Study Finds That Those Infected With COVID-19 Have Increased Risk Of Deep Vein Thrombosis, Pulmonary Embolism And Bleeding For Up To Six Months!
A new Swedish study led by researchers from Umeå University has found that all those who have been infected with the COVID-19 disease have an increased risk of serious blood clots for up to six months.
The study that also involved scientists from the University of Helsinki-Finland, Helsinki University Hospital-Finland and The Open University, Milton Keynes-UK found that the increased risks of deep vein thrombosis, pulmonary embolism and bleeding for up to six months after SARS-CoV-2 infections.
The study involved a self-controlled case series and matched cohort study that involved the national registries in Sweden.
The study involved over 1 057 174 individuals 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.
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).
The study findings showed that 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.
The research 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.
The study findings were published in the peer reviewed British Medical Journal. https://www.bmj.com/content/377/bmj-2021-069590
The research uncovered an increased risk of pulmonary embolism (a blood clot in the lung) up to six months after COVID-19 infection, deep vein thrombosis (a blo
od clot in the leg) up to three months, and a bleeding event up to two months.
Importantly, according to the study findings, there is also a higher risk of events in patients with underlying conditions (comorbidities), patients with more severe COVID-19, and during the first pandemic wave compared with the second and third waves. (The type of SARS-CoV-2 variants at ‘play’ and their unique pathogenesis could be a factor in this.)
The study findings support measures to prevent thrombotic events (thromboprophylaxis), especially for high-risk patients.
To date, it is already well established that COVID-19 increases the risk of serious blood clots (known as venous thromboembolism or VTE), but less evidence exists on the length of time this risk is increased, if risk changed during the various pandemic waves, and whether COVID-19 also increases the risk of major bleeding.
In order to address these uncertainties, the study team set out to measure the risk of deep vein thrombosis, pulmonary embolism, and bleeding after COVID-19.
Utilizing national registries in Sweden, the study team identified more than one million individuals with confirmed SARS-CoV-2 infection (the virus responsible for covid-19) between February 1, 2020 and, May 25, 2021, matched by age, sex, and county of residence to more than four million people who had not had a positive SARS-CoV-2 test result.
The study team then performed two analyses: in the first, they calculated the rates of deep vein thrombosis, pulmonary embolism, and bleeding in covid-19 individuals during a control period (before and long after COVID-19 diagnosis) and compared it to the rates in different time intervals after covid-19 diagnosis (days 1-7, 8-14, 15-30, 31-60, 61-90, and 91-180).
For the second stage analysis, the study team calculated the rates of deep vein thrombosis, pulmonary embolism, and bleeding during the period 1-30 days after COVID-19 diagnosis in the COVID-19 group and compared them to the corresponding rates in the control group.
The study findings showed that compared with the control period, risks were significantly increased 90 days after COVID-19 for deep vein thrombosis, 180 days for pulmonary embolism, and 60 days for bleeding.
The study team found after taking into account a range of potentially influential factors, a fivefold increase in the risk of deep vein thrombosis, a 33-fold increase in the risk of pulmonary embolism, and an almost twofold increase in the risk of bleeding in the 30 days after SARS-CoV-2 infection!
This means in absolute terms that a first deep vein thrombosis occurred in 401 patients with COVID-19 (absolute risk 0.04%) and 267 control patients (absolute risk 0.01%). A first pulmonary embolism event occurred in 1,761 patients with COVID-19 (absolute risk 0.17%) and 171 control patients (absolute risk 0.004%), and a first bleeding event occurred in 1,002 patients with COVID-19 (absolute risk 0.10%) and 1,292 control patients (absolute risk 0.04%).
It was also found that risks were highest in patients with more severe COVID-19 and during the first pandemic wave compared with the second and third waves, which the study team says could be explained by improvements in treatment and vaccine coverage in older patients after the first wave.
Interestingly, even among mild, non-hospitalized COVID-19 patients, the study team found increased risks of deep vein thrombosis and pulmonary embolism.
However, no increased risk of bleeding was found in mild cases, but a noticeable increase was observed in more severe cases.
As this is an observational study, the study team could not establish cause, and they acknowledge several limitations which might have affected their findings. For example, VTE may have been underdiagnosed in patients with COVID-19, testing for COVID-19 was limited, especially during the first pandemic wave, and information on vaccination was not available.
The study findings were however largely consistent after further analyses, and are in line with similar studies on the association between COVID-19 and thromboembolic events, suggesting that they withstand scrutiny.
The study team as such say their findings suggest that COVID-19 is an independent risk factor for deep vein thrombosis, pulmonary embolism, and bleeding, and that the risk of these outcomes is increased for three, six, and two months after COVID-19, respectively.
Corresponding author, Dr Anne-Marie Fors Connolly, a clinical research fellow at the Laboratory for Molecular Infection Medicine, Umeå University told Thailand Medical News
, “Our study findings arguably support thromboprophylaxis to avoid thrombotic events, especially for high risk patients, and strengthen the importance of vaccination against COVID-19.”
Importantly, in a linked editorial, medical scientists from the University of Glasgow point out that despite the potential for new variants of concern, most governments are removing restrictions and shifting their focus to determining how best to “live with COVID.” They however warn that this study “reminds us of the need to remain vigilant to the complications associated with even mild SARS-CoV-2 infection, including thromboembolism.” https://www.bmj.com/content/377/bmj.o817
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