Herpes zoster (HZ) is one of the most common cutaneous adverse reactions associated with the coronavirus disease 2019 (COVID-19) vaccine and has been widely reported. This study aimed to evaluate HZ following COVID-19 vaccination from the viewpoint of pain management.
A retrospective study was conducted on 42 patients with HZ who visited the pain clinic between August 2021 and October 2021. Medical records were reviewed to compare pain severity, treatment methods, treatment duration, and incidence rate of postherpetic neuralgia (PHN) in patients who received COVID-19 vaccination within 6 weeks prior to developing symptoms compared with other patients with HZ.
Fourteen patients developed HZ within 6 weeks after vaccination and were significantly younger than the other HZ groups. There were no significant differences in the frequency of prodromal pain, location of pain, pain severity, treatment methods, treatment duration, or incidence of PHN compared with the other HZ groups.
COVID-19 vaccination-related HZ showed clinical features similar to those of the other HZ.
As coronavirus disease 2019 (COVID-19) was declared a global pandemic, vaccines are being developed rapidly, and mass vaccination has been performed in a short time. Vaccination is an efficient and safe way to resolve the COVID-19 pandemic; however, its adverse reactions have been continuously reported [
Herpes zoster (HZ) is one of the adverse reactions of COVID-19 vaccination and is being continuously reported up to now [
This was a retrospective single-center study. This study was approved by the institutional review board of our hospital (no. 2021-11-046) and registered with the Clinical Research Information Service (no. KCT0006864). The present study was conducted according to the ethical principles for medical research of the Declaration of Helsinki 2013.
Patients who visited the pain clinic of our hospital from August 1, 2021, to October 31, 2021, were screened. During the study period, 475 patients visited the pain clinic, of whom 53 were diagnosed with HZ. Patients whose COVID-19 vaccination history was not clearly verified (n = 8), whose medical records were unreliable (n = 2), and who were referred to dermatologists because of chilblain-like lesions (n = 1) were excluded from this study (
In the pain clinic of our hospital, we recognize the association between COVID-19 vaccination and HZ [
Data are presented as mean (standard deviation) or median (interquartile range). The normality of the quantitative data was tested using the Shapiro–Wilk test, and data were analyzed using the independent
This study included 42 patients with HZ. Of the 32 patients who received COVID-19 vaccination, 14 developed HZ within 6 weeks after the vaccination. Ten patients did not receive any vaccination. The median age of the patients was 63.5 (34.5, 73.3) years, with 17 (40.5%) male and 25 (59.5%) female patients. Patients in the CV-related HZ group (52.0 [30.8, 62.3] years) were significantly younger than those in the control group (66.5 [54.3, 78.8] years) (P = 0.005). Prodromal pain was reported in 26 (61.9%) patients; thereafter, skin lesions developed after a median day of 3.0 (0.0, 4.0). The median pain scores were 3.0 (3.0, 4.0) and 4.0 (3.0, 4.0) in the CV-related HZ and control groups, respectively (P = 0.834). The most common locations of the lesion were the thoracic (64.3%) and cranial (14.3%) nerves. Antiviral agents (100%), anticonvulsants (87.2%), and nerve blocks (43.6%) were used. Moreover, 87.2% of the patients completely recovered within 12 weeks (
In the CV-related HZ group, five patients received BNT162b2 (Pfizer), five received mRNA-1273 (Moderna), and four received ChAdOx1 nCov-19 (AstraZeneca). Ten patients developed symptoms after the second dose. Nine (64.3%) patients developed symptoms within 21 days of vaccination (
The clinical information of patients with CV-related HZ and PHN is presented in
In total, 42 patients with HZ were included in the present study, of whom 14 (33.3%) developed HZ within 6 weeks after COVID-19 vaccination. Except for age, demographic and HZ-related data did not show statistically significant differences between the groups. However, five patients in the control group developed PHN, whereas none of the patients in the CV-related HZ group progressed to PHN, but the difference was not statistically significant.
VZV, which remains latent in the ganglia, can be reactivated and replicated, inducing neuritis that directly damages the nerves. It is transported along the microtubules within the sensory axons in the affected nerve to infect the epithelial cells of the skin. This results in severe pain and skin lesions along the cutaneous distribution. Weakened VZV-specific T-cell-mediated immunity reactivates VZV. Its risk factors include immunosenescence, immunocompromised conditions due to disease, trauma, drug use, and psychological stress [
Although HZ is accompanied by severe pain and is likely to progress to PHN, a neurological complication, most published cases of HZ after COVID-19 vaccination have been approached from the aspect of dermatology regarding skin lesions [
Antiviral therapy is important for the treatment of HZ. Antiviral therapy provided in the acute phase inhibits progression to PHN by inhibiting viral replication and reducing injury to nerve fibers and can also reduce the severity and duration of PHN. In addition, a decreased incidence of PHN was reported when antivirals were administered with gabapentin [
The window in which the risk of HZ increases remains unclear. The risk window for HZ significantly varied, ranging from 21 days to 3 months, depending on the studies reported [
Of COVID-19 vaccines, an association between mRNA COVID-19 vaccination and HZ has been reported more frequently [
The association between COVID-19 vaccination and HZ remains controversial. A meta-analysis by Chu et al. [
The present study has a strength in that it was conducted from the aspect of pain medicine, but its limitations are clear as it was a single-center, retrospective study that included a small sample size.Another limitation of this study is that the incidence of HZ associated with COVID-19 vaccination could not be evaluated. To overcome this limitation, a multicenter, prospective, large-scale study targeting a large population must be conducted in the future.
In the present study, patients with HZ associated with COVID-19 vaccination showed similar manifestations to general patients with HZ. They recovered after treatment with antiviral agents, anticonvulsants, and nerve blocks, and none of the patients developed PHN.
None.
No potential conflict of interest relevant to this article was reported.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Conceptualization: Ji Hye Lee. Data curation: Hyun Joo Heo, Ji Hun Park, Hyung Gu Cho, Geonbo Kim. Writing - original draft: Yu Yil Kim. Writing - review & editing: Ji Hye Lee. Supervision: Yu Yil Kim. Validation: Hyun Joo Heo.
Study flowchart. COVID-19: coronavirus disease 2019, CV-related HZ: coronavirus disease 2019 vaccination-related herpes zoster.
Recovery time for herpes zoster. The recovery rates within 8 weeks in the CV-related HZ and control groups are 85.7% and 68.0%, respectively. CV-related HZ: coronavirus disease 2019 vaccination-related herpes zoster.
Demographic Data and Characteristics of Herpes Zoster-related Data
Variable | CV-related HZ (n = 14) | Control (n = 28) | P value |
---|---|---|---|
Demographic data | |||
Age (yr) | 52.0 (30.8, 62.3) | 66.5 (54.3, 78.8) | 0.005 |
Sex, M/F | 6 (42.9)/8 (57.1) | 11 (39.3)/17 (60.7) | 0.824 |
Medical history | |||
Total | 9 (64.3) | 20 (71.4) | 0.447 |
Cardiovascular | 3 (21.4) | 12 (42.9) | |
Endocrine | 3 (21.4) | 8 (28.6) | |
Pulmonary | 1 (7.1) | 2 (7.1) | |
Nephrotic | 0 (0.0) | 2 (7.1) | |
Cerebrovascular | 0 (0.0) | 5 (17.9 | |
Allergy | 3 (21.4) | 3 (10.7) | |
Malignant | 0 (0.0) | 4 (14.3) | |
Characteristics of herpes zoster | |||
Prodromal pain | 9 (64.3) | 17 (60.7) | 0.822 |
Interval between prodromal pain and rash (d) | 3.0 (0.0, 4.0) | 3.0 (0.0, 4.75) | 0.661 |
Pain score, NRS | |||
Initial pain | 3.0 (3.0, 4.0) | 4.0 (3.0, 4.0) | 0.843 |
Peak pain | 4.0 (3.0, 4.3) | 4.0 (3.3, 5.0) | 0.535 |
Location | |||
Cranial | 2 (14.3) | 4 (14.3) | 0.689 |
Cervical | 2 (14.3) | 2 (7.1) | 0.407 |
Thoracic | 9 (64.3) | 18 (64.3) | 0.629 |
Lumbar | 1 (7.1) | 1 (3.6) | 0.561 |
Sacral | 0 (0.0) | 3 (10.7) | 0.285 |
Patients number | 14 | 25 |
|
Treatment | |||
Antiviral agents | 14 (100) | 25 (100) | |
Anticonvulsants | 12 (85.7) | 22 (88.0) | 0.600 |
Nerve block | 6 (42.9) | 11 (44.0) | 0.945 |
Recovery time (wk) | |||
1–4 | 8 (57.1) | 10 (40.0) | 0.303 |
5–8 | 4 (28.6) | 7 (28.0) | 0.624 |
8–12 | 2 (14.3) | 3 (12.0) | 0.600 |
> 12 | 0 (0.0) | 5 (20.0) | 0.092 |
Postherpetic neuralgia | 0 (0.0) | 5 (20.0) | 0.092 |
Values are presented as median (1Q, 3Q) or number (%). CV-related HZ: coronavirus disease 2019 vaccination-related herpes zoster, NRS: numerical rating scale.
Three patients were excluded: one patient was transferred to another hospital, one was lost to follow-up, and one was transferred to the emergency room at the second visit due to a high fever.
Characteristics of Vaccination-related Herpes Zoster (n = 14)
Characteristics | ||
---|---|---|
Vaccine and dose | 1st dose | 2nd dose |
Pfizer | 2 | 3 |
Moderna | 1 | 4 |
AstraZeneca | 1 | 3 |
Time of symptom onset after vaccination | ||
1 - 21 days | 9 (64.3) | |
22 - 42 days | 5 (35.7) |
Values are presented as number (%).
Characteristics of Patients with COVID-19 Vaccination-related Herpes Zoster and Herpes Zoster-associated Data
Characteristics | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Variable | Age (yr) | Sex, M/F | COVID-19 vaccination |
Time interval of HZ onset after vaccination (d) | Comorbidities | |||||||||
Types | Dose | |||||||||||||
Patient 1 | 30 | F | Pfizer | 1st | 31 | Food allergy | ||||||||
Patient 2 | 71 | M | AstraZeneca | 2nd | 1 | Hypertension, type 2 diabetes, gastrectomy | ||||||||
Patient 3 | 63 | F | AstraZeneca | 1st | 1 | Nontoxic goiter | ||||||||
Patient 4 | 57 | F | Moderna | 2nd | 28 | None | ||||||||
Patient 5 | 21 | F | Pfizer | 2nd | 33 | Atopic dermatitis, appendectomy | ||||||||
Patient 6 | 54 | M | Moderna | 2nd | 2 | Atrial fibrillation, appendectomy | ||||||||
Patient 7 | 59 | M | Moderna | 2nd | 30 | None | ||||||||
Patient 8 | 50 | M | Moderna | 2nd | 12 | Asthma | ||||||||
Patient 9 | 31 | M | Pfizer | 1st | 6 | Mite allergy | ||||||||
Patient 10 | 66 | F | AstraZeneca | 2nd | 33 | Angina | ||||||||
Patient 11 | 62 | F | AstraZeneca | 2nd | 5 | Gastrointestinal disease, hyperlipidemia | ||||||||
Patient 12 | 50 | M | Moderna | 1st | 10 | Type 2 diabetes, hyperlipidemia | ||||||||
Patient 13 | 28 | F | Pfizer | 2nd | 14 | None | ||||||||
Patient 14 | 32 | F | Pfizer | 2nd | 3 | None | ||||||||
Herpes zoster-associated data |
||||||||||||||
Variable | Interval between prodromal pain and rash (d) | Pain score, NRS (0–10) |
Skin lesion severity | Location | HZ treatment |
|||||||||
Initial | Peak | Antiviral agents | Anticonvulsants | Antidepressants | Nerve blocks | |||||||||
Patient 1 | 4 | 3 | 3 | Mild | T1, T2 | + | + | – | – | |||||
Patient 2 | 0 | 3 | 3 | Mild | T10 | + | + | + | + | |||||
Patient 3 | 3 | 6 | 6 | Mild | L4, L5 | + | + | + | + | |||||
Patient 4 | 4 | 3 | 3 | Mild | T6, T7 | + | + | + | + | |||||
Patient 5 | 0 | 4 | 4 | Severe | T7, T8 | + | + | + | + | |||||
Patient 6 | 0 | 3 | 3 | Mild | T10 | + | + | – | + | |||||
Patient 7 | 0 | 3 | 3 | Mild | V1 | + | + | – | – | |||||
Patient 8 | 0 | 4 | 4 | Mild | C2 | + | + | – | – | |||||
Patient 9 | 4 | 3 | 3 | Mild | V1 | + | + | + | + | |||||
Patient 10 | 4 | 4 | 4 | Mild | T10, T11 | + | – | – | – | |||||
Patient 11 | 7 | 4 | 4 | Mild | T6, T8 | + | + | – | – | |||||
Patient 12 | 3 | 2 | 2 | Mild | T11 | + | + | – | – | |||||
Patient 13 | 4 | 5 | 5 | Mild | T5 | + | + | + | – | |||||
Patient 14 | 2 | 3 | 3 | Mild | C3 | + | – | – | – |
HZ: herpes zoster, NRS: numerical rating scale, COVID-19: coronavirus disease 2019.
Characteristics of Patients with Postherpetic Neuralgia
Variable | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 |
---|---|---|---|---|---|
Age (yr) | 73 | 66 | 58 | 82 | 64 |
Sex, M/F | M | F | F | F | M |
COVID-19 vaccination, yes/no | Yes | No | No | No | No |
(AstraZeneca 1st dose) | |||||
60 | |||||
Time interval of HZ onset after vaccination (d) | |||||
Comorbidities | Hypertension, asthma | Osteoporosis | Breast and thyroid cancers | Diabetes, cerebral infarction, dementia | Hypertension, diabetes |
Interval between prodromal pain and rash (d) | 5 | 0 | 0 | 0 | 7 |
Pain score, initial/peak/PHN pain, | 3/4/2 | 5/5/2 | 4/4/3 | 3/4/2 | 4/5/4 |
NRS (0–10) | |||||
Skin lesion severity | Severe | Moderate | Severe | Severe | Severe |
Location | C3, C4, Lt | T3, T4, Lt | T3, T4, Rt | T4, T5, Lt | S1, S2, Rt |
HZ treatment | |||||
Antiviral agents | + | + | + | + | + |
Anticonvulsants | + | + | + | + | + |
Antidepressants | + | – | + | – | + |
Nerve blocks | + | – | – | + | + |
HZ: herpes zoster, PHN: postherpetic neuralgia, COVID-19: coronavirus disease 2019, NRS: numerical rating scale, Lt: left, Rt: right.