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Background and aim: The COVID-19 pandemic has led to a proliferation of intubation barriers designed to protect healthcare workers from infection. We developed the Suction-Assisted Local Aerosol Containment Chamber (SLACC) and tested it in the operating room. The primary objectives were to determine the ease and safety of airway management with SLACC, and to measure its efficacy of aerosol containment to determine if it significantly reduces exposure to health care workers. Method(s): In this randomized clinical trial, adult patients scheduled to undergo elective surgery with general endotracheal anesthesia were screened and informed consent obtained from those willing to participate. Patients were randomized to airway management either with or without the SLACC device. Patients inhaled nebulized saline before and during anesthesia induction to simulate the size and concentration of particles seen with severe symptomatic SARS-CoV-2 infection. Result(s): 79 patients were enrolled and randomized. Particle number concentration (PNC) at the patients' and healthcare workers' locations were measured and compared between the SLACC vs. control groups during airway management. Ease and success of tracheal intubation were recorded for each patient. All intubations were successful and time to intubation was similar between the two groups. Healthcare workers were exposed to significantly lower particle number concentrations (#/cm3) during airway management when SLACC was utilized vs. control. The particle count outside SLACC was reduced by 97% compared to that inside the device. Conclusion(s): The SLACC device does not interfere with airway management and significantly reduces healthcare worker exposure to aerosolized particles during airway management.Copyright © 2023 Elsevier Ltd
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Background. Although COVID-19 is a viral infection, it is known that antibiotics are often prescribed due to concerns about combined bacterial infection. Therefore, we aimed to analyze how many patients with COVID-19 received the antibiotic prescription as well as what kinds of factors contributed to it using the National Health Insurance database. Methods. We retrospectively reviewed claims data for adults 19 years of age and older hospitalized for COVID-19 from December 1, 2019 to December 31, 2020. According to severity classification of the National Institutes of Health guidelines, we calculated not only the proportion of patients receiving antibiotics but also days of treatment per 1000 patient days. In addition, we investigated the factors contributing to antibiotic use by linear regression analysis. Results. Of the 55,228 patients, 47% were male, 55% were older than 50 years of age, and most patients (89%) had no underlying diseases. The majority (84%, 46,576) were classified as having mild to moderate illness, with 11% (6,168) and 5% (2,484) having severe and critical, respectively. Antibiotics were prescribed in a total of 27% (15,081). While 74% of patients with severe illness and 88% of those with critical illness received antibiotic treatment, even 18% of mild to moderate cases were prescribed antibiotics. Fluoroquinolones were the most commonly prescribed antibiotics (8,348), followed by third generation cephalosporins (5,729) and beta-lactam/betalactamase inhibitors (3,822) as shown in Figure 1. Older age, severity of disease and underlying medical conditions contributed to overall prescription rates as well as days of antibiotic use significantly (Table 1). Conclusion. Although most of COVID-19 patients had mild to moderate illness, more than a quarter were prescribed antibiotics. Judicious use of broad-spectrum antibiotics is necessary for COVID-19 patients, considering the severity of disease and the risk of bacterial co-infection.
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Recent clinical observations that some coronavirus infections induced complete remissions in lymphoma patients emphasized again the potential of cancer virotherapy. Infection of cancer cells with oncolytic viruses reshapes the tumor microenvironment by activating anti-viral and anti-tumor immunity. A phase 1 clinical trial using oncolytic adenovirus Delta-24-RGD (DNX-2401) to treat recurrent malignant gliomas demonstrated activation of CD8+ T-cells and significant clinical benefits for a subset of patients. However, both anti-virus and anti-tumor immune responses are contingent on the activation of respective clones of CD8+ T-cells, which compete for clonal expansion. Thus, overexpansion of T-cells against viral antigens reduces the frequency of subdominant clones against tumor antigens. We hypothesized that inducing immune tolerance for viral antigens will decrease anti-viral immunity and in turn derepress anti-tumor immunity, resulting in enhanced efficacy of cancer virotherapy. In this work, we used nanoparticles encapsulating adenoviral antigens E1A, E1B and hexon that distributed to liver resident macrophages (P<0.0001) and induced peripheral immune tolerance. Functional experiments to restimulate immune cells with viral or tumor antigens showed that injection of nanoparticles induced virus-specific immune tolerance and redirected the focus of the immune response towards tumor peptides as measured by interferon-gamma secretion (P<0.0001). Co-culture experiments also showed increased activation of immune cells against fixed tumor cells after nanoparticle treatment (P<0.0001). Reduction of virus-specific T-cells and concurrent expansion of tumor-specific T-cell clones were further confirmed with E1A or OVA tetramers (P<0.05). Flow cytometry analysis suggested increased anti-tumor responses were due to differences in T-cell clones and not due to other immune populations including natural killer cells or myeloid-derived suppressor cells (P=0.3). Importantly, virotherapy in combination with nanoparticle-induced immune tolerance towards viral antigens in tumor-bearing mice increased the overall survival and doubled the percentage of long-term survivors compared to virus treatment alone. Our data should propel the development of a future clinical trial aiming to maximize the potential of anti-tumor immunity during cancer virotherapies.
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The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), results in serious chaos all over the world. In addition to the available vaccines, the development of treatments to cure COVID-19 should be done quickly. One of the fastest strategies is to use a drug-repurposing approach. To provide COVID-19 patients with useful information about medicines currently being used in clinical trials, twenty-four compounds, including antiviral agents, were selected and assayed. These compounds were applied to verify the inhibitory activity for the protein function of 3CLpros (main proteases) of SARS-CoV and SARS-CoV-2. Among them, viral reverse-transcriptase inhibitors abacavir and tenofovir revealed a good inhibitory effect on both 3CLpros. Intriguingly, sildenafil, a cGMP-specific phosphodiesterase type 5 inhibitor also showed significant inhibitory function against them. The in silico docking study suggests that the active-site residues located in the S1 and S2 sites play key roles in the interactions with the inhibitors. The result indicates that 3CLpros are promising targets to cope with SAR-CoV-2 and its variants. The information can be helpful to design treatments to cure patients with COVID-19.
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Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is seriously impacting health and economies all over the world. With more than 8 million diagnosed cases and close to 450.000 deaths worldwide by mid-June 2020, the need of safe and effective treatments is extremely urgent. Drug repurposing is a suitable approach to bring new treatments to the clinics in a very fast and cost-effective way. Methods: We have applied an artificial intelligence screening technology based on molecular fields to find drugs that could inhibit the SARS-CoV-2 3-chymotrypsin- like cysteine protease (3CLpro) among a library of compounds with clinical experience, approved drugs and drugs in clinical development. The results were refined by covalent docking at the catalytic domain of the protein and thirty compounds were chosen for experimental validation on a protease assay with recombinant SARS-CoV-2 3CLpro. The compounds were also tested for their inhibition of SARS-CoV and MERSCoV 3CLpro. Positive hits were further tested in a VeroE6 cell infection assay with pathogenic SARS-CoV-2 using nucleocapsid protein staining at 24h post infection as a readout. Results: Eravacycline was identified at the top positions of the screening and its potent inhibitory activity was demonstrated in vitro against recombinant SARSCoV- 2, SARS-CoV and MERS-CoV 3CL proteases, with IC50 of 1.65, 10.04 and 16.36 μM respectively. In addition, eravacycline inhibited infection of VeroE6 cells by pathogenic strains of SARS-CoV-2, with an IC50 of 30.61 μM in the absence of drug induced cell toxicity. Conclusion: Eravacycline is an FDA and EMA-approved antibiotic that was launched in the US in 2018. It is a safe drug that is known to accumulate in the lungs at concentrations that are compatible with its in vitro activity against SARS-CoV-2. This, together with its known antibacterial activity that could help prevent secondary infections in hospitalized COVID-19 patients, and the known anti-inflammatory actions of tetracyclines, warrant further research on the potential role of eravacycline for the treatment of patients with COVID-19 or infected with SARS-CoV-2 but with milder symptoms.