Posted on by Dr. Francis Collins
Clinical trials have shown the COVID-19 vaccines now being administered around the country are highly effective in protecting fully vaccinated individuals from the coronavirus SARS-CoV-2. But will they continue to offer sufficient protection as the frequency of more transmissible and, in some cases, deadly emerging variants rise?
More study and time is needed to fully answer this question. But new data from Israel offers an early look at how the Pfizer/BioNTech vaccine is holding up in the real world against coronavirus “variants of concern,” including the B.1.1.7 “U.K. variant” and the B.1.351 “South African variant.” And, while there is some evidence of breakthrough infections, the findings overall are encouraging.
Israel was an obvious place to look for answers to breakthrough infections. By last March, more than 80 percent of the country’s vaccine-eligible population had received at least one dose of the Pfizer/BioNTech vaccine. An earlier study in Israel showed that the vaccine offered 94 percent to 96 percent protection against infection across age groups, comparable to the results of clinical trials. But it didn’t dig into any important differences in infection rates with newly emerging variants, post-vaccination.
To dig a little deeper into this possibility, a team led by Adi Stern, Tel Aviv University, and Shay Ben-Shachar, Clalit Research Institute, Tel Aviv, looked for evidence of breakthrough infections in several hundred people who’d had at least one dose of the Pfizer/BioNTech vaccine . The idea was, if this vaccine were less effective in protecting against new variants of concern, the proportion of infections caused by them should be higher in vaccinated compared to unvaccinated individuals.
During the study, reported as a pre-print in MedRxiv, it became clear that B.1.1.7 was the predominant SARS-CoV-2 variant in Israel, with its frequency increasing over time. By comparison, the B.1.351 “South African” variant was rare, accounting for less than 1 percent of cases sampled in the study. No other variants of concern, as defined by the World Health Organization, were detected.
In total, the researchers sequenced SARS-CoV-2 from more than 800 samples, including vaccinated individuals and matched unvaccinated individuals with similar characteristics including age, sex, and geographic location. They identified nearly 250 instances in which an individual became infected with SARS-CoV-2 after receiving their first vaccine dose, meaning that they were only partially protected. Almost 150 got infected sometime after receiving the second dose.
Interestingly, the evidence showed that these breakthrough infections with the B.1.1.7 variant occurred slightly more often in people after the first vaccine dose compared to unvaccinated people. No evidence was found for increased breakthrough rates of B.1.1.7 a week or more after the second dose. In contrast, after the second vaccine dose, infection with the B.1.351 became slightly more frequent. The findings show that people remain susceptible to B.1.1.7 following a single dose of vaccine. They also suggest that the two-dose vaccine may be slightly less effective against B.1.351 compared to the original or B.1.1.7 variants.
It’s important to note, however, that the researchers only observed 11 infections with the B.1.351 variant—eight of them in individuals vaccinated with two doses. Interestingly, all eight tested positive seven to 13 days after receiving their second dose. No one in the study tested positive for this variant two weeks or more after the second dose.
Many questions remain, including whether the vaccines reduced the duration and/or severity of infections. Nevertheless, the findings are a reminder that—while these vaccines offer remarkable protection—they are not foolproof. Breakthrough infections can and do occur.
In fact, in a recent report in the New England Journal of Medicine, NIH-supported researchers detailed the experiences of two fully vaccinated individuals in New York who tested positive for COVID-19 . Though both recovered quickly at home, genomic data in those cases revealed multiple mutations in both viral samples, including a variant first identified in South Africa and Brazil, and another, which has been spreading in New York since November.
These findings in Israel and the United States also highlight the importance of tracking coronavirus variants and making sure that all eligible individuals get fully vaccinated as soon as they have the opportunity. They show that COVID-19 testing will continue to play an important role, even in those who’ve already been vaccinated. This is even more important now as new variants continue to rise in frequency.
Just over 100 million Americans aged 18 and older—about 40 percent of adults—are now fully vaccinated . However, we need to get that number much higher. If you or a loved one haven’t yet been vaccinated, please consider doing so. It will help to save lives and bring this pandemic to an end.
 Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2 mRNA vaccinated individuals. Kustin T et al. medRxiv. April 16, 2021.
 Vaccine breakthrough infections with SARS-CoV-2 variants. Hacisuleyman E, Hale C, Saito Y, Blachere NE, Bergh M, Conlon EG, Schaefer-Babajew DJ, DaSilva J, Muecksch F, Gaebler C, Lifton R, Nussenzweig MC, Hatziioannou T, Bieniasz PD, Darnell RB. N Engl J Med. 2021 Apr 21.
 COVID-19 vaccinations in the United States. Centers for Disease Control and Prevention.
COVID-19 Research (NIH)
Stern Lab (Tel Aviv University, Israel)
Ben-Shachar Lab (Clalit Research Institute, Tel Aviv, Israel)
NIH Support: National Institute of Allergy and Infectious Diseases
Posted on by Dr. Francis Collins
Considerable research is underway around the world to monitor the spread of new variants of SARS-CoV-2, the coronavirus that causes COVID-19. That includes the variant B.1.351 (also known as 501Y.V2), which emerged in South Africa towards the end of 2020 [1, 2]. Public health officials in South Africa have been busy tracing the spread of this genomic variant and others across their country. And a new analysis of such data reveals that dozens of distinct coronavirus variants were already circulating in South Africa well before the appearance of B.1.351.
A study of more than 1,300 near-whole genome sequences of SARS-CoV-2, published recently in the journal Nature Medicine, shows there were in fact at least 42 SARS-CoV-2 variants spreading in South Africa within the pandemic’s first six months in that country . Among them were 16 variants that had never before been described. Most of the single-letter changes carried by these variants didn’t change the virus in important ways and didn’t rise to significant frequency. But the findings come as another critical reminder of the value of genomic surveillance to track the spread of SARS-CoV-2 to identify any potentially worrisome new variants and to inform measures to get this devastating pandemic under control.
SARS-CoV-2 was first detected in South Africa on March 5, 2020, in a traveler returning from Italy. By November 2020, despite considerable efforts to slow the spread, more than 785,000 people in South Africa were infected, accounting for about half of all reported COVID-19 cases on the African continent.
Recognizing the importance of genomic surveillance, researchers led by Houriiyah Tegally and Tulio de Oliveira, University of KwaZulu-Natal, Durban, South Africa, wasted no time in producing 1,365 near-complete SARS-CoV-2 genomes by mid-September, near the end of the coronavirus’s first peak in the country. Those samples had been collected in hundreds of clinics over the course of the pandemic in eight of South Africa’s nine provinces, offering a broad picture of the spread and emergence of new variants across the country.
The data revealed three main variants, dubbed B.1.1.54, B.1.1.56, and C.1, that were responsible for 42 percent of all the infections in South Africa’s first wave. Of the 16 newly described variants, most carried single-letter changes that haven’t been identified in other countries.
The majority of changes were what scientists refer to as “synonymous,” meaning that they don’t change the structure or function of any of the virus’s essential proteins. The exception is the newly identified C.1, which includes 16 single-letter changes compared to the original sequence from Wuhan, China. One of those 16 changes swaps a single amino acid for another on SARS-CoV-2’s spike protein. That’s notable because the spike protein is a key target of antibodies and also is essential to the virus’s ability to infect human cells.
In fact, four of the most prevalent variants in South Africa all carry this same mutation. The researchers also saw three other changes that would alter the spike protein in different ways, although the significance of these for viral spread and our efforts to stop it isn’t yet clear.
Importantly, the data show that the bulk of introductions to South Africa happened early on, before lockdown and travel restrictions were implemented in late March. Subsequently, much of the spread within South Africa stemmed from hospital outbreaks. For example, an outbreak of the C.1 variant in the North West Province in April ultimately led this variant to become the most geographically widespread in South Africa by the end of August. Meanwhile, an earlier identified South African-specific variant, B.1.106, first identified in April, vanished altogether after outbreaks were controlled in KwaZulu-Natal Province, where the researchers reside.
Genomic surveillance has remarkable power for understanding the evolution of SARS-CoV-2 and tracking the dynamics of its transmission. Tegally and de Oliveira’s team notes that this type of intensive genomic surveillance now can be used on a large scale across Africa and around the world to identify new variants of SARS-CoV-2 and to develop timely measures to control the spread of the virus. They’re now working with the African CDC to expand genomic surveillance across Africa .
Such genomic surveillance was crucial in the subsequent identification of the B.1.351 variant in South Africa that we’ve been hearing so much about, with its potential to evade our current treatments and vaccines. By picking up on such concerning mutations early through genomic surveillance and understanding how the virus is spreading over time and space, the hope is we’ll be better informed and more adept in our efforts to get this pandemic under control.
 Emerging SARS-CoV-2 variants. Centers for Disease Control and Prevention.
 Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. Tegally H, Wilkinson E, Giovanetti M, Iranzadeh A, Bhiman J, Williamson C, de Oliveira T, et al. medRxiv 2020 Dec 22.
 Sixteen novel lineages of SARS-CoV-2 in South Africa. Tegally H, Wilkinson E, Lessells RJ, Giandhari J, Pillay S, Msomi N, Mlisana K, Bhiman JN, von Gottberg A, Walaza S, Fonseca V, Allam M, Ismail A, Glass AJ, Engelbrecht S, Van Zyl G, Preiser W, Williamson C, Petruccione F, Sigal A, Gazy I, Hardie D, Hsiao NY, Martin D, York D, Goedhals D, San EJ, Giovanetti M, Lourenço J, Alcantara LCJ, de Oliveira T. Nat Med. 2021 Feb 2.
 Accelerating genomics-based surveillance for COVID-19 response in Africa. Tessema SK, Inzaule SC, Christoffels A, Kebede Y, de Oliveira T, Ouma AEO, Happi CT, Nkengasong JN.Lancet Microbe. 2020 Aug 18.
COVID-19 Research (NIH)
Houriiyah Tegally (University of KwaZulu-Natal, Durban, South Africa)
Tulio de Oliveira (University of KwaZulu-Natal)
Posted on by Dr. Francis Collins
Just this year, we’ve reached the point where we can sequence an entire human genome for less than $1,000. That’s great news—and rather astounding, since the first human genome sequence (finished in 2003) cost an estimated $400,000,000! Does that mean we’ll be able to use each person’s unique genetic blueprint to guide his or her health care from cradle to grave? Maybe eventually, but it’s not quite as simple as it sounds.
Before we can use your genome to develop more personalized strategies for detecting, treating, and preventing disease, we need to be able to interpret the many variations that make your genome distinct from everybody else’s. While most of these variations are neither bad nor good, some raise the risk of particular diseases, and others serve to lower the risk. How do we figure out which is which?
Jay Shendure, an associate professor at the University of Washington in Seattle, has an audacious plan to figure this out, which is why he is among the 2013 recipients of the NIH Director’s Pioneer Award.