Risk Factors For Severe Disease Research Articles

Virologic Response and Safety of Ibuzatrelvir, a Novel SARS-CoV-2 Antiviral, in Adults With COVID-19.

Despite effective vaccines and treatments for COVID-19, clinical burden persists. An unmet need exists for additional effective agents with safety profiles allowing use across a broad population. Ibuzatrelvir is an orally bioavailable SARS-CoV-2 Mpro inhibitor that has demonstrated in vitro antiviral activity and low potential for safety concerns, including drug-drug interactions. This phase 2b, double-blind, randomized clinical trial enrolled US adults aged 18‒<65 years with symptomatic COVID-19 and no risk factors for severe disease. Participants were randomized 1:1:2:2 to receive 100, 300, or 600 mg ibuzatrelvir or placebo orally twice daily for 5 days. Nasopharyngeal specimens were collected on Days 1 (baseline), 3, 5, 10, 14, and 21; adverse events (AEs) were recorded through Day 33. The primary endpoint was change in SARS-CoV-2 RNA level (viral load [VL]) from baseline to Day 5 among participants with baseline VL ≥4 log10 copies/mL. Of 240 enrollees, 237 received ≥1 dose and 199 were included in the primary analysis. Placebo-adjusted least squares mean (80% CI) change from baseline in VL at Day 5 was significant across all doses: 100 mg, ‒0.7 (‒1.1, ‒0.3) log10 copies/mL, P=0.02; 300 mg, ‒0.8 (‒1.3, ‒0.3) log10 copies/mL, P=0.01; and 600 mg, ‒1.2 (‒1.5, ‒0.8) log10 copies/mL, P<0.0001. AEs occurred in similar percentages of participants across groups. No deaths from any cause or treatment-related serious AEs occurred through Day 33, and no participants reported dysgeusia. All 3 ibuzatrelvir doses were associated with robust antiviral activity and an acceptable safety profile, supporting continued clinical development. Clinicaltrials.gov identifier: NCT05799495.

Diagnostic et prise en charge de l'infection congénitale à cytomégalovirus

AbstractCongenital cytomegalovirus (CMV) infection affects almost 1 % of newborns, with a risk of sequelae of 17-20 %. Primary maternal infection during the first trimester of pregnancy is the most significant risk factor for severe disease. To prevent primary maternal infection, primary prevention strategies (hygiene and information measures) have been shown to be effective but are still insufficient. Although not yet recommended by the health authorities, screening enables cases of primary maternal infection to be detected as early as possible, so that transmission can be prevented by administering valaciclovir. This strategy has proved effective, reducing maternal-fetal transmission of CMV by 70 %. Screening is based on CMV serology (IgG and IgM), supplemented by IgG avidity testing if IgM are present. It is essential that screening and initiation of treatment should be as early as possible to optimize the efficacy of this strategy. PCR on amniotic fluid, proposed in the case of a first trimester maternal primary infection, can be used to diagnose fetal infection. It is also indicated in the event of abnormalities detected on ultrasound. CMV infection in newborns can be confirmed by PCR on saliva or urine, and treatment with valaganciclovir can be initiated in cases of symptomatic congenital infection.

A large-scale retrospective study in China explores risk factors for disease severity in plaque psoriasis

Severe psoriasis has a long course and poor outcome, and it has long been a problem for patients. Understanding the independent risk factors that contribute to patients with severe psoriasis is critical for the development of effective treatment strategies. This large, multicenter study recruited 2,109 plaque psoriasis patients from 12 hospitals across China (October 31, 2019 – May 31, 2022). The logistic regression model underwent internal validation and external validation using two independent cohorts over future time periods (June 1, 2022 – January 31, 2023). The discriminative power of our model was substantiated by a C-index of 0.863 (95% CI: 0.848–0.879) in internal validation, further affirmed through 1,000 bootstrap validation (C-index: 0.860, 95% CI: 0.836–0.885) and external validation cohorts, where the C-index reached up to 0.910 (95% CI: 0.868–0.953) and 0.951 (95% CI: 0.924–0.977) in 2 external validation cohorts. To enhance accessibility for clinicians, the model has been made available as a dynamic nomogram and QR code. Our study identified 10 risk factors (the “DELPHI” consensus dichotomy, the DLQI index, the extent of skin involvement as measured by body surface area, the age of the patient at the time of clinical visit, sex, body weight in kilograms, career, the presence of scalp involvement, facial involvement, and arthropathy) for the overall severity of psoriasis (PASI ≥ 10). “Nomogram-10” provides clinicians with a practical tool to develop personalized intervention strategies based on an individual’s risk profile.Trial registration: Chinese Clinical Trial Registry: ChiCTR1900024852.

Clinical features and risk factors for outcome in hemodialysis patients with COVID-19 after complete liberalization of epidemic control in China.

Patients undergoing hemodialysis (HD) are highly vulnerable during the COVID-19 pandemic. We aimed to investigate the risk factors associated with the severity of COVID-19 and death after the complete liberalization of epidemic control in China. We followed the outcomes of the HD patients of Central Hospital of Dalian University of Technology, from December 6, 2022 to January 8, 2023. The non-contrast enhanced chest computed tomography (CT) was performed on all COVID-19-infected hospitalized patients. We recorded the patient's clinical characteristics, demographic features, vaccination history, treatments, and lung lesions. Odds ratios and 95% confidence intervals were calculated using logistic regression models to identify independent risk factors for COVID-19-related severity and mortality. This study included a total of 858 hemodialysis patients, of which 660 were infected with COVID-19. The mean age was (55.61±14.61) years, with a median (interquartile range) dialysis duration of 44.5 (69.5) months. Over half (60%) of the study participants were male, and the majority had hypertension as a comorbidity. Multivariable analysis revealed that age, pre-dialysis diastolic pressure, fever, white blood cell (WBC) count, potassium, β2-microglobulin level and calcium were independent risk factors for disease severity, while platelets, urea nitrogen and creatinine were identified as independent protective factors. Furthermore, total iron- binding capacity and vaccination were found to be independent protective factors against mortality, and WBC count was an independent risk factor for in-hospital mortality (p &lt; 0.05). The most frequent CT finding among hospitalized patients with chest symptoms was patchy shadow or pleural effusion, observed in 64.8% of cases. More than half of the patients exhibited bilateral lung lesions, and over 60% involved two or more lobes. The majority of HD patients are susceptible to COVID-19. Demographic, clinical features and laboratory indicators can be used to predict the severity and mortality associated with COVID-19. Our findings will assist clinicians in identifying markers for the early detection of high mortality risk in HD patients with COVID-19.

Risk factor analysis and prediction model construction for severe adenovirus pneumonia in children

BackgroundSevere adenovirus pneumonia in children has a high mortality rate, but research on risk prediction models is lacking. Such models are essential as they allow individualized predictions and assess whether children will likely progress to severe disease.MethodsA retrospective analysis was performed on children with adenovirus pneumonia who were hospitalized at the Children’s Hospital of Nanjing Medical University from January 2017 to March 2024. The patients were grouped according to clinical factors, and the groups were compared using Ridge regression and multiple logistic regression to identify risk factors associated with severe adenovirus pneumonia. A prediction model was constructed, and its value in clinical application was evaluated.Results699 patients were included in the study, with 284 in the severe group and 415 in the general group. Through the screening of 44 variables, the final risk factors for severe adenovirus pneumonia in children as the levels of neutrophils (OR = 1.086, 95% CI: 1.054‒1.119, P < 0.001), D-dimer (OR = 1.005, 95% CI: 1.003‒1.007, P < 0.001), fibrinogen degradation products (OR = 1.341, 95% CI: 1.034‒1.738, P = 0.027), B cells (OR = 1.076, 95%CI: 1.046‒1.107, P < 0.001), and lactate dehydrogenase (OR = 1.008, 95% CI: 1.005‒1.011, P < 0.001). The value of the area under the receiver operating characteristic curve was 0.974, the 95% CI was 0.963–0.985, and the P-value of the Hosmer-Lemeshow test was 0.547 (P > 0.05), indicating that the model had strong predictive power.ConclusionIn this study, the clinical variables of children with adenovirus pneumonia were retrospectively analyzed to identify risk factors for severe disease. A prediction model for severe disease was constructed and evaluated, showing good application value.

Severe Clinical Outcomes Due to Human Adenoviral Respiratory Infections in Hospitalized Immunocompetent Adults

Background Human adenoviral infections typically result in upper respiratory tract infections, conjunctivitis, and gastroenteritis that is classically self-limiting but can be life-threatening in immunocompromised individuals. In relatively rare cases, adenovirus infections in immunocompetent patients can result in hospitalizations and severe outcomes that include need for critical care or death. The risk factors that are associated with severe adenoviral infections in immunocompetent hosts have not been thoroughly investigated and are currently poorly understood. Methods Retrospective cohort of 78 patients with ages ranging from 18–85 years who were admitted to Yale New Haven-affiliated hospitals over a period of 2 years with positive adenovirus tests on a nasopharyngeal respiratory viral panel. Immunocompromised patients were excluded from the study. Patient charts were reviewed to obtain demographic information, comorbid conditions, smoking history, and clinical outcomes. Results Of the 78 patients admitted, 15 (19.2%) were admitted as observation, 44 (56.4%) were admitted to the hospital for over 48 hours, 15 (19.2%) required critical care, and 4 (5.1%) expired during hospitalization. Pulmonary disease as a comorbidity in the form of asthma (33.3%) or chronic obstructive pulmonary disease (12.8%), and smoking history (59.0%) were more common in those with severe adenoviral infections. With severe disease, 13 (16.7%) required mechanical ventilation, 10 (12.8%) required pressor support, and 2 (2.6%) required extracorporeal membrane oxygenation. Conclusions This retrospective study characterizes severity of adenoviral infections in adult immunocompetent patients, highlights the lack of treatment available, and identifies potential risk factors for severe disease, including asthma, smoking, absence of fever, and presence of coinfection.

Tumor Necrosis Factor Receptors and C-C Chemokine Receptor-2 Positive Cells Play an Important Role in the Intraerythrocytic Death and Clearance of Babesia microti.

Babesia microti is an Apicomplexan parasite that infects erythrocytes and causes the tick-transmitted infection, babesiosis. B. microti can cause a wide variety of clinical manifestations ranging from asymptomatic to severe infection and death. Some risk factors for severe disease are well-defined, an immune compromised state, age greater than 50, and asplenia. However, increasing cases of severe disease and hospitalization in otherwise healthy individuals suggests that there are unknown risk factors. The immunopathology of babesiosis is poorly described. CD4+ T cells and the spleen both play a critical role in parasite clearance, but few other factors have been found that significantly impact the course of disease. Here, we evaluated the role of several immune mediators in B. microti infection. Mice lacking TNF receptors 1 and 2, the receptors for TNFα and LTα, had a higher peak parasitemia, reduced parasite killing in infected red blood cells (iRBCs), and delayed parasite clearance compared to control mice. Mice lacking CCR2, a chemokine receptor involved in the recruitment of inflammatory monocytes, and mice lacking NADPH oxidase, which generates superoxide radicals, demonstrated reduced parasite killing but had little effect on the course of parasitemia. These results suggest that TNFR-mediated responses play an important role in limiting parasite growth, the death of parasites in iRBCs, and the clearance of iRBCs, and that the parasite killing in iRBCs is being primarily mediated by ROS and inflammatory monocytes/macrophages. By identifying factors involved in parasite killing and clearance, we can begin to identify additional risk factors for severe infection and newer therapeutic interventions.

Frailty as a Predictor of COVID-19 Mortality in the South Indian Population: An Observational Study.

Background Frailty is a clinical syndrome characterized by diminished strength, endurance, and physiological function that significantly increases vulnerability to adverse health outcomes, including infections. In the context of COVID-19, frailty has emerged as a critical risk factor for severe disease, complications, and mortality, particularly in older adults. The severity and fatality rates among the geriatric group were notably high, as the virus's pathogenesis, marked by prolonged inflammation, contributed to increased morbidity and mortality in this age group. The study was conducted to explore the role of frailty in influencing mortality among the elderly affected by COVID-19. Objective The objective of this study was to identify the association between frailty and mortality in COVID-19-affected elderly patients. Methods We conducted a prospective observational study among elderly patients who tested positive for COVID-19 and received treatment in a tertiary care hospital. Data were collected from 250 patients from March 2021 to December 2021. Lab parameters, the necessity for mechanical ventilation, the need for oxygen use, and the number of days of hospital stay were recorded. The Clinical Frailty Score (CFS) was used to evaluate frailty. The chi-square test with Fisher's exact test was used to assess the association between frailty and mortality in the data set. Multivariate binary logistic regression was employed to identify the most significant predictors of mortality. Results Among the 250 patients, 159 (63.6%) survived and were discharged, while 91 (36.4%) succumbed to the illness. Fifty-eight patients were not identified as frail, and there were no deaths in the group. On the contrary, among the 192 COVID-positive patients who were identified as frail, 91 (47.4%) patients died, and 101 (52.6%) patients were alive. This depicted the association between frailty and mortality in COVID-19 geriatric patients. While assessing comorbidities, malignancy (53.3%, p-value = 0.009) and chronic kidney disease (CKD) (43.3%) had a significant association with mortality. Symptoms like fever (43.6%), dyspnea (68.6%), myalgia (20%), and altered sensorium (84%) showed a strong correlation with mortality (p<0.001). Frailty was a significant predictor of mortality, with 47.4% of frail patients not surviving (p<0.001). Biochemical markers including leukocytosis (64.8%), neutrophilia (65.3%), eosinopenia (66.9%), anemia (57.8%), hypoalbuminemia (63.5%), hypoproteinemia (70.1%), elevated alanine aminotransferase (ALT) (66%),aspartate aminotransferase (AST) (65.2%), alkaline phosphatase (ALP) (67.5%), elevated creatinine (68.9%), hypernatremia (100%), hyperkalemia (80%), and elevated D-dimer (44.7%) were all significantly linked to mortality. Additionally, patients requiring oxygen (65%), ventilation (96.8%), or bilevel positive airway pressure (BiPAP) (77.8%) had higher mortality rates. A shorter length of hospital stay was also associated with increased mortality (24%). Conclusion Frailty, combined with certain comorbidities such as cancer and CKD, along with various clinical and biochemical markers, played a significant role in predicting mortality among geriatric COVID-19 patients. Incorporating frailty assessments into routine evaluations for elderly COVID-19 survivors could be beneficial. Early detection and focused management of these high-risk factors are essential for improving outcomes in frail patients within tertiary care settings.

A single-center experience in home management of mild and moderate COVID-19 cases.

The use of telemedicine for treatment of coronavirus disease 2019 (COVID-19) infection has been effective in lowering the risk of infection and relieving strain on the healthcare system. This study aimed to describe the clinical characteristics of COVID-19 cases, their follow-up, risk factors of disease severity, and predictors of hospital admission while using telemedicine. The study included 611 Egyptian patients with mild and moderate COVID-19 disease. The patients were isolated at home and monitored daily. Based on the World Health Organization classification, 79% of studied patients had mild illness while 20.5% had moderate illness. The initial symptoms included cough (51.7%), fever (50.8%), fatigue (45.9%), sore throat (41.1%), dyspnea (35.2%), and headache (34%); 25.2% patients had prolonged symptoms (≥ 21 days). Dyspnea was the most frequent (15.5%) long-term symptom. Age, co-existing diabetes, and COVID-19 infection with moderate severity, were associated with the need for hospitalization. We compared patients with COVID-19 infection who required hospital admission (n = 37) versus patients who continued in home isolation (n = 574). High neutrophil/lymphocyte ratio, transaminases, and ferritin significantly correlated with the need for hospitalization. 18.9% of the patients who required hospital admission had diabetes. Multivariate analysis described age and diabetes as independent predictors of disease severity. Age and high neutrophil/lymphocyte ratio were independent predictors of hospital admission. Telemedicine is effective in-home management of mild/moderate COVID-19 patients, which may ease the pressure on the healthcare system, even beyond the pandemic.

Hereditary thrombophilia as a possible risk factor for severe disease in COVID-19: a case series.

The risk factors that modulate one's susceptibility for severe COVID-19 have been well documented. Despite this, hypercoagulability remains an often overlooked risk factor for severe disease for COVID-19. Because COVID-19 infection is a risk factor for hypercoagulability, a reasonable presumption/hypothesis is that patients with hereditary thrombophilia would be at a higher risk of thrombotic complications associated with COVID-19 infection. This case report details two cases where previously unknown hereditary thrombophilias likely contributed to the mortality of COVID-19 patients. The first COVID-19 patient's cause of death was pulmonary thromboemboli from deep vein thrombosis due to heterozygous MTHFR C667T and heterozygous PAI-1 4G/5G mutations. The second COVID-19 patient's cause of death was an acute myocardial infarct due to a coronary artery thrombosis in the setting of heterozygous MTHFR A1298C and homozygous PAI-1 4G/5G mutations. In each case, COVID-19 infection was also considered contributory to death. The occurrence of these fatal thrombotic events in COVID-19 patients with hereditary thrombophilias raises questions as to whether this combination of thrombotic risk factors for hypercoagulability may have placed patients at a significant enough risk to experience these fatal thrombotic complications. Thus, while not sufficient alone to prove that SARS-CoV-2 patients with hereditary thrombophilias are at increased risk for thrombotic complications, these two cases indicate that further investigation is warranted into elucidating the relationship between thrombotic risk factors as it may identify an additional high-risk medical condition for COVID-19 and have important diagnostic and therapeutic ramifications.

Insights from a multicenter nationwide cohort analysis in Japan on the association of underlying conditions and pharmacological interventions with COVID-19 disease severity

BackgroundIn 2019, coronavirus disease 2019 (COVID-19) emerged in China, spreading globally with significant impacts in Japan, including the Delta and Omicron variants. The research identified risk factors such as age, chronic diseases, and lifestyle choices, emphasizing the need for further study on the association between underlying health conditions, treatments, and COVID-19 severity in Japan.MethodsThis study used a nationwide medical database to analyze the association between COVID-19 underlying conditions and pharmacological interventions to identify risk factors for disease severity. We examined the Japanese COVID-19 dataset from Medical Data Vision, selecting patients diagnosed with COVID-19 between January 2020 and December 2022. Logistic regression was used to calculate the odds ratios (ORs) for intensive care unit treatment- or ventilator use-related risk factors.ResultsAmong 650,317 patients (mean age: 52.1 ± 20.9 years; male individuals: 324,127; female individuals: 326,190), factors that significantly increased the severe disease risk (OR [95% confidence interval]) included age > 65 years (1.31 [1.27–1.36]), hypertension (1.34 [1.28–1.41]), cardiovascular disease (1.74 [1.67–1.81]), and use of beta-blockers (2.09 [2.00–2.17]), calcium blockers (1.97 [1.89–2.06]), angiotensin-converting enzyme inhibitors (1.41 [1.33–1.49]), low-dose aspirin (1.38 [1.32–1.45]), and insulin (7.14 [6.87–7.43]). Conversely, factors that reduced the severe disease risk included female sex and the use of sulfonylureas, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide-1 receptor agonists, and alpha-glucosidase inhibitors.ConclusionsPatients using cardiovascular medications faced a higher risk, whereas those receiving diabetes treatment had a lower risk. Appropriate pharmacotherapy and risk factor identification can aid in the prevention of severe COVID-19.

Feature Identification Using Interpretability Machine Learning Predicting Risk Factors for Disease Severity of In-Patients with COVID-19 in South Florida.

Objective: The objective of the study was to establish an AI-driven decision support system by identifying the most important features in the severity of disease for Intensive Care Unit (ICU) with Mechanical Ventilation (MV) requirement, ICU, and InterMediate Care Unit (IMCU) admission for hospitalized patients with COVID-19 in South Florida. The features implicated in the risk factors identified by the model interpretability can be used to forecast treatment plans faster before critical conditions exacerbate. Methods: We analyzed eHR data from 5371 patients diagnosed with COVID-19 from South Florida Memorial Healthcare Systems admitted between March 2020 and January 2021 to predict the need for ICU with MV, ICU, and IMCU admission. A Random Forest classifier was trained on patients' data augmented by SMOTE, collected at hospital admission. We then compared the importance of features utilizing different model interpretability analyses, such as SHAP, MDI, and Permutation Importance. Results: The models for ICU with MV, ICU, and IMCU admission identified the following factors overlapping as the most important predictors among the three outcomes: age, race, sex, BMI, diarrhea, diabetes, hypertension, early stages of kidney disease, and pneumonia. It was observed that individuals over 65 years ('older adults'), males, current smokers, and BMI classified as 'overweight' and 'obese' were at greater risk of severity of illness. The severity was intensified by the co-occurrence of two interacting features (e.g., diarrhea and diabetes). Conclusions: The top features identified by the models' interpretability were from the 'sociodemographic characteristics', 'pre-hospital comorbidities', and 'medications' categories. However, 'pre-hospital comorbidities' played a vital role in different critical conditions. In addition to individual feature importance, the feature interactions also provide crucial information for predicting the most likely outcome of patients' conditions when urgent treatment plans are needed during the surge of patients during the pandemic.

SARS-CoV-2 infections in patients, health care workers and hospital outbreaks during the first 3 waves of the pandemic: a retrospective analysis in a secondary care hospital network in Germany

BackgroundHospital infections with SARS-CoV-2 continued during the initial waves of the pandemic worldwide. So far, Data on the dynamics of these infections and the economic burden of outbreaks are rare.MethodsWe retrospectively analysed SARS-CoV-2 infections in patients, hospital employees and nosocomial infections resulting in outbreaks in two hospitals of a secondary care hospital network in Germany during the initial 3 pandemic waves (03/2020–06/2021). In addition to hospital infections, we evaluated infection prevention strategies and the economic burden of hospital outbreaks.ResultsA total of 396 patients with SARS-CoV-2 infection were hospitalized in both hospitals. The risk factors for severe disease and death increased with age, male sex and a CRB-65 score > 0. The most frequent symptom was dyspnoea (30.1%). Sixty-five patients died, most of whom were in the 2nd wave. A total of 182 (12.5%) hospital employees were infected, 63 (34.6%) of whom were involved in outbreaks. An occupational risk of infection during outbreaks was particularly common among nurses and HCWs working on regular wards. Eleven hospital outbreaks led to high economic impact on both hospitals through the loss of manpower as result of infected employees, temporary locked wards, blocked beds, a reduced number of total hospitalized patients and increased personnel costs.ConclusionContinuously adaptation of infection prevention strategies is a valuable tool to keep hospitals safe places for patients and employees. We do need more analyses of the different pandemic waves and applied infection prevention strategies to learn from weak points.Trial registrationThis research was conducted in accordance with the Declaration of Helsinki and national standards. The study protocol was approved by the relevant ethics committee of the Chamber of Physicians Westphalia-Lippe and University of Münster (no. 2021–475-f-S). The study was registered on 25th August 2021 at the German Clinical Trials Register (DRKS00025865).

An Increase in Aspartate Aminotransferase Can Predict Worsening Disease Severity in Japanese Patients with COVID-19.

The prognostic significance of liver dysfunction in COVID-19 patients remains unclear. In this study, we investigated the association between liver function test results and severe disease progression in COVID-19 patients. This retrospective study included consecutive Japanese COVID-19 patients admitted between February 2020 and July 2021. Predictive variables for severe disease progression were identified by multivariate logistic regression analysis. Severe disease-free survival was estimated with the Kaplan-Meier method and Cox regression analysis. Aspartate aminotransferase (AST) was divided into three grades: grade 1, AST < 30 U/L; grade 2, 30 U/L ≤ AST < 60 U/L; and grade 3, AST > 60 U/L. Among 604 symptomatic patients, 141 (23.3%) developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were the significant predictive variables. Severe disease-free survival time was significantly different between the different AST grades (hazard ratio (HR): grade 2 vs. grade 1, 4.07 (95% confidential interval (CI): 2.06-8.03); grade 3 vs. grade 1, 7.66 (95% CI: 3.89-15.1)). The AST level at admission was an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19.

Effect of spirulina on risk of hospitalization among patients with COVID-19: the TOGETHER randomized trial

BackgroundAlgae-derived nutraceuticals, such as spirulina, have been reported to have biological activities that may minimize clinical consequences to COVID-19 infections. ObjectivesThis study aimed to determine whether spirulina is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting. MethodsThe TOGETHER trial is a placebo-controlled, randomized, platform trial conducted in Brazil. Eligible participants were symptomatic adults with a positive rapid test for SARS-CoV-2 older than 50 y or with a known risk factor for disease severity. Patients were randomly assigned to receive placebo or spirulina (1 g twice daily for 14 d). The primary end point was hospitalization defined as either retention in a COVID-19 emergency setting for >6 h or transfer to tertiary hospital owing to COVID-19 at 28 d. Secondary outcomes included time-to-hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to compare spirulina with placebo. ResultsWe recruited 1126 participants, 569 randomly assigned to spirulina and 557 to placebo. The median age was 49.0 y, and 65.3% were female. The primary outcome occurred in 11.2% in the spirulina group and 8.1% in the placebo group (odds ratio [OR]: 1.24; 95% credible interval: 0.84, 1.86). There were no differences in emergency department visit (OR: 1.21; 95% credible interval: 0.81, 1.83), nor time to symptom relief (hazard ratio: 0.90; 95% credible interval: 0.79, 1.03). Spirulina also not demonstrate important treatment effects in the prespecified subgroups defined by age, sex, BMI, days since symptom onset, or vaccination status. ConclusionsSpirulina has no any clinical benefits as an outpatient therapy for COVID-19 compared with placebo with respect to reducing the retention in an emergency setting or COVID-19–related hospitalization. There are no differences between spirulina and placebo for other secondary outcomes.This trial was registered at clinicaltrials.gov as NCT04727424.

Epidemiological Analysis of Legionella Pneumonia in Japan: A National Inpatient Database Study.

Legionella pneumonia, a severe form of pneumonia, is caused by Legionella bacteria. The epidemiology of Legionnaires' disease in Japan, including seasonal trends, risk factors for severe disease, and fatality rates, is unclear. This study examined the epidemiology of Legionella pneumonia in Japan. This retrospective cohort study included data of adult patients hospitalized for Legionella pneumonia (identified using the International Classification of Diseases, 10th revision code, A481) in the Japanese Diagnosis Procedure Combination inpatient database, from April 2011 to March 2021. We performed multivariable logistic regression analysis to explore the prognostic factors of in-hospital mortality. Of 7,370 enrolled hospitalized patients from 1,140 hospitals (male, 84.4%; aged >50 years, 87.9%), 469 (6.4%) died during hospitalization. The number of hospitalized patients increased yearly, from 658 in 2016 to 975 in 2020. Multivariable logistic regression analysis revealed that higher in-hospital mortality was associated with older age, male sex, lower body mass index, worsened level of consciousness, comorbidities (congestive heart failure, chronic renal diseases, and metastasis), hospitalization from November to May, and ambulance use. However, lower in-hospital mortality was associated with comorbidity (liver diseases), hospitalization after 2013, and hospitalization in hospitals with higher case volume. The characterized epidemiology of Legionella pneumonia in Japan revealed a high mortality rate of 6.4%. To the best of our knowledge, this is the first study to demonstrate a higher mortality rate in winter and in patients with congestive heart failure and metastasis. Further research is needed to understand the complex interplay between the prognostic factors of Legionella pneumonia.

Clinical Picture and Risk Factors for Severity of SARS-CoV-2 and Dengue Coinfection in Children: Experience From a Tertiary Hospital in Vietnam.

Introduction Dengue is an infectious disease that is a burden in Asia-Pacific and Latin America. The COVID-19 pandemic in dengue-endemic areas has caused a "double burden" because of the possibility of coinfection, especially in children who are vulnerable to both COVID-19 and dengue. This study aimed to describe the characteristics and identify risk factors for the severity of the coinfection in Vietnamese children. Methods This was a retrospective cohort study, undertaken at Children's Hospital 1 (Ho Chi Minh City, Vietnam) during the fourth wave of the COVID-19 pandemic. All children under 16 years old who were admitted to the hospital from April 27, 2021 to June 30, 2022, and diagnosed with SARS-CoV-2 and dengue coinfection were included. Results From April 2021 to June 2022, a total of 31 patients with the coinfection were included, with 19 of them being male (61.3%). The median age was 10.8 years old (IQR, 5.1-14.1). Fourteen children (45.2%) had preexisting comorbidities, with the most common comorbidity being overweight/obesity (ten children). Nearly two-thirds of the children were diagnosed with dengue without/with warning signs (61.3%) and were classified as having mild COVID-19 (83.9%). The most frequently observed clinical characteristics were fever (n=29, 93.6%), followed by abdominal pain, vomiting, and petechiae. All patients had high serum ferritin, and 83.9% presented with thrombocytopenia. None of thecases died. Overweight/obesity, abdominal pain, and petechiae were factors independently associated with severe disease. Conclusion Most of the children had mild COVID-19 and disease progression similar to patients with dengue alone. However, some children may have severe COVID-19 and dengue coinfection. Obesity, abdominal pain, and petechiae were identified as independent risk factors for disease severity in pediatric cases. Further studies with multicenters and a larger sample size are needed to assess the coinfection more thoroughly.

Enhancing Immune Responses against SARS-CoV-2 Variants in Aged Mice with INDUK: A Chimeric DNA Vaccine Encoding the Spike S1-TM Subunits.

Currently available vaccines against COVID-19 showed high efficacy against the original strain of SARS-CoV-2 but progressively lower efficacy against new variants. In response to emerging SARS-CoV-2 strains, we propose chimeric DNA vaccines encoding the spike antigen, including a combination of selected key mutations from different variants of concern. We developed two DNA vaccines, pVAX-S1-TM-D614G and pVAX-S1-TM-INDUK (INDUK), encoding the SARS-CoV-2 S1 spike subunit in fusion with the transmembrane region that allows protein trimerization as predicted by in silico analysis. pVAX-S1-TM-D614G included the dominant D614G substitution, while the chimeric vaccine INDUK contained additional selected mutations from the Delta (E484Q and L452R) and Alpha (N501Y and A570D) variants. Considering that aging is a risk factor for severe disease and that suboptimal vaccine responses were observed in older individuals, the immunogenicity of pVAX-S1-TM-D614G and INDUK was tested in both young and aged C57BL/6 mice. Two vaccine doses were able to trigger significant anti-SARS-CoV-2 antibody production, showing neutralizing activity. ELISA tests confirmed that antibodies induced by pVAX-S1-TM-D614G and INDUK were able to recognize both Wuhan Spike and Delta variant Spike as trimers, while neutralizing antibodies were detected by an ACE2:SARS-CoV-2 Spike S1 inhibitor screening assay, designed to assess the capacity of antibodies to block the interaction between the viral spike S1 protein and the ACE2 receptor. Although antibody titer declined within six months, a third booster dose significantly increased the magnitude of humoral response, even in aged individuals, suggesting that immune recall can improve antibody response durability. The analysis of cellular responses demonstrated that vaccination with INDUK elicited an increase in the percentage of SARS-CoV-2-specific IFN-γ producing T lymphocytes in immunized young mice and TNF-α-producing T lymphocytes in both young and aged mice. These findings not only hold immediate promise for addressing evolving challenges in SARS-CoV-2 vaccination but also open avenues to refine strategies and elevate the effectiveness of next-generation vaccines.

Clinical characteristics of pediatric noninfectious uveitis and risk factors for severe disease: a single-center study

ObjectivesWe aimed to present the demographic, clinical, laboratory, and treatment data of children with non-infectious uveitis and to evaluate the risk factors for the development of complications and the need for biological treatment.MethodPatients diagnosed with non-infectious uveitis in childhood and followed up for at least 1 year were included in the study. Demographic data, including age, gender, age at diagnosis, uveitis in first-degree relatives, and rheumatologic diseases, were obtained retrospectively from medical records. The presence of complications or the need for biologic therapy was considered a composite outcome suggesting severe disease.ResultsThe study included 123 patients (female: n = 59, 48%). The mean age at diagnosis was 14.89 ± 4.86 years. Uveitis was symptomatic in 104 patients (84.6%). Approximately one-quarter of the patients had at least one rheumatic disease (n = 35, 28.5%), the most common being juvenile idiopathic arthritis. Thirty-three patients (26.8%) had anti-nuclear antibody positivity. Biologic agents were needed in 60 patients (48.8%). Complications developed in 14 patients (11.4%). Early age at disease onset (aOR, 0.875; 95% C.I. 0.795–0.965, p = 0.007) and female gender (aOR, 2.99; 95% C.I. 1.439–6.248, p = 0.003) were significantly associated with the need for biologic treatment, while Behçet’s disease (BD) was strongly associated with uveitis-related complications (aOR, 14.133; 95% C.I. 2.765–72.231, p = 0.001).ConclusionWe suggest that among pediatric patients with non-infectious uveitis, females, those with an early age of disease onset, and those with BD need to be closely monitored due to a significantly increased risk of severe disease.Key Points• Limited data exist on the clinical course of non-infectious uveitis in children and the associated risk factors for severe disease.• Our study reveals that nearly a quarter of pediatric patients with non-infectious uveitis also have a rheumatic disease.• Among pediatric patients diagnosed with non-infectious uveitis, we observed an increased risk of severe disease in those with an earlier onset age, in female patients, and in those diagnosed with Behçet’s disease.

Clinical Features and Risk Factors for Severe Disease of Rickettsiosis: A Military Hospital-Based Study in Bangkok, Thailand

Clinical Features and Risk Factors for Severe Disease of Rickettsiosis: A Military Hospital-Based Study in Bangkok, Thailand