Severe Clinical Outcomes Research Articles

The acceptance and hesitancy of COVID-19 vaccination among chronic obstructive pulmonary disease (COPD) patients.

Severe acute respiratory syndrome coronavirus 2, which is responsible for the coronavirus disease 2019 (COVID-19), causes severe clinical outcomes in old individuals and patients with underlying diseases, including chronic obstructive pulmonary disease (COPD). Considering vaccination is still the most effective method to prevent COVID-19-associated death, it is imperative to evaluate COPD patients' attitudes toward the COVID-19 vaccine. This cross-sectional design study was conducted to assess vaccine acceptance and hesitancy among 212 COPD patients who attended the outpatient department from January 1, 2021, to July 31, 2022. All of the patients were not vaccinated and had undertaken lung function test at the time of our survey. Of 212 participants, 164 (77.4%) were willing to be vaccinated immediately while 48 (22.6%) were hesitant to be vaccinated. Compared with the acceptance group, patients who did not accept the vaccination instantly tended to have more comorbidities, like hypertension, coronary heart disease, recent cancers, and higher Modified British Medical Research Council score, or more frequent acute exacerbation. For the patients willing to be vaccinated, the main factors motivating them were an authorities-endorsed vaccine, free vaccination, and no obvious adverse reactions. For the hesitant group, no recommendation from the treating physician was the biggest obstacle for them to accept vaccination. Our results provide useful guidance for making intervention measures to enhance COPD patients' acceptance of a new COVID-19 vaccine. For those patients with comorbidities, treating physicians promoting messages framing the safety of vaccination is necessary to increase immunization rates.

Liver abscess caused by Clostridium perfringens after left hepatic trisectionectomy for perihilar cholangiocarcinoma: a case report

BackgroundClostridium perfringens sepsis has been reported to have a rapid onset and severe clinical outcome. We herein report a case of C. perfringens sepsis associated with massive intravascular hemolysis after left hepatic trisectionectomy for perihilar cholangiocarcinoma.Case presentationA 72-year-old woman underwent left hepatic trisectionectomy for perihilar cholangiocarcinoma. Her postoperative course was uneventful except for bile leakage. She was discharged on postoperative day (POD) 35. On POD 54, she was readmitted because of abdominal pain with a high fever. Although her vital signs were stable on arrival at the hospital, a laboratory examination showed a severe inflammatory reaction and hemolysis, and she had developed disseminated intravascular coagulation. Abdominal contrast-enhanced computed tomography showed a 70-mm irregular shape and low-density containing air in liver segment 6, which suggested a liver abscess. The abscess was immediately drained of pus containing air. The pus showed multiple Gram-positive bacilli, and two blood cultures showed Gram-positive bacilli and hemolysis. Empirical antibiotic therapy with vancomycin and meropenem was started because C. perfringens was detected from the preoperative bile culture. Four hours after arrival, tachypnea and decreased oxygen saturation were observed. Her general condition deteriorated rapidly with significant hypoglycemia, progressive acidosis, anemia, and thrombocytopenia. Despite rapid drainage and empiric therapy, she died six hours after her arrival. At autopsy, the abscess consisted of coagulation necrosis of liver cells with inflammatory cell infiltration, and clusters of Gram-positive large bacilli were observed in the necrotic debris. C. perfringens was detected in the drainage fluid and blood culture. She was diagnosed with a liver abscess and severe sepsis caused by C. perfringens and treated promptly, but the disease progressed rapidly and led to her death.ConclusionsSepsis caused by C. perfringens can progress rapidly and lead to death in a few hours, so prompt treatment is needed. When patients who have undergone highly invasive hepatobiliary-pancreatic surgery show hemolysis and hepatic abscesses with gas, C. perfringens should be considered the most likely bacterium.

Risk of breakthrough SARS-CoV-2 infection and clinical outcomes among vaccinated patients with type 2 diabetes.

To explore the risk of breakthrough infection among patients with type 2 diabetes (T2D) and risk of severe clinical outcomes after SARS-CoV-2 infection according to vaccination status. We conducted a population-based cohort study using South Korea's linked database of nationwide COVID-19 registry and claims data between 2018 and 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breakthrough infections were measured in1:1 propensity-score (PS)-matched fully vaccinated patients with versus without T2D (full-vaccination cohort), and HRs for all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) use, and hospitalizations after SARS-CoV-2 infection were measured in 1:1 PS-matched T2D patients with versus without full-vaccination (T2D cohort). After 1:1 PS matching, 2 109 970 patients with and without T2D were identified (age 63.5 years; 50.9% male). Patients with T2D showed an increased risk of breakthrough infections compared to those without T2D (HR 1.10, 95% CI 1.06-1.14). The increased risk of breakthrough infections was more notable among T2D patients receiving insulin treatment. However, the risk of severe COVID-19 outcomes was lower in fully vaccinated T2D patients compared with unvaccinated T2D patients (all-cause mortality: HR 0.54, 95% CI 0.43-0.67; ICU admission/MV use: HR 0.31, 95% CI 0.23-0.41; hospitalization: HR 0.73, 95% CI 0.68-0.78). While patients with T2D remain a vulnerable population to SARS-CoV-2 infection even after full-vaccination, full-vaccination was associated with a lower risk of adverse clinical outcomes after SARS-CoV-2 infection. These findings support the guidelines recommending patients with T2D as a priority vaccination group.

Feasible intervention combinations for achieving a safe exit of the Zero-COVID policy in China and its determinants: an individual-based model study

BackgroundAlthough several pathways have been proposed as the prerequisite for a safe phase-out in China, it is not clear which of them are the most important for keeping the mortality rate low, what thresholds should be achieved for these most important interventions, and how the thresholds change with the assumed key epidemiological parameters and population characteristics.MethodsWe developed an individual-based model (IBM) to simulate the transmission of the Omicron variant in the synthetic population, accounting for the age-dependent probabilities of severe clinical outcomes, waning vaccine-induced immunity, increased mortality rates when hospitals are overburdened, and reduced transmission when self-isolated at home after testing positive. We applied machine learning algorithms on the simulation outputs to examine the importance of each intervention parameter and the feasible intervention parameter combinations for safe exits, which is defined as having mortality rates lower than that of influenza in China (14.3 per 100, 000 persons).ResultsWe identified vaccine coverage in those above 70 years old, number of ICU beds per capita, and the availability of antiviral treatment as the most important interventions for safe exits across all studied locations, although the thresholds required for safe exits vary remarkably with the assumed vaccine effectiveness, as well as the age structure, age-specific vaccine coverage, community healthcare capacity of the studied locations.ConclusionsThe analytical framework developed here can provide the basis for further policy decisions that incorporate considerations about economic costs and societal impacts. Achieving safe exits from the Zero-COVID policy is possible, but challenging for China’s cities. When planning for safe exits, local realities such as the age structure and current age-specific vaccine coverage must be taken into consideration.

Escherichia coli encoding Shiga toxin subtype Stx2f causing human infections in England, 2015-2022.

Introduction. Shiga toxin-producing Escherichia coli (STEC) belong to a diverse group of gastrointestinal pathogens defined by the presence of Shiga toxin genes (stx) of which there are at least ten subtypes (Stx1a-Stx1d and Stx2a-Stx2g).Gap Statement. Initially thought to be associated with mild symptoms, more recently STEC encoding stx2f have been isolated from cases of haemolytic uraemic syndrome (HUS) and the clinical significance and public health burden require further investigation.Aim. We analysed clinical outcomes and genome-sequencing data linked to patients infected with STEC encoding-stx2f in England to assess the risk to public health.Methodology. One hundred and twelve E. coli (n=58 isolates encoded stx2f; n=54 isolates E. coli belonging to CC122 or CC722 that had eae but were negative for stx) isolated from patients' faecal specimens between 2015 and 2022 were genome sequenced and linked to epidemiological and clinical outcome data. All isolates were investigated for the presence of virulence genes and a maximum-likelihood phylogeny of isolates belonging to CC122 and CC722 was constructed.Results. There were 52 cases infected with STEC harbouring stx2f between 2015 and 2022, with the majority identified in 2022. Most cases resided in the North of England (n=39/52, 75 %), were female (n=31, 59.6 %) and/or aged five and under (n=29, 55.8 %). Clinical outcome data were available for 40/52 cases (76.9 %) and 7/40(17.5 %) were diagnosed with STEC-HUS. In the two most common clonal complexes, CC122 and CC722, the presence of the stx2f-encoding prophage correlated with the presence of additional virulence genes, astA, bfpA and cdt, located on an 85kbp IncFIB plasmid.Conclusions. Certain serotypes of E. coli harbouring stx2f cause severe clinical outcomes, including STEC-HUS. Public health advice and possible interventions are limited, as little is known about the animal and environmental reservoirs and transmission routes. We recommend more comprehensive and standardized collection of microbiological and epidemiological data, and routine sharing of sequencing data between public health agencies worldwide.

Effectiveness of SARS-CoV-2 vaccines against Omicron infection and severe events: a systematic review and meta-analysis of test-negative design studies.

A rapidly growing body was observed of literature evaluating the vaccine effectiveness (VE) against Omicron in test-negative design studies. We systematically searched papers that evaluated VE of SARS-CoV-2 vaccines on PubMed, Web of Science, Cochrane Library, Google Scholar, Embase, Scopus, bioRxiv, and medRxiv published from November 26th, 2021, to June 27th, 2022 (full doses and the first booster), and to January 8th, 2023 (the second booster). The pooled VE against Omicron-associated infection and severe events were estimated. From 2,552 citations identified, 42 articles were included. The first booster provided stronger protection against Omicron than full doses alone, shown by VE estimates of 53.1% (95% CI: 48.0-57.8) vs. 28.6% (95% CI: 18.5-37.4) against infection and 82.5% (95% CI: 77.8-86.2) vs. 57.3% (95% CI: 48.5-64.7) against severe events. The second booster offered strong protection among adults within 60 days of vaccination against infection (VE=53.1%, 95% CI: 48.0-57.8) and severe events (VE=87.3% (95% CI: 75.5-93.4), comparable to the first booster with corresponding VE estimates of 59.9% against infection and 84.8% against severe events. The VE estimates of booster doses against severe events among adults sustained beyond 60 days, 77.6% (95% CI: 69.4-83.6) for first and 85.9% (95% CI: 80.3-89.9) for the second booster. The VE estimates against infection were less sustainable regardless of dose type. Pure mRNA vaccines provided comparable protection to partial mRNA vaccines, but both provided higher protection than non-mRNA vaccines. One or two SARS-CoV-2 booster doses provide considerable protection against Omicron infection and substantial and sustainable protection against Omicron-induced severe clinical outcomes.

Classification of porcine reproductive and respiratory syndrome clinical impact in Ontario sow herds using machine learning approaches.

Since the early 1990s, porcine reproductive and respiratory syndrome (PRRS) virus outbreaks have been reported across various parts of North America, Europe, and Asia. The incursion of PRRS virus (PRRSV) in swine herds could result in various clinical manifestations, resulting in a substantial impact on the incidence of respiratory morbidity, reproductive loss, and mortality. Veterinary experts, among others, regularly analyze the PRRSV open reading frame-5 (ORF-5) for prognostic purposes to assess the risk of severe clinical outcomes. In this study, we explored if predictive modeling techniques could be used to identify the severity of typical clinical signs observed during PRRS outbreaks in sow herds. Our study aimed to evaluate four baseline machine learning (ML) algorithms: logistic regression (LR) with ridge and lasso regularization techniques, random forest (RF), k-nearest neighbor (KNN), and support vector machine (SVM), for the clinical impact classification of ORF-5 sequences and demographic data into high impact and low impact categories. First, baseline classifiers were evaluated using different input representations of ORF-5 nucleotides, amino acid sequences, and demographic data using a 10-fold cross-validation technique. Then, we designed a consensus voting ensemble approach to aggregate the different types of input representations for genetic and demographic data for classifying clinical impact. In this study, we observed that: (a) for abortion and pre-weaning mortality (PWM), different classifiers gained improvement over baseline accuracy, which showed the plausible presence of both genotypic-phenotypic and demographic-phenotypic relationships, (b) for sow mortality (SM), no baseline classifier successfully established such linkages using either genetic or demographic input data, (c) baseline classifiers showed good performance with a moderate variance of the performance metrics, due to high-class overlap and the small dataset size used for training, and (d) the use of consensus voting ensemble techniques helped to make the predictions more robust and stabilized the performance evaluation metrics, but overall accuracy did not substantially improve the diagnostic metrics over baseline classifiers.

Real-world healthcare resource utilization (HCRU) and costs among patients with hematologic or solid tumor malignancy (STM) with COVID-19 in a commercially insured or Medicare Advantage population.

e18789 Background: Patients with hematologic or STM may be at increased risk for COVID-19 and severe clinical and economic outcomes. This study estimates the incidence rate (IR) of COVID-19 in patients with hematologic and STM and evaluates the associated HCRU and costs. Methods: Patients with hematologic or STM were retrospectively identified from the HealthCore Integrated Research Database between 4/1/2018 and 3/31/2022 (study end date). The first cancer diagnosis date or 4/1/2020 was set as the index date, whichever came last. Patients were enrolled in a commercial or Medicare Advantage insurance plan for 1 year prior to index and followed until disenrollment in the health plan, study end date or death, whichever came first. COVID-19 was identified through outpatient laboratory results and diagnosis codes on medical claims. IRs were calculated for COVID-19. Hospitalized patients were classified as severe (evidence of an intensive care unit stay with noninvasive high flow oxygen or invasive respiratory/cardiovascular support or discharge status of expired) or moderate (all other hospitalizations); length of stay (LOS) and inpatient costs were calculated. Those with only a COVID-related emergency room, outpatient claim or a positive outpatient COVID-19 test were classified as mild/asymptomatic. All-cause HCRU and costs were calculated for the 30 days pre/post-COVID-19 infection. Results: In total, 895,861 patients were identified with a hematologic or STM (mean age: 63 years; 48% male) and followed for 17 months on average. Prior to index, 10% of patients were on immunosuppressive treatments. During follow up, 10% of the hematologic or STM patients developed COVID-19. The overall IR was 72.9 per 1,000 patient years, with IRs of 57.4, 8.9, and 6.6 per 1,000 patient years for mild/asymptomatic, moderate, and severe COVID-19, respectively. Among the 17% of hematologic or STM patients hospitalized for COVID-19, 43% had severe infection with a mean LOS of 13 days and total cost of $43,229, while 57% had moderate infection with a LOS of 8 days and total cost of $20,046. Total mean all-cause cost among patients with hematologic or STM who developed COVID-19 increased from $3,410 pre-infection to $9,207 post-infection, which was predominately driven by increased inpatient costs post-infection. Conclusions: Among patients with hematologic or STM, the IR of mild COVID-19 was highest (49.5 per 1,000 patient years); however, those with moderate and severe COVID-19 had high costs associated with hospitalization ($20,046 and $43,229, respectively). These findings illustrate high burden of managing moderate and severe COVID-19, as well as opportunities to improve prevention and care of COVID-19 for patients with hematologic or STM for better clinical and economic outcomes.

Efficacy and effectiveness of inactivated vaccines against symptomatic COVID-19, severe COVID-19, and COVID-19 clinical outcomes in the general population: a systematic review and meta-analysis

Inactivated, whole-virion vaccines have been used extensively in the SARS-CoV-2 pandemic. Its efficacy and effectiveness across regions have not been systematically evaluated. Efficacy refers to how well a vaccine performs in a controlled environment. Effectiveness refers to how well it performs in real world settings. This systematic review and meta-analysis reviewed published, peer-reviewed evidence on all WHO-approved inactivated vaccines and evaluated their efficacy and effectiveness against SARS-CoV-2 infection, symptomatic infection, severe clinical outcomes, and severe COVID-19. We searched Pubmed (including MEDLINE), EMBASE (via OVID), Web of Science Core Collection, Web of Science Chinese Science Citation Database, and Clinicaltrials.gov. The final pool included 28 studies representing over 32 million individuals reporting efficacy or effectiveness estimates of complete vaccination using any approved inactivated vaccine between January 1, 2019 and June 27, 2022. Evidence was found for efficacy and effectiveness against symptomatic infection (OR 0.21, 95% CI 0.16-0.27, I2=28% and OR 0.32, 95% CI 0.16-0.64, I2=98%, respectively) and infection (OR 0.53, 95% CI 0.49-0.57, I2=90% and OR 0.31, 95% CI 0.24-0.41, I2=0%, respectively) for early SARS-CoV-2 variants of concern (VoCs) (Alpha, Delta), and for waning of vaccine effectiveness with more recent VoCs (Gamma, Omicron). Effectiveness remained robust against COVID-related ICU admission (OR 0.21, 95% CI 0.04-1.08, I2=99%) and death (OR 0.08, 95% CI 0.00-2.02, I2=96%), although effectiveness estimates against hospitalization (OR 0.44, 95% CI 0.37-0.53, I2=0%) were inconsistent. This study showed evidence of efficacy and effectiveness of inactivated vaccines for all outcomes, although inconsistent reporting of key study parameters, high heterogeneity of observational studies, and the small number of studies of particular designs for most outcomes undermined the reliability of the findings. Findings highlight the need for additional research to address these limitations so that more definitive conclusions can be drawn to inform SARS-CoV-2 vaccine development and vaccination policies. Health and Medical Research Fund on COVID-19, Health Bureau of the Government of the Hong Kong SAR.

Association of Serum Vit D level with in-Hospital Outcome in Patients with Acute Myocardial Infarction

Background: Low Vitamin D (Vit D) level is associated with disease severity amongst critical acute myocardial infarction (AMI) patients. This leads to the hypothesis that Vit D plays a role in the emergence of cardiac risk factors, contributing to worsening AMI patients' short- and long-term prognoses. Therefore, there is still unclear data showing the potential impact of Vit D insufficiency or deficiency on the morbidity and mortality of AMI patients. So far, there has been no research conducted in Pakistan examining whether or not Vit D status are association to the outcome of hospitalization for coronary artery disease. Objective: The objective of the study is to examine the relationship between Vit D status on hospital admission and subsequent mortality and morbidity among patients with acute myocardial infarction. Study Design: Cross sectional observational study Study Setting: This study was conducted in the department of Interventional Cardiology, National Institute of Cardiovascular Diseases (NICVD), Karachi from Ist August 2022 to 31st January 2023. Methodology: Total 250 subjects were enrolled in the study and divided in to two groups. Group A with normal Vit D (30ng/ml or above) and Group B included lower Vit D level than 30ng/ml, all patients were suffering from AMI. Baseline demographic characteristics, including age, and gender (male/female), was recorded. The patients were tested for Vit D status and distributed in their respective groups. The history, complications, and clinical data were included. The stay in the hospital and any adverse outcomes that appeared during the stay were also recorded. The clinical results include HDL, TG, and troponin I of every patient were noted for the clinical correlation of AMI patients with adequate and deficiency of Vit D level. All the data was collected in the form of a questionnaire. The statistical analysis was done by using SPSS version 20. Results: Participants' mean ages were 53.8 and 5.9 years old. Group A (patients with low Vit D status) averaged 59.6 years of age, whereas Group B (58.9 years) had normal Vit D status. The analysis showed a statistically non- significant (p>0.05) difference in average age between the groups. There were 250 patients, with male 43.6% and female 56.4%. Men (63.2%) and women (36.8%) were in Group A. There were 71.4% males and 28.6% females in Group B. We found out the 137(60.6%) significant adverse hospital outcomes (p<0.001) in Group B and had a more significant proportion of patients with diabetes mellitus and who had smoked (p = 0.002 and 0.001, respectively). In a multivariate logistic regression smoking, diabetes, Troponin I and low vitamin showed the significant risk association (p<0.001). Practical Implication: There is still a lack of conclusive evidence on the relationship between vitamin D insufficiency or deficiency and the morbidity and mortality of AMI patients. Until far, there has been no research in Pakistan linking serum vitamin D levels to in-hospital outcomes for patients suffering from acute myocardial infarction. Conclusion: The research shows an association between low Vit D status, adverse outcomes, and clinical parameters after AMI. A low blood Vit D level is independently associated to an increased risk of developing severe clinical outcomes during hospitalization, including death after an AMI. Keyword: Vit D, AMI, Vit D deficiency, low Vit D, Cardiovascular disease

In Vitro and In Vivo Therapeutic Potential of 6,6'-Dihydroxythiobinupharidine (DTBN) from Nuphar lutea on Cells and K18-hACE2 Mice Infected with SARS-CoV-2.

We have previously published research on the anti-viral properties of an alkaloid mixture extracted from Nuphar lutea, the major components of the partially purified mixture found by NMR analysis. These are mostly dimeric sesquiterpene thioalkaloids called thiobinupharidines and thiobinuphlutidines against the negative strand RNA measles virus (MV). We have previously reported that this extract inhibits the MV as well as its ability to downregulate several MV proteins in persistently MV-infected cells, especially the P (phospho)-protein. Based on our observation that the Nuphar extract is effective in vitro against the MV, and the immediate need that the coronavirus disease 2019 (COVID-19) pandemic created, we tested here the ability of 6,6'-dihydroxythiobinupharidine DTBN, an active small molecule, isolated from the Nuphar lutea extract, on COVID-19. As shown here, DTBN effectively inhibits SARS-CoV-2 production in Vero E6 cells at non-cytotoxic concentrations. The short-term daily administration of DTBN to infected mice delayed the occurrence of severe clinical outcomes, lowered virus levels in the lungs and improved survival with minimal changes in lung histology. The viral load on lungs was significantly reduced in the treated mice. DTBN is a pleiotropic small molecule with multiple targets. Its anti-inflammatory properties affect a variety of pathogens including SARS-CoV-2 as shown here. Its activity appears to target both pathogen specific (as suggested by docking analysis) as well as cellular proteins, such as NF-κB, PKCs, cathepsins and topoisomerase 2, that we have previously identified in our work. Thus, this combined double action of virus inhibition and anti-inflammatory activity may enhance the overall effectivity of DTBN. The promising results from this proof-of-concept in vitro and in vivo preclinical study should encourage future studies to optimize the use of DTBN and/or its molecular derivatives against this and other related viruses.

Characteristics and Clinical Implications of Anti-IFN-α cytokine antibodies in partial Recombinase Activating Gene Deficiency patients before and during the COVID-19 Pandemic

Introduction: With the onset of the COVID-19 pandemic, there was increased attention on anti- IFN-α autoantibodies and its correlation with severe clinical outcomes in a large group of patients. However, this correlation has not been extensively investigated in patients with partial Recombinase Activating Gene Deficiency (pRD) who are known to have increased prevalence of anti- IFN-α autoantibodies. Therefore, there is a need to assess the presence of anti- IFN-α antibodies in pRD patients before and after the COVID-19 pandemic and explore the relationship between anti- IFN-α antibody presence and clinical outcomes. MethodsSera was collected from the whole blood after informed consent and Enzyme-Linked Immunosorbent Assay was conducted to confirm the presence of IgG-specific anti- IFN-α autoantibodies. Positive samples were determined as OD values above 3 standard deviations of the healthy donor OD mean. ResultsOur cohort included both adult (n = 13) and pediatric (n = 9) patients with variants in RAG1 and RAG2. Eleven patients (50%) out of the 22 showed elevated anti- IFN-α autoantibodies levels. Five patients (23%) were defined as low positive for anti- IFN-α autoantibodies, and 6 patients had no autoantibody titers. Of the 22 patients, 16 were symptomatic with infectious and non-infectious complications including recurrent viral and/or bacterial infections, autoimmune cytopenias, and lymphoproliferation. Ten (63%) of the symptomatic patients demonstrated high anti-IFN-α autoantibodies titers. Of the 11 patients with no or low neutralizing anti- IFN-α autoantibodies levels, 5 were asymptomatic.In temporal comparison, 16 samples were collected pre-COVID-19 pandemic; 8 samples were collected during the pandemic, 2 of which belonged to patients with samples collected before and during the pandemic. In the pre-pandemic cohort, 66% had anti- IFN-α autoantibodies. Conversely, during the COVID-19 pandemic, 89% had anti- IFN-α autoantibodies. Of note, one patient who had neutralizing anti- IFN-α autoantibodies remained positive both before and during the pandemic despite HSCT. Patient also had a SARS-CoV-2 infection in summer of 2022 with a mild clinical course.Conclusions & Next Steps: We observed persistence of anti-IFN-α autoantibodies in our cohort post-pandemic and even post-HSCT. It is unclear whether the presence of anti-cytokine antibodies are risk factor for severe COVID-19.

Postpartum Maternal Echocardiography and Its Effect on Hospital Management in Patients With Severe Preeclampsia [ID: 1378829

INTRODUCTION: Maternal echocardiography has demonstrated cardiac changes in the setting of preeclampsia; however, its effect on hospital management has not been well studied. The objective of this study was therefore to determine whether abnormal postpartum echocardiography is associated with a change in hospital management in patients with severe preeclampsia. METHODS: This was a retrospective cohort study of patients with severe preeclampsia (20–42 weeks) who received postpartum echocardiogram before discharge at a single academic institution from 2019 to 2021. The decision to obtain an echocardiogram was made by the primary physician. Patients with clinical indications for echocardiography (suspicion of heart failure and cardiomyopathy) were excluded. Hospital management outcomes included length of hospital stay, diuretic use, increasing antihypertensives, hospital readmission, and cardiology consultation. Patients with normal versus abnormal echocardiograms were compared using the chi-square test or Fisher’s exact test for categorical data and the two-sample t test or Mann-Whitney test for continuous data, with a value of P<.05 considered significant. RESULTS: One hundred forty five patients with preeclampsia who received maternal echocardiograms were included. Twenty-one (14%) had an abnormal echocardiogram, including left ventricle hypertrophy (n=9, 6%), pulmonary hypertension (n=5, 3.4%), moderate pericardial effusion (n=4, 2.7%), and enlarged atrial size (n=3, 2%). Patients with abnormal maternal echocardiograms were more likely to have a longer hospital stay (median stay of 7 days [5, 10] versus 5 days [4, 6], P=.003) and were more likely to receive diuretics (19.1% versus 4%, P=.03). There was no difference in adjustment of antihypertensives (61.9% versus 49.2%, P=.3), cardiology consultation (9.5% versus 6.5%, P=.6), or hospital readmission (4.8% versus 6.5%, P=1). CONCLUSION: Abnormal echocardiograms were associated with change in hospital management including longer hospital stay and more diuretic use. Abnormal postpartum echocardiography may be used to identify patients with more severe disease and adverse clinical outcomes. Further clinical utility of abnormal echocardiograms in severe preeclampsia should be evaluated.

SARS-CoV-2 induced HDL dysfunction may affect the host's response to and recovery from COVID-19.

Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia, dysregulation of high-density lipoprotein (HDL), and low-density lipoprotein (LDL). Furthermore, SARS-Co-2 infection is associated with noteworthy changes in lipid profile, which is suggested as a possible biomarker to support the diagnosis and management of Covid-19. This paper adopts the literature review method to obtain information about how Covid-19 affects high-risk group patients and may cause severe and critical effects due to the development of acute lung injury and acute respiratory distress syndrome. A narrative and comprehensive review is presented. Reducing HDL in Covid-19 is connected to the disease severity and poor clinical outcomes, suggesting that high HDL serum levels could benefit Covid-19. SARS-CoV-2 binds HDL, and this complex is attached to the co-localized receptors, facilitating viral entry. Therefore, SARS-CoV-2 infection may induce the development of dysfunctional HDL through different mechanisms, including induction of inflammatory and oxidative stress with activation of inflammatory signaling pathways. In turn, the induction of dysfunctional HDL induces the activation of inflammatory signaling pathways and oxidative stress, increasing Covid-19 severity. Covid-19 is linked with the development of cardio-metabolic disorders, including dyslipidemia in general and dysregulation of high-density lipoprotein and low-density lipoprotein. Therefore, the present study aimed to overview the causal relationship between dysfunctional high-density lipoprotein and Covid-19.

The relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted to hospital with COVID-19

BackgroundMicronutrients have been associated with disease severity and poorer clinical outcomes in patients with COVID-19. However, there is a paucity of studies examining if the relationship with micronutrient status and clinical outcomes is independent of recognised prognostic factors, specifically frailty and the systemic inflammatory response (SIR). The aim of the present study was to examine the relationship between micronutrient status, frailty, systemic inflammation, and clinical outcomes in patients admitted with COVID-19.MethodsRetrospective analysis of prospectively collected data was performed on patients with confirmed COVID-19, admitted to hospital between the 1st April 2020–6th July 2020. Clinicopathological characteristics, frailty assessment, biochemical and micronutrient laboratory results were recorded. Frailty status was determined using the Clinical Frailty scale. SIR was determined using serum CRP. Clinical outcomes of interest were oxygen requirement, ITU admission and 30-day mortality. Categorical variables were analysed using chi-square test and binary logistics regression analysis. Continuous variables were analysed using the Mann–Whitney U or Kruskal Wallis tests.Results281 patients were included. 55% (n = 155) were aged ≥ 70 years and 39% (n = 109) were male. 49% (n = 138) of patients were frail (CFS > 3). 86% (n = 242) of patients had a serum CRP > 10 mg/L. On univariate analysis, frailty was significantly associated with thirty-day mortality (p < 0.001). On univariate analysis, serum CRP was found to be significantly associated with an oxygen requirement on admission in non-frail patients (p = 0.004). Over a third (36%) of non-frail patients had a low vitamin B1, despite having normal reference range values of red cell B2, B6 and selenium. Furthermore, serum CRP was found to be significantly associated with a lower median red cell vitamin B1 (p = 0.029).ConclusionVitamin B1 stores may be depleted in COVID-19 patients experiencing a significant SIR and providing rationale for thiamine supplementation. Further longitudinal studies are warranted to delineate the trend in thiamine status following COVID-19.

Factors associated with negative conversion of viral RNA in hospitalized children infected with SARS-CoV-2 Omicron variant in Shanghai, China: a retrospective analysis

ObjectivesThis study aimed to identify the related risk factors and potential predictors of SARS-CoV-2 RNA negative conversion by describing the dynamics of viral shedding in infected children admitted to two hospitals from Shanghai during the Omicron variant outbreak.MethodsThis retrospective cohort included laboratory-confirmed cases of SARS-CoV-2 infection from Shanghai between March 28 and May 31, 2022. Clinical characteristics, personal vaccination, and household vaccination rates were collected through electronic health records and telephone interviews.ResultsA total of 603 paediatric patients confirmed to have COVID-19 were included in this study. Both univariate and multivariate analyses were performed to filter independent factors for the duration to viral RNA negative conversion. Data on the redetection of SARS-CoV-2 in the patients after they showed negative results on the RT‒PCR test (intermittent negative status) were also analysed. The median duration of virus shedding was 12 (interquartile range, IQR: 10–14) days. The severity of clinical outcome, personal vaccination-2doses, household vaccination rates, and abnormal defecation were factors indecently affecting negative conversion of SARS-CoV-2 RNA, suggesting that patients who had abnormal defecation or with more severe conditions would have delayed virological clearance, while patients who previously had 2 doses of vaccination or had higher household vaccination rates would have accelerated virological clearance. Loss of appetite (odds ratio (OR): 5.343; 95% CI: 3.307–8.632) and abnormal defecation (OR: 2.840; 95% CI: 1.736–4.645) were significantly associated with intermittent negative status.ConclusionThese findings could provide clues for the early identification of paediatric patients with prolonged viral shedding and could enrich the evidence for the development of prevention and control strategies, especially vaccination policies for children and adolescents.

Association of Physical Activity With SARS-CoV-2 Infection and Severe Clinical Outcomes Among Patients in South Korea

The association of moderate to vigorous physical activity (MVPA) with COVID-19 outcomes is unclear and needs to be investigated. To identify the association of longitudinal changes in MVPA with SARS-CoV-2 infection and severe COVID-19 outcomes. This nested case-control study used data from 6 396 500 adult patients in South Korean who participated in National Health Insurance Service (NHIS) biennial health screenings from period 1 (2017-2018) to period 2 (2019-2020). Patients were followed from October 8, 2020, until the diagnosis of COVID-19 or December 31, 2021. Moderate to vigorous physical activity was measured by self-report on questionnaires during both NHIS health screenings and calculated by adding the frequency (times per week) of each moderate (≥30 minutes per day) and vigorous (≥20 minutes per day) physical activity. The main outcomes were a positive diagnosis of SARS-CoV-2 infection and severe COVID-19 clinical events. Adjusted odds ratio (aORs) and 99% CIs were calculated using multivariable logistic regression analysis. A total of 183 350 patients with COVID-19 (mean [SD] age, 51.9 [13.8] years; female, 89 369 [48.7%]; male, 93 981 [51.3%]) among 2 110 268 participants were identified. For participants with vs without COVID-19, the proportion of MVPA frequency at period 2 was 35.8% vs 35.9% for physically inactive, 18.9% vs 18.9% for 1 to 2 times per week, 17.7% vs 17.7% for 3 to 4 times per week, and 27.5% vs 27.4% for 5 or more times per week. Among unvaccinated, physically inactive patients at period 1, the odds for infection increased when engaged in MVPA 1 to 2 times per week (aOR, 1.08; 99% CI, 1.01-1.15), 3 to 4 times per week (aOR, 1.09; 99% CI, 1.03-1.16), or 5 or more times per week (aOR, 1.10; 99% CI, 1.04-1.17) at period 2. Conversely, among unvaccinated patients with MVPA of 5 or more times per week at period 1, the odds for infection decreased when engaged 1 to 2 times per week (aOR, 0.90; 99% CI, 0.81-0.98) or physically inactive (aOR, 0.80; 99% CI, 0.73-0.87) at period 2. The trend of MVPA and incident infection was mitigated when participants were fully vaccinated. Furthermore, the odds for severe COVID-19 showed significant but limited associations with MVPA. The findings of this nested case-control study show a direct association of MVPA with risk of SARS-CoV-2 infection, which was mitigated after completion of the COVID-19 vaccination primary series. In addition, higher levels of MVPA were associated with a lower risk of severe COVID-19 outcomes to limited proportions.

PM10 promotes an inflammatory cytokine response that may impact SARS-CoV-2 replication in vitro.

In the last decades, a decrease in air quality has been observed, mainly associated with anthropogenic activities. Air pollutants, including particulate matter (PM), have been associated with adverse effects on human health, such as exacerbation of respiratory diseases and infections. High levels of PM in the air have recently been associated with increased morbidity and mortality of COVID-19 in some regions of the world. To evaluate the effect of coarse particulate matter (PM10) on the inflammatory response and viral replication triggered by SARS-CoV-2 using in vitro models. Peripheral blood mononuclear cells (PBMC) from healthy donors were treated with PM10 and subsequently exposed to SARS-CoV-2 (D614G strain, MOI 0.1). The production of pro-inflammatory cytokines and antiviral factors was quantified by qPCR and ELISA. In addition, using the A549 cell line, previously exposed to PM, the viral replication was evaluated by qPCR and plaque assay. SARS-CoV-2 stimulation increased the production of pro-inflammatory cytokines in PBMC, such as IL-1β, IL-6 and IL-8, but not antiviral factors. Likewise, PM10 induced significant production of IL-6 in PBMCs stimulated with SARS-CoV-2 and decreased the expression of OAS and PKR. Additionally, PM10 induces the release of IL-1β in PBMC exposed to SARS-CoV-2 as well as in a co-culture of epithelial cells and PBMCs. Finally, increased viral replication of SARS-CoV-2 was shown in response to PM10. Exposure to coarse particulate matter increases the production of pro-inflammatory cytokines, such as IL-1β and IL-6, and may alter the expression of antiviral factors, which are relevant for the immune response to SARS-CoV-2. These results suggest that pre-exposure to air particulate matter could have a modest role in the higher production of cytokines and viral replication during COVID-19, which eventually could contribute to severe clinical outcomes.

The Antiviral Effect of Nirmatrelvir/Ritonavir during COVID-19 Pandemic Real-World Data.

Vaccination against SARS-CoV-2 and the prevalence of Omicron variants have reduced the risk of the severe clinical progress of COVID-19. However, the risk of breakthrough infections has increased, and early administration of an effective antiviral treatment is significant in order to prevent the severe progression of COVID-19 in vulnerable patients with comorbidities. Adults with confirmed SARS-CoV-2 infection were included in a matched-pair retrospective study based on age, gender, comorbidities and vaccination status. They were divided into two groups: group A (n = 200) consisted of outpatients at increased risk of severe clinical progress who were treated with nirmatrelvir/ritonavir and group B (n = 200) consisted of non-hospitalized patients who did not receive antiviral treatment. Demographic data, clinical outcome (death, intubation), days of hospitalization, time for recovery, adverse events and treatment compliance were reported. The median age (75.24 ± 13.12 years in the study group and 76.91 ± 14.02 years in the comparison group) and the proportion of males (59% vs. 60.5%, respectively) were similar between the two groups. A total of 6.5% of patients in group A and 10.5% in group B were unvaccinated against SARS-CoV-2. Three patients from group A (1.5%) and one hundred eleven (55.5%) from group B required hospitalization. The duration of hospitalization (3 days vs. 10 days in group B, p < 0.001) and the total time needed for recovery (5 days vs. 9 days, p < 0.001) was shorter in the study group. A rebound of SARS-CoV-2 infection within 8-12 days after diagnosis was documented in 6.5% of patients in group A and 8% of patients in group B. Oral treatment with nirmatrelvir/ritonavir in high-risk non-hospitalized patients was safe and effective in preventing the severe clinical progress of COVID-19 pneumonia. Early administration of antiviral agents in vulnerable outpatients combined with a full vaccination scheme is significant in order to avoid hospitalization and severe clinical outcomes.

Glycaemic profile of children undergoing anaesthesia (GLYCANA) at Mercy James Centre in Malawi: an observational study

BackgroundHypoglycaemia and hyperglycaemia may develop during anaesthesia and surgery in children and can lead to severe adverse clinical outcomes. No study, as far as we know, has investigated glucose homeostasis in children undergoing surgery in Malawi. The aim of this study was to assess perioperative glucose levels of the children undergoing anaesthesia at Mercy James Centre (MJC) for Paediatric Surgery, Blantyre, Malawi.MethodologyThis was an observational cross-sectional study. We looked at 100 children aged 1 day to 15 years anaesthetised at MJC. Data were analysed using SPSS 28. Student t test and Analysis of the variance (ANOVA) were used to compare means. The level of significance was 5%.ResultsMale children represented 68%. The median age was 2.2 years. Sixten percents of patient were underweight. Fasting times were prolonged for 87%. Maintenance IV fluid with 2.5% dextrose was given to 14%. Overall, there was a significant increase of glycaemia from induction of anaesthesia to the end of the procedure. Hypoglycaemia was rare. The mean fasting glycaemia was 99.04 mg/dL ± 1.8, 116.95 mg/dL ± 34.2 at 30 min into the procedure and 127.62 mg/dL ± 46.8 at the end of the procedure. The differences in means were statistically significant (p < 0.001). Prolonged fasting times was associated with lower blood glucose means whereas nutrition status, type of the procedure, addition of dextrose in the fluid, and duration of procedure were associated with higher glycaemia means.ConclusionGlycaemia increases under anaesthesia and surgery. Recommended fasting times, optimising nutritional status, when possible, no dextrose or lower than 2.5% dextrose in IV maintenance fluid are possible strategies to maintain blood sugar homeostasis during paediatric surgery and anaesthesia.