# **LETTERS TO THE EDITOR**

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# **Cutaneous reactions after COVID-19 vaccination: A single-center retrospective study in China with 61 cases**

### To the Editor:

As the mass vaccination strategies had been carried, cutaneous adverse reactions to COVID-19 vaccines have been progressively reported. But previous studies were mainly about mRNA vaccines and the cutaneous reactions of Chinese people to the CoronaVac or ZF2001 vaccines were rarely reported.

In this letter, we report a case series of 61 patients who developed cutaneous reaction after CoronaVac or ZF2001 COVID-19 vaccination from a single center between May 1 and November 30, 2021.

The age of 61 patients ranged from 18 to 71 years, and the median age was 30 (23–41.5) years. Out of the 61 patients, who were all yellow race, the vast majority (62.3%) were females (Table [S1](#page-2-0)). About half of the patients (50.8%) were healthy (Table [S2](#page-2-0)), and the rest reported suffering from allergic or chronic diseases without significant difference between females and males. There were 6 patients lost to follow-up, and 55 patients completed the follow-up. Of the 55 patients, 10 suspended their vaccination course due to concerns about the skin side effects, including 5 patients injected only one dose and 5 patients injected two doses. Actually, expect the 5 patients just mentioned, there are another 12 injected two doses, because it is not yet the time that they should injected the third dose when we called them at the last time. Forty-four patients developed cutaneous reactions only once, and only 11 patients suffered cutaneous reactions twice or thrice. (Figure [S1B](#page-2-0)).

A broad spectrum of reactions after vaccination were observed. The local reactions were most common, followed by urticarial eruptions, morbilliform rash, psoriatic lesions, herpes, pityriasis rosea-like reactions, acne-like reactions, dermatomyositis, and atopic dermatitis. (Figure [S2](#page-2-0)). All patients' conditions were improved after receiving the traditional treatment, including antihistamine, antiviral, glucocorticoid, glycyrrhizin, and Chinese patent medicine. Otherwise, one urticaria case and two worsening psoriasis cases received biologics to treat. In our study, alopecia areata was not observed, while others reported alopecia areata following SARS-CoV-2 vaccination.[1](#page-2-1)

It is worth noting that there are significant differences in types of cutaneous reactions and duration time between males and females (Table [1](#page-1-0) and Table [2](#page-1-1)). Females (68.4%) are more likely to suffer local reactions compared to males (17.4%), while males (17.4%) were significantly more affected by psoriasis than females (0%). Besides, the cutaneous reactions of males are more diverse. The females only reported five kinds of reactions while males reported nine kinds. In our report, males (36.4%) were more likely to experience initial cutaneous reactions to the third dose, compared to females (4.5%). A majority (74.6%) of patients experienced cutaneous symptoms within 3 days, with no significant difference across gender groups in terms of reaction time. With regard to duration time, females (60.6%) were more likely to resolve within 7 days compared to males (27.3%). All nine patients reported chronic course were males, who experienced urticaria, psoriasis, dermatomyositis, or atopic dermatitis over 3 months (Figure [S1C](#page-2-0)). The gender difference of cutaneous reactions after COVID-19 vaccination has also been noted by other scholars. In a multicenter study involving 2097 individuals received the CoronaVac vaccine conducted in Turkey, systemic reactions and local injection site reactions were statistically significantly higher in women.[2](#page-2-2) This gender-related difference may relate to be that men and women differ in their innate, humoral, and cell-mediated responses to viral vaccines.[3](#page-2-3)

The most frequently reported patterns in each vaccine group were local reaction (ZF2001, 69.0%) and morbilliform (CoronaVac, 31.6%). Out of 61 patients, the most common reaction is local reaction, which also named COVID-ARM.[4](#page-2-4) Compared with results of others,[5](#page-2-5) our patients (86.7%) occurred local reaction more quickly (3 days) (Figure [S1C](#page-2-0),D). Morbilliform rash is regarded as the initial manifestation of COVID-19[6](#page-2-6) ; Morbilliform reaction after injecting CoronaVac (inactivated vaccines) seems to resemble COVID-19 skin manifestations.[7](#page-2-7) By contrast, local reaction seems an allergic reaction. So, we speculate the types of vaccines maybe the reason of different reactions (Table [2](#page-1-1)).

In summary, the most common cutaneous reaction in our study was local reaction, which is also the most common in females and ZF2001 group. Urticaria rash was most frequently reported in males, and morbilliform rash was the most common in CoronaVac group. Totally, most cutaneous reactions after vaccination are mild, and a large proportion of patients could resolve through conventional therapy within 7–14 days. This study may help physicians to provide relevant advice for vaccine counseling and to treat cutaneous reactions.

This is an open access article under the terms of the [Creative Commons Attribution](http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

© 2022 The Authors. *Journal of Cosmetic Dermatology* published by Wiley Periodicals LLC.

**368 |** LETTERS TO THE EDITOR



| | TABLE 1 Differences in cutaneous reactions between males and females. | |
|--|-----------------------------------------------------------------------|--|
|--|-----------------------------------------------------------------------|--|

| Variable | Outcome | Male | Female | Total | p Value |
|-----------------------------|-------------------|-----------|-----------|-----------|---------|
| Cutaneous Reactions | Local Reaction | 4(17.4%) | 26(68.4%) | 30(49.2%) | <0.001 |
| | Urticaria | 5(21.7%) | 5(13.2%) | 10(16.4%) | 0.481* |
| | Morbilliform | 2(8.7%) | 5(13.2%) | 7(11.5%) | 0.700* |
| | Herpes | 4(17.4%) | 1(2.6%) | 5(8.2%) | 0.062* |
| | Psoriasis | 4(17.4%) | 0(0%) | 4(6.6%) | 0.017* |
| | Acne | 1(4.3%) | 0(0%) | 1(1.6%) | 0.377* |
| | Pityriasis Rosea | 1(4.3%) | 1(2.6%) | 2(3.3%) | 1.000* |
| | Dermatomyositis | 1(4.3%) | 0(0%) | 1(1.6%) | 0.377* |
| | Atopic Dermatitis | 1(4.3%) | 0(0%) | 1(1.6%) | 0.377* |
| | Total | 23(37.7%) | 38(62.3%) | 61(100%) | <0.001* |
| Reaction Time | 3 day | 14(66.7%) | 30(78.9%) | 44(74.6%) | 0.234 |
| | 7 day | 4(9.5%) | 6(15.8%) | 10(13.6%) | 0.476* |
| | >7 day | 5(21.7%) | 2(5.3%) | 7(11.5%) | 0.093* |
| | Total | 23(37.7%) | 38(62.3%) | 61(100%) | 0.119* |
| Duration Time | 7 days | 6(27.3%) | 20(60.6%) | 26(47.3%) | 0.015 |
| | 14 days | 6(27.3%) | 10(30.3%) | 16(29.1%) | 0.808 |
| | >14 days | 2(9.1%) | 3(9.1%) | 5(9.1%) | 1.000* |
| | Chronic Course | 8(36.4%) | 0(0%) | 8(16.4%) | <0.000* |
| | Total | 22(40.0%) | 33(60.0%) | 55(100%) | 0.007* |
| Initial Cutaneous Reactions | First Dose | 5(15.2%) | 8(36.4%) | 13(23.6%) | 0.070 |
| | Second Dose | 16(48.5%) | 13(59.1%) | 29(52.7%) | 0.440 |
| | Third Dose | 12(36.4%) | 1(4.5%) | 13(23.6%) | 0.007 |
| | Total | 33(60.0%) | 22(40.0%) | 55(100%) | 0.025 |

*Note*: The data based on the situation at the time of the patients' visit. Chi-squared test and Fisher's exact test (\*) used with a significance level (*p* Value) of ≤0.05.

**TABLE 2** Dermatologic findings reported after the CoronaVac or ZF2001 COVID-19 vaccines.

| Characteristic | Outcome | CoronaVac | ZF2001 | Total | p Value |
|---------------------|-------------------|-----------|-----------|-----------|---------|
| Cutaneous Reactions | Local reaction | 1(5.3%) | 29(69.0%) | 30(49.2%) | <0.001 |
| | Urticaria | 3(15.8%) | 7(16.7%) | 10(16.4%) | 1.000* |
| | Morbilliform | 6(31.6%) | 1(2.4%) | 7(11.5%) | 0.003* |
| | Psoriasis | 3(15.8%) | 1(2.4%) | 4(6.6%) | 0.085* |
| | Herpes | 3(15.8%) | 2(4.8%) | 5(8.2%) | 0.313* |
| | Acne | 1(5.3%) | 0(0%) | 1(1.6%) | 0.311* |
| | Pityriasis Rosea | 1(5.3%) | 1(2.4%) | 2(3.3%) | 1.000* |
| | Dermatomyositis | 1(5.3%) | 0(0%) | 1(1.6%) | 1.000* |
| | Atopic Dermatitis | 0(0%) | 1(2.4%) | 1(1.6%) | 1.000* |
| | Total | 19(31.1%) | 42(69.9%) | 61(100% | <0.001* |

*Note*: Chi-squared test and Fisher's exact test (\*) used with a significance level (*p* Value) of ≤0.05.

# **AUTHOR CONTRIBUTIONS**

Qian Li, Qing Li, and Y.L. designed this research. Qing Li and Y.S. did the work of literature search. Qing Li and Qian Li performed the research. Qing Li, Qian Li, Y.S, S.S., H.H, L.L., and Y.M. did the work of data acquisition. Qing Li, Qian Li, S.S., and Y.L. analyzed the data. Qing Li wrote the paper. Qian Li and Y.L. revised and polished the paper. All authors have read and approved the final manuscript.

## **FUNDING INFORMATION**

None.

## **CONFLICT OF INTEREST**

No potential conflict of interest was reported by the author.

#### **PATIENTS CONSENT**

The patients in this manuscript have given oral informed consent to the publication of their case details.

## **DATA AVAILABILITY STATEMENT**

The data that support the findings of this study are available from the corresponding author upon reasonable request.

#### **ETHICAL APPROVAL**

Ethical approval of the study was granted by the Hebei Medical University Third Affiliated Hospital Research Ethics Committee (2022-012-1).

> Qing Li MBBS Yaqiong Shi MM Shaomin Shi MD Huanrong Hu MM Lichao Liu MM Yan Mao MM Yaling Liu PhD Qian Li MD

*Department of dermatology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, China*

#### **Correspondence**

Yaling Liu and Qian Li, Department of Hebei Medical University Third Affiliated Hospital, 139 Ziqiang Street, Shijiazhuang 050011, China.

Email: [yzling\\_liu1214@126.com](mailto:yzling_liu1214@126.com) and [lqflying1986@163.com](mailto:lqflying1986@163.com)

#### **ORCID**

*Yaling Li[u](https://orcid.org/0000-0003-4321-399X)* <https://orcid.org/0000-0003-4321-399X>

### **REFERENCES**

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- 2. Cebeci Kahraman F, Savas Erdogan S, Aktas ND, et al. Cutaneous reactions after COVID-19 vaccination in Turkey: a multicenter study. *J Cosmet Dermatol*. 2022;21(9):3692-3703. doi[:10.1111/](https://doi.org//10.1111/jocd.15209) [jocd.15209](https://doi.org//10.1111/jocd.15209)
- 3. Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. *Lancet Infect Dis*. 2010;10(5):338-349. doi:[10.1016/](https://doi.org//10.1016/s1473-3099(10)70049-9) [s1473-3099\(10\)70049-9](https://doi.org//10.1016/s1473-3099(10)70049-9)
- 4. Bogdanov G, Bogdanov I, Kazandjieva J, Tsankov N. Cutaneous adverse effects of the available COVID-19 vaccines. *Clin Dermatol*. 2021;39(3):523-531. doi[:10.1016/j.clindermatol.2021.04.001](https://doi.org//10.1016/j.clindermatol.2021.04.001)
- 5. McMahon DE, Amerson E, Rosenbach M, et al. Cutaneous reactions reported after moderna and Pfizer COVID-19 vaccination: a registry-based study of 414 cases. *J Am Acad Dermatol*. 2021;85(1):46-55. doi:[10.1016/j.jaad.2021.03.092](https://doi.org//10.1016/j.jaad.2021.03.092)
- 6. Kulkarni RB, Lederman Y, Afiari A, Savage JA, Jacob J. Morbilliform rash: an uncommon herald of SARS-CoV-2. *Cureus*. 2020;12(7):e9321. doi[:10.7759/cureus.9321](https://doi.org//10.7759/cureus.9321)
- 7. Bellinato F, Maurelli M, Gisondi P, Girolomoni G. Cutaneous adverse reactions associated with SARS-CoV-2 vaccines. *J Clin Med*. 2021;10(22):5344. doi[:10.3390/jcm10225344](https://doi.org//10.3390/jcm10225344)

# **SUPPORTING INFORMATION**

Additional supporting information can be found online in the Supporting Information section at the end of this article.

Journal of Cosmetic Dermatology

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Cutaneous reactions after <scp>COVID</scp>‐19 vaccination: A single‐center retrospective study in China with 61 cases

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What was studied

Key findings

Study limitations

Clinical implications

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