Even mild COVID-19 raises the risk of blood clots

  • A new nationwide study conducted in Sweden reports that individuals with COVID-19 were at greater risk of developing a blood clot at least up to 3 months after the infection.
  • Although individuals hospitalized with severe COVID-19 were at the highest risk of developing blood clots, even those with mild COVID-19 were at increased risk of blood clots.
  • The study highlights the importance of treatments to reduce blood clots, especially in high risk COVID-19 patients, and vaccination against COVID-19.

According to a nationwide Swedish study published in the journal BMJ, individuals with COVID-19 could be at a 33-fold greater risk of developing serious blood clots in their lungs in the first 30 days of infection than those who have not contracted the virus.

The risk of developing blood clots was highest in individuals with severe COVID-19 or those with preexisting medical conditions. However, even individuals with mild illness were at increased risk of blood clots than those who had not yet had COVID-19.

Dr. Frederick Ho, a lecturer at the University of Glasgow, told Medical News Today:

“This study confirms that the elevated risk of blood clots also exists among people with mild non-hospitalized COVID-19. [It] reminds us that even though the current Omicron variant is relatively mild, especially with the protection of vaccination, there could still be complications associated with the infection, and it should be considered when we’re in the stage of ‘living with COVID-19.’”

COVID-19 and blood clots

Venous thromboembolism refers to blood clots in the veins and includes deep vein thrombosis and pulmonary embolism. Deep vein thrombosis involves the formation of a blood clot in a vein deep in the body, usually in the legs, and is generally not life threatening.

A potentially fatal complication of deep vein thrombosis includes pulmonary embolism, which occurs when a blood clot in a vein in the periphery dislodges and travels to one of the arteries that carry blood to the lungs and blocks it.

Previous studies had produced conflicting results regarding the risk of blood clots from COVID-19. Therefore, the scientists conducting the current study decided to carry out a very large study using data from Swedish national registries to assess how long the risk of blood clots persists after a SARS-CoV-2 infection and what factors affected the size of risk.

Self-controlled case series approach 

The present study included 1,057,174 individuals who tested positive for a SARS-CoV-2 infection between February 2020 and May 2021. The data from these individuals with COVID-19 were analyzed using two different approaches—a self-controlled case series design and a matched cohort study design.

In the self-controlled case series approach, the researchers compared the incidence rate of blood clots during the 6 months after the SARS-CoV-2 infection with the individuals’ risk before and after that 6-month period. Such an approach using the participants as their own control helps to account for the potential role of genetic and other risk factors that may influence the risk of blood clots.

The incidence rates of deep vein thrombosis and pulmonary embolism were higher up to 3 and 6 months, respectively, after the SARS-CoV-2 infection. Similarly, the risk of bleeding remained higher until the first two months after the SARS-CoV-2 infection than before the infection.

Cohort study approach

In the matched cohort study, the researchers compared the risk of blood clots or bleeding during the 30-day period following an infection in the individuals with COVID-19 with a control group consisting of over four million uninfected individuals matched for age, sex, and country of residence.

The researchers found that individuals with COVID-19 were at a 5-fold higher risk of deep vein thrombosis and a 33-fold greater risk of pulmonary embolism during the first month after the infection.

Moreover, the risk of bleeding was twice as high in individuals with a SARS-CoV-2 infection than in those who had not yet had COVID-19.

Significantly, the risk of blood clots was higher in individuals with COVID-19, regardless of the severity of the illness. However, individuals with comorbidities or those who were hospitalized, especially those admitted to an intensive care unit due to severe COVID-19, were at greater risk of blood clots than those with milder disease.

In contrast, the risk of bleeding was only higher in individuals with severe COVID-19 but not in those with mild illness.

The study’s co-author, Dr. Anne-Marie Fors Connolly, a researcher at Umeå University, Sweden, noted that thromboprophylaxis, which involves treatments to prevent the development of blood clots, could explain these findings.

Dr. Connolly told MNT:

“One surprising finding is that mild COVID-19 patients did not have an increased risk of bleeding, and one potential explanation is that bleeding could be a side effect of thromboprophylaxis. However, the large risk of pulmonary embolism indicates that thromboprophylaxis is needed since pulmonary embolism can be potentially fatal.”

The study period covered three waves of COVID-19 in Sweden. Both the cohort study and the self-controlled study approaches found a higher risk of blood clots during the first wave than in the two subsequent waves. The researchers think this could be due to implementing measures to prevent blood clots during the subsequent waves.

Strengths and limitations

Dr. Connolly said the study avoided selection bias by using data from “every single individual that tested positive for SARS-CoV-2 infection”. Using two different statistical methods also confirmed the same results, she added.

However, she also acknowledged some limitations.

“[T]his is an observational study which means we established association and not causality. In addition, there was a shortage of test kits in the first pandemic wave, which means there are individuals with SARS-CoV-2 infection that were not tested and are therefore not part of the data,” she said.

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