Despite dizzying spikes in U.S. COVID cases over the holidays, I've been blanketed by a deep sense of levity since December when the FDA first approved two novel and highly effective vaccines against SARS-CoV-2 and initial doses were injected into Americans. Every day since, the weight of COVID-19 lifts from my soul a little more as pictures of health care workers receiving their vaccinations hit my Facebook stream, states move into Tier 2 vaccination populations, and family members in high risk populations are invited to schedule their vaccines.
Quiet joy and a renewed sense of hope are common sentiments right now after bearing the weight of this pandemic for nearly a year, but news in early January of a new "highly infectious" COVID strain infiltrating the U.S. from the U.K. is tempering many's optimism. Calls from local governments to "be vigilant," media reports of a new COVID "super strain", and misleading headlines meant to incite fear ( "Close To A Worst-Case Scenario’—Former CDC Director Issues ‘Horrifying’ Outlook For New Covid Strain.") return us all to a state of vulnerability rather than one of power.
But is there cause to feel vulnerable again? Should our expressions of hope in conversations with colleagues, friends, and loved ones be interrupted by the word "but?"
The story of B.1.1.7 SARS-CoV-2, the official designation of the U.K. variant of interest, is absolutely one we should hear and heed, but the media leaves out the most important details: the objective ones. In this post I share the current scientific and epidemiological data for B.1.1.7 SARS-CoV-2 to reassure your optimism and convince you that we still have the upper hand in this battle.
First, where did B.1.1.7 come from?
B.1.1.7 is a genetic lineage or "cluster" of related SARS-CoV-2 viruses with similar characteristics. As of December 15th, 2020, 1,623 B.1.1.7 family members were identified, all within the U.K. and all derived from a similar ancestor. This genetic "tree" stands out among other SARS-CoV-2 lineages for multiple reasons.
The first is that B.1.1.7 viruses have an unusually high number of genetic mutations compared to other SARS-CoV-2 strains. All organisms mutate their genomes to adapt to environmental pressures, but viruses mutate faster than any other biological organism. In paticular, SARS-CoV-2 and similar viruses mutate one million times faster than what is observed in the human genome, and this correlates with rapid virus evolvability and adaptation, traits essential for virus survival. But B.1.1.7 stands out even further.
Twelve months into the pandemic and other SARS-CoV-2 strains carry no more than a few mutations relative to the 'L' strain detected in Wuhan, China in December 2019, but B.1.1.7 viruses have 17 new productive mutations. Many of these affect the structure and function of essential viral proteins, making B.1.1.7 more "fit" than other SARS-CoV-2 viruses and enabling the strain to infect its hosts more efficiently. But the current mutation rate of B.1.1.7 is identical to other circulating SARS-CoV-2 strains (Figure 1), so how did B.1.1.7 accrue its multitude of mutations?
Figure 1. Comparison of genetic mutation rates in the B.1.1.7 lineage and a related circulating SARS-CoV-2 strain.
The number of genetic mutations (y-axis) in B.1.1.7 viruses (silver) and a closely related SARS-CoV-2 strain (gold) on different dates (x-axis). For each set of dots, the slope (rise over run) of the line gives the rate (mutation per time) of mutation. The slopes are equal.
B.1.1.7 is likely a product of a COVID-infected patient with a very weak immune system. Studies of immunodeficient hosts with chronic SARS-CoV-2 infections report high numbers of productive viral mutations accumulating over very short periods of time (Choi et al. 2020; Avanzato et al. 2020; Kemp et al. 2020). These patients were unsuccessfully treated with COVID therapies like convalescent plasma and the drug remdesivir. In each case patients showed a large, dynamic shift in their SARS-CoV-2 populations after drug therapy and the emergence of new dominant intra-patient viral strains.
The environment of SARS-CoV-2 in these patients is vastly different than in a typical infection. The selective pressures like the drugs that failed to eradicate infections coupled with time afforded by weak immune systems enabled the original intra-patient strains to mutate swiftly and significantly, generating "super viruses" if you will. This is likely how nascent B.1.1.7 arose.
But is B.1.1.7 truly a Super Virus?
Worrisome to public health officials is the effect that B.1.1.7's 17 mutations may have on the strain's transmissibility, the severity of its infections, and our ability to both detect and prevent infections. Arguably, if B.1.1.7 is highly transmissible, significantly increases human fatality rates, goes undetected by current testing methods, and evades immunity induced by current vaccines, then yes - B.1.1.7 can fairly be called a super virus. But fortunately for us, most of these are not true.
Transmissibility
The alarming news headlines for B.1.1.7 are a direct result of U.K. data published in early January that indicate B.1.1.7 is more transmissible than other circulating SARS-CoV-2 strains.
According to Public Health England (England's CDC equivalent), B.1.1.7, first identified in September, was the dominant circulating strain in England by mid-December (Figure 2). While in November it represented less than 4% of all COVID cases, by December 15th the number rose to 60% and today B.1.1.7 comprises 90% of all cases in England. Of particular note is that B.1.1.7 cases climbed substantially in December when non-B.1.1.7 infections were largely stable, indicating higher rates of transmission among the B.1.1.7 strain.
Figure 2. Percentage of B.1.1.7 sequences of analyzed SARS-CoV-2 cases in England from September 1, 2020 to January 5, 2021 by week
Dark purple or 'Confirmed SGTF' are the number of B.1.1.7 cases over time while light purple or "Confirmed S-gene" are non B.1.1.7 strains. The red line gives the percentage of B.1.1.7 cases of total cases analyzed.
But how much more contagious is B.1.1.7 and what does that mean for the U.S.?
The transmissibility of a virus is measured by its 'R' number, which equals the expected number of secondary cases produced by a single infection. The size of an outbreak is often proportional to the magnitude of a pathogen's initial R number and when R > 1 an outbreak is expected to continue and R < 1, to end.
Mathematical models estimate the initial R number for the SARS-CoV-2 L strain was 2.5 (Peterson, et al). This means that when the pandemic first began, one contagious person passed COVID onto approximately 2.5 people, giving us the "doubling curves" we grew to fear and the rapidly increasing case numbers last spring.
But R numbers can change over time and space. They depend on both the intrinsic biological characteristics of a pathogen and on extrinsic factors that influence contact rate (human-human or human-virus), like population density, social organization, and the development of specific immunity. So, while an initial R number serves as a useful tool for predicting the size of an outbreak and measuring the need for public health measures, a changing R number over time is a metric used to asses the success of interventions like city shut-downs and vaccination campaigns.
Importantly, the public health measures we took as a nation over the past 12 months and that we continue to take have significantly reduced the R numbers of SARS-CoV-2 strains in the U.S. As of January 23, 2021, only eight U.S. states had COVID-19 R > 1 and these were still relatively low, ranging from 1.01-1.11 (Figure 3) (Statista.com).
Figure 3. R numbers by U.S. state as of January 23, 2021.
States in blue have an R number < 1, meaning COVID transmission is diminishing in these areas. States in red have an R > 1, meaning the virus is still spreading, though at a significantly slower rate than at the start of the pandemic.
Scientists estimate that B.1.1.7's R number is 0.4 to 0.7 higher than other circulating strains in the U.K. (Volz et al.), and a second report estimated an average 56% increase in transmissibility (Davies, et. al.) for B.1.1.7 based on U.K. data.
Assuming the factors that influence B.1.1.7 transmission are the same in the U.S. as in the U.K., this means we can expect an increase in U.S. case numbers by approximately 56% in upcoming weeks. Though the impact will vary state to state, the concern is that the difference in B.1.1.7's transmissibility will result in a "surge" of COVID cases that hospitals cannot accommodate.
As an example, let's consider two states, California and Vermont:
California reported 18,974 new COVID cases on February 1, 2021 and has a recent R of 0.86. Based on these numbers we expect the Feb. 1 cases to give rise to approximately 16,318 new cases (fewer than what we started with) representing 86% case growth, with subsequent case numbers diminishing over time. However, if B.1.1.7 increases the state's R by 56% to 1.3 then the cases reported on Feb. 1 could instead result in 130% case growth or 24,666 new cases, with a successive increase in case numbers with time. In a populous state that reported 90% ICU capacity use in mid-January, this difference in R could significantly impact the available beds for those in need.
Vermont recently had the highest R of 1.11 in the country but only reported 113 new infections on February 1, 2021. In this example, B.1.1.7 may increase Vermont's R by 56% to 1.7, meaning that the 113 cases reported on Feb. 1 would give rise to 176 new cases rather than the currently predicted 124 cases. In both scenarios with R > 1, Vermont's case rate is expected to increase with time but based on its current hospital capacity, the state is better able to absorb this growth in COVID cases.
Though this increase in B.1.1.7's transmissibility may be daunting, it is important to recognize that this strain is still subject to the same laws of physics as other SARS-CoV-2 strains. This means that its contact rate can be hindered by the same measures we've already taken: mask wearing, distancing, hand washing, ventilation, and time outdoors. So we can still staunch the spread of B.1.1.7 as we've done for earlier strains, it may just require a little more diligence on everyone's part in upcoming weeks.
Silver Linings
Though B.1.1.7 is more transmissible than earlier strains, evidence so far suggests that disease is no more severe, our ability to detect it clinically is still robust, and current vaccines are effective immunizing agents against it.
Disease Severity
B.1.1.7 may be more transmissible than other SARS-CoV-2 strains but two published reports indicate that B.1.1.7 disease is no more severe (Volz et al., Davies, et. al.), and initial findings by Public Health England support this conclusion. A third paper just released by Britain’s New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) highlights conflicting reports on B.1.1.7 cases and suggests that, in fact, there may be an increase in mortality associated with B.1.1.7. However, NERVTAG scientists noted that the rates of death per infection 'remain low' and that the new data is based on a 'relatively small number of people from a small number of settings'.
Hopefully as more data accrue in the coming weeks these analyses will become more definitive and can inform our response to B.1.1.7 here in the U.S., but as of now, this variant is not expected to impact our current hospitalization on death rates.
Detection
Another initial concern for B.1.1.7 was that its novel mutations may affect our ability to clinically detect it using existing tools, but this is not the case. The biotechnology companies that developed and produce the PCR tests for SARS-CoV-2 researched and determined that there is less than a 0.01% chance that B.1.1.7's mutations will impact the accuracy of virus detection. In fact, conversely, these PCR tests have become incredibly useful in identifying the B.1.1.7 strain in an infected individual and are the basis for much of England's current B.1.1.7 epidemiological data.
Prevention
Finally, prevention, and perhaps the best new of all. Both SARS-CoV-2 vaccines currently approved for use by the U.S. FDA (Moderna and Pfizer-BioNTech) remain effective against B.1.1.7 (Muik, et al, Moderna Press Release). This means that our current vaccination strategy will be effective in curbing this pandemic.
As of February 2, 2021, there were 541 reported cases of B.1.1.7 in 33 different states within the U.S. Though this number will grow in the coming months and may cause an increase in COVID numbers that we would not otherwise see, we are well poised as a nation and from a public health perspective to eradicate SARS-CoV-2. Despite reports of slow vaccine roll-outs, nearly 10% of the U.S.'s population has already received their first dose, and experts predict a transition to normalcy in the second quarter of 2021 and herd immunity in the third and fourth quarters. In the meantime, we cannot lose hope. We must find optimism, celebrate as our loved ones and neighbors receive their COVID vaccinations, and continue to stay diligent in our personal efforts to minimize the spread of this virus.
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