standard testing, del Rio said that he would recommend that patients get vaccinated, if they haven't already, though he cautioned that there is no evidence at this time that the vaccines are therapeutic.

Long COVID is not the first post-viral infection condition the medical community has seen, so it is also important to remember there is literature available about other similar conditions that could inform patient care, noted Aluko Hope, MD, MSCE, the medical director of Oregon Health & Science University's Long COVID-19 Program.

"The core of what we are seeing in these clinics is a post-viral fatigue syndrome," Hope said. "And that's actually been studied before this, and we would behoove ourselves to merge what we're doing with the previous work."

Experts agreed that the best course of action is to eventually refer these patients to post-COVID centers for further help. It is also worth considering whether the closest center is participating in the NIH's Researching COVID to Enhance Recovery (RECOVER) initiative, the nationwide trial for studying the long-term effects of COVID-19, they said.

del Rio highlighted the need for primary care physicians to be prepared to treat these patients, since the volume of those with long COVID symptoms is simply too great for all of the post-infection clinics to manage.

He pointed out the similarities to the early days of the HIV epidemic, noting that many of the people we consider experts on HIV today started as internists treating patients with HIV. These physicians learned about the virus from a case-by-case method, and eventually developed an expertise in its treatment. The medical community has the same opportunity with long COVID, he said.

"I think that, at the end of the day, we're learning as we go and we're going to learn more," del Rio added.

Primary Source

Annals of Internal Medicine

Source Reference: Laine C, Cotton D "Care of patients with new, continuing, or recurring symptoms after acute SARS-CoV-2 infection" Ann Intern Med 2022; DOI: 10.7326/M22-1636.

https://www.medpagetoday.com/special-reports/exclusives/99047

Mainstream Menopause Narrative Is Misleading Women

 Given how many women are affected by menopausal symptoms (about 75% of women experience hot flashes, for example), menopause is an important subject to talk about. There seems to be a renewed popular interest in this, and recently, a certain widely-disseminated podcast episode was dedicated to the subject. In an effort to share high-quality, accurate information, the podcast hosts interviewed a physician who is regarded as a menopause expert. (For simplicity, I'll refer to the podcast hosts as The Host and the physician they interviewed as The Physician.)

However, in both this particular podcast episode and in the broader sociocultural conversation about menopause, some claims are shaping the narrative in concerning ways. As clinicians, we need to be aware of the messages influencing our patients. I'm not suggesting the messages are ill-intentioned -- in fact, quite the opposite. The push to demystify menopause and empower women are worthy goals that go hand-in-hand. But the history of medicine when it comes to menopause is incredibly fraught, and the subject warrants careful scrutiny.

Claim: Concerns about breast cancer have unduly robbed women of the benefits of hormone therapy

"Every time someone dares to whisper 'hormone therapy,'" The Host says, "[...] the reflexive response is, 'But it causes breast cancer!'" She laments how, according to her understanding, "the premature release of that early data [from the Women's Health Initiative] and the media frenzy caused millions of women to go off hormone therapy overnight and [...] robbed a generation of women from the therapeutic benefit of hormone therapy."

But it's not just breast cancer, and it's not just one study.

Cochrane, an independent organization that synthesizes evidence in order to help facilitate evidence-based medical decision making, conducted a systematic review to help clarify the clinical effects of hormone therapy (HT) in perimenopausal and postmenopausal women. The review, which included 22 double-blinded randomized controlled trials, found: "In relatively healthy postmenopausal women, using combined continuous HT for 1 year increased the risk of a heart attack from about 2 per 1000 to between 3 and 7 per 1000, and increased the risk of venous thrombosis (blood clot) from about 2 per 1000 to between 4 and 11 per 1000. With longer use, HT also increased the risk of stroke, breast cancer, gallbladder disease and death from lung cancer."

That being said, assessing the risks and benefits of hormone therapy at the level of the individual can be complex, and we're always working with imperfect information. Some women experiencing intolerable menopausal symptoms may decide the benefits of hormone therapy outweigh the risks, and this could be a completely reasonable decision. But there's a big difference between destigmatizing an individual's well-informed medical decision and re-popularizing the use of hormone therapy at scale.

Claim: Menopause is undertreated

Historically, hormone therapy for the treatment of menopausal symptoms was one of the most widely prescribed drug therapies of all time. But these days, The Host reports, "73% of women are never treated for their menopause symptoms." Curious where this number came from, I googled it and found a Forbes article with the headline, "73% Of Women Don't Treat Their Menopause Symptoms, New Survey Shows."

Scanning the article, I looked for the original source of the statistic and found it almost immediately. The Forbes article indicates this number comes from "new research from Bonafide, a company that sells products to treat women's health conditions, including menopause." In other words, a company with a vested interest in selling menopause-related products is actively promoting the message that menopause is extremely undertreated. Digging a little deeper, I clicked on the link to Bonafide's study. What I found was not a research paper published in a reputable scientific journal but a polished set of slides that looked like a pitch deck.

Women need access to healthcare and deserve to have their menopausal symptoms taken seriously, but it's worth being aware of the bigger picture. Emerging direct-to-consumer health tech companies are seeking to broaden the market for their products and services, and women who are interested in treatment for menopause are a prime target. There's an unjust void, these companies claim. But no need to worry! We're prepared to step in and fill it. This isn't good medicine, it's Marketing 101.

Claim: Seeking treatment for menopause is a feminist act

The Host compares the way society treats erectile dysfunction and the way it treats menopause. She notes that information about the treatment options for erectile dysfunction is pervasive, whereas women are told that menopause is a natural process and they should "just deal." Because of the patriarchy, she argues, men experiencing erectile dysfunction are assured that they don't have to live like this. Meanwhile, women experiencing debilitating symptoms due to menopause are expected to adjust to a lower quality of life.

The Host has a point here, but framing menopause in this way runs the risk of undermining the patient/provider relationship. Consider a typical scenario: a woman presents to the clinic, tells her doctor about the menopausal symptoms she's experiencing, and lets him* know she'd like to start HT. He's reluctant due to the risks, and he uses the rest of the short 15-minute appointment to explain that, in her case, the risks of HT actually outweigh the benefits. Although the patient understands what he's saying, she mostly feels like he isn't taking her symptoms seriously. When she leaves without the prescription she came in for, she feels frustrated. In her mind, she didn't get the treatment she needed and deserved.

Again, this dynamic creates the perfect opportunity for direct-to-consumer health tech companies to step in. You don't have to deal with all that patriarchal nonsense. There's an easier way! Yet, although getting treatment for menopause through these companies may be easier, they may not be offering patients what's best.

Claim: You need a doctor who will follow the guidelines

At one point during the interview, The Physician recommends the North American Menopause Society (NAMS) as a great resource. A little while later, she adds, "[NAMS] has their guidelines for physicians [...] so if you have a doctor who is not willing to follow those guidelines, then you need another doctor." However, what most podcast listeners don't realize is that these kinds of guidelines are often heavily influenced by pharmaceutical companies' interests. Of the 20 clinicians and researchers recruited to be on the NAMS 2017 Hormone Therapy Position Statement Advisory Panel, 10 of them reported financial conflicts of interest. More generally, the NAMS website concedes that the organization's funding comes in part from "charitable contributions from corporations" -- i.e. pharmaceutical companies.

Unfortunately, the messages our patients end up hearing about menopause are often carefully crafted by companies that are prioritizing their own best interests -- whether pharmaceutical companies or health tech companies. Although the narrative presented sounds empowering, it's only part of the story.

As clinicians, we need to equip our patients with a more well-rounded understanding of the various factors and forces that are shaping these messages. Knowing the whole story is what's truly empowering.

*Him in this case because most family medicine physicians are male.

https://www.medpagetoday.com/opinion/second-opinions/99035

Potential strategy to reduce fatigue after COVID-19 vaccination

 Despite their strong effectiveness against SARS-CoV-2, mRNA-based COVID-19 vaccines are associated with adverse post-vaccination effects, such as fatigue; how can this be avoided? In a new study publishing May 31st in the open-access journal PLOS Biology, Ayesa Syenina of the Duke–NUS Medical School in Singapore and colleagues report that a new analysis of blood samples from people vaccinated for COVID-19 has identified distinct molecular characteristics linked to an increased likelihood of post-vaccination fatigue. Additionally, experiments in mice suggest that switching the vaccine injection strategy could potentially ease such adverse effects.

Adverse post-vaccination effects may influence people’s willingness to get vaccinated or receive a booster dose, hampering efforts to reduce the spread and severity of COVID-19. However, the molecular underpinnings of adverse post-vaccination effects have been unclear.

To improve understanding, Syenina and colleagues analyzed blood samples from 175 healthcare workers who received BNT162b2, the Pfizer-BioNTech COVID-19 vaccine. Specifically, they used the blood samples to analyze a snapshot of each participant's gene expression, or which genes are turned on or off.

This analysis revealed that people who experienced moderately severe fatigue after vaccination were more likely to have higher baseline expression of genes related to the activity of T cells and natural killer cells—two key cell types in the human immune system.

The researchers also tested two different vaccination injection strategies in mice. Some mice received BNT162b2 through intramuscular injection, the current method used for human patients, in which the vaccine is injected into the muscles. Other mice received a subcutaneous injection, in which the vaccine is injected into tissue just under the skin.

After vaccination, compared to mice that received intramuscular vaccination, mice that received subcutaneous vaccination showed immune-system responses that are in line with a lower likelihood of adverse effects such as fatigue. However, subcutaneous injection did not appear to compromise the protective effects of vaccination.

Further research will be needed to build on these findings and explore their clinical significance. Still, they boost understanding of post-vaccination fatigue and offer a potential strategy to reduce its likelihood.

Coauthor Eng Eong Ooi adds, “This study provides a first insight into the molecular basis of a side effect that many have experienced following mRNA vaccination. We hope that this finding would spur more studies to fully understand the underpinning mechanisms behind vaccine-associated side effects and collectively contribute to developing even more tolerable vaccines.”

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In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology:   http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3001643

Citation: Syenina A, Gan ES, Toh JZN, de Alwis R, Lin LZ, Tham CYL, et al. (2022) Adverse effects following anti–COVID-19 vaccination with mRNA-based BNT162b2 are alleviated by altering the route of administration and correlate with baseline enrichment of T and NK cell genes. PLoS Biol 20(5): e3001643. https://doi.org/10.1371/journal.pbio.3001643

 

Author Countries: Singapore

 

Funding: This study was supported by the National Medical Research Council (NMRC) Open Fund-Large Collaborative Grant (OFLCG19May-0034) and Senior Clinician-Scientist Award (MOH-000135-00) to E.E.O, and the Open Fund-Young Investigator Research Grant (MOH-OFIRG18nov-0004) to R.D.A. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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JOURNAL

PLoS Biology

DOI

10.1371/journal.pbio.3001643 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Cells

COI STATEMENT

Competing interests: The authors have declared no competing interests exists.

https://www.eurekalert.org/news-releases/953725

First head-to-head comparison of four COVID-19 vaccines

 Scientists at La Jolla Institute for Immunology (LJI) have published the first analysis of how four types of COVID-19 vaccines prepare the body to fight SARS-CoV-2. Their in-depth look at how T cells, B cells, antibody levels shift in the six months following vaccination is critical for understanding of how to protect people in the ongoing pandemic.

The new investigation, published in Cell, is the first study in history to compare how three different vaccine platforms trigger an immune response against the same pathogen.

“This study is important because it lets us answer how different vaccine platforms perform in terms of inducing immune responses,” says LJI Professor Alessandro Sette, Dr. Biol. Sci..

The researchers studied human immune responses to an mRNA platform (Pfizer-BioNTech and Moderna vaccines), a recombinant protein-based adjuvanted vaccine platform (Novavax), and a viral vector-based platform (Janssen/J&J). All four vaccines in this study were designed to prepare the immune system to fight the same target, called the SARS-CoV-2 Spike protein.

“We aren’t giving a vaccine scorecard,” says LJI Research Assistant Professor Daniela Weiskopf, Ph.D., who co-led the study with Sette and LJI Professor Shane Crotty, Ph.D. “This kind of side-by-side analysis has never been done before with people who received different vaccines at the same time—in a real life setting. Just understanding the immune responses to these vaccines will help us integrate what is successful into vaccine designs going forward.”

Key findings:

• Antibodies: After six months, those given Moderna had highest levels of neutralizing antibodies, followed by those given the Pfizer-BioNTech and Novavax vaccines. The Janssen/J&J vaccine led to the lowest neutralizing antibody levels.
• B cells: Participants given the Janssen/J&J vaccine had the highest percentage of memory B cells after six months.
• CD4+ T cells: All participants retained a similar percentage of memory CD4+ “helper” T cells against the virus.
• CD8+ T cells: The Novavax vaccine led to the lowest levels of CD8+ “killer” T cells. A higher CD8+ response was seen in those given Pfizer-BioNTech, Moderna, or Janssen/J&J vaccines. Overall, after six months, only 60 to 70 percent of participants retained memory CD8+ T cells.

“This is a very valuable, comprehensive immunological evaluation of these four different vaccines,” says Crotty.

The new study confirms that most people retain some immune response to SARS-CoV-2, regardless of which vaccine they receive. The researchers caution that this immune memory may not prevent infection, but it appears to help fight severe disease.

“Even if it is difficult to maintain a high level of neutralizing antibodies long term, the presence of a stable cellular immunity shows that the immune system can be reactivated very quickly, in a matter of days, if there is an infection,” says Sette.

LJI serves as a COVID-19 research hub

This research was possible thanks to the efforts of LJI’s recently opened John and Susan Major Center for Clinical Investigation. The center staff and scientists drew blood from local volunteers and processed many samples sent by study collaborators. The study leaders then worked with these samples to compare the four vaccines.

“LJI is a great place for collaboration in science,” adds Crotty. “We were doing fifteen kinds of immune system measurements, and there are very few places that can handle that kind of complexity and have that kind of expertise.”

“With this study, we have the same people, in the same lab, using the same tests to study immune responses,” says Weiskopf.

Going forward, the researchers are interested in the effects of COVID-19 vaccine booster shots on long-term immune memory. The scientists are also keeping a close eye on immune cell responses to SARS-CoV-2 variants and are currently analyzing immune responses in people who were vaccinated and experienced “breakthrough” infections.

Authors of the study, “Humoral and cellular immune memory to four COVID-19 vaccines,” include first authors Zeli Zhang, Jose Mateus, Camila H. Coelho, Jennifer M. Dan, and Carolyn Rydyznski Moderbacher. Additional authors include Rosa Isela Gálvez, Fernanda H. Cortes, Alba Grifoni, Alison Tarke, James Chang, E. Alexandar Escarrega, Christina Kim, Benjamin Goodwin, Nathaniel I. Bloom, and April Frazier.

This study was supported by the National Institute of Allergy and Infectious Diseases (CCHI AI142742, Contract No. 75N9301900065; U01 CA260541-01 and AI135078) and by LJI Institutional Funds.

DOI: 10.1016/j.cell.2022.05.022

https://www.eurekalert.org/news-releases/954429