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From number-crunching to chemistry: how research is used in the coronavirus outbreak

As the world comes to terms with the scale of the coronavirus pandemic, confusion reigns about the reliability and relevance of many statistics. While the death toll continues to rise, the total number of infections is impossible to know and estimates of the fatality rate continue to vary.

Published: 26 March 2020 11:08 CET

From number-crunching to chemistry: how research is used in the coronavirus outbreak

Photo: Stockholm University

The crisis has been made worse by shortages of essential medical supplies, which has led to chemists and other researchers at Stockholm University teaming up to solve the problem.

With no vaccine and no effective treatment, one thing that is abundantly clear is that there is no magic solution. But Tom Britton, professor of mathematics at Stockholm University and a specialist in modelling the spread of infectious diseases, says there is a magic number for public health experts to keep in mind: R = 1.

The reproduction number (R) is the number of individuals the average person with the virus infects early in an outbreak; knowing that allows models to predict its spread. Many estimates put the global reproduction number for coronavirus at 2 to 2.5. By comparison, Professor Britton says it is roughly 1.5 for flu and 15 for measles.

“With coronavirus, there’s no immunity and no vaccine, so even if R was 1.5 more than half would get infected,” he says. “At 2.5, then 60 to 70 percent would be infected if no restrictions or measures are implemented. That shows how much we must change our behaviour.”

Those changes are to help us get below the magic number: if preventive measures and increasing immunity bring the effective reproduction number below one, Professor Britton says an outbreak will soon end.

Hopes of building immunity

Professor Britton works with SIR models that map the number of people who are susceptible, infected and recovered. Chinese experts say patients with COVID-19 do develop a protective antibody – although it remains unclear how long that lasts and isolated cases of reinfection have been reported.

Evidence is also mounting that many people with coronavirus are only mildly affected. One new study suggests 17.9 per cent have no symptoms at all. For some, this stokes fears about the spread of an invisible disease. But the mathematician has a different perspective. “Essentially, that is good news because it means immunity will build up in the community quicker than we had thought,” he says.

Prof Tom Britton, Stockholm University/Photo by Konstantin Kriechbaum

Mathematical modelling of diseases starts with just a few basic parameters to understand fundamental trends. “As you make models more realistic, you add heterogeneities,” explains Professor Britton. This can make models more relevant to different societies. “For example, you divide the population into age groups and households and make assumptions about who has most contact with whom.”

Find out about opportunities to study at Stockholm University

Complete lockdowns that dramatically reduce personal contact can ensure an outbreak does not explode, as demonstrated in China, by bringing R well below 1. “But if you do it for two months and then go back to normal, coronavirus will come back,” warns Professor Britton, who is in contact with the Swedish Public Health Agency’s modelling team to offer suggestions several times per day. So, with the preventive steps taken, what does Professor Britton expect Sweden’s final rate of coronavirus infection to be?

“I think that eventually, say within a year, around 60 percent of us will get infected,” he says. “The importance lies in slowing it down so that it does not happen too quickly and overburden healthcare. I also think the fatality rate is smaller than initially expected, perhaps 0.2 to 0.4 percent.”

Fighting for the future

Amid warnings that COVID-19 could return annually, Stockholm University is carrying out research to develop an antiviral treatment for the coronavirus. The Fight-nCoV project is one of 17 being funded by European Union grants worth €47.5 million aimed at vaccine development, treatment and diagnostics.

Anna-Lena Spetz, professor of immunology at the Department of Molecular Biosciences, The Wenner-Gren Institute, is leading the efforts to produce a new type of antiviral drug that would also fight other viruses that attack the upper airways. Developing a “broad-spectrum” antiviral treatment also means “building preparedness for future epidemics, when the next animal-human viral transmission occurs,” says Professor Spetz.

Find out more about Stockholm University’s EU grant for coronavirus research

Fight-nCoV will receive €2.8 million for two years of research. The Stockholm University team will work with colleagues in Sweden, Germany, Denmark and France to test the effect of drugs on the coronavirus in test tubes and animal models.

Chemists lend a helping hand in current healthcare crisis

In parallel to research being conducted at the University, solidarity actions and concrete help have also been part of researchers’ support in the current coronavirus crisis, for instance by Stockholm University’s chemists. The Swedish healthcare system is facing shortages of hand sanitiser and disposable protective equipment due to coronavirus.

Photo by Konstantin Kriechbaum/Stockholm University

Chemistry Department heads spoke to one hospital and were asked if they could manufacture hand sanitiser as the demand is currently very high. Chemists began collecting the ingredients for alcohol production and set to work. In next to no time, they had a consignment of over 200 litres of hand sanitiser, as well as plastic gloves, face masks and other items.

Danderyd Hospital in Stockholm was the first to collect vital supplies and more hand sanitiser continues to be produced, destined for Karolinska University Hospital in Huddinge. “This is teamwork where many people do a fantastic job,” says Berit Olofsson, a professor of organic chemistry and section dean about the initiative, which has now spread to several other universities in Sweden following Stockholm University’s example.

This article was produced by The Local Creative Studio and sponsored by Stockholm University .

FACT CHECK: Did Sweden have lower pandemic mortality than Denmark and Norway?

At one point in May 2020, Sweden had the highest Covid-19 death rate in the world, spurring newspapers like the New York Times and Time Magazine to present the country as a cautionary tale, a warning of how much more Covid-19 could ravage populations if strict enough measures were not applied.

“Per million people, Sweden has suffered 40 percent more deaths than the United States, 12 times more than Norway, seven times more than Finland and six times more than Denmark,” the New York Times reported in July 2020.

An article in Time in October 2020 declared Sweden’s Covid response “a disaster”, citing figures from Johns Hopkins University ranking Sweden’s per capita death rate as the 12th highest in the world.

So there was undisguised glee among lockdown sceptics when Svenska Dagbladet published data last week showing that in the pandemic years 2020, 2021 and 2022 Sweden’s excess mortality was the lowest, not only in the European Union, but also of all the Nordic countries, beating even global Covid-19 success stories, such as Norway, Denmark and Finland.

Versions of the graph or links to the story were tweeted out by international anti-lockdown figures such as Bjørn Lomborg, a Danish sceptic of climate action, and Fraser Nelson, editor of Britain’s Spectator Magazine, while in Sweden columnists like Dagens Nyheter’s Alex Schulman and Svenska Dagbladet’s opinion editor Peter Wennblad showed that Anders Tegnell, the state epidemiologist who led Sweden’s strategy, had been “right all along”.

Excess mortality — the number of people who die in a year compared to the number expected to die based on previous years — is seen by some statisticians as a better measure for comparing countries’ Covid-19 responses, as it is less vulnerable to differences in how Covid-19 deaths are reported.

But are these figures legitimate, where do they come from, and do they show what they purport to show?

Here are the numbers used by SvD in its chart:

Where do the numbers come from?

Örjan Hemström, a statistician specialising in births and deaths at Sweden’s state statistics agency Statistics Sweden (SCB), put together the figures at the request of Svenska Dagbladet.

He told The Local that the numbers published in the newspaper came from him and had not been doctored in any way by the journalists.

He did, however, point out that he had produced an alternative set of figures for the Nordic countries, which the newspaper chose not to use, in which Sweden had exactly the same excess mortality as Denmark and Norway.

“I think they also could have published the computation I did for the Nordic countries of what was expected from the population predictions,” he said of the way SvD had used his numbers. “It takes into consideration trends in mortality by age and sex. The excess deaths were more similar for Denmark, Sweden, and Norway. Almost the same.”

Here are Hemström’s alternative numbers:

There are two basic ways of measuring excess mortality. The simplest, and the one used by SvD/SCB, is to simply compare the death rates in the relevant period with the mean of previous years, normally five years.

More sophisticated measures attempt to estimate the expected number of deaths by extending mortality trends seen in a certain country, adjusting for the age of the population and other factors. But this can lead to results to vary significantly depending on how mortality trends and expected mortality are calculated.

The issue with the analysis in the SvD graph is that compares deaths in the pandemic years to deaths over just three years, a mean of 2017-2019, and does not properly take into account Sweden’s longstanding declining mortality trend, or the gently rising mortality trend in some other countries where mortality is creeping upwards due to an ageing population, such as Finland.

“It’s very difficult to compare countries and the longer the pandemic goes on for the harder it is, because you need a proper baseline, and that baseline depends on what happened before,” Karin Modig, an epidemiologist at Sweden’s Karolinska Institute whose research focuses on ageing populations, told The Local.

“As soon as you compare between countries, it’s more difficult because countries have different trends of mortality, they have different age structures, and in the pandemic they might have had different seasonal variations.”

She described analyses such as Hemström’s as “quite crude”.

In an interview with SvD to accompany the graph, Tegnell also pushed back against giving the numbers too much weight.

“Mortality doesn’t tell the whole story about what effect a pandemic has had on different countries,” he said. “The excess mortality measure has its weaknesses and depends a lot on the demographic structures of countries, but anyway, when it comes to that measure, it looks like Sweden managed to do quite well.”

Do the numbers match those provided by other international experts and media?

Sweden’s excess mortality over the three years of the pandemic is certainly below average worldwide, but in most other analyses it remains higher than those of Norway and Denmark.

A ranking of excess mortality put together by Our World in Data for the same period as the SvD/SCB table estimates Sweden’s excess mortality between the start of 2020 and the end of 2022 at 5.62 percent, considerably more than the 4.4 percent SvD claims, and above that of Norway on 5.08 percent and Denmark on 2.52 percent.

The Economist newspaper also put together an estimate, using their own method based on projected deaths. In this estimate, Sweden also has a higher rate of excess deaths than Denmark and Norway (but not than Finland).

Our World in Data uses the estimate produced by Ariel Karlinsky and Dmitry Kobak, who manage the World Mortality Dataset (WMD). To produce the estimate, they fit a regression model for each region using historical deaths data from 2015–2019, so a time period of five years rather than the three used by SCB.

What’s clear, is that, whatever method you use, Sweden and the other Nordic countries are among the countries with the lowest excess mortality over the pandemic.

“Most methods seem to put Sweden and the other Nordic countries among the countries in Europe with the lowest cumulative excess deaths for 2020-2022,” Preben Aavitsland, the Director for Surveillance and the Norwegian Institute of Public Health, told The Local.

So if Sweden had similar excess mortality to those of the other Nordics over the period, does that mean it had a similar Covid-19 death rate?

No. Sweden’s per capita death rate from Covid-19 over the period covered by the SvD/SCB figures, at 2,249 per million people, is still more than double Norway’s 959 per million, 60 percent more than the 1,409 per million who died in Denmark, and more than 50 percent more than the 1,612 per million who died in Finland.

Sweden’s death rate is now much closer to those of the other Nordic countries than it was at the end of 2020, however, something Aavitsland put down to the higher number of Covid-19 deaths seen in his country in the later years of the pandemic.

“The most striking difference between Sweden and the other Nordic countries is that only Sweden had large excess mortality in 2020 and the winter of 2020-21,” Aavitsland explained. “In 2022, the field levelled out as the other countries also had excess mortality when most of the population was infected by the omicron variant after all measures had been lifted.”

So why, if the Covid-19 death rates are still so different, are the excess mortality rates so similar?

This largely reflects the fact that many of those who died in Sweden in the first year of the pandemic were elderly people in care homes who would have died anyway by the end of 2022.

About 90 percent of Covid-19 deaths were in people above 70, Aavitsland pointed out, adding that this is the same age group where you find around 80 percent of all deaths, regardless of cause, in a Scandinavian country.

“My interpretation is that in the first year of the pandemic, say March 2020 – February 2021, Sweden had several thousand excess deaths among the elderly, including nursing home residents,” he said. “Most of this was caused by Covid-19. In the other [Nordic] countries, more people like these survived, but they died in 2022. The other countries managed to delay some deaths, but now, three years after, we end up at around the same place.”

So does that mean Sweden’s state epidemiologist Anders Tegnell was right all along?

It depends on how you view the years lost by the several thousand elderly people who caught Covid-19 and died in Sweden in the first wave because Sweden did not follow the example of Denmark, Norway, and Finland and bring in a short three-week lockdown in March and April 2020. Were those two years worth the greater restrictions imposed in Sweden’s neighbours?

Tegnell himself probably said it best in the SvD interview.

“You’ve got to remember that a lot of people died in the pandemic, which is of course terrible in many ways, not least for their many loved ones who were affected, so you need to be a bit humble when presented with these kinds of figures.”

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