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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.
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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.
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COVID-19 , Deficiência de Vitamina D , Animais , Humanos , Feminino , Pandemias , COVID-19/epidemiologia , Deficiência de Vitamina D/epidemiologia , Vitamina D , Vitaminas , Pessoal de SaúdeRESUMO
Background: Antibody testing can easily evaluate the clinical status of patients, aid in the diagnosis of multisystem inflammatory syndrome, and monitor the immunity level in the population. However, the applicability of serological tests in detecting antibodies against the severe acute respiratory syndrome 2 (SARS-CoV-2) spike-binding protein remains limited. This study aimed to quantify both serum-derived neutralizing immunoglobulin-G (IgG) antibody activity and the amount of anti-SARS-CoV-2 Spike-IgG (S-IgG) in convalescent sera/plasmas and evaluate the direct correlation between the in vitro IgG-EC50 values and S-IgG values. Methods: We evaluated the neutralizing activity of purified IgG (IgG-EC50), quantified S-IgG in the serum/plasma of consecutive COVID-19 convalescent individuals using a cell-based virus-neutralizing assay, and determined the correlation between IgG-EC50 and S-IgG. In addition, we evaluated rational cut-off values using the receiver operating characteristic (ROC) curve and calculated the sensitivity and specificity of the quantitative S-IgG assay for moderate and high IgG-EC50. Results: A high correlation was observed between S-IgG and IgG-EC50 with a Spearman's ρ value of -0.748 (95 % confidence interval [CI]: -0.804-0.678). Using an IgG-EC50 of 50 µg/mL and 20 µg/mL as the cut-off values for moderate and high in vitro neutralizing activity, respectively, the Youden's index values of 287.5 binding antibody units (BAU)/mL and 454.1 BAU/mL determined from the ROC curve showed the highest diagnostic accuracy, with Kappa values of 0.884 (95 % CI: 0.823-0.946) and 0.920 (95 % CI: 0.681-0.979), respectively. Conclusions: Quantitative S-IgG tests are a useful and convenient tool for estimating in vitro virus-neutralizing activity, with a high correlation with IgG-EC50 when the rational cut-off value is carefully determined.
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COVID-19 , SARS-CoV-2 , Humanos , Reinfecção , Nucleocapsídeo , Cinética , Anticorpos Antivirais , Anticorpos NeutralizantesRESUMO
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.
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COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Anticorpos Neutralizantes , Infecções Irruptivas , Vacinas contra COVID-19 , Pontuação de Propensão , SARS-CoV-2 , Anticorpos AntiviraisRESUMO
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.
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Vacinas contra COVID-19 , COVID-19 , Feminino , Humanos , Masculino , Idoso , Adulto , COVID-19/prevenção & controle , Anticorpos Antivirais , Imunossupressores , RNA Mensageiro/genética , VacinaçãoRESUMO
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.
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Anticorpos Neutralizantes , Epidemias , Humanos , Vacina BNT162 , Infecções Irruptivas , Vacinação , Anticorpos AntiviraisRESUMO
BACKGROUND: Amoxicillin plus probenecid is an alternative to intramuscular benzathine penicillin G for treating syphilis in the United Kingdom. Low-dose amoxicillin is an alternative treatment option used in Japan. METHODS: We conducted an open-label, randomized, controlled, non-inferiority trial between 31 August 2018, and 3 February 2022, to compare 1500 mg low-dose amoxicillin monotherapy with the combination of 3000 mg amoxicillin and probenecid (non-inferiority margin 10%). Patients with human immunodeficiency virus (HIV) infection and syphilis were eligible. The primary outcome was the cumulative serological cure rate within 12 months post-treatment, measured using the manual rapid plasma reagin card test. Secondary outcomes included safety assessment. RESULTS: A total of 112 participants were randomized into 2 groups. Serological cure rates within 12 months were 90.6% and 94.4% with the low-dose amoxicillin and combination regimens, respectively. Serological cure rates for early syphilis within 12 months were 93.5% and 97.9% with the low-dose amoxicillin and combination regimens, respectively. Non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid overall and for early syphilis was not confirmed. No significant side effects were detected. CONCLUSIONS: This is the first randomized controlled trial to demonstrate a high efficacy of amoxicillin-based regimens for treating syphilis in patients with HIV infection, and the non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid was not seen. Therefore, amoxicillin monotherapy could be a good alternative to intramuscular benzathine penicillin G with fewer side effects. However, further studies comparing with benzathine penicillin G in different populations and with larger sample sizes are needed. TRIALS REGISTRATION: (UMIN000033986).
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Sífilis , Humanos , Amoxicilina/efeitos adversos , Penicilina G Benzatina/uso terapêutico , Antibacterianos/efeitos adversos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV , Probenecid/efeitos adversos , Sífilis/tratamento farmacológicoRESUMO
To describe the trend of cumulative incidence of coronavirus disease 19 (COVID-19) and undiagnosed cases over the pandemic through the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants among healthcare workers in Tokyo, we analysed data of repeated serological surveys and in-house COVID-19 registry among the staff of National Center for Global Health and Medicine. Participants were asked to donate venous blood and complete a survey questionnaire about COVID-19 diagnosis and vaccine. Positive serology was defined as being positive on Roche or Abbott assay against SARS-CoV-2 nucleocapsid protein, and cumulative infection was defined as either being seropositive or having a history of COVID-19. Cumulative infection has increased from 2.0% in June 2021 (pre-Delta) to 5.3% in December 2021 (post-Delta). After the emergence of the Omicron, it has increased substantially during 2022 (16.9% in June and 39.0% in December). As of December 2022, 30% of those who were infected in the past were not aware of their infection. Results indicate that SARS-CoV-2 infection has rapidly expanded during the Omicron-variant epidemic among healthcare workers in Tokyo and that a sizable number of infections were undiagnosed.
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Pesquisa Biomédica , COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Tóquio/epidemiologia , Teste para COVID-19 , PandemiasRESUMO
OBJECTIVES: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection. METHODS: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19. Among these cases, we examined the association between NAb levels and the number of COVID-19-compatible symptoms. RESULTS: Among the 1456 participants for VE analysis, 60 breakthrough infections occurred during the Omicron wave. The third dose VE for infection was 54.6%. Among the third dose recipients, NAb levels against Omicron did not differ between the cases (n = 22) and controls (n = 21). Among the cases, those who experienced COVID-19-compatible symptoms had lower NAb levels against Omicron than those who did not. CONCLUSION: The third vaccine dose was effective in decreasing the risk of SARS-CoV-2 infection during Omicron wave compared with the second dose. Among third dose recipients, higher preinfection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection.
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COVID-19 , Vacinas , Humanos , Anticorpos Neutralizantes , Vacina BNT162 , Infecções Irruptivas , Estudos de Casos e Controles , SARS-CoV-2 , Anticorpos AntiviraisRESUMO
OBJECTIVE: This study aimed to examine the sex-associated differences in the relationship between dyslipidemia and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike immunoglobulin (Ig)G antibodies among BNT162b2 vaccine recipients. METHODS: Participants were staff members (aged 21-75 years) of a medical and research institution who underwent an anti-SARS-CoV-2 spike IgG antibody test after the second (n = 1872) and third doses (n = 1075) of the BNT162b2 vaccine. Dyslipidemia was defined as triglyceride level ≥150 mg/dl, high-density lipoprotein-cholesterol level <40 mg/dl, low-density lipoprotein-cholesterol level ≥140 mg/dl, or lipid-lowering medication use. Multivariable linear regression was used to calculate the ratio of means for SARS-CoV-2 spike IgG titre according to dyslipidemia status. RESULTS: The prevalence of dyslipidemia was 38.0% in men and 19.6% in women. The relationship between dyslipidemia and SARS-CoV-2 spike IgG titres after the second dose differed markedly by sex (P for interaction <0.001). In men, dyslipidemia was associated with significantly lower IgG titres: the ratio of means (95% confidence interval) was 0.82 (0.72-0.93). However, this association disappeared after the third dose (0.96 [0.78-1.18]). Of the dyslipidemia components, hypertriglyceridemia was inversely associated with SARS-CoV-2 spike IgG antibody titre after both the second and third doses (ratio of means: 0.82 [0.70-0.95] and 0.73 [0.56-0.95], respectively). In women, IgG titres did not differ according to dyslipidemia or hypertriglyceridemia status after either dose. CONCLUSIONS: These results suggest a detrimental role of hypertriglyceridemia in the humoral immune response to the BNT162b2 vaccine for COVID-19 in men but not in women.
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COVID-19 , Dislipidemias , Hipertrigliceridemia , Vacinas , Masculino , Feminino , Humanos , Japão/epidemiologia , Vacina BNT162 , Vacinas contra COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , SARS-CoV-2 , Dislipidemias/epidemiologia , Anticorpos Antivirais , Pessoal de Saúde , Imunoglobulina G , ColesterolRESUMO
BACKGROUND: Increased γ-glutamyl transpeptidase (GGT) levels can deplete plasma glutathione, which in turn impairs immune regulation; however, evidence on GGT levels and post-vaccine immunogenicity is lacking. OBJECTIVE: To examine the association between GGT and SARS-CoV-2 spike IgG antibodies. METHODS: Participants were 1479 medical staff (aged 21 to 75 years) who received a SARS-CoV-2 antibody test after their second vaccine and whose GGT levels were measured before the vaccine rollout. Elevated and highly elevated GGT levels were defined as 51-80 and ≥81 U/L, respectively. Multivariable linear regression was used to calculate the means of SARS-CoV-2 spike IgG. RESULTS: In a basic model, both elevated and highly elevated GGT levels were associated with significantly lower antibody titers. The ratio of mean (95% CI) was 0.83 (0.72-0.97) and 0.69 (0.57-0.84) for elevated and highly elevated GGT levels, respectively. However, these associations were largely attenuated after additional adjustment for potential confounders. An inverse association between GGT levels and antibody titers was found in women [0.70 (0.51-0.97)], normal-weight adults [0.71 (0.51-0.98)], and non-drinkers [0.73 (0.46-1.14)] but not in men, overweight adults, and alcohol drinkers. CONCLUSIONS: Circulating GGT concentrations were associated with the humoral immune response after COVID-19 vaccination, but this relationship could be ascribed to confounders such as sex, BMI, and alcohol drinking rather than GGT per se.
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Background: Hyperglycemia can alter the activation of innate and acquired immunity, but epidemiological evidence linking hyperglycemia to post-vaccination immunogenicity is limited. Objective: To examine the association between SARS-CoV-2 spike antibody titers after the COVID-19 vaccine and impaired fasting glucose (IFG) and diabetes. Methods: Participants were 953 health care workers aged 21−75 years who were tested for SARS-CoV-2 spike IgG antibodies and underwent a health checkup two months after their second dose of the BNT162b2 vaccine. IFG was defined as a fasting plasma glucose (FPG) level of 100−125 mg/dL, and diabetes was defined as an FPG level ≥ 126 mg/dL or being under medical care for diabetes. Multivariable linear regression was used to calculate the ratio of the mean. Result: Spike IgG antibody titers were lower in the presence of hyperglycemia; the ratios of the means (95% CI) were 1.00, 0.79 (0.60−1.04), and 0.60 (0.42−0.87) for individuals with normoglycemia, IFG, and diabetes, respectively (p trend < 0.001). Restricted cubic spline regression analysis showed that IgG spike antibody titers decreased linearly with increasing concentrations of FPG. Conclusion: Diabetes and, to a lesser extent, IFG may be associated with poor humoral immune response after BNT162b2 vaccination.
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OBJECTIVE: This study investigated the sex-associated difference in the impact of obesity on antibody response to a COVID-19 vaccine. METHODS: This study included 2,435 health care workers who received two doses of the BioNTech, Pfizer (BNT162b2) vaccine and participated in a serological survey, during which they were tested for anti-SARS-CoV-2 spike immunoglobin G (IgG) antibodies and asked for information on height, weight, and vaccination history via a questionnaire. Multivariable linear regression analysis was used to estimate the geometric mean titers (GMT) of antibodies for each sex and BMI category. RESULTS: The relationship between BMI and anti-SARS-CoV-2 spike IgG titers markedly differed by sex (p value for interaction = 0.04). Spike IgG antibody titers tended to decrease with increasing BMI in men (p value for trend = 0.03); GMT (95% CI) were 6,093 (4,874-7,618) and 4,655 (3,795-5,708) for BMI < 18.5 and ≥30 kg/m2 , respectively. In contrast, spike IgG antibody titers did not significantly differ across BMI categories in women (p value for for trend = 0.62); GMT (95% CI) were 6,171 (5,714-6,665) and 5,506 (4,404-6,883) for BMI <18.5 and ≥30, respectively. CONCLUSIONS: Higher BMI was associated with lower titers of SARS-CoV-2 spike antibodies in men, but not in women, suggesting the need for careful monitoring of vaccine efficacy in men with obesity, who are at high risk of severe COVID-19 outcomes.