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BACKGROUND: Dialysis patients are susceptible to developing severe coronavirus disease 2019 (COVID-19) due to hypoimmunity. Antibody titers against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) after the primary vaccinations are lower in hemodialysis (HD) patients than in healthy individuals. This study aimed to evaluate the effect of a SARS-CoV-2 booster vaccination in HD and peritoneal dialysis (PD) patients based on antibody titers and cellular and humoral immunity. METHODS: Participants of the control, HD, and PD groups were recruited from 12 facilities. SARS-CoV-2 antigen-specific cytokine and IgG-antibody levels were measured. Regulatory T cells and memory B cells were counted using flow cytometry at 6 months after primary vaccination with BNT162b2 and 3 weeks after the booster vaccination in HD and PD patients and compared with those of a control group. RESULTS: Booster vaccination significantly enhanced the levels of antibodies, cytokines, and memory B cells in three groups. The HD group showed significantly higher levels of IgG-antibodies, IL-1ß, IL-2, IL-4, IL-17, and memory B cells than those in the control group at 3 weeks after the booster dose. The PD group tended to show similar trends to HD patients but had similar levels of IgG-antibodies, cytokines, and memory B cells to the control group. CONCLUSIONS: HD patients had significantly stronger cellular and humoral immune responses than the control 3 weeks after the booster dose. Our findings will help in developing better COVID-19 vaccination strategies for HD and PD patients.
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Anticuerpos Antivirales , Vacuna BNT162 , COVID-19 , Inmunidad Humoral , Inmunización Secundaria , Diálisis Renal , Humanos , Masculino , Femenino , COVID-19/inmunología , COVID-19/prevención & control , Persona de Mediana Edad , Anciano , Anticuerpos Antivirales/sangre , Vacuna BNT162/inmunología , Citocinas/sangre , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Inmunidad Celular , Inmunoglobulina G/sangre , Japón , Células B de Memoria/inmunología , Linfocitos T Reguladores/inmunología , Adulto , Diálisis Peritoneal , Pueblos del Este de AsiaRESUMEN
AIM: The effectiveness of the coronavirus disease (COVID-19) vaccine in Japanese patients undergoing haemodialysis has previously not been evaluated on a large scale. We analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR), covering nearly all Japanese patients undergoing dialysis (~95% coverage), to examine the association between COVID-19 vaccination and infection or mortality. METHODS: We used data from the JRDR end-of-year surveys conducted in 2020 and 2021, including information on the COVID-19 vaccination and infection months. COVID-19 infection incidence and its associated mortality rates based on vaccination status (time updated) and odds ratio (OR) (vaccinated vs. unvaccinated) were estimated monthly from April 2021, when vaccination commenced in Japan. RESULTS: COVID-19 infection analysis included 228 865 patients (215 941 vaccinated and 12 924 unvaccinated patients at the end of 2021). The age- and sex-adjusted ORs (aORs) were significantly lower in August, September, October and November 2021, especially in September (aOR [95% confidence interval (CI)]: 0.25 [0.18-0.36]). Additional adjustments for past medical history and laboratory results rarely affected these results. Similarly, in the COVID-19-related mortality analysis with 228 731 patients, including 216 781 vaccinated and 11 950 unvaccinated at the end of 2021, COVID-19-related mortality risk was significantly lower in the vaccinated group in August, September, October and November (aOR [95% CI]: August, 0.32 [0.12-0.84], September, 0.04 [0.01-0.11]; October, 0.10 [0.01-0.81]; November, 0.05 [0.00-0.79]). CONCLUSION: In Japanese patients undergoing haemodialysis, the first or second COVID-19 vaccine dose was significantly associated with decreased COVID-19 infection and mortality rates, suggesting its effectiveness in this population.
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BACKGROUND: Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. METHODS: From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. RESULTS: Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0-1 L/min within 3 weeks post-administration. CONCLUSION: TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation.
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Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Síndrome de Liberación de Citoquinas/prevención & control , Glucocorticoides/administración & dosificación , Enfermedades Renales/terapia , Metilprednisolona/administración & dosificación , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , COVID-19/diagnóstico , COVID-19/inmunología , COVID-19/mortalidad , Síndrome de Liberación de Citoquinas/diagnóstico , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/mortalidad , Quimioterapia Combinada , Femenino , Glucocorticoides/efectos adversos , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/inmunología , Enfermedades Renales/mortalidad , Masculino , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Quimioterapia por Pulso , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The mortality rate of Coronavirus disease 2019 (COVID-19) is extremely high in hemodialysis patients (HDP). These patients also develop lower antibody titers after vaccination. Therefore, factors associated with antibody titers and vaccine efficacy in HDP with breakthrough infection need to be investigated. METHODS: We measured anti-S1 antibody titers in HDP (n = 104) and controls (n = 35), evaluating the influence of background on HDP by multivariable regression analysis. We classified 26 HDP patients admitted with COVID-19 into the unvaccinated (n = 15) and breakthrough infection group (n = 11), performing between-group comparisons of laboratory findings and prognosis. Vaccinated COVID-19 patients were classified into HDP and non-HDP controls, and compared the relationship between antibody titer and severity, and the prognosis of breakthrough infection. RESULTS: The antibody titer was significantly lower in the HDP group than in the control group. Among HDP, age and smoking history were significantly independent factors associated with antibody titer. The breakthrough infection group had significantly better laboratory findings (KL-6 and LDH), severity, and hospitalization period than the unvaccinated group even if antibody titers were lower than the known threshold for neutralization (p < 0.05). There was no significant difference in prognosis between the HDP and non-HDP with breakthrough infection. Severity of COVID-19 tended to be higher with lower antibody titer in non-HDP, but not in HDP. CONCLUSION: Vaccines improved the severity of COVID-19 and hospitalization period of breakthrough infection in HDP, although HDP, especially in elderly smokers had lower antibody titers than control. There was no significant association between antibody titer and severity in HDP.
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COVID-19 , SARS-CoV-2 , Anciano , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , Humanos , Pronóstico , Diálisis RenalRESUMEN
A 70-year-old woman, who started on hemodialysis 7 months before for end-stage renal disease due to diabetic nephropathy and was diagnosed with symptomatic multiple myeloma 1 month before, was admitted to our hospital with critical coronavirus disease 2019 and treated with long-term immunosuppressive therapy such as steroids and tocilizumab. During treatment, Bacillus subtilis was detected in the blood cultures. We could not exclude the association of natto (fermented soybeans) with B. subtilis var. natto, which the patient had been eating every day from 8 days after admission. She was prohibited from eating natto and treated with vancomycin. Later, B. subtilis detected in the blood culture was identified as B. subtilis var. natto, which was identical with those contained in the natto that the patient consumed daily using a next-generation sequencer. Gut dysbiosis due to old age, malignant tumor, diabetes mellitus, end-stage renal disease, and intestinal inflammation caused by severe acute respiratory syndrome coronavirus 2 increased intestinal permeability and the risk of bacterial translocation, causing B. subtilis var. natto bacteremia. Therefore, careful consideration might be given to the intake of fermented foods containing live bacteria in patients with severe immunocompromised conditions.
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Bacteriemia , Tratamiento Farmacológico de COVID-19 , COVID-19 , Fallo Renal Crónico , Mieloma Múltiple , Alimentos de Soja , Anciano , Bacillus subtilis , Bacteriemia/tratamiento farmacológico , COVID-19/complicaciones , Ingestión de Alimentos , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Diálisis Renal , Alimentos de Soja/microbiologíaRESUMEN
BACKGROUND: Ceftazidime encephalopathy is reported to be caused by the repeated administration of ceftazidime in patients with renal impairment because of the high serum concentration of ceftazidime. Ceftazidime encephalopathy has been considered to be caused by the elevation of the cerebrospinal fluid (CSF) concentration. However, as no reports have measured CSF concentrations, the relationship with ceftazidime encephalopathy and CSF concentration has not been clarified. CASE PRESENTATION: Case 1: An 80-year-old Japanese man under a combination therapy with peritoneal dialysis and hemodialysis, who had been treated for a cellulitis with ceftazidime, developed altered consciousness and was diagnosed as ceftazidime encephalopathy. His serum concentration of ceftazidime was elevated, but CSF concentration was only under 0.1 µg/mL. Case 2: An 88-year-old Japanese man with chronic kidney disease, who had been treated for a urinary tract infection with ceftazidime, developed altered consciousness and was diagnosed as ceftazidime encephalopathy. His serum concentration of ceftazidime was elevated, but CSF concentration was within the therapeutic range. However, his serum and CSF concentration of quinolinic acid was markedly increased. CONCLUSIONS: Patients with renal failure are more likely to develop ceftazidime encephalopathy. We need to pay attention to the dosage of ceftazidime and to the appearance of neurological symptoms. Ceftazidime encephalopathy was considered to be caused by the high CSF concentration, but it could be caused by quinolinic acid as neurotoxic substance.
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Encefalopatías , Diálisis Peritoneal , Insuficiencia Renal , Anciano de 80 o más Años , Ceftazidima/efectos adversos , Humanos , Masculino , Ácido QuinolínicoRESUMEN
A 60-year-old man presented with dyspnea four days after the second dose of the coronavirus disease (COVID-19) vaccine. Imaging revealed extensive ground-glass opacification. Blood tests were notable for elevated KL-6 levels. Bronchoalveolar lavage fluid analysis showed increased lymphocyte-dominant inflammatory cells and decreased CD4/CD8 ratio. These findings were consistent with the diagnosis of drug-induced interstitial lung disease (DIILD). To the best of our knowledge, this has never been reported in previous literature. Treatment with glucocorticoids relieved his symptoms. This paper highlights that although extremely rare, COVID-19 vaccine could cause DIILD, and early diagnosis and treatment are crucial to improve patient outcomes.
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COVID-19 , Enfermedades Pulmonares Intersticiales , Vacunas contra la COVID-19 , Disnea , Humanos , Pulmón , Enfermedades Pulmonares Intersticiales/inducido químicamente , Enfermedades Pulmonares Intersticiales/diagnóstico , Masculino , Persona de Mediana Edad , SARS-CoV-2RESUMEN
BACKGROUND: There are no reports of a large-scale survey on the infection prevention measures against coronavirus disease 2019 (COVID-19) in nephrology facilities. This study investigated the facility-level nephrology practices adopted during the COVID-19 pandemic and their associated challenges. Additionally, the treatment patterns and outcomes of chronic kidney disease (CKD) patients with COVID-19 were reviewed. METHODS: We conducted a nationwide questionnaire survey of 704 educational facilities that were certified by the Japanese Society of Nephrology (JSN) from October 20, 2020 to November 16, 2020. The questionnaire reviewed the facility characteristics, infection prevention measures taken during routine nephrology practice, impact of COVID-19 on nephrology practice, experiences in managing CKD patients with COVID-19, and nosocomial transmission in the nephrology unit. RESULTS: Of the 347 facilities that responded, 95.1% checked outpatients' body temperatures and COVID-19 symptoms at their visits. To reduce face-to-face contact, 80% and 70% of the facilities lengthened the intervals between outpatient visits and introduced online/telephonic consultations, respectively. As a result, more than half of the hospitals experienced a decrease in the numbers of outpatients and inpatients (64% and 50%, respectively). During the study period, 347 facilities managed 479 CKD patients with COVID-19. Oxygen administration and mechanical ventilation were performed for 47.8% and 16.5% of the patients, respectively, with a 9.2% total mortality rate. CONCLUSION: This survey demonstrated that JSN-certified educational nephrology facilities adopted multiple measures to manage the COVID-19 pandemic; however, they faced several challenges. Sharing these experiences could standardize these approaches and prepare us better for the future.
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Centros Médicos Académicos , COVID-19/prevención & control , COVID-19/terapia , Control de Infecciones , Nefrología/educación , Diálisis Renal , Insuficiencia Renal Crónica/terapia , COVID-19/diagnóstico , COVID-19/mortalidad , Prestación Integrada de Atención de Salud , Encuestas de Atención de la Salud , Necesidades y Demandas de Servicios de Salud , Hospitales Universitarios , Humanos , Japón , Pautas de la Práctica en Medicina , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Factores de Riesgo , Sociedades Médicas , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIM: Recently, obesity patients have been diagnosed as metabolic syndrome. The aim of this study was to evaluate which angiotensin type 1 receptor blockers (ARBs), telmisartan or candesartan, is superior for the control of home blood pressure (BP) in the morning when the outpatient clinic BP was well controlled in the patients with metabolic syndrome. METHODS: The patients with metabolic syndrome were enrolled. Home BP was monitored by using a telemedicine system. After a 2- to 4-week control period to establish baseline home BP values, these patients were randomly divided into telmisartan (20-80 mg) and candesartan (4-12 mg) groups. These end points were evaluated by using the telemedicine system during steady-state active therapy. A total of 356 patients attending 60 outpatient Japanese centers were recruited. RESULTS: On a day of active therapy, telmisartan significantly lowered both systolic and diastolic home BP in the morning to a greater extent compared to candesartan. At the end of the study, reductions in systolic and diastolic home BP in the morning, in telmisartan group were significantly larger compared to the changes in the candesartan group (systolic; Tel: 12.0 ± 8.9 versus Can: 8.1 ± 17.1 mmHg, p = 0.0292, diastolic; Tel: 7.4 ± 6.1 versus Can: 3.7 ± 6.8 mmHg, p = 0.0053). Additionally in the telmisartan treated group, LDL-cholesterol showed significant reduction (p = 0.037), but candesartan did not. CONCLUSION: The present study by using the telemedicine system clearly demonstrated that telmisartan has a strong effect on reducing morning home BP, and a good effect on lipid metabolism in patients with metabolic syndrome.
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Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Síndrome Metabólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Obesidad/fisiopatología , Anciano , Pueblo Asiatico , Bencimidazoles/administración & dosificación , Benzoatos/administración & dosificación , Compuestos de Bifenilo , Presión Sanguínea/efectos de los fármacos , Monitoreo Ambulatorio de la Presión Arterial , LDL-Colesterol/sangre , Femenino , Humanos , Hipertensión/complicaciones , Japón , Masculino , Síndrome Metabólico/complicaciones , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Obesidad/complicaciones , Estudios Prospectivos , Telemedicina , Telmisartán , Tetrazoles/administración & dosificaciónRESUMEN
Background: Peritoneal dialysis (PD)-related peritonitis is a major complication of PD. Wide variations in peritonitis prevention, treatment strategies and consequences are seen between countries. These between-country differences may result from modifiable risk factors and clinical practices. Methods: A total of 1225 Japanese PD patients were included and prospectively followed in the Peritoneal Dialysis Outcomes and Practice Patterns Study phase 1 (2014-2018) and phase 2 (2018-2022). Associations between PD-related peritonitis and various risk factors were assessed by Cox proportional hazards survival models. Results: During follow-up (median 1.52 years), 539 peritonitis episodes were experienced by 364 patients. The country crude peritonitis rate was 0.27 episodes/patient-year. In the fully adjusted model, noticeable patient-level factors associated with experiencing any peritonitis included age {hazard ratio [HR] 1.07 per 5-year increase [95% confidence interval (CI) 1.01-1.14]}, serum albumin level [HR 0.63 per 1 g/dl higher (95% CI 0.48-0.82)] and continuous ambulatory peritoneal dialysis (PD) [HR 1.31 versus automated PD (95% CI 1.05-1.63)]. The adoption of antibiotic prophylaxis practice at the time of PD catheter insertion [HR 0.63 (95% CI 0.51-0.78)] or when having complicated dental procedures [HR 0.74 (95% CI 0.57-0.95)] or lower endoscopy [HR 0.69 (95% CI 0.54-0.89)] were associated with lower hazards of any peritonitis, while a routine facility practice of having more frequent regular medical visits was associated with a higher hazard. Conclusion: Identification of risk factors in Japan may be useful for developing future versions of guidelines and improving clinical practices in Japan. Investigation of country-level risk factors for PD-related peritonitis is useful for developing and implementing local peritonitis prevention and treatment strategies.
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Peritonitis is one of the most important complications in patients with peritoneal dialysis (PD). Appropriate antibiotic treatment against PD-associated peritonitis is necessary to prevent PD catheter removal and withdrawal from PD. Chryseobacterium indologenes is a Gram-negative rod that occurs in the natural environment. C. indologenes is thought to acquire resistance to ß-lactam drugs through the production of metallo-ß-lactamase and to become resistant to antibiotic therapy through the formation of biofilms. Only a few cases of PD-associated peritonitis caused by C. indologenes have been reported to date, and appropriate treatment strategies have not been clarified. In the past, 5 cases of PD-associated peritonitis caused by C. indologenes have been reported and 2 patients required catheter removal because of recurrence or refractoriness. In this case, a 51-year-old man with PD-associated peritonitis caused by C. indologenes was treated with 2 susceptible antibiotics, including fluoroquinolones to prevent acquired resistance and biofilm formation. There was no recurrence, and catheter removal was not necessary in this case. Collectively, the present case highlighted that PD-associated peritonitis caused by C. indologenes should be treated with 2 susceptible antibiotics including fluoroquinolones for 3 weeks.
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BACKGROUND: Although severe atherosclerotic renal artery stenosis (ARAS) is a predictor of future cardiovascular events, large trials have not shown the benefits of percutaneous transluminal renal angioplasty (PTRA). This study aimed to validate the safety and efficacy of PTRA using low-concentration digital subtraction angiography (LC-DSA) in patients with severe ARAS and advanced chronic kidney disease (CKD). MATERIALS AND METHODS: This prospective study was conducted between August 2018 and October 2021. Eighteen patients with 20 lesions, CKD stage 3b or worse, and significant renal artery stenosis were included and underwent PTRA using ultra-low-dose contrast medium. The primary endpoint was a change in renal function based on serum creatinine (sCr) level. RESULTS: The mean sCr level significantly improved from 3.34 ± 1.8 mg/dL pre-PTRA to 2.48 ± 1.19 mg/dL at 1 month post-PTRA (P = .02). The mean amount of contrast used was 8.3 ± 3.9 mL per vessel. More severe stenosis and rapid deterioration of renal function before treatment were associated with improved kidney function. No cardiovascular or renal complications such as stroke or contrast-induced nephropathy were observed during the 30-day period. CONCLUSIONS: PTRA using an ultra-low-dose contrast medium is safe and provides acceptable results.
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Angioplastia de Balón , Obstrucción de la Arteria Renal , Insuficiencia Renal Crónica , Humanos , Obstrucción de la Arteria Renal/diagnóstico por imagen , Obstrucción de la Arteria Renal/etiología , Obstrucción de la Arteria Renal/terapia , Estudios Prospectivos , Resultado del Tratamiento , Riñón/fisiología , Angioplastia/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/terapia , Angioplastia de Balón/efectos adversosRESUMEN
INTRODUCTION: Inadequate dialysis and fluid overload are corrected after starting combined therapy with peritoneal dialysis (PD) and hemodialysis (HD). However, the effects on anemia management has not been elucidated. METHODS: We conducted a prospective, multicenter, observational cohort study of 40 PD patients (age, 60 ± 10 years; male, 88%; median PD duration, 28 months) starting combined therapy and investigated changes in several clinical parameters, including erythropoiesis-stimulating agent (ESA) resistance index (ERI). RESULTS: ERI decreased significantly during 6 months after switching to combined therapy (from 11.8 [IQR 8.0-20.4] units/week/kg/(g/dL) to 7.8 [IQR 3.9-18.6] units/week/kg/(g/dL), p = 0.047). Body weight, urinary volume, serum creatinine and the dialysate-to-plasma creatinine ratio (D/P Cr) decreased, whereas hemoglobin and serum albumin increased. In subgroup analysis, the changes in ERI were not affected by cause for starting combined therapy, PD holiday and D/P Cr. CONCLUSION: Although detailed mechanism was unclear, ESA responsiveness improved after switching from PD alone to combined therapy.
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Hematínicos , Fallo Renal Crónico , Diálisis Peritoneal , Humanos , Masculino , Persona de Mediana Edad , Anciano , Hematínicos/uso terapéutico , Hematínicos/farmacología , Eritropoyesis , Estudios Prospectivos , Japón , Diálisis Renal , Hemoglobinas/análisis , Fallo Renal Crónico/terapiaRESUMEN
INTRODUCTION: This study compared the outcomes of dialysis patients who received SARS-CoV-2 vaccine with those who did not use data from the Japanese COVID-19 registry. METHODS: A total of 1260 dialysis patients with confirmed positive SARS-CoV-2 infection was included in this study. Patients were divided into two groups: patients who experienced breakthrough infection and those who were unvaccinated. The need of oxygen supplementation and mortality risks were compared using multivariate logistic regression analysis. RESULTS: The mortality rate was 24.2% in unvaccinated patients and 8.6% in breakthrough patients. The odds ratio of need of oxygen supplementation in the breakthrough patients relative to unvaccinated patients was 0.197. The hazard ratio of mortality in the breakthrough patients relative to unvaccinated patients was 0.464. CONCLUSION: Our prospective observational study showed that SRAS-CoV-2 vaccination in hemodialysis patients is vital for reducing need of oxygen supplementation and mortality risk.
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Vacunas contra la COVID-19 , COVID-19 , Humanos , Estudios de Cohortes , COVID-19/prevención & control , Japón/epidemiología , SARS-CoV-2 , Oxígeno , Diálisis Renal , VacunaciónRESUMEN
INTRODUCTION: In the present study, the efficacy of sotrovimab and molnupiravir in dialysis patients with COVID-19 was investigated using a registry of COVID-19 in Japanese dialysis patients. METHODS: Dialysis patients with confirmed SARS-CoV-2 during the COVID-19 (Omicron BA.1 and BA.2) pandemic were analyzed. Patients were classified into four treatment groups: molnupiravir monotherapy (molnupiravir group), sotrovimab monotherapy (sotrovimab group), molnupiravir and sotrovimab combination therapy (combination group), and no antiviral therapy (control group). The mortality rates in the four groups were compared. RESULTS: A total of 1480 patients were included. The mortality of the molnupiravir, sotrovimab, and combination groups were significantly improved compared to the control group (p < 0.001). Multivariate analysis indicated that antiviral therapy improves the survival of dialysis patients with COVID-19 (hazard ratio was 0.184 for molnupiravir, 0.389 for sotrovimab, and 0.254 for combination groups, respectively). CONCLUSION: Sotrovimab showed efficacy in Omicron BA.1 but attenuated in BA.2. Molnupiravir also showed efficacy in BA.2, suggesting administration of molnupiravir would be important.
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Antivirales , COVID-19 , Humanos , COVID-19/terapia , Pueblos del Este de Asia , Pandemias , Diálisis Renal , SARS-CoV-2 , Antivirales/uso terapéutico , Tratamiento Farmacológico de COVID-19RESUMEN
Coronavirus disease 2019 (COVID-19) following primary immunization (breakthrough infection) has been reported in hemodialysis patients; however, their post-infection immune status remains unclear. We evaluated the humoral and cellular immunity of hemodialysis patients after breakthrough infection. Hemodialysis patients who had received primary immunization against COVID-19 at least six months prior to the study but developed mild/moderate COVID-19 before a booster dose (breakthrough infection group) and hemodialysis patients who were not infected with COVID-19 but received a booster dose (booster immunization group) were recruited. In both groups, SARS-CoV-2 antigen-specific cytokines and IgG levels were measured three weeks after infection or three weeks after receiving a booster dose. Memory T and B cells were also counted in the breakthrough infection group using flow cytometry three weeks after infection. Significantly higher SARS-CoV-2 antigen-specific IgG, IFN-γ, IL-5, TNF-α, and IL-6 levels occurred in the breakthrough infection group compared to the booster immunization group (p = 0.013, 0.039, 0.024, 0.017, and 0.039, respectively). The SARS-CoV-2 antigen-specific IgG and cytokine levels were not significantly different between the two groups. The breakthrough infection group had significantly higher percentages of central and effector memory T cells and regulatory T cells than the comparison group (p = 0.008, 0.031, and 0.026, respectively). Breakthrough infections may induce stronger cellular and humoral immune responses than booster immunizations in hemodialysis patients.
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A COVID-19 patient surge in Japan from July to September 2021 caused a mismatch between patient severity and bed types because hospital beds were fully occupied and patient referrals between hospitals stagnated. Japan's predominantly private healthcare system lacks effective mechanisms to coordinate healthcare providers to address the mismatch. To address the surge, in August 2021, Tokyo Saiseikai Central Hospital started a scheme to exchange patients with other hospitals to mitigate the mismatch. In this article, we outline a retrospective observational study using medical records from a tertiary care medical center that treated severe COVID-19 cases. We describe daily patient admissions to our hospital's COVID-19 beds from July to September 2021, and compared the moving average of daily admissions before and after the exchange scheme was introduced. Bed occupancy reached nearly 100% in late July when the patient surge began and continued to exceed 100% in August when the surge peaked. However, the average daily admission did not decrease in August compared with July: the median daily admission (25th to 75th percentile) during each period was 2 (1 to 2.5) in late July and 3 (2 to 4) in August. The number of patients referred in from secondary care hospitals and the number of patients referred out was balanced in August. During the patient surge, the exchange scheme enabled the hospital to maintain and even increase the number of new admissions despite the bed shortage. Coordinating patient referrals in both directions simultaneously, rather than the usual 1-way transfer, can mitigate such mismatches.
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COVID-19 , Humanos , Japón , Ocupación de Camas , Derivación y Consulta , Centros de Atención Terciaria , Capacidad de ReacciónRESUMEN
Tools that can be used to estimate antibody waning following COVID-19 vaccinations can facilitate an understanding of the current immune status of the population. In this study, a two-compartment-based mathematical model is formulated to describe the dynamics of the anti-SARS-CoV-2 antibody in healthy adults using serially measured waning antibody concentration data obtained in a prospective cohort study of 673 healthcare providers vaccinated with two doses of BNT162b2 vaccine. The datasets of 165 healthcare providers and 292 elderly patients with or without hemodialysis were used for external validation. Internal validation of the model demonstrated 97.0% accuracy, and external validation of the datasets of healthcare workers, hemodialysis patients, and nondialysis patients demonstrated 98.2%, 83.3%, and 83.8% accuracy, respectively. The internal and external validations demonstrated that this model also fits the data of various populations with or without underlying illnesses. Furthermore, using this model, we developed a smart device application that can rapidly calculate the timing of negative seroconversion.
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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.