The Superspreading Problem

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Feature /GETTY /GETTY TRIBUNE STAR LAVINSKY/ AARON Restaurants and other crowded indoor spaces are prime spots for superspreading events, in which one person passes the virus to many others. THE SUPERSPREADING PROBLEM Uneven transmission of the SARS-CoV-2 coronavirus has had tragic consequences — but also offers clues for how best to target control measures. By Dyani Lewis

n 5 December last year — the eve of Akira Endo, an infectious-diseases modeller in 2003, and MERS-CoV, the source of Middle traditional Christmas gift-giving in at the London School of Hygiene & Tropical East respiratory syndrome. A similar mode of Belgium — residents of the Hemelrijck Medicine, noticed the telltale signs of super- transmission occurs with the pathogens that care home near Antwerp were treated spreading before such events became a staple cause Ebola, smallpox and tuberculosis. to a visit by Sinterklaas, or Santa. But of COVID-19 news coverage. One clue came As the pandemic enters its second year — a the festive event, intended to spread from early investigations of cases in which a sin- time marked by news of fast-spreading vari- cheer, turned tragic. Forty staff mem- gle person infected up to ten others1. Another ants of the virus — researchers are now more bers and more than 100 residents curious fact was that outside Wuhan, China, convinced than ever of the importance of super- O— at least 26 of whom have since died — were home to the first big outbreak, infected individ- spreading in how the COVID-19 pandemic has unintentionally infected with the coronavirus uals weren‘t immediately causing exponential played out, and how it will do so in the future. SARS-CoV-2 by the costumed volunteer, who local outbreaks, says Endo, who was one of the They have found that superspreading events also subsequently tested positive. earliest to quantify the phenomenon. are one of the main ways in which SARS-CoV-2 Superspreading events like this, in which This uneven, sputtering form of trans- has gained a foothold in communities around many people are infected at once, typically by mission, in which some individuals infect the world, so far infecting more than 100 million a single individual, are a now-familiar feature of many people but most infect only a few, if people and killing more than 2.4 million. With- the COVID-19 pandemic. Choir practices, funer- any, is shared by the coronavirus’s cousins — out effective control measures, superspread- als, family gatherings and gym classes have all SARS-CoV, which caused the deadly epidemic ing events might even become larger and more spawned dangerous outbreaks. of severe acute respiratory syndrome (SARS) frequent as more-transmissible variants first

identified in the United Kingdom, South Africa variant called B.1.1.7 (ref. 3), “there will likely children’s immune systems respond to infec- and Brazil push out other strains of the virus. be an increase in both the frequency and size tion are thought to be why they catch and pass With a year’s worth of data, researchers have of superspreading events”, she says. on the coronavirus less frequently than adults amassed ample evidence of some chief ingre- A team led by Bronwyn MacInnis, a geneti- do7. It’s possible that a spectrum of immune dients of superspreading events: prolonged cist at the Broad Institute of MIT and Harvard in responses exists in adults, too, says Dwyer. At indoor gatherings with poor ventilation. Cambridge, Massachusetts, traced the impact the far end of the spectrum, “if somebody is Activities such as singing and aerobic exer- of superspreading events using viral genome immune-suppressed, then generally they’re cise, which produce many of the tiny infectious sequences. One superspreading event — a two- more likely to shed more virus for longer”, he says. droplets that can be inhaled by others, are also day international business conference held in A study of aerosol emissions from nearly common components. Boston in late February 2020 — seeded more 200 healthy people, published this month8, But key questions remain. “We have some than 90 cases in attendees and their close con- lends weight to the idea that biological differ- ideas of what factors are involved, but we still tacts4. But the true impact was much greater, ences could affect transmission of the virus. don’t know what is the main driver of the super- says MacInnis. She estimates that roughly The measurements showed that 20% of the spreading,” says Endo. Foremost are uncertain- 20,000 infections in Boston and its surrounding study participants accounted for 80% of the ties about how much individual differences in areas could be traced back to the conference. aerosol particles emitted, and that people who people’s behaviour and biology matter — or can were older or overweight produced more aer- be controlled — and how best to target high- Are there superspreaders? osols than others. risk settings while keeping the cogs of society Although a few people account for the lion’s But researchers using mathematical mod- turning. Understanding the underlying factors share of transmission, researchers are still teas- elling to chart outbreaks say they don’t need that drive superspreading is crucial, says Lucy ing out whether some people have biological to invoke biological differences to explain Li, an infectious-diseases modeller at the Chan factors that cause them to pass the virus to superspreading events. In a study9 that is yet Zuckerberg Biohub in San Francisco, California. many others. For instance, some individuals to be peer reviewed, physicist Mara Prentiss at Experts say that we already know enough naturally speak louder or expel more air when Harvard University in Cambridge, Massachu- about the main factors of superspreading to they exhale. So they would naturally emit more setts, and her colleagues calculated how many use this phenomenon to our advantage. They aerosols — the tiny virus-laden particles that viral particles were emitted by a single infected are calling on policymakers to harness this travel through the air, says Christian Kähler, a person at each of five superspreading events. knowledge to target control measures that physicist who studies aerosol production and Despite the events differing drastically — one will slow — or even stamp out — the pandemic. dynamics at the University of the Federal Armed took place in a spacious call centre, one in an One of the most basic steps is closing crowded, Forces in Munich, Germany. Also, children and exercise class, two others in buses and another indoor hotspots to prevent superspreading women tend to emit less than men owing to in a choir rehearsal — the amount of virus emit- events. Researchers also recommend follow- their smaller lung capacities, says Kähler. ted by the infected person was remarkably sim- ing Japan’s lead, by using backwards contact But he and other researchers are sceptical ilar. “We were kind of surprised,” says Prentiss, tracing to uncover superspreading events. about biological differences beyond that. “The because it suggests that individual differences are minimal when superspreading occurs. Explosive transmission In all of the cases Prentiss and her team On average, each person who contracts SARS- looked at, the person most likely to have CoV-2 will pass it on to between two and three infected others was either mildly symptomatic others. But that tidy population-level estimate If you have a chain or hadn’t yet developed symptoms. This is a key — known as the basic reproduction number of superspreaders, similarity between the events and is probably (R0) — hides immense variation at the individ- shared by other occurrences of superspread- ual level. In reality, most infections arise from then the cases could ing. “It’s transmission in young, healthy, mobile just a handful of people (see ‘Infection connec- explode in a really populations that actually does the most dam- tions’). Endo’s early analysis estimated that age,” says MacInnis. “Just because you feel well around 10% of cases in countries outside China short period of time.” doesn’t mean that you’re not infected and accounted for 80% of secondary infections up potentially spreading,” she says. to the end of February2. Although transmission patterns might not Estimates from places such as Israel, India, belief in the super-emitter, that’s too simple,” depend much on biological differences between Hong Kong and other parts of China back up he says. people, the same can’t be said for their behav- this observation. And although this pattern Kähler thinks that a person’s behaviour — iour. A person whose job or lifestyle brings them occurs in other infectious diseases, it is espe- whether they fail to keep a safe distance from into contact with numerous people or who is cially pronounced in COVID-19. Influenza, by others during conversations, say, or refuse to more gregarious during social gatherings might contrast, has less individual variation, says wear a mask — is much more likely to heighten be more likely to be a superspreader than some- Endo, and tends to spread more evenly. transmission risk than is the amount of aerosol one who is a wallflower, according to Kähler. The upshot of superspreading is that a they emit. Actions such as singing and shout- few infections can rapidly blossom into a ing also boost that amount, he says. Estimates Problem places raging outbreak, says Li, who has studied the suggest that speaking loudly can increase the One of the most important lessons to have phenomenon in locations across the United number of particles emitted by up to 50 times emerged over the past year is that the spaces States, Europe and China. “If you have a chain of compared with normal speaking5, and singing where people congregate matter when it comes superspreaders, then the cases could explode can produce up to 99 times more, according to infection risk. Numerous superspreading in a really short period of time,” she says. to a study that has not been peer reviewed6. events have occurred in crowded indoor spaces New variants of SARS-CoV-2 that first Individual variation in immune responses with poor ventilation. This aligns with other attracted attention in the United Kingdom, could affect how much virus a person produces, pieces of evidence that airborne transmission South Africa and Brazil could make super- says virologist Dominic Dwyer at NSW Health through aerosols is an important — if not the spreading worse, says Li. On the basis of a Pathology, the state’s public pathology service, main — mode by which SARS-CoV-2 passes from reported 50% higher transmission rate in a in Sydney, Australia. Differences in how young one person to the next.

Feature INFECTION tracers have a good chance of uncovering such events in this way. Endo’s modelling shows CONNECTIONS that backwards contact tracing has an over- Coloured dots represent 12 people infected with sized effect on controlling transmission . SARS-CoV-2 in early 2020 But this type of contact tracing is in Hunan province, China. labour-intensive, and can usually be adopted Researchers reconstructed chains of transmission for only when case numbers are already coming 1,178 people, represented down. At this point, “backwards tracing can by lines connecting the dots. Most individuals did work pretty well as the final hammer to finish not infect anybody else, the outbreak”, says Endo. but 15% of people Ideally, public-health measures should pre- accounted for 80% of secondary infections vent superspreading events from happening — an indication that in the first place. But, says MacInnis, pinning superspreading played down some of the finer points of superspread- a major part in transmissions. ing becomes harder as case numbers surge — as they have recently in the United States, the United Kingdom and large parts of Europe. (2021) , EABE2424 371 Prefectures in Hunan Leskovec’s work suggests a way to limit trans- Changsha

mission. By simulating various scenarios, he SCIENCE Yueyang Shaoyang found that restaurants account for 20% of the Loudi future month’s transmissions if all businesses Changde reopen. That implies that restaurants are par- Zhuzhou Yiyang ticularly risky, and could be targeted for restric-

Others tions, rather than requiring all businesses to ET AL . K. SUN SOURCE: close. Leskovec is currently in discussions with Japan recognized this issue early, and in Feb- Leskovec. These differences could explain the policymakers to use his model to fine-tune reo- ruary 2020 promoted awareness of ‘the 3Cs’ observed higher infection rates in these neigh- pening measures that maximize disease control that put people at risk of infection — closed bourhoods, he says, and indicate that resources and minimize disruption to businesses. spaces, crowded places and close-contact set- — education or masks, say — could help to stem But not all risks can be addressed easily, says tings. The World Health Organization’s Western transmission in such communities. Li. Essential workers who spend time in close Pacific Region adopted the 3Cs public-health Max Lau, a disease modeller at Emory Uni- proximity to others, such as meat processors, message in July. Limits on the number of people versity in Atlanta, Georgia, also used mobile- will continue to be exposed to high-risk envi- allowed to gather indoors have been a staple of phone data to track transmission dynamics11. ronments. “There will always be an underlying worldwide public-health measures designed to By calculating the variation in individual trans- risk of superspreading events just because of curb the spread of the virus. mission in parts of Georgia — a value known as the way that society is structured,” she says. But researchers are working to improve their the dispersion parameter, k — he was able to Many nations started off this year with some understanding of precisely what makes for a compare rates of superspreading in different of the worst outbreaks of the pandemic. And, risky indoor environment, so that restrictions populations. A small k corresponds to clumpier as more-infectious variants spread world- can be better targeted and less disruptive. Jure transmission, or more superspreading. wide, an end to the pandemic seems distant. Leskovec, a computer scientist at Stanford Lau found that superspreading was particu- But when outbreaks do start to peter out — University in California, and his team used larly prominent in people younger than 60 — the whether as a result of lockdowns or of mass human-mobility data to see which venues are working, socializing portion of the population. vaccination — superspreading will account for particularly risky. The group used anonymized It was also an important driver of transmission an even greater share of the case load, says Lau. mobile-phone location data to model the hour- in rural areas, perhaps because there was less That makes it especially important to stay the by-hour movements of around 100 million peo- adherence to shelter-in-place orders, he says. course with prevention measures, even when ple in the United States over a 2-month period case numbers are low. “If we see the decline of from March to May last year. By making the sim- Superspreading as an advantage cases, we have to be even more careful about ple assumption that venues carry a greater risk The growing understanding of superspread- avoiding these superspreading events,” he says. if they are smaller, more densely occupied and ing — and its role in driving transmission — has visited for longer, he found that restaurants, pointed to ways to squash outbreaks when Dyani Lewis is a freelance science journalist in cafes and gyms are transmission hotspots10. they emerge. One of these is intensive contact Melbourne, Australia. Ten per cent of the locations accounted for 80% tracing to find and alert everyone who might 1. Liu, Y., Eggo, R. M. & Kucharski, A. J. Lancet 395, E47 (2020). of predicted infections, he says. have been exposed to a superspreading event. 2. Endo, A. et al. Wellcome Open Res. 5, 67 (2020). Leskovec’s model also provides clues as to In February last year, Japan successfully 3. Volz, E. et al. Preprint at medRxiv https://doi. why lower-income communities are dispro- implemented this type of strategy, called org/10.1101/2020.12.30.20249034 (2021). 4. Lemieux, J. E. et al. Preprint at medRxiv https://doi. portionately affected by the pandemic. People cluster-focused backwards contact tracing. org/10.1101/2020.08.23.20178236 (2020). from low-income neighbourhoods reduced Instead of working forwards and finding close 5. Asadi, S. et al. Sci. Rep. 9, 2348 (2019). their movements less in response to lockdowns contacts who might have been exposed to a 6. Mürbe, D. et al. Preprint at https://doi.org/10.14279/ depositonce-10375.3 (2020). — perhaps owing to work obligations — than did particular individual, backwards contact 7. Viner, R. M. et al. JAMA Paediatr. 175, 143–156 (2021). people in wealthy areas. But venues were also tracing follows the transmission chain back 8. Edwards, D. A. et al. Proc. Natl Acad. Sci. USA 118, e2021830118 (2021). more risky in low-income areas. Grocery stores in time to locate the individual who infected 9. Prentiss, M., Chu, A. & Berggren, K. K. Preprint at medRxiv were more densely occupied, and people stayed the person in question. Each newly infected https://doi.org/10.1101/2020.10.21.20216895 (2020). there for longer. “A single trip to a grocery store person is more likely to have been infected 10. Chang, S. et al. Nature 589, 82–87 (2021). 11. Lau, M. S. Y. et al. Proc. Natl Acad. Sci. USA 117, 22430– was about twice as risky for a low-income indi- in a superspreading event than by someone 22435 (2020). vidual” due to differences in mobility alone, says who passed the virus only to them. So contact 12. Endo, A. et al. Wellcome Open Res. 5, 239 (2021).