Clinical outcomes of COVID-19 treated with remdesivir across the continuum of care.

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results: Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p < 0.001). Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.

Current status of hydroxychloroquine and azithromycin for the treatment of COVID-19: an observational review

Though the effect of the coronavirus has known to be a catastrophic pandemic since a 100 years ago, severe acute respiratory syndrome-2 coronavirus (SARS2-CoV) was first claimed to be emerged in December 2019 at the city of Wuhan, China. Abruptly, the virus dominated more than 218 countries with 157,566,607 confirmed cases and the death figure has reached nearly 3,284,551 till time. Recently the pandemic is getting worse day-by-day, people are suffering from hypoxia and severe respiratory problems despite the continuous services provided by the healthcare sector. Prior concern behind this emergency is that, till date, researchers and scientists failed to invent any productive pharmaceutical treatment to weed out the infection completely. Although vaccination is publicly available, it is applicable only for precautionary purposes and not evident of preventive measures. This review focuses on the therapeutic status to control the severity of SAS2-CoV agent. The approach aims at implicating a low toxic metabolite anti-malarial drug, hydroxychloroquine combined with an antibiotic called azithromycin for the treatment of acute respiratory disturbance and hypoxia. This article briefly demonstrates the phramaco-potential of both these medications, their effects on patients based on a clinical observation and ongoing status of dosage to validate its implication.

Pharmaceutical services department strategies and patient perception to maintain healthcare services during COVID-19 crisis.

Background: In March 2020, the World Health Organization (WHO) declared Severe Acute Respiratory Syndrome Coronavirus 2 (SARS2-CoV-2) as global pandemic. This health crisis has overwhelmed the healthcare system, leading to unprecedented morbidity and mortality rates. During this pandemic, pharmacies tried to maintain their services either through remote services or face-to-face dispensing and consultation. Objectives: This study aimed to share the strategies and plans adopted by the pharmaceutical services department to maintain the healthcare services during the SARS2-CoV-2 crisis and evaluate the patient's perspective. Methods: A cross-sectional analytical survey was conducted among patients/patient relatives who attended King Hamad University Hospital (KHUH) outpatient pharmacies in the Kingdom of Bahrain between February 2021 and May 2021. Patients have two options: either to submit the survey online through barcode scanning or to fill it as a physical paper and submit it to the pharmacy staff (Online-based and paper-based). A total of 641 responses were received. Hospital applied safety logistics to ensure staff and patient safety. Results: Post-hoc analysis revealed that patients aged between 20 and 39 years had less agreement than patients ≤ 19 years old in terms of preferring to continue the same services after the pandemic (p = 0.009). More level of understanding of pharmacy services was seen among patients with higher educational levels compared to elementary and secondary levels in cases of services related to adverse events (p = 0.038) and wrong/missed medication rectification (p = 0.018). Unemployed patients were more in agreement than employed ones regarding continuing the same procedure after the pandemic, services related to wrong/missed medication rectification, and safety while staying in the pharmacy waiting area. Conclusion: Most patients were satisfied with the face-to-face counseling, pharmacy-adapted strategies, and services during the SARS2-CoV-2 pandemic. Face-to-face service during the pandemic was equally comfortable across all age groups and gender.

Research on COVID-19 and air pollution: A path towards advancing exposure science.

The COVID-19 pandemic has resulted in an extraordinary incidence of morbidity and mortality, with almost 6 million deaths worldwide at the time of this writing (https://covid19.who.int/). There has been a pressing need for research that would shed light on factors - especially modifiable factors - that could reduce risks to human health. At least several hundred studies addressing the complex relationships among transmission of SARS-CoV-2, air pollution, and human health have been published. However, these investigations are limited by available and consistent data. The project goal was to seek input into opportunities to improve and fund exposure research on the confluence of air pollution and infectious agents such as SARS-CoV-2. Thirty-two scientists with expertise in exposure science, epidemiology, risk assessment, infectious diseases, and/or air pollution responded to the outreach for information. Most of the respondents expressed value in developing a set of common definitions regarding the extent and type of public health lockdown. Traffic and smoking ranked high as important sources of air pollution warranting source-specific research (in contrast with assessing overall ambient level exposures). Numerous important socioeconomic factors were also identified. Participants offered a wide array of inputs on what they considered to be essential studies to improve our understanding of exposures. These ranged from detailed mechanistic studies to improved air quality monitoring studies and prospective cohort studies. Overall, many respondents indicated that these issues require more research and better study design. As an exercise to solicit opinions, important concepts were brought forth that provide opportunities for scientific collaboration and for consideration for funding prioritization. Further conversations on these concepts are needed to advance our thinking on how to design research that moves us past the documented limitations in the current body of research and prepares us for the next pandemic.

Neuropsychiatric manifestation of the drugs used in the treatment of SARS-2-CoV-2019 (COVID-19) infection and their management: An overview and practice implications.

Treatment guidelines for the COVID-19 treatment are still evolving, moreover, the changing variants of the virus with varying virulence, pose challenges for the healthcare professionals (HCP) not only in managing the primary infection but also a myriad of physical and neuropsychiatric complications. The neuropsychiatric adverse consequences associated with the COVID-19 are attributable to the direct effect of the virus, secondary complications, drug-drug interaction, and neuropsychiatric manifestations of drugs used in its treatment. These neuropsychiatric manifestations not only complicate the ongoing treatment but also adversely affect the prognosis. As the treatment guidelines for the management of the COVID are still evolving, the use of non-evidence-based medications, including their off-label use, are rampant that often extend to their non-judicious or irrational use (more than the recommended dose, multiple medications, etc.). Despite the significance of the topic, literature is sparse. Knowing about the risk factors and the potential neuropsychiatric adverse effects with various anti-COVID-19 medications would help HCPs in effectively preventing, early identifying, and promptly managing these neuropsychiatric symptoms. Therefore, this narrative review is aimed to highlight the neuropsychiatric symptoms associated with medications/interventions used in the management of COVID-19 and how to manage them, especially in view of the world facing the third wave of COVID-19.

Early Transfusion of Convalescent Plasma Improves the Clinical Outcome in Severe SARS-CoV2 Infection.

INTRODUCTION: Plasma harvested from convalescent COVID-19 patients (CCP) has been applied as first-line therapy in the early phase of the SARS-CoV2 pandemic through clinical studies using various protocols. METHODS: We present data from a cohort of 267 hospitalized severe COVID-19 patients who received CCP. No transfusion-related complications were reported, indicating the overall safety of CCP therapy. RESULTS: Patients who eventually died from COVID-19 received CCP significantly later (3.95 versus 5.22 days after hospital admission) and had higher interleukin 6 (IL-6) levels (28.9 pg/ml versus 102.5 pg/ml) than those who survived. In addition, CCP transfusion caused a significant reduction in the overall inflammatory status of the patients regardless of the severity of disease or outcome, as evidenced by decreasing C-reactive protein, IL6 and ferritin levels. CONCLUSION: We conclude that CCP transfusion is a safe and effective supplementary treatment modality for hospitalized COVID-19 patients characterized by better expected outcome if applied as early as possible. We also observed that IL-6 may be a suitable laboratory parameter for patient selection and monitoring of CCP therapy effectiveness.

Pediatric Airway Management in Times of COVID-19-a Review of the Evidence and Controversies.

PURPOSE OF REVIEW: This review summarizes and provides a comprehensive narrative synthesis of the current evidence on pediatric airway management during the COVID-19 pandemic. RECENT FINDINGS: The safe care of children undergoing airway management is a primary concern for pediatric anesthesiologists. The COVID-19 pandemic has brought challenges related to airway management and the use of personal protective equipment, aerosol barriers, and the need for simulation and intubation teams. The risk of COVID-19 transmission to the health care worker may be lower in children due to the smaller volume of aerosol dispersal. The implementation of vaccinations may further reduce the risk to health care workers. Evidence demonstrating the impact of COVID-19 on airway outcomes in children is necessary to inform their care. SUMMARY: This review shows that pediatric airway management can be a safe procedure for both the patient and provider in the right setting. The use of appropriate personal protective equipment, particularly focusing on protection from aerosolized particles, is paramount to reduce infection risk. However, there are opportunities for future research.

Drug Repurposing and Polypharmacology to Fight SARS-CoV-2 Through Inhibition of the Main Protease.

The outbreak of a new coronavirus (SARS-CoV-2), which is responsible for the COVID-19 disease and is spreading rapidly around the world, urgently requires effective therapeutic treatments. In this context, drug repurposing represents a valuable strategy, as it enables accelerating the identification of drug candidates with already known safety profiles, possibly aiding in the late stages of clinical evaluation. Moreover, therapeutic treatments based on drugs with beneficial multi-target activities (polypharmacology) may show an increased antiviral activity or help to counteract severe complications concurrently affecting COVID-19 patients. In this study, we present the results of a computational drug repurposing campaign that aimed at identifying potential inhibitors of the main protease (Mpro) of the SARS-CoV-2. The performed in silico screening allowed the identification of 22 candidates with putative SARS-CoV-2 Mpro inhibitory activity. Interestingly, some of the identified compounds have recently entered clinical trials for COVID-19 treatment, albeit not being assayed for their SARS-CoV-2 antiviral activity. Some candidates present a polypharmacology profile that may be beneficial for COVID-19 treatment and, to the best of our knowledge, have never been considered in clinical trials. For each repurposed compound, its therapeutic relevance and potential beneficial polypharmacological effects that may arise due to its original therapeutic indication are thoroughly discussed.

Baseline results of a living systematic review for COVID-19 clinical trial registrations.

Background: Since the coronavirus disease 2019 (COVID-19) outbreak was first reported in December 2019, many independent trials have been planned that aim to answer similar questions. Tools allowing researchers to review studies already underway can facilitate collaboration, cooperation and harmonisation. The Infectious Diseases Data Observatory (IDDO) has undertaken a living systematic review (LSR) to provide an open, accessible and frequently updated resource summarising characteristics of COVID-19 study registrations. Methods: Review of all eligible trial records identified by systematic searches as of 3 April 2020 and initial synthesis of clinical study characteristics were conducted. In partnership with Exaptive, an open access, cloud-based knowledge graph has been created using the results.  Results: There were 728 study registrations which met eligibility criteria and were still active. Median (25 th, 75 th percentile) sample size was 130 (60, 400) for all studies and 134 (70, 300) for RCTs. Eight lower middle and low income countries were represented among the planned recruitment sites. Overall 109 pharmacological interventions or advanced therapy medicinal products covering 23 drug categories were studied. Majority (57%, 62/109) of them were planned only in one study arm, either alone or in combination with other interventions. There were 49 distinct combinations studied with 90% (44/49) of them administered in only one or two study arms. The data and interactive platform are available at https://iddo.cognitive.city/. Conclusions:  Baseline review highlighted that the majority of investigations in the first three months of the outbreak were small studies with unique treatment arms, likely to be unpowered to provide solid evidence.  The continued work of this LSR will allow a more dependable overview of interventions tested, predict the likely strength of evidence generated, allow fast and informative filtering of relevant trials for specific user groups and provide the rapid guidance needed by investigators and funders to avoid duplication of efforts.

Out of Sight but Not Out of Mind: Caring for Patients Receiving OPAT During the SARS-CoV-2 Pandemic.

In an effort to "flatten the curve" of SARS-CoV-2, society is urged to practice social distancing. However, the management of other disease states may require some patients to undergo outpatient parenteral antimicrobial therapy (OPAT). Practical considerations for OPAT management during an infectious pandemic are reviewed. These include shortening durations of therapy, utilizing the oral route, avoiding medications requiring therapeutic drug monitoring, selecting antimicrobials with long durations, decreasing frequency of laboratory blood draws, and performing tele-health visits.

Potential Inhibitors for Novel Coronavirus Protease Identified by Virtual Screening of 606 Million Compounds.

The rapid outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China followed by its spread around the world poses a serious global concern for public health. To this date, no specific drugs or vaccines are available to treat SARS-CoV-2 despite its close relation to the SARS-CoV virus that caused a similar epidemic in 2003. Thus, there remains an urgent need for the identification and development of specific antiviral therapeutics against SARS-CoV-2. To conquer viral infections, the inhibition of proteases essential for proteolytic processing of viral polyproteins is a conventional therapeutic strategy. In order to find novel inhibitors, we computationally screened a compound library of over 606 million compounds for binding at the recently solved crystal structure of the main protease (Mpro) of SARS-CoV-2. A screening of such a vast chemical space for SARS-CoV-2 Mpro inhibitors has not been reported before. After shape screening, two docking protocols were applied followed by the determination of molecular descriptors relevant for pharmacokinetics to narrow down the number of initial hits. Next, molecular dynamics simulations were conducted to validate the stability of docked binding modes and comprehensively quantify ligand binding energies. After evaluation of potential off-target binding, we report a list of 12 purchasable compounds, with binding affinity to the target protease that is predicted to be more favorable than that of the cocrystallized peptidomimetic compound. In order to quickly advise ongoing therapeutic intervention for patients, we evaluated approved antiviral drugs and other protease inhibitors to provide a list of nine compounds for drug repurposing. Furthermore, we identified the natural compounds (-)-taxifolin and rhamnetin as potential inhibitors of Mpro. Rhamnetin is already commercially available in pharmacies.

Management of neurological care during the COVID-19 pandemic. / La gestión de la asistencia neurológica en tiempos de la pandemia de Covid-19.

INTRODUCTION: The COVID-19 epidemic has led to the need for unprecedented decisions to be made to maintain the provision of neurological care. This article addresses operational decision-making during the epidemic. DEVELOPMENT: We report the measures taken, including the preparation of a functional reorganisation plan, strategies for hospitalisation and emergency management, the use of telephone consultations to maintain neurological care, provision of care at a unit outside the hospital for priority patients, decisions about complementary testing and periodic in-hospital treatments, and the use of a specific telephone service to prioritise patients with epileptic seizures. CONCLUSION: Despite the situation of confinement, neurology departments must continue to provide patient care through different means of operation. Like all elements of management, these must be evaluated.