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Table 1 Characteristics of the included observational studies with their main findings

From: Herpesviruses reactivation following COVID-19 vaccination: a systematic review and meta-analysis

ID

Author

Year

Country

Type of study (Registry/ Duration)

Population

Total patients

Vaccine

Reactivated virus

Main findings

1

Birabaharan, M

2022

USA

Retrospective cohort (TriNetX/ December 15, 2020 and July 15, 2021)

Patients aged > 18 years who received the mRNA COVID-19 vaccine either as the first or as the second dose

1,306,434

mRNA based

VZV

1- Incidence of VZV reactivation after 28 days of COVID-19 vaccination = 0.1% (1228 of 1,306,434 patients)

2- After matching for baseline variables, there were no significant difference between those who received mRNA COVID-19 vaccine and controls

2

Català, A

2022

Spain

Nationwide, multicenter, cross-sectional observational study (16 February–15 May 2021)

People of any age with any skin reactions within 21 days after any dose of a vaccine

405

BNT162b2, AZD1222

VZV, HSV

1- Among cutaneous reactions, VZV, n = 41 (10.1%); and herpes simplex virus (HSV), n = 15 (3.7%) were present

2- Varicella-zoster virus reactivation was among the most reported cutaneous reactions

3

Cebeci Kahraman, F

2022

Turkey

Prospective, cross- sectional study (15 April and 15 July 2021)

Patients aged over 18 years, who presented to dermatology or emergency outpatient clinics after having been vaccinated after either the first or second dose

2290

CoronaVac, BioNTech vaccine

VZV, HSV

1- Herpes zoster among those who received the first n = 9 (0.4%) and second dose n = 10 (0.5%) of CoronaVac;

2- Herpes zoster among those who received the first dose n = 8 (4.4%) of BioNTech vaccine;

3- Triggering of herpes simplex [n = 90 (4.3%) for CoronaVac and n = 9 (4.9%) for BioNTech]

4

Hertel, M

2022

Germany

Retrospective cohort (TriNetX/ 25 November 2021 to 2y backwards

1- Individuals who had received at least one mRNA or adenovirus vector-based COVID-19 vaccine,

2- Those who were not vaccinated against COVID-19

2,190,172

BNT162b2, mRNA-1273, Ad26.COV2.S

VZV

1- 2204 patients developed HZ within 60 days of COVID-19 vaccination;

2- The risk ratio and odds ratio were 1.802 (95% confidence interval [CI] = 1.680; 1.932) and 1.804 (95% CI = 1.682; 1.934) when compared to those not received

5

Lee, T. J

2022

Taiwan

Retrospective cohort (center-based, July 2021 and September 2021)

Patients receiving at least one dose of primary SARS-CoV- 2 vaccine

265

AZD1222, mRNA-1273

VZV

1- Herpes zoster reactivation occurred in 10 patients among mRNA-1273 group versus none in AZD1222 group (6.2% vs 0%, p value = 0.019)

2- Nine patients experienced the first herpes zoster event in their lives

6

Préta, L. H

2022

France

Case/non-case statistical approach (VigiBase up to 30 June 202)

Patients received mRNA COVID-19 vaccines

716 928

BNT162b2 and mRNA-1273

VZV

1- 5931 HZ cases with BNT162b2 and 1797 with mRNA-1273;

2- mRNA COVID-19 vaccines were associated with an increased HZ reporting for BNT162b2 (ROR 2.0, 95% CI 1.8–2.2), mRNA-1273 (ROR 1.5, 95% CI 1.2–1.8) and overall (ROR 1.9, 95% CI 1.8–2.1) compared with those who received influenza vaccine;

3- Reduced risk among younger patients (ROR 0.39, 95% CI 0.36–0.41)

7

Machado, P. M

2022

EULAR Coronavirus Vaccine (COVAX) registry

Cohort from 5 February 2021 to 27 July 2021

Patients vaccinated against SARS-CoV- 2

5121

Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna

VZV

1- 10 HZ cases during the cohort

8

Gringeri, M

2022

U.S. Vaccine Adverse Event Reporting System database

Cohort from 12/13/2020 and 12/03/2021

Patients vaccinated against SARS-CoV- 2

588,323

Pfizer: 548,578,240; Moderna: 361,897,609; Janssen: 33,849,124

VZV, HSV

Out of the 6,195 cases examined in the study, consisting of 5,934 cases of herpes zoster and 273 cases of herpes simplex, more than 90% were classified as non-serious. The analysis revealed a slightly increased likelihood of reporting both herpes zoster (with a relative reporting odds ratio of 1.49) and herpes simplex (with a relative reporting odds ratio of 1.51) infections following vaccination with the Pfizer–BioNTech vaccine. The estimated incidence rates for herpes zoster and herpes simplex were approximately 0.7 per 100,000 and 0.03 per 100,000 cases, respectively

9

Florea, A

2023

Kaiser Permanente Southern California (KPSC)

Cohort from 12/2020–05/2021

Patients vaccinated against SARS-CoV- 2

2,107,823

mRNA-1273 and BNT162b2

VZV

The study cohort consisted of 1,052,362 recipients of the mRNA-1273 vaccine, 1,055,461 recipients of the BNT162b2 vaccine, and 1,020,334 individuals in the comparison group. When compared to individuals who were not vaccinated, the adjusted hazard ratio (aHR) for herpes zoster (HZ) within 90 days after receiving the second dose of the mRNA-1273 vaccine was 1.14 (with a confidence interval of 1.05–1.24), and for the BNT162b2 vaccine, it was 1.12 (with a confidence interval of 1.03–1.22). Among individuals aged 50 years and above who had not received the zoster vaccine, the aHR was also elevated after the second dose of the mRNA-1273 vaccine (1.18 with a confidence interval of 1.06–1.33) and the BNT162b2 vaccine (1.15 with a confidence interval of 1.02–1.29) compared to unvaccinated individuals

10

Fathy, R. A

2022

USA

Cohort as of April 2021

Patients vaccinated against SARS-CoV- 2

588,323

Moderna or the Pfizer–BioNTech

VZV, HSV

Out of 40 reactivated cases, 35 were VZV and 5 were HSV

11

Chen, J

2023

China

Cross‐sectional survey

Autoimmune inflammatory rheumatic diseases vaccinated against SARS-CoV- 2

636

Sinopharm (Vero Cell), Sinovac COVID‐19 Vaccine (Vero Cell), Sinopharm/WIBP, CanSinoBio, Zhifei Longcom, KCONECAVAC

VZV

11 cases with HZ