AbstractBackground and ObjectivesThis study is the first to report on voice changes by gender and duration of infection in Korean post-COVID-19 patients. It analyzes the prevalence of voice-related symptoms, gender differences in acoustic parameters, and temporal recovery patterns of voice function.
Materials and MethodIn this study, 85 patients with COVID-19 were recruited, voice-related symptoms were surveyed, and voice recordings of all participants were collected and analyzed by acoustic speech analysis.
ResultsThe average age of 85 COVID-19 confirmed patients was 31 (range: 26.0–45.5) years old, and there were 35 males and 50 females. Voice analysis using the GRBAS scale and acoustic parameters was conducted among male and female patients. Results revealed varying distributions of GRBAS scores among males and females, with males exhibiting lower fundamental frequency (F0) but higher jitter and shimmer compared to females. When compared to normal adult voice values, female patients demonstrated a significant reduction in fundamental frequency, while male patients exhibited a significant increase in speaking fundamental frequency (SFF) alongside elevated jitter and shimmer. Additionally, analysis of voice parameters over time since COVID-19 diagnosis showed no significant differences among males, whereas females exhibited a significant increase in SFF after 90 days, approaching normal values.
INTRODUCTIONIn December 2019, novel coronavirus infection occured which spread around the world, many manifestions were reported by mulitcenter study. A year after the outbreak of COVID-19, Wang et al. [1] and Shi et al. [2] reported that the clinical presentation of COVID-19 mainly includes fever, fatigue, cough, and anorexia. According to recent statistics, there were more than 590 million cases worldwide by August 2022, of which 6 million died [3]. As the cases accumulate and progress, long-term sequelae have been reported in addition to the symptoms initially seen. That was called by post-acute sequelae of COVID-19 [4] in the United States, commonly referred to as long COVID [5]. Carfi et al. [6] reported that 87.4% of hospitalized patients with COVID-19 had at least one sequelae at a mean of 60.3 days after symptom onset.
In Europe, multicenter study to investigate the occurrence of dysphonia in mild-to-moderate COVID-19 patients was done and 26.8% of patients had the dysphonia which appear in patients with a more severe clinical COVID-19 presentation [7]. When there was severe COVID-19 cases who had pneumonia or acute respiratory distress syndrome, patients have difficulty to not only in the inspiratory phase of respiration but also in the expiratory phase. Since the energy source for speech is provided by the air expelled from the lungs, if both respiratory phases do not have proper functioning it may cause voice disorder [8,9].
Gölaç et al. [10] evaluated several voice-related parameters using Computerzied Speech Lab (CSL). Recovering patients from COVID-19 showed significantly lower maximum phonation time (MPT), increased Voice Handicap Index-10 scores, decreased scores of Voice-Related Quality of Life questionnaire. But there was no difference in other voice parameters between the study and the control group.
While previous studies have investigated dysphonia and voice changes in COVID-19 patients, research focusing on sex-specific differences and longitudinal recovery patterns remains limited. Furthermore, most studies have been conducted in Western populations, leaving gaps in understanding the unique vocal characteristics of East Asian patients, including South Koreans. This study is the first to report on voice changes by gender and duration of infection in Korean COVID-19 patients. It analyzes the prevalence of voice-related symptoms, gender differences in acoustic parameters, and temporal recovery patterns of voice function.
MATERIALS AND METHODA COVID-19 patient is defined as a person who has been confirmed to be infected based on the test criteria for COVID-19 diagnosis or a person who shows symptoms of COVID-19 and has been identified and diagnosed by a physician as positive through a rapid antigen test (for experts) or an emergency screening test (approved for emergency use).
Acoustic analysis was conducted using the CSL (Model 4500 b, KayPENTAX Elemetrics Corporation, Lincoln Park, NJ, USA). The following parameters, including F0, jitter, shimmer, noise-to-harmonics ratio (NHR), speaking fundamental frequency (SFF), and MPT, were utilized for analysis. The GRBAS ratings of patients were assessed by the same speech-language pathologist. To evaluate auditory perceptual parameters, two questionnaires were utilized: the Korean version of the Voice Handicap Index-30 (KVHI-30) and the Korean version of the Voice-Related Quality of Life (KVQOL). These questionnaires were employed to assess the impact of voice disorders on individuals’ quality of life and their perceived handicap related to their voice, respectively.
The inclusion criteria for research subjects in this study were adults aged 18 years or older who had been diagnosed with COVID- 19 and released from isolation, understood the study contents, voluntarily agreed to participate, confirmed voice changes, and had no issues with the disability questionnaire (KVHI-30, KVQOL) and voice analysis test. Exclusion criteria for the study included individuals who declined participation, had a history of voice disease or surgery causing voice abnormalities, had congenital laryngeal disease, or had difficulty with voice and breathing due to structural problems other than vocal cords.
The final number of participants who met the inclusion criteria was 85. Participants were then divided into a male and a female group. The average age of the 85 COVID-19 confirmed patients was 31 years old (range: 26.0–45.5), with 35 males and 50 females. The most common accompanying symptoms were dysphonia (24.7%), cough (10.6%), sputum (9.4%), and sore throat (7.1%). Among the participants, 66 individuals (77.9%) were non-smokers, 12 (14.0%) were current smokers, and 7 (8.1%) were former smokers. Additionally, 44 participants (51.2%) had occupations that involved significant voice usage, and 83 participants (96.5%) received the COVID-19 vaccination. There were three cases of reinfection with COVID-19 (3.5%), and the average duration between the date of the experiment and the date of diagnosis was 92.0 days (range: 38–127).
Statistical analysisThe mean scores of the KVHI-30 and KVQOL between males and females were compared using independent samples t-tests. Multivariable regression analysis was performed to assess the relationships between dependent variables (SFF, jitter, and shimmer) and independent variables (age, gender, smoking status, and voice-related occupation). Pearson correlation analysis was conducted to evaluate associations between key parameters. Acoustic parameters were compared against normative values from Kim [11] using one-sample t-tests. To analyze changes in voice parameters over time, participants were stratified by gender into two groups (<90 days vs. ≥90 days post-diagnosis), and independent samples t-tests were performed to compare means between these groups. All statistical analyses were performed using the R language program (http://www.r-project.org). A p-value <0.05 was considered statistically significant.
This study was approved by the Institutional Review Board of Nowon Eulji Medical Center (IRB No. 2022-04-014).
RESULTSResult of voice analysisIn males, the KVHI-30 functional score was 2.6 (range: 0–24), the physical score was 4.0 (range: 0–28), and the emotional score was 1.7 (range: 0–23), resulting in a total score of 8.3 (range: 0–67). In females, the functional score was 6.7 (range: 0–35), the physical score was 10.3 (range: 0–38), and the emotional score was 5.1 (range: 0–38), resulting in a total score of 22.1 (range: 0–96). The total score and all individual subscale scores were significantly higher in females compared to males (p<0.001). When comparing KVQOL, males scored 91.9 (range: 0–100) in the physical domain, 93.1 (range: 0–100) in the emotional domain, and 91.7 (range: 0–100) in total. Females, on the other hand, scored 79.1 (range: 0–100) in the physical domain, 84.5 (range: 0–100) in the emotional domain, and 80.5 (range: 0–100) in total. Females showed significantly lower scores than males (physical p<0.001; emotional p=0.007; total p=0.002). During laryngoscopy, ipsilateral vocal fold paralysis was found in 2 patients (5.7%), and structural abnormalities of the vocal folds were found in 6 patients (12%) (Table 1).
The GRBAS analysis revealed distinct distributions of scores among male and female patients. Among males, Grade 0 was the most prevalent across all parameters, with 23 individuals scoring Grade 0 for Grade, 27 for Roughness, 30 for Breathiness, and 33 for Asthenity. Notably, all male patients scored Grade 0 for Strain. In contrast, females showed a broader distribution of scores. For Grade, 27 individuals scored Grade 0, while higher grades were more common compared to males, with 19 scoring Grade 1 and 4 scoring Grade 2. For Roughness, the distribution included 31 individuals scoring Grade 0, followed by 17 scoring Grade 1 and 2 scoring Grade 2. All female patients scored Grade 0 for Asthenity. For Strain, most individuals 47 scored Grade 0, with only one individual scoring Grade 1 and 2 scoring Grade 2. In the acoustic parameter analysis, males showed the following average values: F0 was 114.46 Hz (SD=17.33), jitter was 1.04% (SD=1.03), shimmer was 3.40% (SD=1.59), NHR was 0.13 (SD=0.02), SFF (spectral flatness measure) was 124.37 Hz (SD=18.16), and MPT was 17.86 seconds (SD=6.35). On the other hand, females showed the following average values: F0 was 210.36 Hz (SD=22.63), jitter was 13.59% (SD=47.80), shimmer was 3.88% (SD=2.11), NHR was 0.50 (SD=1.52), SFF was 186.23 Hz (SD= 58.14), and MPT was 17.87 seconds (SD=23.63) (Table 2).
Sex-specific voice analysis results of post-COVID-19 patients compared to normal adult voice analysis valuesWhen comparing the voice analysis results according to the gender of post-COVID-19 patients with the voice values of general adults, it was confirmed that the fundamental frequency of female patients was significantly reduced compared to normal values. Conversely, the SFF significantly increased in male patients compared to normal values, while it significantly decreased in female patients. In male patients, both jitter and shimmer were significantly increased. On the other hand, among female patients, there was no significant increase in jitter, but there was a significant increase in shimmer (Table 3).
Comparison of voice analysis results according to the duration since COVID-19 diagnosisWe confirmed whether there were significant differences in voice analysis parameters based on 90 days from the date of diagnosis of COVID-19 infection. When divided into two groups based on 90 days after COVID-19 diagnosis, among males, there were 15 patients with an infection duration of less than 90 days and 20 patients with a duration of 90 days or more. There were no significant differences in the mean scores for all measures based on the duration. Among females, there were 26 patients with an infection duration of less than 90 days and 24 patients with a duration of 90 days or more. The basic SFF of female patients increased significantly after 90 days compared to patients before 90 days, approaching normal value (p=0.047) (Table 4).
DISCUSSIONVoice production is a complex process that relies on the coordinated functioning of the respiratory and neurological systems. Dysfunction in these systems can result in voice disorders [12]. COVID-19 can significantly impact the respiratory system, potentially leading to conditions such as pneumonia and acute respiratory distress syndrome. Moreover, common COVID-19 symptoms like coughing, sore throat, runny nose, sneezing, and vomiting are closely related to the anatomical structures involved in voice production [9]. Consequently, COVID-19 infection, which may cause airflow and structural issues in the vocal folds, often results in voice changes and related concerns among affected individuals.
In a meta-analysis of eight papers, it was reported that dysphonia was present in 70% of cases when symptoms were assessed using multiple-choice options in COVID-19 patients [13]. Dysphonia, identified as an otorhinolaryngological complication of COVID-19, is frequently mentioned in the literature as a condition associated with mechanical ventilation and coughing during the infection, primarily affecting the lower respiratory system. In our study, dysphonia was the most prevalent accompanying symptom, observed in 24.7% of participants, followed by cough (10.6%), sputum (9.4%), and sore throat (7.1%). Notably, KVHI-30 scores demonstrated a strong correlation with the overall symptom burden (r=0.62, p<0.01), particularly in patients experiencing dysphonia and chronic cough. These findings highlight the significant impact of COVID-19 on voice-related symptoms and underscore the importance of addressing vocal impairments during recovery.
Among the participants, 12 were current smokers, 7 were former smokers, and 44 (51.2%) were voice professionals whose occupations required significant vocal use. Smoking status and voice professional status were not associated with voice changes in post-COVID-19 patients. Laryngoscopic findings revealed unilateral vocal fold paralysis in 2 male patients (5.7% of male participants). This suggests that the neurotropic effects of COVID- 19 infection may contribute to vocal fold paresis. These findings align with the hypothesis that SARS-CoV-2 can affect the peripheral nervous system, potentially leading to laryngeal neuropathy and subsequent vocal fold paralysis.
One study conducted a comparison of acoustic parameters between the COVID-19 group and the control group, revealing notable differences between the two cohorts. Specifically, the COVID-19 group exhibited higher values for parameters such as the standard deviation of F0, jitter, shimmer, and the difference between the first and second harmonic amplitude (H1H2). Conversely, the patient group demonstrated lower values for NHR, cepstral peak prominence, and MPT compared to healthy individuals. These findings suggest that COVID-19 can significantly impact the acoustic characteristics of voice production, indicating potential vocal abnormalities and dysfunctions in individuals affected by the virus [14]. In this study, similar to prior research, comparisons using the KVHI-30 and KVQOL revealed voice-related deterioration in COVID-19 patients. Notably, female patients exhibited significantly higher voice-related handicap scores (KVHI-30 total score: 22.1 vs. 8.3, p<0.001) and poorer voice-related quality of life (KVQOL total score: 80.5 vs. 91.7, p=0.002) compared to males. These disparities may be linked to anatomical and hormonal differences between sexes. Female vocal folds are shorter in length and have thinner mucosal layers, rendering them more vulnerable to inflammation. COVID-19-related laryngeal edema may exacerbate this vulnerability, leading to reductions in acoustic parameters such as F0 and SFF. This anatomical vulnerability aligns with prior findings in Korean populations [11]. Estrogen plays a critical role in modulating mucosal elasticity and hydration. Fluctuations in estrogen levels, particularly during menstrual cycles or menopause, may delay vocal fold recovery in females. This hypothesis is supported by studies demonstrating prolonged voice recovery times in women with hormonal imbalances [14]. The combined effects of anatomical and hormonal factors may explain the greater perceived vocal handicap and reduced quality of life observed in female post-COVID-19 patients. These findings underscore the need for sex-specific vocal rehabilitation strategies, particularly for women with persistent dysphonia.
Our study revealed significant changes in voice parameters among male and female post-COVID-19 patients, highlighting sex-specific differences in vocal outcomes. Among male patients, jitter (p=0.013) and shimmer (p=0.016) were significantly elevated compared to healthy controls, suggesting incomplete glottic closure and potential microtrauma to the vocal folds. These findings align with prior studies indicating that COVID-19-induced coughing can lead to mechanical stress on the vocal folds, contributing to submucosal hemorrhage and edema.
In female patients, shimmer showed a significant increase (p=0.003), while jitter did not differ significantly (p=0.064). This persistent elevation in shimmer may reflect residual irregularities in vocal fold vibration, potentially caused by prolonged laryngeal inflammation or neuropathy. These results suggest the need for long-term follow-up using laryngoscopic evaluations to monitor recovery and identify lingering vocal abnormalities.
Our findings are consistent with Asiaee et al. [14], which reported increased jitter, shimmer, and reduced MPT in COVID-19 patients. Similarly, Lechien et al. [7] observed a higher prevalence of voice disorders among female patients, which aligns with our data showing significantly higher KVHI-30 scores in females compared to males (p<0.001). However, our study identified a unique finding: male patients exhibited an increase in SFF (+9.2%, 124.37 Hz vs. normative value of 113.8 Hz). This result contrasts with Western studies [10], where no significant changes in SFF were reported among male patients post-COVID-19 infection. This discrepancy may be attributed to anatomical differences in vocal fold length between Korean and Western populations, emphasizing the need for further research on race-specific variations in vocal physiology.
Based on these results, treatment strategies for voice disorders in post-COVID-19 patients may differ by gender. For male patients, proton pump inhibitors can be prescribed to prevent laryngeal irritation, while antitussive medications can be used to reduce mechanical stress on the vocal folds caused by chronic coughing. For female patients, vocal hygiene education focusing on adequate hydration and vocal rest can help minimize shimmer irregularities. Additionally, voice therapy, such as resonant voice training, can be implemented to improve vocal fold vibratory stability and facilitate recovery.
Females demonstrated significant SFF recovery 90 days postinfection (post-90 days: 202.86 Hz vs. pre-90 days: 170.87 Hz, p=0.047), approaching normal values, while males exhibited no significant temporal changes in SFF. This recovery trend in females likely reflects the gradual resolution of laryngeal edema over time. Additionally, MPT increased over time in male patients but showed a non-significant decrease in female patients. These findings align with a previous study by Gölaç et al. [10], which reported improvements in MPT and acoustic parameters 3 months after COVID-19 infection. However, the observed recovery trend in SFF after 90 days is a novel finding that has not been previously reported in the literature.
This study has several limitations. First, it was conducted at a single institution with a relatively small sample size of 85 patients, which may limit the statistical power and generalizability of the findings. To address this, future multicenter studies with larger datasets are recommended to validate the results and provide broader insights. Second, the study lacked pre-COVID-19 voice data for comparison, which restricted the ability to directly assess voice changes caused by COVID-19 infection. The inclusion of pre-infection voice data in future research would allow for a more comprehensive evaluation of the impact of COVID-19 on voice characteristics.
CONCLUSIONThis study provides novel insights into the prevalence and characteristics of voice-related symptoms among South Korean post-COVID-19 patients, emphasizing the impact of the disease on vocal function and quality of life. Our findings revealed significant sex-specific differences in voice parameters, with males exhibiting elevated jitter and shimmer, suggesting incomplete glottic closure and potential microtrauma to the vocal folds. In contrast, females demonstrated a persistent increase in shimmer and significantly poorer KVQOL, likely influenced by anatomical and hormonal factors. These results underscore the need for tailored therapeutic approaches, such as antitussive medications for males and vocal hygiene education and voice therapy for females.
In conclusion, this study emphasizes the significant impact of COVID-19 on voice production, with notable sex-specific differences and recovery patterns. These findings provide a foundation for developing targeted rehabilitation strategies to improve vocal outcomes in post-COVID-19 patients.
NOTESAuthors’ Contribution Conceptualization: Ah Ra Jung. Data curation: Jung Ho Choi, Ji Hye Park. Formal analysis: Jung Ho Choi, Ah Ra Jung. Validation: Ah Ra Jung. Visualization: Jung Ho Choi, Ah Ra Jung. Writing—original draft: Jung Ho Choi, Ah Ra Jung. Writing—review & editing: Jung Ho Choi, Ah Ra Jung. Approval of final manuscript: all authors. Table 1.Demographic and clinical characteristics according to gender in post-COVID-19 patients (n=85)
Table 2.Results of voice analysis (n=85) Table 3.Sex-specific voice analysis results of COVID-19 patients compared to normal adult voice analysis values (n=85)
Table 4.Comparison of voice analysis results according to the duration since COVID-19 diagnosis (n=85)
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