A quantitative model used to compare within-host SARS-CoV-2, MERS-CoV, and SARS-CoV dynamics provides insights into the pathogenesis and treatment of SARS-CoV-2.

The scientific community is focused on developing antiviral therapies to mitigate the impacts of the ongoing novel coronavirus disease 2019 (COVID-19) outbreak. This will be facilitated by improved understanding of viral dynamics within infected hosts. Here, using a mathematical model in combination with published viral load data, we compare within-host viral dynamics of SARS-CoV-2 with analogous dynamics of MERS-CoV and SARS-CoV. Our quantitative analyses using a mathematical model revealed that the within-host reproduction number at symptom onset of SARS-CoV-2 was statistically significantly larger than that of MERS-CoV and similar to that of SARS-CoV. In addition, the time from symptom onset to the viral load peak for SARS-CoV-2 infection was shorter than those of MERS-CoV and SARS-CoV. These findings suggest the difficulty of controlling SARS-CoV-2 infection by antivirals. We further used the viral dynamics model to predict the efficacy of potential antiviral drugs that have different modes of action. The efficacy was measured by the reduction in the viral load area under the curve (AUC). Our results indicate that therapies that block de novo infection or virus production are likely to be effective if and only if initiated before the viral load peak (which appears 2-3 days after symptom onset), but therapies that promote cytotoxicity of infected cells are likely to have effects with less sensitivity to the timing of treatment initiation. Furthermore, combining a therapy that promotes cytotoxicity and one that blocks de novo infection or virus production synergistically reduces the AUC with early treatment. Our unique modeling approach provides insights into the pathogenesis of SARS-CoV-2 and may be useful for development of antiviral therapies.

Urine oxygenation predicts COVID-19 risk.

Since February, 2023, the omicron variant has accounted for essentially all new coronavirus infections in Japan. If future infections involve mutant strains with the same level of infectivity and virulence as omicron, the government's basic policy will be to prevent the spread of infection, without compromising socioeconomic activities. Objectives include protecting pregnant women and elderly persons, and focusing on citizens requiring hospitalization and those at risk of serious illness, without imposing new social restrictions. Although the government tries to raise public awareness through education, most people affected by COVID-19 stay at home, and by the time patients become aware of the seriousness of their disease, it has often reached moderate or higher severity. In this review, we discuss why this situation persists even though the disease seems to have become milder with the shift from the delta variant to omicron. We also propose a pathophysiological method to determine the risk of severe illness. This assessment can be made at home in the early stages of COVID-19 infection, using urine analysis. Applicability of this method to drug discovery and development is also discussed.

Association between seasonal influenza vaccination and antimicrobial use in Japan from the 2015-16 to 2020-21 seasons: from the VENUS study.

BACKGROUND: Seasonal influenza vaccination might be considered an antimicrobial resistance (AMR) countermeasure because it can reduce unnecessary antimicrobial use for acute respiratory infection by mitigating the burden of such diseases. OBJECTIVES: To examine the association between seasonal influenza vaccination and antimicrobial use (AMU) in Japan at the community level and to examine the impact of influenza vaccination on the frequency of unnecessary antimicrobial prescription for upper respiratory infection. METHODS: For patients who visited any healthcare facility in one of the 23 wards of Tokyo, Japan, due to upper respiratory infection and who were aged 65 years or older, we extracted data from the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study database, which includes all claims data and vaccination records from the 2015-16 to 2020-21 seasons. We used the average treatment effect (ATE) with 1:1 propensity score matching to examine the association of vaccination status with frequency of antibiotic prescription, frequency of healthcare facility consultation, risk of admission and risk of death in the follow-up period of the same season (from 1 January to 31 March). RESULTS: In total, 244 642 people were enrolled. Matched data included 101 734 people in each of the unvaccinated and vaccinated groups. The ATE of vaccination was -0.004 (95% CI -0.006 to -0.002) for the frequency of antibiotic prescription, -0.005 (-0.007 to -0.004) for the frequency of healthcare facility consultation, -0.001 (-0.002 to -0.001) for the risk of admission and 0.00 (0.00 to 0.00) for the risk of death. CONCLUSIONS: Our results suggest that seasonal influenza vaccination is associated with lower frequencies of unnecessary antibiotic prescription and of healthcare facility consultation.

Should a viral genome stay in the host cell or leave? A quantitative dynamics study of how hepatitis C virus deals with this dilemma.

Virus proliferation involves gene replication inside infected cells and transmission to new target cells. Once positive-strand RNA virus has infected a cell, the viral genome serves as a template for copying ("stay-strategy") or is packaged into a progeny virion that will be released extracellularly ("leave-strategy"). The balance between genome replication and virion release determines virus production and transmission efficacy. The ensuing trade-off has not yet been well characterized. In this study, we use hepatitis C virus (HCV) as a model system to study the balance of the two strategies. Combining viral infection cell culture assays with mathematical modeling, we characterize the dynamics of two different HCV strains (JFH-1, a clinical isolate, and Jc1-n, a laboratory strain), which have different viral release characteristics. We found that 0.63% and 1.70% of JFH-1 and Jc1-n intracellular viral RNAs, respectively, are used for producing and releasing progeny virions. Analysis of the Malthusian parameter of the HCV genome (i.e., initial proliferation rate) and the number of de novo infections (i.e., initial transmissibility) suggests that the leave-strategy provides a higher level of initial transmission for Jc1-n, whereas, in contrast, the stay-strategy provides a higher initial proliferation rate for JFH-1. Thus, theoretical-experimental analysis of viral dynamics enables us to better understand the proliferation strategies of viruses, which contributes to the efficient control of virus transmission. Ours is the first study to analyze the stay-leave trade-off during the viral life cycle and the significance of the replication-release switching mechanism for viral proliferation.

Comparison of the clinical characteristics and outcomes of Japanese patients with COVID-19 treated in primary, secondary, and tertiary care facilities.

AIM: To compare the characteristics and clinical course of patients with coronavirus disease (COVID-19) according to the healthcare level of the admitted hospital, to provide an insight into determining the appropriate level of care for each patient. METHODS: This retrospective, observational study utilized data from the COVID-19 Registry Japan (COVIREGI-JP), the largest Japanese registry of hospitalized patients with COVID-19. Datasets were obtained from reports filed as of May 31, 2022. RESULTS: A total of 59,707 patients (2004 in the primary care group, 41,420 in the secondary care group, and 16,283 in the tertiary care group) from 585 facilities were included in the analysis. Patients with established risk factors for severe disease, such as old age and the presence of comorbidities, were treated at higher care facilities and had poorer initial conditions and in-hospital clinical course, as well as higher mortality. Analysis of the fatality rates for each complication suggested that patients with complications requiring procedures (e.g. pleural effusions, myocardial ischemia, and arrhythmia) may have better survival rates in facilities with specialist availability. The number of deaths and severe COVID-19 cases in this study were notably less than those reported overseas. CONCLUSION: Our results showed that more difficult COVID-19 cases with poor outcomes were treated at higher care level facilities in Japan. Attending to possible complications may be useful for selecting an appropriate treatment hospital. Healthcare providers need to maintain a broad perspective on the distribution of medical resources.

Characteristics of hospitalized COVID-19 patients with other respiratory pathogens identified by rapid diagnostic test.

Rapid diagnostic tests (RDTs) significantly impact disease treatment strategy. In Japan, information on the use of RDTs for patients with COVID-19 is limited. Here, we aimed to investigate the RDT implementation rate, pathogen detection rate, and clinical characteristics of patients positive for other pathogens by using COVIREGI-JP, a national registry of hospitalized patients with COVID-19. A total of 42,309 COVID-19 patients were included. For immunochromatographic testing, influenza was the most common (n = 2881 [6.8%]), followed by Mycoplasma pneumoniae (n = 2129 [5%]) and group A streptococcus (GAS) (n = 372 [0.9%]). Urine antigen testing was performed for 5524 (13.1%) patients for S. pneumoniae and for 5326 patients (12.6%) for L. pneumophila. The completion rate of M. pneumonia loop-mediated isothermal amplification (LAMP) testing was low (n = 97 [0.2%]). FilmArray RP was performed in 372 (0.9%) patients; 1.2% (36/2881) of patients were positive for influenza, 0.9% (2/223) for the respiratory syncytial virus (RSV), 9.6% (205/2129) for M. pneumoniae, and 7.3% (27/372) for GAS. The positivity rate for urine antigen testing was 3.3% (183/5524) for S. pneumoniae and 0.2% (13/5326) for L. pneumophila. The positivity rate for LAMP test was 5.2% (5/97) for M. pneumoniae. Five of 372 patients (1.3%) had positive FilmArray RP, with human enterovirus being the most frequently detected (1.3%, 5/372). The characteristics of patients with and without RDTs submission and positive and negative results differed for each pathogen. RDTs remain an important diagnostic tool in patients with COVID-19 in whom coinfection with other pathogens needs to be tested based on clinical evaluation.

Temporal trends in microbial detection during the COVID-19 pandemic: Analysis of the Japan surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE) database.

The impact of the COVID-19 pandemic on the incidence of microbial infections and other metrics related to antimicrobial resistance (AMR) has not yet been fully described. Using data from Japan Surveillance for Infection Prevention and Healthcare Epidemiology (J-SIPHE), a national surveillance database system that routinely collects clinical and epidemiological data on microbial infections, infection control practices, antimicrobial use, and AMR emergence from participating institutions in Japan, we assessed the temporal changes in AMR-related metrics before and after the start of the COVID-19 pandemic. We found that an apparent decrease in the incidence of microbial infections in 2020 compared with 2019 may have been driven primarily by a reduction in bed occupancy, although the incidence showed a constant or even slightly increasing trend after adjusting for bed occupancy. Meanwhile, we found that the incidence of Streptococcus pneumoniae dramatically decreased from April 2020 onward, probably due to stringent non-pharmaceutical interventions against COVID-19. Antimicrobial use showed a weak increasing trend, while the use of hand sanitiser at the included medical institutions increased by about 50% in 2020 compared with 2019.

Clinical efficacy of remdesivir for COVID-19 in children: A propensity-score-matched analysis.

Clinical efficacy of remdesivir in children with COVID-19 is unclear. This propensity-score-matched retrospective cohort study of children with COVID-19 showed that the rate of patients achieving defervescence on Day 4 was higher in the remdesivir group than in the non-remdesivir group, but was not statistically different (86.7% vs 73.3%, P = 0.333).

Comparison of clinical characteristics of COVID-19 in pregnant women between the Delta and Omicron variants of concern predominant periods.

BACKGROUND: Information regarding effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant strains on clinical manifestations and outcomes of coronavirus disease 2019 (COVID-19) in pregnant women is limited. METHODS: A retrospective observational study was conducted using the data from the nationwide COVID-19 registry in Japan. We identified pregnant patients with symptomatic COVID-19 hospitalized during the study period. The Delta and Omicron variants of concern (VOC) predominant periods were defined as August 1 to December 31, 2021 and January 1 to May 31, 2022, respectively. Clinical characteristics were compared between the patients in the Delta and Omicron VOC periods. In addition, logistic regression analysis was performed to identify risk factors for developing moderate-to-severe COVID-19. RESULTS: During the study period, 310 symptomatic COVID-19 cases of pregnant women were identified; 111 and 199 patients were hospitalized during the Delta and Omicron VOC periods, respectively. Runny nose and sore throat were more common, and fatigue, dysgeusia, and olfactory dysfunction were less common manifestations observed in the Omicron VOC period. In the multivariable logistic regression analysis, onset during the later stage of pregnancy (OR: 2.08 [1.24-3.71]) and onset during the Delta VOC period (OR: 2.25 [1.08-4.90]) were independently associated with moderate-to-severe COVID-19, whereas two doses of SARS-CoV-2 vaccine were protective against developing moderate-to-severe COVID-19 (OR: 0.34 [0.13-0.84]). CONCLUSIONS: Clinical manifestations of COVID-19 in pregnant women differed between the Delta and Omicron VOC periods. SARS-CoV-2 vaccination was still effective in preventing severe COVID-19 throughout the Delta and Omicron VOC periods.

Characteristics of preventive intervention acceptance for international travel among clients aged 60 years and older from a Japanese multicenter pretravel consultation registry.

OBJECTIVES: Pretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR). METHODS: Clients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV. RESULTS: In total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80-0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14-0.63) were significantly associated with YFV. CONCLUSIONS: Preventive interventions other than YFV should be offered to older adults.

Tin(II)-Based Metal-Organic Frameworks Enabling Efficient, Selective Reduction of CO2 to Formate under Visible Light.

Certain metal complexes are known as high-performance CO2 reduction photocatalysts driven by visible light. However, most of them rely on rare, precious metals as principal components, and integrating the functions of light absorption and catalysis into a single molecular unit based on abundant metals remains a challenge. Metal-organic frameworks (MOFs), which can be regarded as intermediate compounds between molecules and inorganic solids, are potential platforms for the construction of a simple photocatalytic system composed only of Earth-abundant nontoxic elements. In this work, we report that a tin-based MOF enables the conversion of CO2 into formic acid with a record high apparent quantum yield (9.8 % at 400 nm) and >99 % selectivity without the need for any additional photosensitizer or catalyst. This work highlights a new MOF with strong potential for photocatalytic CO2 reduction driven by solar energy.

Clinical Characteristics and Outcomes of Coronavirus Disease 2019 (COVID-19) in Pregnant Women: A Propensity Score-Matched Analysis of Data From the COVID-19 Registry Japan.

BACKGROUND: Several studies have investigated whether pregnancy is a risk factor for developing severe coronavirus disease 2019 (COVID-19); however, the results remain controversial. In addition, the information regarding risk factors for developing severe COVID-19 in pregnant women is limited. METHODS: A retrospective cohort study analyzing the data from the nationwide COVID-19 registry in Japan was conducted. Propensity score-matched analysis was performed to compare COVID-19 severity between pregnant and nonpregnant women. Multivariate analysis was also conducted to evaluate risk factors for developing moderate-to-severe COVID-19 in pregnant women. RESULTS: During the study period, 254 pregnant and 3752 nonpregnant women of reproductive age were identified. After propensity score matching, 187 pregnant women and 935 nonpregnant women were selected. A composite outcome of moderate-to-severe COVID-19 was more frequently observed in pregnant women than that of nonpregnant women (n = 18 [9.6%] vs n = 46 [4.9%]; P = .0155). In multivariate analysis, the presence of underlying diseases and being in the second-to-third trimester of pregnancy were recognized as risk factors for moderate-to-severe COVID-19 in pregnant women (odds ratio [95% confidence interval]: 5.295 [1.21-23.069] and 3.871 [1.201-12.477], respectively). CONCLUSIONS: Pregnancy could be a risk factor for moderate-to-severe COVID-19 for women in Japan. In addition to the presence of comorbidities, advanced pregnancy stages may contribute to greater risks for developing moderate-to-severe COVID-19 in pregnant women.

Effect of disease duration on fecal biomarkers in ulcerative colitis: a prospective cohort study.

BACKGROUND: Biomarkers such as fecal calprotectin (FC) and fecal immunochemical occult blood tests (FIT) for ulcerative colitis (UC) are used in clinical practice. In this study, the effect of UC disease duration on FC was investigated and compared to that on FIT. METHODS: One hundred twenty-eight colonoscopic examinations and two fecal biomarkers measurements were performed. The cases of UC were divided into short- and long-term disease-duration groups or categorized into three groups with disease durations of 0-5, 6-13, and 14-38 years. We analyzed correlations between biomarker levels and endoscopic scores, including the Mayo endoscopic subscore (MES), ulcerative colitis endoscopic index of severity, and the sum of MES. RESULTS: In the analysis of short- and long-term disease durations, the three endoscopic scores and biomarker levels showed significant correlations in both long-term and short-term groups. Most of the correlation coefficients for the individual long-term group were lower than the corresponding values for all cases, while most of the correlation coefficients for the individual short-term groups were higher than the corresponding values for all cases. In the three-group analysis (disease durations of 0-5, 6-13, and 14-38 years), the two biomarkers and three endoscopic scores showed significant correlations, and most of the correlation coefficients between biomarkers and endoscopic scores tended to be lower in the long-term follow-up group. In the receiver operating characteristic analysis for predicting mucosal healing in the three groups, the area under the curve for FC and FIT concentrations in the 0-5 year disease-duration group showed particularly higher values than those for the other two groups. CONCLUSIONS: Similar to FIT, FC is affected by the duration of UC, indicating that FC may be a highly useful biomarker, especially in short-term disease.

Cardiovascular Complications of Hospitalized Patients With Coronavirus Disease 2019 in a Japanese Registry in 2020.

BACKGROUND: Cardiovascular complications of coronavirus disease 2019 (COVID-19) are critical for prognosis but have not been elucidated in Japan.Methods and Results:The COVID-19 Registry Japan, which included data from 19,853 individuals at the end of 2020, was analyzed. The incidences of cardiovascular complications were 0.098% for myocarditis/pericarditis/cardiomyopathy, 0.48% for ventricular tachycardia/fibrillation, 0.17% for myocardial ischemia, 0.062% for endocarditis, 0.59% for deep vein thrombosis, 0.19% for pulmonary embolism, and 0.37% for cerebral infarction/hemorrhage. Excluding endocarditis, all complications were associated with increased in-hospital mortality. CONCLUSIONS: Cardiovascular complications of COVID-19 were infrequent in Japan but were associated with poor prognosis.

Impact of the COVID-19 pandemic on racial and ethnic minorities in Japan.

This study compared clinico-epidemiological characteristics between Japanese and non-Japanese coronavirus disease 2019 (COVID-19) patients under the pandemic in Japan. We retrospectively analysed nationwide data of hospitalised COVID-19 patients before 31 March 2021. Epidemic curves were constructed to identify the case distribution over time. A total of 28 093 patients were Japanese and 1335 patients were non-Japanese. The major racial and ethnic minorities were East Asians (n = 521), South Asians (n = 260) and Latin Americans (n = 270). Non-Japanese patients were younger and more likely to travel to COVID-19 endemic countries (7.7%), had meals with other people (17.8%), stayed in crowded places (17.9%) and worked mainly in restaurants (6.6%) and service facilities in nightlife businesses (5.2%). In the matched cohorts, we found no clear disparities in time to admission and clinical prognoses. The epidemic curve for non-Japanese patients showed a small peak in the first wave and no definite waves for the second or third waves. Racial and ethnic minorities were at less risk of severe disease but were at a greater risk of COVID-19 exposure; however, the healthcare system in Japan may provide them with equal opportunities to access inpatient care with Japanese. Further research on their social determinants of health in Japan is required.

Comorbidities as Risk Factors for Severe Disease in Hospitalized Elderly COVID-19 Patients by Different Age-Groups in Japan.

INTRODUCTION: Old age is an independent risk factor (RF) for severe COVID-19; evidence for clinico-epidemiological characteristics among elderly COVID-19 patients is scarce. We aimed to analyze clinical and epidemiological characteristics and comorbidities associated with COVID-19 inpatients in age-stratified populations of an elderly COVID-19 cohort. METHODS: We conducted a retrospective cohort study, using nationwide registry data of COVID-19 patients hospitalized before October 31, 2020 (major information entered in the registry as of December 28, 2020). Participants were divided by age according to the Japan Geriatrics Society and the Japan Gerontological Society: pre-old (65-74 years), old (75-89 years), and super-old (≥90 years). Multivariable logistic regression (MLR) analyses were conducted to identify stratified risk and relationships with comorbidities associated with worse outcomes in different age-groups of elderly patients. Demographics and supportive care were evaluated by category. RESULTS: Data of 4,701 patients from 444 hospitals were included. Most patients (79.3%) had at least one comorbidity; the proportion of patients with hypertension was high in all categories. The proportion of patients with dementia, cardiovascular disease, and cerebrovascular disease increased with age. The percentage of patients who underwent invasive mechanical ventilation/extracorporeal membrane oxygenation was lower in the super-old group. In total, 11.5% of patients died (5.3%, pre-old; 15.2%, old; and 22.4%, super-old). MLR showed that the risk of critical illness differed among age-groups. Male sex was a significant RF in all ages. Collagen disease, moderate to severe renal disorder, and dialysis were significant RFs in older patients, while hematological malignancies and metastatic tumors were more important RFs for severe disease in relatively younger patients. Most of the RFs for critical illnesses were associated with death. CONCLUSION: Differences in the epidemiological and clinical characteristics among the different age-groups were found.

Impact of regional heterogeneity on the severity of COVID-19.

The main objective of the study is to assess the impact of regional heterogeneity on the severity of COVID-19 in Japan. We included 27,865 cases registered between January 2020 and February 2021 in the COVID-19 Registry of Japan, to examine the relationship between the National Early Warning Score (NEWS) of COVID-19 patients on the day of admission and the prefecture where the patients live. A hierarchical Bayesian model was used to examine the random effect of each prefecture in addition to the patients' backgrounds. Additionally, we compared the results of two models; one model included the number of beds secured for COVID-19 patients in each prefecture as one of the fixed effects, and the other model did not. The results indicated that the prefecture had a substantial impact on the severity of COVID-19 on admission, even when considering the effect of the number of beds separately. Our analysis revealed a possible association between regional heterogeneity and increased/decreased risk of severe COVID-19 infection on admission. This heterogeneity was derived not only from the number of beds secured in each prefecture but also from other factors.

Predictors of silent hypoxia in hospitalized patients with COVID-19 in Japan.

INTRODUCTION: Silent hypoxia (SH) is common in patients with coronavirus disease (COVID-19) in Japan and other countries. Early identification of SH is important as more treatment options for COVID-19 have become available. This study aimed to identify predictors of SH using a nationwide COVID-19 registry of hospitalized patients. METHODS: Adult patients who were admitted to hospital with COVID-19 between January 2020 and June 2021 and who were hypoxic on admission (SpO2: 70-93%), not transferred from another facility, and who did not have disturbance of consciousness, confusion, or dementia, were included. SH was defined as hypoxia in the absence of shortness of breath/dyspnea upon admission. Predictors of SH were identified using univariable and multivariable logistic regression. RESULTS: The study included 1904 patients, of whom 990 (52%) satisfied the criteria for SH. Compared to patients without SH, patients with SH were older, more likely to be female, and had a slightly higher SpO2 on admission. Compared to patients without SH, patients with SH had a lower prevalence of chronic lung disease (CLD) other than chronic obstructive pulmonary disease (COPD), asthma, and obesity. Multivariable analysis revealed that the independent predictors of SH were older age, a shorter interval from symptom onset to admission, higher SpO2, and an absence of CLD or COPD. CONCLUSIONS: The absence of underlying lung disease and older age were important predictors of SH. The results of this study, which is the largest such study reported to date in Japan, may help clarify the mechanism of SH.

Comparison of the clinical characteristics and outcomes of COVID-19 in children before and after the emergence of Delta variant of concern in Japan.

Delta variant of concern (VOC) is the current predominant severe acute respiratory coronavirus type 2 strain causing coronavirus disease 2019 (COVID-19); however, information regarding the impact of the Delta VOC on clinical features and outcomes in pediatric patients with COVID-19 is limited. We conducted a retrospective observational study using the data of patients <18 years of age in COVIREGI-JP, the COVID-19 registry in Japan. The patients were divided into two groups according to the timing of enrollment in the registry (pre-Delta VOC era, October 2020 to May 2021; and Delta VOC era, August to October 2021), and the clinical characteristics and outcomes were compared between the two groups. During the study period, 950 and 349 pediatric patients were registered in the pre-Delta VOC and Delta VOC eras, respectively. The median patient age was younger and the proportion of patients with underlying diseases was higher in the Delta VOC era than that in the pre-Delta VOC era (10.0 vs 7.0 years, P < 0.001, and 7.4% [n = 70] vs. 12.6% [n = 44], P = 0.004, respectively). Significantly more patients were admitted to the intensive care unit in the Delta VOC era than in the pre-Delta VOC era (1.4% [ n = 5] vs. 0.1% [n = 1], P = 0.006), but no patient in either group died or required mechanical ventilation or extracorporeal membrane oxygenation throughout the study period, suggesting that the overall outcomes in children with COVID-19 remained favorable even in the Delta VOC era in Japan.

Clinical characteristics and prognosis of immunosuppressed inpatients with COVID-19 in Japan.

INTRODUCTION: We aimed to analyze the clinical characteristics and outcomes of immunosuppressed inpatients with coronavirus disease 2019 (COVID-19). METHODS: In this observational study, we utilized a large nationwide registry of hospitalized patients with COVID-19 in Japan. Patients' baseline characteristics and outcomes were compared according to the immunosuppressed states of the patients. The impact of different therapeutic agents on the clinical courses of the patients was evaluated. RESULTS: Data of 14,760 patients were included, and 887 (5.9%) were immunosuppressed. The immunosuppressed state of the patient resulted from solid tumor (43.3%, n = 384), chemotherapy within 3 months (15.6%, n = 138), collagen disease (16.9%, n = 150), use of immunosuppressive agents (16.0%, n = 142), and metastatic solid tumor (13.5%, n = 120). Immunosuppressed patients were older and had a higher severity of illness at admission and during hospitalization than non-immunosuppressed patients. The mortality rates for major diseases causing immunosuppression were as follows: solid tumor, 12.5% (48/384; P < 0.001; relative risk [RR], 3.41); metastatic solid tumor, 31.7% (38/120; P < 0.001; RR, 8.43); leukemia, 23.1% (9/39; P < 0.001; RR, 5.87); lymphoma, 33.3% (20/60; P < 0.001; RR, 8.63); and collagen disease, 15.3% (23/150; P < 0.001; RR 3.97). Underlying diseases with high mortality rates were not necessarily associated with high rates of invasive supportive care. CONCLUSIONS: The prognosis of immunosuppressed COVID-19 inpatients varied according to the different immunosuppressed states. Multiple factors, including the severity of the underlying diseases, might have affected their invasive supportive care indications.