Personal protective equipment for COVID-19 among healthcare workers in an emergency department: An exploratory survey of workload, thermal discomfort and symptoms of heat strain.

OBJECTIVES: To examine workload, thermal discomfort and heat-related symptoms among healthcare workers (HCWs) in an Australian ED during the COVID-19 pandemic. METHODS: A cross-sectional study design was employed among HCWs in an ED at a metropolitan hospital in Brisbane, Australia. Respondents provided demographic information including their self-reported age, sex, height, weight, role (e.g. doctor, nurse), and whether they wore personal protective equipment (PPE) during their shift, rated as either Full PPE, Partial PPE, or usual uniform or scrubs. The workload of HCWs was assessed with the National Aeronautics and Space Administration's task load index (NASA-TLX). Thermal discomfort was evaluated using scales from the International Organisation for Standardisation. Responders rated their subjective heat illness using the Environmental Symptoms Questionnaire. RESULTS: Fifty-nine HCWs completed the survey (27 male, 31 female, one prefer not to answer). Overall workload from the NASA-TLX was 64.6 (interquartile range [IQR] 56.5-73.3) for doctors, 72.5 (IQR 63.3-83.3) for nurses and 66.7 (IQR 58.3-74.17) for other staff, representing moderate to high ratings. Eighty-one percent reported thermal sensation to be slightly warm, warm, or hot, and 88% reported being uncomfortable, ranging from slightly to extremely. Ninety-seven percent reported at least one heat-strain symptom. More than 50% reported light-headedness or headache and approximately 30% reported feeling dizzy, faint, or weak. CONCLUSIONS: ED HCWs experience thermal discomfort when wearing PPE. Combined with their workloads, HCWs experienced symptoms related to heat strain. Therefore, careful consideration should be given to managing heat strain among HCWs when wearing PPE in an ED.

Expressive Interviewing Agents to Support Health-Related Behavior Change: A Study of COVID-19 Behaviors.

BACKGROUND: Expressive writing and motivational interviewing are well-known approaches to help patients cope with stressful life events. While these methods are often applied by human counselors, it is less well understood if an automated AI approach can benefit patients. Providing an automated method would help expose a wider range of people to the possible benefits of motivational interviewing, with lower cost and more adaptability to sudden events like the COVID-19 pandemic. OBJECTIVE: This study presents an automated writing system and evaluates possible outcomes among participants with respect to behavior related to the COVID-19 pandemic. METHODS: We developed a rule-based dialogue system for "Expressive Interviewing" to elicit writing from participants on the subject of how COVID-19 has impacted their lives. The system prompts participants to describe their life experiences and emotions, and provides topic-specific prompts in response to participants' use of topical keywords. In May-June 2021, we recruited participants (N=151) via Prolific to complete either the Expressive Interviewing task or a control task. We surveyed participants immediately before the intervention, immediately after, and again two weeks after the intervention. We measured participants' self-reported stress, general mental health, COVID-related health behavior, and social behavior. RESULTS: Participants generally wrote long responses during the task (53.3 words per response). In aggregate, task participants experienced a significant decrease in stress in the short-term (~23% decrease, P<.001) and a slight difference in social activity compared to the control group (P=.030). No significant differences in short-term or long-term outcome were detected between participant sub-group (e.g., male versus female participants), except for some within-condition differences by ethnicity (e.g., higher social activity among African American people participating in Expressive Interviewing vs. participants of other ethnicities). For short-term effects, participants showed different outcomes based on their writing. Using more anxiety-related words was correlated with a greater short-term decrease in stress (R=-0.264, P<.001), and using more positive emotion words was correlated with a more meaningful experience (R=0.243, P=.001). As for long-term effects, writing with more lexical diversity was correlated with an increase in social activity (R=0.266, P<.001). CONCLUSIONS: Expressive Interviewing participants exhibited short term positive changes in mental health, but not long-term, and some linguistic metrics of writing style were correlated with positive change in behavior. While there were no significant long-term effects observed, the positive short term effect suggests that the Expressive Interviewing intervention could be used in cases where a patient lacks access to traditional therapy and needs a short-term solution.

Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries, can effectively trap SARS-CoV-2 virus-like particles in fresh human airway mucus. IN-006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

Stable nebulization and muco‐trapping properties of regdanvimab/IN‐006 support its development as a potent, dose‐saving inhaled therapy for COVID‐19

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID‐19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self‐dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc‐mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID‐19 in several countries, can effectively trap SARS‐CoV‐2 virus‐like particles in fresh human airway mucus. IN‐006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN‐006 resulted in 100‐fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN‐006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS‐CoV‐2 and other respiratory pathologies.

A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19.

The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19. DESIGN: Retrospective cohort study. SETTING: Nine participating ICUs. PATIENTS: COVID-19 patients treated with Seraph 100 (n = 53) and control patients matched by study site (n = 53). INTERVENTION: Treatment with Seraph 100. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41-65) compared with controls (median age, 64 yr; IQR, 56-69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0-3) compared with the control group (3; IQR, 2-4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9-17) compared with controls (16; IQR, 12-21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded. CONCLUSIONS: Although this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines.

Nanoformulated Remdesivir with Extremely Low Content of Poly(2-oxazoline)-Based Stabilizer for Aerosol Treatment of COVID-19.

The rise of the novel virus SARS-CoV2 which causes the disease known as COVID-19 has led to a global pandemic claiming millions of lives. With no clinically approved treatment for COVID-19, physicians initially struggled to treat the disease, and a need remains for improved antiviral therapies in this area. It is conceived early in the pandemic that an inhalable formulation of the drug remdesivir which directly targets the virus at the site of infection could improve therapeutic outcomes in COVID-19. A set of requirements are developed that would be conducive to rapid drug approval: 1) try to use GRAS reagents 2) minimize excipient concentration and 3) achieve a working concentration of 5 mg/mL remdesivir to obtain a deliverable dose which is 5-10% of the IV dose. In this work, it is discovered that Poly(2-oxazoline) block copolymers can stabilize drug nanocrystal suspensions and provide suitable formulation characteristics for aerosol delivery while maintaining antiviral efficacy. The authors believe POx block copolymers can be used as a semi-ubiquitous stabilizer for the rapid development of nanocrystal formulations for new and existing diseases.

A Review of Extracorporeal Blood Purification Techniques for the Treatment of Critically Ill Coronavirus Disease 2019 Patients.

In late 2019, a novel betacoronavirus, later termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in patients with an unknown respiratory illness in Wuhan, China. SARS-CoV-2 and the disease caused by the novel coronavirus, coronavirus disease 2019 (COVID-19), spread rapidly and resulted in the World Health Organization declaring a pandemic in March 2020. In a minority of patients infected with SARS-CoV-2, severe illness develops characterized by a dysregulated immune response, acute respiratory distress syndrome, and multisystem organ failure. Despite the development of antiviral and multiple immunomodulatory therapies, outcomes of severe illness remain poor. In response, the Food and Drug Administration in the United States authorized the emergency use of several extracorporeal blood purification (EBP) devices for critically ill patients with COVID-19. Extracorporeal blood purification devices target various aspects of the host response to infection to reduce immune dysregulation. This review highlights the underlying technology, currently available literature on use in critically ill COVID-19 patients, and future studies involving four EBP platforms: 1) oXiris filter, 2) CytoSorb filter, 3) Seraph 100 Microbind blood affinity filter, and 4) the Spectra Optia Apheresis System with the Depuro D2000 Adsorption Cartridge.

Falling through the cracks: Evaluating the role of nonacute surgical liaison personnel during COVID-19-A narrative review.

BACKGROUND: In March 2020, in response to the COVID-19 pandemic, the New Zealand government instituted a 4-level alert system, which resulted in the rapid dissolution of nonurgent surgical services to minimize occupational exposure to both patients and staff, with the primary health sector bearing most of the diverted caseload. Consequently, the study authors sought to collate information around the establishment of a supportive nonacute surgical liaison role in a public hospital surgical department, with an interest in establishing this role in New Zealand. METHODS: The narrative review conducted systematically in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Databases searched included Pubmed, MEDLINE, Embase, and Cochrane Controlled Register of Trials. A deductive analysis was applied using a demand management model developed by the Institute for Innovation and Improvement at Waitemata District Health Board. All included studies were rated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool. RESULTS: Collation of 19 studies resulted in 3 key findings: first, that a surgical liaison could be utilized at the primary care to specialist interface to improve communication and workflow between services. Second, a liaison could be utilized directly communicating with patients as a means of increasing engagement and self-management. Finally, this service can be offered through multiple modalities including a noncontact telehealth service. CONCLUSION: Evidence of nonacute surgical liaisons both internationally and specifically within New Zealand has been collated to provide evidence for its application.

Seraph-100 Hemoperfusion in SARS-CoV-2-Infected Patients Early in Critical Illness: A Case Series.

There is an urgent need for therapeutic interventions to alter the course of critically ill coronavirus disease 2019 (CO-VID-19) patients. We report our experience with the Seraph-100 Microbind Affinity Blood Filter (Seraph-100) in 4 patients with COVID-19 early in the course of their critical respiratory illnesses. Patients were diagnosed with COVID-19 and were admitted to intensive care with worsening respiratory failure but did not require dialysis or vasopressors. Patients had to have a PaO2 to FiO2 (P/F ratio) <150 to qualify for hemoperfusion therapy. All patients received standard medical therapy including oral vitamins C and D and zinc in addition to intravenous dexamethasone and remdesivir. Patients received a single 5- to 7-h session with Seraph-100 on a conventional dialysis machine (Fresenius 2008T) via a nontunneled central venous dialysis catheter with a goal of processing at least 100 L of blood. Patients received weight-based subcutaneous enoxaparin anticoagulation, as well as systemic intravenous heparin (70 units/kg), just prior to hemofiltration. Treatment with Seraph-100 hemoperfusion was well tolerated, and all patients were able to finish their prescribed therapy. All patients treated with Seraph-100 survived to be discharged from the hospital. Well-designed clinical trials are needed to determine the overall safety and efficacy of the Seraph-100 Microbind Affinity Blood Filter in COVID-19 patients.

Inhaled antibodies: Quality and performance considerations.

The use of antibodies in the treatment of lung diseases is of increasing interest especially as the search for COVID-19 therapies has unfolded. Historically, the use of antibody therapy was based on multiple targets including receptors involved in local hyper-reactivity in asthma, viruses and micro-organisms involved in a variety of pulmonary infectious disease. Generally, protein therapeutics pose challenges with respect to formulation and delivery to retain activity and assure therapy. The specificity of antibodies amplifies the need for attention to molecular integrity not only in formulation but also during aerosol delivery for pulmonary administration. Drug product development can be viewed from considerations of route of administration, dosage form, quality, and performance measures. Nebulizers and dry powder inhalers have been used to deliver protein therapeutics and each has its advantages that should be matched to the needs of the drug and the disease. This review offers insight into quality and performance barriers and the opportunities that arise from meeting them effectively.