Next-Generation COVID-19 Vaccines Could Stimulate Another Arm of the Immune System

Next-Generation COVID-19 Vaccines Could Stimulate Another Arm of the Immune System

  • June 17, 2021

A new study looking at the way human cells activate the immune system in response to SARS-CoV-2 infection could open the door to even more effective and powerful vaccines against the coronavirus and its rapidly emerging variants keeping the global pandemic smoldering.

Researchers from Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL) and the Broad Institute of MIT and Harvard say it’s the first real look at exactly what types of “red flags” the human body uses to enlist the help of T cells—killers sent out by the immune system to destroy infected cells. Until now, COVID vaccines have been focused on activating a different type of immune cell, B cells, which are responsible for creating antibodies. Developing vaccines to activate the other arm of the immune system—the T cells—could dramatically increase immunity against coronavirus, and importantly, its variants.

In their findings, published in Cell, the researchers say current vaccines might lack some important bits of viral material capable of triggering a holistic immune response in the human body. Based on the new information, “companies should reevaluate their vaccine designs,” says Mohsan Saeed, a NEIDL virologist and the co-corresponding author of the paper.

Saeed, a BU School of Medicine assistant professor of biochemistry, performed experiments on human cells infected with coronavirus. He isolated and identified those missing pieces of SARS-CoV-2 proteins inside one of the NEIDL’s Biosafety Level 3 (BSL-3) labs. “This was a big undertaking because many research techniques are difficult to adapt for high containment levels [such as BSL-3],” Saeed says. “The overall coronavirus research pipeline we’ve created at the NEIDL, and the support of our entire NEIDL team, has helped us along the way.”

Saeed got involved after he was contacted by genetic sequencing experts at the Broad Institute, computational geneticists Pardis Sabeti and Shira Weingarten-Gabbay. They hoped to identify fragments of SARS-CoV-2 that activate the immune system’s T cells.

“The emergence of viral variants, an active area of research in my lab, is a major concern for vaccine development,” says Sabeti, a leader in the Broad Institute’s Infectious Disease and Microbiome Program. She is also a Harvard University professor of systems biology, organismic and evolutionary biology, and immunology and infectious disease, as well as a Howard Hughes Medical Institute investigator.

“We swung into full action right away because my laboratory had [already] generated human cell lines that could be readily infected with SARS-CoV-2,” Saeed says. The group’s efforts were spearheaded by two members of the Saeed lab: Da-Yuan Chen, a postdoctoral associate, and Hasahn Conway, a lab technician.

From the outset of COVID pandemic in early 2020, scientists around the world knew the identity of 29 proteins produced by SARS-CoV-2 virus in infected cells—viral fragments that now make up the spike protein in some coronavirus vaccines, such as the Moderna, Pfizer-BioNTech, and Johnson & Johnson vaccines. Later, scientists discovered another 23 proteins hidden inside the virus’ genetic sequence; however, the function of these additional proteins was a mystery until now. The new findings of Saeed and his collaborators reveal—unexpectedly and critically—that 25 percent of the viral protein fragments that trigger the human immune system to attack a virus come from these hidden viral proteins.

How exactly does the immune system detect these fragments? Human cells contain molecular “scissors”—called proteases—that, when the cells are invaded, hack off bits of viral proteins produced during infection. Those bits, containing internal proteins exposed by the chopping-up process—like the way the core of an apple is exposed when the fruit is segmented—are then transported to the cell membrane and pushed through special doorways. There, they stick outside the cell acting almost like a hitchhiker, waving down the help of passing T cells. Once T cells notice these viral flags poking through infected cells, they launch an attack and try to eliminate those cells from the body. And this T cell response isn’t insignificant—Saeed says there are links between the strength of this response and whether or not people infected with coronavirus go on to develop serious disease.

“It’s quite remarkable that such a strong immune signature of the virus is coming from regions [of the virus’ genetic sequence] that we were blind to,” says Weingarten-Gabby, the paper’s lead author and postdoctoral fellow in the Sabeti lab. “This is a striking reminder that curiosity-driven research stands at the basis of discoveries that can transform the development of vaccines and therapies.”

“Our discovery … can assist in the development of new vaccines that will mimic more accurately the response of our immune system to the virus,” Sabeti says.

T cells not only destroy infected cells but also memorize the virus’ flags so that they can launch an attack, stronger and faster, the next time the same or a different variant of the virus appears. That’s a crucial advantage, because Saeed and his collaborators say the coronavirus appears to delay the cell’s ability to call in immune help.

“This virus wants to go undetected by the immune system for as long as possible,” Saeed says. “Once it’s noticed by the immune system, it’s going to be eliminated, and it doesn’t want that.”

Based on their findings, Saeed says, a new vaccine recipe, incorporating some of the newly discovered internal proteins making up the SARS-CoV-2 virus, would be effective in stimulating an immune response capable of tackling a wide swath of newly emerging coronavirus variants. And given the speed with which these variants continue to appear around the world, a vaccine that can provide protection against all of them would be a game changer. 

Reference:
 Weingarten-Gabbay S, Klaeger S, Sarkizova S, et al. Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs. Cell. doi: 10.1016/j.cell.2021.05.046.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

Jeannie Baumann

NIH Chief Mulls ‘Precision’ Booster Shots Against Covid-19

  • June 16, 2021

Advances in precision medicine may help transform Covid-19 booster shots from a community-wide effort to one that’s tailored to individual immune responses.

There’s no conclusive data that follow-up vaccinations will be necessary, but Pfizer Inc. and Moderna Inc. are studying the issue to stay ahead of variants. A key element that vaccine makers will need to pinpoint is the specific measurable marker in the immune system—called correlates of protections—that determines if a vaccine is still providing protection.

“It’s going to be really interesting, because we’re all different people,” Francis S. Collins, director of the National Institutes of Health, said Wednesday at the Biotechnology Innovation Organization’s annual conference.

“Those experiments are getting done right now for the Moderna and the Pfizer trial. So we’ll know pretty soon what is thought to be the most reliable correlate,” he said.

Traditionally, the need for booster shots stems from an evaluation of aggregate data to determine when the level of protection has waned to the point where additional vaccinations are necessary.

“But we’re pretty good now at switching from one-size-fits-all to individual information, what I might call precision medicine,” Collins said. “Do we need precision boosters, to basically have some individual analysis of your immune response to say whether it’s ready for a boost or whether you can take your time?”

He added that precision boosters “is potentially going to be part of the answer this time, but it hasn’t been before.”

It’s unclear whether the NIH is funding research on precision boosters for Covid-19 vaccines specifically. But research to apply precision medicine to vaccinations is ongoing. Boston Children’s Hospital has a precision vaccines program to classify individuals into subgroups based on how likely they are to contract certain diseases and how likely they are to benefit from vaccination.

Virus Variants

Antibodies levels appear to protect both against the original coronavirus strain and the variants six to eight months after the original vaccination, based on evaluation of clinical trial participants.

“That’s the good news. But the bad news is they are trending down,” Collins said.

The mRNA vaccines by Pfizer and Moderna appear to offer protection against the known variants of concern, although that level of protection may be somewhat diminished. Public health leaders have urged people to get both doses of the vaccine as quickly as possible both to protect themselves, their communities, and to help stop the spread of variants.

Pfizer CEO Albert Bourla has said a booster may be necessary between eight and 12 months after receiving the second dose of the Pfizer-BioNTech vaccine. Early results from a Moderna study released last month indicated a booster shot the company developed appears to protect against the Beta variant, which was first identified in South Africa.

Anthony S. Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases, said at a White House press briefing recently the agency is studying both variant-specific boosters and boosting against the wild type, which is the background strain that contains no major mutations.

“The higher your degree of immune response against the wild-type, the greater the secondary coverage you have against a wide array of variants,” Fauci said. “When you look at particularly the double doses—primary and boost of the mRNA vaccines, which we have the most data—there is rather good protection that spills over against multiple variants.”

The complex situation for immunocompromised people and COVID-19 vaccines

The complex situation for immunocompromised people and COVID-19 vaccines

  • June 16, 2021

When Margaret Collins, a 43-year-old geologist from Fort Worth, Texas, got her first dose of the Moderna vaccine January 6, she came home and cried.

“I was finally getting the shot,” she says. “I saw it as a step back to the life that I loved.”

A self-described extrovert, Collins became a hermit during the pandemic. She and her husband rarely stepped outside, and never without a mask. Her caution is warranted because she suffers from a generalized autoimmune disorder that includes hepatitis, psoriatic arthritis, vitiligo, and type 1 diabetes. Collins is also particularly vulnerable to COVID-19 because she received a donated pancreas and kidney in 2014 and takes three medications to suppress her immune system so her body doesn’t reject those organs. Yet, vaccines work by harnessing the capability of a fully competent immune system.

Since the FDA authorized the first COVID-19 vaccine, people with compromised immune systems have lived in limbo, waiting to find out whether, or how much, vaccination might protect them. The vaccine clinical trials excluded nearly all immune-compromised people because including them might interfere with determining vaccine effectiveness for the general population. But that’s left this group with little data on what vaccination means for them. Now studies are trickling in.

“We’re starting to learn some of the things we don’t know, whereas before, it was a bunch of we don’t know what we don’t know,” says Peter Martin, a hematologist and oncologist at Weill Cornell Medicine in New York City.

It’s difficult to gauge the number of immune-compromised people in the U.S. One study estimates that 2.8 percent of people with private insurance take immune-suppressing drugs—about nine million Americans. But that doesn’t include Medicare or Medicaid patients, who are more likely to have some conditions requiring immunosuppression, says study author Beth Wallace, a rheumatologist at University of Michigan Medicine. It also doesn’t include people with immune-compromising conditions who aren’t taking immune-suppressing medications.

From the very beginning of the pandemic Collins worried how her body would respond to the vaccine. But when she later read a study of organ transplant recipients that found low antibody levels after the first mRNA vaccine dose, she panicked.

Even though she had been vaccinated and wore a mask, she thought “How safe was I? It really scared me.”

A follow-up study that found about half of transplant recipients responded to the vaccine offered her little comfort. “That’s essentially the flip of a coin,” Collins says. But a small study published Monday offers a flicker of hope.

After two doses of mRNA vaccine, 30 transplant recipients with no or low antibodies got a third shot, though not necessarily of the same vaccine they received first. The six people with low antibody levels subsequently developed higher levels, and a quarter of the others, who had never responded to the COVID-19 vaccine, developed antibody levels thought to be high enough to prevent COVID-19 after the third dose.

But this study has substantial limitations: It’s very small and involves a grab bag of different vaccine combinations. Further, the Food and Drug Administration has not authorized a third dose, and the Centers for Disease Control and Prevention currently advises against it. The authors concluded that their findings suggest the need for more studies to test third doses in people without fully functioning immune systems.

A diverse population

Immune-compromised people fall into two broad categories: Either they have an underlying condition that weakens their immune system, such as people with leukemia, uncontrolled HIV, or a rare genetic disease, or they have an underlying condition requiring immune-suppressing therapy, such as organ transplant recipients and people with rheumatic diseases (inflammatory, autoimmune conditions) or some cancers. A few conditions, such as chronic lymphocytic leukemia and lupus, fall into both categories.

Factors that might affect someone’s response to a vaccine include the medication they’re taking and what it does, how long they’ve been taking it, their specific disease, and their history of infection. For organ transplant recipients, the time since their transplant may also matter.

“That’s why it’s really important for people who have these immune-suppressed conditions to talk to an expert about their specific situation, because there is such a great amount of variability,” says Aaron Richterman, an infectious disease fellow at the University of Pennsylvania Perelman School of Medicine, regarding how immune-compromised people can assess their infection risk after vaccination.

Evidence so far is mixed

The wide range of conditions and drugs that weaken the immune system explain why the response to COVID-19 vaccines is so mixed. The evidence so far shows that transplant recipients, certain leukemia patients, and people taking a handful of specific medications have the poorest vaccine response. The drugs that appear linked with the poorest response include mycophenolate (prevents organ rejection), rituximab (treats some blood cancers and autoimmune diseases like rheumatoid arthritis), belatacept (prevents organ rejection), and methotrexate (treats a wide range of cancers and autoimmune diseases).

For example, the organ transplant study Collins read found only 54 percent of 658 organ transplantrecipients had any antibodies after two doses of the mRNA vaccine, particularly if they were taking a drug like mycophenolate. A similar study of 609 kidney transplant recipients found half had detectable antibodies after mRNA vaccination, but only 5 percent of those taking belatacept did. Transplant recipients produced even fewer antibodies in response to the one-dose Johnson & Johnson vaccine.

Studies in people with autoimmune disease have similarly shown that vaccine response typically depends on the specific drug they’re taking.

In a study of 404 people with rheumatic disease who had both doses of an mRNA vaccine, almost all had detectable antibodies, but those taking rituximab or mycophenolate had very low levels. Meanwhile, everyone taking anti-inflammation drugs called tumor necrosis factor (TNF) inhibitors to treat Crohn’s disease or rheumatoid or psoriatic arthritis, had strong antibody responses.

Another study (preprint) of 133 people had similar findings: Antibody levels were 1/50 as high in people taking rituximab, a drug that intentionally depletes antibody-producing B cells, as in people with competent immune systems. Those taking certain chemotherapy drugs, rheumatoid arthritis drugs, or prednisone—a steroid that treats inflammation—also had lower antibody levels.

People with certain types of leukemia or lymphomas, particularly non-Hodgkin’s lymphoma and chronic lymphocytic leukemia, also don’t produce many antibodies after vaccination, though people with most other cancers fare better. That’s particularly concerning since some people with CLL don’t know they have it, says study author Mounzer Agha, director of the Mario Lemieux Center for Blood Cancers at University of Pittsburgh Medical Center.

Those are just a sampling of the studies examining different immunecompromising conditions and medications, but all are small, providing only some insight into these specific conditions or therapies.

“What matters is how much immunosuppression you’re getting, what agents you’re getting, and possibly how long you’ve been getting them,” says Dorry Segev, a transplant surgeon and researcher at Johns Hopkins Medicine who wrote the organ transplant studies and several others above.

More than just antibodies

These studies also focus only on antibody response, which is just one component of the immune response.

“We think antibody levels may correlate to clinical protection to a degree,” Richterman says. But even in healthy people, he says, we don’t know the minimum antibody levels necessary to assure protection. Since the significance of antibody levels is ambiguous, the FDA and CDC recommend against antibody testing because it is unclear how to interpret the findings.

“Immunologic responses and effectiveness of a vaccine are two different things,” says Emily Blumberg, director of Transplant Infectious Diseases at Penn Medicine in Philadelphia. “We think vaccinating [transplant] patients may have a benefit above and beyond what you can measure with antibodies.”

That’s partly because vaccines induce immunity in multiple ways. One way is stimulating B cells to make antibodies, which explains why medications that reduce B cells—such as rituximab, methotrexate, mycophenolate, and steroids—result in such poor responses. But vaccines can also stimulate killer T cells, which attack infected cells, and helper T cells, which aid B cells and killer T cells.

“Our understanding of what’s happening on the T cell side is pretty close to zero,” Segev says. Studying T cell responses is difficult and costly, he adds, though his group and others are working on it.

Vaccines can also trigger the production of memory B cells, which remember how to make antibodies. “If you get the virus and the memory cells are there, then you can have a better and faster antibody response the next time around,” explains Ignacio Sanz, chief of rheumatology at Emory University School of Medicine. He believes that presence of memory B cells might partly explain why a third vaccine dose led to antibody production in transplant recipients without previous responses.

The only way to find out how effective the vaccines actually are in immune-compromised people is to wait fordata comparing infections between vaccinated and unvaccinated people in different immune-compromised groups, and that takes time.

What comes next

Where does all this leave the millions of people who don’t know if they are protected by the vaccine, especially with the CDC’s advice that vaccinated people can stop masking?

For now, “get vaccinated, act unvaccinated,” Segev says. But that’s a difficult message to communicate.

“One of the unintended consequences of [that message] is fueling vaccine hesitancy in patients who say, ‘Why should I bother if I’m not going to have a response?’” Blumberg says.

A February study of more than 1,200 people with autoimmune disease found that more than half wanted to get vaccinated, and a third were uncertain, despite studies showing the vaccines are safe for those with inflammatory diseases.

Alfred Kim, a rheumatologist at the Washington University School of Medicine who conducted one of the studies on people with rheumatic disease, agrees it can be confusing to advise patients to get vaccinated without being able assure it protects them, but “even partial protection is better than no protection,” he says.

That introduces another problem: How safely can immune-compromised people go out in public even if vaccinated?

“The CDC guidelines assume everybody is socially responsible, which unfortunately is not the case,” Agha says.

“Masks work, but masks work best if everybody is wearing them,” Segev says. “If you have a superspreader walking around Kroger spewing their Delta variant all over the store, and they’re standing next to an immunosuppressed transplant patient who tried their best to get vaccinated and is still wearing a mask, that [immunosuppressed] person is still at risk.”

While immune-compromised patients have always been more susceptible to infections, even before the pandemic, the stakes are higher now.

“With influenza, it was not such a great concern because patients do survive influenza even when they get quite ill,” Mounzer says. “With COVID, it’s a different story. There’s a real risk of dying from the disease.”

In a post-masking world, that makes even brief trips to the grocery store more complicated—and perilous—for immune-compromised people.

“As a society I think we have an obligation to come up with strategies to prevent those people from getting acutely sick so they can re-enter society like the rest of us are all ready to do,” Martin, the hematologist, says. “They’re just as ready as anybody else, and it’s terrifying to be in their position.”

Blumberg tells her patients to encourage friends, family members, and coworkers to get vaccinated. “The better job we do with vaccinating everybody, the less COVID there will be to make them sick,” she says.

That’s exactly what Collins, the vaccinated transplant recipient from Texas, is doing. But she has friends and family members who refuse to get vaccinated, and that frightens her, not only for herself but also for other immune-compromised family members and friends.

“If we reach herd immunity, then I have less to worry about,” Collins says. But she doesn’t think the country will reach that milestone, “which is scary for people like me.”

If social responsibility does not motivate people to get vaccinated, there’s also the specter of new variants. Evidence suggests that people whose immune systems don’t respond properly to infection could provide an ideal environment for mutations, says John Moore, a microbiologist and immunologist at Weill Cornell Medicine in New York City. “They have a lot of ongoing viral replication in their bodies for prolonged periods of time,” Moore says. “Virus replication in an antibody-low individual can drive the emergence of variants that are problematic on a societal basis, so this is not a trivial issue.”

In other words, protecting the most vulnerable members of society is ultimately the best way to protect all of society.

“These are the patients that are going to be a source of continued infection in the population,” Blumberg says. “If we don’t protect these immuno-suppressed hosts, we will have a harder time getting rid of the virus.”

COVID-19 Pandemic Easing: Go See Your Doctor

COVID-19 Pandemic Easing: Go See Your Doctor

  • June 15, 2021

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Experts say scheduling a medical checkup is an important step in a post-pandemic world. Supersizer/Getty Images
  • Health officials report that deaths related to heart disease, diabetes, and high blood pressure have all increased during the COVID-19 pandemic.
  • Experts say a major reason may be that people delayed their regular medical checkups.
  • They say now is a good time to schedule physical exams and diagnostic tests.
  • They add that focusing on eating habits and daily exercise routines is also a good idea.

As COVID-19 pandemic restrictions are fading in the United States, people are returning to restaurants, movie theaters, and sporting events.

Experts note there is another place in particular people may not have visited in more than a year where they should return as soon as possible.

The doctor’s office.

A recent report from the Centers for Disease Control and Prevention states that in the past year, deaths from both diabetes and heart disease have increased noticeably.

Specifically, heart disease-linked deaths rose by 32,000 over the previous year, a 3-percent jump, and only the second time in 20 years the rate has gone up.

Diabetes-related deaths increased by 13,000, or 14 percent. Deaths related to high blood pressure also ticked up 12 percent.

“I’m not surprised,” said Dr. Salim Virani, FACC, FAHA, FASPC, chair of the writing committee for the American Heart Association/American Stroke Association 2021 Statistical Update and an associate professor in cardiology and cardiovascular research sections at Baylor College of Medicine in Texas.

“Almost 40 percent of U.S. adults deferred care (in that time),” he told Healthline, adding that 12 percent of people who needed emergency care deferred as well.

In other words, Virani said, “Patients who actually need more care were deferring that care.”

Now, experts agree, is a good time to schedule a medical checkup to see where you are after a year of staying at home.

The first step in tackling this issue, according to Dr. Ping H. Wang, a professor and chair of the Department of Diabetes, Endocrinology & Metabolism at City of Hope in California, is realizing this: There actually is no blame.

“I don’t think this is anybody’s fault,” Wang told Healthline. “This is the biggest pandemic in [modern] human history. We all did the best we could.”

That’s why, he said, it’s not fair to blame people who deferred care or blame the medical community for advising people to stay home and be safe.

Even for those with comorbidities that usually require frequent medical visits, the message during lockdown seemed clear: Don’t venture out if you don’t have to.

That, Wang said, could have dissuaded many.

So, too, could the setup in clinics and hospitals at the time. Most people could not bring another person in with them, something that created a challenge for older as well as less independent individuals.

“People just didn’t feel comfortable,” he said.

Virani pointed out that early in the pandemic, emergency room visits dropped by more than 25 percent, something that foreshadowed these numbers.

“It’s not like during a pandemic there is less heart disease,” he said.

Virani also saw other signs.

Fitbit reported that in the first months of lockdown, even usually physically active people saw their activity levels decrease.

At the same time, he said, eating habits took a hit. In his research, Virani found that almost 40 percent of people reported a weight gain during the pandemic.

At the same time, he said, issues relating to mental health — something that can impact both heart health and diabetes — increased dramatically.

There were also issues related to limited access to medical staff and the financial impact of the pandemic.

With COVID-19 restrictions easing in most of the United States, experts say this is a good time to get back on track with your health.

The place to start, Virani said, is seeing your primary care physician.

“They are the person you should have a long-term relationship with,” he said.

Reaching out now to set an appointment — even if you have to wait for it — is the right move, he said.

He added that we have yet to learn just how long-term the elevated death rates from the pandemic will last.

“We have every reason to suspect that, unfortunately, [in] the next few years to come, we will continue to see this,” he said.

Going forward, Virani suggests focusing on a healthy daily diet, a regular exercise routine, and getting vaccinated against COVID-19 as well as other illnesses.

Among other things, he said, there’s some evidence that vaccines can help with inflammation, a component of heart disease and other ailments.

What can we learn from the COVID-19 pandemic should we face something like this again?

Wang said the medical community probably needs to adapt its messaging and availability going forward.

“How can we make resources available and accessible to those who need them (in another lockdown?),” Wang asked. “I don’t have an easy answer here,” he said. “But our community needs to address it.”

Smoking, central obesity, hypertension may lower antibody response to COVID-19 vaccine

Smoking, central obesity, hypertension may lower antibody response to COVID-19 vaccine

  • June 15, 2021


Disclosures:
The authors report no relevant financial disclosures.


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Compared with healthy adults, those who smoke or have central obesity or hypertension may produce fewer antibodies following Pfizer-BioNTech COVID-19 vaccination, according to a study published in Diabetes/Metabolism Research and Reviews.

Mikiko Watanabe

“Patients with central obesity, hypertension and smoking habit respond in a different way to Pfizer-BioNTech COVID-19 vaccine, where antibody titers are significantly lower compared to healthy subjects,” Mikiko Watanabe, MD, PhD, a specialist in endocrinology and metabolism at Sapienza University in Rome, told Healio. “Although lower antibody titers do not necessarily mean that protection against COVID-19 is hampered, it is necessary to plan follow-up studies to investigate this aspect, also considering the possibility that these patients might require earlier vaccine boosters over time.”



Central obesity, smoking, hypertension and dislipidemia were associated with fewer COVID-19 antibodies in people receiving the Pfizer-BioNTech COVID-19 vaccine. Data were derived from Watanabe M, et al. Diabetes Metab Res Rev. 2021;doi:10.1002/dmrr.3465.

Watanabe and colleagues conducted an observational study of 86 health care workers (mean age, 29 years; 39.5% men) at Policlinico Umberto I in Rome who received the Pfizer-BioNTech COVID-19 vaccine in January and February. All participants were older than 18 years, had stable body weight during the previous 3 months, had no previous COVID-19 infection, did not have immunodepression or use any medications known to affect the immune system and were not pregnant. Two doses of the vaccine were administered 21 days apart. Participants had blood drawn before the first dose and again 1 to 4 weeks after the second dose.

No major adverse events requiring hospitalization were reported after vaccination. Waist circumference, waist-to-hip ratio, BMI and body fat were not associated with more adverse events.

After the second dose, larger waist circumference was associated with fewer antibody titers (P = .004). Adults with hypertension had fewer antibodies compared with those without hypertension (650 U/mL vs. 1,911 U/mL; P = .001). Participants who habitually smoked had fewer antibodies vs. nonsmokers (1,099 U/mL vs. 1,921 U/mL; P = .007). Those with dyslipidemia also had fewer antibodies compared with those who had a normal lipid profile and were not on lipid-lowering drugs (534 U/mL vs. 1,872 U/mL; P = .005).

“We did not expect smoking to be a risk factor for lower antibody titers, as there is virtually zero available evidence suggesting that smoking is associated with reduced response to vaccines,” Watanabe said. “Conversely, we expected patients with central obesity being less protected similar to what observed by our team in a previous study regarding the association between central obesity and need of intubation in patients with COVID-19.”

In a multivariate model adjusting for sex, age and BMI, waist circumference, time since last vaccination, hypertension and smoking were significantly associated with fewer COVID-19 antibodies after vaccination.

Watanabe said more studies with a larger sample size and participants with more diverse BMI are needed, and cell-mediated immunity must be examined to confirm the study’s findings.

“Should these preliminary data be confirmed, identifying ways to boost the immune system so that these patients respond better to the vaccine is definitely advisable,” Watanabe said.

For more information:

Mikiko Watanabe, MD, PhD, can be reached at mikiko.watanabe@uniroma1.it.

After COVID-19, Kids Can Develop MIS-C: Here Are the Signs

After COVID-19, Kids Can Develop MIS-C: Here Are the Signs

  • June 15, 2021

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Young people who contract the coronavirus can also develop multisystem inflammation syndrome in children (MIS-C). Marko Geber/Getty Images
  • Among children who get COVID-19, a small proportion develop multisystem inflammation syndrome (MIS-C).
  • This serious complication can appear weeks after the initial infection.
  • MIS-C causes widespread inflammation that can affect multiple tissues and organs.

While COVID-19 tends to be less severe in children than in adults, some kids do become seriously ill with the disease or related complications.

Among young people who contract the coronavirus, a small proportion develop multisystem inflammation syndrome in children (MIS-C). This serious complication can appear weeks after the initial infection.

“MIS-C is a postinfectious inflammatory condition, where your body’s immune system kind of goes into overdrive,” said Dr. Christina Johns, MEd, FAAP, a pediatric emergency physician and the senior medical adviser for PM Pediatrics in Lake Success, New York.

“The ripple effect of that means that there can be lots of inflammatory processes going on in many different organs,” she said.

In a study published last week in JAMA Network Open, researchers looked at 1 million cases of people under age 21 who contracted the coronavirus and later developed MIS-C.

“While it is rare complication — and the numbers from this new study certainly support that — it is not one without consequence. It is not a small deal to get MIS-C,” Johns said.

The new study was conducted by researchers from Boston Children’s Hospital and the Centers for Disease Control and Prevention (CDC).

The researchers analyzed MIS-C surveillance data from seven jurisdictions: Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania.

They found that among people under age 20 in those jurisdictions, 248 cases of MIS-C were reported from April to June 2020.

Among children who developed COVID-19, Black, Latino or Hispanic, and Asian or Pacific Islander children were more likely than white children to develop MIS-C.

“We previously knew that MIS-C cases seem to be higher in Black Americans or Latino Americans, but we also knew that those groups have a higher risk of COVID,” said Dr. Lorry Rubin, director of pediatric infectious diseases at Cohen Children’s Medical Center of Northwell Health in New Hyde Park, New York.

“Now this study shows that certain racial groups are at higher risk, independent of their risk for getting COVID,” he said.

MIS-C causes widespread inflammation that can affect multiple tissues and organs.

“It triggers inflammation that affects a lot of the systems in the body: the heart, the gastrointestinal tract, the skin, the eye, and so forth,” Rubin said.

One of the most common symptoms is a fever that lasts for at least 3 to 4 days.

Other potential symptoms include:

  • skin rash
  • bloodshot eyes
  • red or swollen lips
  • abdominal pain
  • diarrhea
  • vomiting

The specific symptoms can vary from one child to another.

Several cases of the syndrome have also been reported in adults (MIS-A).

If you think your child might have MIS-C, the CDC advises you to contact their doctor, nurse, or clinic right away.

“What really concerns me about MIS-C is just how quickly children can go from seemingly completely OK, to not feeling well, to being highly critically ill,” Johns told Healthline.

“If parents have some significant concerns that something just isn’t quite right, trust that instinct,” she said.

Healthcare professionals treat MIS-C with supportive care, such as:

  • intravenous fluids
  • medications to reduce inflammation
  • treatments to improve heart function and breathing

“Inflammation involving the heart is perhaps the most serious feature, and many children come to medical attention with the severe impairment of heart function known as cardiogenic shock,” said Michael Grosso, MD, medical director and chair of pediatrics at Northwell Health’s Huntington Hospital in Long Island, New York.

“In such cases, children will require admission to a pediatric intensive care unit and life support,” he continued.

MIS-C is only one of several complications that children and adolescents can potentially develop from COVID-19.

“I want to sort of debunk the argument that if you’re in a pediatric age group, COVID’s no big deal,” Rubin said. “It is still a source of a lot of infection, morbidity, and even death in the pediatric age group.”

The only known way to prevent MIS-C and other COVID-19-related complications is to avoid contracting the coronavirus.

“That is best done by doing all the things we did throughout the pandemic: social distancing, hand hygiene, and masks,” Grosso said.

“Most important is getting immunized, at least for pediatric patients greater than 12 years of age,” he said.

The CDC currently recommends that everyone ages 12 and up get vaccinated against COVID-19.

Scientists are still studying COVID-19 vaccines in younger children. As more findings from those studies come out, Grosso expects that a vaccine will be granted emergency use authorization for younger kids “in the near future.”

Health expert explains how COVID-19 vaccines strengthen immune system to fight the virus

Health expert explains how COVID-19 vaccines strengthen immune system to fight the virus

  • June 15, 2021

BIRMINGHAM, Ala. (WBRC) – When getting vaccinated for the COVID-19 shot, it can make you feel crummy for a couple days but doctors say that doesn’t mean your immune system is slacking.

Even if you experience side effects, doctors say the vaccine does not weaken your immune system, instead, it strengthens it.

COVID-19 vaccines strengthen the immune system’s response to the virus, and the body having chills or fatigue is your immune system ramping up its power.

“We know that immune response can vary,” explained ADPH’s Dr. Karen Landers.

The data supports the conclusion that getting the vaccine will lessen the potential of a really bad case of COVID if you’re one of the people to contract it after getting the shot.

“Persons are less likely to have a severe illness, less likely to be hospitalized and they are less likely to die,” said Dr. Landers.

The vaccine arms the immune system with fighters, but they don’t always win; 800 Alabama residents who got the vaccine, got COVID after.

“We’ve had 54 people hospitalized which is an exceedingly small number,” said Dr. Landers.

She says the shot is the only surefire way to give your body the tools to effectively ward off worse case-scenarios.

Breakthrough cases are usually identified in people who go to the doctor with symptoms, so if you do have symptoms go get tested.

Copyright 2021 WBRC. All rights reserved.

Extra COVID-19 vaccine may help protect transplant patients

Extra COVID-19 vaccine may help protect transplant patients

  • June 14, 2021

A small study offers the first hint that an extra dose of COVID-19 vaccine might give some organ transplant recipients a boost in protection.

Even as most vaccinated people celebrate a return to near normalcy, millions who take immune-suppressing medicines because of transplants, cancer or other disorders remain in limbo — uncertain as to how protected they are against the coronavirus. It’s simply harder for vaccines to rev up a weak immune system.

The study published Monday tracked just 30 transplant patients, but it’s an important step toward learning if booster doses could help.

Of the 24 patients who appeared to have no protection after the routine two COVID-19 vaccinations, eight developed virus-fighting antibodies after an extra shot, researchers from Johns Hopkins University reported in Annals of Internal Medicine. And six others who’d had only minimal antibodies got a big boost from the third dose.

“It’s very encouraging,” said Dr. Dorry Segev, a Hopkins transplant surgeon who helped lead the research. “Just because you’re fully negative after two doses doesn’t mean that there’s no hope.”

Working with the National Institutes of Health, Segev’s team hopes to begin a more rigorous test of a third vaccination in 200 transplant recipients this summer.

Immune-suppressing drugs prevent rejection of transplant patients’ new organs but leave them extremely vulnerable to the coronavirus. Transplant patients were excluded from initial testing of COVID-19 vaccines, but doctors urge that they get vaccinated in hopes of at least some protection.

There is some benefit. The Hopkins team tested more than 650 transplant recipients and found that about 54% harbored virus-fighting antibodies after receiving two doses of the Pfizer-BioNTech or Moderna vaccines — although generally fewer than in otherwise healthy vaccinated people.

Protection against COVID-19 is also a concern for those with autoimmune disorders. One study of patients with rheumatoid arthritis, lupus and other autoimmune disorders found that 85% developed antibodies, said Dr. Alfred Kim of Washington University in St. Louis. But those who used certain immune-suppressing drugs produced dramatically lower levels, a cause for concern.

“We tell our patients to act like the vaccine is not going to work as well as it does for their family and friends,” said Kim, who would like to test a third dose in autoimmune patients. “This is very frustrating news to them.”

Guidelines issued in France recommend a third COVID-19 shot for certain severely immune-suppressed people, including transplant recipients, Segev noted.

Doctors sometimes give extra doses of other vaccines, such as the hepatitis B shot, to people with weak immune systems.

The U.S. hasn’t authorized extra COVID-19 vaccinations. But around the country, immune-compromised patients are seeking third doses on their own; those are the people Hopkins sought to test.

In San Francisco, Gillian Ladd agreed to blood tests before and after receiving an extra dose. The transplant recipient of a kidney and pancreas, Ladd, 48, was terrified to leave her house after learning she had no measurable COVID-19 antibodies, despite two Pfizer shots.

With the additional dose, she said, “I had gotten what I needed in order to survive,” but she’s sticking with masks and other precautions.

“I am being as careful as I possibly can while acknowledging that I’m coming back into the world of the living,” she said.

Additional research is needed to tell if a third dose really helps, who are the best candidates and if different brands of vaccine offer different benefits — plus whether the extra immune stimulation could increase the risk of organ rejection.

Segev notes that in addition to antibodies, vaccinations normally spur protections such as T-cells that can fend off severe illness. He and other research groups are testing whether immune-compromised patients get that benefit.

But for now, said Washington University’s Kim, “the best way to protect these people is for others to get vaccinated.”

‘This gives hope’: A third COVID-19 vaccine dose can boost protection for organ transplant recipients | Science

‘This gives hope’: A third COVID-19 vaccine dose can boost protection for organ transplant recipients | Science

  • June 14, 2021

RLT Illustrations/iStock

Science’s COVID-19 reporting is supported by the Heising-Simons Foundation.

A few months ago, transplant surgeon Dorry Segev was despondent about how COVID-19 vaccines were performing in patients like his, who have a donated organ and take powerful drugs to suppress their immune system. After one dose of a highly effective messenger RNA (mRNA) vaccine, for example, just 17% of those patients churned out protective antibodies against the pandemic coronavirus, and after the standard two doses, only 54% did. The very medications his patients took to protect their transplanted organ precluded them from mounting a healthy immune response after the vaccine. Even people who did make the antiviral antibodies often had very low levels, raising questions about how well they were shielded from COVID-19.

But now Segev, at Johns Hopkins University, has become cautiously optimistic. He and his colleagues have found that a third dose of vaccine may help: Among 24 organ transplant patients who had no antibodies after two doses, eight people generated protective antibodies after they sought out a third on their own. Six people who had few antibodies against the coronavirus after two doses all wound up with high levels after a third shot, the researchers reported today in the Annals of Internal Medicine. Although Segev didn’t conduct a systematic study—the 30 patients got combinations of different vaccines at different time intervals—“this gives hope, which is critical right now,” he says. “There is some encouraging evidence that we will be able to help the immune system do what it needs to do.”

The organ transplant recipients are participants in a research project Segev and his colleagues are running, studying COVID-19 vaccine responses in people with compromised immune systems. In this case, “We just got emails from people saying, ‘Hey, I’m getting a third dose, do you want my blood?’” Segev says. He jumped at the opportunity. (In the United States, determined individuals can secure extra vaccine doses despite the current authorized mRNA vaccines using just two.)

Segev’s study is the first to report outcomes after a third dose of vaccine, and it’s part of a broader discussion about whether and when to offer extra doses to vulnerable individuals. In France, health officials in April recommended a third dose for all of the country’s organ recipients. Because of that policy shift, 383 kidney transplant recipients at Strasbourg University Hospital have received a third dose of Moderna’s mRNA vaccine, and doctors have antibody results for 184 of them. Although the results aren’t yet published, they roughly match Segev’s small cohort: Twenty-eight percent of the French patients who had no antibodies after two doses developed them after the third shot, and 82% who had a weak reaction after two shots had a stronger response after the third, says Sophie Ohlmann, a nephrologist at the hospital.

In the United States, people with organ transplants number about 500,000, but they aren’t the only ones worrying about how well the vaccines are working for them—others include people with autoimmune diseases and those with cancer who got COVID-19 vaccines while their immune system was suppressed by chemotherapy. “It wouldn’t surprise me to see that higher doses work, but we have to do it systematically and find out,” says Deepali Kumar, director of transplant infectious diseases at Toronto General Hospital.

She argues that clinical trials studying third doses are crucial to provide clarity on ideal timing and potential risks in vulnerable populations. One of her concerns is whether an extra dose of vaccine, which revs up the immune system, could induce rejection of a donated organ; in Segev’s study, a heart transplant patient had a mild rejection episode 1 week after her third dose, though doctors can’t say whether it was linked to the additional dose. She recovered without incident.

Kumar expects results in July from a clinical trial she’s running in 120 transplant patients, only about one-third of whom had any antibodies after two doses of Moderna’s vaccine. The trial provided one-half of all participants a third dose 2 months after their second shot, and the rest got a placebo injection.

In Germany, 11 centers running a COVID-19 vaccine study are recruiting volunteers with a range of conditions that, by their nature or because of their medications, can affect immune functioning, including people with transplanted organ or autoimmune diseases, and those on kidney dialysis. Researchers will study antibodies and T cells after the second dose of vaccine, and may eventually offer some participants a third vaccine dose, says Leif Erik Sander, an infectious disease expert at the Charité University Hospital in Berlin, who is helping lead the work. And Segev is in discussions with the National Institutes of Health to start a trial this summer in transplant patients.

 “We have a strong biologic rationale for a third dose in specific populations,” says Ravi Parikh, a health policy researcher and medical oncologist at the University of Pennsylvania. His patients haven’t asked him yet about third doses, but he imagines himself supporting that strategy for some.

When it comes to people with cancer, Parikh is not deeply worried about the effectiveness of two doses. Last month, a study in JAMA Oncology reported that 90% of a group of cancer patients on chemotherapy and other drugs produced antibodies after two doses of Pfizer’s mRNA vaccine. (Parikh co-wrote a commentary accompanying that paper.) Another study in Cancer Cell this month reported that 94% of 200 cancer patients had antibodies after vaccination. Those numbers are “excellent news,” says Salomon Stemmer, a medical oncologist at Tel Aviv University who led the JAMA Oncology study.

But in Stemmer’s cohort of 102 patients on treatment, antibody levels were between one-quarter and one-third of their healthy family members’ after they got a vaccine. The difference doesn’t strongly concern Stemmer, but because the level of SARS-CoV-2 antibodies declines naturally over time, he wonders whether they may drop worryingly low in cancer patients sooner, because they start from a lower level. Parikh agrees this is a big question: “We don’t know how quickly these antibody titers are going to fall,” he says.

Stemmer is continuing to follow his cohort and plans to test antibody levels every 2 to 3 months. He also wants to learn more about the small group of patients that produced no antibodies to SARS-CoV-2 at all: They include three women with breast cancer getting “dose-dense” chemotherapy, which means less time between treatments. Third vaccine doses might be helpful in some cases, but Stemmer says he would only offer them as part of a clinical trial.

Segev hopes more information to help these populations will come soon. Right now, he acknowledges, “There is a lack of guidance and a lack of knowledge.” In the meantime, Segev recognizes that some people may prefer to take matters into their own hands, whereas others would eagerly join a clinical trial—though he urges anyone considering a third vaccine dose to speak to their doctor first. “Whatever is happening out there, we are going to learn from as much as we possibly can,” he says.

Do I need a vaccine if I’ve already had COVID-19?

Do I need a vaccine if I’ve already had COVID-19?

  • June 14, 2021

The Centers for Disease Control announced that in most cases, vaccinated adults in the U.S. could start going without masks, even indoors — a long-awaited benchmark to signal a return to a more normal life. But many people still have lingering questions about the COVID-19 vaccines and whether or not they’re needed, especially if you’ve already had COVID-19. 

Jennifer Pisano is an Associate Professor of Medicine in Infectious Diseases at the University of Chicago. She serves as medical director of antimicrobial stewardship and infection control at the University of Chicago Medicine.

“As an infectious diseases expert and someone who contracted COVID-19 myself, I’m here to share my insights,” said Pisano. 

I’m young and healthy and I haven’t caught COVID yet. Do I need to get a vaccine?

Yes, absolutely. The SARS-CoV-2 virus is still circulating in our communities, and we haven’t reached herd-immunity levels of vaccination yet. Even if you are young and don’t have any underlying health conditions that would put you at extra risk, the way individual people respond to COVID-19 is unpredictable — that’s part of what makes it so dangerous.

 In almost every case, I would recommend getting vaccinated. It protects not only you, but also those who are close to you and the people you love. If you don’t want to get it for your own protection, get it for them.

Do I still need the vaccine if I’ve already had COVID-19?

Absolutely. While we know recovering from a COVID-19 infection means you will have circulating antibodies in your system, we are still learning about how the immune system handles the antibody response after a natural infection. We’re not sure how protective the antibodies are from different kinds of infections — such as an asymptomatic infection versus a symptomatic infection. With vaccination, we know that people with healthy immune systems are getting a great antibody response. So I would recommend vaccination even after a COVID-19 infection to get the best protection. 

On top of that, if you live with people who are at higher risk of severe infection or may not develop a strong antibody level after vaccination, getting your own COVID-19 vaccination may make it less likely that you will transmit the virus to them. 

When should I get vaccinated after having COVID-19?

The current guidance says that as long as you are no longer at risk of exposing other people to the virus, you can get your vaccine at any time. That means that once you are no longer in isolation and are no longer infectious, any time is fine. 

The exception is for people who received monoclonal antibodies as part of their COVID-19 treatment. The current recommendation is that these patients wait at least 90 days after their treatment to be vaccinated, because they will already have COVID-19 antibodies circulating in their system and we just don’t know enough about the virus or its antibodies to know if this particular treatment could interfere with the vaccine’s effectiveness.

Is it better to gain immunity through exposure to COVID-19 or through a vaccine?

With some viruses, such as chicken pox, being infected with the virus itself grants stronger immune protection than the chicken pox vaccine; however, in those cases, you then have to deal with all the complications of having the virus. When it comes to COVID-19, it’s really hard to know whether being exposed to the virus is more protective of future infection than the vaccine, simply because we don’t know the SARS-CoV-2 virus well enough yet.

With natural immunity, which is the protection we get after being infected with a virus, the immune response can be variable. For example: the number of antibodies your body produces may depend on how much of the virus you’re exposed to. And there is likely beneficial variation in the types of antibodies being produced. The vaccinations currently available in the U.S. have been shown to effectively stimulate antibodies against the virus’ spike protein. New vaccines are being created that make antibodies to other parts of the virus as well. Both immunity from natural infection and vaccination stimulate a T-cell response that will hopefully provide you with protection from the virus for a longer time. 


While it’s possible some people may have a higher antibody response after a natural infection than they would after vaccination, we’re still learning about this new virus, and we don’t know how protective natural immunity really is, especially when there is such a continuum of different types of infections. We don’t have clear data on how antibody responses from a mild infection compare to a severe infection, or how protective those antibody responses are.

On the other hand, we do know that the vaccine is very protective. In most people, getting vaccinated generates a lot of antibodies. So far, the vaccines appear to be incredibly effective, especially when it comes to preventing severe infections, hospitalizations and death.

Is there any extra risk if I get the vaccine after having had COVID-19?

There are a lot of anecdotal reports that many people who have had COVID-19 experience stronger side effects after their first vaccine dose, while most people who have never had COVID-19 have a stronger response after the second dose. But each person’s experience is unique. Different people have different side effects and some people who haven’t had COVID-19 report very strong side effects, too.

It’s also important to note that it’s possible many people who are being vaccinated were exposed to COVID-19 and had an asymptomatic infection without realizing it, which could contribute to the variation in side effects.

Personally, I found the side effects of my first vaccine to be pretty strong — it felt like I had COVID-19 again — but this time without the scary cough and shortness of breath. I had a high fever, chills and muscle aches, but it was not as overwhelming as I had feared. After a day or two, I was back to normal, and the side effects were certainly easier to manage than being sick with COVID-19. It was helpful to expect the side effects and to know my immune system was getting a boost. I was lucky to be able to plan to spend a day or two in bed. After my second vaccine, I just had a sore arm.

Can I still get COVID-19 after having the vaccine?

Yes, you can still get COVID-19 after getting the vaccine. In fact, we’re sometimes seeing people pop up with reinfections. In the majority of cases, these are people who are being screened asymptomatically and just happen to be positive for the virus, or who show mild symptoms of the virus. The vaccine is intended to prevent severe infections and hospitalizations and it’s doing an excellent job!

We can predict who might not have the best immune response to the vaccine — these are usually people who have other health conditions affecting the strength of their immune system, such as organ transplants or cancer. These people are likely to have already been taking precautions to prevent illness even before the pandemic and will most benefit from continuing to follow other guidance on preventing COVID-19 even after their vaccination, such as mask wearing and social distancing.

We also think that the amount of virus a person is exposed to can influence the severity of infection. So even as masking guidance changes and people start gathering in larger crowds again, individuals should be aware of their own comfort levels and remember that even after vaccination, there is still some risk of possible infection.

I’m still nervous! 

I understand. I was nervous about getting my vaccine, too! After dealing with COVID-19, I was worried about the possible side effects, and the clinical trials hadn’t really looked at whether there were any extra risks to getting the vaccine if a person already had the virus. But when my ticket came up, I decided to get my vaccine. I knew that it would give me more protection in the long term, and I had other personal reasons, too.

I wanted to feel comfortable seeing my parents again — to spend time with my family and not worry about spreading the virus. I recently had the one-year anniversary of my COVID-19 diagnosis, and I get a little emotional to think about how far we’ve come. To think that we’re able to start seeing people in person again, thanks to these vaccines. 

I am grateful to have had the opportunity to be vaccinated, and I hope that my patients will choose to be vaccinated, too.

—Adapted from an article first published by the University of Chicago Medicine.

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