Background: The epidemiology of domestically acquired intestinal parasites (IPs) in developed countries remains poorly understood, although Entamoeba histolytica is increasingly recognized as a domestically prevalent sexually transmitted infection. We assessed the burden of IPs in routine clinical practice in Japan. Methods: We analyzed stool specimens submitted during 2022–2024 from patients with suspected infectious gastroenteritis at a tertiary referral center in Tokyo, and compared IP detection rates according to patients’ recent travel histories (overseas travelers or non-travelers). Risk factors were assessed by logistic regression. Molecular analyses were performed to identify circulating strains. Findings: Among 624 analyzable stool specimens, 68 IPs were detected from 62 cases, including 32 non-travelers. IPs in non-travelers were confined to three protozoa—E. histolytica, G. duodenalis, and Cryptosporidium spp. Overseas travelers showed broader parasite diversity. Independent predictors of IP positivity were MSM status, travel abroad, and animal contact; MSM was the only independent predictor among non-travelers. Molecular analyses identified two putative Giardia clusters within Assemblage B and two C. hominis gp60 subtype groups (IaA14R1 and IaA16R5) were prevalent among MSM in Tokyo during the study period. Interpretation: In Japan, giardiasis and cryptosporidiosis among MSM might reflect ongoing domestic transmission rather than sporadic imported infections. Current routine diagnostic practice is likely to underestimate these intestinal protozoa in patients with no travel history.

Giardiasis and Cryptosporidiosis are common diarrheal diseases that are often underdiagnosed due to non-specific symptoms and diagnostic limitations. While multiplex-PCR and rapid antigen tests (rapid-IC) offer high accuracy, their cost and restricted pathogen coverage, especially for parasites, limit their use. This study evaluates newly developed diagnostic method for these protozoa, named fluorescent antibody microscopy (FAM).TABLE 1Sensitivity and specificity of each method for detection of Giardia with reference to multiplex PCRTABLE 2Sensitivity and specificity of each method for detection of Cryptosporidium with reference to multiplex PCR For performing FAM, stool samples are mixed with DyLight 488-conjugated antibodies against G. duodenalis cysts and Cryptosporidiumoocysts, thereafter, the samples are examined by fluorescence microscopy to detect these protozoa. All samples showing positive for FAM, and unbiasedly selected those with FAM negative result were subjected to multiplex-PCR, and rapid-IC. Diagnostic accuracies of FAM and rapid-IC were assessed by the result of multiplex-PCR as a reference standard. Cases with discordant results among these tests were examined by conventional PCR with sequencing to confirm infection. FAM was examined for 694 stool samples during study period, which identified 35 “FAM positive samples”. Also, “FAM negative samples” were selected from all cases with negative results at any one month (49 samples). In total, a subset of 84 samples underwent further analysis. For Giardiasis, FAM showed 88.0% sensitivity and 100% specificity, which was exactly the same results with rapid-IC, including 3 samples showing false negative by both tests. (Table 1) For cryptosporidiosis, FAM had 93.8% sensitivity and 100% specificity, which represents comparable diagnostic accuracy with rapid-IC. (Table 2) Interestingly, conventional PCR for G. duodenalis oppositely showed negative results for 3 samples with multiplex-PCR positive, and FAM/rapid-IC negative results, which raised 2 possibilities; false negative results of FAM/rapid-IC due to extremely low pathogen burden, or false positive result of multiplex-PCR. FAM, a newly developed low-cost morphological stool examination for Giardia and Cryptosporidium, showed comparably high diagnostic accuracy with rapid-IC. It could be a cost-effective option for routine stool testing. All Authors: No reported disclosures

In developed countries, intestinal parasites are generally considered as an agent occurring among people who are traveling to or immigrants from endemic area with poor sanitation. Also, recent epidemiological studies showed that Entamoeba histolytica could happen as sexually transmitted infection (STI). However, the epidemiology of the other intestinal parasite infestations (IPIs) is still unclear in many developed countries.Figure 1.Distribution of intestinal parasites.Intestinal parasitic infections were determined by modified O&P in the present study. (A) Intestinal parasites seen in imported cases were presented, in which multiple parasites were detected from one sample in two cases. (B) Intestinal parasites seen in domestic cases are presented, in which multiple parasites are detected from one sample in four cases.Table 1.Impact of patients’ characteristics and symptoms on the incidence of IPIs.*Multivariate analysis was calculated for an independent variables, which were adjusted by sex, age, and variables with relatively low p value (p < 0.2). For stool samples from the patients with suspicion of infectious gastroenteritis, modified stool ova and parasite examination (modified O&P) was performed as following. Firstly, stool samples are mixed with fluorescent conjugated antibodies against Giardia cyst, and Cryptosporidium oocyst, thereafter, the sample is examined by both fluorescent microscopy and bright-field microscopy. It has compatibly high sensitivity as antigen detection test or PCR for the detection of these protozoa. During 3-year study period, 624 stool samples were examined by modified O&P. IPIs were confirmed in 62 cases (9.9%); 30 as imported cases and 32 as domestic cases (Fig. 1). The most common parasites were G. duodenalis, E. histolytica, and Cryptosporidium spp. Interestingly, domestic parasite infections were limited to these three protozoa, in which four cases showed multiple protozoa. In contrast, various types of parasites were detected in imported cases. Multivariate logistic regression identified not only recent travel history to endemic area but also men who have sex with men and animal contact as independent risk factors for IPIs (Table 1). G. duodenalis and Cryptosporidium spp. are commonly reported as domestic cases, whose frequency was the same level as that of E. histolytica. Also, the results from regression analysis suggest that these protozoa are spreading as sexually transmitted infection among MSM, and zoonoses. Molecular epidemiological study is currently underway. Active epidemiological surveillance is warranted in the other developed countries. All Authors: No reported disclosures

Haemophilus influenzae is a rare cause of pyogenic osteomyelitis, with only eleven reported adult cases. We present a case of H. influenzae vertebral osteomyelitis and psoas abscess in a 48-year-old woman who had received prior antibiotic therapy before the event. She subsequently developed worsening lower back pain, and magnetic resonance imaging revealed L4/L5 osteomyelitis with psoas abscess. Despite empiric cefazolin therapy, her condition deteriorated. All microbiological cultures remained negative, including blood and aspirated pus from the lesion. Broad-range 16S ribosomal RNA gene polymerase chain reaction and sequencing analysis identified β-lactamase-negative ampicillin-susceptible H. influenzae as the causative pathogen. After switching to cefotaxime, the patient improved and completed treatment with oral levofloxacin without recurrence. This case demonstrates the value of molecular techniques in diagnosing culture-negative infections, particularly in antibiotic-pretreated patients.

BACKGROUND & AIMS:The association between circulating vitamin D levels and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or seasonal influenza infection in vaccine recipients remains unclear. We prospectively examined these associations among healthcare workers. METHODS:This study included 1434 staff members at a tertiary hospital who completed a questionnaire and provided blood samples in December 2023. Participants were followed for SARS-CoV-2 and seasonal influenza infections until March 2024, based on data from an in-house registry and responses to a follow-up questionnaire. Baseline serum 25-hydroxyvitamin D levels were categorized as sufficient (≥20 ng/mL), insufficient (12-19 ng/mL), or deficient (<12 ng/mL). Cox proportional hazard models were used to estimate the hazard ratio for SARS-CoV-2 or seasonal influenza infection risk across vitamin D categories, adjusting for potential confounders. RESULTS:Among the participants (median age: 40 years; 73 % female), 1372 (96 %) had received at least three doses of a COVID-19 vaccine, and 1196 (83 %) had received a seasonal influenza vaccine. Baseline vitamin D status was not associated with SARS-CoV-2 infection risk; the adjusted hazard ratios (95 % confidence intervals) for those with vitamin D insufficiency and deficiency, compared to those with vitamin D sufficiency, were 0.69 (0.43, 1.10) and 0.95 (0.49, 1.83), respectively. No association was observed between vitamin D status and the risk of seasonal influenza infection. CONCLUSIONS:Our findings suggest that sufficient vitamin D levels may not offer additional protection against SARS-CoV-2 and seasonal influenza infection after vaccination.

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.

Background Dexamethasone is currently administered for Coronavirus disease 2019(COVID-19); however, there are concerns about its effect on specific antibodies’ production. The aim of this study was to evaluate whether specific antibodies were affected by COVID-19 severity and corticosteroid treatment. Methods Of 251 confirmed COVID-19 patients admitted to our hospital between January 26 and August 10, 2020, the early period of the pandemic, 75 patients with sera within 1 month of onset and 1month or longer were included in the research. A total of 253 serum samples from these patients were collected. The levels of specific antibodies for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), immunoglobulin G (IgG) and M (IgM), were measured retrospectively. The results were compared separately of each COVID-19 severity, and with or without corticosteroid treatment. Results Among the 75 patients, 47, 18, and 10 had mild, moderate, and severe disease, respectively. The median age was 53.0 years and 22 (29%) were women. The most common comorbidities were hypertension and dyslipidemia. Corticosteroids were administered to 20 (27%) and 10 (53%), patients with moderate and severe disease, respectively. The positivity rates IgM increased first, and IgG was almost always positive after day 16, regardless of the severity of COVID-19. On days 6–10, both IgG and IgM positivity rates were higher in patients with moderate disease than in those with mild or severe disease. In patients with moderate disease, IgG positivity was similar over time, regardless of corticosteroid treatment. Conclusions In COVID-19 patients, specific IgG is positive and maintained for a long period of time, even after corticosteroid treatment. The effect of corticosteroid treatment in a COVID-19 epidemiological study using specific IgG antibodies was considered minor. COVID-19 patients were more likely to receive oxygen if IgM was positive 1 week after onset, but not mechanical ventilation. IgM measurement 1 week after onset may predict COVID-19 severity.

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.

Necrotizing fasciitis (NF) is a life-threatening disease with high mortality and rapidly progressive clinical manifestations. Early detection and surgical management coupled with antibiotic treatment are crucial for the survival, and the patient survival is heavily dependent on clinical decisions. However, it is not widely known that NF does not always follow a typical clinical course, and there have been no case reports of NF following an atypical clinical course. Although the course of the disease depends on the individual patient, it remains a challenge for physicians to determine the precise timing when patients are most likely to survive multiple surgical interventions. We encountered a challenging case presenting with an atypical clinical course. We herein report a 31 year-old man who followed a deteriorating biphasic-like clinical course and presented with extensive NF and streptococcal toxic shock syndrome due to Group A Streptococcus. This case serves to inform physicians of the existence of NF with an atypical and deteriorating biphasic-like clinical course, emphasizing the need for a careful evaluation of the patient condition.

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. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/li censes/by-nc-nd/4.0/).

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] x 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.

Background: The risk factors for coronavirus disease (COVID-19) among healthcare workers (HCWs) might have changed since the emergence of the highly immune evasive Omicron variant.Aim: To compare the risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among HCWs during the Delta- and Omicron-predominant periods.Methods: Using data from repeated serosurveys among the staff of a medical research centre in Tokyo, two cohorts were established: Delta period cohort (N = 858) and Omicron period cohort (N = 652). The potential risk factors were assessed using a questionnaire. Acute/current or past SARS-CoV-2 infection was identified by polymerase chain reaction or anti-nucleocapsid antibody tests, respectively. Poisson regression was used to calculate the risk ratio (RR) of infection risk. Findings: The risk of SARS-CoV-2 infection during the early Omicron-predominant period was 3.4-fold higher than during the Delta-predominant period. Neither working in a COVID19-related department nor having a higher degree of occupational exposure to SARS-CoV-2 was associated with an increased infection risk during both periods. During the Omicronpredominant period, infection risk was higher among those who spent >30 min in closed spaces, crowded spaces, and close-contact settings without wearing mask (>= 3 times versus never: RR: 6.62; 95% confidence interval: 3.01-14.58), whereas no such association was found during the Delta period.

Macrophage cell lines were used in these studies as a model system to dissect the biochemical and functional mosaic of the macrophage activation process. In particular, the requirements for the induction of tumoricidal and bactericidal activity in the RAW 264.7 and WEHI-3 cell lines by interferon-γ (IFN-γ) and bacterial lipopolysaccharide (LPS) were determined. Changes in expression of a series of macrophage markers traditionally associated with macrophage activation were monitored during stimulation of the cells in order to determine whether a detectable pattern of activation-associated changes is associated with the development of a particular functional activity. These markers included changes in the cell surface expression of major histocompatibility complex-encoded Class I and Class II antigens and antigens in the Mac-1/LFA-1 family, alterations in the levels of membrane enzymes (5′ nucleotidase and alkaline phosphodiesterase), and production of secretory products including hydrogen peroxide and the monokines interleukin-1, interferons-αβ, and tumor necrosis factor-α. Our results demonstrate that a given homogeneous macrophage population expresses a distinct subset of functional activities in response to single, defined activating signals such as IFN-γ and LPS. The display of a variety of macrophage surface antigens, enzymes, and secreted products is activated simultaneously by such treatment; however, the particular pattern of such activation-associated markers cannot reproducibly be used to predict the ability of an activated cell to perform a particular function. The results also suggest that macrophage cell lines expressing differential response patterns following IFN-γ stimulation provide a valuable system for dissection of the molecular and cell biology of macrophage activation.

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  = 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. 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. 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.

After 3.5 years of the COVID-19 pandemic, as a large proportion of the population has been infected globally, reinfection is a major public health concern. Given that sizable SARS-CoV-2 infections are undiagnosed, 1 Mizoue T. Yamamoto S. Konishi M. Oshiro Y. Inamura N. Nemoto T. et al. Cumulative and undiagnosed SARS-CoV-2 infection among the staff of a medical research center in Tokyo after the emergence of variants. Epidemiol Infect. 2023; 151: e48 Crossref PubMed Scopus (1) Google Scholar it is of interest to clarify whether antibodies can be used to define reinfection. In this regard, we read with interest the study reported by Dowell et al. 2 Dowell A.C. Waiblinger D. Wright J. Ladhani S.N. Moss P. Nucleocapsid-specific antibodies as a correlate of protection against SARS-CoV-2 reinfection in children. J Infect. 2023; 87: 267-269 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar in the Journal of Infection, who operationally defined reinfection as a 1.5-fold rise in the anti-SARS-CoV-2 nucleocapsid (N) antibody titer from the baseline. N antibody is known to decrease over time and is not influenced by mRNA vaccination; thus, it would be reasonable to assume that its rise during the follow-up indicates reinfection. Data are scarce, however, on the kinetics and durability of N antibody titer after reinfection relative to that after initial infection. Here, we described the trajectory of the N antibody titer among healthcare workers who experienced reinfection.

Background:We aimed to investigate chronological changes in the characteristics of participants in a coronavirus disease 2019 convalescent plasma donation study that may benefit optimal collection methods in the future. Methods:Data from a convalescent plasma donation study from April 30, 2020 to November 5, 2021 were collected and analyzed. After August 23, 2021, an interim analysis of factors linked to higher antibody titers led us to restrict our participant recruitment criteria to participants who were within 4 months of disease onset and to patients who were otherwise most likely to have sufficiently high antibody titers. Overall, 1299 samples from 1179 patients were analyzed. Results:Over the duration of the study, 35.9% of the samples were deemed eligible for convalescent plasma collection. The overall eligibility rate initially declined, dipping to <20% after one year. During this period, the proportion of enrolled samples from patients who had severe illness also declined, and the proportion of samples from participants who were >120 days post disease onset increased. After the addition of days from onset and vaccination status to our participant recruitment criteria, the eligibility rate improved significantly. Conclusions:As outbreaks of emerging infectious disease occur, it is desirable to construct and implement a scheme for convalescent plasma donation promptly and to monitor the eligibility rate over time. If it declines, promptly analyze and resolve the associated factors. Additionally, vaccine development and infection prevalence are likely to influence the effective recruitment of participants with high antibody titers.

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.

Clostridium ramosum infections have been rarely reported, probably due to underestimating in clinical practice. Seven patients with bacteremia from gastrointestinal sources and skin and soft tissue were recognized between 2009 and 2020. Most of them were older and in compromised status, and they had risk factors including cancer, diabetes, liver cirrhosis, gangrene, and pressure ulcers. The source of infections was considered bacterial translocation from the gastrointestine and the skin and soft tissue infections. All patients were treated with antimicrobials, and two received surgical interventions. Four patients died secondary to sepsis due to C. ramosum. The bacteremia of C. ramosum should be appropriately evaluated and treated, especially in compromised hosts.

Objectives: To investigate the role of immunogenicity after the third vaccine dose against Omicron infec- tion 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 be- tween 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. © 2023 The Author(s). Published by Elsevier Ltd on behalf

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-naive 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. Shohei Yamamoto, Clin Microbiol Infect 2023;29:1201.e1 -1201.e5 (c) 2023 The Author(s). Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).