10.5826/dpc.1303a145
Introduction: Based on the existing literature, omalizumab (OMZ) is considered a safe treatment modality in chronic spontaneous urticaria (CSU) during the coronavirus disease 19 (COVID-19) era. 
Objectives: The aim of this study is to evaluate the effects of OMZ on CSU patients regarding COVID-19 infection.
Methods: In this retrospective study, files of CSU patients using OMZ during the COVID-19 pandemic were reviewed in terms of demographic features, medical history including COVID-19 vaccination status, clinical characteristics, pretreatment laboratory parameters, duration, and dosing regimen of OMZ treatment. Patients with a history of COVID-19 infection while on OMZ therapy and patients without COVID-19 history were compared with respect to these parameters. The urticaria activations following COVID-19 infection or vaccination were also recorded.
Results: Sixty-eight patients with CSU (female:male ratio= 1.8:1; mean age=  47.2 ± 15.1 years) continued to receive OMZ treatment. The median duration of OMZ treatment was 12 months (range: 6-60). Twelve patients (17.6%) were diagnosed with COVID-19 showing no exacerbation in urticaria. The duration of OMZ treatment was significantly higher in the group with COVID-19 infection history compared to patients with no history of COVID-19 (p=0.01). Among 51 patients (75%) vaccinated against COVID-19, urticaria activation occurred in four patients without any recurrence following booster vaccinations.
Conclusions: Considering the likelihood of increased COVID-19 infection risk in the setting of long-term OMZ in CSU patients, the duration of OMZ therapy might be kept at a minimum, or a temporary interruption of the treatment period might be preferred, particularly in high-risk patients regarding COVID-19.
text/xml
2160-9381
2912
en
Sevgi Öztürk
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
activation
Long-term Omalizumab Therapy in Patients with Chronic Spontaneous Urticaria: Does it Increase the Risk of COVID-19?
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-07-31
2022-10-15
2023-07-31
2023-08-24
e2023145
Dermatol Pract Concept
Introduction: Based on the existing literature, omalizumab (OMZ) is considered a safe treatment modality in chronic spontaneous urticaria (CSU) during the coronavirus disease 19 (COVID-19) era. 
Objectives: The aim of this study is to evaluate the effects of OMZ on CSU patients regarding COVID-19 infection.
Methods: In this retrospective study, files of CSU patients using OMZ during the COVID-19 pandemic were reviewed in terms of demographic features, medical history including COVID-19 vaccination status, clinical characteristics, pretreatment laboratory parameters, duration, and dosing regimen of OMZ treatment. Patients with a history of COVID-19 infection while on OMZ therapy and patients without COVID-19 history were compared with respect to these parameters. The urticaria activations following COVID-19 infection or vaccination were also recorded.
Results: Sixty-eight patients with CSU (female:male ratio= 1.8:1; mean age=  47.2 ± 15.1 years) continued to receive OMZ treatment. The median duration of OMZ treatment was 12 months (range: 6-60). Twelve patients (17.6%) were diagnosed with COVID-19 showing no exacerbation in urticaria. The duration of OMZ treatment was significantly higher in the group with COVID-19 infection history compared to patients with no history of COVID-19 (p=0.01). Among 51 patients (75%) vaccinated against COVID-19, urticaria activation occurred in four patients without any recurrence following booster vaccinations.
Conclusions: Considering the likelihood of increased COVID-19 infection risk in the setting of long-term OMZ in CSU patients, the duration of OMZ therapy might be kept at a minimum, or a temporary interruption of the treatment period might be preferred, particularly in high-risk patients regarding COVID-19.
Sevgi Öztürk
2023/07/31
10.5826/dpc.1303a145
e2023145
Department of Dermatology and Venereology, Çanakkale Onsekiz Mart University Faculty of Medicine, Çanakkale, Turkey
2160-9381
activation
en
e2023145
Parohan M, Yaghoubi S, Seraji A, Javanbakht MH, Sarraf P, Djalali M. Risk factors for mortality in patients with Coronavirus disease 2019 (COVID-19) infection: a systematic review and meta-analysis of observational studies. Aging Male. 2020;23(5):1416-1424. DOI: 10.1080/13685538.2020.1774748. PMID: 32508193.
Long-term Omalizumab Therapy in Patients with Chronic Spontaneous Urticaria: Does it Increase the Risk of COVID-19?
https://dpcj.org/index.php/dpc/article/download/2912/2209
    Long-Term Omalizumab Therapy in Patients with
    Chronic Spontaneous Urticaria: Does it Increase
                the Risk of COVID-19?
 Özge Kaya1, Zeynep Keskinkaya1, Selda Işık Mermutlu1 ,Sevilay Oğuz Kılıç1, Sevgi Öztürk1


1 Department of Dermatology and Venereology, Çanakkale Onsekiz Mart University Faculty of Medicine, Çanakkale, Turkey



Key words: angiotensin-converting enzyme 2, chronic spontaneous urticaria, COVID-19, omalizumab, activation
Citation: Kaya Ö, Keskinkaya Z, Işık Mermutlu S, Oğuz Kılıç S, Öztürk S. Long-term omalizumab therapy in patients with chronic
spontaneous urticaria: Does it increase the risk of COVID-19?. Dermatol Pract Concept. 2023;13(3):e2023145.
DOI: https://doi.org/10.5826/dpc.1303a145
Accepted: December 2, 2022; Published: July 2023
Copyright: ©2023 Kaya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Özge Kaya, MD , Çanakkale Onsekiz Mart Üniversitesi Tıp Fakültesi Deri ve Zührevi Hastalıklar Anabilim Dalı,
17110, Çanakkale, Türkiye Tel: +0902862635950 Fax: +0902862635956 E-mail: ozgetrkz@hotmail.com




                       Introduction: Based on the existing literature, omalizumab (OMZ) is considered a safe treatment
  ABSTRACT
                       modality in chronic spontaneous urticaria (CSU) during the coronavirus disease 19 (COVID-19) era.
                       Objectives: The aim of this study is to evaluate the effects of OMZ on CSU patients regarding
                       COVID-19 infection.
                       Methods: In this retrospective study, files of CSU patients using OMZ during the COVID-19 pandem-
                       ic were reviewed in terms of demographic features, medical history including COVID-19 vaccination
                       status, clinical characteristics, pretreatment laboratory parameters, duration, and dosing regimen of
                       OMZ treatment. Patients with a history of COVID-19 infection while on OMZ therapy and patients
                       without COVID-19 history were compared with respect to these parameters. The urticaria activations
                       following COVID-19 infection or vaccination were also recorded.
                       Results: Sixty-eight patients with CSU (female:male ratio = 1.8:1; mean age = 47.2 ± 15.1 years) con-
                       tinued to receive OMZ treatment. The median duration of OMZ treatment was 12 months (range:
                       6-60). Twelve patients (17.6%) were diagnosed with COVID-19 showing no exacerbation in urticaria.
                       The duration of OMZ treatment was significantly higher in the group with COVID-19 infection his-
                       tory compared to patients with no history of COVID-19 (P = 0.01). Among 51 patients (75%) vacci-
                       nated against COVID-19, urticaria activation occurred in 4 patients without any recurrence following
                       booster vaccinations.




Original Article | Dermatol Pract Concept. 2023;13(3):e2023145                                                                       1
                     Conclusions: Considering the likelihood of increased COVID-19 infection risk in the setting of long-
                     term OMZ in CSU patients, the duration of OMZ therapy might be kept at a minimum, or a tempo-
                     rary interruption of the treatment period might be preferred, particularly in high-risk patients regard-
                     ing COVID-19.




Introduction                                                      laboratory findings (including pre-treatment Ig-E levels and
                                                                  blood eosinophil counts), OMZ treatment duration and dos-
    Chronic spontaneous urticaria (CSU) is a disease last-        ing frequency. The disease activity was evaluated with urti-
ing more than six weeks and characterized by recurrent            caria activity score 7 (UAS7) [1,2]. The rate of COVID-19
erythematous, indurated lesions. Infections, drugs, and           infection in patients during OMZ therapy was recorded.
vaccines are possible triggers that may cause CSU exac-           Patients with a history of COVID-19 infection while on
erbations. The current CSU management guideline rec-              OMZ therapy and patients without COVID-19 history were
ommends non-sedative antihistamines in standard or                compared with respect to the parameters mentioned above.
up to 4-fold higher dosages as the first-line treatment.          Moreover, urticaria exacerbations following COVID-19 and
In refractory cases, the anti-immunoglobulin E (anti-IgE)         COVID-19 vaccines were noted.
antibody omalizumab (OMZ) is the therapy of choice [1,2].            The Kolmogorov-Smirnov test was used to verify the
    Coronavirus disease 2019 (COVID-19) had significant           normality of the distribution of continuous variables which
impacts on general health practices. Several cases of urticaria   were expressed as mean ± standard deviation (SD) or median
triggered by COVID-19 or the vaccines developed against           (min-max) in the presence of abnormal distribution, and cat-
the virus have recently been reported [3-5].                      egorical variables were expressed as percentages. Compari-
    CSU adversely affects the quality of life of the patients     sons between the groups were made by using chi-square or
[1,2]. Moreover, patients with treatment-resistant CSU may        Fisher exact test for categorical variables, independent sam-
be concerned about the reactivation of their disease. For this    ples t-test for normally distributed continuous variables, and
reason, they may refrain from the newly developed thera-          Mann-Whitney U test when the distribution was skewed.
peutic options. At the beginning of the COVID-19 pandemic,        A P -value less than 0.05 was considered statistically signif-
many patients even considered discontinuing their regular         icant. All statistical procedures were performed using SPSS
medications due to possible immunosuppression. A similar          software version 14.0 (SPSS Inc.).
situation was observed for OMZ treatment, which has no               The Ethics Committes of 18 Mart University approved
immunosuppressive effect.                                         the study with the decision number 2022/14-09.


Objectives                                                        Results
    In this study, we aimed to investigate the effect of OMZ         A total of 68 patients with CSU continued to receive
treatment on CSU patients regarding COVID-19 incidence            OMZ treatment during the study period. The demographic
and prognosis.                                                    and clinical characteristics of patients are summarized in
                                                                  Table 1. The female: male ratio was 1.8:1, while the mean

Methods                                                           age of the patients was 47.2 ± 15.1 years.
                                                                     Urticaria was accompanied by angioedema in 25 patients
    In this retrospective cohort study, CSU patients who          (36.8%). The median IgE level measured prior to OMZ
were followed up in a tertiary referral center and used at        treatment was 281 kU/L (range: 2-2730). Pre-treatment
least six months OMZ therapy between April 2020 and               eosinophilia was detected in six patients (9%).
April 2022 were assessed. Patients under the age of 18 and           The median duration of OMZ treatment was 12 months
those receiving OMZ treatment for less than six months            (range: 6-60). A standard dose regimen (300 mg every four
were excluded.                                                    weeks subcutaneously) was initiated for all patients, while
    The medical files of the patients were evaluated regarding    two patients required a reduction in dosing intervals (300 mg
demographic characteristics (gender, age), medical history        every two weeks). An oral H1-antihistamine was required in
(comorbidities, concomitant treatments including antihis-         addition to OMZ in 24 patients (35.3%) to maintain the
tamines, COVID-19 vaccination status), clinical features          disease control. The most commonly used H1-antihistamine
(presence of urticaria, angioedema or both, disease activity),    was levocetirizine (N = 17, 70.8%).



2                                                                     Original Article | Dermatol Pract Concept. 2023;13(3):e2023145
                Table 1. Demographic and clinical characteristics of the chronic spontaneous
                             urticaria patients using omalizumab treatment.
                                             Characteristics
 Number of patients, N (%)                                                                                 68 (100%)
 Gender, N (%)
    Female                                                                                                 44 (64.7)
 Age (years), mean ±SD                                                                                     47.2±15.1
 Comorbidities                                                                                               4 (5.8)
 Hypothyroidism                                                                                              2 (2.9)
 Hypertension                                                                                                1 (1.5)
 Depression                                                                                                  1 (1.5)
 Oral H1 antihistamine therapy, N (%)                                                                      24 (35.3)
 Levocetirizine                                                                                             17 (25)
 Ebastine                                                                                                   2 (2.9)
 Hydroxyzine                                                                                                2 (2.9)
 Bilastine                                                                                                  1 (1.59
 Rupatadine                                                                                                 1 (1.5)
 Fexofenadine                                                                                               1 (1.5)
 Vaccination status, N (%)
    No vaccination                                                                                         10 (14.7)
    Inactivated vaccinea                                                                                   27 (39.7)
    mRNA vaccineb                                                                                          19 (27.9)
    Inactivated vaccinea+mRNAvaccineb                                                                      12 (17.6)
 Presence of angioedema, N (%)                                                                             25 (36.8)
 Total IgE prior to OMZ treatment(kU/L), median (range)                                                  281 (2-2730)
 Presence of eosinophilia prior to OMZ treatment, n (%)                                                       6 (9)
 OMZ treatment duration (month), median (range)                                                            12 (6-60)
 Dosing regimen of OMZ, N (%)
    300 mg every 4 weeks                                                                                   66 (97.1)
    300 mg every 2 weeks                                                                                    2 (2.9)

OMZ = omalizumab; SD = standard deviation.
a
 Inactivated vaccine produced by SinovacBiotech®.
b
  mRNA vaccine produced by Pfizer/BioNTech®.




    Twelve of the 68 CSU patients (17.6%) receiving              significantly higher in the group with COVID-19 infection
OMZ were diagnosed with COVID-19 during OMZ                      history (P = 0.01) (Table 2).
treatment. All twelve patients (17.6%) were diagnosed               Fifty-one (75%) patients had been vaccinated against
with COVID-19, confirmed by polymerase chain reaction            COVID-19 while using OMZ. Urticaria activation follow-
(PCR) test. None of the other 56 patients had a history of       ing vaccination occurred in four patients: one patient who
COVID-19 before or during OMZ treatment. All patients            had received inactivated vaccine (Sinovac®) and three pa-
had mild symptoms during the course of the disease and did       tients who had received the mRNA vaccine (BioNTech®).
not require hospitalization. Furthermore, no urticaria acti-     Activation developed in all patients after the first dose of
vation was observed in any patients following COVID-19.          vaccination and within an average of two days. The urticaria
The UAS7 score was noted to be zero before and after             symptoms subsided rapidly in all patients with the adminis-
COVID-19. When the patients with confirmed COVID-19              tration of oral antihistamine treatment (levocetirizine BID).
were compared with those who did not acquire the infec-          No recurrence was observed following booster vaccinations
tion, no difference was detected regarding gender, age, co-      in any of the patients.
morbidities, COVID-19 vaccination status, pre-treatment
Ig E levels, pre-treatment eosinophilia, and treatment reg-
                                                                 Conclusions
imens utilized for CSU. In four of 12 patients, the total
IgE level prior to OMZ treatment was below 110 kU/L.                Severe acute respiratory syndrome coronavirus 2 (SARS-
On the other hand, the duration of OMZ treatment was             CoV-2) has direct and indirect impacts on the immune system.



Original Article | Dermatol Pract Concept. 2023;13(3):e2023145                                                              3
                Table 2. Comparison of demographic and clinical characteristics of patients
                                according to Covid-19 infection history.
                                                                                  COVID-19 (+)           COVID-19 (-)

                                                                                 N=12 (17.6%)           N=56 (82.4%)            P
 Gender, N (%)
    Female                                                                          10 (83.3)              34 (60.7)          0.190
 Age (years), mean ±SD                                                              39.6±12.8             48.8±15.1           0.056
 c
    Comorbidity, N (%)                                                                1 (8.3)                3(5.4)           0.549
 Oral H1-antihistamine therapy, N (%)                                                 4 (33.3)             20 (35.7)            1
 Vaccination status, N (%)                                                                                                    0.699
    No vaccination                                                                    2 (16.7)              8 (14.3)
    Inactivated vaccinea                                                               3 (25)              24 (42.9)
    mRNA vaccineb                                                                     4 (33.3)             15 (26.8)
    Inactivated vaccinea+mRNA vaccineb                                                 3 (25)               9 (16.1)
 Presence of angioedema, N (%)                                                        6 (50)               19 (33.9)          0.335
 Total IgE prior to OMZ treatment (kU/L), median (range)                         312.5 (31-740)          280 (2-2730)         0.876
 Presence of eosinophilia prior to OMZ treatment, N (%)                               2 (16.7)              4 (7.7)           0.291
 OMZ treatment duration (months), median (range)                                   22.5 (10-60)            12 (6-60)          0.01
 Dosing regimen of OMZ, N (%)                                                                                                   1
    300 mg every 4 weeks                                                             12 (100)              54 (96.4)
    300 mg every 2 weeks                                                               0 (0)                2 (3.6)

OMZ = omalizumab; SD = standard deviation.
a
  Inactivated vaccine produced by SinovacBiotech®.
b
  mRNA vaccine produced by Pfizer/BioNTech®.
c
 In the COVID-19 + group, one patient had hypertension, while in the COVID-19 -group, two patients had hypothyroidism and one patient
had depression.



The virus is considered to cause a three-phase disease. The         the level of IgE and FcεRIs [8-10]. Moreover, OMZ has been
initial phase begins with the entry of the virus into the host      demonstrated to improve nasal sinus function, which has
and lasts about 5-7 days. The second phase, namely the pul-         a significant role in the first line of defense against SARS-
monary phase, is characterized by pulmonary involvement             CoV-2 [11,12]. Hence, patients using OMZ might benefit
and occurs within 7-15 days following the disease onset.            from the treatment during the initial phase of COVID-19,
In the third phase, the inflammatory phase, overactivation          and some studies highlighted that OMZ might be a prefera-
of the immune system leads to cytokine storm and conse-             ble treatment option for COVID-19 [12,13].
quent development of acute respiratory distress syndrome                OMZ also lessens the disease severity by reducing FcεRIs
(ARDS) [6]. An adequate immune response during the initial          on the surface of mast cells, which play a key role in the
phase is desirable, while the primary goal of the treatment         inflammatory response during the second and third phases
is the prevention of the over-activation encountered during         of COVID-19 and the prolonged COVID-19 symptoms re-
the following two phases resulting in cytokine storm [7].           ferred to as “long-COVID” [12-14].
     OMZ is a recombinant human IgE antibody that exerts                In our study, among 68 patients using OMZ during the
its effect by preventing the binding of IgE with high-affinity      COVID-19 pandemic, twelve contracted the SARS-CoV-2
IgE receptors (FcεRI). It is utilized in disorders in which IgE     infection. All patients recovered without progressing to
plays a major role in pathogenesis, such as CSU and asthma.         the second pulmonary phase. Apart from these twelve pa-
Furthermore, the antiviral effect of OMZ has been reported          tients whose diagnoses were established with a positive
in various studies. This antiviral effect occurs in several dif-    PCR test, there might be asymptomatic and underdiag-
ferent ways. There is a considerable number of FcεRIs on            nosed patients.
the surface of plasmacytoid dendritic cells (pDCs) respon-              The duration of OMZ treatment was significantly lon-
sible for IFN- α production. In several studies, it has been        ger in the patient group with a history of COVID-19 com-
suggested that elevated serum IgE levels and increased pDC          pared to patients who did not acquire the infection in our
FcεRI expression might reduce IFN- α secretion from pDCs.           series, although there was no difference between the two
Thus, OMZ contributes to the release of IFN-α by reducing           groups in terms of COVID-19 vaccination status. This might



4                                                                        Original Article | Dermatol Pract Concept. 2023;13(3):e2023145
be attributed to a paucity in immune response in the ini-          of OMZ therapy following control of CSU symptoms to
tial COVID-19 phase in patients on long-term OMZ ther-             allow ET-1 and eosinophil levels to return to levels before
apy. SARS-CoV-2 enters the host cells through binding the          OMZ administration.
angiotensin-converting enzyme 2 (ACE2) via S-protein [15].
ACE2 receptor possesses a significant role in the initiation
of COVID-19 since SARS-CoV-2 can only enter cells with             References
ACE2 receptors. Zietkowski et al demonstrated lowered
                                                                    1. Zuberbier T, Aberer W, Asero R, et al. The EAACI/GA²LEN
endothelin-1 (ET-1) levels in patients receiving OMZ. The              /EDF/WAO guideline for the definition, classification, diagnosis
authors reported that the reduction was more pronounced                and management of urticaria. Allergy. 2018;73(7):1393-1414.
in patients with more extended treatment duration [16]. In             DOI:10.1111/all.13397. PMID: 29336054.
another study, a negative correlation was revealed between          2. Zuberbier T, Abdul Latiff AH, Abuzakouk M, et al. The inter-
                                                                       national EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline
ET-1 and ACE2 receptor, ie, the number of ACE2 receptors
                                                                       for the definition, classification, diagnosis, and management of
was elevated as the ET-1 level declined [17]. In addition, pa-
                                                                       urticaria. Allergy. 2022;77(3):734-766. DOI: 10.1111/all.15090.
tients with higher ACE2 receptor levels were shown to have             PMID: 34536239.
a better COVID-19 prognosis [18]. It might be a possible            3. Muntean IA, Pintea I, Bocsan IC, Dobrican CT, Deleanu D.
explanation for the higher incidence of COVID-19 in our                COVID-19 Disease Leading to Chronic Spontaneous Urticaria
patients with a longer duration of OMZ therapy and the low             Exacerbation: A Romanian Retrospective Study. Healthcare
                                                                       (Basel). 2021;9(9):1144. DOI: 10.3390/healthcare9091144.
disease activity that did not necessitate hospitalization in any
                                                                       PMID: 34574918. PMCID: PMC8470475.
of these patients.
                                                                    4. Allegra A, Asero R, Giovannetti A, Isola S, Gangemi S. Urticaria
    In the aforementioned study, Zietkowski et al observed             and coronavirus infection: a lesson from SARS-CoV-2 pan-
a reduction in the eosinophilic cationic protein (ECP) levels            demic. Eur Ann Allergy Clin Immunol. 2021;53(2):51-54. DOI:
and the blood eosinophil counts in subjects on OMZ therapy               10.23822/EurAnnACI.1764-1489.173. PMID: 33034169.
in proportion to the treatment duration [16]. Studies investi-      5.   Algaadi SA. Urticaria and COVID-19: A review. Dermatol
                                                                         Ther. 2020;33(6):e14290. DOI: 10.1111/dth.14290. PMID:
gating the relation between COVID-19 and eosinophil levels
                                                                         32902087.
indicated eosinopenia, particularly in the initial disease phase
                                                                    6.   Siddiqi HK, Mehra MR. COVID-19 illness in native and im-
[19,20]. On the other hand, COVID-19 incidence was rela-                 munosuppressed states: A clinical-therapeutic staging pro-
tively low in patients with asthma, a disease associated with            posal. J Heart Lung Transplant. 2020;39(5):405-407. DOI:
elevated eosinophil count, suggesting eosinophilia might be              10.1016/j.healun.2020.03.012. PMID: 32362390. PMCID:
a protective factor against COVID-19 [21-22]. In the light of            PMC7118652.
                                                                    7.   Nicastri E, Petrosillo N, Ascoli Bartoli T, et al. National Insti-
these findings, it might be speculated that the extended use
                                                                         tute for the Infectious Diseases “L. Spallanzani”, IRCCS. Recom-
of OMZ facilitated the entry of SARS-CoV-2 in the host cell
                                                                         mendations for COVID-19 clinical management. Infect Dis Rep.
by increasing the ACE2 receptors and reducing eosinophil                 2020 Mar 16;12(1):8543. DOI: 10.4081/idr.2020.8543. PMID:
counts, while hindering the progression of the disease into              32218915. PMCID: PMC7097833.
more severe forms with its antiviral and anti-inflammatory          8.   Esquivel A, Busse WW, Calatroni A, et al. Effects of Omali-
effects.                                                                 zumab on Rhinovirus Infections, Illnesses, and Exacerbations
                                                                         of Asthma. Am J Respir Crit Care Med. 2017;196(8):985-992.
    Various case reports and studies confirmed urticaria ac-
                                                                         DOI: 10.1164/rccm.201701-0120OC. PMID: 28608756. PM-
tivation triggered either with COVID-19 or COVID-19 vac-
                                                                         CID: PMC5649984.
cines [23-25]. In contrast, none of the patients in our series      9.   Gill MA, Bajwa G, George TA, et al. Counterregulation between
who had COVID-19 showed activation of urticaria. Simi-                   the FcepsilonRI pathway and antiviral responses in human plas-
larly, some studies observed no urticaria activation in pa-              macytoid dendritic cells. J Immunol. 2010;184(11):5999-6006.
tients on OMZ in the setting of COVID-19 [13,25]. On the                 DOI:10.4049/jimmunol.0901194. PMID: 20410486. PMCID:
                                                                         PMC4820019.
other hand, the urticaria flares following vaccination were
                                                                   10.   Durrani SR, Montville DJ, Pratt AS, et al. Innate immune re-
not uncommon and were mainly detected following mRNA
                                                                         sponses to rhinovirus are reduced by the high-affinity IgE re-
vaccines as in our patients [24].                                        ceptor in allergic asthmatic children. J Allergy Clin Immunol.
    In conclusion, our study highlights the positive relation-           2012;130(2):489-495. DOI:10.1016/j.jaci.2012.05.023. PMID:
ship between the duration of OMZ treatment and the risk of               22766097. PMCID: PMC3437329.
acquiring SARS-CoV-2. Older age (≥65 years old), male gen-         11.   Gevaert P, Calus L, Van Zele T, et al. Omalizumab is effective in
                                                                         allergic and nonallergic patients with nasal polyps and asthma.
der, hypertension, cardiovascular diseases, diabetes, chronic
                                                                         J Allergy Clin Immunol. 2013;131(1):110-6.e1. DOI: 10.1016/j.
obstructive pulmonary disease, and malignancies were asso-
                                                                         jaci.2012.07.047. PMID: 23021878.
ciated with a higher risk of death from COVID-19 infection         12.   Farmani AR, Mahdavinezhad F, Moslemi R, et al. Anti-IgE
[26]. In this regard, in patients with aforementioned risk fac-          monoclonal antibodies as potential treatment in COVID-19. Im-
tors, the physicians might consider a temporary interruption             munopharmacol Immunotoxicol. 2021;43(3):259-264. DOI: 10



Original Article | Dermatol Pract Concept. 2023;13(3):e2023145                                                                           5
      .1080/08923973.2021.1925906. PMID: 34018464. PMCID:                        J Allergy Clin Immunol. 2020;146(1):1-7. DOI: 10.1016/j.
      PMC8146297.                                                                jaci.2020.04.021. PMID: 32344056. PMCID: PMC7194727.
13.   Passante M, Napolitano M, Dastoli S, et al. Safety of omalizumab     20.   Tanni F, Akker E, Zaman MM, Figueroa N, Tharian B, Hupart
      treatment in patients with chronic spontaneous urticaria and               KH. Eosinopenia and COVID-19. J Am Osteopath Assoc. 2020
      COVID-19. Dermatol Ther. 2021;34(6):e15111. DOI: 10.1111                   Jul 16. DOI: 10.7556/jaoa.2020.091. Epub ahead of print.
      /dth.15111. PMID: 34427028. PMCID: PMC8646731.                             PMID: 32672799.
14.   Lam HY, Tergaonkar V, Kumar AP, Ahn KS. Mast cells: Ther-            21.   Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140
      apeutic targets for COVID-19 and beyond. IUBMB Life.                       patients infected with SARS-CoV-2 in Wuhan, China. Allergy.
      2021;73(11):1278-1292. DOI: 10.1002/iub.2552. PMID:                        2020;75(7):1730-1741. DOI:10.1111/all.14238. PMID: 32077115.
      34467628. PMCID: PMC8652840.                                         22.   Li X, Xu S, Yu M, et al. Risk factors for severity and mortality in
15.   Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT,                       adult COVID-19 inpatients in Wuhan. J Allergy Clin Immunol.
      Veesler D. Structure, Function, and Antigenicity of the SARS-              2020;146(1):110-118. DOI:10.1016/j.jaci.2020.04.006. PM-
      CoV-2 Spike Glycoprotein Cell. 2020;181(2):281-292.e6.                     CID: PMC7152876.
      DOI:10.1016/j.cell.2020.02.058. PMID: 32155444. PMCID:               23.   Polly S, Fernandez AP. Common skin signs of COVID-19 in
      PMC7102599.                                                                adults: An update. Cleve Clin J Med. 2022;89(3):161-167. DOI:
16.   Zietkowski Z, Skiepko R, Tomasiak-Lozowska MM,                             10.3949/ccjm.89a.21126. PMID: 35232829.
      Bodzenta-Lukaszyk A. Anti-IgE therapy with omalizumab de-            24.   Sun Q, Fathy R, McMahon DE, Freeman EE. COVID-19 Vac-
      creases endothelin-1 in exhaled breath condensate of patients with         cines and the Skin: The Landscape of Cutaneous Vaccine
      severe persistent allergic asthma. Respiration. 2010;80(6):534-            Reactions Worldwide. Dermatol Clin. 2021;39(4):653-673.
      542. DOI: 10.1159/000317137. PMID: 20588001.                               DOI: 10.1016/j.det.2021.05.016. PMID: 34556254. PMCID:
17.   Zhang H, Li Y, Zeng Y, Wu R, Ou J. Endothelin-1 downregulates              PMC8165093.
      angiotensin-converting enzyme-2 expression in human bronchial        25.   Ayhan E, Öztürk M, An İ, Bekçibaşi M. COVID-19 infection
      epithelial cells. Pharmacology. 2013;91(5-6):297-304. DOI:                 under omalizumab therapy for chronic spontaneous urticaria:
    10.1159/000350395. PMID: 23751363.                                         three cases. Int J Dermatol. 2021;60(2):253- 254. DOI: 10.1111
18. Chen J, Jiang Q, Xia X, et al. Individual variation of the SARS-           /ijd.15379. PMID: 33332576.
    CoV-2 receptor ACE2 gene expression and regulation. Aging              26. Parohan M, Yaghoubi S, Seraji A, Javanbakht MH, Sarraf P, Djalali
    Cell. 2020;19(7):e13168. DOI:10.1111/acel.13168. PMID:                     M. Risk factors for mortality in patients with Coronavirus disease
    32558150. PMCID: PMC7323071.                                               2019 (COVID-19) infection: a systematic review and meta-analysis
19. Lindsley AW, Schwartz JT, Rothenberg ME. Eosinophil responses              of observational studies. Aging Male. 2020;23(5):1416-1424.
    during COVID-19 infections and coronavirus vaccination.                    DOI: 10.1080/13685538.2020.1774748. PMID: 32508193.




6                                                                                Original Article | Dermatol Pract Concept. 2023;13(3):e2023145
