Objective: To evaluate the otolaryngology-specific symptoms that occur after receiving the Covid-19 vaccine and its possible side effects in patients who had Covid-19 infection in the last 6 months before the vaccination. Patients and Methods: The study comprised 3383 health care workers who were vaccinated against Covid 19. After excluding, the study was conducted with 1710 (51%) participants who agreed to answer the study questions. The participants were divided into 2 groups according to the history of Covid-19 positivity in the last 6 months before vaccination. The presence of symptoms related to otolaryngology practice, including cough, nasal congestion, rhinorrhea, sore throat, hearing loss, dizziness, loss of smell, loss of taste, ear pressure, and facial paralysis was recorded. Results: The mean age of the study population was 35.79 ± 10.2 (19-71) years and 1454 (85%) of the patients had a history of Covid-19 infection in the last 6 months. Regarding otolaryngology-related symptoms, the most common complaints were rhinorrhea (4.4%), sore throat (3.2%), and nasal congestion (2.9%). The presence of smell and taste loss, nasal congestion, rhinorrhea, sore throat, and hearing loss was significantly more common in patients with a history of Covid-19 infection. Conclusions: The patients with a history of Covid-19 disease might have otolaryngology-specific symptoms more commonly than those without a history of Covid-19 disease in the last 6 months before vaccination.
Keywordsanosmia, coronavirus, smell disorders, vaccination
The coronavirus disease 2019 (Covid-19) is a contagious disease that affects mainly the respiratory system.1 After it was first described in China, the World Health Organization (WHO) announced the disease as a pandemic in March 2020.1,2 At the time this study was conducted, a total of 97 831 595 confirmed Covid-19 cases and 2 120 877 related deaths had been reported by the WHO.3 The most common symptoms of this disease include fever, cough, dyspnea, rhinorrhea, sore throat, headache, and myalgia.4,5 In addition, it has been reported that a sudden loss of smell or taste due to olfactory dysfunction may also be associated with the disease.6
Following the advances in recent vaccination studies, governments took action to vaccinate all risk groups such as health care workers, patients with comorbidities, the elderly patients, and social care workers.7 However, the utilization of new vaccine technologies, the origin of vaccine companies, and common negative thoughts against vaccination arose some concerns.8
As the common side effects of the vaccines have been reported to be flu-like symptoms, myalgia, pain in the injection site, headache, and anaphylaxis, there is no robust evidence concerning the side effects of inactivated Covid-19 vaccines in terms of otolaryngology-related symptoms.7 Moreover, there is also a concern regarding the efficacy of vaccination and potential side effects in people who have been previously infected with Covid-19.7,9
This study aimed to evaluate the otolaryngology-specific symptoms that occur after receiving the Covid-19 vaccine in individuals who had the Covid-19 disease in the last 6 months before the vaccination.
Ethical approval was obtained from the institutional review board of the local ethics committee of our hospital (IRB: 2021/514/194/46). The research was conducted ethically in accordance with the World Medical Association Declaration of Helsinki. The patients (or their parents or legal guardians) have given their written informed consent.
The study comprised 3383 health care workers who were vaccinated with the inactivated Covid-19 vaccine (CoronaVac, Sinovac Life Sciences) in our hospital between January 14, 2021, and January 18, 2021.
The study was conducted with patients older than 18 years who were vaccinated with the inactivated Covid-19 vaccine, did not have active Covid-19 infection or flu-like symptoms at the time of vaccination and were able to answer the study questions. The inactivated Covid-19 vaccine has shown good immunogenicity both in experimental and in human studies with vaccine-induced neutralizing antibodies to severe acute respiratory syndrome coronavirus 2, the causative agent of Covid-19. The recommended dosing schedule is 2 doses of vaccination with a 28-day interval (ie, vaccination on day 0 and day 28).9
The exclusion criteria were defined as current olfactory or gustatory dysfunction, positive Covid-19 polymerase chain reaction (PCR) test at the time of vaccination, and unwillingness to participate in the study. After exclusion, the study was conducted with 1710 (51%) participants who agreed to answer the study questions.
The participants were stratified into 2 groups as those who had a recent (within 6 months) confirmed Covid-19 infection and those who never experienced any Covid-19 symptoms or those who had a positive Covid-19 PCR test result more than 6 months prior to vaccination. The characteristics of patients, such as age, gender, smoking habit, the presence of comorbidities, history of Covid-19 infection, and the presence of affected family members, were recorded. Information was obtained on the presence of symptoms related to otolaryngology practice, including cough, nasal congestion, rhinorrhea, sore throat, hearing loss, dizziness, loss of smell, loss of taste, ear pressure, and facial paralysis. Other symptoms likely related to the disease, such as weakness, fatigue, headache, myalgia, fever, vomiting, nausea, and anaphylaxis, were also recorded.
The data analysis was performed with the SPSS statistical software, version 20.0 (SPSS). The continuous variables are presented as mean and standard deviation. The categorical data are presented as numbers and percentages. The Shapiro-Wilk test was performed to analyze the distribution of the data. The Student t test was used to compare parametric variables. The χ2 test was used to compare categorical variables or Fisher exact test was used when more than 20% of the expected frequencies were <5. A P value of <.05 was considered statistically significant.
The mean age of the study population was 35.79 ± 10.2 (19-71) years. The study population comprised 985 (57.6%) female and 725 (42.4%) male participants. About 2/3 of the patients were nonsmokers and most of the participants had no comorbidities. Although 1454 (85%) of the patients reported a Covid-19 infection in the last 6 months, 256 had not experienced the Covid-19 disease. A total of 15.8% of the participants had a family member with a history of Covid-19 positivity (Table 1). Regarding otolaryngology-related symptoms, the most common complaints were rhinorrhea (4.4%), sore throat (3.2%), and nasal congestion (2.9%; Table 2). As for the general vaccine-related complaints, headache was the most common symptom with a rate of 18%. Weakness was the second most common symptom (17.2%), and myalgia was observed in 8.8% of the participants (Table 3).
The study participants were compared according to their Covid-19 history in the last 6 months. The mean age was 34.87 ± 9.9 years in those with a history of Covid-19 infection and 35.95 ± 10.3 years in those without Covid-19 history (P = .11). No significant difference was observed regarding smoking habit in participants with and without history of Covid-19 (46.1% vs 40%, P = .06). The presence of smell and taste loss, nasal congestion, rhinorrhea, sore throat, and hearing loss was significantly more common in those with a history of Covid-19 infection (Table 4).
Regarding the general symptoms, only headache and nausea were significantly more common in participants with previous Covid-19 infection. No significant difference was observed between the study groups regarding weakness, myalgia, fever, vomiting, and anaphylaxis (Table 5).
This study revealed that the incidence of otolaryngology-specific symptoms such as loss of smell, loss of taste, nasal congestion, rhinorrhea, sore throat, and hearing loss may be higher after inactivated Covid-19 vaccination in individuals with a history of Covid-19 disease.
The current literature postulates that patients who experience influenza-like symptoms and smell loss are 6 to 10 times more likely to have Covid-19 infection.10,11 In a multicenter study by Lechien et al, olfactory and gustatory deteriorations were observed in patients with mild to moderate Covid-19 disease.12 Moreover, smell loss was reported to be an independent risk factor for detecting patients with mild Covid-19 infection.10 Our previous study, which was one of the most extensive series on this patient, investigated the relation between Covid-19 positivity and presenting symptoms. The study concluded that loss of smell may be observed in 44.2% of patients with the early stage of the Covid-19 disease.13 There are more than 160 ongoing Covid-19 vaccine development trials, and 25 of them are currently in different study phases.14
Conventional vaccines are based on the relevant virus or its protein structure.15 Virus-based vaccines are divided into 2 types as inactivated or live-attenuated virus vaccines. Inactivated virus vaccines require adjuvants to stimulate the immune system. Protein-based vaccines include a purified or recombinant virus protein or virus-like particles.15 Covid-19 vaccine trials have been based on inactivated virus or protein-based vaccines. To speedup vaccine production, the majority of clinical trials have used next-generation platforms that generate viral vector or nucleic acid–based vaccines. DNA or messenger RNA (mRNA) fragments introduced to and translated in human cells are used in nucleic acid–based vaccines.15
In a recent study, the efficacy of the mRNA-1273 vaccine was evaluated in 15 210 participants.16 The Covid-19 disease was observed in 11 participants in the mRNA1273 group (3.3 per 1000 person-years), and the vaccine efficacy was 94.1% (95% CI, 89.3%-96.8%; P < .001). The most common adverse event was injection site pain in both the vaccine and placebo groups. Fever, fatigue, myalgia, and arthralgia were also observed in both groups.16
Inactivated vaccines have been used worldwide for the prevention of respiratory viruses to date.17 CoronaVac, an inactivated Covid 19 vaccine, has been reported to provide seroconversion on day 28 after the injection in 114 (97%) of the 117 patients in the 3 mg group, 118 (100%) of the 118 in the 6 mg group, and none (0%) of the 59 participants in the placebo group in a phase II vaccine trial. The most common adverse events were reported as injection site pain, fever, and fatigue in the first 0 to 14 days after vaccination both in the vaccination and placebo groups.9 Based on our study results, we may postulate that the inactivated virus can activate local host immune response and thereby cause flu-like symptoms.
Previous data reported that viral infections may deteriorate olfactory epithelium and invade the olfactory nerves.10,12,18 The higher rate of otolaryngology-specific symptoms in individuals with previous Covid-19 disease may be attributed to the hypothesis of chronic olfactory dysfunction. Furthermore, vaccination may play a triggering role in the activation of these symptoms in those with previous Covid-19 infection.
The vaccines against viral infections are also associated with nonspecific symptoms such as injection site pain, myalgia, fever, and dry cough.7,9 In our study, the majority of patients presented with headache, weakness, and myalgia after vaccination. On the other hand, in our research, headache and vomiting were the most common symptoms in patients with a history of Covid-19 disease.
The strength of our study is the inclusion of a large scale of patients vaccinated with an inactivated Covid-19 virus vaccine. However, the lack of data regarding antibody positivity against the SARS Cov 2 virus before vaccination may be considered a limitation of our study.
Future studies evaluating the symptoms that occur after vaccines developed with mRNA technology may further contribute to the body of knowledge.
This study demonstrated that individuals with a history of Covid-19 disease may have otolaryngology-specific symptoms more commonly than those without previous Covid-19 infection in the last 6 months before vaccination. It may be prudent to inform individuals who have a history of Covid-19 disease and receive an inactivated Covid-19 vaccine about the potential symptoms before immunization.
This is an original article and all authors have read and agreed with the content of this study and no part of this work has been published previously or is under consideration for publication elsewhere. Hakan Avcı, Burak Karabulut, Hazal Duygu Eken, Abdussamet Faraşoğlu, Tolga Çakil, and Sedef Çoruk conceptualized the study design. Hakan Avcı, Burak Karabulut, Hazal Duygu Eken, Hanife Özel, Namık Kemal Kaya, and Seva Öztürk Özbalta contributed to writing of the manuscript, collection of samples, and interpretation of data. Hakan Avcı performed the statistical analysis of data. All authors read and agreed with the final draft of the manuscript.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Hakan Avcı https://orcid.org/0000-0003-0703-4978
Burak Karabulut https://orcid.org/0000-0002-3958-3683
1 Department of Ear, Nose and Throat Diseases, University of Health Sciences, Istanbul Kartal Dr Lutfi Kirdar Training and Research Hospital, Istanbul, TurkeyReceived: April 11, 2021; revised: June 07, 2021; accepted: June 10, 2021
Corresponding Author:Hakan Avcı, MD, Department of Ear, Nose and Throat Diseases, University of Health Sciences, Istanbul Kartal Dr Lutfi Kirdar Training and Research Hospital, Cevizli Mh Şemsi Denizer Cad. E-5 Karayolu Cevizli Mevkii, 34890 Kartal, Istanbul Turkey.Email: hakanavcikbb@hotmail.com
