Is COVID-19 vaccination protective against thrombotic complications?

A new study published on the preprint server Research Square*, researchers explore the potential association of both arterial and venous thrombosis with coronavirus disease 2019 (COVID-19) vaccination.

Study: Impact of vaccination on the association of COVID-19 with arterial and venous thrombotic diseases: an OpenSAFELY cohort study using linked electronic health records. Image Credit: Kateryna Kon /

*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

COVID-19 and the risk of cardiovascular events

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been strongly associated with an increased risk of arterial clots leading to heart attacks and ischemic strokes, as well as venous clots that could result in pulmonary embolism (PE) and deep vein thrombosis (DVT) in the lower limbs. The greatest risk for these cardiovascular events is shortly after the infection, with severely infected patients at the greatest danger for such complications.

As new SARS-CoV-2 variants emerge, it remains unclear which variant has been associated with higher risks of major vascular events. The Delta variant, which appeared towards the latter part of 2020, caused severe COVID-19 with more hospitalizations and deaths than the Alpha variant.

COVID-19 vaccines began to be distributed in the United Kingdom in December 2020, with different groups, such as the elderly, chronically ill, healthcare workers, and social care workers, prioritized. By June 18, 2021, all adults in England could be vaccinated if they desired, with the second dose available for all adults by August of the same year.

Previous studies have demonstrated that clotting events were less likely to arise in patients who had been vaccinated against COVID-19 as compared to unvaccinated individuals. Similarly, both heart attacks and ischemic strokes were reduced at one to four months following COVID-19 in vaccinated people as compared to unvaccinated.

This effect has also been observed with seasonal flu shots. However, younger people have, albeit rarely, developed myocarditis and thrombotic thrombocytopenia following vaccination with the nucleic acid vaccines from Pfizer/BioNTech or Moderna, as well as the adenovirus vector vaccines from Oxford-AstraZeneca. Conversely, the risk of severe or fatal COVID-19 has been significantly reduced in this patient population.

About the study

In the current study, researchers use electronic health records (EHRs) from about 40% of the England population to examine possible associations between vaccine administration and cardiovascular diseases, including clots in arteries and veins.

The scientists compared a group of about 18.2 million people who were exposed to the wild-type SARS-CoV-2 or the Alpha variant, both of which circulated widely before COVID-19 vaccines were approved for use. The second group consisted of 13.5 and 3.1 million Delta-exposed vaccinated and unvaccinated individuals, respectively. The aim was to quantify the risk for cardiovascular sequelae following COVID-19 and vaccination, respectively.

What did the study show?

In the pre-vaccination cohort, about 1.1 million were diagnosed with COVID-19, about 6.5% of whom were hospitalized. In the vaccinated cohort, there were about 844,000 COVID-19 cases, with less than 2% hospitalized. In contrast, among the unvaccinated people, there were about 162,000 reports of COVID-19, about 5.5% of whom were hospitalized.

The pre-vaccinated cohort had a median age of 49 years, the majority being White. The median age of the vaccinated cohort and unvaccinated cohort was 54 and 36 years, respectively.

Most vaccinated people were White, with almost equal proportions of males and females. Among unvaccinated people, about 60% were White, and 42% were female. About 16% and 30% of people in these two cohorts lived in the poorest areas, respectively.

Smoking was more common among the unvaccinated, who also tended to have less documented medical histories.

Arterial thrombi and venous thrombi accounted for over 210,000, 57,400, and 3,300 events in the prevaccination, vaccinated, and unvaccinated cohorts, respectively. These events were consistently more frequent after COVID-19 as compared to before COVID-19 diagnosis.

The highest rates occurred among people hospitalized with COVID-19. However, younger people, though unvaccinated, had lower incidences compared to older people following vaccination.

The highest risk for cardiovascular events was during the first four weeks following acute COVID-19 and returned to one thereafter in all cohorts. The risk level was lower in the vaccinated cohort during the first month after recovering from COVID-19.

During the second year following recovery from COVID-19, the incidence of subarachnoid hemorrhage and hemorrhagic stroke increased by 32% and 42%, respectively.

The risks for venous and arterial clots were lower in females and Whites. The excess risk for post-COVID-19 arterial clots was above 640 and 700 in the pre-vaccinated and unvaccinated cohorts, respectively, compared to about 230 in the vaccinated cohort for every 100,000 COVID-19 cases. Venous clots were in excess by about 800 and over 1,000 in pre-vaccinated and unvaccinated cohorts, respectively, as compared to 270 in the vaccinated cohort. 

What are the implications?

COVID-19 vaccination substantially attenuates the elevated incidence of arterial and venous thrombotic events after COVID-19.”

The Alpha and Delta variants appear to have been associated with similar risks of thrombotic events. Following recovery from COVID-19, the risk of both types of events remained persistently higher by about 20% during the second year, especially among those hospitalized with COVID-19.

This large study controlled for multiple confounding factors, thus adding to the value of the findings. However, several limitations may reduce its usefulness, such as the fact that routine COVID-19 testing during the pandemic led to incidental diagnoses of infection in patients admitted for other conditions, including cardiovascular events.

*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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