Patients who have been hospitalized with severe COVID-19 have permanent changes in their cholesterol three months after recovery, according to a new study. This can increase their risk of developing heart disease later in life.

Many clinicians and scientists have wondered whether COVID-19 disease affects people's health later in life. Several recent studies have shown that there is an association between COVID-19 and heart disease. Does being severely ill with COVID-19 increase people's risk of developing heart disease?

"Recent studies have suggested that COVID-19 increases the risk of cardiovascular disease. However, the mechanisms for this are still unclear," Ida Gregersen, a researcher at the University of Oslo and Oslo University Hospital, says.

Norwegian researchers have found that patients, who had been hospitalized with severe COVID-19, have permanent changes in their cholesterol after their recovery.

"We believe that COVID-19 increases the risk of developing heart disease later in life, and that the changes in cholesterol are a possible explanation for this increased risk," Bente Halvorsen, Professor at the University of Oslo and the Principal Investigator of the study, says.

'Bad' LDL cholesterol increases the risk of heart disease

Cholesterol is one of the body's fatty substances and is an important building block in the body. There are different types of cholesterol, one of which is LDL, which is comprised of several LDL particles.

"LDL is responsible for transporting fat in the body and is sometimes called the "bad cholesterol," Gregersen says.

This is because high levels of LDL cholesterol in the blood raises your risk for heart disease and stroke.

"It is a well-known fact that the risk of cardiovascular disease increases with high levels of LDL in the blood. In addition, the risk also increases when there are changes in the composition of the LDL particles," she says.

Changes in LDL particles seen in patients who have recovered from severe COVID-19

The researchers observed such changes in LDL composition in patients with severe COVID-19, 3 months after they recovered.

"Patients who have had severe COVID-19 have had the composition of these LDL particles changed after their illness. Among other things, they contain several inflammatory substances," says Gregersen.

Such changes can influence these LDL particles to collect in the walls of your blood vessels. This can drive the development of heart disease in the long term.

"We therefore believe that severe COVID-19 causes long-term changes in the composition of LDL particles, i.e. in the body's system for transporting fat around the body. It could potentially give the patients an increased risk of cardiovascular disease later, but we don't know that yet," she says.

We can prevent heart disease when we know more about the risk

It is important that people who have had severe COVID-19 are aware of their increased risk of cardiovascular disease, according to the researchers.

"It is incredibly important that patients who have had severe COVID-19 know that they may have a changed composition of cholesterol in their body. We know from previous research that they have a greater risk of cardiovascular disease later in life," Halvorsen says.

By identifying people who have an increased risk, it is possible to engage in preventive measures. Among other things, there are effective measures aimed at people with high levels of LDL cholesterol in their blood.

"The more we know, the more we can prevent and treat that risk. We have tools to treat the risk of heart disease in people with elevated LDL," she says.

Lifestyle factors such as smoking and obesity are also important

Halvorsen recommends that those who have had severe COVID-19 disease follow up with their general practitioner. To find out if you have a higher risk of developing cardiovascular disease, you can ask for a blood test.

"We cannot say for sure that these patients actually will develop cardiovascular diseases. Environmental factors and lifestyle factors such as smoking, obesity and high blood pressure will play a role in whether this will develop further," Halvorsen says.

New method can isolate and measure changes in LDL particles

As stated, changes in the composition of the smaller LDL particles also increases the risk of cardiovascular disease. Therefore, the researchers investigated a specific characteristic of the LDL particles, so-called LDL aggregation, which is when the LDL particles group together in the blood vessels.

To investigate LDL aggregation, the researchers collaborated with the Wihuri Research Institute in Finland that have established a method that can isolate and measure these changes in LDL.

"We know that LDL can aggregate, i.e. group together. However, this method can obtain quantitative measures that can demonstrate whether there is a change in LDL aggregation in the blood," Halvorsen explains.

"We can therefore use this as a measure of risk for cardiovascular," she adds.

Persistent changes in LDL indicate an active immune activation

"The fact that these differences in LDL composition are seen 3 months after patients recovered from COVID-19, is important," Halvorsen points out.

LDL has a plasma half-life of only a few days before it is renewed. Half-life means the time it takes for LDL to decrease by half. After a few days, new LDL is produced. Normally, one would thus expect the changes in LDL composition to disappear after a few days.

"When we still see changes in LDL composition after 3 months, it suggests that COVID-19 can lead to long-term disturbances in the system that transports fat in our body. In addition, the LDL carries inflammatory markers. This shows us that there is still immune activation in the body 3 months after recovering from COVID-19," Halvorsen explains.

The professor believes the findings are astounding.

"We saw significant differences in the way LDL grouped together, between healthy people who did not have COVID-19, and these patients, who had been ill and hospitalized with severe COVID-19. For me, this is quite sensational," Halvorsen says.

"This is a new finding, and it will be interesting to see how this develops further," she adds.

Blood samples from the first COVID-19 patients in Norway

The researchers analyzed blood samples from 66 people who had been hospitalized with severe COVID-19, taken during a check-up 3 months after being discharged from hospital.

These patients were hospitalized during the first wave of COVID-19 in March 2020.

The researchers compared these samples with 42 healthy adults who served as controls, and checked whether factors such as age, gender and ethnicity played a role.

"Our data suggest new mechanisms for increased cardiovascular risk in patients who have had COVID-19. However, further studies that can examine the connection between these LDL characteristics and the development of cardiovascular diseases, is needed," Halvorsen concludes.

The research was published in the Journal of Infection.