Monday, April 27, 2020

Can you catch Covid-19 twice?

By William Park 22nd April 2020
Immunity to Covid-19 is not as clear cut as we might hope – but understanding who is immune and why will be key to finding a treatment.
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As the news of potential new vaccines and tests for Covid-19 developed by labs around the world seems to make the news each day, the optimists among us have started to look for signs that we might be moving towards the easing of lockdown restrictions in Europe and the US, following from the relaxing of measures in New Zealand and Australia. The phrase on everyone’s lips is “exit strategy”.
Much of the debate about how we might begin to lift restrictions has centred around the need for an antibody test. If we were able to tell who had been infected and had recovered, and if those people could demonstrate immunity against catching the virus again, could we begin to allow them to go back to work?
This is dependent on a number of things, including developing a proven antibody test. Antibodies are proteins produced by the immune system to target a virus, bacterium or other pathogen. They destroy the pathogen by binding to it and making it harmless, or by flagging it for destruction by immune cells. Antibodies typically linger on in the bloodstream after an infection, in case the virus returns. If it does, the antibodies are ready and waiting, which means immune response much faster – so much so that it might barely register as a second infection. What this means is that convalescent patients – those who have recovered – have resistance to reinfection.
Unfortunately, it might not be as simple as that, the World Health Organization (WHO)’s Maria van Kerkhove warned over the weekend – and the reason has much to do with the fact that this is a virus that had never been in a human host until the end of last year.

Determining who gets the disease and why is really important, and in some cases it is the most important question. If no one was getting sick we would not have a concern – Katrina Pollock

“We are learning all the time about how it behaves and the disease it causes,” says Katrina Pollock, a senior clinical research fellow in vaccinology at the NIHR Clinical Research Facility at Imperial College London.
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“Determining who gets the disease and why is really important, and in some cases it is the most important question,” says Pollock. “If no one was getting sick we would not have a concern.
“When you are naive to the virus – you have not been in contact before – your immune system responds quickly with a first response, which is non-specific, to control the infection immediately,” she says. How you respond in that first, non-specific reaction is based on the dose you received, your genetic background and how your immune system is already programmed to respond to new infections. These can all be affected by your general health and age – both of which seem to have a particular influence on the severity of Covid-19.
We develop flu-like symptoms to respiratory infections during this first, non-specific response. The fever, achiness and tiredness we feel, and the production of mucus are all general strategies our immune system employs to neutralise an infection. We try to make our bodies hostile to the virus cells by raising our temperature and deploying general virus-eating cells called phagocytes.
“As part of that response, part of the immune system gets programmed like software programming,” says Pollock. “The response is refined and replaced with a specific response. That specific response tries to completely clear the infection. Most of the time this can be done.”
This is called the adaptive immune response. Key to our adaptive response are two types of cells: T and B cells. “B cells are responsible for memory, they produce antibodies that are already specific to flu or cold antigens, that allows them to quickly bind with the surface of the virus to stop replication,” says Aikiko Iwasaki, a professor of immunobiology and molecular, cellular and developmental biology at Yale. T cells destroy virus-infected cells completely.
An empty street under lockdown in Kiev (Credit: Getty Images)
Understanding how our immune systems respond to infection with Covid-19 is thought to be key to formulating an exit strategy (Credit: Getty Images).
For most viruses, then, the first time you catch the infection your body takes a little time to develop the requisite antibodies, but you should be better equipped to fight off the infection a second time.
That is the theory, although in practice we don’t know how people might react to reinfection with Covid-19. One recent paper looked at reinfection in rhesus macaques, who, after being infected with the virus once, were not able to catch the infection a second time. However, the macaques were exposed to a standard dose of the virus, meaning the researchers predetermined how much of the virus the monkeys should get.
In reality, the dose that you might receive varies depending on whether you breathed in airborne particles or, say, touched a contaminated surface and rubbed your eyes, as well as factors such as how close you stood to an infected person, and how long the virus had been outside of another host, and a whole multitude of other factors. If someone were only exposed to a small dose of the virus in the first instance, who can say how they might react if the second dose were much greater.
“It is unknown why some people have mild infections, but one potential factor that can influence them is the exposure rate,” says Iwasaki. “We have done experiments in mice with exposure to influenza; just 10 viral particles can cause asymptomatic infection, but no immunity. But up to one million viral particles cause the production of antibodies, they are immune. There is a dose response.”
It’s also unclear whether having a stronger response will leave you any better off. “It is sometimes the case where if you have a strong reaction you might have immunity persist for longer but it might also be the case that those people are not able to respond to infections as easily,” says Pollock.
The hope is that a recovered patient has developed enough Covid-19-specific antibodies to fight off a secondary infection. However, in one study on convalescent patients in China, 30% of those studied had very little or no detectable antibodies in their blood plasma. It would seem that those people were able to neutralise the infection without the need to develop antibodies, either because their innate immune response or the T cells in their adaptive immune response, or a combination of both, were sufficient. Those with the lowest counts of antibodies were most likely to be the youngest patients.

Antibodies are not the only answer – Aikiko Iwasaki

“Antibodies are not the only answer,” says Iwasaki. “We don’t know why the people recovered but I suspect it was because they had a very good T cell response.”
The sample size in this study was small, so whether that ratio of convalescent patients with and without antibodies scales up to the larger population remains to be seen.
A worker taking a sample for Covid-19 testing (Credit: Getty Images).
The first time a person is infected with Covid-19, it will take their body a while to make antibodies – but these might help to prevent a second infection (Credit: Getty Images).
If some convalescent patients are able to recover without developing antibodies, it leaves a big question mark over one of the proposed short-term treatments. Some infections can be treated with blood plasma transfusions. A small amount of blood from convalescent patients is extracted, stripped of red and white blood cells, clotting agents and the other things that you find in blood until only the serum, containing antibodies, remains. These antibodies are known to be effective against the virus because they have come directly from patients who have recovered from the disease.
This treatment has existed for a long time. In fact, the first Nobel Prize in Physiology or Medicine was awarded for the development of serum therapy as a treatment for diphtheria. Blood plasma transfusions from convalescent Covid-19 patients are currently the subject of clinical trials in the UK.
The reason that plasma transfusions cannot be a long-term solution is that, unlike vaccines, the treatment cannot be scaled up and rolled out to the whole population. One patient might donate 200-500ml of plasma. Like with giving blood, this can be exhausting, invasive, is recommended only for otherwise healthy patients and takes some time to recover from.
Iwasaki says 200 to 500ml “is a really large volume,” says Iwasaki. “It is a lot of plasma to take from one person.” One patient might be able to donate their serum to a couple of other people, but no more than that. And over time the antibody count in the serum will drop. On top of that, if only 70% of convalescent patients develop antibodies, your pool of potential donors decreases further.
This treatment will be best-done in hospitals where there are a large number of potential donors, but might be tricker to administer to patients who are in remote places or recovering outside of hospitals, like those in care homes.
A man wearing a face mask stands in a deserted street in Turkey (Credit: Getty Images).
Some scientists have suggested that social distancing might be required until 2022 (Credit: Getty Images).
The other consideration when discussing immunity is the length of time that someone might remain immune for. Winter flu vaccines have to be re-administered each year, in part because over time your flu antibody count drops. Most of us are repeatedly exposed to the viruses that cause the common cold, so our antibody counts are topped up each year. “With time they might not be replaced,” says Pollock. “Being re-exposed is like getting a wake-up call to make more of them.”
If for any reason we are not exposed to them for a period of time, or our immune system is weakened, we feel those familiar cold symptoms.
There is no reason to think that Covid-19 will not act in the same way – being fought off when our antibody counts are high in the medium term and causing us symptoms when they drop in the long term or when our immune systems are vulnerable. Although, again, Iwasaki and Pollock stress that we do not know definitively, and some have suggested that it could take years for this kind of immunity to become prevalent. A paper published in Science last week suggested that social distancing might still be required until 2022.
There is also a limit to what we can infer from previous coronavirus outbreaks. There is still no effective vaccine for either Mers or Sars, and instead stringent public health measures were necessary to contain the outbreaks. While social distancing measures are effective in containing Covid-19, they have not been fast or efficient enough to stop its global spread.
Is a convalescent patient clear to go back to work? “It depends on when you get clearance of the virus [and are therefore not infectious anymore],” says Pollock. “A PCR test [one that relies on detecting the virus’ genetic material] cannot distinguish between live and dead viruses.” Although in all likelihood, anyone who has recovered will only continue to test positively for the virus for a short period of time. Those dead virus particles would be destroyed and removed from the body shortly afterwards.
Workers on a Covid-19 testing kit production line in South Korea (Credit: Getty Images).
Scientists are currently trying to figure out if Covid-19 patients develop enough antibodies to stop them being infected twice (Credit: Getty Images).
Checking if a person still has symptoms is not a good measure either. A paper in the journal Nature found that patients continued to shed the virus after symptoms ended.
A PCR test, which has to be done in a lab, is the best way to know who is infected or had been infected until very recently. But the complicated science around immunity is why the WHO has cast doubt about how useful antibody tests might be.
“There are many reasons why antibody testing might be a problem,” says Iwasaki. “One is sensitivity. The test might be negative because the test is not sensitive enough, even with highly sensitive tests 30% of patients have no antibodies [according to the paper published on Medrxiv]. Antibody count alone is not a good measure of immunity protection – only one proxy for immune response.”
But the main thing to emphasise, says Pollock, “is that the research is happening at the same time as the pandemic is unfolding and it is not possible to give people the information they want immediately”.
As an award-winning science site, BBC Future is committed to bringing you evidence-based analysis and myth-busting stories around the new coronavirus. You can read more of our Covid-19 coverage here.
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By Harriet Constable26th April 2020
The new coronavirus has spread rapidly in cities around the globe. How might the virus make us think differently about urban design in the future?
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The pandemic has turned the world outside our doorsteps into a newly formed wilderness. Public spaces are now areas to be ventured into sparingly, except by essential workers, so for most of us our worlds have shrunk to the size of our homes.
Modern cities weren’t designed to cope with life during a pandemic, and this upside-down way of living has turned them into “a disorganised array of disconnected bedrooms and studios”, says Lydia Kallipoliti, assistant professor of architecture at The Cooper Union in New York. This layout might have made sense when cities were internationally connected hubs filled with millions of people working, commuting, sightseeing, drinking, dancing and hugging one another without a second thought. But that world seems a long way off now.
The 21st Century has so far seen Sars, Mers, Ebola, bird flu, swine flu and now Covid-19. If we have indeed entered an era of pandemics, how might we design the cities of tomorrow so that the outdoors doesn’t become a no-go zone, but remains a safe and habitable space?
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Cities have already come a very long way when it comes to disease prevention. “It used to be that that living in a city would reduce your life expectancy… they were death traps,” says science journalist and author of The Fever and Pandemic, Sonia Shah. The rapid growth of cities during the Industrial Revolution led to polluted streets that were a hotbed for infection, especially in places like London and New York. As these cities grew, outbreaks of typhoid and cholera became such major public health issues that they led to the construction of entire new sanitation systems: sewers.
The measures put in place to prevent the spread of Covid-19 have meant many people are isolated in their homes (Credit: EPA)
“To store the filth of a city within the city is simply to invite disease and death,” wrote the authors of the 1840 book The Separate System of Sewerage, its Theory and Construction, which called for sewers to be built in New York. It went on to note that, “by sewering certain towns in England, the death rate from pulmonary diseases alone was reduced by 50%”.
Over time, cities also started implementing basic building standards including “apartments to have light and ventilation and, you know, only a certain number of people in each one,” says Shah, who explains that gradually things began to change.
In recent years, calls for cities to focus on health in their planning have been growing. “For the resilient, sustainable cities we all want and need, urban plans need to be designed, evaluated and approved using a health lens,” says Layla McCay, director for the Centre for Urban Design and Mental Health.
There are many examples of this: since 2016, the National Parks Board of Singapore has been building therapeutic gardens in public parks to boost the mental and emotional well-being of citizens. In Tokyo, citizens are working with urban designers to greenify their neighbourhoods to improve their health.

As the world’s cities have grown, urban design has actually made many of them healthy alternatives to suburban or rural living

Over the past century more and more of us have flocked to cities for work opportunities, and to be close to the sources of all our daily needs, from food to healthcare. As the world’s cities have grown, urban design has actually made many of them healthy alternatives to suburban or rural living. A 2017 study found that city living was linked to lower levels of obesity in the UK than life in the suburbs, and the story is similar in the United States. (Read more about the world’s healthiest places to live.)
But that’s not to say that city life is best when it comes to infectious diseases. In a pandemic, busy urban centres are a big part of the problem. Without speedy and efficient public health measures to counter the infection’s spread, the bigger and more well-connected a city, the faster it will travel.
“Precisely because they are hubs for transnational commerce and mobility, densely populated and hyper-connected cities can amplify pandemic risk,” wrote Rebecca Katz, co-director of the Centre for Global Health Science and Security and Robert Muggah, director at the Igarapé Institute, a Brazilian-based think tank in a piece for the World Economic Forum. With estimates that 68% of the world’s population will live in cities by 2050, the need to design cities well for pandemics will only get more pressing.
Urban hotspots
Not all cities are equally vulnerable to disease. Wealthy cities like Copenhagen, with lots of green space and provisions for cycling, are world-famous for their health benefits. But it’s a very different story for those living in the informal settlements of less economically developed cities like Nairobi, Kenya or Dhaka, Bangladesh.
Without proper sanitation or access to clean water to wash “this is where epidemics have the most potential to start and spread”, says Elvis Garcia, an expert in public health and a lecturer at the Harvard Graduate School of Design. “In 10 years, an estimated 20% of the world’s population will live in urban environments with a limited access to appropriate water, health, and sanitation infrastructures,” he says.
Making more space for people to get around and exercise could help to reduce the risk of infections spreading in cities (Credit: Getty Images)
Were a virus like Covid-19, which can go undetected for many days before symptoms show, to emerge among these vulnerable communities it would be disastrous, as was the case with the 2014-2016 Ebola outbreak in West Africa. The countries affected have some of the worst water, sanitation and hygiene (WASH) coverage in the world, which exacerbated the spread and reach of the Ebola outbreak, with fatal consequences, according to Oxfam International. Tackling basic sanitation is the first step in building a healthier city. “That means appropriate water and sanitation systems and good quality houses,” says Garcia. (Read more about how hand hygiene effects the spread of a virus.)
Population density is another factor that can have a big influence on the spread of infectious disease. This is because it can lead to overcrowding, which can increase the frequency of transmission. In 2002 and 2003, a housing estate in Hong Kong was at the centre of the Sars outbreak. The city and special administrative region is one of the most densely packed and unequal places in the world, and the virus eventually killed nearly 800 people.

Even with big green spaces like Central Park in Manhattan residents have struggled to stay far enough away from one another to curb the spread of the disease

Wuhan, the Chinese city where the Covid-19 outbreak began, is the most densely populated in central China, home to 11 million people. Likewise, New York, which has had the worst of the outbreak in the US, is the most densely populated city in the country. Even with big green spaces like Central Park in Manhattan and Prospect Park in Brooklyn, residents have struggled to stay far enough away from one another to curb the spread of the disease.
We can see hints of what the pandemic-resilient cities of tomorrow might look like in the way that urban spaces are being repurposed right now.
One solution to address the overcrowding issue was proposed by New York City councillor Corey Johnson in an interview with Politico: close off parts of the city to traffic and open them up for exercise. “You may be able to deliver more social distancing if you pick certain streets that could be shut down,” he said.
At a daily press conference, the Governor of New York Andrew Cuomo supported the idea of opening streets to reduce density. Their street closures lasted just 11 days, but across the globe, from Calgary to Cologne, cities have been closing off streets to give people more space. Oakland has gone as far as shutting down 74 miles of city streets for walkers and cyclists.  In future cities, planning for pedestrians may even go a step further by building much wider pavements, according to the Centre for Urban Design and Mental Health’s McCay.
Access to lots of green space is also important for the mental and physical health of city residents during a pandemic. Marianthi Tatari, an architect at UNStudio Amsterdam, says, “20 minutes of ‘green time’ a day helps to give us a healthy and humane approach to our present situation”. In the UK, private green spaces were opened and subsequently closed amid fears they were helping spread the disease, but in Portland instead of closing their parks, they shut them to traffic to make more space for people to get outside.  These moves are temporary for now, but as the need to social distance continues we may see more spaces pedestrianised. 
Providing handwashing facilities in public places could help to reduce the risk of passing on infections (Credit: Getty Images)
But with sanitation being such a crucial part of stemming disease, being in a park with no way to keep your hands clean could be a concern. McCay suggests the ramping up the building of hand washing stations in all cities. “If everyone was washing their hands diligently we would see a reduction in all types of infection,” she says. “Perhaps one of the reasons we’re not is because there aren’t these facilities in place.”
Jo da Silva, global sustainable development director at engineering firm ARUP suggests we might need to change the way we build our indoor environments too. In shared buildings “we might think about having more than one lift, and multiple communal staircases,” she says. Doing this avoids “pinch points”, a term for when lots of people are trying to use the same space and getting too close to each other in the process.
If pandemics are to be a regular part of our lives, our cities will need to be more adaptable, according to Johan Woltjer from University of Westminster’s School of Architecture and Cities. “During a crisis like we’re in at the moment, it would mean creating temporary housing and [having] health centres be built more flexibly and have space available in cities for those,” he says. One example of this is the temporary Nightingale Hospital in London, converted in just nine days and able to accommodate 4,000 patients and a 1,000-bed hospital in Wuhan, China, that was built from the ground up in just 10 days. Having both the space and capability to create these rapid, temporary structures will be a fundamental part of a city built for a pandemic.

In shared buildings we might think about having more than one lift, and multiple communal staircases

But cities might go beyond this “to be able to change rapidly, [from the delivery of] essential supplies, shopping and goods, to evacuation routes,” says Woltjer. Materials would need to be sourced which enabled rapid building, like timber and wood, the usage of which is already appealing to many as they are more sustainable. We may see more buildings made from shipping containers too. “There are ready-made houses and smaller buildings that can be put together like a package,” adds Woltjer.
So making different use of our current spaces, implementing further sanitation and transitioning toward more room for pedestrians are all going to be key features in a pandemic-resilient city of the future.
But one of the biggest changes to our cities won’t be so visible as a fancy new building or a big new park, according to Davina Jackson, author of Data cities: How satellites are transforming architecture and design. “Cities of the future are going to have to be designed to deal with completely invisible flows [like a global virus], and that’s where the data mapping comes in.”
She gives an example which brings us back to the urban gut of a city: researchers at the Senseable City Lab at MIT placed sensors into sewers to detect concentrations of illegal drugs and harmful bacteria in specific areas. A city built for a pandemic would likely be filled with hidden sensors to help map the spread of disease.
Self-sufficiency
Another important aspect in building a city resilient to pandemics is thinking about how to source food.
In our globalised world, resources from all corners of the world can end up in the heart of our urban centres within a matter of hours or days, and viruses hitch a ride with them. “Our cities are not citadels,” says Shah. Scientists say coronavirus likely came from bats, which passed through an intermediary species before reaching humans in Wuhan, with its large train station connecting the city to the rest of China and its busy international airport. “Five million people left Wuhan before they locked down that city, because we’re all connected,” says Shah.
The Chinese authorities were able to build a 1,000-bed hospital in Wuhan from the ground up in just 10 days (Credit: Getty Images)
She suggests that to reduce risk, our cities may need to become more localised and self-sufficient in the future. “If you had a city, for example, that could feed itself,” Shah suggests. “It’s not like each place has to be an island, but that there’s some kind of sense of balance and sustainability that you can see within your own settlement.”
There are already examples of urban farming feeding millions when there is little other choice. During World War Two Americans planted 20 million household vegetable plots, producing nine million lbs of produce each year and amounting to 44% of the US harvest, but the challenge of building a self-sufficient city is still a huge one.
Garcia agrees that the city of the future needs to be more localised, not just in food but in access to day-to-day amenities. “Maybe in the mega-cities, you have to create small nuclear entities,” he says. “And each nuclear entity has all the resources inside.” One example of this is the 20-minute city, something that was being trialled in Melbourne, Australia before the coronavirus outbreak. In a 20-minute city, almost everything a citizen needs, from shopping to healthcare to exercise, is within a 20-minute walk or bike ride.
Localisation can also help with another sticking point in the fight against contagion – mass public transport. While hailed as an environmental solution to the pollution caused by individual car usage, public transport is not ideal in a pandemic situation. So cities would need to make more provisions for cycling, and cities may need to “offer more paths and small roads so there are alternative ways to get around: so we’re not all collectively on the same road or in the same public transport”, says Woltjer.
Therapeutic parks in Singapore are designed to boost the mental and emotional well-being of citizens (Credit: Getty Images)
Our homes will need to change too. In an effort to make them more energy and heat efficient, many workspaces, flats and apartment blocks don’t have operable windows. But if we are to going to be spending more time indoors, our houses will need to be better ventilated and offer more light, according to the Irwin S. Chanin School of Architecture’s Kallipoliti. She describes the need to avoid something called “sick building syndrome”, which is what happens “when buildings [are] entirely sealed and start recirculating pathogens through their systems”. Perhaps our homes will even be built to feature “decontamination airlocks like in a Martian environment”, she suggests.
But as the world grapples with the harsh reality of our current situation, we cannot simply build our way out of the problem. A shift in thinking is needed for any city of tomorrow, according to architect Roberto Palomba, who is currently quarantining in his home in Milan.
As a judge on a newly launched Pandemic Architecture competition, which calls for creatives to submit ideas on city design in the face of globalised health threats, he wants to focus not just on design, but on our broader relationship with nature.
“We have abused nature, and [generated] epidemics,” Palomba says. Before thinking about new cities, the focus should be on preventing new diseases from emerging in the first place. “I believe that cities against pandemics will be just that, places where each species will find respect in coexistence.”
So perhaps we shouldn’t be picturing shiny new city-centre plans when envisioning a pandemic-resilient city. The changes will be quite practical, like pop up hand washing stations, and often invisible, like tracking devices built into our sewers. If we do pandemic preparedness right, our cities might look much as they do today – just a little less crowded, with a little more local open space, and with more of the resources they need to support themselves on the doorstep.
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As an award-winning science site, BBC Future is committed to bringing you evidence-based analysis and myth-busting stories around the new coronavirus. You can read more of our Covid-19 coverage here.
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