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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. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 is a global public health concern. As of December 2020, the therapeutic agents approved for coronavirus disease 2019 in Japan were limited to two drugs: remdesivir, an antiviral drug, granted a Special Approval for Emergency on 7 May 2020, and dexamethasone, which has an anti-inflammatory effect. The aim of this study is to evaluate the efficacy of convalescent plasma collected from donors who recovered from coronavirus disease 2019. Methods: This is an open-label, randomized controlled trial comprising two groups: a convalescent plasma and a standard-of-care group. Plasma administered to patients with coronavirus disease 2019 randomized in the convalescent plasma group of this trial will be plasma that has been collected and stored in an associated study. Patients with a diagnosis of mild coronavirus disease 2019 will be included in this trial. The efficacy of convalescent plasma transfusion will be evaluated by comparing the convalescent plasma group to the standard-of-care group (without convalescent plasma transfusion) with respect to changes in the viral load and other measures. The primary endpoint will be time-weighted average changes in the SARS-CoV-2 virus load in nasopharyngeal swabs from day 0 to days 3 and 5. It is hypothesized that the intervention should result in a decrease in the viral load in the convalescent plasma group until day 5. This endpoint has been used as a change in viral load has and been used as an index of therapeutic effect in several previous studies. Discussion: The proposed trial has the potential to prevent patients with mild COVID-19 from developing a more severe illness. Several RCTs of convalescent plasma therapy have already been conducted in countries outside of Japan, but no conclusion has been reached with respect to the efficacy of convalescent plasma therapy, which is likely in part because of the heterogeneity of the types of target patients, interventions, and endpoints among trials. Actually, previous clinical trials on plasma therapy have shown inconsistent efficacy and are sometimes ineffective in COVID-19 patients with severe disease, which is due to unmeasured neutralizing antibody titer in the COVID-19 convalescent plasma. To improve this issue, in this study, we measure neutralizing activity of convalescent plasma before administration and provide the plasma with high neutralizing activity to the subjects. It is hoped that this study will further evidence to support the role of convalescent plasma therapy in COVID-19. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background There is limited understanding of the characteristics of patients with coronavirus disease 2019 (COVID-19) requiring hospitalization in Japan. Methods This study included 2638 cases enrolled from 227 healthcare facilities that participated in the COVID-19 Registry Japan (COVIREGI-JP). The inclusion criteria for enrollment of a case in COVIREGI-JP are both (1) a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and (2) inpatient treatment at a healthcare facility. Results The median age of hospitalized patients with COVID-19 was 56 years (interquartile range [IQR], 40–71 years). More than half of cases were male (58.9%, 1542/2619). Nearly 60% of the cases had close contact to confirmed or suspected cases of COVID-19. The median duration of symptoms before admission was 7 days (IQR, 4–10 days). The most common comorbidities were hypertension (15%, 396/2638) and diabetes without complications (14.2%, 374/2638). The number of nonsevere cases (68.2%, n = 1798) was twice the number of severe cases (31.8%, n = 840) at admission. The respiratory support during hospitalization includes those who received no oxygen support (61.6%, 1623/2636) followed by those who received supplemental oxygen (29.9%, 788/2636) and invasive mechanical ventilation/extracorporeal membrane oxygenation (8.5%, 225/2636). Overall, 66.9% (1762/2634) of patients were discharged home, while 7.5% (197/2634) died. Conclusions We identified the clinical epidemiological features of COVID-19 in hospitalized patients in Japan. When compared with existing inpatient studies in other countries, these results demonstrated fewer comorbidities and a trend towards lower mortality. [ABSTRACT FROM AUTHOR]

While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions) with various determinants were examined and the potency of sera against variants of concerns was determined. Significant rise in NT50s was seen in sera on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation seen between NT50s and adverse effects. NT50s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd dose were greater in women than in men. The average half-life of NT50s was ~ 68 days, and 23.6% (49 out of 208 individuals) failed to show detectable neutralizing activity on day 150. While sera from elite-responders (NT50s > 1,500: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some sera with low NT50s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed. [ABSTRACT FROM AUTHOR]

The Omicron variant of severe acute respiratory syndrome coronavirus 2 has multiple amino acid mutations in its spike proteins, which may allow it to evade immunity elicited by vaccination. We examined the neutralising activity and S1-IgG titres in patients with breakthrough infections caused by the Omicron variant after two doses of vaccination. We found that neutralising activity was significantly lower for the Omicron variant than for the Wuhan strain. Two doses of vaccination might not induce sufficient neutralising activity for the Omicron variant. [ABSTRACT FROM AUTHOR]