T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis.

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group.

Association between a low response to rubella vaccination and reduced anti-severe acute respiratory syndrome coronavirus 2 immune response after vaccination with BNT162b2: a cross-sectional study.

OBJECTIVES: Some vaccinated individuals fail to acquire an adequate immune response against infection. We aimed to determine whether mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination could induce a sufficient immune response against SARS-CoV-2 in low responders to other vaccinations. METHODS: Using data from health-care workers who received two doses of the BNT162b2 vaccine (BioNTech/Pfizer), we conducted a single-centre, cross-sectional study to determine whether low responders to measles, rubella, and hepatitis B virus (HBV) vaccinations could acquire sufficient antibodies after SARS-CoV-2 vaccination. From May 2021 to June 2021, participants were tested for anti-SARS-CoV-2 spike (anti-S) IgG antibodies at least 2 weeks after the second dose of BNT162b2. The association between a low response to measles, rubella, and HBV vaccinations and the post-vaccination anti-S IgG titre was evaluated using the multivariable linear regression analysis. RESULTS: All 714 participants were positive for the anti-S IgG titre (≥50.0 AU/mL) after two doses of BNT162b2 (median, 7126.8 AU/mL; interquartile range, 4496.2-11 296.8). There were 323 (45.2%), 131 (18.3%), and 43 (6.0%) low responders to measles, rubella, and HBV vaccinations, respectively. In the multivariable linear regression analysis, low responders to rubella vaccination had significantly low acquisition of the anti-S IgG titre after two doses of the BNT162b2 vaccine (standardized coefficient ß, -0.110; 95% CI, -0.175 to -0.044). CONCLUSIONS: A low response to rubella vaccination is a potential predictor of a reduced response to SARS-CoV-2 vaccination. Further studies are needed to determine whether a low response to rubella vaccination is associated with the durability of SARS-CoV-2 vaccination-induced immune response.

SARS-CoV-2 Infection upon Leaving the Tokyo 2020 Olympic and Paralympic Games.

Objective Just before the Tokyo 2020 Olympic and Paralympic Games in Japan, the number of people infected with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), started to increase at an unprecedented rate. This study investigated the effectiveness of vaccines in large-scale sporting events under difficult circumstances, such as during adherence to a bubble system and confinement inside the Olympic/Paralympic Village. Methods In collaboration with medical clinics inside and outside the Village, a prospective cohort study was conducted among overseas participants using the results of polymerase chain reaction (PCR) tests for SARS-CoV-2 upon leaving Japan. Results A total of 12,072 foreign participants were enrolled, 13 (0.11%) of whom had a positive PCR test result. None of these cases were broadcasters or members of the press, were tested outside the Olympic Village, or had a history of COVID-19 infection. The effectiveness of full vaccination and vaccination at least once (≥14 days ago) was 74% [95% confidence interval (CI): 6-93%] and 81% (95% CI: 30-95%), respectively. Three breakthrough infections with the Delta variant were observed in 6,485 fully vaccinated participants (0.05%). The positivity rate was 0.09% among adherents to the bubble system and 0.28% among non-adherents, but this difference was not significant. Conclusion These findings indicate that even huge sporting events such as the Olympic and Paralympic Games can proceed while pandemics are ongoing in the host country by combining countermeasures such as vaccination, frequent testing, social distancing, and adherence to a bubble system.

Investigation for the efficacy of COVID-19 vaccine in Japanese CKD patients treated with hemodialysis.

Background: Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers. Methods: Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (Control group), receiving two doses of BNT162b2 vaccine, were recruited through the Japanese Society for Dialysis Therapy (JSDT) Web site in July 2021. Anti-SARS-CoV-2 immunoglobulin (IgG) (SARS-CoV-2 IgG titers) was measured before vaccination, 3 weeks after the first vaccination, 2 weeks after the second vaccination, and 3 months after the second vaccination, and was compared between Control group and HD group. Factors affecting SARS-CoV-2 IgG titers were also examined using multivariable regression analysis and stepwise regression analysis (least AIC). In addition, we compared adverse reactions in Control and HD groups and examined the relationship between adverse reactions and SARS-CoV-2 IgG titers. Results: Our study enrolled 123 participants in the Control group (62.6% men, median age 67.0 years) and 206 patients in the HD group (64.1% men, median age 66.4 years). HD group had significantly lower SARS-CoV-2 IgG titers at 3 weeks after the first vaccination (p < 0.0001), 2 weeks after second vaccination (p = 0.0002), and 3 months after the second vaccination (p = 0.045) than Control group. However, the reduction rate of SARS-CoV-2 IgG titers between 2 weeks and 3 months after the second vaccination was significantly smaller in HD group than in Control (p = 0.048). Stepwise regression analysis revealed that dialysis time was identified as the significant independent factors for SARS-CoV-2 IgG titers at 2 weeks after the second vaccination in HD group (p = 0.002) and longer dialysis time resulted in higher maximum antibody titers. The incidences of fever and nausea after the second vaccination were significantly higher in the HD group (p = 0.039 and p = 0.020). Antibody titers in those with fever were significantly higher than those without fever in both groups (HD: p = 0.0383, Control: p = 0.0096). Conclusion: HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers.

Risk factors associated with hospitalization in patients with asymptomatic or mild COVID-19 in public accommodation facilities in Tokyo.

INTRODUCTION: In Japan, patients with coronavirus disease 2019 (COVID-19) who do not require medical intervention are provided care in recovery accommodation facilities (RAFs). However, some patients may require hospitalization if their symptoms become more severe during their stay. We conducted an observational study using epidemiological data of patients with COVID-19 admitted to RAFs in Tokyo. METHODS: This was an observational cohort study using data from COVID-19 patients admitted to one of the RAFs in Tokyo from December 2020 to November 2021. Admissions to the facilities were limited to patients with asymptomatic or mild COVID-19 with no underlying disease or at least stable underlying disease at the time of admission. Patients were hospitalized when they required oxygen administration or when they had, or persistent fever, or severe respiratory symptoms. We evaluated the association between hospitalization and the risk factors for hospitalization using a Cox regression model. RESULTS: The number of patients with COVID-19 admitted to the RAF was 6176. The number of hospitalized patients was 393 (6.4%), and the median length of stay was 5.50 days (IQR: 4.50, 6.50). In the Cox regression analysis, the hazard ratio increased with age and was significantly higher among patients aged >60 years (HR = 10.23, 95% CI: 6.72-15.57) than those in other age groups. This trend is similar to that observed in the sensitivity analysis. CONCLUSION: Patients with diabetes, the elderly, obesity, and medications for gout and psychiatric diseases may be at a high risk of hospitalization. In particular, an age over 60 years was strongly associated with hospitalization.

Committee report: Questionnaire survey on the treatment of COVID-19 in patients receiving dialysis therapy.

Background: Patients with coronavirus disease 2019 (COVID-19) who receive dialysis therapy develop more severe disease and have a poorer prognosis than patients who do not. Although various data on the treatment of patients not receiving dialysis therapy have been reported, clinical practice for patients on dialysis is challenging as data is limited. The Infection Control Committee of the Japanese Society for Dialysis Therapy decided to clarify the status of treatment in COVID-19 patients on dialysis. Methods: A questionnaire survey of 105 centers that had treated at least five COVID-19 patients on dialysis was conducted in August 2021. Results: Sixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities. Conclusions: Our survey revealed a variety of treatment practices in each facility. Further evidence and innovations are required to improve the prognosis of patients with COVID-19 receiving dialysis therapy.

Seroprevalence and associated factors of Toxoplasma gondii among HIV-infected patients in Tokyo: A cross sectional study.

HIV infection, in particular in patients with developing AIDS, carries a risk of causing toxoplasmosis with encephalitis, which is mostly caused by a form (bradyzoite) of the protozoan parasite Toxoplasma gondii. HIV/AIDS in Japan has been recognized as a serious health issue in recent years. In this study, to elucidate T. gondii seroprevalence in HIV-positive patients in Japan and associated characteristics with Toxoplasma parasite infection, the titer of T. gondii IgG (Tg-IgG) was measured in 399 HIV-positive patients who visited a hospital in Tokyo, Japan, between 2015 and 2017. A questionnaire survey was also conducted to investigate associations between lifestyle and customs. As a result, the overall prevalence of Tg-IgG-positive serum was 8.27% (33 cases of 399). All the cases positive for Tg-IgG were confirmed using the Sabin-Feldman dye test; the titers between each examination correlated robustly (p < 0.001, r = 0.6). A correlation between Toxoplasma infection rate and age was determined (p < 0.001), whereas there was no significant correlation with lifestyle customs such as consuming undercooked meat or owning a cat. An association between Toxoplasma infection and experience of dwelling in the Hokkaido area, the northern part of Japan, was observed (p = 0.001). These results suggested that the proportion of those who were previously exposed to Toxoplasma parasites in the HIV-positive population has been maintained at a similar level as that of the HIV-negative population in Japan, providing clear information about the potential risk of toxoplasmic encephalitis.

Associations of HIV testing and late diagnosis at a Japanese university hospital.

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.

Associations of HIV testing and late diagnosis at a Japanese university hospital

OBJECTIVES: This study was conducted to clarify the rate of late diagnosis of HIV infection and to identify relationships between the reasons for HIV testing and a late diagnosis. METHODS: This retrospective cohort study was conducted among HIV-positive patients at the Jikei University Hospital between 2001 and 2014. Patient characteristics from medical records, including age, sex, sexuality, the reason for HIV testing and the number of CD4-positive lymphocytes at HIV diagnosis, were assessed. RESULTS: A total of 459 patients (men, n=437; 95.2%) were included in this study and the median age at HIV diagnosis was 36 years (range, 18-71 years). Late (CD4 cell count <350/mm3) and very late (CD4 cell count <200/mm3) diagnoses were observed in 61.4% (282/459) and 36.6% (168/459) of patients, respectively. The most common reason for HIV diagnosis was voluntary testing (38.6%, 177/459 patients), followed by AIDS-defining illness (18.3%, 84/459 patients). Multivariate analysis revealed a significant association of voluntary HIV testing with non-late and non-very-late diagnoses and there was a high proportion of AIDS-defining illness in the late and very late diagnosis groups compared with other groups. Men who have sex with men was a relative factor for non-late diagnosis, whereas nonspecific abnormal blood test results, such as hypergammaglobulinemia and thrombocytopenia, were risk factors for very late diagnosis. CONCLUSIONS: Voluntary HIV testing should be encouraged and physicians should screen all patients who have symptoms or signs and particularly hypergammaglobulinemia and thrombocytopenia, that may nonspecifically indicate HIV infection.

Predictive factors for metastatic infection in patients with bacteremia caused by methicillin-sensitive Staphylococcus aureus.

BACKGROUND: Metastatic infections such as infective endocarditis and psoas abscess are serious complications of Staphylococcus aureus bacteremia because failure to identify these infections may result in bacteremia relapse or poor prognosis. In the present study, we determined the predictive factors for metastatic infection due to methicillin-sensitive S. aureus bacteremia. METHODS: A retrospective cohort study was conducted among patients with methicillin-sensitive S. aureus bacteremia at the Jikei University Hospital between January 2008 and December 2012. Factors analyzed included the underlying disease, initial antimicrobial treatment and primary site of infection. RESULTS: During the 5-year study period, 73 patients met the inclusion criteria and were assessed. The most common primary site of bacteremia was catheter-related bloodstream infection (25/73 [34.2%]). Metastatic infection occurred in 14 of 73 patients (19.2%) (infective endocarditis [3], septic pulmonary abscess [3], spondylitis [4], psoas abscess [4], epidural abscess [3] and septic arthritis [1]). Six patients had multiple metastatic infections. Multivariate analysis revealed that the predictive factors associated with the development of metastatic infection were a delay in appropriate antimicrobial treatment of >48 hours, persistent fever for >72 hours after starting antibiotic treatment and lowest C-reactive protein levels of >3 mg/dL during 2 weeks after the onset of bacteremia. CONCLUSIONS: This study demonstrated that additional diagnostic tests should be conducted to identify metastatic infection, particularly in patients with delayed antimicrobial treatment, persistent fever and persistently high C-reactive protein levels.

[Two cases of Paragonimiasis westermani in a Chinese family diagnosed with the Ouchterlony double diffusion method].

We report two cases of Paragonimus westermani infection in a Chinese family in Japan. A 41-year-old husband and his 40-year-old wife were infected with P. westermani after consuming a homemade Chinese traditional "Drunken Crab." They were a family with two children who had lived in Japan for 19 years. The crabs were Eriocheir japonica sent from the Kyusyu area that they had pickled at home with soy sauce and Chinese liquor for 5 days. Their children did not eat any of the crabs. One month after consuming the crabs, the husband came to our outpatient clinic with fever and chest pain and his wife also presented with a persistent cough. Both patients had a high peripheral blood eosinophil count (husband:18,900/µL, wife:10,600/µL) with pulmonary effusion, nodular shadow, and pneumothorax in chest X-ray findings. Paragonimiasis was suspected from the episode of consuming the crabs. No parasite eggs were seen in their sputum and stool samples. A multiple-dot ELISA was performed with the sera to screen for parasitic infections, but the result was only weakly positive for P. westermani antigen in the husband and a slightly positive reaction in the wife. The diagnosis of P. westermani was achieved with the double diffusion Ouchterlony method using P. westermani antigen and P. miyazakii antigen. Praziquantel administration for three days improved the symptoms in both patients. The Ouchterlony method proved useful in diagnosing paragonimiasis in these cases.

A case of NDM-1-producing Acinetobacter baumannii transferred from India to Japan.

A 52-year-old male Japanese businessman with massive cerebral bleeding was transferred from India to Japan and was admitted to our hospital. Multidrug-resistant Acinetobacter baumannii was isolated from his sputum. The minimum inhibitory concentrations for this strain were as follows: imipenem, 64 µg/ml; meropenem, 32 µg/ml; ciprofloxacin, 16 µg/ml; amikacin, 16 µg/ml; aztreonam, 16 µg/ml; colistin, <1 µg/ml. This A. baumannii strain had both bla NDM-1 and bla OXA-23 by polymerase chain reaction analysis. In Japan, NDM-1-producing bacteria are extremely rare in clinical specimens. To date, three NDM-1-positive cases have been detected in Japan, and this is the first case of A. baumannii-producing NDM-1 in Japan. Our case suggests that NDM-1-producing bacteria could be introduced into our country easily. There is concern that various resistant bacteria may be transferred from epidemic countries as a result of international medical care.

An HIV patient with hepatic flare after the initiation of HBV-active antiretroviral therapy.

A 39-year-old man presented a CD4 T cell count of 78/µL and HIV-RNA at 6.6 × 10(5) copies/mL at his first medical examination. After the 58th day, we initiated HBV-active antiretroviral therapy. Three months after the start of antiretroviral therapy, he was diagnosed with hepatic flare on the basis of elevated AST and ALT levels without detecting HBV-DNA. Although after continuing the medication his AST and ALT levels increased to 700 IU/L and 1,400 IU/L, respectively, he showed improvement following a natural course and was discharged from hospital after the 169th day. This is a case of hepatic flare likely caused by immune reconstitution associated with resolved HBV infection.

Comparison of free and anonymous testing for HIV and sexually transmitted infections between the University Hospital and Health Center.

We gathered data regarding age, sex, and positivity rates for human immunodeficiency virus (HIV), syphilis, gonococcus, and chlamydia from individuals who underwent free and anonymous sexually transmitted infection (STI) testing conducted at the Jikei University School of Medicine Hospital (our hospital). These data were compared to results of subjects who underwent similar testing at the Minato Health Center and several private facilities of urologists and gynecologists belonging to the Minato Ward Medical Association. The positivity rate of chlamydia was found to be high in female subjects, particularly at the Minato Health Center, with 15 of 194 subjects (7.73 %) testing positive. In our hospital, we only detected 3 of 133 subjects (2.26 %) who were gonococcus positive. On the other hand, at the doctor's facilities, 10 of 188 male subjects (5.32 %) were syphilis positive, and 8 of 185 male subjects (4.32 %) were chlamydia positive, thus showing high positivity rates for both infections. At our hospital, 1 of 231 subjects was positive for gonococcus and 4 of 230 subjects (1.74 %) were positive for chlamydia, thus showing lower positivity rates for both infections. HIV-positive subjects were, however, only confirmed at our hospital, with 2 of 243 subjects (0.82 %) being positive. We were able to diagnose infected patients using free and anonymous STI testing at hospitals, and the same as at doctors' facilities. This result suggests that the hospitals that have many opportunities to diagnose HIV patients may become potential candidates for the development of new consultation facilities, establishment of testing facilities, and enhancement of consultation processes that include STI prevention.

Clinical characteristics and risk factors for mortality in patients with bacteremia caused by Pseudomonas aeruginosa.

OBJECTIVE: The mortality rates for bacteremia due to Pseudomonas aeruginosa remain high. In our hospital, we performed retrospective analyses to determine risk factors for mortality among patients with bacteremia caused by P. aeruginosa. MATERIALS AND METHODS: This retrospective cohort study was conducted among adult patients with bacteremia due to P. aeruginosa at Jikei University Hospital. We analyzed factors, such as age, gender, underlying disease, initial antimicrobial treatment, and primary site of infection to determine which of these were predictive of mortality in patients with P. aeruginosa bacteremia. RESULTS: One hundred and thirty-four patients with P. aeruginosa bacteremia were identified between April 2003 and March 2010. The 30-day mortality rate among all patients with P. aeruginosa bacteremia was 20.9%. The most common underlying disease was leukemia (20.9%), and the most common primary site of infection was the urinary tract (24.6%). Seventy-one patients (65.7%) were treated with an appropriate initial antimicrobial regimen for P. aeruginosa bacteremia. However, these patients had similar 30-day mortality to that observed in patients not administered appropriate antibiotics. This study revealed that risk factors for the 30-day mortality were thrombocytopenia and polymicrobial P. aeruginosa bacteremia (p<0.01). CONCLUSION: Thrombocytopenia and polymicrobial bacteremia were associated with a greater incidence of 30-day mortality among patients with P. aeruginosa bacteremia. On the other hand, age, underlying disease, and inappropriate initial empirical antimicrobial treatment did not affect mortality.

Meningococcemia without meningitis in Japan.

We report a case of meningococcemia without meningitis, which is a rare infectious disease in Japan. A 32-year-old woman was referred to our hospital with fever and joint pain. Her clinical presentation and the results of laboratory examination on admission suggested viral infection. However, her condition rapidly progressed to septic shock with fulminans purpura. Blood culture grew Neisseria meningitidis. She received antimicrobial therapy and underwent localized therapy for skin lesions. Meningococcal infection should be considered in patients who have fever along with skin rash or petechiae even when there are no signs of meningitis. In this report, we also review case reports of meningococcemia without meningitis in Japan.