Pulmonary embolism after SARS-CoV-2 vaccination

Abstract

Background: During the COVID-19 vaccination campaign in Sweden, pulmonary embolism (PE) was a frequently reported suspected serious adverse drug reaction. The aim was to estimate risk of PE following vaccination for COVID-19 in the Swedish population aged 18 to 84 years.

Methods: Population-based cohort study using the CoVacSafe-SE established platform including national registers. PE-case definition: Individuals discharged from inpatient-care or visiting specialized outpatient-care with a main diagnosis of PE occurring between 27-Dec-2020 and 31-Dec-2022 without simultaneous diagnosis of COVID-19 infection. Time-to-event analysis was performed using multi-variable Cox' proportional hazard's models. Hazard Ratios (HR) adjusted for age, sex and co-morbidities were modelled.The vaccines were BNT162b2/Comirnaty®, mRNA1273/Spikevax® and ChAdOx1 nCoV-19/Vaxzevria® without regard to variants. Doses number one to five were studied.

Results: Eighty percent of the study-population (≈6.1 million people) received at least two doses of COVID-19 vaccine. A total of 12,456 cases of PE were identified. Twenty-eight days after vaccinations we observed 99 cases after 701,455 1st doses of ChAdOx1 nCoV-19, HR_adj, 1.29 (95%-CI, 1.05-1.59). Corresponding for BNT162b2 was 361 cases after 4,708,284 1st doses of BNT162b2 HR_adj of 1.19 (95%-CI, 1.06-1.34) driven by age group 65-84; HR _adj, 1.24 (95%-CI, 1.07-1.44). No increased risks were observed for mRNA1273.

Conclusion: In this nation-wide study, no strong associations were found between COVID-19 vaccinations and pulmonary embolism. Small increases in relative risk for the earliest doses of vaccines may be associated with prioritizing the frailest groups of people in the vaccination campaign, thus selection bias or unmeasured residual confounding is possible.

Keywords: Booster vaccinations; COVID-19 vaccines; Primary vaccinations; Public health; Pulmonary embolism; Regulatory science; Vaccine safety.

Fig. 1

Number of pulmonary emboli cases (bars) during the study period per 5-year intervals for women and men from 18 to 84 years of age and corresponding incidence per 10,000 person-years (dotted lines).

Fig. 2

Hazard Ratios with 95 % confidence intervals for the outcome pulmonary emboli in 13 different age categories with 50–54 year of age as the reference for men (M; blue dots) and women (F; red dots). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

A-B. Forrest plot showing hazard ratios with 95 %-confidence intervals for the outcome pulmonary embolism at different risk windows up to 180 days, adjusted for sex and age in upper panel A and full adjustments in lower panel B for BNT 162b2 vaccine (BNT).

Fig. 4

A-B. Forrest plot showing hazard ratios with 95 %-confidence intervals for the outcome pulmonary embolism at different risk windows up to 180 days, adjusted for sex and age in upper panel A and full adjustments in lower panel B for mRNA-1273 vaccine (MOD).

Fig. 5

A-B. Forrest plot showing hazard ratios with 95 %-confidence intervals for the outcome pulmonary embolism at different risk windows up to 180 days, adjusted for sex and age in upper panel A and full adjustments in lower panel B for ChAdOx1 nCoV-19 vaccine (AZ).