Why did some people become severely ill with COVID-19 while others experienced only mild symptoms? Associate Professor Maria Timofeeva and Assistant Professor Jacob Krabbe Pedersen from the Department of Public Health at the University of Southern Denmark (SDU) and their colleagues investigated this question using data from more than 83,000 Danish twins and over 32,000 of their spouses.
They found no evidence that genetic factors played an important role in determining who was hospitalised with COVID-19. Instead, spouses of hospitalised individuals had more than three times the risk of being hospitalised themselves compared with matched controls.
Spouses had a higher risk
Twins and spouses offer researchers a way to examine the relative importance of genes and shared environment. Identical twins share virtually all their genetic variation, whereas spouses are not genetically related but typically share a home and many environmental exposures.
If genetic susceptibility played a major role in severe COVID-19, researchers would expect twins, and particularly identical twins, to show similar patterns of severe disease. But the co-twins of people hospitalised with COVID-19 had no detectable increase in their own risk of hospitalisation.
Among spouses, the pattern was different. A person whose spouse was hospitalised with COVID-19 had 3.6 times the risk of being hospitalised compared with matched controls. Among couples in which both partners were hospitalised, 71 per cent were admitted within five days of each other.
- The most striking finding is that we found no evidence that genetic factors played an important role in determining who was hospitalised with COVID-19. Who you live with may matter more for severe COVID-19 than who you are genetically related to, says Maria Timofeeva.
Facts: Why twins and spouses?
Twins help researchers study genetics
Identical twins share virtually all their genetic variation, while fraternal twins share, on average, half. Comparing them can therefore provide information about the contribution of genetic factors.
Spouses help researchers study shared environment
Spouses are not genetically related but typically share a home and many environmental and lifestyle factors. This makes it possible to compare the importance of shared genes with shared environment and exposure.
The Danish Twin Registry
The study draws on the Danish Twin Registry at the University of Southern Denmark, one of the world's largest twin registries. Linking information about twins with nationwide Danish health registers allows researchers to study health and disease in large groups of twins over time.
Close exposure may help explain the finding
The study cannot establish why spouses had a higher risk of severe disease. One possible explanation is that close and prolonged contact with an infected person leads to greater exposure to the virus. Previous research has suggested that viral load may influence the severity of respiratory infections, but viral dose was not measured in this study.
- During the pandemic, some people became very seriously ill, including young and otherwise healthy people, while others had few or no symptoms. An important question is why, and what we can learn from this so that we may be better prepared for the next pandemic, says Kaare Christensen, Director of the Danish Twin registry.
The results are consistent with close exposure playing a role, but other shared factors among spouses, including lifestyle and health behaviour, may also contribute. The study therefore cannot determine precisely what explains the higher risk.
Genetics played a modest role in infection
For the risk of becoming infected with SARS-CoV-2, the picture was different. The researchers found little evidence of genetic influence during the first two waves of the pandemic, but observed a modest genetic contribution during the third wave.
The changing pattern may reflect the major changes that took place during the pandemic, including vaccination, restrictions, testing practices, social behaviour and new virus variants.
- Our findings suggest that the relative importance of genes and environment for the risk of getting infected depends on the circumstances. For severe COVID-19, however, the picture was clearer. We only identified an association with sharing an environment and close contact with someone who was severely ill to be a risk factor of severe COVID, says Maria Timofeeva.
The researchers emphasise that the study does not show that genes have no role in severe COVID-19. Other studies have identified specific genetic variants associated with severe disease. Rather, the new study suggests that shared environment and close contact were more important than genetic similarity in the pattern of COVID-19 hospitalisations observed in this Danish population.
Three questions for the researcher
What are you investigating in the study?
We wanted to understand why COVID-19 tends to cluster in families and whether the risk of infection or severe disease is influenced more by a person's genes or by their environment and close contacts. We studied more than 83,000 Danish twins and over 32,000 of their spouses.
What is the key finding?
We found no evidence that genetic factors played an important role in determining who was hospitalised with COVID-19. In contrast, spouses of hospitalised individuals had more than three times the risk of being hospitalised themselves.
What can the results be used for?
The findings can contribute to preparations for future respiratory epidemics and pandemics. They highlight the potential importance of reducing exposure within households when someone becomes seriously ill, although the study did not test specific preventive measures.
About the study
Method and data
The nationwide register-based study included 83,902 Danish twins and 32,719 spouses, who were compared with 1,166,210 matched population controls. Participants were followed from February 2020 to October 2022. The researchers examined SARS-CoV-2 infection and hospitalisation with COVID-19.
Collaboration
The study was conducted by researchers from the University of Southern Denmark, Roskilde University, Copenhagen University Hospital - Rigshospitalet and the University of Copenhagen.
Funding
The study was supported by an Independent Research Fund Denmark grant (number3101-00013B) to Kaare Christensen. Lone Simonsen's contribution was supported by the Danish National Research Foundation (number DNFR170.). The funders had no role in the research or publication process. The authors declare no conflicts of interest.
Read the study
Familial factors in SARS-CoV-2 susceptibility and COVID-19 severity: A nationwide Danish study of adult twins and their spouses. DOI: 10.1093/ije/dyag204
International Journal of Epidemiology: https://academic.oup.com/ije/article-lookup/doi/10.1093/ije/dyag204
International Journal of Epidemiology
Systematic review
People
Familial factors in SARS-CoV-2 susceptibility and COVID-19 severity: A nationwide Danish study of adult twins and their spouses
20-Oct-2026