Investigating the Use of SARS-CoV-2 (COVID-19) Odor Expression as a Non-Invasive Diagnostic Tool-Pilot Study.

Since the beginning of the COVID-19 pandemic, there has been enormous interest in the development of measures that would allow for the swift detection of the disease. The rapid screening and preliminary diagnosis of SARS-CoV-2 infection allow for the instant identification of possibly infected individuals and the subsequent mitigation of the disease spread. Herein, the detection of SARS-CoV-2-infected individuals was explored using noninvasive sampling and low-preparatory-work analytical instrumentation. Hand odor samples were obtained from SARS-CoV-2-positive and -negative individuals. The volatile organic compounds (VOCs) were extracted from the collected hand odor samples using solid phase microextraction (SPME) and analyzed using gas chromatography coupled with mass spectrometry (GC-MS). Sparse partial least squares discriminant analysis (sPLS-DA) was used to develop predictive models using the suspected variant sample subsets. The developed sPLS-DA models performed moderately (75.8% (±0.4) accuracy, 81.8% sensitivity, 69.7% specificity) at distinguishing between SARS-CoV-2-positive and negative -individuals based on the VOC signatures alone. Potential markers for distinguishing between infection statuses were preliminarily acquired using this multivariate data analysis. This work highlights the potential of using odor signatures as a diagnostic tool and sets the groundwork for the optimization of other rapid screening sensors such as e-noses or detection canines.

The Use of Biological Sensors and Instrumental Analysis to Discriminate COVID-19 Odor Signatures.

The spread of SARS-CoV-2, which causes the disease COVID-19, is difficult to control as some positive individuals, capable of transmitting the disease, can be asymptomatic. Thus, it remains critical to generate noninvasive, inexpensive COVID-19 screening systems. Two such methods include detection canines and analytical instrumentation, both of which detect volatile organic compounds associated with SARS-CoV-2. In this study, the performance of trained detection dogs is compared to a noninvasive headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) approach to identifying COVID-19 positive individuals. Five dogs were trained to detect the odor signature associated with COVID-19. They varied in performance, with the two highest-performing dogs averaging 88% sensitivity and 95% specificity over five double-blind tests. The three lowest-performing dogs averaged 46% sensitivity and 87% specificity. The optimized linear discriminant analysis (LDA) model, developed using HS-SPME-GC-MS, displayed a 100% true positive rate and a 100% true negative rate using leave-one-out cross-validation. However, the non-optimized LDA model displayed difficulty in categorizing animal hair-contaminated samples, while animal hair did not impact the dogs' performance. In conclusion, the HS-SPME-GC-MS approach for noninvasive COVID-19 detection more accurately discriminated between COVID-19 positive and COVID-19 negative samples; however, dogs performed better than the computational model when non-ideal samples were presented.

A LAMP sequencing approach for high-throughput co-detection of SARS-CoV-2 and influenza virus in human saliva.

The COVID-19 pandemic has created an urgent need for rapid, effective, and low-cost SARS-CoV-2 diagnostic testing. Here, we describe COV-ID, an approach that combines RT-LAMP with deep sequencing to detect SARS-CoV-2 in unprocessed human saliva with a low limit of detection (5-10 virions). Based on a multi-dimensional barcoding strategy, COV-ID can be used to test thousands of samples overnight in a single sequencing run with limited labor and laboratory equipment. The sequencing-based readout allows COV-ID to detect multiple amplicons simultaneously, including key controls such as host transcripts and artificial spike-ins, as well as multiple pathogens. Here, we demonstrate this flexibility by simultaneous detection of 4 amplicons in contrived saliva samples: SARS-CoV-2, influenza A, human STATHERIN, and an artificial SARS calibration standard. The approach was validated on clinical saliva samples, where it showed excellent agreement with RT-qPCR. COV-ID can also be performed directly on saliva absorbed on filter paper, simplifying collection logistics and sample handling.

Detection of SARS-CoV-2 with RAPID: A prospective cohort study.

COVID-19 has killed over 6 million people worldwide. Currently available methods to detect SARS-CoV-2 are limited by their cost and need for multistep sample preparation and trained personnel. Therefore, there is an urgent need to develop fast, inexpensive, and scalable point-of-care diagnostics that can be used for mass testing. Between January and March 2021, we obtained 321 anterior nare swab samples from individuals in Philadelphia (PA, USA). For the Real-time Accurate Portable Impedimetric Detection prototype 1.0 (RAPID) test, anterior nare samples were tested via an electrochemical impedance spectroscopy (EIS) approach. The overall sensitivity, specificity, and accuracy of RAPID in this cohort study were 80.6%, 89.0%, and 88.2%, respectively. We present a rapid, accurate, inexpensive (<$5.00 per unit), and scalable test for diagnosing COVID-19 at the point-of-care. We anticipate that further iterations of this approach will enable widespread deployment, large-scale testing, and population-level surveillance.

Detection of SARS-CoV-2 RNA using RT-LAMP and molecular beacons.

BACKGROUND: Rapid spread of SARS-CoV-2 has led to a global pandemic, resulting in the need for rapid assays to allow diagnosis and prevention of transmission. Reverse transcription-polymerase chain reaction (RT-PCR) provides a gold standard assay for SARS-CoV-2 RNA, but instrument costs are high and supply chains are potentially fragile, motivating interest in additional assay methods. Reverse transcription and loop-mediated isothermal amplification (RT-LAMP) provides an alternative that uses orthogonal and often less expensive reagents without the need for thermocyclers. The presence of SARS-CoV-2 RNA is typically detected using dyes to report bulk amplification of DNA; however, a common artifact is nonspecific DNA amplification, which complicates detection. RESULTS: Here we describe the design and testing of molecular beacons, which allow sequence-specific detection of SARS-CoV-2 genomes with improved discrimination in simple reaction mixtures. To optimize beacons for RT-LAMP, multiple locked nucleic acid monomers were incorporated to elevate melting temperatures. We also show how beacons with different fluorescent labels can allow convenient multiplex detection of several amplicons in "single pot" reactions, including incorporation of a human RNA LAMP-BEAC assay to confirm sample integrity. Comparison of LAMP-BEAC and RT-qPCR on clinical saliva samples showed good concordance between assays. To facilitate implementation, we developed custom polymerases for LAMP-BEAC and inexpensive purification procedures, which also facilitates increasing sensitivity by increasing reaction volumes. CONCLUSIONS: LAMP-BEAC thus provides an affordable and simple SARS-CoV-2 RNA assay suitable for population screening; implementation of the assay has allowed robust screening of thousands of saliva samples per week.

COVID-19 vaccine hesitancy among patients in two urban emergency departments.

BACKGROUND: Widespread vaccination is an essential component of the public health response to the COVID-19 pandemic, yet vaccine hesitancy remains pervasive. This prospective survey investigation aimed to measure the prevalence of vaccine hesitancy in a patient cohort at two urban emergency departments (EDs) and characterize underlying factors contributing to hesitancy. METHODS: Adult ED patients with stable clinical status (Emergency Severity Index 3-5) and without active COVID-19 disease or altered mental status were considered for participation. Demographic elements were collected as well as reported barriers/concerns related to vaccination and trusted sources of health information. Data were collected in person via a survey instrument proctored by trained research assistants. RESULTS: A total of 1,555 patients were approached, and 1,068 patients completed surveys (completion rate = 68.7%). Mean (±SD) age was 44.1 (±15.5) years (range = 18-93 years), 61% were female, and 70% were Black. A total of 31.6% of ED patients reported vaccine hesitancy. Of note, 19.7% of the hesitant cohort were health care workers. In multivariable regression analysis, Black race (odds ratio [OR] = 4.24, 95% confidence interval [CI] = 2.62 to 6.85) and younger age (age 18-24 years-OR = 4.57, 95% CI = 2.66 to 7.86; age 25-35 years-OR = 5.71, 95% CI = 3.71 to 8.81) were independently associated with hesitancy, to a greater degree than level of education (high school education or less-OR = 2.27, 95% CI = 1.23 to 4.19). Hesitant patients were significantly less likely to trust governmental sources of vaccine information than nonhesitant patients (39.6% vs. 78.9%, p < 0.001); less difference was noted in the domain of trust toward friends/family (51.1% vs. 61.0%, p = 0.004). Hesitant patients also reported perceived vaccine safety concerns and perceived insufficient research. CONCLUSIONS: Vaccine hesitancy is common among ED patients and more common among Black and younger patients, independent of education level. Hesitant patients report perceived safety concerns and low trust in government information sources but less so friends or family. This suggests that strategies to combat hesitancy may need tailoring to specific populations.

A Multicenter Evaluation of Survival After In-Hospital Cardiac Arrest in Coronavirus Disease 2019 Patients.

IMPORTANCE: In-hospital cardiac arrest survival among coronavirus disease 2019 patients has been reported to range from 0% to 12%. These numbers are significantly lower than reported prepandemic in-hospital cardiac arrest survival rates of approximately 20-25% in the United States for non-coronavirus disease 2019 patients. OBJECTIVE: To assess the incidence of in-hospital cardiac arrest survival of coronavirus disease 2019 patients. DESIGN: A retrospective cohort study of adult patients with coronavirus disease 2019 subsequently found to have in-hospital cardiac arrest and underwent cardiopulmonary resuscitation (cardiopulmonary resuscitation). SETTING: Multiple hospitals of the Cleveland Clinic Health System. PATIENTS: All adult patients (age ≥ 18 yr) admitted to Cleveland Clinic Health System with a diagnosis of coronavirus disease 2019 who experienced in-hospital cardiac arrest requiring cardiopulmonary resuscitation. MEASUREMENTS AND MAIN RESULTS: From March 01, 2020 to October 15, 2020, 3,555 patients with coronavirus disease 2019 were hospitalized; 1,372 were admitted to the ICU; 58 patients had in-hospital cardiac arrest. Median age of this cohort was 66.5 years (interquartile range, 55.0-76.0 yr). Patients were predominantly male (62.5%), White (53.4%), with a median body mass index of 29.7 (interquartile range, 25.8-34.6). Most in-hospital cardiac arrests were in critical care environments (ICU), 51 of 58 (87.9%); seven of 58 (12.1%) were on ward locations. Thirty-four of 58 patients (58.6%) were on mechanical ventilation prior to in-hospital cardiac arrest with a median duration of mechanical ventilation of 9 days (interquartile range, 2-18 d). Twenty-four of 58 patients (44%) were on vasopressors prior to arrest. Initial arrest rhythm was pulseless electrical activity at (63.8%), asystole (29.3%), and pulseless ventricular tachycardia/fibrillation (6.9%). Of the 58 patients, 35 (60.3%) attained return of spontaneous circulation, and 13 of 58 (22.4%) were discharged alive. CONCLUSIONS: We report a 22% survival to discharge after in-hospital cardiac arrest in coronavirus disease 2019 patients, a survival rate similar to before the coronavirus disease 2019 pandemic.

Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials.

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/ ). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I² = 0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I² = 0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities.

Rapid response system adaptations at 40 US hospitals during the COVID-19 pandemic.

BACKGROUND: Management of patients with acute deterioration from novel coronavirus disease of 2019 (COVID-19) has posed a particular challenge for rapid response systems (RRSs) due to increased hospital strain and direct risk of infection to RRS team members. OBJECTIVE: We sought to characterize RRS structure and protocols adaptions during the COVID-19 pandemic. DESIGN SETTING AND PARTICIPANTS: Internet-based cross-sectional survey of RRS leaders, physicians, and researchers across the United States. RESULTS: Clinicians from 46 hospitals were surveyed, 40 completed a baseline survey (87%), and 19 also completed a follow-up qualitative survey. Most reported an increase in emergency team resources during the COVID-19 pandemic. The number of sites performing simulation training sessions decreased from 88% before COVID-19 to 53% during the pandemic. CONCLUSIONS: Most RRSs reported pandemic-related adjustments, most commonly through increasing resources and implementation of protocol changes. There was a reduction in the number of sites that performed simulation training.

Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial.

Importance: Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. Objective: To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants. Interventions: Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks. Main Outcomes and Measures: The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants. Results: Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%]; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, -9 to 17; vs placebo: 3 milliseconds; 95% CI, -5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered. Conclusions and Relevance: In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04329923.

In-hospital cardiac arrest in patients with coronavirus 2019.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has caused over 1 200 000 deaths worldwide as of November 2020. However, little is known about the clinical outcomes among hospitalized patients with active COVID-19 after in-hospital cardiac arrest (IHCA). AIM: We aimed to characterize outcomes from IHCA in patients with COVID-19 and to identify patient- and hospital-level variables associated with 30-day survival. METHODS: We conducted a multicentre retrospective cohort study across 11 academic medical centres in the U.S. Adult patients who received cardiopulmonary resuscitation and/or defibrillation for IHCA between March 1, 2020 and May 31, 2020 who had a documented positive test for Severe Acute Respiratory Syndrome Coronavirus 2 were included. The primary outcome was 30-day survival after IHCA. RESULTS: There were 260 IHCAs among COVID-19 patients during the study period. The median age was 69 years (interquartile range 60-77), 71.5% were male, 49.6% were White, 16.9% were Black, and 16.2% were Hispanic. The most common presenting rhythms were pulseless electrical activity (45.0%) and asystole (44.6%). ROSC occurred in 58 patients (22.3%), 31 (11.9%) survived to hospital discharge, and 32 (12.3%) survived to 30 days. Rates of ROSC and 30-day survival in the two hospitals with the highest volume of IHCA over the study period compared to the remaining hospitals were considerably lower (10.8% vs. 64.3% and 5.9% vs. 35.7% respectively, p < 0.001 for both). CONCLUSIONS: We found rates of ROSC and 30-day survival of 22.3% and 12.3% respectively. There were large variations in centre-level outcomes, which may explain the poor survival in prior studies.

A conceptual framework for Emergency department design in a pandemic.

BACKGROUND: The current COVID-19 pandemic is highlighting gaps around the world in the design and workflow of Emergency Departments (ED). These gaps have an impact on both patient care and staff safety and represent a risk to public health. There is a need for a conceptual framework to guide ED design and workflow to address these challenges. Such a framework is important as the ED environment will always remain vulnerable to infectious diseases outbreaks in the future. AIMS: This paper aims to address issues and principles around ED design and workflow amidst the COVID-19 pandemic. We propose a conceptual framework and checklist for EDs to be prepared for future outbreaks as well. METHODS: A scoping literature review was conducted, of the experiences of EDs in managing outbreaks such as SARS, H1N1 and COVID-19. The combined experiences of the authors and the experiences from the literature were grouped under common themes to develop the conceptual framework. RESULTS: Four key principles were derived- (1) situational awareness, surveillance and perimeter defence, (2) ED staff protection, (3) surge capacity management and (4) ED recovery. The findings were integrated in a proposed conceptual framework to guide ED design in response to an infectious disease outbreak. There are various elements which need to be considered at ED input, throughput and output. These elements can be categorised into (1) system (workflow, protocols and communication), (2) staff (human resources), (3) space (infrastructure), and (4) supply (logistics) and are placed in a checklist for pragmatic use. CONCLUSION: The ED needs to be in a constant state of preparedness. A framework can be useful to guide ED design and workflow to achieve this. As all ED systems are different with varying capabilities, our framework may help EDs across the world prepare for infectious disease outbreaks.

COVID-19 and cardiac arrhythmias.

BACKGROUND: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk. OBJECTIVES: The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality. METHODS: We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia. RESULTS: Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality. CONCLUSION: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.