A large Swedish study has linked COVID-19 with greater risk for various of thrombotic events in the months after infection, that of deep vein thrombosis being five times higher.
Cardiovascular complications have been an increasing concern after SARS-CoV-2 infection, but previous studies showed conflicting results on the risk of venous thromboembolism.
Among more than 1m people who tested positive for COVID-19 in the past month, risk for a first pulmonary embolism was 33 times higher compared with a matched control group, after adjusting for multiple potential confounders, reported Dr Anne-Marie Fors Connolly of Umeå University in Sweden and colleagues.
The risk of a first deep vein thrombosis was five times higher and the risk of bleeding was nearly twice as high, according to their findings published in The BMJ.
“This study found an increased risk of a first deep vein thrombosis up to three months after COVID-19, pulmonary embolism up to six months, and a bleeding event up to two months,” the group wrote. “We found an excess risk of outcomes in patients with more severe COVID-19 admitted to hospital, but especially in those admitted to an intensive care unit.”
Their findings “arguably support thromboprophylaxis to avoid thrombotic events, especially for high-risk patients”, they said.
In an accompanying editorial, Dr Frederick Ho and Dr Jill Pell, both of the University of Glasgow in Scotland, said that “since risks of thromboembolism and bleeding were highest among participants with more severe COVID-19, vaccination could reduce the overall risk both by preventing infection and by reducing its severity when it does occur”.
They pointed out that the findings are still relevant now that 65% of the world is vaccinated, since breakthrough infections occur and vaccine effectiveness has reduced with Omicron and over time.
As governments shift their focus to living with COVID, noted Ho and Pell, the current study “reminds us of the need to remain vigilant to the complications associated with even mild SARS-CoV-2 infection, including thromboembolism”.
Fors Connolly and colleagues examined data on 1,057,174 individuals with a first SARS-CoV-2 infection from 1 Feb 2020 to 25 May 2021 in SmiNet, a communicable disease surveillance system in Sweden. Participants were matched by demographics and residential county to a control of another 4,076,342 adults who did not have a positive test result.
The main analysis adjusted for comorbidities, surgery, cancer, long-term anticoagulation treatment, and various other factors.
For severity among the case patients, 94.5% had mild infections, 4.8% required hospital admission, 0.7% required intensive care, and 1.8% died.
For pulmonary embolism, the absolute risk was 0.17% in the first 30 days among COVID-19 patients versus 0.004% among control patients during the same time frame. Absolute risks were 0.039% and 0.007%, respectively, for deep vein thrombosis, and 0.10% and 0.04% for bleeding.
Overall, 51% of the study participants were women, with a mean age of 40. Previous venous thromboembolism had occurred in 1.9% of the case patients and previous bleeding had occurred in 5.8%.
Study limitations included the use of registry data that may contain incomplete or inaccurate information and the fact that deep vein thrombosis could have been under-diagnosed because critically ill patients were not stable for evaluations.
Study details
Risks of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19: nationwide self-controlled cases series and matched cohort study
Ioannis Katsoularis, Osvaldo Fonseca-Rodríguez, Paddy Farrington, Hanna Jerndal,
Erling Häggström Lundevaller, Malin Sund, Krister Lindmark, Anne-Marie Fors Connolly.
Published in The BMJ on 6 April 2022
Abstract
Objective
To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19.
Design
Self-controlled case series and matched cohort study.
Setting
National registries in Sweden.
Participants
1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants.
Main outcomes measures
Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after COVID-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after COVID-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event).
Results
Compared with the control period, incidence rate ratios were significantly increased 70 days after COVID-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after COVID-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after COVID-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after COVID-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical COVID-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with COVID-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding.
Conclusions
The findings of this study suggest that COVID-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after COVID-19.
Accompanying editorial on BMJ article – Thromboembolism and bleeding after Covid-19 (Open access)
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