The panel on the left shows the host cell with an ACE2 receptor, which is the binding target for the SARS-CoV-2 virus spike protein that mediates entry into the cell. An antibody competes for binding with the ACE2 receptor and blocks (or neutralizes) this interaction. The panel on the right shows that even when an individual mutation (highlighted in red) disrupts or reduces the binding affinity of antibodies to one area of the spike protein, the body’s immune response to infection or vaccination typically generates a spectrum of antibodies that target different areas of the virus.
A new variant of SARS-CoV-2, the virus that causes COVID-19, appeared in Great Britain in greater frequency in December and has been reported in New York State. The new variant appears to spread more rapidly than older ones and has a distinct set of genetic changes, or mutations. This prompted renewed vigilance among scientists throughout the world who carefully monitor mutations of the virus within their own countries and share their data on public repositories. The genetic codes of 250,000 virus samples from all over the world have already been shared, according to the World Health Organization. Moreover, another new SARS-CoV-2 variant that appears to spread more quickly, but that is different from the English one, has been found in patients with COVID-19 in South Africa.
The Mount Sinai Health System’s Pathogen Surveillance Program continually studies the evolution of SARS-CoV-2 variants through genetic sequencing, a technique that allows them to examine the genetic composition of the virus and identify changes in its genetic code. The team’s work has yielded a series of firsts. Last spring, they reported that the first wave of SARS-CoV-2 in New York City started with several independent introductions of viruses that could be traced back to Europe. These studies also provided evidence for untracked community transmissions of the virus in February and March of 2020.
Mount Sinai Today recently discussed the latest SARS-CoV-2 variants with two leaders of Mount Sinai’s Pathogen Surveillance Program: Viviana Simon, MD, PhD, Professor of Microbiology, and Medicine (Infectious Diseases); and Harm van Bakel, PhD, Assistant Professor of Genetics and Genomic Sciences.
Has Mount Sinai’s Pathogen Surveillance team found this new UK variant in New York City?
Harm van Bakel, PhD
Dr. van Bakel: Although the UK variant has now been detected in New York State, in Saratoga Springs, we have not yet encountered it in our ongoing surveillance of patients cared for by the Mount Sinai Health System. Considering that New York City is a major hub for international travel we fully expect this to change as we continue to generate more data.
This new variant of SARS-CoV-2 from the United Kingdom has a set of distinct mutations—23 to be precise. Does that make it particularly noteworthy?
Dr. van Bakel: SARS-CoV-2 is a virus that tends to mutate slowly and the multiple mutations in this UK variant do make it different. Usually about one to two mutations occur each month. Mutations occur randomly and most of them do not change anything for the virus. But sometimes an occasional mutation makes it more transmissible or potentially less susceptible to existing immunity.
Viviana Simon, MD, PhD
Dr. Simon: There is some emerging evidence that the UK variant, termed B.1.1.7, is more transmissible, although that data is still being worked on. Importantly, there is no evidence that this variant is more deadly. One of the mutations in the UK variant is located within the receptor binding domain (RBD) of the virus’s spike protein, so that has created some concern. The RBD is an area of the virus that attracts a strong immune response from the human body. It is the area where the spike meets the cell receptor and where many neutralizing antibodies bind to prevent the virus from entering the cell.
Dr. van Bakel: A few months ago another variant arose in Danish mink farms that carried a different mutation in the RBD. We have also occasionally seen other RBD mutations as part of our surveillance efforts in New York City during the past few months. When this happens, the worry is that these variants can reduce the effectiveness of existing immunity, but we have not seen any evidence of that yet. There is also always a concern that the viruses become more infectious when they jump from humans to animals such as mink and back into humans. But thus far, we have not seen anything that points to this.
What can we say about this variant so far?
Dr. Simon: It is really important to note that there is no data suggesting that the UK variant is more dangerous or lethal. We are actively doing surveillance on this British variant. We are also looking at other variants that we know are in our city and in Mount Sinai’s patient populations. Starting in September, we began to notice a slow increase in diversity of SARS-CoV-2 detected in the patients seeking care at the Mount Sinai Health System. This is not surprising because SARS-CoV-2 is an RNA virus, and like other RNA viruses, such as influenza and HIV, the more people are infected, the more viral diversity is observed. SARS-CoV-2 does mutate more slowly than influenza viruses or HIV and the majority of these mutations are meaningless insofar as the properties of the virus remain unchanged.
Dr. van Bakel: We are waiting for functional data on the UK variant to tell us if there are differences with regard to how antibodies neutralize it. These data will come from already ongoing controlled experiments using sera from COVID-19 survivors as well as from vaccine recipients. Some genetic changes can render the virus more transmissible. For example, most of the SARS-CoV-2 variants circulating globally over the past 10 months carry a D614G mutation in the spike protein. Studies in animal models have shown that this mutation allows improved transmission compared to the original viral variant first reported in China. Similar studies are needed to determine if this is also the case for the distinct mutations seen in the UK variant.
Is there any evidence that the newly authorized COVID-19 vaccines will not work against this variant?
Dr. Simon: We believe all of the new vaccines will be effective against this B.1.1.7 variant, as well as other variants, because the vaccines entice the immune system to make antibodies against different regions of the spike protein, and not only the sections of the RBD that are mutated. The immune responses developed upon vaccination will offer protection, even if we find out the RBD of the viral variants has been slightly changed.
Dr. van Bakel: Wearing face masks, maintaining social distancing, and observing all of the measures that have been put in place to protect oneself, as well as others, are still the most effective ways in controlling the spread of the virus until vaccines are more broadly available. Adhering to these guidelines will be effective regardless of the variant that is circulating.
Dr. Simon: Hope is on the horizon. We have highly protective vaccines, which will be delivered to as many people as possible in the coming weeks and months. Since the case numbers in our area remain worrisome, we really need to be careful and follow the guidelines that work for all SARS-CoV-2 variants.