Herpes Zoster in Aging Patients: Risk Factors and Prevention Strategies

Abstract

Herpes zoster (HZ), also known as shingles, is caused by varicella-zoster virus reactivation and can lead to long-term complications such as postherpetic neuralgia (PHN). Risk of HZ and related complications increases with age, presence of chronic conditions, and immunosuppression. The United States (US) has an increasingly aging and multimorbid population; therefore, knowledge of risk factors and prevention opportunities for HZ are of critical importance to inform broad efforts to prevent this disease. To consolidate information on risk factors for adults aged ≥50 years and opportunities to address gaps in HZ prevention, a narrative review was conducted. In addition to well-known risk factors for HZ, such as immunocompromising conditions and immunosuppressive treatments, this review highlights risk factors less recognized in the existing literature. These risk factors (which include certain cardiovascular and chronic respiratory conditions, as well as diabetes, chronic kidney disease, end-stage kidney disease [ESKD], and multimorbidity) are pertinent to comprehensive preventive care. Several studies identified increased risks of adverse HZ outcomes, including PHN and functional decline during and following HZ episodes, in adults aged ≥50 years, with risk usually exacerbated by underlying medical conditions. Observational studies have shown that patients with HZ were at increased risk for certain acute cardiovascular disease events (e.g, major adverse cardiovascular events and post-herpetic cerebrovascular accidents), especially in the weeks and months following HZ. For US adults aged ≥50 years and immunocompromised adults aged ≥19 years, the recombinant zoster vaccine is recommended for the prevention of HZ by the Centers for Disease Control and Prevention. However, gaps in prevention remain. Opportunities exist to improve HZ prevention in adults aged ≥50 years, particularly among those with comorbidities, by expanding medical societies’ dissemination tactics for vaccination guidelines and recommendations, and empowering specialists to both incorporate risk assessment into routine care and encourage vaccination guideline adherence.

Introduction

Herpes zoster (HZ), commonly referred to as shingles, is caused by varicella-zoster virus (VZV) reactivation; primary infection with VZV causes varicella (ie, chickenpox), after which VZV can remain dormant in dorsal root ganglia and reactivate later in life.¹ HZ typically presents as a rash with pain, itching, or tingling, and can result in complications such as postherpetic neuralgia (PHN), HZ ophthalmicus (HZO), hearing or vision loss, encephalitis, and pneumonia.^1,2 Observational studies also suggest an increased risk for certain severe outcomes (eg, cerebrovascular accidents [CVA; stroke] and myocardial infarction [MI]) in patients with HZ.^3,4 In the United States (US), about 99.5% of adults born prior to 1980 have been infected with VZV, and approximately 1 in 3 people will develop HZ in their lifetime.¹ Risk for HZ and related complications is greater in adults aged ≥50 years and increases with age, presence of certain medical conditions, and taking immunosuppressive medications.¹

The increased risk for HZ among older adults is of particular concern in the US, where recent projections predict a 61.1% increase in the US population aged ≥50 years from 137 million to 221 million between 2020 and 2050.⁵ HZ-related burden of disease is also a concern among this population, with claims database studies reporting greater healthcare resource utilization and costs for patients with HZ compared with controls without HZ, and costs increasing with age and PHN diagnosis.^6,7 Along with the aging population, the number of US adults aged ≥50 years with at least one chronic disease is expected to increase significantly, from 72 million to 143 million between 2020 and 2050, representing a projected 99.5% increase.⁵ Notably, further increased healthcare resource utilization has been reported among HZ patients with certain chronic conditions.^8,9 As a result, it is essential for healthcare providers to understand how chronic conditions increase HZ risk, and how prevention can be optimized in this patient population.

As the US population continues to age and experience a high chronic disease burden, prevention of HZ is increasingly important. The recombinant zoster vaccine (RZV) has been available in the US since 2017, and the US Advisory Committee on Immunization Practices (ACIP) recommends two doses of RZV for the prevention of HZ and related complications in adults aged ≥50 years and adults aged ≥19 years who are or will be immunodeficient or immunosuppressed because of disease or therapy.¹⁰ The recommendations further state that adults aged ≥50 years should receive RZV if they have chronic medical conditions, such as chronic renal failure, diabetes mellitus, rheumatoid arthritis (RA), and chronic pulmonary disease.¹¹

This review seeks to consolidate the available information on risk factors for HZ among adults aged ≥50 years, including those with chronic underlying conditions, and highlight opportunities to address gaps in prevention in this population for the awareness of healthcare providers.

Search Methodology

A preliminary literature search of PubMed was performed for English-language clinical studies, comments, editorials, guidelines, and letters indexed since 2015. The search terms used can be found in Table S1. Articles that presented results pertinent to risk factors for HZ or guidelines, recommendations, and best practices for HZ prevention in a population of US adults aged ≥50 years were included for review. These articles were supplemented with collated publications identified by the authors that were pertinent to the risk for and prevention of HZ among this population but not identified in the initial PubMed search. Additional searches were performed to identify publications for certain known risk categories for HZ which were not identified within the preliminary search parameters. Articles were included based on their relevance to the review, as assessed by authors, to support comprehensive coverage and inclusion of high-quality publications. A narrative synthesis of the included studies was conducted.

HZ Incidence and Risk

Fifty-six publications on incidence and risk factors for HZ and HZ outcomes (Table 1 and Table 2) and 58 on HZ prevention were identified, for a total of 105 included publications. Several publications reported on both incidence and risk factors for HZ and HZ outcomes, as well as HZ prevention, and were thus included in both categories for review (Table S2).

Table 1.

Risk Factors for HZ

Risk Factor for HZ & Associated Studies	Measure of Risk/Association	Age Group-Specific Notes on Study Outcomesa	Study Geography
Age as a risk factor
Johnson (2015)12	IR (95% CI) among adults aged ≤19 years: 0.86 (0.84–0.88) per 1000 PYs IR (95% CI) among adults aged ≥50 years: 8.46 (8.39–8.52) per 1000 PYs IR (95% CI) among adults aged ≥60 years: 10.46 (10.35–10.56) per 1000 PYs IR (95% CI) among adults aged ≥80 years: 12.78 (12.49–13.07) per 1000 PYs	–	United States
Wolfson (2020)13	Rate of increase in HZ incidence among adults aged ≥65 years during 1991–1995: 12.4% Rate of increase in HZ incidence among adults aged ≥65 years during 1996–2006: 3.6% Rate of increase in HZ incidence among adults aged ≥65 years during 2007–2016: 1.7%	–	United States
Marra (2020)14	Pooled risk ratio (95% CI) of older age vs younger age: 1.65 (1.37–1.97)	–	Multinational (including US)
Immunosuppressive risk factors
Cancer & cancer treatments
Phillips (2018)15	Of 471 initial dermatologic consultations of 412 patients with primary cancer diagnoses, HZ diagnosis occurred most frequently (4% of 645 diagnoses)	NR	New York, United States
Marra (2020)14	Pooled risk ratio (95% CI) of malignancies vs no malignancies: 2.17 (1.86–2.53)	–	Multinational (including US)
Gatwood (2025)16	New HZ incidence per 1000 PYs (95% CI) among the overall solid tumor cohort was 20.92 (20.33–21.52) and 31.06 (29.64–32.52) among the hematological malignancy cohort Patients were more likely to develop HZ during periods of immunosuppressive treatment than during periods without (adjusted HR [95% CI]: 3.19 [3.01–3.39] for solid tumor; 3.21 [2.89–3.57] for hematological malignancy)	Patients aged ≥80 years had the highest risk of HZ (adjusted HR [95% CI]: 1.81 [1.08–3.05] relative to those aged 18–29 years) among the solid tumor cohort Patients aged 70–79 years had the highest risk of HZ (adjusted HR [95% CI]: 2.80 [1.50–5.23] relative to those aged 18–29 years) among the hematological malignancy cohort	United States
Autologous HCT
Sahoo (2017)17	Up to five years post-autologous HCT, 21% of patients developed at least one HZ episode 82% of patients who developed at least one HZ episode were not on prophylaxis at the time of HZ 16% of patients who developed at least one HZ episode developed a second episode of HZ Patients on prophylaxis had a lower risk of HZ compared with patients not on prophylaxis (adjusted HR [95% CI]: 0.59 [0.37–0.91])	Patients aged ≥55.5 years had an increased risk of HZ compared with patients aged <55.5 years (adjusted HR [95% CI]: 1.42 [1.05–1.90])	Washington, United States
Zhang (2017)18	HZ incidence (95% CI) among overall autologous HCT cohort was 42.4 (36.5–49.0) per 1000 PYs	Risk of HZ increased as age increased (HR=1.016, p=0.038)	United States
Inflammatory bowel disease/ulcerative colitis/tofacitinib treatment
Winthrop (2018)20	5.6% of patients in tofacitinib Phase 2/3/ongoing, open-label, long-term extension ulcerative colitis trials developed HZ HZ IR (95% CI) in the overall cohort treated with tofacitinib was 4.07 (3.14–5.19) per 100 PYs	The highest HZ IR in the overall cohort was reported in patients aged ≥65 years (9.55 [4.77–17.08]) per 100 PYs	Multinational (including US)
Marra (2020)14	Pooled risk ratio (95% CI) of IBD vs no IBD: 1.32 (1.24–1.40)	–	Multinational (including US)
Rheumatoid arthritis/prednisone therapy
Pappas (2015)21	Among rheumatoid arthritis patients, an incidence rate (95% CI) of 7.7 (7.1–8.2) per 1000 PYs was reported Prednisone therapy ≥7.5mg per day was associated with increased HZ risk (HR [95% CI]: 1.81 [1.23–2.67]) compared with no prednisone therapy	Increasing age was associated with increased HZ risk (HR [95% CI]: 1.14 [1.09–1.19] per 5 years of age)	United States
Mareque (2019)22	HZ incidence ranged from 6.6–27.0 per 1000 patients with rheumatic diseases	–	Spain
Marra (2020)14	Pooled risk ratio (95% CI) of rheumatoid arthritis vs no rheumatoid arthritis: 1.51 (1.31–1.75)	–	Multinational (including US)
Psoriasis
Takeshita (2018)23	Patients with moderate-to-severe psoriasis had the greatest risk of HZ compared with no psoriasis (HR [95% CI]: 1.17 [1.06–1.30]) Mild psoriasis was associated with a significant but small increased risk of HZ compared with no psoriasis (HR [95% CI]: 1.07 [1.05–1.10])	Age was not a significant effect modifier	United Kingdom
Lupus nephritis
Reggiani (2023)24	After lupus nephritis diagnosis, HZ occurred in 22.6% of patients, with an incidence of 15.6 per 1000 PYs	NR	Italy
Solid organ transplant
McKay (2020)25	HZ risk among solid organ transplant patients ranged from 0–16% Highest risk was reported among heart transplant recipients (16% and 11%) HZ risk was correlated with intensity of immunosuppression (highest for heart and lung, followed by kidney and liver)	NR	United States
Mareque (2019)22	HZ incidence ranged from 5.0–240.0 per 1000 patients who received transplants	–	Spain
AIDS
Mareque (2019)22	HZ incidence among patients with AIDS was 12.5 per 1000 PYs	–	Spain
Marra (2020)14	Pooled risk ratio (95% CI) of HIV/AIDS vs no HIV/AIDS: 3.22 (2.40–4.33)	–	Multinational (including US)
Chronic condition risk factors
Cardiovascular and cerebrovascular diseases
Cersosimo (2022)26	Patients with cardiovascular disease are more likely to develop severe forms of VZV	Acute coronary syndrome is significantly more common in older patients than younger patients, suggesting that HZ infection in older patients is associated with more severe complications, including a high hospitalization rate per case and a longer average hospital stay HZ in older patients may lead to additional complications and a poorer prognosis	Multinational (including US)
Ecarnot (2025)27	Risk of HZ in patients with cardiovascular conditions has been widely reported in the literature, with increases in risk ranging from a 4% increase among patients with coronary artery disease to a 25-fold increase during 1 year after stroke	NR	Multinational (including US)
Mareque (2019)22	HZ incidence ranged from 11.0 to 11.4 per 1000 patients with COPD or cardiovascular disease HZ incidence ranged from 10.5 to 12.4 per 1000 PYs in patients with cardiopulmonary disease, ischemic heart disease, heart failure, atrial fibrillation, or valvular pathology	–	Spain
Seo (2018)28	Increased risk of HZ hospitalization after myocardial infarction compared with before myocardial infarction (HR [95% CI]: 1.625 [1.144–2.308]) Increased risk of HZ hospitalization after ischemic stroke compared with before ischemic stroke (HR [95% CI]: 1.518 [1.177–1.957]) Increased risk of HZ hospitalization after heart failure compared with before heart failure (HR [95% CI]: 1.485 [1.041–2.117])	NR	Korea
Wu (2015)29	Higher risk of HZ in patients with heart failure compared with controls (aHR [95% CI]: 2.07 [1.54–2.78])	Highest risk of HZ among heart failure patients was among patients aged 41–65 years (HR [95% CI]: 3.14 [1.56–6.21])	Taiwan
Marra (2020)14	Pooled risk ratio (95% CI) of cardiovascular conditions vs no cardiovascular conditions: 1.34 (1.17–1.54)	–	Multinational (including US)
Diabetes
Mareque (2019)22	HZ incidence ranged from 9.4–15.3 per 1000 patients with diabetes mellitus Patients with diabetes mellitus had a 24% higher risk of HZ compared with the general population	–	Spain
Giorda (2024)30	17.9% of 3423 HZ hospitalizations during 2010–2019 were diabetic patients Diabetic patients had higher HZ hospitalization rates compared to non-diabetic patients (15.9 per 100,000 patients compared with 6.0 per 100,000 patients)	Increasing age was associated with an increased risk of HZ hospitalization	Italy
Huang (2022)31	Individuals with diabetes mellitus have an increased risk of HZ compared with the general population (pooled RR [95% CI]: 1.38 [1.21–1.57])	Age did not modify the association between diabetes and risk of HZ	Multinational (including US)
Lai (2021)32	Pooled incidence of HZ in patients with diabetes mellitus was 7.22 per 1000 PYs compared with a pooled incidence of 4.12 per 1000 PYs in patients without diabetes mellitus Risk of HZ was significantly higher in patients with diabetes mellitus compared with those with no diabetes mellitus (IRR [95% CI]: 1.60 [1.33–1.93])	The pooled incidence of HZ was higher in patients aged ≥65 years compared with patients aged 18–64 years (both with and without diabetes) Patients aged ≥65 years with diabetes had the highest incidence rate HZ (11.91 per 1000 PYs)	Multinational (including US)
Poirrier (2022)9	Crude HZ incidence rate in patients with type II diabetes was 9.8 per 1000 PYs compared with 2.6 per 1000 PYs in patients without type II diabetes Type II diabetes patients were more likely to be diagnosed with HZ than patients without type II diabetes (adjusted IRR [95% CI]: 1.84 [1.82–1.85])	Patients with type II diabetes aged 18–49 years had the highest risk of HZ (adjusted IRR [95% CI]: 4.20 [4.10–4.30]) Among patients with type II diabetes, risk of HZ-related complications increased with age. Patients aged ≥75 years had a 1.80 times greater risk of complications compared with patients aged 18–44 years (HR [95% CI]: 1.80 [1.75–1.86])	United States
Saadatian-Elahi (2020)33	Risk of HZ in patients with diabetes was significantly higher compared with patients without diabetes, with the magnitude of risk varying from 1.06 to 2.38 (p<0.05)	Incidence of HZ in patients with diabetes increased with age	Multinational (including US)
Marra (2020)14	Pooled risk ratio (95% CI) of diabetes vs no diabetes: 1.24 (1.14–1.35)	–	Multinational (including US)
Chronic kidney disease
Marra (2020)14	Pooled risk ratio (95% CI) of chronic renal disease vs no chronic renal disease: 1.29 (1.10–1.51)	–	Multinational (including US)
Li (2021)39	72.34% (n=34/47) HZ cases were among patients with stage IV or V CKD	NR	China
Chronic respiratory condition risk factors
Asthma/asthma therapy
Mareque (2019)22	HZ incidence in asthmatic patients was reported as 6.9 HZ cases per 1000 patients	–	Spain
Morena (2023)34	Higher risk of developing HZ among patients with asthma compared with patients without asthma (OR [95% CI]: 1.67 [1.63–1.71])	Highest risk of HZ in population aged >70 years	Spain
Mortimer (2024)35	Pooled HZ incidence (95% CI) in adults aged ≥18 years with asthma was 5.71 (4.68–6.96) per 1000 PYs Pooled rate ratio for developing HZ (95% CI) was 1.23 (1.11–1.35) in adults aged ≥18 years and 1.36 (1.15–1.61) in adults aged ≥50 years HZ risk increased with use of systemic corticosteroids, long-acting beta-agonists and inhaled corticosteroids, and add-on therapy	Pooled HZ incidence (95% CI) in adults aged <60 years was 4.20 (3.09–5.70) per 1000 PYs compared with 10.33 (9.17–11.64) per 1000 PYs in adults aged ≥60 years	Multinational (including US)
Safonova (2023)36	24% increased risk of HZ in those with asthma compared with healthy controls Risk of HZ is increased at any age and may be further elevated by receiving inhaled corticosteroids	Increased risk with asthma in all age groups	Multinational (including US)
Shrestha (2022)37	Risk of HZ infection increases with asthma history	Risk of HZ infection was higher in young adults and the elderly with asthma	Multinational (including US)
Singer (2024)8	Overall adjusted IRR (95% CI) of HZ incidence in patients with asthma compared with patients without asthma: 1.34 (1.32–1.37)	Adjusted IRR (95% CI) for adults aged 18–49 years: 1.40 (1.35–1.45) Adjusted IRR (95% CI) for adults aged ≥50 years: 1.27 (1.24–1.29)	United States
Marra (2020)14	Pooled risk ratio (95% CI) of asthma vs no asthma: 1.24 (1.16–1.31)	–	Multinational (including US)
COPD/COPD therapy
Mareque (2019)22	HZ incidence ranged from 11.0 to 11.4 per 1000 patients with COPD or cardiovascular disease Patients with COPD had a 39% higher risk of HZ compared with the general population Patients with COPD receiving inhaled corticosteroids had a 61% higher risk of HZ compared with the general population	–	Spain
Morena (2023)34	Higher risk of developing HZ among patients with COPD compared with patients with no COPD (OR [95% CI]: 1.16 [1.13–1.19])	Highest risk of HZ in population aged >70 years	Spain
Safonova (2023)36	41% increased risk of HZ in those with COPD compared with healthy controls Risk of HZ is increased at any age and may be further elevated by receiving inhaled corticosteroids	Increased risk with COPD in all age groups	Multinational (including US)
Marra (2020)14	Pooled risk ratio (95% CI) of COPD vs no COPD: 1.41 (1.28–1.55)	–	Multinational (including US)
Yawn (2024)38	Adjusted HR of COPD with long-term inhaled corticosteroid exposure vs COPD with no or short-term inhaled corticosteroid exposure (95% CI): 2.57 (2.55–2.60)	NR	United States
Lung cancer
Morena (2023)34	Higher risk of developing HZ among patients with lung cancer compared with no lung cancer (OR [95% CI]: 1.68 [1.60–1.76])	Highest risk of HZ in population aged >60 years	Spain
Other risk factors
Family history
Marra (2020)14	RR (95% CI) of HZ compared with controls = 2.48 (1.70–3.60)	–	Multinational (including US)
Lai & Yew (2016)40	Cases with HZ had OR (95% CI): 3.03 (1.86–4.94) of reporting first-degree relatives with a history of HZ Cases with HZ had OR (95% CI): 3.27 (1.75–6.10) of reporting total relatives with a history of HZ	NR	Multinational (including US)
Frailty
Zorzoli (2018)41	Significant burden caused by HZ and its complications in the frail elderly	–	Multinational (including US)
Multimorbidity
Cohen (2025)42	HZ IRs increased with increasing number of comorbidities across age groups: 1 comorbidity 18–29 years: 1.48 30–39 years: 4.15 40–49 years: 5.28 50–59 years: 6.87 60–69 years: 7.88 70–79 years: 9.34 ≥80 years: 9.78 2 comorbidities 18–29 years: 1.89 30–39 years: 5.02 40–49 years: 6.29 50–59 years: 8.59 60–69 years: 9.17 70–79 years: 10.73 ≥80 years: 11.18 3+ comorbidities 18–29 years: 2.41 30–39 years: 7.24 40–49 years: 7.38 50–59 years: 9.22 60–69 years: 10.30 70–79 years: 12.04 ≥80 years: 12.92	–	United States

Notes: [a] “NR” is reported if no age-specific data are reported in the study; “–” is reported if age is included in the study’s main findings or can be found elsewhere in the table.

Abbreviations: AIDS, acquired immunodeficiency syndrome; CI, confidence interval; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HCT, hematopoietic cell transplant; HR, hazard ratio; HZ, herpes zoster; HZO, herpes zoster ophthalmicus; IBD, inflammatory bowel disease; IR, incidence rate; IRR, incidence rate ratio; NR, not reported; OR, odds ratio; PHN, postherpetic neuralgia; PYs, person-years; RR, relative risk; US, United States; vs, versus; VZV, varicella zoster virus.

Table 2.

HZ Outcomes and Risk Factors

HZ Outcome and Associated Studies	Measure of Risk/Association	Age Group-Specific Notes on Study Outcomes	Study Geography
HZO
Kong (2020)43	HZO incidence has increased 3.6% per year from 1994–2018	HZO incidence has declined since 2008 in individuals aged <21 years and >60 years HZO incidence has increased since 2008 among individuals aged 31–60 years	United States
Mortimer (2024)35	Asthma was associated with an increased risk of HZO (OR [95% CI]: 1.9 [1.1–3.2])	NR	Multinational (including US)
Functional decline/decline in quality of life
Herpes Zoster and Functional Decline Consortium (2015)48	Strong bidirectional link between HZ and functional decline among older adults	–	Multinational (including US)
Mizukami (2018)49	HZ impaired quality of life in daily activity performance and emotional and physical functioning, with the negative impact on quality of life more prevalent in patients with a longer PHN duration compared with patients without PHN	Quality of life scores were lower in older patients	Japan
Pickering (2016)50	Compared with patients aged 50–70 years, patients aged ≥70 years were more frequently prescribed analgesics for acute pain or PHN, and reported poorer pain relief and questionnaire responses	–	France
Torcel-Pagnon (2017)51	1 to 3 months after onset of HZ, patients with underlying conditions experienced more intense HZ-related pain than patients without underlying conditions Quality of life scores were significantly lower in patients with underlying conditions	Patients with underlying conditions were an average of 10 years older than patients without underlying conditions Among patients with underlying conditions, patients aged ≥65 years reported higher pain intensity than patients aged <65 years	Italy
Risk factors for PHN
Forbes (2016)53	Older age and severe immunosuppression were identified as the strongest risk factors for PHN among HZ patients	Risk of PHN rose with age, with the sharpest increase between 50–79 years (adjusted OR for 10-year increase [99% CI]: 1.70 [1.63–1.78])	United Kingdom
Forbes (2016)54	Older age, severe immunosuppression, and diabetes were identified as risk factors for PHN across multiple studies	Older age was significantly associated with PHN (RR estimates per 10-year increase ranged from 1.22–3.11)	Multinational (including US)
Saadatian-Elahi (2020)33	Incidence of PHN was higher in patients with diabetes	No difference in risk by age found for adults aged >65 years	Multinational (including US)
Tang (2024)55	Blood glucose coefficient of variation had a high predictive value for PHN (area under the curve=0.714, p<0.001)	Age was not associated with PHN (p>0.05)	China
Morena (2023)34	Increased risk of PHN associated with COPD (OR [95% CI]: 1.24 [1.23–1.25]) Increased risk of PHN associated with lung cancer (OR [95% CI]: 1.14 [1.13–1.16])	Highest risk of PHN in population aged >70 years	Spain
Mortimer (2024)35	Asthma was associated with an increased risk of PHN (OR [95% CI]: 1.21 [1.06–1.37])	NR	Multinational (including US)
Cardio- and cerebrovascular diseases
Cersosimo (2022)26	VZV can cause cardiovascular diseases such as heart failure, ischemic stroke, and myocardial infarction HZ can cause ischemia through multiple mechanisms	–	Multinational (including US)
Ecarnot (2025)27	HZ increases the risk of certain cardiovascular events. After HZ infection, risk of stroke was highest at 1 month and risk of myocardial infarction was highest within the first week.	NR	Multinational (including US)
Amlie-Lefond (2016)56	Incidence of stroke after HZ is greater than in age-matched control patients without HZ	VZV and HZ are risk factors for stroke, particularly in individuals with HZ aged <40 years	Multinational (including US)
Curtis (2025)57	Among patients with inflammatory arthritis, risk of venous thromboembolic events was elevated 60–90 days post-HZ No significantly increased risk was observed for other cardiovascular events overall, although increased risks of myocardial infarction, stroke, other major adverse cardiovascular events, and venous thromboembolic events were observed when stratified by age group	An increased risk of myocardial infarction was observed with increasing age (IRR aged <50 years [95% CI]: 1.78 [1.45–2.12]) (IRR aged 50 to <70 years [95% CI]: 8.43 [7.98–8.87]) (IRR aged ≥70 years [95% CI]: 18.94 [18.09–19.79]) An increased risk of stroke was observed with increasing age (IRR aged <50 years [95% CI]: 1.78 [1.45–2.11]) (IRR aged 50 to <70 years [95% CI]: 6.57 [6.17–6.97]) (IRR aged ≥70 years [95% CI]: 18.10 [17.26–18.93]) An increased risk of other major adverse cardiovascular events was observed with increasing age (IRR aged <50 years [95% CI]: 3.72 [3.24–4.20]) (IRR aged 50 to <70 years [95% CI]: 14.92 [14.32–15.52]) (IRR aged ≥70 years [95% CI]: 37.07 [35.86–38.28]) An increased risk of venous thromboembolic events was observed with increasing age (IRR aged <50 years [95% CI]: 1.85 [1.51–2.19]) (IRR aged 50 to <70 years [95% CI]: 5.23 [4.88–5.58]) (IRR aged ≥70 years [95% CI]: 10.06 [9.44–10.68])	United States
Lu (2023)58	Increased risk of stroke after HZ, decreasing with time 14-day RR (95% CI): 1.80 (1.42–2.29) 30-day RR (95% CI): 1.61 (1.43–1.81) 90-day RR (95% CI): 1.45 (1.33–1.58) 180-day RR (95% CI): 1.32 (1.25–1.39) 1-year RR (95% CI): 1.27 (1.15–1.40) After 1-year RR (95% CI): 1.19 (0.90–1.59) Risk of stroke after HZO was higher (maximum RR [95% CI]: 2.26 [1.35–3.78])	Risk of stroke after HZ was higher in patients aged approximately 40 years (RR [95% CI]: 2.53 [1.59–4.02])	Multinational (including US)
Marra (2017)59	RR for stroke after HZ first month after HZ (95% CI): 1.78 (1.70–1.88) RR for stroke after HZ 3 months after HZ (95% CI): 1.43 (1.38–1.47) RR for stroke after HZ 1 year after HZ (95% CI): 1.20 (1.14–1.26) Stroke risk increases by a larger margin during the first month after HZO (RR [95% CI]: 2.05 [1.82–2.31])	In adults aged ≤40 years, risk of stroke one year after HZ was significant (RR [95% CI]: 2.96 [1.05–8.41]) In adults aged >40 years, risk of stroke one year after HZ was significant (RR [95% CI]: 1.19 [1.13–1.24])	Multinational (including US)
Yawn (2016)60	Individuals with HZ were at increased risk for stroke 3 months post-HZ compared to individuals without a history of HZ (OR [95% CI]: 1.53 [1.10–2.33])	Age was significantly associated with stroke risk	Minnesota, United States
Zhang (2017)61	HZ infection was significantly associated with increased risk of stroke/transient ischemic attack (RR [95% CI]: 1.30 [1.17–1.46]) HZ infection was significantly associated with increased risk of myocardial infarction (RR [95% CI]: 1.18 [1.07–1.30]) Risk of stroke after HZO was higher than risk after HZ (RR [95% CI]: 1.91 [1.32–2.76])	Risk of stroke after HZ infection was greater among individuals aged <40 years compared with individuals aged 40–59 years and individuals aged ≥60 years	Multinational (including US)
Zuin (2019)62	HZ and HZO increase the risk of cerebrovascular events over short- and long-term periods	Patients aged <40 years have a higher risk of cerebrovascular events after HZ and HZO	Multinational (including US)
Kawai (2025)63	Pooled risk ratio of coronary heart disease (95% CI): 1.12 (1.08–1.15) Pooled risk ratio of stroke (95% CI): 1.18 (1.09–1.27)	–	Multinational (including US)
Curhan (2022)64	Pooled adjusted HR (95% CI) of stroke 1 to 4 years since HZ: 1.05 (0.88–1.25) Pooled adjusted HR (95% CI) of stroke 5 to 8 years since HZ: 1.38 (1.10–1.74) Pooled adjusted HR (95% CI) of stroke 9 to 12 years since HZ: 1.28 (1.03–1.59) Pooled adjusted HR (95% CI) of stroke ≥13 years since HZ: 1.19 (0.90–1.56) Pooled adjusted HR (95% CI) of coronary heart disease 1 to 4 years since HZ: 1.13 (1.01–1.27) Pooled adjusted HR (95% CI) of coronary heart disease 5 to 8 years since HZ: 1.16 (1.02–1.32) Pooled adjusted HR (95% CI) of coronary heart disease ≥13 years since HZ: 1.25 (1.07–1.46) Pooled adjusted HR (95% CI) of coronary heart disease ≥13 years since HZ: 1.00 (0.83–1.21)	NR	United States
CKD and end-stage kidney disease/CKD stage V
Lin (2014)44	CKD patients with HZ had 1.36 times the risk of developing end stage renal disease than CKD patients without HZ: Adjusted HR HZ cohort (95% CI) = 1.36 (1.09–1.70) Risk of developing end stage renal disease increased in the presence of both hypertension and diabetes: Adjusted HR HZ cohort (95% CI) = 8.71 (5.23–14.5)	Adjusted HR HZ cohort age <40 years (95% CI) = 2.38 (0.66–8.62) Adjusted HR HZ cohort age 40–64 years (95% CI) = 1.08 (0.75–1.54) Adjusted HR HZ cohort age >64 years (95% CI) = 1.53 (1.15–2.05)	Taiwan
Li (2021)39	Among patients with CVD and HZ, 59.6% of patients had stage V CKD	NR	China
Depression and anxiety
Li (2025)52	HZ was associated with increased risk of depressive symptoms, inverse variance weighted β=0.040, false discovery rate=0.008 HZ was associated with increased risk of number of episodes with depressed mood, inverse variance weighted β=0.056, false discovery rate=0.003	NR	Multinational (including US)
Du (2021)65	Anxiety developed in 69.0% of PHN patients Depression developed in 65.8% of PHN patients	OR (95% CI) age and anxiety = 0.991 (0.975–1.006) OR (95% CI) age and depression = 1.008 (0.993–1.023)	China

Abbreviations: AIDS, acquired immunodeficiency syndrome; CI, confidence interval; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HCT, hematopoietic cell transplant; HR, hazard ratio; HZ, herpes zoster; HZO, herpes zoster ophthalmicus; IBD, inflammatory bowel disease; IR, incidence rate; IRR, incidence rate ratio; NR, not reported; OR, odds ratio; PHN, postherpetic neuralgia; PYs, person-years; RR, relative risk; VZV, varicella zoster virus.

HZ Incidence Among Adults Aged ≥50 Years

An increased incidence of HZ was reported with increasing age in the US, as were increases in HZ incidence over time.^12,13 A study of US claims data which stratified by age up to age ≥80 years reported an HZ incidence rate (IR) of 8.46 (95% confidence interval [CI] 8.39–8.52) per 1000 person-years (PYs) among adults aged ≥50 years, an IR of 10.46 (95% CI 10.35–10.56) per 1000 PYs among adults aged ≥60 years, and an IR of 12.78 (95% CI 12.49–13.07) per 1000 PYs among adults aged ≥80 years.¹² Although the highest IR was reported among adults aged ≥80 years, the highest number of HZ cases (29,266/113,861 HZ cases; 26%) occurred among adults aged 50–59 years.¹² Similar trends in incidence increasing with age were seen for the incidence of HZO.⁴³

Risk of HZ in Patients with Chronic Conditions

In a 2020 meta-analysis, an increased risk for HZ was associated with a number of chronic conditions, including cardiovascular conditions, diabetes, chronic obstructive pulmonary disease (COPD), asthma, and chronic kidney disease (CKD).¹⁴

Cardiovascular disease has been associated with an increased risk of HZ in several studies;^14,22,27,28 heart failure has also been associated with a higher risk of HZ^22,29 and HZ episodes requiring hospitalization.²⁸

Diabetes was identified as a risk factor for HZ in multiple studies,^{9,14,22,30–33} and a meta-analysis of cohort studies on diabetes and risk of HZ found that patients with diabetes mellitus had a significantly higher risk of developing HZ compared with patients without diabetes mellitus (incidence rate ratio: 1.60 [95% CI 1.33–1.93]).³² Additionally, in a US claims analysis, HZ infection increased healthcare resource utilization for diabetes patients in the year following HZ infection.⁹

Multiple chronic respiratory conditions have been identified as risk factors for HZ. Across studies spanning diverse geographies, asthma^{8,14,22,34–37} and COPD^14,22,34,36 were found to increase the risk of HZ. One review found that certain asthma medications also increased HZ risk, including systemic corticosteroids, as well as long-acting beta-agonists combined with the use of inhaled corticosteroids.³⁵ Inhaled corticosteroid therapy was also associated with an increased risk of HZ among COPD patients.³⁸

CKD has also been identified as a risk factor,¹⁴ with HZ in patients with CKD found to be associated with higher risk of progression to end-stage kidney disease (ESKD)/CKD stage V.^44,45 This risk was further inflated by the presence of other chronic conditions, such as hypertension and diabetes.⁴⁴ One case-control study found that most (72.3%) HZ cases identified among CKD patients were among patients with stage IV to stage V CKD.³⁹

Other identified risk factors for HZ in older adults included frailty⁴¹ and multimorbidity (the presence of more than one underlying condition).⁴² One retrospective study utilizing a US claims database evaluated IRs for HZ in patients with an increasing number of comorbidities, analyzing this risk among adults of different age groups and with select comorbidities (diabetes, asthma, COPD, CKD, depression, stress, and/or trauma).⁴² This study found that IRs increased with an increasing number of comorbidities (1 comorbidity: 6.87 [aged 50–59 years], 7.88 [aged 60–69 years], 9.34 [aged 70–79 years], 9.78 [aged ≥80 years]; 2 comorbidities: 8.59 [aged 50–59 years], 9.17 [aged 60–69 years], 10.73 [aged 70–79 years], 11.18 [aged ≥80 years]; ≥3 comorbidities: 9.22 [aged 50–59 years], 10.30 [aged 60–69 years], 12.04 [aged 70–79 years], 12.92 [aged ≥80 years]).⁴²

Risk of HZ in Patients with Immunocompromising Conditions or on Immunosuppressive Therapies

Associations between immunocompromising conditions and HZ are well established. Solid organ transplant patients have been found to be at increased risk for HZ compared with immunocompetent older adults, with the highest risk for heart and lung transplants, followed by kidney and liver transplants.²⁵ Two studies identified hematopoietic cell transplant (HCT) as a risk factor for HZ,^17,18 with increased risk among older patients.¹⁷ One study identified a notable proportion of HZ diagnoses among patients with cancer,¹⁵ and several studies identified certain cancer treatments as risk factors for HZ.^16–18 Among patients with cancer, adjusted analyses indicated a higher likelihood of developing HZ during periods of immunosuppressive treatment versus periods without.¹⁶ In a cohort of patients with hematological malignancies, HZ incidence rates were highest in those with non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma; in a cohort of patients with solid tumors, HZ incidence rates were highest in those with lung cancer, non-melanoma skin cancer, and endometrial cancer.¹⁶ Lastly, one study also found an association between lung cancer and HZ risk, with risk increased in older adults and those with comorbidities.³⁴

Other conditions which involve treatment with immunosuppressive therapies have also been associated with an increased HZ risk, including RA,^14,21 psoriasis,²³ lupus nephritis,²⁴ and inflammatory bowel disease (IBD).^19,46,47 Janus kinase inhibitors, in addition to increasing HZ risk in RA patients and psoriatic arthritis patients, were found to increase risk of HZ among ulcerative colitis patients, with further increased rates among patients aged ≥65 years.²⁰

HZ Outcomes and Complications

In several studies, HZ was associated with functional decline (ie, a decrease in the ability to perform activities of daily living) during and after HZ and PHN episodes, as well as negative impacts on quality of life among older adults,^48–51 which may be amplified by underlying conditions such as cardiovascular disease, diabetes, and respiratory diseases⁵¹ (Table 2). Per a post-hoc analysis of one prospective cohort study, patients with these underlying conditions experienced more intense pain and lower quality of life scores one to three months after HZ onset.⁵¹ A Mendelian randomization study of genetic samples (of European ancestry) found that HZ is associated with an increased risk of depressive symptoms and an increased number of episodes with depressed mood.⁵²

Two studies identified older age, in addition to severe immunosuppression, diabetes, asthma, COPD, smoking, and being underweight or obese, as risk factors for PHN;^53,54 odds of developing PHN went up by 19%, 21%, and 53% for HZ patients with diabetes, asthma, and COPD, respectively.⁵³ Among patients with PHN, one retrospective cohort study found high rates of anxiety and depression; these conditions were associated with the magnitude of pain intensity and the spread of the HZ rash.⁶⁵ Among populations with diabetes, a higher likelihood of PHN,⁵⁵ as well as a higher incidence of hospitalization, stroke, and MI following an HZ episode, were identified.³⁰

Numerous studies identified increased risk of CVAs and MI in patients with HZ.^{26,27,56–64} Risk of these CVA events was acute and time-dependent, with the highest risk in the weeks and months after HZ;^{26,27,56,58–63} risk of CVA was highest within the first month following HZ (relative risk: 1.78 [95% CI 1.70–1.88]) and remaining elevated for up to one year.⁵⁹ Limited data also suggest that risk of CVA may remain higher over longer periods, beyond one year.⁶⁴ While the mechanism is not established and thought to be multifactorial,²⁷ it has been hypothesized that VZV traverses along nerves and can infect arterial walls, leading to VZV vasculopathy; this is the likely mechanism for reported ischemia and stroke events following HZ.^26,56,62

Prevalence of Co-Morbid Conditions

Chronic conditions associated with HZ risk have varying prevalences among the US population aged ≥50 years. Centers for Disease Control and Prevention (CDC) reports estimate 12.3% of US adults aged 45–64 years and 33.7% aged ≥65 years have CKD,⁶⁶ and 4.9% of US adults aged 50–64 years and 14.6% of US adults aged ≥65 years had coronary heart disease in 2023,⁶⁷ underscoring a large population segment that is vulnerable to HZ due to underlying comorbidities. CDC reports estimate 29.2% of adults aged ≥65 years have diagnosed or undiagnosed diabetes.⁶⁸ Respiratory conditions associated with HZ risk are also prevalent in this population, with the CDC reporting an 8.0% prevalence of asthma among adults aged ≥65 years⁶⁹ and a 6.1% and 9.6% prevalence of COPD among adults aged 50–64 years and ≥65 years, respectively, in 2023.⁷⁰

Immunocompromising conditions which are risk factors for HZ become more common with advancing age. In recent years, over half of cancer diagnoses in the US have been among adults aged ≥65 years.⁷¹ Additionally, older adults in the US are at greater risk for certain conditions such as RA.⁷²

HZ Prevention

RZV as HZ Prevention in Older Adults

In two Phase 3 clinical trials assessing the efficacy and safety of RZV in immunocompetent adults aged ≥50 years (ZOE-50) and adults aged ≥70 years (ZOE-70), RZV significantly reduced the risk of HZ and PHN, with a vaccine efficacy against HZ of 97.2% (95% CI 93.7–99.0%) in adults aged ≥50 years and a pooled efficacy of 91.3% (95% CI 86.8–94.5%) in adults aged ≥70 years, over approximately 3–4 years of follow-up.^73,74 In a long-term follow-up study of ZOE-50 and ZOE-70 (ZOE-LTFU), RZV efficacy against HZ remained high (82.0%) and the safety profile remained clinically acceptable at 11 years after vaccination; an HZ efficacy of 79.8% was demonstrated during the long-term follow-up period (5.6–11.4 years after vaccination) among adults vaccinated at age ≥50 years.⁷⁵

Identified studies also assessed the safety of RZV in a population aged ≥50 years.^76–80 In a pooled analysis of clinical trials among immunocompromised populations, unsolicited adverse events and serious adverse events were comparable with placebo.⁸⁰ The most commonly reported symptoms following vaccination in clinical trial populations of adults aged ≥50 years were pain, redness, and swelling at the injection site, and fatigue, headache, and myalgia.^77–79 Two of these studies found that the reactogenicity of either dose of RZV in adults aged ≥50 years did not significantly impact quality of life.^77,78 In the post-licensure setting, two observational studies in Medicare populations (individuals aged ≥65 years) reported approximately 3.1–6.6 excess Guillain-Barré syndrome (GBS) cases per million vaccinations during the 42-day period following vaccination.^76,81

Additional analyses in ZOE-50/70 participants assessed RZV efficacy and safety based on frailty status (defined using an index accounting for medical history and questionnaire responses) and presence of common comorbid conditions.^82,83 Efficacy and safety did not vary based on frailty status or common comorbid conditions.^82,83 In the pooled results of the two clinical study cohorts, with subjects aged ≥50 years and ≥70 years, RZV significantly reduced the risk of HZ in frail participants compared with those in the placebo group.⁸² Pre-licensure studies were also conducted in immunocompromised patient populations. In patients aged ≥18 years who had undergone autologous hematopoietic stem cell transplantation, efficacy was 68.2%,⁸⁴ while a post-hoc analysis of another study assessing efficacy in patients with hematological malignancies reported an efficacy of 87.2%.⁸⁵

In a real-world evidence study assessing HZ prevention in both immunocompetent and immunocompromised patients aged ≥50 years, RZV demonstrated a vaccine effectiveness of 76% that waned minimally over four years of follow-up (73% during the third and fourth years).⁸⁶ A cohort study of Medicare beneficiaries aged >65 years found a vaccine effectiveness of 70.1% (95% CI 68.6–71.5%), which was not substantially lower for individuals with autoimmune conditions.⁸³ Vaccine effectiveness also remained high in populations with comorbidities at baseline, ranging from 62.7% (95% CI 50.4–72.0%) among patients with liver disease to 74.5% (95% CI 70.2–78.3%) among patients with diabetes.⁸⁷

RZV co-administration with other vaccines among older adults has been assessed in clinical studies. Two clinical trials were identified which demonstrated the safety and immunogenicity of co-administration of RZV with influenza vaccines.^88,89 Clinical trials have also shown the safety and immunogenicity of RZV co-administration with the 13-valent pneumococcal conjugate vaccine,⁹⁰ the 23-valent pneumococcal polysaccharide vaccine,⁹¹ the reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine,⁹² the coronavirus disease 2019 mRNA-1273 booster vaccine,⁹³ and the adjuvanted respiratory syncytial virus (RSV) prefusion F protein vaccine.⁹⁴ Based in part on these data, the CDC recommends that recombinant and adjuvanted vaccines, such as RZV, can be co-administered with other adult vaccines.⁹⁵

Gaps in HZ Prevention

Multiple studies identified gaps in HZ vaccine coverage and adherence, with opportunities to increase RZV uptake among adults aged ≥50 years.^96–98 Comparing patterns of RZV initiation among immunocompetent and immunocompromised US adults aged 50–64 years, one cohort study found 30% higher initiation (1.30 [95% CI 1.27–1.32]) among immunocompromised patients compared with immunocompetent patients, though series completion was similar.⁹⁹ In patients with chronic conditions, burden of disease may play a role in missed opportunities for vaccination; one claims analysis found that, among patients who had received one RZV dose, most chronic conditions, including both COPD and type 2 diabetes, were associated with lower completion.¹⁰⁰ Further research is needed to elucidate trends of RZV initiation and series completion in risk groups to inform opportunities to improve HZ prevention in these populations. Other studies assessing vaccination practices have shown lower uptake associated with certain social determinants of health, including poverty, lack of internet access, African American race, male gender, healthcare access, and health insurance status.^97,100–102

Regarding addressing gaps in HZ prevention, identified studies reported the impacts of immunization check-ups at employee health screenings and the expansion of vaccination into more medical practices, in order to reach more patients.^103,104 Strategies for patient populations with specific comorbidities have also been explored; one study in a population of hospitalized diabetes patients found that hospitalization and multidisciplinary care management may be key opportunities to increase vaccination coverage.¹⁰⁵

Guidelines and Recommendations for the Prevention of HZ

The CDC recommends two doses of RZV for adults aged ≥50 years and adults aged ≥19 years who are or will be immunodeficient or immunosuppressed because of disease or therapy.¹⁰ In order to increase adult vaccination rates, the National Vaccine Advisory Committee has published Standards for Adult Immunization Practice that include, but are not limited to, RZV.¹⁰⁶ As a provider recommendation is the strongest predictor of patient vaccination, the CDC encourages providers to implement these standards into their practice using the following guidelines: 1) Assess patients’ immunization status at each clinical encounter; 2) Make clear and tailored recommendations for the vaccines that patients need; 3) Administer vaccines or refer patients to a vaccine provider at the same visit as the recommendation; and 4) Document vaccines received by patients.¹⁰⁷ A number of medical societies have reinforced these recommendations in their society guidelines or consensus reports (Table 3).

Table 3.

HZ Vaccination Guidelines

Disease Area	Organization	HZ Vaccination Guidelines
General population and broad comorbidities	ACIP/CDC (2024)10,95	Two doses of RZV separated by 2–6 months for immunocompetent adults aged ≥50 years Two doses of RZV in adults aged ≥19 years who are or will be immunodeficient or immunosuppressed due to disease or therapy
	WHO (2025)108
	ACR (2022)109
Cardiovascular disease	AHA (2025)4	Two doses of RZV separated by 2–6 months for immunocompetent adults aged ≥50 years Two doses of RZV in adults aged ≥19 years who are or will be immunodeficient or immunosuppressed due to disease or therapy
	ACC (2025)110	Two doses of RZV separated by 2–6 months for immunocompetent adults aged ≥50 years
Respiratory disease	GOLD (2025)111	Two doses of RZV separated by 2–6 months for immunocompetent adults aged ≥50 years Two doses of RZV in adults aged ≥19 years who are or will be immunodeficient or immunosuppressed due to disease or therapy
	American Lung Association (2025)112
Endocrine/metabolic disease	AACE (2022)113	Two doses of RZV separated by 2–6 months for all adults aged ≥50 years
	ADA (2025)114
Renal disease	National Kidney Foundation115,116	Two doses of RZV separated by 2–6 months for adults aged ≥50 years with advanced CKD or on dialysis Two doses of RZV separated by 2–6 months for adults aged ≥19 years with a weakened immune system (including kidney transplant)
Cancer	ASCO (2024)117	Two doses of RZV separated by at least 4 weeks for adults aged ≥19 years with cancer
Ophthalmology	AAO (2020)118	Two doses of RZV separated by 2–6 months for immunocompetent adults aged ≥50 years
HIV	IDSA (2024)119	Two doses of RZV separated by 2–6 months for adults aged ≥18 years with HIV

Abbreviations: AACE, American Association of Clinical Endocrinology; AAO, American Academy of Ophthalmology; ACC, American College of Cardiology; ACG, American College of Gastroenterology; ACIP, Advisory Committee on Immunization Practices; ACR, American College of Rheumatology; ADA, American Diabetes Association; AGA, American Gastroenterological Association; AHA, American Heart Association; ASCO, American Society of Clinical Oncology; CDC, Centers for Disease Control and Prevention; CKD, Chronic Kidney Disease; COPD, Chronic Obstructive Pulmonary Disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; HIV, human immunodeficiency virus; HZ, herpes zoster; IDSA, Infectious Diseases Society of America; RZV, recombinant zoster vaccine; US, United States; WHO, World Health Organization.

Several medical organizations recommend RZV for patients with chronic medical conditions, including the National Kidney Foundation, for adults with advanced CKD, who have kidney failure or ESKD, or on dialysis,¹¹⁵ and the American Association of Clinical Endocrinology and the American Diabetes Association, for patients with diabetes.^113,114 The Global Initiative for Chronic Obstructive Lung Disease 2025 Report recommends routine vaccination against HZ for adults with COPD,¹¹¹ and the American Lung Association recommends that patients with asthma or COPD stay up to date on vaccinations, including those for HZ.¹¹² The American Heart Association and the American College of Cardiology also recommend that all adults aged ≥50 years receive RZV.^4,110 Some medical organizations, including the American College of Cardiology, have also adopted the CDC standards for adult immunization practice, and have made a commitment to advancing adult immunization.¹²⁰

Several identified studies and guidelines also highlight the importance of HZ prevention through vaccination in populations with certain immune-related conditions, such as IBD,^19,46,47 rheumatic diseases,¹⁰⁹ myeloma,¹²¹ HCT treatment,^18,84,85 and solid organ transplant.¹²² Candidates for and recipients of solid organ transplant are recommended to receive a two-dose series of RZV.¹²² For adult patients with cancer, the American Society of Clinical Oncology guidelines also recommend the RZV series.¹¹⁷

Specialists play a growing role in the care of US older adults, and therefore in the prevention of HZ, as reflected by a 20% increase in mean specialist visits from 4.05 in 2000 to 4.87 in 2019 among Medicare beneficiaries (for adults aged ≥65 years).¹²³ Additionally, in 2019, 30.1% of Medicare beneficiaries saw ≥5 physicians annually.¹²³ Among healthcare providers, knowledge and vaccine confidence can influence the recommendations made to their patients,¹²⁴ making knowledge and endorsement of RZV recommendations and HZ prevention practices increasingly pertinent to specialists, particularly those working with older adults or specializing in conditions which may place their patients at an increased risk for HZ. To prevent HZ and its outcomes in an aging, increasingly comorbid US population, specialists play a crucial role in routinely assessing immunization status and providing strong recommendations for RZV as part of comprehensive prevention efforts, rather than relying solely on primary care providers.

Limitations

This review is subject to those limitations which are typical of literature searches and narrative reviews, such as reviewer bias and potential for noncomprehensive study identification. Additionally, all syntheses were descriptive and did not include quantitative analyses; however, this approach is inherent to narrative reviews, for which the aim is to summarize available evidence and distill insights to inform directions for future research and ongoing conversations in relevant clinical and policy settings. Due to the inclusion of studies conducted outside of the US, the generalizability of findings of these studies to a population of US adults may be limited and should be interpreted with the study geography in mind. The included studies report outcomes, such as increases in HZ risk, using different measures and study designs, which may influence the comparability of the results.

Conclusions

Due to the increasing proportion of US older adults living with chronic conditions and increased HZ risk and burden among those with comorbid conditions, understanding the risk factors for HZ in adults aged ≥50 years in the US, including those beyond age-related immunosenescence, will continue to grow in importance. The improvement of HZ prevention, particularly the vaccination of those aged ≥50 years with underlying conditions, is crucial, with opportunities for wider endorsement of vaccination by medical societies and healthcare providers of patients with comorbid disease.

Specialists and primary care providers are central to reducing HZ burden in adults aged ≥50 years, particularly those with chronic conditions. By embedding risk assessment into routine care, recommending vaccination without hesitation, and working together across disciplines, clinicians can protect patients from serious complications and drive a unified approach to prevention.

Funding Statement

This study was sponsored by GSK. Support for third-party writing assistance for this article, provided by Madeline Block, Costello Medical, US was funded by GSK in accordance with Good Publication Practice (GPP 2022) guidelines (https://www.ismpp.org/gpp-2022).

Data Sharing Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

CO has no disclosures to declare. BA has no disclosures to declare. RC is employed by GSK and holds financial equities in GSK, has received consulting fees and support for attending meetings from Neurelis Inc., and was formerly employed by and held financial equities in UCB Inc. CH has received consulting fees from Polarean Inc and payment for GSK Educational Videos, Boehringer Ingelheim Speakers Bureau, and GSK Advisory Board, and has stock options in Polarean Inc. HH has no disclosures to declare. JG has received grants from Merck & Co, AstraZeneca, and GSK; has received consulting fees from Genentech and Janssen; has received payment from Janssen and Merck & Co; has received support for attending meetings from the Hematology/Oncology Pharmacy Association; and is employed by GSK and holds financial equities in GSK. RP is employed by GSK and holds financial equities in GSK. The authors report no other conflicts of interest in this work.