Meat intake and type 2 diabetes among Japanese workers: a prospective study.

Red meat and processed meat intake has been linked to increased risk of type 2 diabetes; however, evidence from Asia is limited and inconsistent. We prospectively examined the association of intake of total meat and its subtype with type 2 diabetes in a Japanese working population. Participants were 2709 workers aged 18-78 years who reported no history of diabetes when they responded to a health survey for the first time between 2012 and 2019. Dietary intake was assessed using a validated self-administered diet history questionnaire. The incidence of type 2 diabetes was assessed via annual health checkups from baseline through March 2023. Type 2 diabetes was defined as fasting blood glucose ≥ 126 mg/dl, casual blood glucose ≥ 200 mg/dl, HbA1c ≥ 6·5 %, self-report of diabetes or current use of anti-diabetic drugs. Hazard ratios according to tertile of meat intake were estimated using Cox proportional hazards regression. During 16 119 person-years of follow-up, 135 (5·0 %) workers developed type 2 diabetes. Intakes of total meat, red meat, processed meat and poultry were not associated with risk of type 2 diabetes. After adjustment for covariates, hazard ratios for the highest v. lowest tertile of meat intake were 1·01 (95 % CI 0·63, 1·62) for total meat, 1·02 (95 % CI 0·66, 1·58) for red meat, 0·99 (95 % CI 0·65, 1·49) for processed meat and 1·13 (95 % CI 0·71, 1·80) for poultry. Our findings suggest that meat intake is not associated with the risk of type 2 diabetes among Japanese workers.

Development and Validation of a Cardiovascular Disease Risk Prediction Model for the Japanese Working Population: The Japan Epidemiology Collaboration on Occupational Health Study.

AIMS: This study aimed to develop a cardiovascular disease (CVD) risk model using data from a large occupational cohort. METHODS: A risk prediction model was developed using the routine health checkup data of 96,117 Japanese employees (84.0% men) who were 30-64 years of age and had no CVD at baseline. Cox proportional hazards regression models were employed to develop a risk model for assessing the 10-year CVD risk. Measures of discrimination and calibration were used to assess the predictive performance of the model and internal validation was used to examine potential overfitting. RESULTS: During a mean follow-up period of 6.7 years (range, 0.1-11.0 years), 422 cases of incident CVD were confirmed. The final model, which included predictor variables of age, smoking, diabetes, systolic blood pressure, and low- and high-density lipoprotein cholesterol levels, demonstrated a good predictive ability (Harrell's C-statistic, 0.796; 95% confidence interval, 0.775-0.817) with excellent calibration between observed and predicted values. Internal validation revealed minimal overfitting. CONCLUSIONS: The developed model can accurately predict the 10-year CVD risk. Because it is based on routine health checkup data, the prediction model can be easily implemented in the workplace. Further studies are required to assess the external validity and transferability of the proposed CVD risk model.

Protection of Omicron Bivalent Vaccine, Previous Infection, and Their Induced Neutralizing Antibodies Against Symptomatic Infection With Omicron XBB.1.16 and EG.5.1.

Background: Data are limited on the protective role of the Omicron BA bivalent vaccine, previous infection, and their induced neutralizing antibodies against Omicron XBB.1.16 and EG.5.1 infection. Methods: We conducted a nested case-control analysis among tertiary hospital staff in Tokyo who had received ≥3 doses of COVID-19 vaccines and donated blood samples in June 2023 (1 month before the Omicron XBB.1.16 and EG.5.1 wave). We identified 206 symptomatic cases between June and September 2023 and selected their controls with 1:1 propensity score matching. We examined the association of vaccination, previous infection, and preinfection live virus neutralizing antibody titers against Omicron XBB.1.16 and EG.5.1 with the risk of COVID-19 infection. Results: Previous infection during the Omicron BA- or XBB-dominant phase was associated with a significantly lower infection risk during the XBB.1.16 and EG.5.1-dominant phase than infection-naive status, with 70% and 100% protection, respectively, whereas Omicron BA bivalent vaccination showed no association. Preinfection neutralizing titers against XBB.1.16 and EG.5.1 were 39% (95% CI, 8%-60%) and 28% (95% CI, 8%-44%) lower in cases than matched controls. Neutralizing activity against XBB.1.16 and EG.5.1 was somewhat detectable in the sera of individuals with previous infection but barely detectable in those who were infection naive and received the Omicron bivalent vaccine. Conclusions: In the era when the Omicron XBB vaccine was unavailable, the Omicron BA bivalent vaccine did not confer the neutralizing activity and protection against Omicron XBB.1.16 and EG.5.1 symptomatic infection. The previous infection afforded neutralizing titers and protection against symptomatic infection with these variants.

Correlates of Nucleocapsid Antibodies and a Combination of Spike and Nucleocapsid Antibodies Against Protection of SARS-CoV-2 Infection During the Omicron XBB.1.16/EG.5-Predominant Wave.

Background: We aimed to examine the association among nucleocapsid (N) antibodies, a combination of N and spike (S) antibodies, and protection against SARS-CoV-2 reinfection. Methods: We conducted a prospective cohort study among staff at a national medical research center in Tokyo and followed them for the incidence of SARS-CoV-2 infection between June and September 2023 (Omicron XBB.1.16/EG.5 wave). At baseline, participants donated blood samples to measure N- and S-specific antibodies. Cox regression was used to estimate the hazard ratio and protection ([1 - hazard ratio] × 100) against subsequent SARS-CoV-2 infection across these antibody levels. Results: Among participants with previous infection, higher pre-reinfection N antibodies were associated with a lower risk of reinfection, even after adjusting S antibody levels (P < .01 for trend). Estimation of the protection matrix for N and S antibodies revealed that high levels in N and S antibodies conferred robust protection (>90%) against subsequent infection. In addition, a pattern of low pre-reinfection N antibodies but high vaccine-enhanced S antibodies showed high protection (>80%). Conclusions: Pre-reinfection N antibody levels correlated with protection against reinfection, independent of S antibodies. If the N antibodies were low, vaccine-boosted S antibodies might enhance the reinfection protection.

Association of conventional cigarette smoking, heated tobacco product use, and dual use with hearing loss: A working population-based study.

INTRODUCTION: Although conventional cigarette smoking has been linked to an increased risk of hearing loss, the association between heated tobacco products (HTPs) and hearing loss is unknown. The objective of this study was to investigate the association between cigarette and HTP use and hearing loss. METHODS: This cross-sectional study examined the data of 7769 employees from five companies (Study I) and 34404 employees from a large company (Study II), all participants in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into five groups based on their self-reported tobacco use: never smokers, former smokers, exclusive cigarette smokers, exclusive users of HTPs, and those who used both cigarettes and HTPs. Hearing levels were measured using pure-tone audiometry at 1 and 4 kHz frequencies. Separate analyses were carried out for each study, and the results were then combined using fixed-effect models to pool the estimates. RESULTS: The analysis included 42173 participants, with a prevalence of 12.9% for exclusive cigarette smoking, 9.8% for exclusive HTP use, and 5.5% for dual use. The pooled adjusted odds ratios with 95% confidence intervals for unilateral hearing loss at 4 kHz were 1.21 (95% CI: 1.10-1.33) for former smokers, 1.83 (95% CI: 1.64-2.05) for exclusive cigarette smokers,1.46 (95% CI: 1.28-1.67) for exclusive HTP users, and 1.66 (95% CI: 1.41-1.96) for dual users, compared to never smokers. Additionally, the adjusted odds ratios for hearing loss at 4 kHz among exclusive cigarette smokers, exclusive HTP users, and dual users increased with the intensity of cigarette/HTP consumption (all p for trend <0.001). No significant associations were found between exclusive HTP use, dual use, and hearing loss at 1 kHz, apart from exclusive cigarette smoking. CONCLUSIONS: In this cross-sectional study, associations were found between exclusive cigarette smoking, exclusive HTP use, dual use, and hearing loss, particularly at 4 kHz. Further research is needed to confirm these findings.

Blood pressure classification using the Japanese Society of Hypertension Guidelines for the Management of Hypertension and cardiovascular events among young to middle-aged working adults.

The Japanese Society of Hypertension updated guidelines for hypertension management (JSH2019), changing the blood pressure (BP) classification. However, evidence is sparse regarding the association of the classification with cardiovascular disease (CVD) events among young to middle-aged workers in Japan. We examined this issue using longitudinal data from Japan Epidemiology Collaboration on Occupational Health Study with a prospective cohort design. Participants were 81,876 workers (aged 20-64 years) without taking antihypertensive medication at baseline. BP in 2011 or 2010 was used as exposure. CVD events that occurred from 2012 to 2021 were retrieved from a within-study registry. Cox regression was used to calculate multivariable-adjusted hazard ratios of CVD events. During 0.5 million person-years of follow-up, 334 cardiovascular events, 75 cardiovascular deaths, and 322 all-cause deaths were documented. Compared with normal BP (systolic BP [SBP] < 120 mmHg and diastolic BP [DBP] < 80 mmHg), multivariable-adjusted hazard ratios (95% confidence intervals) of cardiovascular events were 1.98 (1.49-2.65), 2.10 (1.58-2.77), 3.48 (2.33-5.19), 4.12 (2.22-7.64), and 7.81 (3.99-15.30) for high normal BP (SBP120-129 mmHg and DBP < 80 mmHg), elevated BP (SBP130-139 mmHg and/or DBP80-89 mmHg), stage 1 hypertension (SBP140-159 mmHg and DBP90-99 mmHg), stage 2 hypertension (SBP160-179 mmHg and/or DBP100-109 mmHg), and stage 3 hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg), respectively. The highest population attributable fraction was observed in elevated BP (17.8%), followed by stage 1 hypertension (14.1%). The present data suggest that JSH2019 may help identify Japanese workers at a higher cardiovascular risk.

Association between Fish Intake and Serum Testosterone Levels in Older Males: The Hitachi Health Study II.

Background: Fish are rich in omega-3 polyunsaturated fatty acids and vitamin D, which can promote testosterone synthesis and secretion. However, some contaminants present in fish may disrupt testosterone production. Objective: This study aimed to investigate the association between fish intake (total, fatty, and lean fish) and serum testosterone levels in older males. Methods: This cross-sectional study included 1545 Japanese males aged 60-69 y who participated in the baseline survey of the Hitachi Health Study II. Fish intake was estimated using a validated brief-type self-administered diet history questionnaire. Total testosterone levels were measured by chemiluminescence immunoassay. Multivariable linear regression analysis was used to analyze the association between fish intake and serum testosterone levels. Results: Higher total fish intake was associated with higher levels of serum testosterone, with an adjusted mean [95% confidence interval (CI) of 5.63 (5.43, 5.83) and 5.99 (5.78, 6.20)] ng/mL for the 1st and 4th quartiles of total fish intake, respectively (P for trend = 0.06). When analyzing fatty and lean fish separately, higher intake of lean fish, but not fatty fish, was associated with higher levels of serum testosterone: adjusted mean (95% CI): 5.63 (5.43, 5.82) and 6.00 (5.79, 6.20) ng/mL for the 1st and 4th quartiles of lean fish intake, respectively (P for trend = 0.01). Conclusions: Among older males, higher intake of total fish, particularly lean fish, was associated with higher serum testosterone levels. Curr Dev Nutr 20xx;x:xx.

Vitamin D deficiency during the coronavirus disease 2019 (COVID-19) pandemic among healthcare workers.

BACKGROUND & AIMS: Vitamin D deficiency is a common nutritional problem worldwide that may have worsened during the coronavirus disease 2019 (COVID-19) pandemic. The present study sought to examine the prevalence and correlates of vitamin D deficiency among healthcare workers three years after the start of the COVID-19 pandemic. METHODS: Participants comprised 2543 staff members from a medical research institute, who completed a questionnaire and donated blood samples in June 2023. 25-hydroxyvitamin D (25[OH]D) levels were measured using an electrochemiluminescence immunoassay. Logistic regression was used to calculate the odds ratio and its 95% confidence interval while adjusting for covariates. RESULTS: The proportions of participants with vitamin D insufficiency (25[OH]D 20-29 ng/mL) and deficiency (25[OH]D < 20 ng/mL) were 44.9% and 45.9%, respectively. In a multivariable-adjusted model, factors associated with a higher prevalence of vitamin D deficiency included younger age, female sex, fewer hours of daytime outdoor physical activity during leisure time (without regular use of sunscreen), lower intake of fatty fish, no use of vitamin D supplements, smoking, and no alcohol consumption. Occupational factors, including shift work, were not independently associated with vitamin D deficiency. CONCLUSIONS: Our results suggest that vitamin D insufficiency and deficiency are highly prevalent among healthcare workers. Health education regarding lifestyle modifications for this occupational group are warranted to improve their vitamin D status in the COVID-19 era.

Coffee and Green Tea Consumption With the Risk of COVID-19 Among the Vaccine Recipients in Japan: A Prospective Study.

BACKGROUND: While coffee and green tea have been suggested to have immunoprotective effects, it remains elusive whether they can decrease the risk of coronavirus disease 2019 (COVID-19). OBJECTIVE: We prospectively examined the associations of coffee and green tea consumption with the risk of COVID-19 among mRNA vaccine recipients during the epidemic of the Omicron variant. METHODS: Participants were 2,110 staff (aged 18 to 76 years) of a large medical facility in Tokyo, who attended a serosurvey in June 2022, predominantly received ≥3 doses of vaccine, and were followed for COVID-19 until December 2022. Coffee and green tea consumption was ascertained via a questionnaire. COVID-19 was identified through the in-house registry. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of COVID-19 across the categories of beverage consumption. RESULTS: During 6 months of follow-up, 225 (10.6%) cases of COVID-19 were identified. Contrary to the expectation, higher consumption of coffee was associated with a significant increase in the risk of COVID-19; multivariable-adjusted HRs were 1.00 (reference), 0.92 (95% confidence interval [CI], 0.62-1.35), 1.48 (95% CI, 0.99-2.22), and 1.82 (95% CI, 1.20-2.76) for <1 cup/day, 1 cup/day, 2 cups/day, and ≥3 cups/day, respectively (P trend = 0.003). Green tea consumption was not significantly associated with the risk of COVID-19. The association with coffee was attenuated if serologically detected infection was added to the cases. CONCLUSION: In a cohort of Japanese hospital staff who received COVID-19 vaccine, higher consumption of coffee was associated with an increased risk of COVID-19 during the epidemic of the Omicron variant. There was no evidence of a significant association between green tea consumption and COVID-19 risk.

Diabetes, Prediabetes, and the Risk of a Composite Outcome of Long-term Sickness Absence and Pre-retirement Death Due to Physical Disorders.

BACKGROUND: Diabetes and prediabetes have been linked with morbidity or mortality from cardiovascular disease, cancer, or other physical disorders among working-age populations, but less is known about outcomes directly related to labor loss (eg, Tlong-term sickness absence [LTSA] or pre-retirement death due to physical disorders).This prospective study aimed to examine the association of diabetes and prediabetes with the risk of a composite outcome of LTSA and pre-retirement death due to physical disorders. The present study also examined the associations of severe outcomes (LTSA or death) due to specific physical disorders or injuries/external causes in relation to diabetes and prediabetes. METHODS: Data were derived from the Japan Epidemiology Collaboration on Occupational Health study. A total of 60,519 workers from 12 companies were followed for 8 years. Diabetes and prediabetes were defined based on the American Diabetes Association criteria. A Cox proportional hazards regression model was used to examine the association between diabetes/prediabetes and severe outcomes due to physical disorders or injuries/external causes. RESULTS: The adjusted hazard ratios of severe outcomes due to all physical disorders were 1.22 (95% confidence interval [CI], 1.02-1.45) and 2.32 (95% CI, 2.04-2.64) for prediabetes and diabetes, respectively. In cause-specific analyses, an increased risk was observed for severe outcomes due to cancers, cardiovascular diseases, diseases of the musculoskeletal system, and injuries/external causes in relation to either or both diabetes and prediabetes. CONCLUSION: Diabetes and prediabetes were associated with an increased risk of severe outcomes due to physical disorders or injuries/external causes among Japanese workers.

Development and Validation of Prediction Models for the 5-year Risk of Type 2 Diabetes in a Japanese Population: Japan Public Health Center-based Prospective (JPHC) Diabetes Study.

BACKGROUND: This study aimed to develop models to predict the 5-year incidence of type 2 diabetes mellitus (T2DM) in a Japanese population and validate them externally in an independent Japanese population. METHODS: Data from 10,986 participants (aged 46-75 years) in the development cohort of the Japan Public Health Center-based Prospective Diabetes Study and 11,345 participants (aged 46-75 years) in the validation cohort of the Japan Epidemiology Collaboration on Occupational Health Study were used to develop and validate the risk scores in logistic regression models. RESULTS: We considered non-invasive (sex, body mass index, family history of diabetes mellitus, and diastolic blood pressure) and invasive (glycated hemoglobin [HbA1c] and fasting plasma glucose [FPG]) predictors to predict the 5-year probability of incident diabetes. The area under the receiver operating characteristic curve was 0.643 for the non-invasive risk model, 0.786 for the invasive risk model with HbA1c but not FPG, and 0.845 for the invasive risk model with HbA1c and FPG. The optimism for the performance of all models was small by internal validation. In the internal-external cross-validation, these models tended to show similar discriminative ability across different areas. The discriminative ability of each model was confirmed using external validation datasets. The invasive risk model with only HbA1c was well-calibrated in the validation cohort. CONCLUSION: Our invasive risk models are expected to discriminate between high- and low-risk individuals with T2DM in a Japanese population.

The association between living alone and depressive symptoms and the role of pet ownership among Japanese workers.

BACKGROUND: Living alone has been positively associated with the prevalence of depressive symptoms. We examined how a combination of living alone and pet ownership relates to depressive symptoms. METHODS: As part of the Japan Epidemiology Collaboration on Occupational Health Study, we conducted a survey on health-related lifestyles, including living arrangements and pet ownership, among 12,763 employees of five companies in 2018-2021. Depressive symptoms were assessed using the 11-item Center for Epidemiological Studies-Depression Scale (cutoff score ≥ 9). A Poisson regression model with a robust variance estimator was used to calculate prevalence ratio and 95% confidence interval (CI) while adjusting for covariates. RESULTS: Among the participants, 30.9% were depressed, 17.7% had pets, and 29.1% lived alone. Compared to individuals living with others but not with a pet, those living alone and not with a pet had a 1.17 times higher prevalence ratio of depressive symptoms (95% CI: 1.08-1.26). The corresponding figures were 1.03 (95% CI: 0.95-1.11) for those living with others and pet(s) and 1.42 (95% CI: 1.18-1.69) for those living alone but with pet(s). CONCLUSION: Living alone was significantly associated with a higher prevalence of depressive symptoms. The association was rather stronger among individuals with vs. without pets. Pet ownership may not be associated with decreased depressive symptoms.

Preinfection Neutralizing Antibodies, Omicron BA.5 Breakthrough Infection, and Long COVID: A Propensity Score-Matched Analysis.

BACKGROUND: Data are limited on the role of preinfection humoral immunity protection against Omicron BA.5 infection and long coronavirus disease (COVID) development. METHODS: We conducted nested case-control analysis among tertiary hospital staff in Tokyo who donated blood samples in June 2022 (1 month before Omicron BA.5 wave), approximately 6 months after receiving a third dose of COVID-19 mRNA vaccine. We measured live virus-neutralizing antibody titers against wild type and Omicron BA.5, and anti-receptor-binding domain (RBD) antibody titers at preinfection, and compared them between cases and propensity-matched controls. Among the breakthrough cases, we examined association between preinfection antibody titers and incidence of long COVID. RESULTS: Preinfection anti-RBD and neutralizing antibody titers were lower in cases than controls. Neutralizing titers against wild type and Omicron BA.5 were 64% (95% confidence interval [CI], 42%-77%) and 72% (95% CI, 53%-83%) lower, respectively, in cases than controls. Individuals with previous Omicron BA.1/BA.2 infections were more frequent among controls than cases (10.3% vs 0.8%), and their Omicron BA.5 neutralizing titers were 12.8-fold higher than infection-naive individuals. Among cases, preinfection antibody titers were not associated with incidence of long COVID. CONCLUSIONS: Preinfection immunogenicity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may play a role in protecting against the Omicron BA.5 infection but not preventing long COVID.

Cross-Sectional Association between Estimated Hardness of the Habitual Diet and Depressive Symptoms in Older Japanese Men.

This cross-sectional study aimed to investigate the association between dietary hardness and depressive symptoms in older Japanese men. Participants were 1487 men aged 60-69 years enrolled in the baseline survey of the Hitachi Health Study II (2017-2020). Habitual dietary intake was estimated by a brief-type, self-administered diet history questionnaire. Dietary hardness was defined as the magnitude of masticatory muscle activity necessary to consume solid foods. The participants who scored ≥ 9 points on a short version of the Center for Epidemiologic Studies Depression Scale were considered to have depressive symptoms. The prevalence of depressive symptoms was 12.7%. The ORs (95% CIs) for depressive symptoms in the third tertile of dietary hardness were significantly lower after adjustment for sociodemographic and lifestyle-related variables and mood-modulating nutrients (ORs [95% CIs]: 0.93 [0.63, 1.36] and 0.58 [0.35, 0.97] for the second and third tertile, respectively [p-value for trend = 0.04]). Dietary hardness was inversely associated with the prevalence of depressive symptoms in older Japanese men. Future studies should confirm these findings and clarify the role of consuming a hard diet in preventing depressive disorders.

Association between Dietary Hardness and Cognitive Dysfunction among Japanese Men in Their 60s: A Cross-Sectional Study.

We aimed to examine the cross-sectional association between dietary hardness and cognitive dysfunction among Japanese men in their 60s. Participants were 1494 men aged 60-69 years from the baseline survey of Hitachi Health Study II (2017-2020). Dietary hardness was defined as an estimate of masticatory muscle activity involved in consuming solid foods. Habitual intake of these foods was assessed using a brief-type, self-administered diet history questionnaire. Cognitive dysfunction was defined as a score ≤ 13 points on the test battery for screening for Alzheimer's disease (MSP-1100). The mean (SD) age of participants was 63.5 (3.5) years. The prevalence of cognitive dysfunction was 7.5%. The ORs (95% CIs) for cognitive dysfunction in the second and third tertiles were: 0.77 (0.47, 1.26) and 0.87 (0.54, 1.41), respectively, after adjustment for socio-demographic factors (p for trend = 0.73). After further adjustment for protective nutrient intake against cognitive dysfunction, the corresponding figures were 0.72 (0.43, 1.21) and 0.79 (0.43, 1.46), respectively (p for trend = 0.57). Dietary hardness was not associated with the prevalence of cognitive dysfunction among Japanese men in their 60s. Future prospective studies are necessary to investigate the association between dietary hardness estimated by a validated questionnaire and cognitive dysfunctions.

Metabolic syndrome and the risk of severe cancer events: a longitudinal study in Japanese workers.

BACKGROUND: Metabolic syndrome (MetS) is associated with cancer risk; however, little is known regarding its relationship with the risk of cancer-related premature death and long-term sick leave (LTSL), which can lead to a substantial loss in working years. The present study aimed to quantify the all-site and site-specific associations between MetS and the risk of severe cancer events (a composite outcome of LTSL and mortality due to cancer) in a large working population in Japan. METHODS: We recruited 70,875 workers (59,950 men and 10,925 women), aged 20-59 years, who attended health check-ups in 2011 (10 companies) and 2014 (2 companies). All workers underwent follow up for severe cancer events until March 31, 2020. MetS was defined in accordance with the Joint Interim Statement. Cox regression models were used to quantify the association between baseline MetS and severe cancer events. RESULTS: During 427,379 person-years of follow-up, 523 participants experienced the outcome consisting of 493 LTSLs of which 124 eventually resulted in death, and 30 deaths without taking LTSL. The adjusted hazard ratios (HR) (95% confidence intervals [CI]) for composite severe events due to all-site, obesity-related, and non-obesity-related cancer among those with vs. without MetS were 1.26 (1.03, 1.55), 1.37 (1.04, 1.82), and 1.15 (0.84, 1.56), respectively. In cancer site-specific analyses, MetS was associated with an increased risk of severe events due to pancreatic cancer (HR, 2.06; 95% CI, 0.99-4.26). When mortality was treated solely as the endpoint, the association was significant for all-site (HR, 1.58; 95% CI, 1.10-2.26), and obesity-related (HR, 1.59; 95% CI, 1.00-2.54) cancer. Additionally, a greater number of MetS components was associated with a greater risk of both severe cancer events and cancer-related mortality (P trend < 0.05). CONCLUSION: Among Japanese workers, MetS was associated with an increased risk of severe cancer events, especially those due to obesity-linked cancer.

Omicron BA.1 neutralizing antibody response following Delta breakthrough infection compared with booster vaccination of BNT162b2.

BACKGROUND: Longitudinal data are lacking to compare booster effects of Delta breakthrough infection versus third vaccine dose on neutralizing antibodies (NAb) against Omicron. METHODS: Participants were the staff of a national research and medical institution in Tokyo who attended serological surveys on June 2021 (baseline) and December 2021 (follow-up); in between, the Delta-dominant epidemic occurred. Of 844 participants who were infection-naïve and had received two doses of BNT162b2 at baseline, we identified 11 breakthrough infections during follow-up. One control matched to each case was selected from boosted and unboosted individuals. We compared live-virus NAb against Wild-type, Delta, and Omicron BA.1 across groups. RESULTS: Breakthrough infection cases showed marked increases in NAb titers against Wild-type (4.1-fold) and Delta (5.5-fold), and 64% had detectable NAb against Omicron BA.1 at follow-up, although the NAb against Omicron after breakthrough infection was 6.7- and 5.2-fold lower than Wild-type and Delta, respectively. The increase was apparent only in symptomatic cases and as high as in the third vaccine recipients. CONCLUSIONS: Symptomatic Delta breakthrough infection increased NAb against Wild-type, Delta, and Omicron BA.1, similar to the third vaccine. Given the much lower NAb against Omicron BA.1, infection prevention measures must be continued irrespective of vaccine and infection history while the immune evasive variants are circulating.

Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine.

OBJECTIVES: To examine the differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination. METHODS: Throughout the pandemic, we evaluated the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients over time among the staff of a medical and research center in Tokyo. Linear mixed models were used to estimate trajectories of antibody titers from 14 to 180 days after the last immune-conferred event (vaccination or infection) and compare antibody waning rates across prior infection and vaccination status, and across background factors in infection-naïve participants. RESULTS: A total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (percentage per 30 days [95% CI]) was slower after 3 doses (25% [23-26]) than 2 doses (36% [35-37]). Participants with hybrid immunity (vaccination and infection) had further slower waning rates: 2-dose plus infection (16% [9-22]); 3-dose plus infection (21% [17-25]). Older age, male sex, obesity, coexisting diseases, immunosuppressant use, smoking, and alcohol drinking were associated with lower antibody titers, whereas these associations disappeared after 3 doses, except for sex (lower in female participants) and immunosuppressant use. Antibody waned slightly faster in older participants, females, and alcohol drinkers after 2 doses, whereas it did not differ after 3 doses across except sex. DISCUSSION: The 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection modestly enhanced its durability. The antibody levels at a given time point and waning speed after 2 doses differed across background factors; however, these differences mostly diminished after 3 doses.