Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database.

PURPOSE: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination. DESIGN: Matched cohort and self-controlled case series (SCCS) studies. PARTICIPANTS: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events. METHODS: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods. MAIN OUTCOME MEASURES: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis. RESULTS: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively. CONCLUSIONS: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The Association of Timing of Tracheostomy and Survival of Patients with COVID-19.

Tracheostomy is performed for critically ill patients with prolonged endotracheal intubation including COVID-19 to mitigate the risk of airway complications. We analyzed the difference in mortality of COVID-19 patients undergoing early tracheostomy within 14 days of intubation compared to later tracheostomy than 14 days after intubation. The mortality was not significantly higher in early tracheostomy compared to later tracheostomy.

Pulse Methylprednisolone Versus Dexamethasone in COVID-19: A Multicenter Cohort Study.

Although pulse (high-dose) methylprednisolone therapy can hypothetically control immune system flare-ups effectively, the clinical benefit of pulse methylprednisolone compared with dexamethasone in COVID-19 remains inconclusive. OBJECTIVES: To compare pulse methylprednisolone to dexamethasone as a COVID-19 treatment. DESIGN SETTING AND PARTICIPANTS: Using a Japanese multicenter database, we identified adult patients admitted for COVID-19 and discharged between January 2020 and December 2021 treated with pulse methylprednisolone (250, 500, or 1,000 mg/d) or IV dexamethasone (≥ 6 mg/d) at admission day 0 or 1. Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes were 30-day mortality, new ICU admission, insulin initiation, fungal infection, and readmission. Multivariable logistic regression was conducted to differentiate the dose of pulse methylprednisolone (250, 500, or 1,000 mg/d). Additionally, subgroup analyses by characteristics such as the need for invasive mechanical ventilation (IMV) were also conducted. RESULTS: A total of 7,519, 197, 399, and 1,046 patients received dexamethasone, 250, 500, and 1,000 mg/d of methylprednisolone, respectively. The crude in-hospital mortality was 9.3% (702/7,519), 8.6% (17/197), 17.0% (68/399), and 16.2% (169/1,046) for the different doses, respectively. The adjusted odds ratio (95% CI) was 1.26 (0.69-2.29), 1.48 (1.07-2.04), and 1.75 (1.40-2.19) in patients starting 250, 500, and 1,000 mg/d of methylprednisolone, respectively, compared with those starting dexamethasone. In subgroup analyses, the adjusted odds ratio of in-hospital mortality was 0.78 (0.25-2.47), 1.12 (0.55-2.27), and 1.04 (0.68-1.57) in 250, 500, and 1,000 mg/d of methylprednisolone, respectively, among patients with IMV, whereas the adjusted odds ratio was 1.54 (0.77-3.08), 1.62 (1.13-2.34), and 2.14 (1.64-2.80) among patients without IMV. CONCLUSIONS AND RELEVANCE: Higher doses of pulse methylprednisolone (500 or 1,000 mg/d) may be associated with worse COVID-19 outcomes when compared with dexamethasone, especially in patients not on IMV.

Safety monitoring of COVID-19 vaccines in Japan.

The assessment of the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines in actual practice is extremely important, and monitoring efforts are being implemented worldwide. In Japan, a joint council in the Ministry of Health, Labour and Welfare is held every two to three weeks to summarise information on the adverse events following COVID-19 vaccination, with careful assessment of individual case safety reports and comparison with background incidence rates. In 2021, the joint council mainly reviewed anaphylaxis, death, myocarditis/pericarditis, and thrombosis with thrombocytopenia syndrome. These activities resulted in several safety-related regulatory actions, including the revision of vaccine package inserts with warnings about myocarditis/pericarditis. International sharing of vaccine safety information, as well as details of the evaluation systems, is important for international discussion and decision-making on better safety monitoring of COVID-19 vaccines.

Protective effect of COVID-19 vaccination against long COVID syndrome: A systematic review and meta-analysis.

BACKGROUND: The relationship between coronavirus disease 2019 (COVID-19) vaccination and long COVID has not been firmly established. We conducted a systematic review and meta-analysis to evaluate the association between COVID-19 vaccination and long COVID. METHODS: PubMed and EMBASE databases were searched on September 2022 without language restrictions (CRD42022360399) to identify prospective trials and observational studies comparing patients with and without vaccination before severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We also included studies reporting symptomatic changes of ongoing long COVID following vaccination among those with a history of SARS-CoV-2 infection. Odds ratios (ORs) for each outcome were synthesized using a random-effects model. Symptomatic changes after vaccination were synthesized by a one-group meta-analysis. RESULTS: Six observational studies involving 536,291 unvaccinated and 84,603 vaccinated (before SARS-CoV-2 infection) patients (mean age, 41.2-66.6; female, 9.0-67.3%) and six observational studies involving 8,199 long COVID patients (mean age, 40.0 to 53.5; female, 22.2-85.9%) who received vaccination after SARS-CoV-2 infection were included. Two-dose vaccination was associated with a lower risk of long COVID compared to no vaccination (OR, 0.64; 95% confidence interval [CI], 0.45-0.92) and one-dose vaccination (OR, 0.60; 95% CI, 0.43-0.83). Two-dose vaccination compared to no vaccination was associated with a lower risk of persistent fatigue (OR, 0.62; 95% CI, 0.41-0.93) and pulmonary disorder (OR, 0.50; 95% CI, 0.47-0.52). Among those with ongoing long COVID symptoms, 54.4% (95% CI, 34.3-73.1%) did not report symptomatic changes following vaccination, while 20.3% (95% CI, 8.1-42.4%) experienced symptomatic improvement after two weeks to six months of COVID-19 vaccination. CONCLUSIONS: COVID-19 vaccination before SARS-CoV-2 infection was associated with a lower risk of long COVID, while most of those with ongoing long COVID did not experience symptomatic changes following vaccination.

Intensive Care Unit versus High-Dependency Care Unit for COVID-19 Patients with Invasive Mechanical Ventilation.

RATIONALE: High-dependency care units (HDUs), also termed "intermediate care units," "step-down units," or "respiratory high-dependency units" are areas where patient care levels and costs are between those of the intensive care unit (ICU) and the general ward. In general, patients requiring mechanical ventilation are treated in the ICU rather than in the HDU, except for the use of HDU beds as surge capacity beds during a massive strain; however, the HDU as well as ICU are used as the standard care units for mechanically ventilated patients with coronavirus disease 2019 (COVID-19) in Japan. OBJECTIVES: To assess the outcomes of COVID-19 patients with invasive mechanical ventilation treated in the HDU versus those treated in the ICU. METHODS: In this retrospective cohort study, we used a multicenter inpatient database in Japan to identify mechanically ventilated patients with COVID-19 in the ICU or HDU on the start day of invasive mechanical ventilation from February 10, 2020 to November 30, 2021. The primary outcome was in-hospital mortality within 30 days from the start of the first invasive mechanical ventilation. Propensity score matching was performed to compare the outcomes of patients treated in the ICU with those treated in the HDU. RESULTS: Of 1,985 eligible COVID-19 patients with invasive mechanical ventilation, 1,303 (66%) were treated in the ICU and 682 (34%) were treated in the HDU on the start day of invasive mechanical ventilation. After propensity score matching, patients treated in the ICU had significantly lower in-hospital mortality within 30 days than those treated in the HDU (18.3% vs. 24.2%; risk difference, -5.8%; 95% confidence interval, -10.9% to -0.8%). CONCLUSIONS: This multicenter observational study in Japan suggests that care for mechanically ventilated COVID-19 patients in the ICU may significantly reduce in-hospital mortality within 30 days compared with care in the HDU. Establishing a critical care system that would allow COVID-19 patients requiring ventilators to be treated in the ICU is desirable. Because this study was an observational study, our finding represents an association, not a causation. Further studies of different critical care systems are warranted to confirm our findings.

Assessment of Efficacy and Safety of mRNA COVID-19 Vaccines in Children Aged 5 to 11 Years: A Systematic Review and Meta-analysis.

Importance: Evidence of the efficacy and safety of messenger RNA (mRNA) COVID-19 vaccines in children aged 5 to 11 years has been emerging. Collecting these data will inform clinicians, families, and policy makers. Objective: To evaluate the efficacy and safety of mRNA COVID-19 vaccines in children aged 5 to 11 years in a systematic review and meta-analysis. Data Sources: PubMed and Embase databases were searched on September 29, 2022, without language restrictions. Study Selection: Randomized clinical trials and observational studies comparing vaccinated vs unvaccinated children aged 5 to 11 years and reporting efficacy or safety outcomes were included. Studies reporting safety outcomes in vaccinated children only (ie, no control group) were also included. Data Extraction and Synthesis: Two investigators independently extracted relevant data from each study. Odds ratios (ORs) for efficacy and safety outcomes and incidences of adverse events (AEs) following vaccination were synthesized using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines. Main Outcomes and Measures: The primary outcome was SARS-CoV-2 infections with or without symptoms. The secondary outcomes included symptomatic SARS-CoV-2 infections, hospitalizations, and multisystem inflammatory syndrome in children. The incidences of each AE following vaccination were also evaluated. Results: Two randomized clinical trials and 15 observational studies involving 10 935 541 vaccinated children (median or mean age range, 8.0-9.5 years) and 2 635 251 unvaccinated children (median or mean age range, 7.0-9.5 years) were included. Two-dose mRNA COVID-19 vaccination compared with no vaccination was associated with lower risks of SARS-CoV-2 infections with or without symptoms (OR, 0.47; 95% CI, 0.35-0.64), symptomatic SARS-CoV-2 infections (OR, 0.53; 95% CI, 0.41-0.70), hospitalizations (OR, 0.32; 95% CI, 0.15-0.68), and multisystem inflammatory syndrome in children (OR, 0.05; 95% CI, 0.02-0.10). Two randomized clinical trials and 5 observational studies investigated AEs among vaccinated children. Most vaccinated children experienced at least 1 local AE following the first injection (32 494 of 55 959 [86.3%]) and second injection (28 135 of 46 447 [86.3%]). Vaccination was associated with a higher risk of any AEs compared with placebo (OR, 1.92; 95% CI, 1.26-2.91). The incidence of AEs that prevented normal daily activities was 8.8% (95% CI, 5.4%-14.2%) and that of myocarditis was estimated to be 1.8 per million (95% CI, 0.000%-0.001%) following the second injection. Conclusions and Relevance: In this systematic review and meta-analysis, COVID-19 mRNA vaccines among children aged 5 to 11 years were associated with measures of efficacy in preventing SARS-CoV-2 infection and severe COVID-19-related illnesses. While most children developed local AEs, severe AEs were rare, and most of AEs resolved within several days. These data provide evidence for future recommendations.

Diagnosing Influenza Infection from Pharyngeal Images using Deep Learning: Machine Learning Approach.

BACKGROUND: The global burden of influenza is substantial. It is a major disease that causes annual epidemics and occasionally, pandemics. Given that influenza primarily infects the upper respiratory system, it may be possible to diagnose influenza infection by applying deep learning to pharyngeal images. OBJECTIVE: We aimed to develop a deep learning model to diagnose influenza infection using pharyngeal images and clinical information. METHODS: We recruited patients who visited clinics and hospitals because of influenza-like symptoms. In the training stage, we developed a diagnostic prediction artificial intelligence (AI) model based on deep learning to predict polymerase chain reaction (PCR)-confirmed influenza from pharyngeal images and clinical information. In the validation stage, we assessed the diagnostic performance of the AI model. In additional analysis, we compared the diagnostic performance of the AI model with that of three physicians and interpreted the AI model using importance heatmaps. RESULTS: We enrolled a total of 7,831 patients at 64 hospitals between Nov 1, 2019 and Jan 21, 2020 in the training stage and 659 patients (including 196 patients with PCR-confirmed influenza) at 11 hospitals between Jan 25, 2020 and Mar 13, 2020 in the validation stage. The area under the receiver operating characteristic curve for the AI model was 0.90 (95% confidence interval, 0.87-0.93), and its sensitivity and specificity were 76% (70%-82%) and 88% (85%-91%), respectively, outperforming three physicians. In the importance heatmaps, the AI model often focused on follicles on the posterior pharyngeal wall. CONCLUSIONS: We developed the first AI model that can accurately diagnose influenza from pharyngeal images, which has the potential to help physicians to make a timely diagnosis.

A post-marketing safety assessment of COVID-19 mRNA vaccination for serious adverse outcomes using administrative claims data linked with vaccination registry in a city of Japan.

INTRODUCTION: The safety profiles of COVID-19 vaccines are incompletely evaluated in Japan. OBJECTIVES: To examine the risk of serious adverse effects after COVID-19 mRNA vaccination (BNT162b2 and mRNA-1273) in cohort studies and self-controlled case series (SCCS). METHODS: Using an administrative claims database linked with the COVID-19 vaccination registry in a city in Japan between September 2020 and September 2021, we identified health insurance enrolees aged ≥ 18 years. We evaluated the risk of acute myocardial infarction, appendicitis, Bell's palsy, convulsions/seizures, disseminated intravascular coagulation, immune thrombocytopenia, pulmonary embolism, haemorrhagic or ischemic stroke, venous thromboembolism, and all-cause mortality, 21 days following any COVID-19 mRNA vaccination, compared with non-vaccination periods. For the cohort studies, we estimated incidence rate ratios (IRRs) by Poisson regression and rate differences (IRDs) by weighted least-squares regression, adjusting for sex, age, and Charlson comorbidity index. We applied a modified SCCS design to appropriately treat outcome-dependent exposures. For the modified SCCS, we estimated within-subject IRRs by weighted conditional Poisson regression. Subgroup analyses stratified by sex and age were also conducted. RESULTS: We identified 184,491 enrolees [male: 87,218; mean (standard deviation) age: 64.2 (19.5) years] with 136,667 first and 127,322 s dose vaccinations. The risks of any outcomes did not increase in any analyses, except for the fact that the modified SCCS indicated an increased risk of pulmonary embolism after the first dose in women (within-subject IRR [95%CI]: 3.97 [1.18-13.32]). CONCLUSION: The findings suggested that the COVID-19 mRNA vaccine was generally safe, whilst a signal of pulmonary embolism following the first dose of the COVID-19 mRNA vaccine was observed.

Peripartum Outcomes Associated With COVID-19 Vaccination During Pregnancy: A Systematic Review and Meta-analysis.

Importance: The risk and benefits of COVID-19 vaccination during pregnancy are under investigation. Pooled evidence regarding neonatal and maternal outcomes in association with COVID-19 vaccination during pregnancy is scarce. Objective: To evaluate the association between COVID-19 vaccination during pregnancy and peripartum outcomes. Data Sources: PubMed and EMBASE databases were searched on April 5, 2022. Language restrictions were not applied. Study Selection: Prospective trials and observational studies comparing the individuals who received at least 1 COVID-19 vaccination during pregnancy with those who did not and reporting the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, neonatal intensive care units (NICU) admission, and intrauterine fetal death (IFD). Data Extraction and Synthesis: Two independent investigators extracted relevant data from each study. Odds ratios (ORs) were calculated using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Main Outcomes and Measures: The primary outcomes were the neonatal outcomes, including preterm birth, small for gestational age, low Apgar score, NICU admission, and IFD. The secondary outcomes were maternal outcomes, including maternal SARS-CoV-2 infection, cesarean delivery, postpartum hemorrhage, and chorioamnionitis. Results: Nine observational studies involving 81 349 vaccinated (mean age, 32-35 years) and 255 346 unvaccinated individuals during pregnancy (mean age, 29.5-33 years) were included. COVID-19 vaccination during pregnancy was associated with lower risk of NICU admission (OR, 0.88; 95% CI, 0.80-0.97) and IFD (OR, 0.73; 95% CI, 0.57-0.94), whereas there was no statistically significant association with preterm birth (OR, 0.89; 95% CI, 0.76-1.04), small for gestational age (OR, 0.99; 95% CI, 0.94-1.04), and low Apgar score (OR, 0.94; 95% CI, 0.87-1.02). COVID-19 vaccination during pregnancy was associated with a lower risk of maternal SARS-CoV-2 infection (OR, 0.46; 95% CI, 0.22-0.93), whereas it was not associated with increased risk of cesarean delivery (OR, 1.05; 95% CI, 0.93-1.20), postpartum hemorrhage (OR, 0.95; 95% CI, 0.83-1.07), and chorioamnionitis (OR, 0.95; 95% CI, 0.83-1.07). Conclusions and Relevance: COVID-19 vaccination during pregnancy was not associated with an increase in the risk of peripartum outcomes, was associated with a decreased risk of NICU admission, IFD, and maternal SARS-CoV-2 infection. Thus, COVID-19 vaccination should be encouraged for pregnant individuals.

Characteristics and Clinical Ocular Manifestations in Patients with Acute Corneal Graft Rejection after Receiving the COVID-19 Vaccine: A Systematic Review.

This study aimed to determine the characteristics and clinical ocular manifestations of acute corneal graft rejection after coronavirus disease 2019 (COVID-19) vaccination. We conducted an online search of the PubMed and EMBASE databases. Data on recipients' characteristics, corneal transplantation types, interval between vaccination and allograft rejection, clinical manifestations, and graft rejection medication were extracted. Thirteen articles on 21 patients (23 eyes) with acute corneal graft rejection after COVID-19 vaccination, published between April and December 2021, were included. The median (interquartile range) age at the onset of rejection was 68 (27-83) years. Types of transplantation included penetrating keratoplasty (12 eyes), Descemet membrane endothelial keratoplasty (six eyes), Descemet stripping automated endothelial keratoplasty (four eyes), and living-related conjunctival-limbal allograft (one eye). The interval between vaccination and rejection ranged from 1 day to 6 weeks. Corneal edema was the leading clinical manifestation (20 eyes), followed by keratic precipitates (14 eyes) and conjunctival or ciliary injection (14 eyes). Medications included frequently applied topical corticosteroids (12 eyes), followed by a combination of topical and oral corticosteroids (four eyes). In addition, the clinical characteristics of corneal allograft rejection after COVID-19 vaccination were identified. Corneal transplant recipients may require further vaccination, necessitating appropriate management and treatment.

Hospital factor and prognosis of COVID-19 in New York City, the United States of America: insights from a retrospective cohort study.

BACKGROUND: April 22nd, 2020, New York City (NYC) was the epicenter of the pandemic of Coronavirus disease 2019 (COVID-19) in the US with differences of death rates among its 5 boroughs. We aimed to investigate the difference in mortality associated with hospital factors (teaching versus community hospital) in NYC. DESIGN: Retrospective cohort study. METHODS: We obtained medical records of 6509 hospitalized patients with laboratory confirmed COVID-19 from the Mount Sinai Health System including 4 teaching hospitals in Manhattan and 2 community hospitals located outside of Manhattan (Queens and Brooklyn) retrospectively. Propensity score analysis using inverse probability of treatment weighting (IPTW) with stabilized weights was performed to adjust for differences in the baseline characteristics of patients initially presenting to teaching or community hospitals, and those who were transferred from community hospitals to teaching hospitals. RESULTS: Among 6509 patients, 4653 (72.6%) were admitted in teaching hospitals, 1462 (22.8%) were admitted in community hospitals, and 293 (4.6%) were originally admitted in community and then transferred into teaching hospitals. Patients in community hospitals had higher mortality (42.5%) than those in teaching hospitals (17.6%) or those transferred from community to teaching hospitals (23.5%, P < 0.001). After IPTW-adjustment, when compared to patients cared for at teaching hospitals, the hazard ratio (HR) and 95% confidence interval (CI) of mortality were as follows: community hospitals 2.47 (2.03-2.99); transfers 0.80 (0.58-1.09)). CONCLUSIONS: Patients admitted to community hospitals had higher mortality than those admitted to teaching hospitals.

One-year follow-up CT findings in COVID-19 patients: A systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19) often causes radiological and functional pulmonary sequelae. However, evidence on 1-year follow-up of pulmonary sequelae is limited. We aimed to investigate the characteristics and time-course of pulmonary sequelae after recovery from COVID-19 through 1-year follow-up. We searched PubMed and EMBASE databases on 25 February 2022, and included studies with computed tomography (CT) findings at the 1-year follow-up. The extracted data on CT findings were analysed using a one-group meta-analysis. We further analysed the data in relation to COVID-19 severity, improvement rate and lung function. Fifteen eligible studies (N = 3134) were included. One year after COVID-19, 32.6% (95% CI 24.0-42.6, I2  = 92.9%) presented with residual CT abnormalities. Ground-glass opacity and fibrotic-like changes were frequently observed in 21.2% (95% CI 15.4-28.4, I2  = 86.7%) and 20.6% (95% CI 11.0-35.2, I2  = 91.9%), respectively. While the gradual recovery was seen on CT (52.9% [mid-term] vs. 32.6% [1 year]), the frequency of CT abnormalities was higher in the severe/critical cases than in the mild/moderate cases (37.7% vs. 20.7%). In particular, fibrotic changes showed little improvement between 4-7 months and 1 year after COVID-19. Pulmonary function tests at 1 year also showed the decline in diffusing capacity of the lung for carbon monoxide, especially in severe/critical cases. Our meta-analysis indicated that residual CT abnormalities were common in hospitalized COVID-19 patients 1 year after recovery, especially fibrotic changes in severe/critical cases. As these sequelae may last long, vigilant observations and longer follow-up periods are warranted.

Comparison of the Characteristics and Outcomes of COVID-19 Patients Treated by a Hospital-at-Home Service in Japan during the Alpha and Delta Waves.

Coronavirus infections occurred in repeated waves caused by different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the number of patients increasing during each wave. A private after-hours house-call (AHHC) service provides hospital-at-home (HaH) services to patients in Japan requiring oxygen when hospital beds are in short supply. This retrospective study aimed to compare the characteristics of COVID-19 patients treated by the AHHC service during the COVID-19 waves caused by the Alpha (March-June 2021) and Delta (July-December 2021) SARS-CoV-2 variants. All patients with COVID-19 treated by the AHHC service from March to December 2021 while awaiting hospitalization were included. The data were collected from medical records and follow-up telephone interviews. The AHHC service treated 55 and 273 COVID-19 patients during the Alpha and Delta waves, respectively. The patients treated during the Delta wave were significantly younger than those treated during the Alpha wave (median: 63 years and 47 years, respectively; p < 0.001). Disease severity did not differ significantly between the two waves, but the crude case-fatality rate was significantly higher during the Alpha wave (10/55, 18.2%) than during the Delta wave (4/273, 1.4%; p < 0.001). The patient characteristics and outcomes differed between the Alpha and Delta waves.

COVID-19 and kidney disease: insights from epidemiology to inform clinical practice.

Over the course of the COVID-19 pandemic, numerous studies have aimed to address the challenges faced by patients with kidney disease and their caregivers. These studies addressed areas of concern such as the high infection and mortality risk of patients on in-centre haemodialysis and transplant recipients. However, the ability to draw meaningful conclusions from these studies has in some instances been challenging, owing to barriers in aspects of usual care, data limitations and problematic methodological practices. In many settings, access to SARS-CoV-2 testing differed substantially between patient groups, whereas the incidence of SARS-CoV-2 infection varied over time and place because of differences in viral prevalence, targeted public health policies and vaccination rates. The absence of baseline kidney function data posed problems in the classification of chronic kidney disease and acute kidney injury in some studies, potentially compromising the generalizability of findings. Study findings also require attentive appraisal in terms of the effects of confounding, collider bias and chance. As this pandemic continues and in the future, the implementation of sustainable and integrated research infrastructure is needed in settings across the world to minimize infection transmission and both prevent and plan for the short-term and long-term complications of infectious diseases. Registries can support the real-world evaluation of vaccines and therapies in patients with advanced kidney disease while enabling monitoring of rare complications.

Association between pre-admission anticoagulation and in-hospital death, venous thromboembolism, and major bleeding among hospitalized COVID-19 patients in Japan.

PURPOSE: The coagulation activation leads to thrombotic complications such as venous thromboembolism (VTE) in patients with coronavirus disease-2019 (COVID-19). Prophylactic anticoagulation therapy has been recommended for hospitalized COVID-19 patients in clinical guidelines. This retrospective cohort study aimed to examine the association between pre-admission anticoagulation treatment and three outcomes: in-hospital death, VTE, and major bleeding among hospitalized COVID-19 patients in Japan. METHODS: Using a large-scale claims database built by the Medical Data Vision Co. in Japan, we identified patients hospitalized for COVID-19 who had outpatient prescription data at least once within 3 months before being hospitalized. Exposure was set as pre-admission anticoagulation treatment (direct oral anticoagulant or vitamin K antagonist), and outcomes were in-hospital death, VTE, and major bleeding. We conducted multivariable logistic regression analyses, adjusting for a single summarized score (a propensity score of receiving pre-admission anticoagulation) for VTE and major bleeding, due to the small number of outcomes. RESULTS: Among the 2612 analytic patients, 179 (6.9%) had pre-admission anticoagulation. Crude incidence proportions were 13.4% versus 8.5% for in-hospital death, 0.56% versus 0.58% for VTE, and 2.2% versus 1.1% for major bleeding among patients with and without pre-admission anticoagulation, respectively. Adjusted odds ratios (95% confidence intervals) were 1.25 (0.75-2.08) for in-hospital death, 0.21 (0.02-1.97) for VTE, and 2.63 (0.80-8.65) for major bleeding. Several sensitivity analyses did not change the results. CONCLUSIONS: We found no evidence that pre-admission anticoagulation treatment was associated with in-hospital death. However, a larger sample size may be needed to conclude its effect on VTE and major bleeding.

Clinical Features and Mortality of COVID-19-Associated Mucormycosis: A Systematic Review and Meta-Analysis.

The recent increase of COVID-19-associated mucormycosis (CAM) has been commanding global attention. However, basic epidemiologic characteristics have not firmly been established. In this systematic review and meta-analysis, we sought to determine the clinical manifestations, potential risk factors, and outcomes of CAM. Observational studies reporting CAM were searched with PubMed and EMBASE databases in January 2022. We collected data on comorbidities and treatment for COVID-19, and performed a one-group meta-analysis on the frequency of orbital exenteration procedure and mortality of CAM using a random-effect model. Fifty-one observational studies, including a total of 2,312 patients with proven CAM, were identified. Among the 51 studies, 37 were conducted in India, 8 in Egypt, and 6 in other countries. The most common comorbidity was diabetes mellitus (82%). While 57% required oxygenation, 77% received systemic corticosteroids. Among CAM, 97% were rhino-orbital-cerebral (ROCM), and 2.7% were pulmonary mucormycosis. Usual presentations were headache (54%), periorbital swelling/pain (53%), facial swelling/pain (43%), ophthalmoplegia (42%), proptosis (41%), and nasal discharge/congestion (36%). Regarding the outcomes, orbital exenteration was performed in 17% (95% CI: 12-21%, I2 = 83%) of the COVID-19-associated ROCM patients. The mortality of CAM was 29% (95% CI; 22-36%, I2 = 92%). In conclusion, this systematic review and meta-analysis indicated that the most prevalent type of CAM was ROCM, and most CAM patients had diabetes mellitus and received systemic glucocorticoids. Clinicians in the endemic areas should have a high index of suspicion for this invasive fungal complication of COVID-19 when a diabetic patient who received high-dose systemic glucocorticoids developed rhino-orbital symptoms.

The role of after-hours house-call medical service in the treatment of COVID-19 patients awaiting hospital admission: A retrospective cohort study.

ABSTRACT: Due to the increasing number of coronavirus disease 2019 (COVID-19) cases in Japan, hospitals are unable to provide admission and immediate inpatient care. The after-hours house call (AHHC) service offers telephone consultations and in-home care to patients awaiting admission. Currently, there is no report on the management of COVID-19 patients when inpatient beds are insufficient.We aimed to describe the clinical characteristics and outcomes of COVID-19 patients treated by an AHHC medical service in Osaka and Tokyo, between April and May 2021 (during the fourth wave in Japan). Patients were classified into 2 groups: Moderate I and Moderate II, according to the severity of infection under Japanese guidelines. A retrospective study of the hospital records and follow-up telephone consultations was performed.The AHHC treated a total of 55 COVID-19 patients (17 with Moderate I, 38 with Moderate II disease). The median ages (interquartile range) were 63 (49-80.5) and 64 (50.8-81), respectively. In each group, approximately 30% of AHHC patients received out-of-hospital oxygen therapy for the duration of their treatment until it was no longer required. Major symptoms, including shortness of breath or difficulty breathing (47.1% and 78.9%, respectively) and fever or chills (41.2% and 76.3%, respectively) were lower in the Moderate I group than in the Moderate II group. Overall, 16.4% of patients died, with 17.6% in the Moderate I group and 15.8% in the Moderate II group.We found the proportion of mortality in patients treated by the AHHC was slightly higher to that of patients treated in Japanese hospitals. This study will provide an alternative management of patients requiring oxygen in situations where hospital beds are in short supply.

Association between Nafamostat Mesylate and In-Hospital Mortality in Patients with Coronavirus Disease 2019: A Multicenter Observational Study.

Nafamostat mesylate may be effective against coronavirus disease 2019 (COVID-19). However, it is not known whether its use is associated with reduced in-hospital mortality in clinical practice. We conducted a retrospective observational study to evaluate the effect of nafamostat mesylate in patients with COVID-19 using the Medical Data Vision Co. Ltd. hospital-based database in Japan. We compared patients with COVID-19 who were (n = 121) and were not (n = 15,738) administered nafamostat mesylate within 2 days of admission between January and December 2020. We conducted a 1:4 propensity score matching with multiple imputations for smoking status and body mass index and combined the 20 imputed propensity score-matched datasets to obtain the adjusted odds ratio for in-hospital mortality. Crude in-hospital mortality was 13.2% (16/121) and 5.0% (790/15,738), respectively. In the propensity score-matched analysis with multiple imputations, the adjusted odds ratio (use vs. no use of nafamostat mesylate) for in-hospital mortality was 1.27 (95% confidence interval: 0.61-2.64; p = 0.52). Sensitivity analyses showed similar results. The results of this retrospective observational study did not support an association between nafamostat mesylate and improved in-hospital outcomes in patients with COVID-19, although further studies with larger sample sizes are warranted to assess the generalizability of our findings.