HIGHLIGHTS
-
•
This study evaluated green tea gargling versus water in Japan.
-
•
A total of 22.8% lower COVID-19 incidence was observed with green tea use.
-
•
Gargling with green tea may help prevent COVID-19.
-
•
Results lack statistical significance; more research is needed to confirm effects.
Keywords: Green tea, catechin, gargling, COVID-19, prophylaxis
Abstract
Introduction
Catechins, a type of flavonoid and a major component of green tea, are expected to serve as a complementary preventive measure against COVID-19. However, to date, clinical evidence has not been established. This study aimed to evaluate the preventive effects of green tea gargling against COVID-19 in a multicenter RCT.
Methods
A total of 1,012 adults aged 18–70 years who provided written informed consent and met the eligibility criteria were randomly assigned to either a green tea or a water gargling group. Participants gargled 3 times a day for 12 weeks from December 2023 to February 2025 using commercially available green tea powder according to the package instructions. Background characteristics, incidence of COVID-19, and other preventive measures were assessed using self-administered questionnaires. Group differences were analyzed using multivariate logistic regression and Cox proportional hazards models.
Results
The incidence of COVID-19 in the full analysis population was 5.4% (27 of 503) in the green tea gargling group and 5.4% (27 of 500) in the water gargling group. In the per-protocol set population with a gargling adherence ≥80%, the incidence was 4.4% (17 of 386) in the green tea group and 5.7% (23 of 403) in the water group. Multivariate logistic regression adjusted for preventive measures showed an OR of 0.818 (95% CI=0.422, 1.556), and Cox proportional hazards analysis yielded a hazard ratio of 0.824 (95% CI=0.439, 1.546). Pneumonia and hospitalization occurred in 1 participant in the water group. No gargling-related adverse events were observed during the 12-week intervention.
Conclusions
In the per-protocol set population, green tea gargling showed a 22.8% relative reduction in COVID-19 incidence compared with water gargling, although the difference was not statistically significant. Further studies are needed to confirm the preventive effects of optimizing gargling frequency and catechin concentration.
INTRODUCTION
Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease emerged in late 2019 and spread rapidly worldwide, resulting in a global pandemic.1,2 Although most people are mildly infected, elderly individuals and/or those with underlying diseases are at an increased risk of developing severe illness.3 The development of vaccines against SARS-CoV-2, antiviral agents, and public health interventions has helped avert the pandemic; however, the epidemic is still continuing.4,5 Moreover, post–COVID-19 conditions (generally called long COVID) have emerged, adversely affecting patients’ quality of life.6,7 Therefore, prevention of COVID-19 remains a critical global concern.
Vaccination constituted a major pharmacological approach for the prevention of COVID-19,8,9 whereas public health measures primarily involved handwashing,10,11 mask wearing,12,13 and alcohol-based hand sanitization.14,15 Vaccination, particularly with RNA vaccines, rapidly became widely used worldwide and represents the most reliable preventive method; however, its effectiveness has been reported to be approximately 60% after the outbreak of the Omicron variant.8,16 Moreover, the severity of adverse reactions and high costs are considered disadvantages. In public health measures, experimental studies have demonstrated reductions in the SARS-CoV-2 viral load or barrier effects for handwashing, mask use, and alcohol-based hand sanitization; however, clinical trials assessing their preventive effectiveness against COVID-19 in humans are limited. In Japan, gargling with water is commonly practiced for preventing common cold and acute upper respiratory tract infections.17 However, that study was conducted before the COVID-19 outbreak, and its effectiveness against COVID-19 has not yet been investigated.
Catechins, a type of flavonoid and major components of green tea, exhibit antiviral activities against various viruses.18 In vitro studies have reported that epigallocatechin gallate (EGCG), a major catechin found in green tea, reduces the amount of SARS-CoV-2 in vitro.19, 20, 21 The proposed mechanisms include inhibition of viral entry into host cells by binding to angiotensin-converting enzyme 2 (ACE2) receptors on the oral mucosa22 and the direct interaction of EGCG with the viral surface protein (receptor-binding domain), thereby preventing the attachment of the virus to host cells.19,23, 24, 25, 26 Therefore, green tea may serve as a complementary preventive measure against COVID-19. However, to date, clinical studies in humans remain limited; most have lacked control groups27,28 or involved small sample sizes,29 and thus, clinical evidence has not yet been established. In vitro antiviral activity and clinical preventive effects are fundamentally different levels of evidence. Thus, this study aimed to evaluate the preventive effects of green tea gargling against COVID-19 through a large-scale, multicenter RCT using water gargling as a control.
METHODS
Study Sample
This open-label RCT consisted of 2 parallel groups: a green tea gargling group and a water gargling group. Participants were recruited through 5 organizations from 4 prefectures in Japan: the University of Shizuoka (Shizuoka Prefecture), Meiji University (Kanagawa Prefecture), Kagoshima University (Kagoshima Prefecture), Hakujyujikai (Tokyo metropolitan area), and Seirei Hamamatsu General Hospital (Shizuoka Prefecture). The intervention period comprised 2 winter seasons: December 2023–February 2024 and December 2024–February 2025.
The inclusion criteria were as follows: male and female aged 18–70 years who were able to gargle for 12 weeks and complete the survey. The exclusion criteria included possible allergies to green tea, dysphagia, chronic systemic infection, and inadequate participation, as determined by physicians.
The primary endpoint was the incidence of COVID-19 during the 12-week intervention. Secondary endpoints included the time from the intervention to the onset of COVID-19, complications such as pneumonia, and gargling-related adverse events.
Eligible participants were enrolled and randomly assigned to either group in a 1:1 ratio on the basis of a computer-generated pseudorandom number table by TI. Randomization was conducted using the stratified block randomization method, with organization serving as the stratification factor. Concealment of allocation for participants was conducted at each organization.
This study was approved by the University of Shizuoka Research Ethics Committee (Protocol Number 5-14) and registered at the University Hospital Medical Information Network (Registry Number UMIN000052116). This study was performed in accordance with the Declaration of Helsinki and the Ethical Guidelines for Medical and Biological Research Involving Human Subjects. Before commencing the study, participants were given a face-to-face explanation of the study, viewed an online video detailing it, and signed a written informed consent form.
Measures
Before participating in the study, participants completed a self-administered questionnaire. The questionnaire was primarily paper based; however, participants who could not complete it on paper were allowed to use the web-based version. The questionnaire items included background information such as sex; age; occupation (students, healthcare workers, others); public transportation use; alcohol drinking habits; smoking habits; and tea drinking habits, such as green tea, black tea, and oolong tea as well as tea consumption. Before the intervention, participants received a stainless-steel water bottle and a survey form in diary format to record their implementation status. Those assigned to the green tea gargling group additionally received commercially available green tea powder Oi o-cha (ITO EN, Ltd., Tokyo, Japan) and were instructed to dissolve 2 sticks of the powder in about 400 mL of water according to the instructions on the package (matching the catechin concentration of commercially available green tea bottles) every morning during the intervention periods. The participants gargled 3 times daily (morning before going to work or school, noon at lunchtime, and evening after returning home) with their assigned gargle solution. The gargling procedure involved rinsing the oral cavity with the allocated solution and gargling the pharyngeal area. This process was repeated 3 times per gargling session and repeated 3 times daily. The gargling method used in this study was similar to that of Satomura et al.’s study,17 which is the common method of gargling in Japan. During the intervention period, the participants were instructed to drink tea without changing their drinking habits. The participants recorded their daily physical condition using a questionnaire. The questionnaire included the following items: implementation of gargling, hand washing, wearing masks, alcohol hand sanitization, vaccination against COVID-19, and the occurrence of complications such as pneumonia or any adverse events. According to the adverse events, 2 physicians (HY and NT) evaluated the causal relationships with gargling. For vaccine items, participants were asked about their vaccination history from the 6 months prior to the intervention until the end of the intervention, and the diagnosis of COVID-19 was defined by a positive polymerase chain reaction or antigen test performed at a hospital or medical clinic.
The questionnaire was administered every 4 weeks at each organization, and participants were interviewed and monitored for any problems with the study at the time of data collection. YK and YN collected the data from April 1, 2024, to August 28, 2025; YI and TI analyzed the data for research purposes from August 29, 2025, to November 10, 2025.
Statistical Analysis
Statistical analyses were performed using SAS software (Version 9.4; SAS Institute, Cary, NC). Given that no previous studies have been conducted on the incidence of COVID-19 with green tea gargling, the sample size was estimated according to previous studies30,31 on the incidence of influenza infection with green tea gargling. On the basis of the incidence proportion observed in the previous studies, the incidence proportion of COVID-19 was estimated as 3.6% in the green tea gargling group and 7.8% in the water gargling group, and considering potential dropouts, the sample size for this study was set at 550 participants per group according to the predicted outcome.
The full analysis set (FAS) population was determined on the basis of intention-to-treat principles. The FAS excluded participants who did not receive the intervention, had no available data, or refused to allow the use of the data. The per-protocol set (PPS) population comprised participants whose gargling adherence rates were at least 80% during the 12-week intervention. Missing data were not imputed.
Continuous variables were reported as mean±SD or median (minimum–maximum), whereas qualitative variables were expressed as frequency (%). To analyze the differences in background characteristics and preventive measures, the Wilcoxon rank-sum test was used to compare the median values, whereas the 222square test was used for frequency variables.
The primary endpoint, the incidence of COVID-19 during the 12-week intervention, was compared using multivariate logistic regression analysis, incorporating covariates considered to influence preventive factors. For the secondary endpoints, the cumulative incidence rates of the groups were determined using the Kaplan–Meier method, and the differences were evaluated using the log-rank test. In addition, the Cox proportional hazards model was used to incorporate the same covariates used for the primary endpoint. The numbers of complications, admissions, and adverse events in each group were compared. A p<0.05 was considered statistically significant.
RESULTS
As shown in Figure 1, 1,015 candidates gave informed consent (2023–2024 winter season: 452 candidates; 2024–2025 winter season: 563 candidates). Of these, 1,012 candidates who met the eligibility criteria were randomly allocated to the green tea or water gargling group, whereas 3 were excluded owing to the age criterion (being aged >70 years). Because of missing data (no survey form could be collected), 4 participants in the green tea gargling group and 5 participants in the water gargling group were excluded from the FAS population. On the basis of gargling adherence rates of less than 80%, 117 participants in the green tea gargling group and 97 participants in the water gargling group were excluded from the PPS population.
Figure 1.
Flow diagram for the study.
FAS, full analysis set; PPS, per-protocol set.
Table 1 shows the background characteristics and implementation rates of the preventive measures. Regarding the background characteristics of the FAS and PPS populations, no significant statistical differences were observed between the green tea and water gargling groups in terms of sex, age, occupation, use of public transportation, smoking, alcohol consumption, tea drinking habits, and tea consumption.
Table 1.
Background Characteristics and Implementation Rates of Preventive Measures
| Characteristics | FAS |
PPS |
|||||
|---|---|---|---|---|---|---|---|
| Green tea gargling group n=503 |
Water gargling group n=500 |
p-value | Green tea gargling group n=386 |
Water gargling group n=403 |
p-value | ||
| Background characteristic of the study participants | |||||||
| Sex (female/male) | 364 (72.4%)/139 (27.6%) | 343 (68.6%)/157 (31.4%) | 0.191a | 277 (71.8%)/109 (28.2%) | 285 (70.7%)/118 (29.3%) | 0.747a | |
| Age, years | 42.05 (14.99) | 42.26 (14.90) | 0.716b | 42.75 (14.90) | 43.23 (14.44) | 0.598b | |
| Occupation (students/healthcare workers/others) | 109 (21.7%)/273 (54.3%)/121 (24.1%) | 94 (18.8%)/286 (57.2%)/120 (24.0%) | 0.495a | 79 (20.5%)/208 (53.9%)/99 (25.6%) | 61 (15.1%)/245 (60.8%)/97 (24.1%) | 0.082a | |
| Public transportation use | 112 (22.3%) | 100 (20.0%) | 0.379a | 79 (20.5%) | 68 (16.9%) | 0.195a | |
| Smoking habits | 51 (10.1%) | 48 (9.6%) | 0.775a | 33 (8.6%) | 38 (9.4%) | 0.666a | |
| Alcohol drinking habits | 98 (19.5%) | 100 (20.0%) | 0.837a | 70 (18.1%) | 80 (19.9%) | 0.539a | |
| Tea drinking habits | 322 (64.0%) | 324 (64.8%) | 0.795a | 257 (66.6%) | 264 (65.5%) | 0.807a | |
| Tea consumption: | |||||||
| Green tea, mL | 120 (0–1500) | 100 (0–2500) | 0.921b | 200 (0–1500) | 200 (0–2500) | 0.737b | |
| Black tea, mL | 0 (0–1500) | 0 (0–1000) | 0.536b | 0 (0–1500) | 0 (0–1000) | 0.137b | |
| Oolong tea, mL | 0 (0–1500) | 0 (0–2000) | 0.142b | 0 (0–1500) | 0 (0–2000) | 0.282b | |
| Implementation rates of preventing measures | |||||||
| Gargling, % | 87.20 (14.08) | 88.34 (14.10) | 0.073b | 93.57 (5.87) | 93.93 (5.81) | 0.302b | |
| Hand washing, % | 94.58 (11.99) | 94.75 (11.76) | 0.876b | 96.51 (8.67) | 96.76 (7.49) | 0.785b | |
| Wearing mask, % | 77.64 (27.59) | 79.89 (26.45) | 0.183b | 79.87 (26.48) | 84.26 (22.85) | 0.027b | |
| Hand sanitization, % | 68.30 (33.77) | 70.91 (32.63) | 0.251b | 68.84 (34.31) | 74.76 (31.21) | 0.035b | |
| COVID-19 vaccination | 87 (17.6%) | 103 (21.0%) | 0.176a | 67 (17.4%) | 87 (21.6%) | 0.134a | |
Note: Age and gargling, hand washing, wearing mask, hand sanitization are expressed as mean (SD). Tea consumptions of green tea, black tea, and oolong tea are expressed as median (minimum–maximum). Other factors are expressed as frequencies (%).
p-values are based on the chi-square test.
p-values are based on the Wilcoxon rank-sum test.
FAS, full analysis set; PPS, per-protocol set.
Regarding the implementation rates of prevention measures in the FAS population, no significant differences were observed between the green tea and water gargling groups for gargling, hand washing, wearing masks, alcohol hand sanitization, and COVID-19 vaccination. However, in the PPS population, the implementation rate of wearing masks (mean±SD) was significantly higher in the water gargling group (84.26±22.85%) than in the green tea gargling group (79.87±26.48%) (p=0.027, Wilcoxon rank-sum test). Similarly, the rate of alcohol hand sanitization was higher in the water gargling group (74.76±31.21%) than in the green tea gargling group (68.84±34.31%) (p=0.035, Wilcoxon rank-sum test).
For the primary endpoint, Table 2 shows the incidence of COVID-19 during the 12-week intervention. The incidence proportion of COVID-19 in the FAS population was 5.4% (27 of 503) in the green tea gargling group and 5.4% (27 of 500) in the water gargling group. In contrast, the incidence proportion of COVID-19 in the PPS population was 4.4% (17 of 386) in the green tea gargling group and 5.7% (23 of 403) in the water gargling group. In the PPS population, the calculation of the index of evidence-based medicine showed the following: RR reduction of 22.8%, absolute risk reduction of 1.3%, and number needed to treat of 77. A multivariate logistic regression analysis conducted subsequently in the PPS population, adjusting for preventive measures, showed an OR for green tea gargling of 0.818 (95% CI=0.422, 1.556) (Table 3).
Table 2.
Incidence of COVID-19 in 12 Weeks Intervention
| Study period | FAS |
PPS |
||
|---|---|---|---|---|
| Green tea gargling group |
Water gargling group |
Green tea gargling group |
Water gargling group |
|
| December 2023–February 2024 | 14 (6.3%) (n=221) |
18 (8.0%) (n=226) |
9 (5.3%) (n=169) |
15 (8.5%) (n=176) |
| December 2024–February 2025 | 13 (4.6%) (n=282) |
9 (3.3%) (n=274) |
8 (3.7%) (n=217) |
8 (3.5%) (n=227) |
| Total | 27 (5.4%) (n=503) |
27 (5.4%) (n=500) |
17 (4.4%) (n=386) |
23 (5.7%) (n=403) |
Note: Incidence of COVID-19 is expressed as frequencies (%).
FAS, full analysis set; PPS, per-protocol set.
Table 3.
The Results of Multivariate Logistic Regression Analysis in the PPS Population
| Variable | OR | 95% CI |
|---|---|---|
| Allocation (green tea gargling versus water gargling) | 0.818 | 0.422, 1.556 |
| Hand washing | 0.987 | 0.954, 1.041 |
| Wearing mask | 1.017 | 0.997, 1.044 |
| Hand sanitization | 1.008 | 0.995, 1.023 |
| COVID-19 vaccination | 0.971 | 0.422, 2.038 |
PPS, per-protocol set.
As secondary endpoints, Figure 2 shows the cumulative incidence rates of COVID-19 plotted using the Kaplan–Meier method. In the FAS population, there were no significant differences in the curves between the 2 groups. In the PPS population, a slightly lower incidence rate was observed in the green tea gargling group than in the water gargling group; however, the result of the log-rank test was not significant (p=0.401).
Figure 2.
Cumulative incidence rates of COVID-19 plotted using the Kaplan–Meier method.
(A) FAS analysis. (B) PPS analysis.
Note: p-value is based on the log-rank test.
FAS, full analysis set; PPS, per-protocol set.
Subsequently conducted using the Cox proportional hazards model adjusted with the same preventive measures selected in the primary endpoint, the hazard ratio for green tea gargling was 0.824 (95% CI=0.439, 1.546). Pneumonia and hospitalization occurred in 1 participant in the water gargling group. No gargling-related adverse events were observed during the 12-week intervention.
Monitoring of green tea catechins in the green tea gargling solution conducted during the intervention period (n=10) showed that total catechin and EGCG concentrations (mean±SD) were 35.53±4.44 and 11.88±1.46 mg/dL, respectively. The approximate daily catechin exposure during the intervention was 142.12 mg. The catechin contents in the gargling solution were analyzed by high-performance liquid chromatography with ultraviolet detection.32
DISCUSSION
This study represents the largest multicenter RCT worldwide to date evaluating the gargling effects of green tea, with 1,012 participants. The quality of the study was ensured by an extremely low dropout rate of 0.9% (9 of 1,012 allocated participants) and mean adherence rates to gargling exceeding 87% in both groups.
Contrary to expectations, no difference in the incidence of COVID-19 was observed between the 2 groups in the FAS population. In contrast, in the PPS population, multivariate logistic regression analysis adjusted for other preventive measures demonstrated an 18.2% reduction in the point estimate calculated by the OR in the green tea gargling group; however, this finding did not reach statistical significance. The Cox proportional hazards model yielded similar results. These results suggest that it remains unclear whether green tea gargling is superior to water gargling in preventing the spread of COVID-19.
There are several possible explanations for the lack of statistical significance. One possible explanation concerns gargling frequency and catechin concentration. The daily frequency of gargling was set to 3 times, according to the common Japanese lifestyle. Previously, catechin levels in the pharyngeal mucosa were detected after drinking green tea components for up to 60 minutes,33 suggesting that a frequency of more than 3 times daily may be required to block the ACE2 receptor in the oral cavity.26 Therefore, gargling more frequently than 3 times daily may confer greater preventive effects. Regarding catechin concentrations, an in vitro study has shown that SARS-CoV-2 in saliva is reduced at catechin concentrations similar to those found in commercially available green tea beverages.19 However, in actual clinical settings, higher catechin concentrations may be required to maintain sufficient catechin levels in the pharyngeal mucosa. In addition, it is possible that mutated virus strains altered the effects observed in the in vitro studies.
Green tea catechins, such as EGCG, inhibit SARS-CoV-2 entry by interacting with ACE2 receptors and viral spike proteins.19,22, 23, 24, 25 However, these mechanisms may occur through both local exposure in the oral cavity (gargling) and systemic exposure after drinking green tea. In this study, the baseline characteristics showed that 64%–67% of participants had habitual tea-drinking behavior. Therefore, the difference in effect size between green tea and water gargling may have been attenuated owing to the additive effect of green tea drinking in both groups. According to the additional multivariate logistic regression analysis, which added habitual green tea consumption as a covariate, the OR for gargling was 0.810 (95% CI=0.424, 1.549), indicating a slightly greater decreasing tendency, although this was not statistically significant.
In the multivariate logistic regression analysis, the ORs of preventive measures showed that handwashing, mask use, alcohol-based hand sanitization, and even vaccination were not statistically significant. These preventive measures are recommended for the prevention of COVID-19.8, 9, 10, 11, 12, 13, 14, 15, 16 However, systematic reviews have demonstrated that their effectiveness in clinical settings varies and may be limited.8,10,12,14,16 These findings should be interpreted with caution because their effectiveness might be influenced by differences in adherence intensity to preventive measures.
In the safety assessment, no adverse events related to gargling were observed, and only 1 hospitalization due to pneumonia as a complication of COVID-19 occurred in the water gargling group. Green tea gargling was found to be extremely safe and may be considered a safe public health preventive measure. Future clinical trials that consider gargling frequency and catechin concentration are required to elucidate the preventive effect of green tea gargling on COVID-19.
Limitations
This study has several limitations. First, blinding was not possible because water was used as the control gargling solution, which may have introduced performance bias in participants and those delivering the intervention. Second, the water gargling group showed significantly higher adherence rates to other preventive measures, such as mask wearing and alcohol-based hand sanitization, in the PPS population, which may have confounded the results despite adjustments in the multivariate logistic regression analysis. Third, the sample size calculation assumed a COVID-19 incidence of approximately 7.8% in the control group; however, the observed incidence was 5.4%, suggesting that the study may have been underpowered to detect moderate protective effects. Fourth, approximately 64%–67% of participants in both groups reported habitual green tea consumption, which may have attenuated the difference in effect size between the 2 groups, and residual confounding from real-time green tea consumption could not be excluded. Fifth, the primary endpoint was the incidence of COVID-19 infection; however, the antiviral activity of catechins is primarily associated with a reduction of viral infectivity, inhibition of viral entry, and a reduction of viral load.19, 20, 21, 22, 23, 24, 25, 26 Therefore, measuring only infection incidence may have underestimated potential biological effects, such as salivary viral load, symptom severity, and duration of viral shedding. Finally, the gargling frequency of 3 times daily and the catechin concentration used in this study may not have been sufficient to maintain adequate catechin levels in the pharyngeal mucosa throughout the day.
CONCLUSIONS
A large-scale RCT was conducted to evaluate the preventive effects of green tea gargling on COVID-19. In the PPS population, the incidence of COVID-19 was reduced by 22.8% compared with that in the water gargling group, although this reduction was not statistically significant. Further clinical studies are required to determine the optimal gargling frequency and catechin concentration.
Acknowledgments
ACKNOWLEDGMENTS
The authors express their sincere gratitude to the participants at the University of Shizuoka, Meiji University, Kagoshima University, Hakujujikai, and Seirei Hamamatsu General Hospital. The authors also thank the study coordinators at each organization, the Mori Town Office, Shizuoka Prefectural Department of Health and Welfare, Kikugawa General Hospital, Industrial Research Institute of Shizuoka Prefecture, Hamamatsu Pharmaceutical Association Drug Information Management Center, Shizuoka Medical Communication Group, Shizuoka Prefectural General Hospital, Shizuoka City Shizuoka Hospital, and Niji-no-Sato Taniyama Nursing Home.
Funding: This work was funded by a grant from ITO EN, Ltd. (DF24324-10).
Declaration of interest: YK received a grant from ITO EN, Ltd. (DF24324-10). CT, MK, MI, TT, HK, and IK are employees of ITO EN, Ltd. HY received a grant from ITO EN, Ltd. (DF24324-10) and a scholarship donation from ITO EN, Ltd. (A24507). No other financial disclosures were reported.
CRediT AUTHOR STATEMENT
Yasue Kawai: Investigation, Funding acquisition, Methodology, Writing – original draft, Writing – review & editing. Yoshihiko Ito: Formal analysis, Methodology. Takahiro Nakamura: Investigation, Methodology. Daisuke Furushima: Investigation, Methodology. Yuina Nakai: Investigation. Motoyasu Miura: Investigation, Methodology. Shinya Uchida: Investigation, Methodology. Keiko Unno: Investigation. Yoriyuki Nakamura: Investigation. Norikata Takuma: Investigation. Takatsugu Ikukawa: Formal analysis. Mitsuo Kimata: Investigation. Chika Tagata: Data curation. Makoto Kobayashi: Data curation. Masaki Ichitani: Data curation. Takanobu Takihara: Data curation. Hitoshi Kinugasa: Data curation. Ichiro Kato: Data curation. Hiroshi Yamada: Conceptualization, Funding acquisition, Methodology, Project administration, Writing – review & editing.
REFERENCES
- 1.WHO COVID-19 dashboard. World Health Organization. https://data.who.int/dashboards/covid19/cases?n=c. Updated May 17, 2026. Accessed October 24, 2025.
- 2.Sachs J.D., Karim S.S.A., Aknin L., et al. The Lancet Commission on lessons for the future from the COVID-19 pandemic. Lancet. 2022;400(10359):1224–1280. doi: 10.1016/S0140-6736(22)01585-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Underlying conditions and the higher risk for severe COVID-19. U.S. Centers for Disease Control and Prevention. https://www.cdc.gov/covid/hcp/clinical-care/underlying-conditions.html. Updated February 6, 2025. Accessed December 9, 2025.
- 4.World Health Organization. Tracking SARS-CoV-2 variants. https://www.who.int/activities/tracking-SARS-CoV-2-variants. Accessed December 9, 2025.
- 5.Kaku Y., Yo M.S., Tolentino J.E., et al. Virological characteristics of the SARS-CoV-2 KP.3, LB.1, and KP.2.3 variants. Lancet Infect Dis. 2024;24(8):e482–e483. doi: 10.1016/S1473-3099(24)00415-8. [DOI] [PubMed] [Google Scholar]
- 6.Honda H., Takamatsu A., Miwa T., et al. Prolonged symptoms after COVID-19 in Japan: a nationwide survey of the symptoms and their impact on patients’ quality of life. Am J Med. 2025;138(1):98–107.e4. doi: 10.1016/j.amjmed.2023.04.040. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Kinugasa Y., Llamas-Covarrubias M.A., Ozaki K., et al. Post-coronavirus disease 2019 syndrome in Japan: an observational study using a medical database. JMA J. 2023;6(4):416–425. doi: 10.31662/jmaj.2023-0048. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Song S., Madewell Z.J., Liu M., Longini I.M., Yang Y. Effectiveness of SARS-CoV-2 vaccines against Omicron infection and severe events: a systematic review and meta-analysis of test-negative design studies. Front Public Health. 2023;11 doi: 10.3389/fpubh.2023.1195908. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Arashiro T., Arima Y., Kuramochi J., et al. Effectiveness of BA.1- and BA.4/BA.5-containing bivalent COVID-19 mRNA vaccines against symptomatic SARS-CoV-2 infection during the BA.5-dominant period in Japan. Open Forum Infect Dis. 2023;10:ofad240. doi: 10.1093/ofid/ofad240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Gozdzielewska L., Kilpatrick C., Reilly J., et al. The effectiveness of hand hygiene interventions for preventing community transmission or acquisition of novel coronavirus or influenza infections: a systematic review. BMC Public Health. 2022;22(1):1283. doi: 10.1186/s12889-022-13667-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Karout L., Serwat A., El Mais H., Kassab M., Khalid F., Ruiz Mercedes B. COVID-19 prevalence, risk perceptions, and preventive behavior in asymptomatic Latino population: a cross-sectional study. Cureus. 2020;12 doi: 10.7759/cureus.10707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Floriano I., Silvinato A., Bacha H.A., Naime Barbosa4 A., Tanni5 S., Marques Bernardo2,6 W. Effectiveness of wearing masks during the COVID-19 outbreak in cohort and case-control studies: a systematic review and meta-analysis. J Bras Pneumol. 2023;49 doi: 10.36416/1806-3756/e20230003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Ueki H., Furusawa Y., Iwatsuki-Horimoto K., et al. Effectiveness of face masks in preventing airborne transmission of SARS-CoV-2. mSphere. 2020;5(5) doi: 10.1128/mSphere.00637-20. e00637-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Price L., Gozdzielewska L., Alejandre J.C., et al. Systematic review on factors influencing the effectiveness of alcohol-based hand rubbing in healthcare. Antimicrob Resist Infect Control. 2022;11(1):16. doi: 10.1186/s13756-021-01049-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Leslie R.A., Zhou S.S., Macinga D.R. Inactivation of SARS-CoV-2 by commercially available alcohol-based hand sanitizers. Am J Infect Control. 2021;49(3):401–402. doi: 10.1016/j.ajic.2020.08.020. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Lin D.Y., Xu Y., Gu Y., et al. Effectiveness of bivalent boosters against severe omicron infection. N Engl J Med. 2023;388(8):764–766. doi: 10.1056/NEJMc2215471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Satomura K., Kitamura T., Kawamura T., et al. Prevention of upper respiratory tract infections by gargling: a randomized trial. Am J Prev Med. 2005;29(4):302–307. doi: 10.1016/j.amepre.2005.06.013. [DOI] [PubMed] [Google Scholar]
- 18.Tominaga T., Furushima D., Yamada H. In: Tea as a Food Ingredient Properties, Processing, and Health Aspects. Yin J., Fu Z., Xu Y., editors. CRC Press; Boca Raton, FL: 2022. Tea polyphenols for the prevention of influenza and the common cold; pp. 127–138. [DOI] [Google Scholar]
- 19.Shin-Ya M., Nakashio M., Ohgitani E., et al. Effects of tea, catechins and catechin derivatives on Omicron subvariants of SARS-CoV-2. Sci Rep. 2023;13(1) doi: 10.1038/s41598-023-43563-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Ohgitani E., Shin-Ya M., Ichitani M., et al. Rapid inactivation in vitro of SARS-CoV-2 in saliva by black tea and green tea. Pathogens. 2021;10(6):721. doi: 10.3390/pathogens10060721. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Ohgitani E., Shin-Ya M., Ichitani M., et al. Significant inactivation of SARS-CoV-2 in vitro by a green tea catechin, a catechin-derivative, and black tea galloylated theaflavins. Molecules. 2021;26(12):3572. doi: 10.3390/molecules26123572. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Ohishi T., Hishiki T., Baig M.S., et al. Epigallocatechin gallate (EGCG) attenuates severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection by blocking the interaction of SARS-CoV-2 spike protein receptor-binding domain to human angiotensin-converting enzyme 2. PLoS One. 2022;17(7) doi: 10.1371/journal.pone.0271112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Liu J., Bodnar B.H., Meng F., et al. Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor. Cell Biosci. 2021;11(1):168. doi: 10.1186/s13578-021-00680-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Lu C.K., Lung J., Shu L.H., et al. The inhibiting effect of GB-2, (+)-catechin, theaflavin, and theaflavin 3-gallate on interaction between ACE2 and SARS-CoV-2 EG.5.1 and HV.1 variants. Int J Mol Sci. 2024;25(17):9498. doi: 10.3390/ijms25179498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Alanzi A.R., Parvez M.K., Al-Dosari M.S. Structure-based virtual identification of natural inhibitors of SARS-CoV-2 and its Delta and Omicron variant proteins. Future Virol. 2023;18(7):421–438. doi: 10.2217/fvl-2022-0184. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Matsumoto F., Nagai S., Ikeda N., et al. Pyrogallol B-ring enhances catechin binding to the SARS-CoV-2 spike receptor-binding domain to inhibit interaction with ACE2. Sci Rep. 2026;16(1) doi: 10.1038/s41598-026-41170-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Yin X., Zhu W., Tang X., et al. Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer. BMC Cancer. 2024;24(1):486. doi: 10.1186/s12885-024-12228-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Bettuzzi S., Gabba L., Cataldo S. Efficacy of a polyphenolic, standardized green tea extract for the treatment of COVID-19 syndrome: a proof-of-principle study. COVID. 2021;1(1):2–12. doi: 10.3390/covid1010002. [DOI] [Google Scholar]
- 29.Tominaga T., Ikukawa T., Furushima D., Nakamura T.J., Yamada H. An exploratory randomized controlled study to investigate concentration-dependence of green tea catechin gargling on acute upper respiratory tract infections. Biol Pharm Bull. 2024;47(7):1331–1337. doi: 10.1248/bpb.b24-00113. [DOI] [PubMed] [Google Scholar]
- 30.Toyoizumi K., Yamada H., Matsumoto K., Sameshima Y. Gargling with green tea for influenza prophylaxis: a pilot clinical study. Jpn J Clin Pharmacol Ther. 2013;44(6):459–461. doi: 10.3999/jscpt.44.459. [DOI] [Google Scholar]
- 31.Ide K., Yamada H., Matsushita K., et al. Effects of green tea gargling on the prevention of influenza infection in high school students: a randomized controlled study. PLoS One. 2014;9(5) doi: 10.1371/journal.pone.0096373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Goto T., Yoshida Y., Kiso M., Nagashima H. Simultaneous analysis of individual catechins and caffeine in green tea. J Chromatogr A. 1996;749(1–2):295–299. doi: 10.1016/0021-9673(96)00456-6. [DOI] [Google Scholar]
- 33.Furushima D., Otake Y., Koike N., et al. Investigation of the oral retention of tea catechins in humans: an exploratory interventional study. Nutrients. 2021;13(9):3024. doi: 10.3390/nu13093024. [DOI] [PMC free article] [PubMed] [Google Scholar]