Every fifteen minutes, three masked individuals troop into two research centres in the suburbs of Bonn, Germany, to participate in a study that is determining whether people have antibodies against the COVID-19 coronavirus. With 28 millilitres less blood, the participants leave through a separate door and will soon learn whether they have survived a coronavirus infection.
They are part of a population cohort called the Rhineland Study, and have been going to the centres six days a week since 24 April. Around 5,000 people from the region have donated blood plasma to the initiative so far.
The effort, led by epidemiologist Monique Breteler, is one of several long-term cohort studies that originally focused on other diseases but have swiftly been repurposed to study the coronavirus. Population cohorts collect genetic, health and lifestyle information from thousands of people over years or even decades to find out which genetic and environmental factors collude to increase risk of diseases. The Rhineland Study, for instance, was set up in 2016 to study neurodegenerative disorders, such as Alzheimer’s disease.
But researchers hope that using cohorts to study the coronavirus will create rich data sets that, in the short term, could help policymakers to decide how to best control the disease and ease the lockdowns implemented to stem the virus’s spread. In the long term, they will be able to track physical, mental and socioeconomic consequences of the pandemic, and allow scientists to address questions such as whether exposure to the virus increases health risks later in life.
“For one thing, they can help us understand why some people have no symptoms while others become seriously ill,” says Breteler. This knowledge could, for instance, inform decisions about who should be vaccinated first once limited vaccine batches become available, she says.
Cohort studies differ from efforts that are using antibody measurements to calculate the proportion of a population that has been infected with SARS-CoV-2. Many repurposed cohort studies will take blood samples from participants at multiple time intervals, to see how long antibody immunity might last. But their design also allows them to answer detailed questions about the biology of COVID-19 infections by combining this information with participants’ genetic, health and lifestyle data.
This information will be made available to researchers from diverse fields who are seeking to find out which factors influence susceptibility or resistance to infection and the seriousness of disease. Genes, immunological and metabolic status and environmental factors could all be at play.
“We are all different and these larger pre-existing cohorts will be very valuable in helping us understand which of our biological or lifestyle factors put us at risk,” says Ralf Reintjes, an epidemiologist at the Hamburg University of Applied Sciences in Germany. “They will give us a better understanding of the steps needed in the near future to come back to a safe but normal life — not based on gut feeling but on evidence.”
Large cohorts have a “baked-in focus on genetic and environmental factors”, so are in a great position to identify which factors influence the risk of getting a serious disease, Francis Collins, director of the US National Institutes of Health (NIH), said at the annual meeting of the International 100K Cohort Consortium (IHCC) on 5 May. The IHCC was launched 2 years ago to encourage the sharing of data and methods among 66 cohorts representing 4 million people.
Cohort data will also be important for tracking how the COVID-19 crisis might exacerbate socioeconomic inequalities, says Alissa Goodman, an economist who directs the Centre for Longitudinal Studies at University College London. The centre runs four UK birth cohorts including one that follows babies born in 1958, and is asking 50,000 participants to complete a questionnaire to gather insights into how COVID-19 has affected their lives, including physical and mental health, relationships and finances. Their strategy, she says, was “in part determined by some of the policymakers — as well as academics — in our scientific networks”.
The German Center for Neurodegenerative Diseases (DZNE) launched the Rhineland Study in Bonn to try to understand factors that, over a lifetime, lead some people to develop disorders such as Alzheimer’s. Recruits underwent some eight hours of investigation including interviews about their medical history and lifestyles and extensive biomedical investigations, from detailed genomic analyses to brain scans. This information is updated periodically over the decades.
The study’s scientists had barely recruited one-fifth of the participants for the original study when Germany’s lockdown on 22 March closed its two centres. Breteler says it was a “no brainer” to turn over the study’s rich resources to help to address the COVID-19 crisis.
Other cohorts followed, and began assessing whether participants had antibodies against the coronavirus. Norway’s birth cohort — the Norwegian Mother and Child Cohort — began sampling its participants at the end of April. It collects blood from 400 or so people each week and has not yet decided how many it will sample. Iceland’s government has enlisted the Reykjavik-based genomics company deCODE to monitor antibodies in about 50,000 people. That began on 11 May, and the results might later be linked to participants’ health, lifestyle and genomic information, which is held in a government data centre, and made accessible to scientists. And on 18 May, the UK Biobank — which holds genomic and health information on its participants — began a programme to gather blood samples from 10,000 of its participants along with 10,000 of their children and grandchildren to test for antibodies.
Most of the studies are conducting 1–3 validated laboratory tests for each person to measure their antibody level. The Rhineland Study is also including a time-consuming but informative test to assess whether the antibodies are capable of actually ‘neutralizing’ the virus, preventing it from entering cells.
All of these large-scale studies have been confronted with the logistical and technical challenges of getting taking blood samples from thousands of people amid a pandemic, and of getting reliable antibody measurements. Regional studies, such as the Rhineland Study and the Norwegian cohort, can ask participants to come into centres or hospitals to donate blood and answer questions about their recent health. The UK Biobank study is posting blood-collection kits to recruits, who will draw around half a millilitre of blood and mail it back. They receive a new kit every month for at least six months. They won’t be given their individual results, but will be informed of the study’s progress in determining antibody prevalence in a population.
The IHCC is also coordinating international efforts to test any biological samples that the cohorts might have collected in October or November last year. If it detects SARS-CoV-2, this could build a picture of when the virus began circulating, and its path around the world.
The cohorts might be able to play an even bigger part in the COVID-19 crisis, said Collins at the IHCC meeting. He said that the NIH was discussing whether cohorts might provide volunteers to test new vaccines and therapies, to get a better picture from around the world of who responds well and who doesn’t.
Nature 582, 326 (2020)