Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 was identified by the World Health Organization as a variant of concern on November 26, 2021, and named Omicron [1]. The Omicron variant is extremely contagious. Omicron BA.1 and Omicron BA.2 spread rapidly worldwide and have superseded the SARS-CoV-2 Delta variant [2]. In South Korea, the first two patients infected with the Omicron variant were identified on November 25, 2021 [3], and by July 2022 more than 35 million had been infected.

The clinical characteristics of the Omicron variation are distinct from those of the earlier forms of SARS-CoV-2. The emergence of new mutations in the Omicron variant raises the overall risk of reinfection and partially compromises the effectiveness of existing vaccinations [4]. However, at the same time, its virulence may have been reduced by these mutations, and in vitro studies indicate that the Omicron variant has less efficient replication and fusion than the Delta variant, which may explain why Omicron is associated with milder disease and a shorter period of illness [4,5].

Representative symptoms of Omicron variant infection are runny nose, cough, fever, and sore throat, which are similar to other variants [6]. However, several studies have found that Omicron has distinct clinical characteristics that are different from other variants. Symptoms of the Omicron variant were more frequent in adults between the ages of 18 and 65 than in younger or older people, and people aged 16 to 49 were more likely to report more serious symptoms than older patients [2]. In contrast, Delta variant symptoms worsened with age [6]. Also, children with the Omicron variant infection experience fewer severe symptoms than the Delta variant [6]. Although information on the clinical presentation of the Omicron variant is growing rapidly, research in South Korea is limited and restricted to only a few publications.

We aimed to identify the characteristics and symptoms of the Omicron variant, which has replaced other variants as the most prevalent, and to clarify how clinical factors affect the manifestation of the Omicron infection. Additionally, we aimed to contribute to the improved understanding of the disease and provide valuable insights that can inform public health strategies and clinical practices by comprehensively showing symptom changes from diagnosis to release from quarantine.

We assessed self-reported questionnaires of COVID-19 patients from March 2022 to October 2022, which is defined to be the “Omicron variant dominant season” in Korea, at two points: at the diagnosis and release from quarantine. Since the first reported case on November 25, 2021, it can be assumed that most cases in this study were infected with the Omicron variant. This assumption is acceptable given that the Omicron version has been the major variant throughout 2022 in South Korea. The methodology of this study, which involved collecting data through self-reported questionnaires from outpatients visiting otorhinolaryngology clinics rather than hospitalized patients, sets it apart from previous research. Many prior studies have been conducted with the collaboration of specialists in internal medicine, critical care, and emergency medicine. These studies typically included respiratory and systemic symptoms, with clinicians performing objective examinations and assessments to collect data. For instance, a study by Wang, et al. [7], published in the early stages of the COVID-19 pandemic, comprehensively analyzed the clinical characteristics of hospitalized COVID-19 patients in Wuhan, China. Like other multidisciplinary studies, it relied on objective clinical evaluations conducted by healthcare professionals across various specialties. In contrast, our study focused on patients visiting otorhinolaryngology outpatient clinics. However, it did not limit data collection to otolaryngologic symptoms alone but instead used a structured questionnaire to comprehensively assess systemic symptoms and complications [8]. Several previous studies have also utilized self-reported data to analyze COVID-19, particularly in outpatient settings. Unlike studies conducted in hospital environments, where symptoms are assessed by healthcare professionals, self-reported symptom tracking allows for real-time monitoring of disease progression and captures a broader range of mild to moderate cases that may not require hospitalization. One study reported that this approach effectively tracked changes in COVID-19 clinical manifestations and facilitated early diagnosis. Additionally, a study from the United Kingdom found that self-reported anosmia, sore throat, and headache were more pronounced during the Omicron wave, demonstrating their clinical significance in the early detection of COVID-19. These findings highlight the potential advantages of self-reported symptom tracking in capturing a more comprehensive spectrum of disease presentation in non-hospitalized patients [7].

The RAT kit utilized in the otorhinolaryngology clinics, the length of the swab is longer than that of self-testing kits, and a healthcare professional directly collects swab samples from the oropharynx or nasopharynx. In this study, 28.4% were reported to be negative on self-testing kit but were later found to be positive on RAT at the clinic. This could be due to the low sensitivity of the self-testing kits themselves, individual lack of testing skills, the shorter length of swabs, and the likelihood of false negative when testing during the early stages of symptoms [9]. Improving the diagnostic accuracy of self-testing kits, which serve as an important tool during the COVID-19 era, is essential. These findings highlight the importance of educating the public on proper testing techniques to ensure more reliable results. Additionally, technical modifications, such as extending the length of swabs included in self-testing kits, may be necessary to enhance their diagnostic performance.

After their diagnosis, most of the patients received treatment at home, and about 96% took medicine. Most of these patients took over-the-counter or prescribed drugs for relieving symptoms. Paxlovid is allowed only for individuals aged 60 and over or in their 40s and 50s with high-risk or immunocompromising condition. In our study, although 26% of patients were eligible for Paxlovid, only 1.6% of patients were prescribed. The prescription rate was significantly lower than expected, and there are several possible reasons. From the physician’s perspective, the main reason was a lack of drug supply. In early 2022, the supply could not keep up with demand, and it was prescribed only at designated pharmacies. The second reason was the fear of adverse effects from the new drugs by both the doctors and patients. Therefore, to ensure that Paxlovid is effectively prescribed and accessible to those who need it during a potential COVID-19 resurgence, several key steps should be taken. First, the government should stabilize the supply chain and establish a reliable distribution system so that healthcare facilities and pharmacies can access the medication without delays. Additionally, clear guidelines and proper training for healthcare professionals will help build confidence in prescribing Paxlovid and ease concerns about its use.

Body temperatures varied between 34°C and 39.9°C (mean, 37.1). During the pandemic, to prevent the spread of COVID-19, body temperatures are mostly measured using noncontact thermometers. The reason of reporting body temperatures below 36°C due to the potential errors associated with non-contact thermometers. In this study, body temperatures below 36°C were measured in 30 patients.

From November 1, 2021, to March 1, 2022, the South Korean government introduced a system whereby individuals required COVID-19 digital vaccination certification to access indoor multi-use facilities, including restaurants and cafes, as well as infection-vulnerable facilities. Additionally, to address the increasing number of pediatric cases, vaccination was also administered to children aged 5 to 11 years old [10]. With these policies, South Korea has achieved a relatively high COVID-19 vaccination rate. In the patient group included in this study, it was found that 93% had received more than the first dose of the vaccination (Table 1). Sufficient data on post-vaccination side effects were collected in this study and indicated that the occurrence of fever or severe body aches due to the COVID-19 vaccination did not correlate significantly with the severity of actual COVID-19 clinical symptoms (Fig. 2). This suggests that post-vaccination side effects may not necessarily predict the severity of subsequent COVID-19 symptoms, underscoring the importance of individualized patient monitoring rather than assumptions based on vaccination reaction history.

The most prevalent symptoms at the time of COVID-19 diagnosis were a sore throat, globus sensation, myalgia, cough, fever, and sputum, regardless of severity. This differs slightly from other studies. In a Canadian study involving 1063 Omicron cases, the most common symptoms reported were nasal congestion (73%), cough (65%), and headache (54%) [11]. A French study with 468 patients conducted from November 2021 to January 2022 reported fatigue (57%), cough (52%), fever (48%), and headache (44%) in that order [12]. In a UK study that focused exclusively on vaccinated individuals, the most common symptoms reported were runny nose (77%), headache (75%), sore throat (71%), and sneezing (63%), in that order [5]. However, there may be differences between the symptoms a patient self-reports and the symptoms observed during an in-person consultation with a doctor.

When asked about the most distressing symptoms at the time of COVID-19 diagnosis, they responded in the following order: sore throat, myalgia, fever, globus sensation, cough, and sputum. This is different from some other studies. An Indian study with 1175 participants reported fever (43%), body ache (23%), runny nose (22%), and cough (21%) as the most predominant symptoms [13].

Regarding the severity of symptoms across different age groups, because we did not assess the overall severity of other symptoms using Visual Analog Scale (VAS) scores or other measures, we evaluated symptom severity by using the degree of fever, a key clinical symptom of COVID-19. When analyzing body temperature at the time of diagnosis according to age groups, it was observed that those under 20 years of age had the highest average body temperature, while individuals in their 50s and 60s had significantly lower body temperatures compared to all other groups (Table 4). Also, older patients had longer periods between the onset of initial symptoms and subsequent development of fever or body aches compared to younger patients (Table 6). This finding is consistent with prior studies, which found that people aged 16 to 49 had considerably more severe symptoms than the older population [6], and that Omicron symptoms were consistently more common in adults aged 18-65 years than in children or the elderly [2]. These findings have important clinical implications. The significantly lower body temperature and delayed fever onset in older adults suggest that fever may not be a reliable early diagnostic indicator for COVID-19 in older population. This highlights the need for clinicians to consider other early symptoms, such as sore throat and cough, when assessing older adults for potential COVID-19 infection. Additionally, the delayed onset of systemic symptoms in this group may contribute to underestimation of disease severity and delayed medical intervention, which could increase the risk of complications. Healthcare providers should be aware of these differences and emphasize the importance of early medical consultation for older patients, even in the absence of fever. From a public health perspective, the delay in outpatient visits among older individuals suggests potential gaps in symptom recognition and healthcare-seeking behavior in this population. Older patients may not perceive their symptoms as severe enough to need medical attention, leading to delayed diagnosis and potentially increased transmission risk. Targeted public health messaging should emphasize the importance of early symptom recognition and prompt medical consultation, especially for individuals aged 50 and above.

Fig. 1 shows the profile of the most distressing symptom reported by each subgroup when analyzed by different age group. Although there were some differences between the groups, the profile of the most distressing symptoms was similar. This suggests that despite age-related variations in fever onset and progression, the overall symptom burden remains comparable across different age groups. This finding supports the need for a uniform yet flexible symptom management approach that can be tailored based on individual risk factors rather than solely on age.

Although the number of individuals in the cohort did not allow for a subgroup analysis of pediatric patients, symptoms in children with the Omicron variant are reported to be relatively milder than with the Delta variant [6]. Furthermore, even in hospitalized children who exhibited severe clinical manifestations due to underlying comorbidities, the mortality rate was relatively low when they received appropriate care in an ICU [14]. Nonetheless, older age and a higher comorbidity burden are well-known factors associated with adverse outcomes and more severe disease in patients with COVID-19 [15].

Persistent symptoms after a week after diagnosis were reported in the following order: cough, sputum, fatigue, hoarseness, and loss of smell or taste. Persistent symptoms showed quite a different profile from the initial manifestations. However, this study was unable to collect long-term symptom follow-up data. Persistent respiratory symptoms such as cough and sputum production may result from post-viral airway inflammation, increased bronchial sensitivity, and residual lung tissue damage following COVID-19, as described by Carfi, et al. [16] Fatigue, one of the most frequently reported long-term symptoms, may be driven by prolonged immune activation, cytokine imbalance, and autonomic nervous system dysfunction, as noted by Townsend, et al. [17]. These findings support recent research on long COVID, indicating that some patients continue to experience symptoms even after the virus has been cleared.

In this study, there were no reported cases of ICU admission or mortality, and instances of severe complications were also very rare. This is consistent with other research findings, indicating that the Omicron variant tends to exhibit relatively lower severity even among high-risk older individuals [18]. Mayr, et al. [18] evaluated the severity of COVID-19 based on admission rates, ICU admissions, organ support measures, and death. In most reported indicators, high-risk older individuals exhibited significantly lower disease severity compared to previous variants of the virus. The rate of pneumonia diagnosis in this study was 0.13%, which was significantly lower than in previous studies. This is probably because the Omicron variant mostly causes upper respiratory tract infection, and illness severity has decreased compared to prior variants due to the broad use of COVID-19 vaccines and spike protein mutation [19]. Other studies have found that greater age and the presence of comorbidities are related to a higher likelihood of disease progression to severe manifestations [15]. It is assumed, however, that the patient group included in this study comprised a small proportion of individuals with severe comorbidities.

By including the largest patient cohort in South Korea, this study analyzed the clinical characteristics of COVID-19 during the Omicron-dominant era. Its broad coverage across all age groups and large sample size allowed subgroup analyses to be conducted based on vaccination status and age and the possibility of overestimating symptoms was decreased. Also, this is the first article in South Korea to report the clinical progress of Omicron patients from the initial diagnosis to the release of quarantine.

This study has some limitations. First, symptoms were self-reported, which are inherently susceptible to recall and response bias, potentially leading to both under- and overestimation of symptom severity. This concern is particularly relevant in pediatric patients, as parents were likely to respond on behalf of the pediatric patient, potentially causing bias in response accuracy. To improve the validity of future research, integrating objective data sources, such as medical records, alongside self-reported data is recommended. Second, the decrease in follow-up survey response rates (736 respondents out of the initial 2842) may have affected the representativeness of the study findings, and the possibility of selection bias due to differences between respondents and non-respondents cannot be excluded. Patients with a more favorable disease course may have been more likely to complete the follow-up survey, potentially leading to an underestimation of the severity and progression of symptoms associated with the Omicron variant. Therefore, these findings should be interpreted with caution. Third, this study focused on tracking symptom change over time but did not incorporate quantitative measures such as the VAS to assess symptom severity. As a result, changes in symptoms could not be analyzed using quantitative scale. Fourth, as this study focused on patients seen in otorhinolaryngology clinics, excluding those treated in tertiary hospitals, the risk of selection bias may have been further amplified. Nevertheless, this approach also serves as a strength, as it differentiates the study from previous research that primarily relied on tertiary hospital data and focused on severe cases. By utilizing data from primary and secondary healthcare institutions, this study provides more practical and clinically relevant insights for frontline physicians managing patients in routine clinical practice. Lastly, this study was lack of comparison with the other seasons during the pandemic. it would have been more ideal if we could compare the three groups, prior to omicron variant dominant era, omicron dominant era, and post-omicron dominant era. However, due to limitations in the data collection period, such comparisons were not possible.

In conclusion, the Omicron variant demonstrated a higher vaccine avoidance rate, and the severity and fatality were relatively lower than other variants. Most of the initially distressing symptoms tended to subside after a week of quarantine. There was a different symptom profile from the time of diagnosis and after release from quarantine, which may serve as a point of differential diagnosis from other respiratory viruses.