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BackgroundEpidemiological data regarding differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination are scarce.MethodsWe repeatedly assessed the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients 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.ResultsA total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (per 30 days [95% CI]) was slower after 3-dose (25% [23–26]) than 2-dose (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-dose, except for sex (lower in female participants) and immunosuppressant use. Antibody waning was faster in older participants, females, and alcohol drinkers after 2-dose, whereas it did not differ after 3-dose across except sex.ConclusionsThe 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection further enhanced its durability. The antibody levels at a given time point and waning speed after 2-dose differed across background factors; however, these differences mostly diminished after 3-dose.

ImportanceInvestigating the role of pre-infection humoral immunity against Omicron BA.5 infection risk and long COVID development is critical to inform public health guidance.ObjectiveTo investigate the association between pre-infection immunogenicity after the third vaccine dose and the risks of Omicron BA.5 infection and long coronavirus disease.Design, Setting, and ParticipantsThis nested case-control analysis was conducted among tertiary hospital staff in Tokyo, Japan who donated blood samples in June 2022 (1 month before Omicron BA.5 dominant wave onset [July–September 2022]) approximately 6 months after receiving the third dose of the historical monovalent coronavirus disease 2019 mRNA vaccine.ExposuresLive virus-neutralizing antibody titers against Wuhan and Omicron BA.5 (NT50) and anti-SARS-CoV-2 spike protein antibody titers with Abbott (AU/mL) and Roche (U/mL) assays at pre-infection.Main Outcomes and MeasuresSymptomatic SARS-CoV-2 breakthrough infections during the Omicron BA.5 dominant wave vs. undiagnosed controls matched using a propensity score. Incidence of long COVID (persistent symptoms ≥4 weeks after infection) among breakthrough infection cases.ResultsAnti-spike antibody titers were compared between 243 breakthrough infection cases and their matched controls among the 2360 staff members who met the criteria. Neutralizing antibodies in 50 randomly selected matched pairs were measured and compared. Pre-infection anti-spike and neutralizing antibody titers were lower in breakthrough cases than in undiagnosed controls. Neutralizing antibody titers against Wuhan and Omicron BA.5 were 64% (95% CI: 42–77) and 72% (95% CI: 53–83) lower, respectively, in breakthrough cases than in undiagnosed controls. Individuals with previous SARS-CoV-2 infections were more frequent among undiagnosed controls than breakthrough cases (19.3% vs. 4.1%), and their neutralizing antibody titers were higher than those of infection-naïve individuals. Among the breakthrough cases, pre-infection antibody titers were not associated with the incidence of long COVID.Conclusions and RelevancePre-infection immunogenicity against SARS-CoV-2 may play a role in protecting against the Omicron BA.5 infection, but not in preventing long COVID.Key PointsQuestionDoes pre-infection anti-SARS-CoV-2 humoral immunity protect against Omicron BA.5 infection and long-COVID development?FindingsPre-infection neutralizing antibody titers against Omicron BA.5 were lower in subsequent Omicron BA.5 breakthrough infection cases than in matched controls in this nested case-control study of healthcare workers who received the third dose of historical COVID-19 mRNA vaccines approximately 6 months prior. Pre-infection antibody titers could not predict the incidence of long COVID among breakthrough infection cases.MeaningHigher pre-infection humoral immunity approximately 6 months after the third vaccination may correlate with protection against Omicron BA.5 infection but not against long-COVID development.

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.

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.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=1,872) and third doses (n=1,075) of the BNT162b2 vaccine. Dyslipidemia was defined as triglyceride level ≥150 mg/dL, high-density lipoprotein-cholesterol level40 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 titer according to dyslipidemia status.The prevalence of dyslipidemia was 38.0% in men and 19.6% in women. The relationship between dyslipidemia and SARS-CoV-2 spike IgG titers after the second dose differed markedly by sex (P for interaction0.001). In men, dyslipidemia was associated with significantly lower IgG titers: ratio of means [95% confidence interval (CI)] was 0.82 (0.72-0.93). However, this association disappeared after the third dose (0.96 [0.78-1.18]). Of dyslipidemia components, hypertriglyceridemia was inversely associated with SARS-CoV-2 spike IgG antibody titer 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 titers did not differ according to dyslipidemia or hypertriglyceridemia status after either dose.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. This article is protected by copyright. All rights reserved.

BackgroundData on the role of immunogenicity following the third vaccine dose against Omicron infection and coronavirus disease 2019 (COVID-19)-compatible symptoms of infection are limited.MethodsFirst 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 a cohort of third vaccine recipients, we compared the pre-infection levels of live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls, who had close contact with COVID-19 patients. Among these cases, we examined the association between pre-infection NAb levels and the number of COVID-19-compatible symptoms experienced during the Omicron wave.ResultsAmong the 1456 participants for VE analysis, 60 (4%) breakthrough infections occurred during the Omicron wave (January to March 2022). The third-dose VE for infection, relative to the second dose was 54.6% (95% CI: 14.0–76.0). Among the recipients of the third vaccine, pre-infection NAb levels against Omicron did not significantly differ between the cases and controls. Among the cases, those who experienced COVID-19-compatible symptoms had lower pre-infection NAb levels against Omicron than those who did not.ConclusionsThe third vaccine dose was effective in decreasing the risk of severe acute respiratory syndrome coronavirus 2 infection during the Omicron wave compared with the second dose. Among third-dose recipients, higher pre-infection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection.SummaryThe third vaccine dose reduced SARS-CoV-2 infection risk during the Omicron wave. Higher neutralizing antibody levels may not reduce Omicron infection risk in third-dose patients. On the contrary, it may be associated with fewer symptoms of infection.

We assessed the consistency of seropositive results of three rapid immunoassays (Kits A, B, and C) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to highly accurate serological tests (Abbott and Roche) among healthcare workers in a hospital in Tokyo. The seroprevalence of SARS-CoV-2 immunoglobulin G was 0.41%, 2.36%, and 0.08% using Kits A, B, and C, respectively. Of the 51 samples that were seropositive on any rapid test, all were seronegative on both the Abbott and the Roche assays. Given that the seroprevalence of SARS-CoV-2 immunoglobulin G varied widely according to the choice of rapid test and the rapid test results were inconsistent with the results of highly accurate tests, the diagnostic accuracy of rapid serological tests for SARS-CoV-2 should be assessed before introducing these tests for point-of-care testing or surveillance.

BackgroundLongitudinal data are lacking to compare booster effects of Delta breakthrough infection versus the third vaccine dose on neutralizing antibodies (NAb) against Omicron.MethodsParticipants 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 the follow-up. One control matched to each case was randomly selected from those who completed the booster vaccine and those who were unboosted by the follow-up. We used the generalized estimating equation model to compare live-virus NAb against Wuhan, Delta, and Omicron across groups.ResultsPersons who experienced breakthrough infection showed marked increases in NAb titers against Wuhan (4.1-fold) and Delta (5.5-fold), and 64% had detectable NAb against Omicron at follow-up, although the NAb against Omicron after breakthrough infection was 6.7- and 5.2-fold lower than that against Wuhan and Delta, respectively. The increase was apparent only in symptomatic cases and as high as in the third vaccine recipients. In contrast, these titers largely decreased (Wuhan, Delta) or remained undetected (Omicron) at follow-up in infection-naïve and unboosted persons.ConclusionsSymptomatic breakthrough infection during the Delta predominant wave was associated with significant increases in NAb against Wuhan, Delta, and Omicron, similar to the third BNT162b2 vaccine. Given the much lower cross-NAb against Omicron than other virus types, however, infection prevention measures must be continued irrespective of vaccine and infection history while the immune evasive variants are circulating.Key pointsSymptomatic, not asymptomatic, SARS-CoV-2 breakthrough infection after the second BNT162b2 vaccination during the Delta-predominant wave enhanced neutralizing antibodies against Wuhan, Delta, and Omicron comparable to the three vaccine doses, although immunity against Omicron was much lower than Wuhan and Delta.

This study investigated the sex-associated difference in the impact of obesity on antibody response to a COVID-19 vaccine.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.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 BMI18.5 and ≥30 kg/mHigher 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.

Obesity may downregulate vaccine-induced immunogenicity, but the epidemiological evidence for the COVID-19 vaccine is limited, and the sex-associated difference is unknown. It was observed that a higher body mass index was associated with lower titers of spike IgG antibodies against SARS-CoV-2 in men but not in women.

Hypervirulent Klebsiella pneumoniae has been associated with community-acquired liver abscesses in relatively healthy subjects since the 1990s, occasionally accompanied by disseminated disease. While isolates of capsular genotype K1 belonging to sequence type (ST) 23 have been the most prominent causative pathogen of this syndrome, other virulent clones have been implicated sporadically in recent years.A 68-year-old woman with diabetes in Okinawa, Japan suffered from a K. pneumoniae liver abscess, which recurred after a prolonged antibacterial treatment. The clinical course was further complicated with multiple sites of dissemination. Another 45-year-old woman living in Okinawa without underlying conditions was also diagnosed with a community-acquired K. pneumoniae liver abscess, which was cured with antibacterial treatment alone. Both of the causative isolates carried rmpA and aerobactin genes, and were confirmed as capsular genotype K2 and ST375.K. pneumoniae K2-ST375 is a hypervirulent clone of epidemiological significance causing severe community-acquired infections in relatively healthy subjects. More information about clinical characteristics and molecular epidemiology of hypervirulent K. pneumoniae clones other than K1-ST23 should be accumulated. Keywords: Community-acquired liver abscess, Hypervirulent Klebsiella pneumoniae, Capsular genotype K2, ST375

A 77-year-old man had undergone left-lobe liver resection and a choledochojejunostomy six years previously, and thereafter he suffered from a postoperative relapse of cholangitis. He was admitted to our hospital due to liver abscesses and bacteremia caused by multidrug-resistant Pseudomonas aeruginosa. Empirical treatment with piperacillin/tazobactam was started, and the patient initially recovered. However, he developed a second case of sepsis caused by piperacillin/tazobactam-resistant P. aeruginosa bacteremia originating from a new liver abscess. We changed the piperacillin/tazobactam to colistin and flomoxef and continued the two antibiotics for one month. During the antibiotic therapy, the patient successfully underwent bile duct stent placement.

17-year-old man had been involved in a traffic accident. He underwent a bilateral craniotomy with artificial dura mater to remove bilateral acute subdural hematomas. Seven months later, a right cranioplasty was performed using frozen auto-bone, and he developed extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae meningitis and an epidural abscess. Since his general status was poor, we could not remove the foreign body (artificial dura mater). He was successfully treated with meropenem and chronic suppression with oral trimethoprim-sulfamethoxazole. By describing this case and the results of a review of the pertinent literature, we discuss the importance of ESBL-producing Klebsiella pneumoniae meningitis in posttraumatic/postoperative patients.

A 77-year-old man had undergone left-lobe liver resection and a choledochojejunostomy six years previously, and thereafter he suffered from a postoperative relapse of cholangitis. He was admitted to our hospital due to liver abscesses and bacteremia caused by multidrug-resistant Pseudomonas aeruginosa. Empirical treatment with piperacillin/tazobactam was started, and the patient initially recovered. However, he developed a second case of sepsis caused by piperacillin/tazobactam-resistant P. aeruginosa bacteremia originating from a new liver abscess. We changed the piperacillin/tazobactam to colistin and flomoxef and continued the two antibiotics for one month. During the antibiotic therapy, the patient successfully underwent bile duct stent placement.