Prior herpes zoster vaccination mitigates long-term complications after infection

For individuals who sustained herpes zoster infection, prior receipt of recombinant zoster vaccine (RZV) appears to reduce the long-term risks of major adverse cardiovascular events (MACE), dementia, and death, according to a retrospective study.

Analysis of data from the TriNetX Analytics Network database showed that compared with common cold, herpes zoster was associated with an increased risk of MACE (hazard ratio [HR], 1.20, 95 percent confidence interval [CI], 1.14–1.26; p<0.001), myocardial infarction (HR, 1.27, 95 percent CI, 1.17–1.37; p<0.001), ischaemic stroke (HR, 1.17, 95 percent CI, 1.09–1.25; p<0.001), venous thromboembolism (VTE) (HR, 1.14, 95 percent CI, 1.08–1.21; p<0.001), all-cause dementia (HR, 1.12, 95 percent CI, 1.05–1.19; p<0.001), vascular dementia (HR, 1.29, 95 percent CI, 1.05–1.58; p=0.016), and mortality (HR, 1.29, 95 percent CI, 1.23–1.36; p<0.001). [IDWeek 2025, abstract 218]

Some of these risks were attenuated by RZV, reported primary study author Dr Ali Dehghani from Case Western Reserve University in Cleveland, Ohio, US, at a session in the IDWeek annual meeting.

In the early window analysis, individuals who had previously received RZV had fewer MACE (HR, 0.74, 95 percent CI, 0.58–0.93; p=0.009), ischaemic stroke (HR, 0.72, 95 percent CI, 0.52–0.99; p=0.045), and all-cause mortality events (HR, 0.63, 95 percent CI, 0.47–0.84; p=0.002) 6–18 months after the index infection as compared with pneumococcal conjugate vaccine (PCV) recipients. There was a trend toward lower VTE events with RZV, although the difference was not significant, Dehghani noted.

In the late window analysis, 1.5–3.5 years after the index infection, RZV recipients also had lower risks of VTE (HR, 0.73, 95 percent CI, 0.59–0.91; p=0.005) and vascular dementia (HR, 0.50, 95 percent CI, 0.25–0.98; p=0.039), aside from MACE (HR, 0.78, 95 percent CI, 0.64–0.94; p=0.008), ischaemic stroke (HR, 0.76, 95 percent CI, 0.59–0.99; p=0.038), and all-cause mortality (HR, 0.79, 95 percent CI, 0.63–0.99; p=0.037) compared with PCV recipients.

These findings indicate that the virus that causes shingles can cast a long shadow, according to Dehghani.

Herpes zoster is “not just a localized rash.” It is a systemic inflammatory event characterized by a dual-phase pattern, which includes an acute immunothrombotic surge and then the vascular and cognitive hazard that persists for years, the author explained.

But the good news is that “RZV interrupts both phases, lowering MACE, stroke, VTE, vascular dementia, and mortality,” Dehghani said. “[The vaccine] induces durable Th1 control, which suppresses subclinical reactivation and prevents adventitial seeding. And these effects persist beyond 3 years.”

As such, RZV should be integrated with influenza and PCV vaccination programs to expand uptake, he added.

For the study, Dehghani and colleagues applied propensity score matching to establish balanced cohorts. The infection analysis included 87,051 adults at least 50 years of age with a fist-time herpes zoster diagnosis and 87,051 counterparts with acute nasopharyngitis.

The vaccine analyses included 6,906 pairs of RZV and PCV recipients for the early window period and 6,593 pairs for the late window period. RZV or PCV was received within 5 years before to ≤6 months after index herpes zoster infection event.