Keywords: COVID-19, prevention, post-COVId-19 sequelae, mortality, MACE, cardiovascular

Background:

COVID-19 long-term health consequences continue to be an active area of research. While it is well-established that COVID-19 vaccines are effective in preventing severe disease and COVID-19 itself poses a significant risk for cardiovascular complications-, it remains uncertain to what extent COVID-19 vaccines impact long-term cardiovascular complications and mortality among individuals infected with SARS-CoV-2, and how persistent this effect is over time.

Research questions:

How does pre-infection COVID-19 vaccination modify the risk trajectory of major cardiovascular events and all-cause mortality over the year following SARS-CoV-2 infection?

Method:

This target trial emulation study utilized real-world electronic medical records (April 2021 - March 2023) to dissect the time-varying impact of pre-infection COVID-19 vaccination on the incidence of major acute cardiovascular events (MACE) and all-cause mortality in individuals aged 40 to 85 years within 365 days following SARS-CoV-2 infection.

Results:

Among individuals with COVID-19 (n = 18,223 vaccinated, n = 15,331 not vaccinated), pre-infection vaccination conferred significant protection against MACE (weighted incidence rate ratio [wIRR] 0.71, 95% CI 0.58 - 0.84) and all-cause mortality (wIRR 0.32, 95% CI 0.28 - 0.36). This protective benefit waned approximately three months after the acute infection, being more pronounced in females of all age groups and males under 70 years. In contrast, males over 70 years old demonstrated an increased incidence of MACE, peaking around 60 days post-infection.

Conclusions:

These findings reveal the nuanced, time-dependent effects of pre-COVID-19 vaccination on long-term COVID-19 outcomes, identifying vulnerable subgroups that necessitate tailored post-infection preventive strategies to mitigate COVID-19 sequelae. Considering the essential role of family physicians in addressing COVID-19-related health complications, these findings provide additional evidence for enhanced patient monitoring in primary health care.

Points for discussion:

Broader concept of post-infectious mortality

time-varying effect of vaccination on post-COVID-19 sequelae

delayed MACE incidence after infections in vaccinated population