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.

Cumulative and undiagnosed SARS-CoV-2 infection among the staff of a medical research centre in Tokyo after the emergence of variants.

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.

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.

Coronavirus Disease 2019 (COVID-19) Breakthrough Infection and Post-Vaccination Neutralizing Antibodies Among Healthcare Workers in a Referral Hospital in Tokyo: A Case-Control Matching Study.

BACKGROUND: While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity. METHODS: We describe incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2415 fully vaccinated staff (BNT162b2) for breakthrough infection and selected 3 matched controls. We measured post-vaccination neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the 2 groups. RESULTS: No COVID-19 cases occurred 1-2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2-4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and participants had returned to work early. There was no measurable difference between cases and controls in post-vaccination neutralizing antibody titers against the wild-type, Alpha, Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type. CONCLUSIONS: Post-vaccination neutralizing antibody titers were not decreased among patients with breakthrough infection relative to their controls under the Delta variant outbreak. The result points to the importance of infection-control measures in the post-vaccination era, irrespective of immunogenicity profile.

Clinical characteristics and risk factors for multidrug-resistant bacterial isolation in patients with international travel history.

BACKGROUND: International travelers are at risk of carrying resistant bacteria. It is critical to identify risk factors associated with multidrug-resistant organism (MDRO) colonization in travelers. METHODS: A retrospective chart review observational study was conducted at two tertiary centers in Japan for inpatients who had been hospitalized or visited an outpatient clinic overseas within the previous 12 months. These patients underwent MDRO screening upon admission. To identify independent predictors for the isolation of MDROs, multivariable analyses were performed using logistic regression. RESULTS: In total, 77 (36%) of the 216 patients were positive for MDROs at admission. The majority of bacteria detected in stool samples were extended-spectrum beta-lactamase-producing Escherichia coli (ESBLEC) (n = 67 [89%]). ESBLEC was detected in nearly 40% of patients who traveled to Asia. Travel to Asia was an independent risk factor for any MDRO and ESBLEC isolation. For non-ESBLEC MDRO isolation, a history of surgery abroad was an independent risk factor for detection. DISCUSSION AND CONCLUSIONS: A history of hospitalization abroad has previously been found to be associated with MDRO colonization in travelers, which was not identified as a risk factor in this study. The risk factors for MDRO colonization were different between ESBLEC and non-ESBLEC MDROs.

A novel protocol for de-isolating moderately and severely immunocompromised COVID-19 patients.

Immunocompromised coronavirus disease 2019 patients are at a higher risk of prolonged viral shedding than immunocompetent patients. However, as of August 2023, there is no clear international standard for de-isolating vulnerable patients. A comprehensive assessment is advisable based on various information, such as the increase in immune escape of specific mutant strains as well as the patient's innate immunity and vaccination status; therefore, consultation with an infectious disease specialist is recommended. The patient population defined as moderately or severely immunocompromised by the Centers for Disease Control and Prevention and the European Centre for Disease Prevention and Control is significantly broad. A boundary between the two remains to be delineated, and the existing protocols allow the release of patients based on their symptoms alone. This may lead to an unnecessary extension or premature termination of isolation. In this study, we searched for studies, particularly those that used real-world data, discussed the results with experts in our hospital, and proposed new isolation criteria based on both testing and clinical symptoms. We classified patients into three groups namely severely, moderately, and mildly immunocompromised, defined by their background and the administration of immunosuppressive drugs. A separate flowchart for ending isolation is indicated for each group. This standard may be a useful support material, especially for non-specialists. Nevertheless, our criteria must be revised and added continuously; accumulating real-world data to support revision of and addition to the list is becoming increasingly important.

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.

Neutralizing antibodies after three doses of the BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron-predominant wave.

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.

"Syndromic surveillance within a hospital" for the early detection of a nosocomial outbreak of acute respiratory infection.

We have performed intra-hospital syndromic surveillance to rapidly detect nosocomial acute respiratory infection outbreaks in both inpatients and health care workers in a hospital. Syndromic surveillance allows the rapid detection of sudden outbreaks, including infections caused by unknown pathogens. This approach depends on the identification of specific "symptoms" as signs of a possible outbreak, with no need for specific diagnoses. Moreover, syndromic surveillance is quick, easy, and inexpensive. Nosocomial infection surveillance is usually performed on inpatients only. However, during the outbreaks of SARS and seasonal influenza, for example, many hospital personnel were infected. In cases of this kind, in order to quickly detect the prevalence of such infections, a surveillance system that includes hospital personnel is essential. This surveillance is promising as a strategy to prepare for re-outbreaks of SARS and the emergence of novel influenza pandemics.

Molecular epidemiology of outbreaks and containment of drug-resistant Pseudomonas aeruginosa in a Tokyo hospital.

We witnessed outbreaks of multidrug-resistant (MDR) and drug-resistant Pseudomonas aeruginosa at a hospital in Tokyo, Japan, during the period September 2004 through May 2005. The first outbreak occurred in September and October 2004. Three isolates of MDR P. aeruginosa were identified from urine samples obtained from three nonambulatory immunodeficient patients in one ward. After 3 weeks, another outbreak of P. aeruginosa occurred in the hematology ward on the same floor of the hospital. During the outbreaks, environmental surveys were conducted twice in each of the two wards, at 2-week intervals, to identify the sources of the pathogens. A total of 23 P. aeruginosa isolates, including 11 from environmental sources, were analyzed for chromosomal DNA typing by pulsed-field gel electrophoresis, for O-antigen serotyping, and for other typing. Results revealed two causative clones, as well as environmental contamination by P. aeruginosa clones on the surfaces of urine volume-measuring devices in rooms where urine is handled, which may have been sources of the pathogens during the outbreaks. To prevent further outbreaks, we performed the following: (a) environmental surface monitoring for drug-resistant P. aeruginosa, (b) active surveillance of specimens, (c) strict isolation of infected patients or carriers of MDR P. aeruginosa, (d) rigorous contact precautions, and (e) disinfection with 70% alcohol on the surfaces of apparatuses contaminated by MDR or drug-resistant P. aeruginosa and in the rooms where urine is handled. As a result, the outbreaks were contained.