Viral Evolution May Herald New Pandemic Phase Scientists Worry About Another ‘Very, Very Bad’ Wave, Argue for Stricter Control Measures
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IN DEPTH Downloaded from http://science.sciencemag.org/ Streets in downtown Glasgow were deserted on 5 January after the United Kingdom imposed a strict lockdown to curtail the spread of a new SARS-CoV-2 variant. COVID-19 Viral evolution may herald new pandemic phase Scientists worry about another ‘very, very bad’ wave, argue for stricter control measures By Kai Kupferschmidt more people rapidly (see p. 109). But as makes it hard to pinpoint the effect of the on January 11, 2021 the new variant surfaces in multiple coun- new variant, says evolutionary biologist or COVID-19 researchers, the new tries, many scientists are calling for gov- Oliver Pybus of the University of Oxford. year brings a strong sense of déjà ernments to strengthen existing control Yet evidence has rapidly increased that vu. As in early 2020, the world is measures as well. U.K. Prime Minister B.1.1.7’s many mutations, including eight anxiously watching a virus spread in Boris Johnson announced tough new re- in the crucial spike protein, do enhance one country and trying to parse the strictions on 4 January, including closing spread. “We’re relying on multiple streams risk for everyone else. This time it is schools and asking people not to leave of imperfect evidence, but pretty much all Fnot a completely new threat, but a rapidly their homes unless strictly necessary. But that evidence is pointing in the same direc- spreading variant of SARS-CoV-2. In south- other countries have hesitated. “I do feel tion now,” says Adam Kucharski, a modeler eastern England, where the B.1.1.7 variant like we are in another situation right now at the London School of Hygiene & Tropi- first caught scientists’ attention last month, where a lot of Europe is kind of sitting and cal Medicine. For instance, an analysis by it has quickly replaced other variants, and it looking,” says virologist Emma Hodcroft of Public Health England showed about 15% of may be the harbinger of a new, particularly the University of Basel. “I really hope that the contacts of people infected with B.1.1.7 perilous phase of the pandemic. this time we can recognize that this is our in England went on to test positive them- “One concern is that B.1.1.7 will now be- early alarm bell, and this is our chance to selves, compared with 10% of contacts of come the dominant global variant with get ahead of this variant.” those infected with other variants. its higher transmission and it will drive In announcing the U.K. restrictions, If other countries that have detected another very, very bad wave,” says Jeremy Johnson said the new variant is between B.1.1.7 also see it surge, it will be “the Farrar, an infectious disease expert who 50% and 70% more transmissible. But re- strongest evidence we will have,” Pybus heads the Wellcome Trust. Whereas the searchers have been careful to point out says. Data from Denmark, which leads pandemic’s trajectory in 2020 was fairly uncertainties. Cases have soared in the the European Union in the sequencing of predictable, “I think we’re going into an un- United Kingdom over the past month, but SARS-CoV-2, are not reassuring. Routine predictable phase now,” as a result the virus’ the rise occurred while different parts of surveillance there has picked up the vari- evolution, Farrar says. the country had different levels of restric- ant dozens of times; its frequency went The concern has led some countries to tions and amid changes in people’s behavior from 0.2% of sequenced genomes in early speed up vaccine authorizations or dis- and regional infection rates in the run-up December to 2.3% 3 weeks later. “We have cuss dosing regimens that may protect to Christmas—“a complex scenario” that had what looks like a poster child example IMAGES BUCHANAN/AFP/GETTY ANDY PHOTO: 108 8 JANUARY 2021 • VOL 371 ISSUE 6525 sciencemag.org SCIENCE Published by AAAS NEWS of exponential growth these last 4 weeks in COVID 19 Denmark,” says genomicist Mads Albertsen of Aalborg University. The lack of evidence—so far—that the Dosing debates, transparency new variant makes people sicker is little consolation. Increased transmissibility of a virus is much more treacherous than in- issues roil vaccine rollouts creased pathogenicity because its effects grow exponentially, Kucharski says. “If you U.K. decision to delay booster shots sparks concerns have something that kills 1% of people but a huge number of people get it, that’s going to By Jon Cohen single dose of the vaccine, which uses an result in more deaths than something that adenovirus to deliver a gene that codes for a small number of people get but it kills 2% ast-minute vaccine dosing changes that the surface protein, spike, of SARS-CoV-2. of them.” could gamble away proven COVID-19 This, oddly, was higher than the 62% ef- If the U.K. estimates of a 50% to 70% in- protection and undermine public trust. ficacy after two full doses reported in The crease in the virus’ reproduction number, or Controversial approvals without any Lancet. Oxford’s Adrian Hill, who co-led the R, hold true, “keeping the virus from spread- efficacy data. Vaccinemakers at odds vaccine’s development, notes its efficacy ing has become a lot harder,” says Viola with countries hosting their clinical tri- trials started earlier than other groups, Priesemann, a physicist at the Max Planck Lals. The COVID-19 vaccine landscape keeps which may explain the discrepancy. “I’m Institute for Dynamics and Self-Organization changing almost daily, simultaneously raising afraid it’s possible that what’s happening Downloaded from who has been modeling the pandemic and hopes and triggering confusion and scientific is efficacy is declining over time,” Hill says. the effects of nonpharmaceutical interven- debates. “It’s crazy,” says vaccine researcher (The 62% figure has itself brought confu- tions, such as physical distancing and school John Moore of Weill Cornell Medicine. “Every sion, as the vaccine had a reported 90% ef- closures. “In Germany you would need two morning, it’s just, ‘What’s going on?’” ficacy when the first dose was halved.) big additional measures to keep the repro- Over the past few weeks, COVID-19 vac- For all two-dose vaccines, intervals be- duction number below 1 ,” Priesemann says. cines developed in the United Kingdom, tween a prime and booster are somewhat http://science.sciencemag.org/ Isolating patients and tracing, quarantin- China, and India moved toward widespread arbitrary, says pediatrician Paul Offit of ing, and testing their contacts is one part rollout, offering new weapons in the face of the Children’s Hospital of Philadelphia, a of any attempt at doing so; those measures fast-spreading viral variants that threaten member of an independent U.S. vaccine ad- alone can reduce R from about to deepen the crisis (see p. 108). visory committee. But some physicians and 2 to about 1, Priesemann has shown But many came with controver- scientists worry that last-minute debates for Germany. But that effect breaks Science’s sies, and U.K. regulators sparked on dosing strategies will increase vaccine down when case numbers reach a COVID-19 a debate when they endorsed a hesitancy. “Mixed messages and lack of evi- critical threshold and public health reporting is sharp departure from the expected dence will inevitably lead to undermining authorities are overwhelmed, supported by the dosing schedule for a newly autho- the public trust in the vaccine and could Pulitzer Center which means tougher measures and the rized vaccine from AstraZeneca negatively impact on uptake,” the Doctors’ now can help contain spread of the Heising-Simons and the University of Oxford and Association UK wrote in a letter of concern on January 11, 2021 new variant later. “It’s yet another Foundation. one from Pfizer and BioNTech. to the U.K. health minister. reason to go for very low num- The pandemic has driven most The British Society for Immunology bers,” says Priesemann, who co-authored a COVID-19 vaccinemakers to aim for a short issued a statement supporting MHRA’s December 2020 letter to in The Lancet call- 3 or 4 weeks between prime and booster “pragmatic” dosing schedule, but urged ing for Europe to adopt a joint strategy to shots, but the U.K. Medicines and Health- the government to launch a “robust” moni- bring down infections fast. Hodcroft agrees. care products Regulatory Agency (MHRA) toring program to determine how the “The case has never been stronger,” she says. said second shots can be given up to different intervals affect efficacy. Several “What’s the worst-case scenario here? We 12 weeks later. scientists also called for more direct clini- overshoot and we get cases so low that we Biostatistician Natalie Dean of the Uni- cal trial comparisons of dosing intervals. can get rid of a lot of restrictions.” versity of Florida thinks MHRA moved too The United States seems unlikely to fol- Curtailing infections sharply has the quickly and without enough explanation of low the U.K. example. “The MHRA has added benefit of reducing the chances for its dosing decision. “Clearly there were de- taken quite a significant risk,” says Moncef the virus to evolve even further. Already liberations that the U.K. had about this, but Slaoui, chief scientist for the U.S. govern- other variants have emerged, notably one we don’t have access to those discussions.” ment’s Operation Warp Speed program, called 501Y.V2 in South Africa, that are just MHRA didn’t cite the fast-spreading which is now staging its own 30,000-person as worrying as B.1.1.7, Farrar adds.