Herpes Zoster Hospitalizations in Italy

Comorbidities and Coexisting Conditions, Herpes Zoster

Herpes Zoster, Vaccination, Hospitalizations, Comorbidities

In Italy, the 2017-2019 National Immunization Plan recommended specific vaccinations for the elderly, defined as those 65 years old and older, and at-risk adults with age 50+ (adults presenting cardiovascular, respiratory, or metabolic diseases, immunodepression, etc.). However, the coverage target set by the Plan (50% for Herpes Zoster vaccination in 2019) was not reached. Providing additional data on the incidence of Herpes Zoster could improve the risks perception of the disease and the vaccination uptake. The present study will aim to describe a full picture of Herpes Zoster associated hospital admissions in Italy, focusing on co-morbidities which induce reduced varicella-zoster virus-specific cell-mediated immunity response. Furthermore, as varicella-zoster virus reactivation was reported in COVID-19-positive patients, a deepening on a possible relationship between the two infections will be investigated.

Varicella (chickenpox) is a highly contagious illness sustained by an α Herpes virus called varicella-zoster virus (VZV). A replication phase in the penetration site is followed by a viremic phase when VZV spreads to skin and mucosae, leading to the typical rash and infection of sensory nerves in the epithelium, and then the reach of the sensory ganglia where it becomes latent. The reactivation of the latent virus, years or decades after primary infection, causes the typical clinical expression called Herpes Zoster (HZ) or shingles. Post-herpetic neuralgia (PHN), an intractable pain in the dermatome affected by HZ, is the most common complication. It is estimated that it affects 10-20% of all patients with HZ aged ≥ 50 years and up to 30% of those aged ≥80 years. Management of PHN is not easy, but vaccination for prevention of PHN may be a strategic choice. The most common complications of herpes zoster, other than PHN, often requiring hospitalization, include secondary bacterial infections, ophthalmic complications, cranial and peripheral nerve palsies, and segmental zoster paresis. All authors agree that factors such as age, cell-mediated immunity (CMI) depression, intrauterine exposure to VZV and varicella occurring in early age (\<18 months) are typically associated with HZ incidence. It further should be noted that age and CMI depression are strictly related since increasing age leads to CMI decrease. An increased incidence of hospitalization for HZ among patients aged \>72 years (0.46/1000-person year), compared to those aged 15-44 years (0.03/1000-person year) was reported, suggesting that aging is also a risk factor for HZ requiring hospitalization. Besides age, HZ risk can be related to other co-morbidities, including diabetes, major depression or immunosuppressive therapies, that induce reduced VZV-specific CMI response. Immunosuppressed patients are within the high-risk group, with increasing morbidity and mortality associated with herpes zoster. Immunosuppression may be associated with malignancy (especially hematological), human immunodeficiency virus (HIV) infection or medications used for organ transplantation or autoimmune disease. HZ incidence is similar all over the world and its trend is related to population age, with two thirds of the cases affecting subjects aged \>50 years. Among European adult population, the percentage of subjects estimated to be seropositive for anti-VZV antibodies is 95%: all of them are therefore potentially susceptible to develop HZ in their lifetime. In Italy, the annual incidence of HZ is 6.3/1000 person-years, with 73% of cases affecting adults. Italy is one of the countries with the highest proportion of elderly people in its population, and yet data on the epidemiology of HZ and PHN are limited. As the immune system weakens with increasing age, many infectious diseases, such as HZ, are more severe and more closely associated with long-term consequences in the elderly than in younger people. With the growing aging population, a rise in the number of cases of HZ in the near future is expected; thus, this disease will become a public health issue. While awareness of childhood vaccination is well established, the prevention of infectious diseases in groups other than children is a challenging, yet fundamental, objective that public health systems should pursue in order to promote healthy aging. In order to evaluate the epidemiological burden of HZ, hospital discharge records for HZ between 2011 and 2021, with or without complications, will be extracted from the national hospital discharge database (HDD). The characteristics of hospitalizations will be described for the 18 years of age and older adults (2011-2021 years). The characteristics of hospitalizations in 2020-21 will be described in patients with or without concomitant COVID-19 infection.

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