Spouses mattered more than genes for the risk of severe COVID-19

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.

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.