Virologists throughout the world have had difficulty agreeing on the actual fatality rate from COVID-19. Antibody testing in Denmark’s blood banks shows that the fatality rate is very low among people younger than 70 years. Nationwide screening of donated blood may be a cheap and accurate method of estimating the number of unreported cases of disease during future pandemics.
The unreported number of people who have had COVID-19 has been a major controversy in the debate among the general public and health authorities during this global pandemic.
The number of people who have had COVID-19 but not registered and reported strongly affects how deadly SARS-CoV-2 actually is and thereby the decisions on the restrictions to be applied in society.
Christian Erikstrup, Chief Physician and Clinical Professor at Aarhus University Hospital, and several colleagues have contributed to this debate on unreported cases in a new study published in Clinical Infectious Diseases.
From 6 April to 3 May, they tested 20,640 blood donors 17–69 years old across Denmark for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies produced by exposure to SARS-CoV-2. The study found that 1.9% of the blood donors had contracted COVID-19 at some point.
The seroprevalence in the Capital Region of Denmark was higher than the average in Denmark’s other four administrative regions . The researchers used data on deaths from COVID-19 and population statistics to calculate an overall infection fatality rate of 89 per 100,000 for people younger than 70 years who have had COVID-19.
COVID-19 is not usually life-threatening for healthy people
This result is less alarming than what virologists throughout the world have feared in recent months.
“Some have claimed that the death rate is less than 1%, whereas others have concluded that it is as high as 2%. But we have to distinguish between the case fatality rate and the infection fatality rate,” explains Christian Erikstrup.
The case fatality rate means the percentage of deaths among confirmed cases, whereas the infection fatality rate is a more stable and universal rate that includes the estimated number of asymptomatic and undiagnosed people who have had COVID-19. This should therefore more accurately show how deadly COVID-19 really is.
“We started our study when the epidemic peaked in Denmark and many people were hospitalized with COVID-19. We actually started out with being concerned about whether COVID-19 is more dangerous than previously thought. Fortunately, it turned out pretty quickly that very, very few people 17–69 years old died. Further, the prevalence of 1.9% we found would mean many thousands of people had contracted COVID-19 if you apply that to the entire population. So we have a long way to go to achieve herd immunity, but the risk of dying from COVID-19 is really low,” says Christian Erikstrup.
Blood banks can determine the number of unreported cases cheaply and efficiently
For example, blood donors have no comorbidities to COVID-19, because as soon as they get visible symptoms of other illness, they have to take a break from donating. The age range is 17–69 years, and these results do not determine the risk of infection for those who are younger or older. Further, many of the blood donors are middle class, which potentially means more foreign travel and social activity and thus a higher risk of becoming infected with SARS-CoV-2.
“Nevertheless, despite its size, Denmark has about 200 blood banks. An advantage is that very few attend solely for antibody testing and therefore probably show up because they also donate blood. A representative survey of the population that invites people to be tested often has a participation rate of considerably less than half,” explains Christian Erikstrup.
According to Christian Erikstrup, since blood banks operate continually and are geographically dispersed, this type of testing is suitable for determining regional differences and seasonal fluctuation in epidemics. Supplementing this with antibody testing of people older than 69 years and younger than 17 years, with and without comorbidities, will produce fairly nuanced insight into the number of unreported cases.
Testing at blood banks can therefore be a cheap and effective instrument the public health authorities and politicians can implement during future pandemics.
“We already have the blood, so this is a cost-effective way to do research. The only additional cost is getting additional consent, since the donors have to be asked whether they consent to antibody testing. Nobody declined this offer,” says Christian Erikstrup.
Social distancing is important for vulnerable individuals
Unlike countries such as the United Kingdom and Sweden, Denmark’s government reacted decisively and put the country into partial lockdown as early as 11 March. Schools and childcare centres were closed, people were encouraged to work from home and gatherings of more than 100 people were banned. The borders were then closed, the numbers of people permitted to gather were reduced further and the restrictions were tightened.
The data on unreported cases of COVID-19 are important not only for resolving researchers’ disagreements but also for making economic and political decisions.
Christian Erikstrup and his colleagues started their antibody testing when the very first tests became available in Denmark, and the sensitivity was 82.6%.
Since then, the tests have become even more sensitive and specific. But the early numbers were important to shed more light on the number of unreported cases, about which very little was known. That was also when authorities and politicians gradually began to mention herd immunity at press conferences.
One uncertainty about COVID-19 is the extent to which people develop immunity and how long this lasts. Ongoing blood donations enable researchers to map the trends in and levels of antibodies over time. Christian Erikstrup and his colleagues therefore hope to be able to continue to monitor Denmark’s blood donors in the coming months, especially since the number of confirmed COVID-19 cases has increased slightly again.
“We hear from colleagues and notice ourselves that more severely ill individuals with COVID-19 have a higher concentration of antibodies. We could therefore well imagine that the people with no symptoms have very few antibodies. The newest tests can detect antibodies among the vast majority of the people who have had COVID-19. That is good, because it means that we can measure this fairly accurately and that people are probably becoming immune to SARS-CoV-2,” explains Christian Erikstrup.
But even though some individuals appear to be becoming immune, the figures from Denmark’s blood donors also indicate that herd immunity is a long way off.
“Most recently, a new nationwide study from Spain published in The Lancet tested more than 60,000 people for antibodies and found a seroprevalence of 5%. So herd immunity is still far off even in a country more severely affected than Denmark,” says Christian Erikstrup.
Serological studies have therefore not only provided COVID-19-specific but also basic knowledge of which interventions generally succeed during pandemics. If we do not get a real sense of how dangerous the outbreak really is, we risk making rushed and incorrect decisions and perhaps unnecessarily expensive ones, concludes Christian Erikstrup, adding:
“Our data show that COVID-19 is not especially dangerous for otherwise healthy people – individuals 69 years and younger without comorbidities – and that herd immunity cannot be achieved in 3 months. Lockdown is really expensive for society. The study also indicates that younger and healthy people should go to work and keep their distance from vulnerable and older people while society takes care of this group.”
“Estimation of SARS-CoV-2 infection fatality rate by real-time antibody screening of blood donors” has been published in Clinical Infectious Diseases. A co-author is an employee of the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen.