Posted on by Dr. Francis Collins
There’s been great concern about the new Omicron variant of SARS-CoV-2, the coronavirus that causes COVID-19. A major reason is Omicron has accumulated over 50 mutations, including about 30 in the spike protein, the part of the coronavirus that mRNA vaccines teach our immune systems to attack. All of these genetic changes raise the possibility that Omicron could cause breakthrough infections in people who’ve already received a Pfizer or Moderna mRNA vaccine.
So, what does the science show? The first data to emerge present somewhat encouraging results. While our existing mRNA vaccines still offer some protection against Omicron, there appears to be a significant decline in neutralizing antibodies against this variant in people who have received two shots of an mRNA vaccine.
However, initial results of studies conducted both in the lab and in the real world show that people who get a booster shot, or third dose of vaccine, may be better protected. Though these data are preliminary, they suggest that getting a booster will help protect people already vaccinated from breakthrough or possible severe infections with Omicron during the winter months.
Though Omicron was discovered in South Africa only last month, researchers have been working around the clock to learn more about this variant. Last week brought the first wave of scientific data on Omicron, including interesting work from a research team led by Alex Sigal, Africa Health Research Institute, Durban, South Africa .
In lab studies working with live Omicron virus, the researchers showed that this variant still relies on the ACE2 receptor to infect human lung cells. That’s really good news. It means that the therapeutic tools already developed, including vaccines, should generally remain useful for combatting this new variant.
Sigal and colleagues also tested the ability of antibodies in the plasma from 12 fully vaccinated individuals to neutralize Omicron. Six of the individuals had no history of COVID-19. The other six had been infected with the original variant in the first wave of infections in South Africa.
As expected, the samples showed very strong neutralization against the original SARS-CoV-2 variant. However, antibodies from people who’d been previously vaccinated with the two-dose Pfizer vaccine took a significant hit against Omicron, showing about a 40-fold decline in neutralizing ability.
This escape from immunity wasn’t complete. Indeed, blood samples from five individuals showed relatively good antibody levels against Omicron. All five had previously been infected with SARS-CoV-2 in addition to being vaccinated. These findings add to evidence on the value of full vaccination for protecting against reinfections in people who’ve had COVID-19 previously.
Also of great interest were the first results of the Pfizer study, which the company made available in a news release . Pfizer researchers also conducted laboratory studies to test the neutralizing ability of blood samples from 19 individuals one month after a second shot compared to 20 others one month after a booster shot.
These studies showed that the neutralizing ability of samples from those who’d received two shots had a more than 25-fold decline relative to the original virus. Together with the South Africa data, it suggests that the two-dose series may not be enough to protect against breakthrough infections with the Omicron variant.
In much more encouraging news, their studies went on to show that a booster dose of the Pfizer vaccine raised antibody levels against Omicron to a level comparable to the two-dose regimen against the original variant (as shown in the figure above). While efforts already are underway to develop an Omicron-specific COVID-19 vaccine, these findings suggest that it’s already possible to get good protection against this new variant by getting a booster shot.
Very recently, real-world data from the United Kingdom, where Omicron cases are rising rapidly, are providing additional evidence for how boosters can help. In a preprint , Andrews et. al showed the effectiveness of two shots of Pfizer mRNA vaccine trended down after four months to about 40 percent. That’s not great, but note that 40 percent is far better than zero. So, clearly there is some protection provided.
Most impressively (as shown in the figure from Andrews N, et al.) a booster substantially raised that vaccine effectiveness to about 80 percent. That’s not quite as high as for Delta, but certainly an encouraging result. Once again, these data show that boosting the immune system after a pause produces enhanced immunity against new viral variants, even though the booster was designed from the original virus. Your immune system is awfully clever. You get both quantitative and qualitative benefits.
It’s also worth noting that the Omicron variant mostly doesn’t have mutations in portions of its genome that are the targets of other aspects of vaccine-induced immunity, including T cells. These cells are part of the body’s second line of defense and are generally harder for viruses to escape. While T cells can’t prevent infection, they help protect against more severe illness and death.
It’s important to note that scientists around the world are also closely monitoring Omicron’s severity While this variant appears to be highly transmissible, and it is still early for rigorous conclusions, the initial research indicates this variant may actually produce milder illness than Delta, which is currently the dominant strain in the United States.
But there’s still a tremendous amount of research to be done that could change how we view Omicron. This research will take time and patience.
What won’t change, though, is that vaccines are the best way to protect yourself and others against COVID-19. (And these recent data provide an even-stronger reason to get a booster now if you are eligible.) Wearing a mask, especially in public indoor settings, offers good protection against the spread of all SARS-CoV-2 variants. If you’ve got symptoms or think you may have been exposed, get tested and stay home if you get a positive result. As we await more answers, it’s as important as ever to use all the tools available to keep yourself, your loved ones, and your community happy and healthy this holiday season.
 SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. Sandile C, et al. Sandile C, et al. medRxiv preprint. December 9, 2021.
 Pfizer and BioNTech provide update on Omicron variant. Pfizer. December 8, 2021.
 Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern. Andrews N, et al. KHub.net preprint. December 10, 2021.
COVID-19 Research (NIH)
Sigal Lab (Africa Health Research Institute, Durban, South Africa)
Posted on by Dr. Francis Collins
Any of the available COVID-19 vaccines offer remarkable personal protection against the coronavirus SARS-CoV-2. So, it also stands to reason that folks who are vaccinated will reduce the risk of spreading the virus to family members within their households. That protection is particularly important when not all family members can be immunized—as when there are children under age 12 or adults with immunosuppression in the home. But just how much can vaccines help to protect families from COVID-19 when only some, not all, in the household have immunity?
A Swedish study, published recently in the journal JAMA Internal Medicine, offers some of the first hard figures on this topic, and the findings are quite encouraging . The data show that people without any immunity against COVID-19 were at considerably lower risk of infection and hospitalization when other members of their family had immunity, either from a natural infection or vaccination. In fact, the protective effect on family members went up as the number of immune family members increased.
The findings come from a team led by Peter Nordström, Umeå University, Sweden. Like in the United States, vaccinations in Sweden initially were prioritized for high-risk groups and people with certain preexisting conditions. As a result, Swedish families have functioned, often in close contact, as a mix of immune and susceptible individuals over the course of the pandemic.
To explore these family dynamics in greater detail, the researchers relied on nationwide registries to identify all Swedes who had immunity to SARS-COV-2 from either a confirmed infection or vaccination by May 26, 2021. The researchers identified more than 5 million individuals who’d been either diagnosed with COVID-19 or vaccinated and then matched them to a control group without immunity. They also limited the analysis to individuals in families with two to five members of mixed immune status.
This left them with about 1.8 million people from more than 800,000 families. The situation in Sweden is also a little unique from most Western nations. Somewhat controversially, the Swedish government didn’t order a mandatory citizen quarantine to slow the spread of the virus.
The researchers found in the data a rising protective effect for those in the household without immunity as the number of immune family members increased. Families with one immune family member had a 45 to 61 percent lower risk of a COVID-19 infection in the home than those who had none. Those with two immune family members enjoyed more protection, with a 75 to 86 percent reduction in risk of COVID-19. For those with three or four immune family members, the protection went up to more than 90 percent, topping out at 97 percent protection. The results were similar when the researchers limited the analysis to COVID-19 illnesses serious enough to warrant a hospital stay.
The findings confirm that vaccination is incredibly important not only for individual protection, but also for reducing transmission, especially within families and those with whom we’re in close physical contact. It’s also important to note that the findings apply to the original SARS-CoV-2 variant, which was dominant when the study was conducted. But we know that the vaccines offer good protection against Delta and other variants of concern.
These results show quite clearly that vaccines offer protection for individuals who lack immunity, with important implications for finally ending this pandemic. This doesn’t change the fact that all those who can and still need to get fully vaccinated should do so as soon as possible. If you are eligible for a booster shot, that’s something to consider, too. But, if for whatever reason you haven’t gotten vaccinated just yet, perhaps these new findings will encourage you to do it now for the sake of those other people you care about. This is a chance to love your family—and love your neighbor.
 Association between risk of COVID-19 infection in nonimmune individuals and COVID-19 immunity in their family members. Nordström P, Ballin M, Nordström A. JAMA Intern Med. 2021 Oct 11.
COVID-19 Research (NIH)
Peter Nordström (Umeå University, Sweden)
Posted on by Dr. Francis Collins
As long and difficult as this pandemic has been, I remain overwhelmingly grateful for the remarkable progress being made, including the hard work of so many people to develop rapidly and then deploy multiple life-saving vaccines. And yet, grave concerns remain that vaccine hesitancy—the reluctance of certain individuals and groups to get themselves and their children vaccinated—could cause this pandemic to go on much longer than it should.
We’re seeing the results of such hesitancy in the news every day, highlighting the rampant spread of COVID-19 that’s stretching our healthcare systems and resources dangerously thin in many places. The vast majority of those currently hospitalized with COVID-19 are unvaccinated, and most of those tragic 2,000 deaths each day could have been prevented. The stories of children and adults who realized too late the importance of getting vaccinated are heartbreaking.
With these troubling realities in mind, I was encouraged to see a new study in the journal JAMA Network Open that tracked vaccine hesitancy over time in a random sample of more than 4,600 Americans. This national study shows that vaccine hesitancy isn’t set in stone. Over the course of this pandemic, hesitancy has decreased, and many who initially said no are now getting their shots. Many others who remain unvaccinated lean toward making an appointment.
The findings come from Aaron Siegler and colleagues, Emory University, Atlanta. They were interested in studying how entrenched vaccine hesitancy would be over time. The researchers also wanted to see how often those who were initially hesitant went on to get their shots.
To find out, they recruited a diverse, random, national sampling of individuals from August to December 2020, just before the first vaccines were granted Emergency Use Approval and became widely available. They wanted to get a baseline, or starting characterization, on vaccine hesitancy. Participants were asked two straightforward questions, “Have you received the COVID-19 vaccine?” and “How likely are you to get it in the future?” From March to April 2021, the researchers followed up by asking participants the same questions again when vaccines were more readily available to many (although still not all) adults.
The survey’s initial results showed that nearly 70 percent of respondents were willing to get vaccinated at the outset, with the other 30 percent expressing some hesitancy. The good news is among the nearly 3,500 individuals who answered the survey at follow-up, about a third who were initially vaccine hesitant already had received at least one shot. Another third also said that they’d now be willing to get the vaccine, even though they hadn’t just yet.
Among those who initially expressed a willingness to get vaccinated, about half had done so at follow up by spring 2021 (again, some still may not have been eligible). Forty percent said they were likely to get vaccinated. However, 7 percent of those who were initially willing said they were now less likely to get vaccinated than before.
There were some notable demographic differences. Folks over age 65, people who identified as non-Hispanic Asians, and those with graduate degrees were most likely to have changed their minds and rolled up their sleeves. Only about 15 percent in any one of these groups said they weren’t willing to be vaccinated. Most reluctant older people ultimately got their shots.
The picture was more static for people aged 45 to 54 and for those with a high school education or less. The majority of those remained unvaccinated, and about 40 percent still said they were unlikely to change their minds.
At the outset, people of Hispanic heritage were as willing as non-Hispanic whites to get vaccinated. At follow-up, however, fewer Hispanics than non-Hispanic whites said they’d gotten their shots. This finding suggests that, in addition to some hesitancy, there may be significant barriers still to overcome to make vaccination easier and more accessible to certain groups, including Hispanic communities from Central and South America.
Willingness among non-Hispanic Blacks was consistently lowest, but nearly half had gotten at least one dose of vaccine by the time they completed the second survey. That’s comparable to the vaccination rate in white study participants. For more recent data on vaccination rates by race/ethnicity, see this report from the Kaiser Family Foundation.
Overall, while a small number of respondents grew more reluctant over time, most people grew more comfortable with the vaccines and were more likely to say they’d get vaccinated, if they hadn’t already. In fact, by the end of the study, the hesitant group had shrunk from 31 to 15 percent. It’s worth noting that the researchers checked the validity of self-reported vaccination using antibody tests and the results matched up rather well.
This is all mostly good news, but there’s clearly more work to do. An estimated 70 million eligible Americans have yet to get their first shot, and remain highly vulnerable to infection and serious illness from the Delta variant. They are capable of spreading the virus to other vulnerable people around them (including children), and incubating the next variants that might provide more resistance to the vaccines and therapies. They are also at risk for Long COVID, even after a relatively mild acute illness.
The work ahead involves answering questions and addressing concerns from people who remain hesitant. It’s also incredibly important to reach out to those willing, but unvaccinated, individuals, to see what can be done to help them get their shots. If you happen to be one of those, it’s easy to find the places near you that have free vaccines ready to administer. Go to vaccines.gov, or punch 438829 on your cell phone and enter your zip code—in less than a minute you will get the location of vaccine sites nearby.
Nearly 400 million COVID-19 vaccine doses have been administered in communities all across the United States. More than 600,000 more are being administered on average each day. And yet, more than 80,000 new infections are still reported daily, and COVID-19 still steals the lives of about 2,000 mostly unvaccinated people each day.
These vaccines are key for protecting yourself and ultimately beating this pandemic. As these findings show, the vast majority of Americans understand this and either have been vaccinated or are willing to do so. Let’s keep up the good work, and see to it that even more minds will be changed—and more individuals protected before they may find it’s too late.
 Trajectory of COVID-19 vaccine hesitancy over time and association of initial vaccine hesitancy with subsequent vaccination. Siegler AJ, Luisi N, Hall EW, Bradley H, Sanchez T, Lopman BA, Sullivan PS. JAMA Netw Open. 2021 Sep 1;4(9):e2126882.
COVID-19 Research (NIH)
COVID-19 Vaccinations in the United States (Centers for Disease Control and Prevention, Atlanta)
Aaron Siegler (Emory University, Atlanta)
NIH Support: National Institute for Allergy and Infectious Diseases
Posted on by Dr. Francis Collins
As a kid who was home-schooled on a Virginia farm in the 1950s, I wasn’t around other kids very much, and so didn’t get exposed to measles. And there was no vaccine yet. Later on as a medical resident, I didn’t recognize that I wasn’t immune. So when I was hospitalized with a severe febrile illness at age 29, it took a while to figure out the diagnosis. Yes, it was measles. I have never been that sick before or since. I was lucky not to have long-term consequences, and now I’m learning that there may be even more to consider.
With the big push to get kids vaccinated, you’ve probably heard about some of the very serious complications of measles: hearing-threatening ear infections, bronchitis, laryngitis, and even life-threatening forms of pneumonia and encephalitis. But now comes word of yet another way in which the measles can be devastating—one that may also have long-term consequences for a person’s health.
In a new study in the journal Science, a research team, partly funded by NIH, found that the measles virus not only can make children deathly ill, it can cause their immune systems to forget how to ward off other common infections . The virus does this by wiping out up to nearly three-quarters of the protective antibodies that a child’s body has formed in response to past microbial invaders and vaccinations. This immune “amnesia” can leave a child more vulnerable to re-contracting infections, such as influenza or respiratory syncytial virus (RSV), that they may have been protected against before they came down with measles.
The finding comes as yet another reason to feel immensely grateful that, thanks to our highly effective vaccination programs, most people born in the U.S. from the 1960s onward should never have to experience the measles.
There had been hints that the measles virus might somehow suppress a person’s immune system. Epidemiological evidence also had suggested that measles infections might lead to increased susceptibility to infection for years afterwards . Scientists had even suspected this might be explained by a kind of immune amnesia. The trouble was that there wasn’t any direct proof that such a phenomenon actually existed.
In the new work, the researchers, led by Michael Mina, Tomasz Kula, and Stephen Elledge, Howard Hughes Medical Institute and Brigham and Women’s Hospital, Boston, took advantage of a tool developed a few years ago in the Elledge lab called VirScan . VirScan detects antibodies in blood samples acquired as a result of a person’s past encounters with hundreds of viruses, bacteria, or vaccines, providing a comprehensive snapshot of acquired immunity at a particular moment in time.
To look for evidence of immune amnesia following the measles, the research team needed blood samples gathered from people both before and after infection. These types of samples are currently hard to come by in the U.S. thanks to the success of vaccines. By partnering with Rik de Swart, Erasmus University Medical Center, Rotterdam, Netherlands, they found the samples that they needed.
During a recent measles outbreak in the Netherlands, de Swart had gathered blood samples from children living in communities with low vaccination rates. Elledge’s group used VirScan with 77 unvaccinated kids to measure antibodies in samples collected before and about two months after their measles infections.
That included 34 children who had mild infections and 43 who had severe measles. The researchers also examined blood samples from five children who remained uninfected and 110 kids who hadn’t been exposed to the measles virus.
The VirScan data showed that the infected kids, not surprisingly, produced antibodies to the measles virus. But their other antibodies dropped and seemed to be disappearing. In fact, depending on the severity of measles infection, the kids showed on average a loss of around 40 percent of their antibody memory, with greater losses in children with severe cases of the measles. In at least one case, the loss reached a whopping 73 percent.
This all resonates with me. I do recall that after my bout with the measles, I seemed to be coming down with a lot of respiratory infections. I attributed that to the lifestyle of a medical resident—being around lots of sick patients and not getting much sleep. But maybe it was more than that.
The researchers suggest that the loss of immune memory may stem from the measles virus destroying some of the long-lived cells in bone marrow. These cells remember past infections and, based on that immunological memory, churn out needed antibodies to thwart reinvading viruses.
Interestingly, after a measles infection, the children’s immune systems still responded to new infections and could form new immune memories. But it appears the measles caused long term, possibly permanent, losses of a significant portion of previously acquired immunities. This loss of immune memory put the children at a distinct disadvantage should those old bugs circulate again.
It’s important to note that, unlike measles infection, the MMR (measles, mumps, rubella) vaccine does NOT compromise previously acquired immunity. So, these findings come as yet another reminder of the public value of measles vaccination.
Prior to 1963, when the measles vaccine was developed, 3 to 4 million Americans got the measles each year. As more people were vaccinated, the incidence of measles plummeted. By the year 2000, the disease was declared eliminated from the U.S.
Unfortunately, measles has made a come back, fueled by vaccine refusals. In October, the Centers for Disease Control and Prevention (CDC) reported an estimated 1,250 measles cases in the United States so far in 2019, surpassing the total number of cases reported annually in each of the past 25 years .
Around the world, measles continues to infect 7 million people each year, leading to an estimated 120,000 deaths. Based on the new findings, Elledge’s team now suspects the actual toll of the measles may be five times greater, due to the effects of immune amnesia.
The good news is those numbers can be reduced if more people get the vaccine, which has been shown repeatedly in many large and rigorous studies to be safe and effective. The CDC recommends that children should receive their first dose by 12 to 15 months of age and a second dose between the ages of 4 and 6. Older people who’ve been vaccinated or have had the measles previously should consider being re-vaccinated, especially if they live in places with low vaccination rates or will be traveling to countries where measles are endemic.
 Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens. Mina MJ, Kula T, Leng Y, Li M, de Vries RD, Knip M, Siljander H, Rewers M, Choy DF, Wilson MS, Larman HB, Nelson AN, Griffin DE, de Swart RL, Elledge SJ. et al. Science. 2019 Nov 1; 366 (6465): 599-606.
 Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Mina MJ, Metcalf CJE, De Swart RL, Osterhaus ADME, Grenfell BT. Science. 2015 May 8; 348(6235).
 Viral immunology. Comprehensive serological profiling of human populations using a synthetic human virome. Xu GJ, Kula T, Xu Q, Li MZ, Vernon SD, Ndung’u T, Ruxrungtham K, Sanchez J, Brander C, Chung RT, O’Connor KC, Walker B, Larman HB, Elledge SJ. Science. 2015 Jun 5;348(6239):aaa0698.
 Measles cases and outbreaks. Centers for Disease Control and Prevention. Oct. 11, 2019.
Measles (MedlinePlus Medical Encyclopedia/National Library of Medicine/NIH)
Measles History (Centers for Disease Control and Prevention)
Vaccines (National Institute of Allergy and Infectious Diseases/NIAID)
Vaccines Protect Your Community (Vaccines.gov)
Elledge Lab (Harvard Medical School, Boston)
NIH Support: National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases
Posted on by Dr. Francis Collins
Study after study has found no link between autism spectrum disorders (ASD) and the measles-mumps-rubella (MMR) vaccine—or any vaccine for that matter. Yet many parents still refuse or delay vaccinations for their young children based on misplaced fear of ASD, which can be traced back to a small 1998 study that’s since been debunked and retracted . Such decisions can have a major negative impact on public health. With vaccination rates in decline, we’ve recently seen the resurgence of measles and other potentially fatal childhood infectious diseases.
Among the parents most likely to avoid getting their kids vaccinated are those who already have a child with ASD. So, it’s especially important and timely news that researchers have once again found no link between MMR vaccines and ASD—even among children known to be at greater risk for autism because an older sibling has the developmental brain disorder.