Don’t Sleep on B.1.1.7

The ‘UK Variant’ is not done with us yet

In the first weeks of the new year, the historic weight of the January 6th, 2021 capitol insurrection dominated the news and opinion pages of the national media from coast to coast.

On January 5th, Science’s Kai Kupferschmidt reported on a different story¹, the remarkably developed scientific consensus that had emerged surrounding the COVID-19 Variant B.1.1.7 first discovered in the United Kingdom.

“For COVID-19 researchers, the new year brings a strong sense of deja vu. As in early 2020, the world is anxiously watching a virus spread in one country and trying to parse the risk for everyone else. This time it is not a completely new threat, but a rapidly spreading variant of SARS-CoV-2.”

His subjects shared a remarkably consistent outlook, elaborating that B.1.1.7: “will drive another very, very bad wave”, “pretty much all that evidence is pointing in the same direction now”, and “we should start preparing ourselves for the fact that this is happening elsewhere. It’s dispiriting to feel like the world is back where it was in early 2020, but we have to stop this virus. … Fatalism is not a non-pharmaceutical intervention.”

As COVID-19 begins to show encouraging declines in the United States amidst an increasingly comprehensive vaccination campaign, it’s worth revisiting the variant-driven wave which forced the United Kingdom into months of restrictive lockdown and the scientific work which accurately sounded the alarms about the unexpected risks of the year ahead.

As COVID-19 cases rose rapidly in the fall of 2020, the United Kingdom entered its second national lockdown closing pubs, restaurants, gyms and non-essential shops from November 5th to December 2nd. Yet in some regions, especially those surrounding London and the Southeast of the country, cases continued to show alarming increases.

As restrictions were loosened in December, cases once again rose rapidly forcing Boris Johnson to impose even more stringent restrictions on December 23rd, a shutdown that would last well into the spring as the country bought time to successfully avert an even greater new outbreak thanks to the decisive work of the scientific community.

Standard PCR tests detect COVID-19 by testing for a few characteristics of the virus’s genome. Genetic sequencing maps the entire genome, allowing scientists to track the emergence of and spread of new mutations. Most are harmless. A small handful are dangerous.

If some particular set of mutations — a variant — begins to overtake previous lineages, this may indicate that it has some competitive advantage. However this can also occur for other reasons, including chance; telling the difference requires careful study. The United Kingdom was uniquely suited to the task thanks to careful coordination in the early days of the pandemic. The Covid-19 Genomics Consortium had cataloged a full 150,000 samples, fully half of the world’s genetic sequences.

As researchers tracked the variant originally designated VOC 202012/01 for the date of discovery they were aided by a fortuitous quirk. The variant contained a relatively benign mutation also found in other lineages, the deletion of two amino acids on the spike protein. As a result of this mutation, when the variant was run through PCR tests only two of the three tests succeeded. The third, targeting the S-gene of the virus, failed, leaving a trail designated S-gene target failure, or SGTF.

By sequencing a fraction of all SGTF samples, researchers were able to estimate what fraction of these were B.1.1.7. Multiplying this by the fraction of SGTF samples in all PCR tests researchers could track B.1.1.7 far more extensively than would otherwise have been possible. What they found was alarming.

A team of researchers from Imperial College and other institutions² studied the November lockdown by looking at 42 different regions tracked by the National Institute of health across the four weeks of the lockdown, 168 samples in all.

Within these 168 intervals they tracked the growth of B.1.1.7 cases vs that of previous lineages.

In 34 intervals both types of cases increased. In 36 intervals, both decreased. In 97 intervals — a full 57 percent majority, B.1.1.7 continued to increase even as previous lineages decreased in the face of the lockdown. The opposite — an increase of previous lineages and decrease of B.1.1.7 — was trivial. A single week in a single region.

The authors wrote: “Visually, it is clear that while lockdown successfully controlled [previous lineages] cases in virtually every [region and week], [estimated B.1.1.7] case numbers increased during lockdown.” Going forward, managing B.1.1.7 would require even stricter controls.

A group working out of the London School of Hygiene and Tropical Medicine looking at the spread of B.1.1.7 in the hard-hit regions in London, South East, and East of England, created a model to test the possible explanations of the growth of B.1.1.7: increased transmissibility (the chance that a contact would result in a new infection), immune escape (the ability to reinfect individuals previously infected by previous lineages), increased susceptibility in children, and shorter generation time (becoming contagious sooner after the initial infection)³.

They found that while there was some possibility of increased transmission among children, data overwhelmingly supported that B.1.1.7 had a greater chance of infecting new individuals, estimating the effect as over 50%.

From these results, they investigated the potential paths of the epidemic in the United Kingdom in the first half of 2021. With no new measures such as vaccinations and non-pharmaceutical controls, they estimated that the death toll of 2021 could exceed that of 2020. Of the scenarios they tested only one was predicted to keep the ICU burden below that of the first wave; the most stringent level of lockdowns combined with an accelerated vaccination campaign.

Based on the work of these and other groups the government acted quickly. Despite having previously declared that closing the country over Christmas would be “inhumane”, Boris Johnson once again put the country into strict lockdown, from which it is only now beginning to emerge. Combined with one of the world’s earliest and most comprehensive vaccination programs, the United Kingdom successfully brought per capita cases of one of the pandemic’s highest peaks to a level well below that of most European countries and the United States.

In continental Europe, the relatively early arrival of B.1.1.7 triggered both new lockdowns and/or spring waves. Countries such as France and Germany which attempted measured reopenings were forced to backtrack as cases surged amidst troubled vaccination campaigns.

In comparison, the United States has been fortunate. In January, the CDC estimated the incidence of B.1.1.7 in the country at .05%. Subsequent modelling — using the SGTF method first developed in the United Kingdom — estimated that B.1.1.7 would constitute a majority of COVID-19 cases by late March or early April. This is exactly what happened, but only after a sharper than expected decline in cases from the winter peaks, as well as a faster than expected pace of vaccinations.

States such as New York and New Jersey experienced significant spring surges, while Michigan saw its highest case count of the entire pandemic. The country as a whole saw cases rise for a few weeks, as B.1.1.7 became a greater fraction of overall cases, followed by what many hope will become a sustained decline as more and more Americans are vaccinated.

The pandemic is in one of its trickiest phases. In the long run, vaccines will continue to reduce the overall case count substantially. Over the coming weeks, B.1.1.7, along with other Variants of Concern, will complete their displacement of previous lineages, bringing with them an increased ability to overcome control measures.

On May 5th 2021 the CDC released modeling^4 illustrating a range of possible trajectories for the epidemic in the United States given the prevalence of Variants including B.1.1.7 and different scenarios for the rate of vaccinations and the relaxations of non-pharmacutical-interventions which ranged from decisive declines through the first months of the summer to a new surge with a long declines into the beginning of the fall⁴. Compared to the beginning of the projections, real case have tracked at or below the lower bounds, an unambiguously good sign.

The purpose of such modelling, however, is not necessarily to predict a specific level or path but also to illustrate the sensitivity of outcomes to certain inputs, in this case behaviors around vaccinations and re-openings. The CDC’s modelling reflects the same dynamics observed this winter in the United Kingdom — B.1.1.7 (and by implication other Variants of Concern) are extremely unforgiving if given a chance to spread.

Without very high levels of vaccinations, Covid-19, B.1.1.7 and other variants will be hard to knock out. Vaccines are not distributed equally throughout the population — some particular level, say 50% is only an average. In a country as large and diverse as the United States, the fraction in some given population can vary considerably.

Older people and those with underlying conditions have higher rates, which reduces overall hospitalizations and deaths considerably. This is offset by lower rates in younger and healthier groups, who may also be the most likely to have high interaction rates. Disadvantaged populations have lower vaccination rates. Rural areas have lower rates. Rates vary regionally and by partisan affiliation.

The virus transmits from person to person across networks of contacts and, over time, will grow in networks with a high enough fraction of susceptible hosts. Higher vaccination rates afford it fewer opportunities. More transmissible variants afford it more, which combined with slowing vaccination rates and lowered precautions could lead to an extended period in which local outbreaks persist through the summer and beyond even as global case counts continue to fall.

The “Vaccine vs Variants” narrative of early 2021 has led us to a place neither as bad as we might have feared nor as good as we might have hoped; but as tiresome as it may seem, B.1.1.7 isn’t done with us yet.

Note: As a snapshot of the situation as it appeared in early January 2020, this article references pre-publication preprints. The final published versions are also referenced below and represent the most complete version of the work.

[1] Viral evolution may herald new pandemic phase
By Kai Kupferschmidt
Science08 Jan 2021 : 108–109
Scientists worry about another “very, very bad” wave, argue for stricter control measures.

[2]Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data

Erik Volz, Swapnil Mishra, Meera Chand, Jeffrey C. Barrett, Robert Johnson, Lily Geidelberg, Wes R Hinsley, Daniel J Laydon, Gavin Dabrera, Áine O’Toole, Roberto Amato, Manon Ragonnet-Cronin, Ian Harrison, Ben Jackson, Cristina V. Ariani, Olivia Boyd, Nicholas J Loman, John T McCrone, Sónia Gonçalves, David Jorgensen, Richard Myers, Verity Hill, David K. Jackson, Katy Gaythorpe, Natalie Groves, John Sillitoe, Dominic P. Kwiatkowski, The COVID-19 Genomics UK (COG-UK) consortium, Seth Flaxman, Oliver Ratmann, Samir Bhatt, Susan Hopkins, Axel Gandy, Andrew Rambaut, Neil M Ferguson

medRxiv 2020.12.30.20249034; doi: https://doi.org/10.1101/2020.12.30.20249034

published as:

Volz, E., Mishra, S., Chand, M. et al. Assessing transmissibility of SARS-CoV-2 lineage B.1.1.7 in England. Nature 593, 266–269 (2021). https://doi.org/10.1038/s41586-021-03470-x

[3] Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England

Nicholas G. Davies, Rosanna C. Barnard, Christopher I. Jarvis, Adam J. Kucharski, James Munday, Carl A. B. Pearson, Timothy W. Russell, Damien C. Tully, Sam Abbott, Amy Gimma, William Waites, Kerry LM Wong, Kevin van Zandvoort, CMMID COVID-19 Working Group, Rosalind M. Eggo, Sebastian Funk, Mark Jit, Katherine E. Atkins, W. John Edmunds

medRxiv 2020.12.24.20248822; doi: https://doi.org/10.1101/2020.12.24.20248822

published as:
Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England
BY NICHOLAS G. DAVIES, SAM ABBOTT, ROSANNA C. BARNARD, CHRISTOPHER I. JARVIS, ADAM J. KUCHARSKI, JAMES D. MUNDAY, CARL A. B. PEARSON, TIMOTHY W. RUSSELL, DAMIEN C. TULLY, ALEX D. WASHBURNE, TOM WENSELEERS, AMY GIMMA, WILLIAM WAITES, KERRY L. M. WONG, KEVIN VAN ZANDVOORT, JUSTIN D. SILVERMAN, CMMID COVID-19 WORKING GROUP, COVID-19 GENOMICS UK (COG-UK) CONSORTIUM, KARLA DIAZ-ORDAZ, RUTH KEOGH, ROSALIND M. EGGO, SEBASTIAN FUNK, MARK JIT, KATHERINE E. ATKINS, W. JOHN EDMUNDS

SCIENCE09 APR 2021

The major coronavirus variant that emerged at the end of 2020 in the UK is more transmissible than its predecessors and could spark resurgences.

[4] outbreak.info

Julia L. Mullen, Ginger Tsueng, Alaa Abdel Latif, Manar Alkuzweny, Marco Cano, Emily Haag, Jerry Zhou, Mark Zeller, Nate Matteson, Kristian G. Andersen, Chunlei Wu, Andrew I. Su, Karthik Gangavarapu, Laura D. Hughes, and the Center for Viral Systems Biology outbreak.info. Available online: https://outbreak.info/ (2020)

[5] Borchering RK, Viboud C, Howerton E, et al. Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios — United States, April–September 2021. MMWR Morb Mortal Wkly Rep. ePub: 5 May 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7019e3external icon.