Understanding the pathophysiology of COVID-19: Are we investigating survivors appropriately?

Background: In COVID-19 survivors, altered lung diffusion capacity is the most common anomaly followed by a restrictive ventilatory defect. The common respiratory function tests used to investigate these abnormalities include transfer factor (TLco) and static lung volumes (TLC) . Aim(s): To review the appropriateness of the investigative approach at an acute tertiary centre for the management of COVID-19 survivors. Method(s): 448 consecutive post COVID-19 patients were referred into a respiratory physiology service (March 2020 to January 2022) and underwent 955 investigations. These were reviewed to ascertain if the recommended assessments were performed. Result(s): The patient's mean age was 57.6 years and consisted of 244 females and 204 males. The most common investigation requested was pulmonary function tests, which includes spirometry, TLco and TLC. Table 1 presents the other tests in order of frequency. There were 65 patients (15%) who had no referral for either TLco or TLC. Conclusion(s): Although the majority of patients were assessed appropriately, 15% did not have any COVID-19 pathophysiology specific investigations requested. It is recommended that a panel of tests including TLco and TLC is created to ensure patients are suitably investigated. (Table Presented).

Processes and Outcomes for 121,576 Patients With ST Elevation Myocardial Infarction in the AHA Get With the Guidelines-Coronary Artery Disease (GWTG-CAD) Registry, 2018-2021

Introduction: Timely treatment of ST elevation myocardial infarction [STEMI] requires ongoing coordinated care between emergency departments, paramedics, and primary percutaneous coronary (PCI) intervention facilities. Method(s): To provide a current view and a national benchmark, we examined 121,576 patient records submitted by 648 hospitals participating the GWTG-CAD registry from Q2 2018 through Q3 2021 [median age 63, women 29%, Black 11%, Hispanic 8%, admission cardiac arrest 5%, shock 7%, heart failure 7%, Covid 0.2%, presentation EMS 47%, walk in 27%, transfer 22%] Results: Reperfusion method for all patients included primary PCI 87%, fibrinolysis 5%, and no reperfusion 8% [increasing from 7 to 9% during the study period]. Median time from symptom onset to reperfusion was shortest for EMS patients 148 minutes, followed by walk-in 195 minutes, ground transferred 238 minutes, and air transferred 247 minutes. Process times did not improve during the study period. First medical contact to device times increased by 5 minutes for EMS and ground transferred patients in Q2 2020 corresponding with the pandemic onset, and adjusted mortality was significantly higher in the final 3 quarters compared to Q2 2018 [OR, 95% CI 1.28(1.07-1.53);1.35(1.13-1.61);1.23(1.03-1.48)]. Patients treated within guideline goals had significantly lower mortality [Figure]. Conclusion(s): These data reaffirm the association between process times and lower mortality for STEMI patients. They also identify concerning trends and opportunities for improved care. Increasing delays in treatment, particularly for hospital transfer, greater numbers of untreated patients, and increased risk-adjusted in-hospital mortality all provide strong impetus for renewed focus on STEMI systems. Regional collaborative efforts led by coordinators and informed by a common data system have the potential to reverse these trends and improve survival.

Air Flows in Opera

Clusters of contaminations have been identified within rehearsing choirs during the COVID-19 pandemic. In particular, singing and playing wind instruments are known to generate enhanced release of respiratory droplets, which are then transported by the expiratory flows. By tracking the air exhaled by professional opera singers and musicians from the MET Orchestra in New York City, we measure the spatial extent of the various air flows in opera. While loud singing is often associated with fast flows, professional opera singers and musicians are usually exhaling air flows slower than the air jets exhaled by a person breathing at rest. However, we identify a few situations leading to the release of rapid air jets that are able to enhance the transport of pathogenic droplets within an orchestra. Finally, we show how singing with a facemask and covering the bell of a wind instrument provide a strong reduction of the transport of respiratory droplets, in addition to the filtration features of a mask. © 2022 American Physical Society.

CURE ID as a Tool for Curating and Analyzing Drugs Used in COVID-19 Clinical Trials

Background. CURE ID is an internet-based data repository (https://cure.ncats. io/explore) developed collaboratively by FDA and NCATS/NIH. It is designed to capture real-world clinical outcome data to advance drug repurposing and to inform future clinical trials for infectious diseases with high unmet medical need. It also serves as a repository of clinical trials automatically pulled from https://www.clinicaltrials.gov into the CURE ID platform, where they were then manually curated, with the intention of keeping the infectious diseases community updated on the various clinical trials underway. The current study is a descriptive analysis of various therapeutics in clinical trials against COVID-19 on the CURE ID platform. Methods. Using clinicaltrials.gov we selected those trials addressing therapeutics for COVID-19 and reviewed the drugs used, the current status of the trials, and the phases of development. Results. As of May 2021, we identified 2,154 clinical trials and 933 drugs from clinicaltrials.gov that met the inclusion criteria. Hydroxychloroquine (n=251) was the most commonly investigated agent, followed by convalescent plasma (n=147), azithromycin (n=98), ivermectin (n=68), mesenchymal Stem Cells (n=63), tocilizumab (n=58), remdesivir (n=53) and favipiravir (n=51). At the time of our analysis, the majority (45%) of the clinical trials were in the recruiting phase, 12% were in the active phase, and 13% of the studies were completed. The majority (31%) of trials were in phase two, followed by phase three (21%) and phase one (10%). The vast majority of the agents were repurposed (92%), while only 8% of the agents were new molecular entities. Remdesivir was the only drug approved for marketing for treatment of certain patients with COVID-19 at the time of our analysis. Conclusion. Several repurposed and novel drugs are being investigated to treat COVID-19 in clinical trials. CURE ID provides a broad view of the various drugs being researched and serves to keep the scientific community informed. Such a platform may help prevent duplication of efforts and help the scientific community with more coordinated research efforts and larger platform trials that can robustly answer scientific questions during a pandemic.

Inexpensive Multipatient Respiratory Monitoring System for Helmet Ventilation During COVID-19 Pandemic

Helmet continuous positive applied pressure is a form of noninvasive ventilation (NIV) that has been used to provide respiratory support to COVID-19 patients. Helmet NIV is low-cost, readily available, provides viral filters between the patient and clinician, and may reduce the need for invasive ventilation. Its widespread adoption has been limited, however, by the lack of a respiratory monitoring system needed to address known safety vulnerabilities and to monitor patients. To address these safety and clinical needs, we developed an inexpensive respiratory monitoring system based on readily available components suitable for local manufacture. Open-source design and manufacturing documents are provided. The monitoring system comprises flow, pressure, and CO2 sensors on the expiratory path of the helmet circuit and a central remote station to monitor up to 20 patients. The system is validated in bench tests, in human-subject tests on healthy volunteers, and in experiments that compare respiratory features obtained at the expiratory path to simultaneous ground-truth measurements from proximal sensors. Measurements of flow and pressure at the expiratory path are shown to deviate at high flow rates, and the tidal volumes reported via the expiratory path are systematically underestimated. Helmet monitoring systems exhibit high-flow rate, nonlinear effects from flow and helmet dynamics. These deviations are found to be within a reasonable margin and should, in principle, allow for calibration, correction, and deployment of clinically accurate derived quantities. Copyright © 2022 by ASME.

Seizure, abdominal pain, and urine pink in an adolescent female-what's the link?

Case Report A 17 year-old female with history of depression was transferred to the pediatric intensive care unit (PICU) from an emergency department (ED) for first time seizure and subsequent encephalopathy after five days of severe, diffuse abdominal pain and vomiting. The night prior to admission, she complained of lightheadedness and then had a witnessed generalized tonic-clonic seizure lasting 45 seconds. She initially returned to her baseline but then had three additional seizures requiring ED evaluation. She received intravenous doses of lorazepam and levetiracetam that aborted the clinical seizures. She remained encephalopathic and was orotracheally intubated for airway protection. Family denied known ingestions but reported she did vape nicotine. Urine drug screen was positive for benzodiazepines, consistent with seizure management. Cerebrospinal fluid analysis was unrevealing. Urinalysis showed moderate ketones and trace blood. Urine pregnancy test and nasopharyngeal SARS-CoV-2 polymerase chain reaction were negative. Head computerized tomography scan showed no intracranial pathology. On arrival to the PICU, the patient was afebrile, tachycardic, and hypertensive to 171/118 mmHg. She was somnolent on arrival but aroused to sternal rub without focal neurologic deficit. She presented with a Foley catheter that drained pinkorange urine. A nicardipine infusion was started given concern for the development of posterior reversible encephalopathy syndrome (PRES). Thyroid function tests were consistent with euthyroid sick syndrome. BioFire meningitis panel, plasma SARS-CoV-2 IgG, and toxicologic evaluation were all negative. Electrocardiogram showed sinus tachycardia. Magnetic resonance imaging of the brain revealed cortical and subcortical areas of diffusion restriction consistent with PRES. Ultimately, a random urine porphobilinogen and a 24-hour measurement of urine porphyrins collected on hospital day 1 were both markedly elevated. A diagnosis of Acute Intermittent Porphyria (AIP) was made. A gastrointestinal porphyria specialist was consulted and recommended monthly outpatient injections of givosiran upon hospital discharge. Discussion This case illustrates the importance of considering AIP in the differential diagnosis of new onset seizure or encephalopathy associated with hypertension, tachycardia, and abdominal pain in an adolescent. This case also adds to a small number of cases associating AIP with PRES. AIP is often viewed as an adult disease because it typically presents in the third or fourth decade of life. Timely recognition of AIP in the pediatric setting is critical to preventing delays in diagnosis, treatment, and patient education on triggers of acute attacks. AIP attacks are treated with dextrose and hemin infusions to reduce production of porphyrin precursors. Prophylactic treatment of AIP now includes givosiran, an interfering mRNA that reduces levels of intermediates in heme synthesis that are neurotoxic when elevated.

Capturing clinician's experiences repurposing drugs to inform future studies during COVID-19

Background: CURE ID is an internet-based repository developed collaboratively by FDA and NCATS/NIH, with the support of WHO and IDSA. It encourages clinicians globally to share novel uses of existing drugs for patients with difficult-to-treat infections. It is designed to serve as a rapid communication platform for healthcare providers during an outbreak, providing for systematic case-sharing, discussion, and the latest literature. Besides case reports, CURE ID offers a discussion platform for clinicians, disease-specific clinical trials curated from clincialtrials.gov, and a newsfeed that shows relevant journal articles and news related to COVID-19 and other infectious diseases. Methods: The CURE ID team extracted individual case reports on patientlevel treatments and outcomes of COVID-19 infection from the published literature and gathered clinician-submitted cases through the electronic case report form. Additionally, CURE ID partnered with the University of Pennsylvania's CORONA database to further populate the CURE ID database with published cases. Results: As of submission, lopinavir-Ritonavir (n=51) was the most commonly reported drug used. The following were also reported: hydroxychloroquine (n=31), azithromycin (n=28), arbidol (n=22), interferon alfa-2B (n=18), moxifloxacin (n=18), methylprednisolone (n=17), ivermectin (n=14), lopinavir (n=12), oseltamivir (n=12). The other drugs reported were danoprevir-ritonavir, intravenous immunoglobulins, interferon, interferon alfa, and tocilizumab. CURE ID currently includes more than 150 detailed COVID case reports of 65 repurposed drugs. We expect case reporting for specific drugs to be dynamic and additional data to accrue. Updated results will be presented. Conclusion: Several drugs are being repurposed to treat COVID-19. CURE ID gives clinicians an opportunity to share their treatment experiences and discuss their questions with a global community of healthcare providers. By utilizing the CURE ID platform, in conjunction with data gathered from other registries, observational studies and clinical trials, hypotheses can be generated that may inform future clinical trials and ultimately, potentially find safe and effective treatments for this deadly disease.

Can existing routine clinical data be used to predict hypoxaemia for mnd patients undertaking commercial flight?

Introduction: Pre-COVID-19, the total number of passengers traveling by commercial airlines rose to 4.3 billion, with Europe amounting to a 7.2% increase. The risks of respiratory compromised patients developing hypoxaemia during flight is well documented. Assessment of these patients is time consuming and often requires specialised equipment. Furthermore, the majority of evidence is based on research into patients with Chronic Obstructive Pulmonary Disease (COPD). The aim of this study is to investigate potential predictive biomarkers relating to the development of hypoxaemia during flight in patients with Motor Neurone Disease (MND). Methods: 118 MND patients referred into a fitness to fly service (n=118) completed baseline lung function and a Hypoxic Challenge Test (HCT) as part of a risk stratification for (Table presented) planned air travel (77 male). Data from patients requiring inflight oxygen was compared to patients who did not, in accordance with the British Thoracic Society recommendations 2011: Managing passengers with stable respiratory disease planning air travel. Statistical analysis was performed using one-way ANOVA, Kruskal-Wallis, and Chi-Squared tests, as appropriate. Results: There was no significant difference between the pass (n=94) and fail (n=24) groups for age, gender, smoking history or BMI. There was a significant difference for all spirometry data (FEV1, FVC and FEV1/FVC ratio - absolute, percent predicted and standardised residuals). Moreover, the resting blood gases (FiO221%) data showed significant difference for all parameters with the exception of pH (<0.001). The Regression analysis showed limited predictive value of spirometry and/or resting blood gas data with the exception of PaCO2 and base excess (BE). Conclusions: The predictive value of spirometic paraments and resting blood gases are limited in assessing hypoxaemia during commercial flight in MND patients, with the exception of parameters relating to respiratory failure. Despite the significant difference between the two groups, routine physiological data was limited in the predictive regression equations. We recommend that the safest approach in managing this group of patients is to perform an HCT in all patients intending to use air travel until more evidence-based data is available.

Cruise ship travel and the spread of COVID-19 - Australia as a case study

Introduction: Cruise ship linked COVID-19 outbreaks have been identified as a potential source of community transmission of COVID-19 in Australia and worldwide. The risk factors and potential mitigation around COVID-19 infections on cruise ships and communities is a research gap.

Towards improved social distancing guidelines: Space and time dependence of virus transmission from speech-driven aerosol transport between two individuals

It is now recognized that aerosol transport contributes to the transmission of the SARS-CoV-2 virus. Here, we improve existing social distancing guidelines for airborne pathogens, which are typically given in terms of distance with vague statements about contact times. Also, estimates of inhalation of virus in a contaminated space usually assume a well-mixed environment, which is realistic for some, but not all, situations. In particular, we consider a local casual interaction of an infected individual and a susceptible individual, both maskless, account for the air flow and aerosol transport characteristics of speaking and breathing in a poorly ventilated space, and propose social distancing guidelines that involve both space and contact time, based on a conservative model of fluid dynamics of the interactions. © 2020 American Physical Society.

Stretching and break-up of saliva filaments during speech: A route for pathogen aerosolization and its potential mitigation

Speech is a potent route for viral transmission in the COVID-19 pandemic. Informed mitigation strategies are difficult to develop since no aerosolization mechanism has been visualized yet in the oral cavity. Here we show with high-speed imaging how phonation of common stop consonants, found in most of the world's spoken languages, form and extend salivary filaments in a few milliseconds as moist lips open or when the tongue separates from the teeth. Both saliva viscoelasticity and airflow associated with the plosion of stop consonants are essential for stabilizing and subsequently forming centimeter-scale thin filaments, tens of microns in diameter, that break into speech droplets. Moreover, these plosive consonants induce vortex rings that drive meter-long transport of exhaled air, tying this mechanism to transport associated with speech. We demonstrate that a similar mechanism of aerosolization occurs during the vibration of reeds in wind instruments and may occur during the flapping of the glottis folds. Finally, our research suggests a mitigation of droplet production during speech by using a lip balm.