key: cord-1002685-hmcfae6a authors: Nanri, Akiko; Yamamoto, Shohei; Konishi, Maki; Ohmagari, Norio; Mizoue, Tetsuya title: Green tea consumption and SARS-CoV-2 infection among staff of a referral hospital in Japan date: 2022-01-13 journal: Clin Nutr Open Sci DOI: 10.1016/j.nutos.2022.01.002 sha: 41238fe6b796fafc4402bac4fd34bc34bed55213 doc_id: 1002685 cord_uid: hmcfae6a Background & Aim This study examined the association between green tea consumption and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among Japanese. Methods Participants were staff of a large referral hospital in Tokyo. Green tea consumption was ascertained via a questionnaire. SARS-CoV-2 infection was identified through in-house records of PCR-confirmed COVID-19 cases or antibody tests. Multiple logistic regression was used to estimate the odds ratio of SARS-CoV-2 infection according to green tea consumption. Results Of 2640 participants (767 men and 1873 women; aged 21-75 years), 74 (2.8%) were confirmed or suspected to have been infected with SARS-CoV-2 during the epidemic. Overall, SARS-CoV-2 infection was not significantly associated with green tea consumption. There was a suggestion of a decrease in the odds of this infection associated with green tea consumption of ≥4 cups/day (odds ratio 0.51, 95% confidence interval 0.20–1.31). Conclusions Green tea consumption was not appreciably associated with the risk of SARS-CoV-2 infection. A lower odds of infection among those who consumed high green tea consumption deserves further investigation. The pandemic of coronavirus disease (COVID-19) has led to 241.9 million patients and 4.9 million deaths globally as of October 21, 2021 [1] . WHO has recommended infection prevention behaviors, including physical distancing and use of mask as well as vaccination [2] . Green tea has been suggested to lower the risk of influenza and upper respiratory tract infections [3] . Experimental studies show that epigallocatechin gallate, rich in green tea, inhibits infection and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [4, 5] . Countries with higher consumption of green tea are shown to have a lower morbidity/mortality rate of COVID-19 [6] . Here we examined the association of green tea consumption with COVID-19 infection in a cohort of healthcare workers in Japan. The present study used data of ongoing repeat serological survey during the COVID-19 pandemic among workers of the National Center for Global Health and Medicine, Japan (NCGM) [7, 8] . Participants were asked to donate venous blood and answer a questionnaire in each survey. We measured IgG (Abbott ARCHITECT®) and total antibodies (Roche Elecsys®) against the SARS-CoV-2 nucleocapsid (N) protein. Written informed consent was obtained from each participant. This study was approved by the ethics committee of NCGM. Green tea consumption was asked at the third survey, in which 2,779 participated (90%). Of these, we excluded those who lacked data necessary for the analysis, leaving 2640 aged 21-75 years (767 men and 1873 women) for analysis. We defined SARS-CoV-2 infection using two sources of information: the above-mentioned antibody tests (positive on either test at least once in the three surveys) and in-house records of PCR-confirmed COVID-19 cases. We asked about green tea consumption over the last month with six options ranging from "none or ≤2 day/week" to "≥4 cups/day" and divided participants into four ("<1 cup/day" to "≥4 J o u r n a l P r e -p r o o f cups/day"). Baseline characteristics according to green tea consumption were expressed as mean (standard deviation) for continuous variables and percentage for categorical variables. Trend association between confounding factors and green tea consumption were tested using linear regression analysis for continuous variables, treating ordinal number in each category of green tea consumption as a continuous variable, and the Mantel-Haenszel chi-squared test for categorical variables. We run multiple logistic regression to estimate odds ratios of SARS-CoV-2 infection for green tea consumption with adjustment for age, sex, occupation, occupational risk of SARS-CoV-2 infection, infection prevention practice, body mass index (BMI), use of public transportation, high-risk behavior (2 items), and close contact with COVID-19 patient. Trend association was assessed by assigning ordinal numbers to the increasing category of green tea consumption and treating them as continuous. We repeated the analysis by information source (PCR-confirmed or antibody test positive only) and timing of infection (before or after vaccination of Pfizer-BioNTech). Additionally, we performed a sensitivity analysis using dichotomized category of green tea consumption (≤2 cups/day and ≥3 cups/day). Two-side P values <0.05 were regarded as statistically significant. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC. USA). Baseline characteristics of participants according to category of green tea consumption are shown in Table 1 . Participants with higher consumption of green tea tended to have higher BMI and use public transportation (train or bus) compared to those with lower consumption. No other differences according to green tea consumption were observed. J o u r n a l P r e -p r o o f 8 Table 2 Odds ratio (95% confidence intervals) of SARS-CoV-2 infection according to the category of green tea consumption. Green tea consumption (cup/day) <1 Abbreviations: CI, confidence interval; OR, odds ratio; PCR, polymerase chain reaction. In this study among healthcare workers in Japan, where green tea drinking is popular, there was no evidence of a significant association between green tea consumption and SARS-CoV-2 infection, which was confirmed by PCR or suggested by antibody tests. Nevertheless, people who consumed ≥4 cups/day of green tea had a lower, albeit statistically not significant, odds of SARS-CoV-2 infection, a finding compatible with experimental data showing that epigallocatechin gallate inhibits infection and transmission of SARS-CoV-2 [4, 5] . The lower odds of infection associated with high green tea consumption was similarly observed across different outcomes (PCR-confirmed or antibody test positive only) and timings (infection before or after vaccination). This finding suggests green tea consumption prevents both symptomatic or asymptomatic infection, irrespectively of vaccination status. Experimental study shows that green tea can inhibit the infection of both wild-type SARS-CoV-2 and its variants with similar magnitude [4] . As the post-vaccination period of the present study corresponded to the epidemic of the Delta variant, the result may also give some support for the effect of green tea against the variant. The present study was not large enough to detect the observed association with statistical significance. Large-scale investigations are required to confirm the present findings and to explore minimal consumption of green tea associated with lower risk of SARS-CoV-2 infection. The present study did not find significant evidence to support a protective role of green tea consumption against SARS-CoV-2 infection among Japanese. A lower odds of infection among those with high consumption deserves further investigation. J o u r n a l P r e -p r o o f World Health Organization. WHO Coronavirus (COVID-19) Dashboard Coronavirus disease (COVID-19) Prevention Preventive effects of tea and tea catechins against influenza and acute upper respiratory tract infections: a systematic review and meta-analysis Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor The green tea catechin epigallocatechin gallate inhibits SARS-CoV-2 infection COVID -19: could green tea catechins reduce the risks? medRxiv 2021 Seroprevalence of antibodies against SARS-CoV-2 in a large national hospital and affiliated facility in Tokyo Seroprevalence of SARS-CoV-2 antibodies in a national hospital and affiliated facility after the second epidemic wave of Japan We thank Haruka Osawa and Mika Shichishima for their contribution to data collection and the staff of the Laboratory Testing Department for their contribution to measuring antibody testing. Abbott Japan and Roche Diagnostics provided reagents for anti-spike antibody assays.