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Disease and treatment

Major antibody trial in Denmark will determine whether the immune system remembers the new coronavirus

The new coronavirus (SARS-CoV-2) will be around for a while. Occasional outbreaks in schools, mink farms and water parks in Denmark indicate that the virus has probably been tamed but is far from fully controlled. A crucial question that needs to be answered to determine how to keep the virus at bay is whether previously infected people become immune – and whether they remain immune. A new research project will seek to provide some answers by testing up to 40,000 people for antibodies over 1 year.

Being able to remember is not just essential for our brain. Memory also plays a role in our immune system’s defences against viruses and bacteria. SARS-CoV-2 – the new coronavirus that causes COVID-19 and has become public enemy no. 1 – had not infected people before 2019, and people have therefore not developed immune memory or protective immunity. A new antibody testing programme that will test up to 40,000 people will reveal how well our immune system remembers COVID-19.

“Data from China and the United States, and our data, show that most people infected with SARS-CoV-2 will develop antibodies to it, but whether these antibodies provide immunity and how long they remain in the blood is unknown. We will repeatedly test a large group of people in Denmark over an entire year and can then answer some of these very important questions about immunity, thus preparing societies and the healthcare system for a potential second wave of COVID-19,” explains Peter Garred, Professor of Clinical Molecular Medicine at Rigshospitalet and the University of Copenhagen.

Perhaps immunity disappears

The new project is a collaboration between researchers at Rigshospitalet, Herlev & Gentofte Hospital and the University of Copenhagen, Statens Serum Institut, Novo Nordisk A/S and Aarhus University. The trial participants will be drawn from employees of Novo Nordisk A/S, Novozymes A/S, Novo Holdings A/S and the Novo Nordisk Foundation, including their partners and their adult children living with them. This means that more than 40,000 people can potentially volunteer to donate blood to the study, thus providing some of the answers the world is seeking.

“Since this virus is new to humans, knowledge about developing specific immunity after infection is lacking. Recent studies of four other milder coronaviruses, which cause seasonal colds, show that protective immunity does not last long, with antibody levels dropping rapidly, even as little as 6 months after infection. We need to find out whether this applies to the new coronavirus,” explains Peter Garred.

In the research project, the volunteers will initially provide a blood sample and will then complete a questionnaire about their job function, family, travel habits and whether they have had any symptoms that could indicate COVID-19. The blood sample will then be tested for antibodies to SARS-CoV-2 using a newly developed and highly reliable antibody test. The participants will be repeat tested after 6 and 12 months.

“This will enable us to monitor the percentage of people who have antibodies to SARS-CoV-2, but at least as important, we can determine whether the participants retain their antibodies or lose them and maybe even become infected again,” says Peter Garred.

Antibodies are not just antibodies

Although the 40,000 participants have not been randomly selected and the trial thus cannot accurately determine the proportion of the population with antibodies, the trial will nevertheless provide a good estimate of how many people in Denmark’s labour force have antibodies.

“The trial group will become even more representative of the general population since the test is also being offered to employees’ partners and adult children. This can therefore assess the roles of household contact versus workplace contact, which varies depending on employees’ job function and the contacts of their partners and adult children. This will provide considerable information about how this virus is transmitted,” explains Peter Garred.

Subject to the consent of the trial participants, the excess blood from the testing will be stored for later analysis to obtain more knowledge about the immune system and how it responds to infection.

“We have more advanced antibody tests that reveal not only whether you have antibodies but also which antibodies you have, the quantities and whether these can neutralize SARS-CoV-2. This may be important in determining whether someone is actually immune to this virus or not,” says Peter Garred.

People have different types of antibodies, called immunoglobulins. IgM is formed when the immune system initially detects viruses and then declines over time, being replaced by IgA and IgG, which in turn store important information about the infectious agent. Forming IgG usually takes about 14–21 days.

“The virus-specific antibodies to the virus that caused the SARS epidemic in 2002–2004 were retained for 2 years on average, but the quantity of IgG declined substantially. We hope to find out whether this applies to SARS-CoV-2, so we know which factors determine who remains immune in the long term,” says Peter Garred.

Focus on people at higher risk

Preliminary studies indicate that the quantity of antibodies among individuals with COVID-19 can vary by a factor of 100,000 and that the most severe cases have the highest antibody responses whereas milder cases give rise to fewer antibodies.

“In addition to the possibility of investigating community transmission, screening this large cohort also enables it to be followed up over the long term, thus identifying the risk factors for developing severe COVID-19,” says Peter Garred.

The first wave of the pandemic clearly showed that the severity of COVID-19 varied widely, from no symptoms to death. The virus typically attacks the respiratory tract and can cause very serious respiratory complications but especially among people with other comorbid conditions, such as obesity, diabetes, cancer, autoimmune disease and chronic lung disease.

“We will try to identify risk factors that can affect or predict progression to severe COVID-19. If you have one of these comorbid conditions, this new knowledge on immunity will be crucial in determining whether you can interact freely in the community if the pandemic strikes again. This means that, in future waves of COVID-19, we can focus more on protecting the people at higher risk and less on repeating the drastic lockdown measures that had to be implemented this spring,” says Peter Garred.

The Novo Nordisk Foundation has supported the research project Dynamic Characteristics of the Antibody Response towards SARS-CoV-2 in a Company-based Population Cohort. The project is a collaboration between researchers at Rigshospitalet, Herlev & Gentofte Hospital and the University of Copenhagen, Statens Serum Institut, Novo Nordisk A/S and Aarhus University. The new antibody test has been developed from scratch in close collaboration between Rigshospitalet, the University of Copenhagen and Novo Nordisk A/S, with support from the Carlsberg Foundation. The Novo Nordisk Foundation awarded Peter Garred a grant of DKK 4,803,750 for the project The Copenhagen SARS-CoV-2 Antibody Testing Initiative.

Peter Garred
Clinical Professor
Peter Garred has many years of experience in research leadership and education at a high level with deep insights into basic, translational and clinical research, as well as a large network of scientists and clinicians at local, national and international levels. Peter Garred leads a research group at Rigshospitalet and for the past 20 years he has worked on understanding the structure and molecular genetics of the complement system in general and the lectin pathway in particular.