Evidence associating neutrophilia, lung damage, hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality in critically ill COVID-19 patients (preprint)

Background: COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis. Since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes and that they are massively recruited to infected lungs, we investigated whether metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients. Methods: Based on prospective mortality outcome, 102 critically ill-hospitalized COVID-19 patients were divided into two groups: ICU-Survivors (ICU-S, n=36) and ICU-Non-survivors (ICU-NS, n=66). Blood samples were collected from patients and control subjects to explore correlations between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils for glycolytic activities and for apoptosis using high-throughput fluorescence imaging complemented with transcriptomic analyses. Stratified survival analyses were conducted to estimate mortality risk associated with higher lactate among predefined subgroups. Results: Neutrophil counts were consistently higher in critically ill patients while exhibiting remarkably lower apoptosis. Transcriptomic analysis revealed miRNAs associated with downregulation of genes involved in neutrophils apoptosis. Both CT lung damage scores and neutrophil counts predicted mortality. Severinghaus fitting of hemoglobin oxygen saturation curve revealed a right-shift indicating lower oxygen capacity in non-survivors, which is consistent with lower blood-pH observed in the same group. Levels of blood lactate were increased in patients but significantly more in the ICU-NS relative to the control group. ROC analysis followed by Kaplan-Meyer survival analysis stratified to the obtained cut-off values showed that CT damage scores, neutrophil counts, and lactate levels are predictors of mortality within 15 days following blood collection. Conclusion: The current results implicate neutrophilia as a potential player in metabolic acidosis and deranged oxygen delivery associating SARS-CoV-2 infection thus contributing to mortality outcome.

Safety and Effectiveness of Intensive Treatments Administered Outside the Intensive Care Unit to Hematological Critically Ill Patients: An Intensive Care without Walls Trial (preprint)

Historically, admission of hematological patients in the ICU shortly after the start of a critical illness is associated with better survival rates. Early intensive interventions administered by MET could have a role in the management of hematological critically ill patients, eventually reducing ICU admission rate. In this retrospective and monocentric study, we evaluate the safety and effectiveness of intensive treatments administered by the MET in a medical ward frame. The administered interventions were mainly helmet CPAP and pharmacological cardiovascular support. Frequent reassessment by the MET at least every 8 to 12 hours was guaranteed. We analyze data from 133 hematological patients that required MET intervention. In hospital mortality was 38%; mortality doesn’t increase in patients not immediately transferred to the ICU. Only 3 patients died without a former admission in ICU; in these cases, mortality was not related to the acute illness. Moreover, 37% of patients overcame the critical episode in the hematological ward. Higher SOFA and MEWS scores were associated with a worst survival rate, while neutropenia and pharmacological immunosuppression were not. The MET approach seems to be safe and effective. SOFA and MEWS confirmed to be effective tools for prognostication.

Imaging-Based Biomarkers in Neurological Diseases-A Critical Review (preprint)

Imaging-based biomarkers have developed as an effective tool in neurology, providing vital understandings of the structural, functional, and molecular changes associated with neurological disorders. Imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) have been widely employed to record disease-related alterations in the brain. These techniques provide a wide range of biomarkers, such as functional connectivity patterns, volumetric measurements, molecular imaging agents, and perfusion parameters, enabling the correct identification of neurological disorders. These biomarkers have proven useful in early diagnosis, disease progression tracking, therapy response prediction, and surgical planning. This review emphasizes the various obstacles and limitations that are associated with imaging-based biomarkers. Technical constraints, standardization obstacles, ethical concerns, regulatory challenges, and cost-effectiveness concerns all offer substantial barriers to wider use. It is vital to overcome these challenges if imaging biomarkers are to be successfully integrated into routine clinical practice. Imaging technology advancements like high-resolution imaging, multimodal imaging, and artificial intelligence-based analysis hold immense promise for imaging-based biomarkers in the future. While more study and standardization are needed, their ongoing development and integration into clinical practice have the potential to revolutionize the diagnosis, treatment, and management of neurological disorders, resulting in better patient care and outcomes.

Cardiac Laterality: Surgical Results of Right Atrial Isomerism (preprint)

Right atrial isomerism (RAI) is a complex entity whose treatment and outcome are heterogeneous. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted; it included patients diagnosed with RAI who underwent cardiac surgery; their follow-up was from January 1, 2010 to March 31, 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients with RAI were included, the median age was 4 years (IQR 2-9.2), and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock‐Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). The use of inhaled nitric oxide was a marker of postoperative mortality in critically ill patients (OR: 10.33; 95% CI: 1.04 - 102.08; p = 0.02). The overall survival was 86.8%, with a better outcome in those who did not require reintubation (Log Rank, p < 0.01). The survival of RAI was similar to other centers of reference. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.

Distributional Response of the Rare and Critically Endangered Ilex nanchuanensis to Climate Change in East Asia (preprint)

Global climate change, dominated by climate warming, is seriously affecting the balance of global ecosystems, but the risk of species extinction is particularly high in low-altitude mountain areas. To clarify the response of the endemic and critically endangered species Ilex nanchuanensis to climate change, this study used the MaxEnt model to simulate and predict the potential habitat of I. nanchuanensis during the Last Interglacial, Last Glacial Maximum, the current period, and two future periods (the 2050s and 2070s). The results showed that the hottest monthly minimum temperature is the most important climatic factor affecting the geographical distribution of I. nanchuanensis. Furthermore, I. nanchuanensis will be at risk of population shrinkage and extinction in the future, with the center of mass moving further northwest as concentrations of greenhouse gases increase, especially in the 2070s, when its geographical distribution shrinks the most under the RCP6 scenario. Global warming is causing habitat degradation for many species and will continue to migrate to higher altitudes and latitudes in the future, seriously affecting the global ecosystem balance. Therefore, to actively respond to the impacts of climate change, protected areas should be established around the geographical distribution centers of species, and core, buffer, and experimental areas should be scientifically and rationally delineated for the conservation and cultivation of germplasm resources.

Ensitrelvir Fumaric Acid in Patients with SARS-CoV-2: A Retrospective Chart Review (preprint)

Introduction: Antivirals with differing mechanisms of action are needed for COVID 19 treatment; remdesivir is mainly used in hospitalized patients, but additional antivirals are needed in this setting. Ensitrelvir, a 3C like protease inhibitor, received emergency approval in Japan in November 2022, based on evidence of rapid symptom resolution in nonhospitalized patients, but confirmation of its efficacy in hospitalized patients is lacking. Case presentations: This case series reports outcomes for all patients who received ensitrelvir whilst hospitalized with SARS CoV 2 infection at Rinku General Medical Center, Japan (November 2022 to April 2023). Thirty two hospitalized patients received five days of ensitrelvir treatment (375/125 mg). Mean age was 73.5 years and most patients had mild COVID 19. Patients exhibited various underlying diseases, most commonly hypertension (78.1%) and chronic kidney disease (25.0%). Seven (21.9%) patients were on hemodialysis. The most common concomitant medications were antihypertensives (59.4%) and corticosteroids (31.2%); two (6.3%) patients were being treated with rituximab; 27 (84.4%) patients had viral persistence following pretreatment remdesivir failure. Following ensitrelvir treatment, all patients experienced clinical improvement as assessed by the investigator. No ICU admissions or deaths due to COVID 19 occurred. Viral clearance was recorded in 18 (56.3%) patients by day 5 and 25 (78.1%) patients at final measurement. No new safety signals were observed. Discussion: This case series represents ensitrelvir clinical efficacy in hospitalized patients with SARS CoV 2 in a real world setting. Most patients experienced persistent viral shedding despite pretreatment with antivirals, and most were considered high risk due to underlying conditions. Despite this, no patients experienced progression of COVID 19 to severe or critical disease, including those who failed prior remdesivir treatment. The antiviral activity of ensitrelvir demonstrated here indicates it is a viable treatment option for SARS CoV 2 infection in this setting. Conclusion: Ensitrelvir was associated with potent antiviral activity and positive clinical outcomes in high risk, hospitalized patients with various comorbidities. Trial Registration: UMIN000051300

CD4+ T cell senescence is associated with reduced reactogenicity in severe/critical COVID-19 (preprint)

Background: Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may affect vaccine efficacy. However, whether the senescence of T cells impact the progression to severe COVID-19 in the elderly individuals remains unclear. Methods: By using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in the peripheral blood from 100 elderly patients hospitalized for COVID-19 and compared the difference between mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit and Elispot assay respectively, cytokine production profile of COVID-19 reactive T cells as well as plasma soluble factors by cytometric bead array (CBA). Results: We found a significant elevated level of CD4+ Tsens in severe/critical disease compared to mild/moderate illness and patients with a higher level of CD4+ Tsens (>19.78%) showed a decreased survival rate as compared to those with a lower level (<19.78%), especially in the breakthrough infection. The percentage of CD4+ Tsens was negatively correlated with spike-specific antibody titers, neutralization ability and COVID-19 reactive IL-2+ CD4+ T cells. Additionally, IL-2 producing T cells and plasma levels of IL-2 were positively correlated with antibody levels. Conclusion: Our data illustrated that the percentage of CD4+ Tsens in the peripheral blood could act as an efficient biomarker for the capacity of spike-specific antibody production and the prognosis of severe COVID-19, especially in the breakthrough infection. Therefore, restoration of the immune response of CD4+ Tsens is one of the key factors to prevent severe illness and improve vaccine efficacy in older adults.

Antimicrobial peptides and other potential biomarkers of critical illness in Sars-CoV-2 patients with acute kidney injury (preprint)

Antimicrobial peptides (AMPs) are a complex network of 10-100 amino acid sequence molecules, widely distributed in Nature. Even though more than 300 AMPs have been described in mammals, cathelicidins and defensins remain the most investigated to date. Some publications examined the role of AMPs in COVID-19, but the findings are preliminary and in vivo studies are still lacking. Here, we report the plasma levels of five AMPs (LL-37, -defensin 1, -defensin 3, {beta}-defensin 1 and {beta}-defensin 3) and five cytokines (tumor necrosis factor-, interleukin-1{beta}, interleukin-6, interleukin-10, interferon-gamma and monocyte chemoattractant protein-1), in 15 healthy volunteers, 36 COVID-19 patients without Acute Kidney Injury (AKI) and 17 COVID-19 patients with AKI, since AKI is a well-known marker of worse prognosis in Sars-CoV-2 infections. We found increased levels of -defensin 1, -defensin 3 and {beta}-defensin 3, but not LL-37 or {beta}-defensin 3, in our COVID-19 population, when compared with the healthy controls, in conjunction with higher levels of interleukin-6, interleukin-10, interferon-gamma and monocyte chemoattractant protein-1, putting in evidence that these AMPs and cytokines may have an important role in the systemic inflammatory response and tissue damage that characterizes severe COVID-19.

Post-COVID-19 long term impact on lung function and quality of life: who should be concerned? (preprint)

Post-COVID-19 pulmonary sequalae are well-recognized early in the pandemic. Survivorship clinics are crucial for managing at-risk patients. However, it is unclear who requires pulmonary function test (PFT) and when PFTs should be performed. We aim to investigate for whom and how these interval PFTs should be performed. We performed a single-centre, prospective cohort study on COVID-19 survivors between 1st May 2020 to 31st April 2022. These patients were followed up at 6, 9 and 12 months with interval PFT and Short Form-36 (SF-36) Health Survey. Those with PFT defects were offered a computed tomography scan of the thorax. Of the 46 patients recruited, 17 (37%) had severe/critical illness. Compared to those with mild/moderate disease, these patients were more likely to experience DLCO defects (59% versus 17%, p = 0.005) and had lower SF-36 scores (mean physical component summary score of 45 ± 12 versus 52 ± 8, p = 0.046). These differences were most notable at 6 months, compared to the 9- and 12-months intervals. DLCO defects were also associated with older age, raised inflammatory markers and extensive CXR infiltrates. Besides interstitial-like abnormalities, obesity and undiagnosed lung conditions accounted for 39% of the PFT abnormalities. Interval PFTs can be performed earliest 6 months post-COVID-19. Patients with normal tests were unlikely to develop new abnormalities and would not require repeat PFTs. Abnormal PFTs can be followed-up with repeat PFTs 6 monthly until resolution. Non-COVID-19 differentials should be considered for persistent PFT abnormalities.

Evidence of anti-Hcp100 antibodies in COVID-19 critically ill patients with detectable anti-histoplasmin antibodies in a highly endemic area for histoplasmosis.

Patients with severe COVID-19 are at increased risk for invasive fungal infections, which are underestimated. Histoplasmosis reactivation in endemic areas should not be overlooked in this population. In a previous study, seroconversion to anti-histoplasmin antibodies by ELISA was detected in 6/39 (15.4%) patients with severe COVID-19. In this work, samples were further investigated to detect seroconversion to antibodies against the Histoplasma capsulatum 100-kDa antigen (Hcp100) by ELISA. Seroconversion to anti-Hcp100 antibodies was detected in 7/39 patients, of whom 6 also seroconverted anti-histoplasmin antibodies. These results reinforce previous findings that show histoplasmosis as an underdiagnosed fungal entity complicating COVID-19.

This study verifies that patients with severe COVID-19 at intensive care units are at risk for histoplasmosis reactivation in endemic areas. Accurate diagnosis of this deadly fungal disease among critically ill patients with COVID-19 living in endemic areas for histoplasmosis is needed.

Outcomes associated with SARS-CoV-2 reinfection in individuals with natural and hybrid immunity.

BACKGROUND: Studies comparing SARS-CoV-2 reinfection outcomes among individuals with previous infection (natural immunity) and previous infection plus vaccination (hybrid immunity) are limited. METHODS: Retrospective cohort study comparing SARS-CoV-2 reinfection among patients with hybrid immunity (cases) and natural immunity (controls) from March 2020 to February 2022. Reinfection was defined as positive PCR> 90 days after initial laboratory-confirmed SARS-CoV-2 infection. Outcomes included time to reinfection, symptom severity, COVID-19-related hospitalization, critical COVID-19 illness (need for intensive care unit, invasive mechanical ventilation, or death), length of stay (LOS). RESULTS: A total of 773 (42%) vaccinated and 1073 (58%) unvaccinated patients with reinfection were included. Most patients (62.7%) were asymptomatic. Median time to reinfection was longer with hybrid immunity (391 [311-440] vs 294 [229-406] days, p < 0.001). Cases were less likely to be symptomatic (34.1% vs 39.6%, p = 0.001) or develop critical COVID-19 (2.3% vs 4.3%, p = 0.023). However, there was no significant difference in rates of COVID-19-related hospitalization (2.6% vs 3.8%, p = 0.142) or LOS (5 [2-9] vs 5 [3-10] days, p = 0.446). Boosted patients had longer time to reinfection (439 [IQR 372-467] vs 324 [IQR 256-414] days, p < 0.001) and were less likely to be symptomatic (26.8% vs 38%, p = 0.002) compared to unboosted patients. Rates of hospitalization, progression to critical illness and LOS were not significantly different between the two groups. CONCLUSIONS: Natural and hybrid immunity provided protection against SARS-CoV-2 reinfection and hospitalization. However, hybrid immunity conferred stronger protection against symptomatic disease and progression to critical illness and was associated with longer time to reinfection. The stronger protection conferred by hybrid immunity against severe outcomes due to COVID-19 should be emphasized with the public to further the vaccination effort, especially in high-risk individuals.

Targeting CMV Reactivation to Optimize Care for Critically Ill COVID-19 Patients: A Review on the Therapeutic Potential of Antiviral Treatment.

Cytomegalovirus (CMV) reactivation has been linked to adverse clinical outcomes in critically ill patients, with emerging evidence suggesting a potential connection with severe COVID-19. Mechanisms driving this association may include primary lung injury, amplification of systemic inflammation, and secondary immunosuppression. Diagnostic challenges in detecting and assessing CMV reactivation necessitate a comprehensive approach to improve accuracy and inform treatment decisions. Currently, there is limited evidence on the efficacy and safety of CMV pharmacotherapy in critically ill COVID-19 patients. Although insights from non-COVID-19 critical illness studies suggest a potential role for antiviral treatment or prophylaxis, the risks and benefits must be carefully balanced in this vulnerable patient population. Understanding the pathophysiological role of CMV in the context of COVID-19 and exploring the advantages of antiviral treatment are crucial for optimizing care in critically ill patients. This review provides a comprehensive synthesis of available evidence, emphasizing the need for additional investigation to establish the role of CMV treatment or prophylaxis in the management of severe COVID-19 and to develop a framework for future research on this topic.

COVID-19 Severity Shifts the Cytokine Milieu Toward a Proinflammatory State in Egyptian Patients: A Cross-Sectional Study.

Despite extensive research to decipher the immunological basis of coronavirus disease (COVID-19), limited evidence on immunological correlates of COVID-19 severity from MENA region and Egypt was reported. In a single-center cross-sectional study, we have analyzed 25 cytokines that are related to immunopathologic lung injury, cytokine storm, and coagulopathy in plasma samples from 78 hospitalized Egyptian COVID-19 patients in Tanta University Quarantine Hospital and 21 healthy control volunteers between April 2020 and September 2020. The enrolled patients were divided into 4 categories based on disease severity, namely mild, moderate, severe, and critically ill. Interestingly, interleukin (IL)-1-α, IL-2Rα, IL-6, IL-8, IL-18, tumor necrosis factor-alpha (TNF-α), FGF1, CCL2, and CXC10 levels were significantly altered in severe and/or critically ill patients. Moreover, principal component analysis (PCA) demonstrated that severe and critically ill COVID-19 patients cluster based on specific cytokine signatures that distinguish them from mild and moderate COVID-19 patients. Specifically, levels of IL-2Rα, IL-6, IL-10, IL-18, TNF-α, FGF1, and CXCL10 largely contribute to the observed differences between early and late stages of COVID-19 disease. Our PCA showed that the described immunological markers positively correlate with high D-dimer and C-reactive protein levels and inversely correlate with lymphocyte counts in severe and critically ill patients. These data suggest a disordered immune regulation, particularly in severe and critically ill Egyptian COVID-19 patients, manifested as overactivated innate immune and dysregulated T-helper1 responses. Additionally, our study emphasizes the importance of cytokine profiling to identify potentially predictive immunological signatures of COVID-19 disease severity.

Clinical and microbiological patterns in critically ill patients with catheter-associated UTI: A report from Iran.

INTRODUCTION: Catheter-associated urinary tract infections (CAUTIs) are among the most common nosocomial infections with different clinical and microbiological characteristics. We studied these characteristics in critically ill patients. METHODOLOGY: This research was a cross-sectional study conducted on intensive care unit (ICU) patients with CAUTI. Patients' demographic and clinical information and laboratory data, including causative microorganisms and antibiotic susceptibility tests, were recorded and analyzed. Finally, the differences between the patients who survived and died were compared. RESULTS: After reviewing 353 ICU cases, 80 patients with CAUTI were finally included in the study. The mean age was 55.9 ± 19.1 years, 43.7% were male and 56.3% were female. The mean length of infection development since hospitalisation and hospital stay were 14.7 (3-90) and 27.8 (5-98) days, respectively. The most common symptom was fever (80%). The microbiological identification showed that the most isolated microorganisms were Multidrug-resistant (MDR) Enterobacteriaceae (75%), Pseudomonas aeruginosa (8.8%), Gram-positive uropathogens (8.8%) and Acinetobacter baumannii (5%). Fifteen patients (18.8%) died among whom infections with A. baumannii (75%) and P. aeruginosa (57.1%) were associated with more death (p = 0.005). CONCLUSIONS: Although A. baumannii and P. aeruginosa can be the most important pathogens for death, MDR Enterobacteriaceae are still a serious concern as causes of CAUTIs.

Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis.

Angiopoietin-2 (Ang-2) is associated with vascular endothelial injury and permeability in the acute respiratory distress syndrome (ARDS) and sepsis. Elevated circulating Ang-2 levels may identify critically ill patients with distinct pathobiology amenable to targeted therapy. We hypothesized that plasma Ang-2 measured shortly after hospitalization among patients with sepsis would be associated with the development of ARDS and poor clinical outcomes. To test this hypothesis, we measured plasma Ang-2 in a cohort of 757 patients with sepsis, including 267 with ARDS, enrolled in the emergency department or early in their ICU course before the COVID-19 pandemic. Multivariable models were used to test the association of Ang-2 with the development of ARDS and 30-day morality. We found that early plasma Ang-2 in sepsis was associated with higher baseline severity of illness, the development of ARDS, and mortality risk. The association between Ang-2 and mortality was strongest among patients with ARDS and sepsis as compared to those with sepsis alone (OR 1.81 vs. 1.52 per log Ang-2 increase). These findings might inform models testing patient risk prediction and strengthen the evidence for Ang-2 as an appealing biomarker for patient selection for novel therapeutic agents to target vascular injury in sepsis and ARDS.

Interferon gamma-1b for the prevention of hospital-acquired pneumonia in critically ill patients: a phase 2, placebo-controlled randomized clinical trial.

PURPOSE: We aimed to determine whether interferon gamma-1b prevents hospital-acquired pneumonia in mechanically ventilated patients. METHODS: In a multicenter, placebo-controlled, randomized trial conducted in 11 European hospitals, we randomly assigned critically ill adults, with one or more acute organ failures, under mechanical ventilation to receive interferon gamma-1b (100 µg every 48 h from day 1 to 9) or placebo (following the same regimen). The primary outcome was a composite of hospital-acquired pneumonia or all-cause mortality on day 28. The planned sample size was 200 with interim safety analyses after enrolling 50 and 100 patients. RESULTS: The study was discontinued after the second safety analysis for potential harm with interferon gamma-1b, and the follow-up was completed in June 2022. Among 109 randomized patients (median age, 57 (41-66) years; 37 (33.9%) women; all included in France), 108 (99%) completed the trial. Twenty-eight days after inclusion, 26 of 55 participants (47.3%) in the interferon-gamma group and 16 of 53 (30.2%) in the placebo group had hospital-acquired pneumonia or died (adjusted hazard ratio (HR) 1.76, 95% confidence interval (CI) 0.94-3.29; P = 0.08). Serious adverse events were reported in 24 of 55 participants (43.6%) in the interferon-gamma group and 17 of 54 (31.5%) in the placebo group (P = 0.19). In an exploratory analysis, we found that hospital-acquired pneumonia developed in a subgroup of patients with decreased CCL17 response to interferon-gamma treatment. CONCLUSIONS: Among mechanically ventilated patients with acute organ failure, treatment with interferon gamma-1b compared with placebo did not significantly reduce the incidence of hospital-acquired pneumonia or death on day 28. Furthermore, the trial was discontinued early due to safety concerns about interferon gamma-1b treatment.

Thinking Clearly: The History of Brain Dysfunction in Critical Illness.

Brain dysfunction during critical illness (ie, delirium and coma) is extremely common, and its lasting effect has only become increasingly understood in the last two decades. Brain dysfunction in the intensive care unit (ICU) is an independent predictor of both increased mortality and long-term impairments in cognition among survivors. As critical care medicine has grown, important insights regarding brain dysfunction in the ICU have shaped our practice including the importance of light sedation and the avoidance of deliriogenic drugs such as benzodiazepines. Best practices are now strategically incorporated in targeted bundles of care like the ICU Liberation Campaign's ABCDEF Bundle.

Clinical use of remdesivir in COVID-19 treatment: a retrospective cohort study.

OBJECTIVES: This study investigated remdesivir's clinical use to provide direct evidence of effectiveness for a low-middle income Asian setting. DESIGN: A one-to-one propensity score matching retrospective cohort study. SETTING: A tertiary hospital with COVID-19 treatment facilities in Vietnam. PARTICIPANTS: A total of 310 patients in standard of care (SoC) group were matched with 310 patients in SoC+remdesivir (SoC+R) group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was time to critical progression, defined as all-cause mortality or critical illness. The secondary outcomes were length of oxygen therapy/ventilation and need for invasive mechanical ventilation. Outcome reports were presented as HR, OR or effect difference with 95% CI. RESULTS: Patients receiving remdesivir had a lower risk for mortality or critical illness (HR=0.68, 95% CI 0.47 to 0.96, p=0.030). Remdesivir was not associated with a shorter length of oxygen therapy/ventilation (effect difference -0.17 days, 95% CI -1.29 to 0.96, p=0.774). The need for invasive mechanical ventilation was lower in SoC+R group (OR=0.57, 95% CI 0.38 to 0.86, p=0.007). CONCLUSIONS: This study's results showing remdesivir's benefits in non-critical patients with COVID-19 may be extrapolated to other similar low-middle income countries, allowing more regimens for limited resource areas and reducing poor outcomes and equity gap worldwide.

Perforated Stress Ulcer of the Duodenum: a Case of an Unexpected Diagnosis in a COVID-19 Patient Following Dilatation and Curettage Procedure.

Background: Stress ulcers in the upper gastrointestinal tract can arise from pathologies related to erosive or inflammatory insults in critically ill patients. The relationship between stressful bodily events and the ischemia and perforation of stress ulcers is poorly understood. Objective: We present a case of perforated stress ulcer following an abortion that was treated by dilatation and curettage (D&C) and complicated by a coronavirus disease 2019 (COVID-19) infection. Case presentation: A 40-year-old lady presented to the emergency room complaining of diffuse abdominal pain, she was recently diagnosed with an incomplete abortion and managed via a D&C procedure in an external hospital. A computed tomography (CT) scan was done at our center for the abdomen and pelvis, showing extensive pneumoperitoneum, which brought the radiologist's attention to suspect a small bowel perforation presumably accompanying a uterine perforation secondary to the D&C. There were no obvious signs of pelvic small bowel perforation in the initial CT images. The perforated duodenal stress ulcer was diagnosed the next day by a new CT scan following oral contrast ingestion and managed surgically by repair and omental patch, and no other bowel perforations were found upon surgical exploration. After the surgery, the patient was diagnosed with COVID-19, and her clinical status deteriorated gradually during the following week, and she passed away from a cardiac arrest. Conclusion: It is unclear whether septic abortion or COVID-19 has resulted in stress ulcer perforation in our patient. This case report highlights the importance of raising early suspicion in the diagnosis of stress ulcer perforation in critically ill patients to reduce the risk of morbidity and mortality.

Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE:  The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.