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Background Messenger ribonucleic acid (mRNA) is a powerful tool for transferring genetic information. Its advantages include potent but transient gene expression without risk of genomic insertion, tailorable immunogenicity to match therapeutic application, and the potential for efficient, scalable manufacturing.1 The recent success of mRNA-based SARSCoV- 2 vaccines has inspired interest in mRNA as a cancer therapy to deliver immunostimulatory molecules and tumor antigens. However, clinical translation is limited by mRNA instability at physiological conditions and inefficient in vivo delivery.2 A reliable, non-toxic, and stabilizing in vivo delivery system for immunotherapeutic mRNA would help to advance mRNA as a viable cancer therapy. Here, we utilized calcium phosphate mineral-coated microparticles (MCMs) as a delivery system for mRNA-lipid complexes (lipoplexes) to transfect melanoma cells. Methods MCMs were prepared as previously described3 by suspending beta-tricalcium phosphate particles in modified simulated body fluid under rotation for 7 days at 37degreeC, refreshing the media daily. MCMs were then washed in deionized water and freeze dried. Custom-synthesized reporter or therapeutic mRNA constructs were complexed with a lipidic transfecting agent through mixing, then resulting lipoplexes were incubated briefly with MCMs to facilitate electrostatic binding to the porous CaP coating (figure 1a). Loaded MCMs or soluble lipoplexes were added to B16F10 murine melanoma cell culture, and transfection was measured through various assays, including fluorescence microscopy, bioluminescence, and enzymelinked immunosorbent assays. Results Scanning electron microscopy was used to verify platelike, porous coating morphology following MCM fabrication (figure 1b). MCMs enhanced transfection of B16F10 melanoma cells compared to soluble mRNA lipoplex delivery. This was demonstrated with reporter constructs encoding enhanced green fluorescent protein (eGFP, figure 1c) and Gaussia luciferase (G-Luc), as well as with a therapeutic construct encoding interleukin 15 (IL-15), a T cell growth factor. Timelapse imaging also revealed more rapid transfection with MCMs. A close proximity of cells to MCMs was observed as necessary for transfection. Conclusions We demonstrated that MCMs efficiently and locally deliver mRNA lipoplexes to melanoma cells and cause elevated levels of protein expression compared to soluble lipoplex delivery. This enhanced delivery profile makes MCMs a potential drug delivery platform for future in vivo tumor studies and clinical translation. (Figure Presented).
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Aseptic meningitis and encephalitis contribute to acute and chronic neurological disorders throughout the world and have a greater than 5% fatality rate in the United States. Unfortunately, in the vast majority of cases, no causative organism is isolated using conventional molecular and immunologic assays. This is in part due to assays that require prior knowledge of specific virus(es), need for large sample volumes, and significant time to obtain results which precludes usage in the clinical setting. To address these limitations to effectively detect virus in CSF samples, we aimed to use a novel technology called VIRRION (virus capture with rapid Raman spectroscopy detection and identification). VIRRION is a combined microfluidic device and carbon nanotube array for enrichment and capture of virus particles in body fluids that uses Raman spectroscopy for rapid detection of virus in which machine learning algorithms are applied to spectra to develop virus 'signatures'. While VIRRION has been successfully used for respiratory isolates, including SARS-COV-2, here we propose to extend this system for the analysis of cerebrospinal fluid from patients with neurologic disease in which viruses are suspected. In preliminary results with samples containing viruses in culture media, we have demonstrated Raman spectral peaks specific to each cultured virus where machine learning analysis showed a sensitivity of 99%. VIRRION offers the capability to capture virus particles while allowing the background fluids to flow through, thus controlling for variation in the background fluid signatures in clinical samples. These early results show that VIRRION is a promising technology for the rapid detection of virus in the CSF.
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SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: COVID-19 is a systemic infectious and inflammatory disease, with multifactorial immunosuppression during the recovery phase which predisposes to serious infections. Although the gastrointestinal (GI) system is often affected in post-acute COVID-19 patients, liver abscess formation is rare. Here, we present a case of septic shock caused by a bacterial liver abscess in a survivor of severe COVID-19. CASE PRESENTATION: 78-year-old man with no past medical or surgical history was admitted to an outside hospital (OSH) with severe COVID-19 pneumonia and discharged after 14 days. He required high flow nasal cannula and was treated with Remdesevir, Dexamethasone, and Baricitinib. D-dimer was elevated without evidence of acute venous thromboembolism. Four weeks later he returned to the OSH due to dyspnea and was found to be hypotensive and hypoxemic. Laboratories showed leukocytosis, hyperlactatemia, and mild elevation of total bilirubin and transaminases. Whole-body CT scan revealed a small RUL pulmonary embolus and a 7cm multifocal loculated complex fluid collection indicative of a left hepatic lobe abscess. He was managed with supplemental oxygen, anticoagulation, broad-spectrum antibiotics, IV fluids, and vasopressors and transferred to our hospital for abscess drainage. The liver abscess was aspirated after an abdominal MR confirmed the findings and the septic shock subsequently resolved. Body fluid and blood cultures grew pan-sensitive Klebsiella pneumoniae. Antibiotics were narrowed to levofloxacin. He remained hemodynamically stable and was discharged home. DISCUSSION: In our patient, the underlying cause of bacterial inoculation of the liver and abscess formation remains unclear and is not fully explained by drug-induced immunosuppression given the frequency with which these medications are used. Hepatic abscesses often develop after liver injury and, in COVID-19, multiple mechanisms of liver injury have been proposed which may predispose to abscess formation. Specifically, in our case, it is likely that hypoxic hepatitis and arterial/venous thrombosis from hypercoagulability played a role in abscess formation given the need for supplemental oxygen and the presence of a pulmonary embolism. Additionally, in COVID-19, increased hepatobiliary expression of ACE2 may contribute to direct viral cytotoxicity of the liver and substantial dysbiosis may lead to cholestasis and bacterial translocation. CONCLUSIONS: Our case is unique and underlines the importance of having a high index of suspicion and monitoring for "occult infections,” such as liver abscesses in the COVID-19 recovery phase, even in those without prior GI medical history and with non-specific signs and symptoms. Further elucidation of the cause of liver injury and abscess formation are warranted;however, early identification and treatment can reduce morbidity and mortality. Reference #1: Nalbandian, A., et al, 2021. Post-acute COVID-19 syndrome. Nat Med, 27(4): 601–615. Reference #2: Liemarto, A.K., et al, 2021. Liver abscess with necrosis in post COVID-19: A case report. Ann Med Surg (Lond), 72: 103107. Reference #3: Alhaddad O., et al, 2022. A case report of COVID-19 evoked cholangitic liver abscess. Egypt Liver J, 12(1):5. DISCLOSURES: No relevant relationships by Christian Ascoli No relevant relationships by Anna Duchnowska No relevant relationships by Tirsa Ferrer Marrero No relevant relationships by Manasa Reddy
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Objective: Some infectious diseases spread very fast, viruses such as COVID-19, once infected, do great harm to human body. In order to control the spread of infectious diseases, it is necessary to collect microbial samples of infectious diseases for research, understand the nature of infectious diseases and take reasonable measures to prevent them. However, in some places where infectious diseases with great transmission power have occurred, such as hospitals, sending personnel to collect microbial samples is in danger of being infected. In order to reduce this risk, UAV (unmanned aerial vehicle) can be used to collect microbial samples of infectious diseases. Low altitude UAV has the advantages of low cost, high flexibility and easy rapid deployment. Methods: Using wireless communication technology to control the UAV cluster network is a common method of UAV wireless remote control. With its flexible flight characteristics and good channel characteristics, UAV can stay in the air for a long time, and can also be used as an air base station to provide various communication services. If an infectious disease occurs in an area, then use the aviation UAV to enter the highly dangerous infectious disease area. The UAV is equipped with corresponding sensors to identify the specific situation of the disease, and then use special tools to collect microbial samples of infectious diseases, Including exudates, secretions, tissues, various disease body fluids, etc., for researchers to analyze the nature of infectious disease samples. Results: Various infectious diseases with high infectivity, such as COVID-19, are easy to spread. For this highly infectious virus, even if people use appropriate equipment and preventive measures, they may still be infected. The collection of microbial samples of infectious diseases by aviation UAV can prevent the staff from directly contacting with the virus of infectious diseases. This way improves the safety of the staff, which is a very effective way to prevent infectious diseases. Conclusion: Taking advantage of the flexibility of aerial UAV, some microbial samples with highly infectious diseases are collected, which is not only suitable for areas with infectious diseases, but also suitable for hospital wards and other places. Infectious diseases always have certain transmission routes and conditions, infectious diseases can be transmitted in many ways. The same infectious disease can be transmitted in many different ways. Respiratory infectious diseases, such as COVID-19, are mainly transmitted through the respiratory tract. Pathogens exist in the air or form aerosols, forming an air transmission characteristic. Once inhaled into the body, healthy people may be infected. However, as long as we master the mode of transmission of diseases and pay due attention to prevention, we can eliminate the occurrence of infectious diseases. In some areas with poor sanitary conditions and poor hygiene habits, there are more cases of infectious diseases. Therefore, for the prevention of various infectious diseases, especially COVID-19 viruses, we must strengthen personal disinfection, strictly isolate the source of infection, and make reasonable arrangements in management measures to reduce the occurrence of infectious cases.
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Introduction: Sepsis is a common cause of morbidity and mortality with no gold standard diagnostic test for detecting sepsis. Blood cultures are a frequent diagnostic step but the results take at least 48 hours and timely recognition of infection and initiation of appropriate antibiotics remain crucial in the treatment of sepsis. Biomarkers thus come in handy for rapid diagnosis and risk stratification. Objectives: Primary objective: To assess the diagnostic and prognostic value of procalcitonin (PCT), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP) levels in differentiating between Gram-negative and Gram-positive sepsis patients. Secondary objective: To determine the relationship between serum PCT, IL-6, ferritin, and CRP levels and isolated sepsis pathogens. Materials and methods: We are conducting a cross-sectional study for a period of 2 years on 360 adult patients admitted in an intensive care unit (ICU) of a tertiary care hospital with sepsis or septic shock. Our exclusion criteria are patients with burns, suspected or documented non-bacterial infections, viral hepatitis, iron overload states, and active COVID-19 infection. We are using convenience sampling. Demographic details of patients are collected. Blood is drawn for estimation of the four aforementioned biomarkers as well as body fluids of the patient based on clinical suspicion are sent for microbiological evaluation on admission to ICU before administration of antibiotics. Based on the culture reports, patients are classified as culture-positive or culture-negative sepsis and the biomarkers in each group are analyzed for diagnostic and prognostic accuracy. The primary outcome of the study is the survival or death of the patient while the secondary outcome is the number of days of ICU stay. During the time of submission, only 25 patients had been recruited and an interim analysis is being conducted. Results: During the time of submission, only 25 patients had been recruited and an interim analysis is being conducted. The mean age of our patients was 57.16 years. The study population was predominantly males (20 subjects) with ten subjects of urosepsis, three with pancreatitis, two with pneumonia, and the remaining ten had a miscellaneous diagnosis. The mean values of the inflammatory markers were as follows: PCT = 16.672 (±24.3495), CRP = 85.8428 (±62.1224), IL-6 = 610.268 (±723.3846), and ferritin = 625.0832 (±628.5289). The p value of the biomarkers is <0.00001 and is significant at p < 0.05. The following combinations of biomarkers were found to be statistically significant - PCT with IL-6 (p = 0.00018), PCT with ferritin (p = 0.00012), CRP with IL-6 (p = 0.00116), and CRP with ferritin (p = 0.00079). The sensitivity of CRP and IL-6 was 100% while specificity was highest for PCT at 50%. Eight of the subjects had Gram-negative sepsis. The mean days of hospitalization were 19.92 days. Eight of the subjects died contributing to a mortality rate of 3.2 per 10 subjects. Conclusion: The combination of biomarkers reflects different aspects of sepsis pathophysiology and would be feasible to incorporate as a point of care testing. The biomarker panel that would provide diagnostic information for the investigation of a patient with suspected sepsis earlier than cultures is PCT with IL-6 and ferritin.
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Background & Objective: Every operating room has been associated with a variety of occupational hazards, but not many studies have been conducted to assess and address these hazards. We used a qualitative approach to explore operating room personnel's experiences of workplace hazards and how these hazards threaten their occupational safety and health (OSH). Methodology: This qualitative study was conducted in five teaching hospitals in the south-west of Iran from February 2019 to March 2021. The sample was 24 operating room personnel who were selected under convenient sampling technique. Data were collected using semi-structured, individual interviews, document review and non-participant observation. The collected data were analyzed according to the qualitative content analysis method using MAXQDA v. 2020. Results: After prolonged analysis of the data, the researchers extracted 644 codes, 13 subcategories, 4 categories, and 1 main theme. The main theme of the study was working in a context of occupational hazards. Conclusions: Operating rooms are full of potential dangers, which, when combined with the personnel's negligence and management inefficiencies, increase the risk of occupational health and safety. Therefore, making working conditions safe by providing adequate personal protective equipment (PPE), in-service training, and identifying and managing the causes of personnel negligence are recommended. Moreover, strategies should be introduced to manage stress and conflicts among the healthcare personnel, thus controlling psychological hazards.
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Introduction: Since December 2019, coronavirus disease 2019 (COVID-19), which is caused by SARSCoV- 2, has spread locally in Wuhan, China, and later on, a worldwide outbreak occurred. Invasive fungal infections can cause complications in critically ill immunocompromised patients of COVID-19, especially those admitted to intensive care units and who required mechanical ventilation. Candida albicans have been the most common pathogenic species, followed by other Candida spp. Mannan is a major component of the Candida cell wall and can be detected by the enzyme-linked immunosorbent assay (ELISA) in blood and other fluids. Invasive pulmonary aspergillosis is considered a lifethreatening infection, especially among immunocompromised patients. COVID-19-associated pulmonary aspergillosis has emerged as an important complication among patients in the intensive care units. Galactomannan (GM) is a major cell-wall component of Aspergillus spp. and can be found in body fluids. Blood GM can be detected by the enzyme immunoassay. The aim of the current study is to assess the frequency of aspergillosis and candidiasis among COVID-19 patients in some hospitals in Baghdad by using GM and mannan biomarkers. Methods: During the period from February 2020 to May 2021, 175 COVID-19 blood samples of patients were collected and a sandwich ELISA test was performed to detect GM Ag of Aspergillus spp. and mannan Ag of Candida spp. Results: Regarding C-reactive protein (CRP), significant differences were seen among Aspergillus/- COVID-19 patients ( p 0.029). Regarding sex and age group, the results indicated that of a total of 175 adult patients with positive COVID-19, more than half of the patients were males. Regarding the distribution of mannan Ag and GM Ag in COVID-19 patients, it was seen that out of the 175 patients, 167 (95.43%) Candida mannan Ag were negative and only 8 (4.57%) were positive, and 170 (79.14%) Aspergillus GM Ag were negative and only 5 (2.86%) were positive. It was also seen that 2 patients (1.14%) who had both Candida mannan and Aspergillus GM were positive and 173 (98.6%) were negative. No statistically significant difference was seen in candidiasis and aspergillosis among patients with COVID-19 regarding age group, sex, underlying chronic diseases (hypertension and diabetes mellitus), and biochemical tests. Conclusion: COVID-19 infections increased with age and were seen more in males than in females. The percentage of infection with C. albicans and Aspergillus spp. among COVID-19 patients was not significant, and this may come from the random collection of samples from patients with different stages of illness. A significant correlation was found between Aspergillus GM Ag in COVID-19 patients and the CRP test.
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Several reviews and models have suggested that indirect contact transmission involving contaminated surfaces could be the predominant transmission route for certain respiratory viruses. Indeed, contaminated environmental surfaces are considered to represent a significant vector for hospital-acquired viral infections. For any environmental contamination to be relevant, a virus should not only remain infectious on the recipient surface but also persist at a sufficient concentration to enable it to reach the respiratory tract via finger contamination. In general terms, the potential of a fomite to spread a given infectious agent is directly related to the capacity of the agent to survive on that surface. The surface stability of viruses is generally influenced by the type of surface, environmental factors such as relative humidity and temperature, and the presence of body fluid secretions (respiratory excretions, feces, blood.). We investigated the influence of such parameters on the stability of several alpha and betacoronaviruses, including 3 variants of SARS-CoV-2 (SARS-CoV-2 variant 2020, SARS-CoV-2 variant UK and SARS-CoV2 variant delta), on stainless steel discs and porous surface corresponding to borosilicate discs. Assays were done at 7 °C and 25 °C with a relative humidity of 65%. Artificial mucus/saliva or BSA/yeast extract mixtures were used as fluid mimetics for respiratory and enteric viruses, respectively. Our results showed significant variable stability of the viruses depending on both the porous/non-porous nature of the surfaces and the temperature. Beneficial or negative impacts of the body fluids were also observed. This study characterizes for the first time the behaviour of human and animal coronaviruses, including highly pathogenic betacoronaviruses, on several surfaces with fixed environmental parameters.
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In view of the ongoing pandemic, healthcare workers are rightfully concerned about performing autopsies, due to the risk of infection. An autopsy surgeon and his/her team can inadvertently be exposed to infectious diseases. Use of appropriate personal protective equipment (PPE) and mortuaries equipped with negative pressure are essential to protect the autopsy team from exposure to potentially infected bodies, bodily fluids, tissues, and aerosolized particles. Unfortunately, in a developing country like India, due to a lack of funding most mortuaries have only the bare minimum facilities. Taking these issues into consideration, the authors have developed a prototype of a Low-Cost Infection Containment Chamber (LCICC) within which autopsies or sample collection from suspected or confirmed highly infectious cadaver can be performed. This innovation could provide infectious disease experts and pathologists a safer alternative to collect specimens to aid in the management outbreaks of highly infectious diseases.
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Introduction: Despite numerous clinical scoring systems, outcome modeling for COVID-19 patients with sepsis remains poor. To address this deficit, we assessed the impact of culture positivity on in-hospital mortality for COVID-19 patients with sepsis. We report that culture positive sepsis derived from blood, bronchoalveolar lavage (BAL), or cerebrospinal fluid (CSF) is a stronger prognostic indicator of in-hospital mortality for COVID-19 patients than the Sequential Organ Failure Score (SOFA). These results support inclusion of culture status in future clinical scoring systems. Methods: The cohort was defined by inpatients from 03/20 to 09/21 with a COVID-19 + test (PCR, rapid-antigen, antibody) and septic event (n = 792) as defined by Sepsis-3 guidelines [1]. Each patient's worst SOFA score was computed during their suspected infection window (defined as 24 h prior to and 48 h after the first antibiotic administration or body-fluid culture taken). Study groups included culture positive (n = 478) and culture negative (n = 314) sepsis patients. Charlson comorbidity scores for each patient were calculated prior admission. Positive predictors of in-hospital mortality were assessed with multivariate logistic regression and evaluated for statistical significance using the CAR-ANOVA Type-III test with Bonferroni method. Results: Multivariate logistic regression analysis showed that culture positivity had the greatest adjusted odds ratio (OR: 3.19, 95% CI: 2.09- 4.98, p < 0.001, corr. p < 0.001), compared to worst SOFA score (OR: 1.91, 95% CI: 1.61-2.27, p < 0.001, corr. p < 0.001), patient age (OR: 1.46, 95% CI: 1.20-1.80, p < 0.001, corr. p < 0.001), male sex (OR: 1.67, 95% CI: 1.15-2.42, p < 0.006, corr. p = NS) and comorbidity score (OR: 1.02, 95% CI: 0.84-1.22, p = NS, corr. p = NS) (Fig. 1). Conclusions: Culture positivity is a strong prognostic indicator of inhospital mortality for COVID-19 sepsis patients and warrants investigation as a candidate variable for future clinical outcome algorithms.
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The sound management of health care waste has been noted to be a major challenge facing developing countries especially Africa. This has resulted in several health threats to already ailing health systems. The situation could have worsened in recent years considering the current challenges the continent is facing in the midst of the COVID-19 pandemic. The health sector has been confronted with increased volumes of highly infectious wastes from the body fluids of patients patronising health facilities while the use of personal protective equipment (PPEs) such as nose masks, gloves, aprons and face shields during the pandemic have also increased due to the stringent protective practices recommended by the World Health Organization as well as several national ministries of health. This has resulted in the use of millions of PPEs both by health workers and patients. Studies have found that the coronavirus is capable of surviving on surfaces such as plastics, glass and fabric for up to nine days. The wastes from used PPEs therefore end up as wastes potentially infected with micro-organisms including the coronavirus which may persist in the environment for several days. Improper management of these wastes are therefore likely to pose environmental, occupational and public health threats especially in developing countries where sustainable waste management practices are yet to be achieved. Globally, healthcare workers represent less than 3% of the population but account for 14% of COVID-19 cases reported to WHO. It is a challenge to provide corresponding statistics in developing countries, because to date, few countries are able to provide complete counts of infections and deaths among health care works related to COVID-19. To what extent is inadequate management of health care waste likely to be contributing to morbidity and mortality from COVID 19 and other infections among heath care and waste management workers within and outside the confines of healthcare establishments? With the aid of some country examples, the paper demonstrates weaknesses in the waste management cycle that have the potential to militate against the occupational health and safety of healthcare and waste management workers. Other contributory factors to high morbidity and mortality hinge on weaknesses in IPC and WASH measures among others. The paper concludes that a dedicated health care waste management system facilitated by national and sub-national policies and guidelines, human capacity development and public-private partnerships for resource mobilization and investments to support essential infrastructure are needed for sustainability of the waste management function. Closely linked and integral to these measures is the existence of functional national and institutional infection prevention and control (IPC) and WASH programs. Also important are ensuring protection (through access to training, vaccines, testing and psychosocial support) as well as decent work conditions that include protection against excessive workloads and reasonable wages.
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The novel Coronavirus COVID-19 is wrecking a havoc across the globe and has been declared as a pandemic by WHO. Apart from transmission and shedding of the virus through respiratory secretions in the form of droplets (mainly), several studies have shown the presence of the virus in various samples such as stool, urine and occasionally in blood, semen, tears and breastmilk. Whereas government authority guidelines consider a person as cured from COVID-19 when along with clinical improvement no more virus can be detected primarily on respiratory samples along with clinical improvement; the persistence of the virus in these body fluids even after clinical recovery and negative RT-PCR test results on respiratory samples, has raised many questions about the elusive nature of this novel virus along with the possibility of other routes of transmission of this virus in the community. Although studies performed till now across the globe on persistence of SARSCOV-2 in various body fluids are sparse, in this review we would like to present and analyse the results of those studies performed globally on the aforesaid topic to get a better insight of this side of the COVID-19 story.