MOLECULAR DOCKING AND BIOACTIVITY STUDIES OF COVALENT INHIBITORS TARGETING RDRP OF SARS-COV-2

The objective of the study was to examine the compounds which inhibit the enzyme RNA-Dependent RNA-Polymerase (RdRp) of SARS-CoV-2. In this study, we collected 120 similar compounds of Remdesivir, Favipiravir, Novobiocin, and Cortisone inhibitors from PubChem and docked them within the RdRp enzyme using Patchdock/ Firedock server. Seven compounds were screened based on binding affinity and binding mode analysis and further studied the covalent and hydrogen interaction networks using Ligplot+ software. Moreover, the pharmacore properties and bioactivity of the compounds were analyzed with molinspiration cheminformatics software. In this study, we identified the compounds 56832851, 134443512, and 5745 have more binding affinity and mostly covalent/H-bonding interactions occurred with side chain residues Asp161 (B)-Trp187 (B)-Thr367 (A)-Arg377 (A)-Asn387 (A)-Glu588 (A) of RdRp. Furthermore, these three compounds showed up drug-likeness and biologically active, though further in-vitro investigations are needed. © 2022, Rasayan Journal of Chemistry, c/o Dr. Pratima Sharma. All rights reserved.

IMPACTS OF THE COVID-19 PANDEMIC ON THE MENTAL HEALTH OF HOUSE STAFF

SESSION TITLE: Trainees: Mental Well-Being and Performance SESSION TYPE: Original Investigations PRESENTED ON: 10/16/22 10:30 am - 11:30 am PURPOSE: Mental health amongst house staff is poorly understood and at the forefront of many discussions regarding medical education and medical training. The COVID-19 pandemic which reached the United States in 2020, provided a novel situation which many house staff were unaccustomed. Few studies have been performed to assess mental health of house staff in relation to this pandemic. We would like to assess and study the prevalence of post-traumatic stress disorder (PTSD), anxiety, and depression in house staff during the COVID-19 pandemic METHODS: House staff in academic institution were invited to complete a survey anonymously via email from November 2021-January 2022. The survey was a compilation of 3 separate questionnaires: PCL-5 evaluating for PTSD, DASS-21 assessing depression, anxiety, and stress, and GAD-7 assessing anxiety. Scores were reported in mean and standard deviation. Prevalence of each disease was reported in frequency and percentage. T-test was used to compare scores between primary team (internal medicine, emergency medicine (EM), family medicine, and pulmonary and critical care (PCCM)) and non-primary team, and the scores between exposed (Anesthesiology, EM, PCCM) and non-exposed groups. Chi-squared analysis was performed to compare the prevalence of each disease between primary/non-primary and highly exposed/non-exposed groups. RESULTS: 60 house staff from 10 departments responded to the survey. Departments were stratified into primary and non-primary team as well as highly exposed and non-exposed group. Highly exposed group had significant higher mean scores of PTSD (20.92±19.45 vs 11.03±12.31, p=0.02), DASS-21 – depression (13.83±11.16 vs 6.39±8, p=0.004), and DASS-21 - stress (15±11.27 vs 8.17±8.03 p=0.008) compared to non-exposed group. The prevalence of moderate to severe depression (15(62.5%) vs 9(25%) p=0.007), stress (11(45.83%) vs 6(16.67%) p=0.02), and anxiety (7(29.17%) vs 3(8.33%) p=0.03) are significantly higher in exposed group. For primary team, the mean scores and prevalence of each disease are higher than non-primary team, though these are not statistically significant. CONCLUSIONS: Mental health amongst house staff has been impacted by the COVID pandemic. Symptoms of PTSD, Depression, Stress, and Anxiety were noted amongst house staff in relation to the pandemic. Our study demonstrated a clear impact on house staff that were in highly exposed fields. CLINICAL IMPLICATIONS: With continued emphasis on wellness for house staff, early recognition of mental health difficulties will be ideal to promoting wellness. Understanding the implications of pandemics and other high volume clinical scenarios upon the mental health of house staff could aid in early interventions to promote resident wellness. As the COVID pandemic continues to ebb, further studies will need to be done to assess the long term implications of the pandemic on the mental health of medical professionals DISCLOSURES: No relevant relationships by Prangthip Charoenpong No relevant relationships by Anum Sheikh No relevant relationships by Najam Siddiqui

Investigative and probabilistic perspective of the accidental release of styrene: a case study in Vizag, India

In addition to revealing the cracks in global health care, emergency preparedness, and response systems, COVID-19 also exposed the lack of capacity to run chemical plants safely under such conditions. On 7th May 2020, self-polymerization runaway reaction from an atmospheric storage tank in a polymer facility triggered the release of styrene to the atmosphere, resulting in 12 fatalities and hospitalization of more than 1000 individuals. A similar incident had happened 35 years back at Bhopal involving the release of methyl isocyanate resulting in one of the deadliest process safety incidents to date. Therefore, it is very important to understand the causal factors so that such high-risk incidents can be prevented in future. This paper presents a comprehensive investigative study of styrene gas leak at Vizag with special emphasis on probabilistic risk analysis of the loss of containment. Hazard perception study was performed to understand the possible hazardous scenarios in bulk styrene storage facilities for preventing such catastrophic recurrences. Energy barrier analysis was performed to study the inadequacy of pro-active and reactive barriers with respect to the accident case study. The analysis also considers the escalation factors resulting from extremities of COVID-19 lockdown. The self-polymerization reaction that resulted in toxic styrene dispersion was preventable owing to the advancements in safety engineering and loss prevention since Bhopal Gas Tragedy (1984). Based on the investigative analysis, it can be pointed out that this accident would have occurred even in the absence of COVID-19 restrictions, mainly due to negligence and complacency shown towards safety by the company's management. © 2021 Institution of Chemical Engineers

COVID-19 pandemic in Uttarakhand, India: Environmental recovery or degradation?

The human coronavirus disease-2019 (COVID-19) caused by SARS-CoV-2 is now a global pandemic. Personal hygiene such as hand-washing, the use of personal protective equipment, and social distancing via local and national lockdowns are used to reduce the risk of transmission of SARS-CoV-2. COVID-19 and the associated lockdowns may have significant impacts on environmental quality and ergonomics. However, limited studies exists on the impacts of COVID-19 and the associated lockdowns on environmental quality and ergonomics in low-income settings. Therefore, the present study investigated the impacts of the COVID-19 outbreak on socioeconomics, ergonomics and environment (water quality, air quality and noise) in Uttarakhand, India. Approximately 55% of respondents experienced headaches, and the other common health-related issue was back pain, with 45% of respondents having problems with their backs. Water and air quality significantly improved during the lockdown relative to the pre-lockdown period, but was observed to return to their previous characteristics afterwards. Lockdowns significant increased the concentration of indoor air pollutants while noise pollution levels significantly declined. In summary, lockdowns have adverse impacts on ergonomics, resulting in work-related human health risks. The impacts of lockdowns on environmental quality are mixed: temporary improvements on water and air quality, and noise reduction were observed, but indoor air quality deteriorated. Therefore, during lockdowns there is a need to minimize the adverse environmental and ergonomic impacts of lockdowns while simultaneously enhancing the beneficial impacts.

1442O Proactive early palliative care referral for cancer patients in the intensive care unit: Implementing a novel “triggers” checklist

Background: Integrated palliative care (PC) is recommended for all cancer patients. It improves patient experience and communication, reduces symptom burden and futile medical interventions, and shortens length of hospital stay. Despite the mortality of 27-43% for cancer patients admitted to intensive care (ICU), early PC involvement has not been widely adopted. Previous studies have shown the potential for using specific “trigger” criteria to identify ICU patients for early PC referral. We show the benefits of using a novel trigger tool in practice at the time of admission to ICU in a specialist cancer hospital. Methods: We developed a novel electronic tool, combining criteria outlined by Hua et al. (2016) with a locally-developed triggers checklist already used in the outpatient setting. This tool was integrated into the ICU clerking proforma. Patients meeting any of the tool’s criteria were referred to the PC team who provided early advice for symptom control and advanced care planning. Quality improvement methodology was used between February 2020 and January 2021 as we embedded this tool into clinical practice. Results: In a timeline disrupted by two waves of COVID-19, there were 151 admissions of which 74 (49%) had a triggers form completed. Sixty-six cases (89%) were positive (≥1 criterion), leading to 16 (24%) referrals to palliative care. This represented 46% of all PC referrals made from ICU during this period. We show that many patients admitted to ICU have a poor functional baseline (47% had metastatic cancer progressing despite 1st line chemotherapy, 49% had an ECOG score ≥2). Many patients also had severe or uncontrolled symptoms (52%). Early palliative care provided vital input for those patients. Conclusions: Our tool proactively identifies patients for early PC referral, streamlines the referral process, and empowers staff to consider treatment goals in a timely manner for the benefit of patients. Technical, practical, and cultural barriers to implementation were identified and changes made to address these, for example, having PC present at the weekly ICU meeting. We demonstrate a model for collaborative working which can be adapted for use in other ICUs and facilitate early PC for a broader cohort of cancer patients. Legal entity responsible for the study: The authors (all staff at The Royal Marsden NHS Foundation Trust). Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Tocilizumab for cytokine release syndrome in severe COVID-19 pneumonia: A case series

INTRODUCTION: COVID-19 can induce a significant inflammatory response generating an overwhelming cytokine release that in of itself can be fatal. This ?cytokine release syndrome? (CRS), induces profound inflammation affecting nearly all organ systems. Interleukin-6 (IL-6) appears to be a major factor driving this process. In an attempt to mitigate this inflammatory process and IL-6, Tocilizumab (TCZ), an IL-6 receptor antagonist has been used in COVID-19. We report a series of 7 cases who were diagnosed with severe COVID-19 pneumonia and CRS who received TCZ. METHODS: We conducted a retrospective case series evaluating the use of TCZ in patients admitted to the intensive care unit with severe COVID-19 pneumonia and CRS at a single center tertiary care academic hospital in the United States. RESULTS: Seven patients met our inclusion criteria. All seven patients had at least one co-morbidity and required ICU admission. The median age was 57 with each presenting within 7 days of symptom onset. All patients had elevated levels of Il-6, CRP, ferritin, and D-dimer. TCZ was administered within a median of 3.5 days. After 72 hours of TCZ, all patients demonstrated a decrease in CRP levels by >50% and levels continued to downtrend at one week. Of the seven, three were extubated within eight days of TCZ administration;two survived to discharge with their mean SOFA score declining from 9.7 pre-treatment to 7.8 over the next 72 hours. One developed a secondary infection. The five patients that did not survive were older, had a greater number of comorbidities and a higher BMI (37 kg/m2 vs 31.3 kg/m2). Renal failure was also more prominent (mean Cr 3.75mg/ dl vs 0.95mg/dl). The non-survivor SOFA scores pre-TCZ were 11.6 vs 5 for survivors on day one. Non-survivors had significantly higher IL-6 levels (mean 81 pg/ml vs 13.9 pg/ml), but lower CRP levels (15mg/l vs 22mg /l). CONCLUSIONS: Several observational studies have reported mixed results with using TCZ in severe COVID-19. This may be due to small sample size, variability in age, comorbidities and disease severity at presentation or time of TCZ administration. Our case series failed to show a mortality benefit with the exception of younger patients with less severe disease. Efficacy of TCZ needs to be validated in large randomized clinical trials.