N-Heterocycles as Privileged Scaffolds in FDA Approved Different NMEs of 2021: A Review

The presence of N-heterocyclic ring systems as promising features in the molecular skele-ton of FDA-approved drugs, underlie the remarkable contributions of these heterocyclic nuclei in the field of medicine. Despite instability risks associated with the COVID pandemic, the US FDA approved 50 drugs (36 NMEs and 14 biological products) in the year 2021. The active ingredients of 32 drugs out of these 36 NMEs (almost 89%) contain saturated, partially unsaturated and aromatic N-heterocyclic moieties in their molecular assemblies, hence dominating the medicinal approvals. While 27 molecules (75% of these NMEs drugs) are prominent small NMEs. Herein, we have considered profiling those FDA-approved 27 small-molecule drugs which are decorated with N-heterocycles as privileged scaffolds. These drugs are grouped on the basis of a number of N-heterocycles present in their structural framework. The spectrum of these drugs in terms of their structural features and medicinal importance is summarized in this review. Also, the pertinent analyses of their drug-likeliness conferring some general pharmacokinetic principles are highlighted. © 2023 Bentham Science Publishers.

Risk Perception Mental Health Impact and Coping Strategies during Covid 19 Pandemic among Health Care Workers

Objective: To assess the risk perception mental health impact and coping strategies during Covid-19 pandemic among health care workers. Study Design: Cross-sectional study. Place and Duration of Study: Department of Community Dentistry, Frontier Medical & Dental College, Abbottabad from 1st January 2021 to 31st December 2021. Methodology: Two hundred health care workers were given questionnaire for complete detailing their information regarding demographic, occupational, anxiety scoring and depression state. Results: The age of the health care workers was mostly within 26-40 years followed by greater than 18 years. It was observed that anxiety was presented at a mild score within doctors and other health care worker staff while it was seen to a moderate level within the nursing health care workers. Furthermore, the gender distribution of anxiety showed higher level of anxiety among females than males. Within genders a low risk perception was seen within males than females. Among the health care workers, the risk perception was highest in nurses followed by paramedic and other health care staff. Conclusion: Covid-19 has caused devastating effects on the psychological stability of the health care workers which needs to be properly assessed and addressed.

Case Series of New-Onset CNS Immunological Disorders Temporally Associated with mRNAbased COVID-19 Vaccines

Objective: To present a single-health system retrospective analysis of post-mRNA-based COVID-19 vaccination CNS autoimmunity conducted in the greater New York City area. Background: There have been rare reports associating mRNA-based COVID-19 vaccines with central nervous system (CNS) inflammation. We report a case series of five patients with newonset neurological disorders of immunological origin temporally associated with these vaccines. Design/Methods: Case-series. Results: Five cases of post-vaccination CNS disorders of immune origin were observed within two weeks of inoculation with either the first or second dose of mRNA-based COVID-19 vaccines (Moderna = 3, Pfizer = 2). This includes: Fatal ADEM (n = 1), new-onset NMO (n = 2), new-onset fulminant MS (n = 1), and meningoencephalitis (n = 1). The age of our patients ranged from 27 to 81, and three were female. None of the patients had pre-existing neurological illnesses and one had a pre-existing autoimmune condition (immune thrombocytopenia purpura). New-onset focal neurological symptoms were present in all five patients, including quadriparesis, numbness, diplopia, and encephalopathy. CSF pleocytosis was present in all patients, and three had elevated protein. All but one patient (meningoencephalitis) had contrastenhancing lesions involving either the cerebrum or spinal cord. Both NMO patients had longitudinally extensive transverse lesions involving the central thoracic cord. Aquaporin-4 serum antibody was present in one NMO patients and aquaporin-4 CSF antibody present in the other. All but one patient (fatal ADEM) clinically improved with pulse steroids or plasmapheresis. Conclusions: These are among the emerging cases of CNS immunological events temporally associated with mRNA-based COVID-19 vaccines. These findings should be interpreted with great caution as they neither prove a link nor imply a potential long-term increased risk in postvaccination CNS autoimmunity. Larger prospective studies are needed. The mRNA-based SARS-CoV-2 vaccines should continue to be strongly encouraged given their high efficacy in overcoming this pandemic.

SARS-CoV-2 breakthrough infection in a fully vaccinated hemodialysis patient

Introduction: End-stage kidney disease (ESKD) is associated with immunosuppression manifesting as both increased infection rates & impaired vaccine immunoresponsiveness. Nonetheless, COVID-19 vaccines have proven highly effective in dialysis-dependent ESKD patients, with reported seroconversion rates as high as ∼96%. Herein, we describe a case of breakthrough SARS-CoV-2 infection in a fullyvaccinated hemodialysis patient. Case Description: A 69 year-old white male with dialysis-dependent ESKD presented for routine rural in-center hemodialysis with a new intermittent nonproductive cough following known COVID-19 exposure. He tested positive for COVID-19 via both rapid antigen testing & RT-PCR despite full mRNA-1273/Moderna SARS-CoV-2 vaccination ∼2 mo prior, & was admitted for inpatient management pending availability of isolated outpatient dialysis. He was afebrile, normoxemic, & clinically stable at presentation & throughout his subsequent hospital course. Following 10 d of uneventful isolation, during which he received thrice-weekly hemodialysis but no COVID-19-specific therapies, he resumed maintenance outpatient dialysis. Of note, he was current on all recommended vaccinations for dialysis patients, but had required multiple courses of hepatitis B vaccination for a documented history of impaired serocoversion. The patient ultimately developed both anti-nucleocapsid IgM & anti-spike IgG antibodies directed against SARS-CoV-2, & viral genome sequencing revealed a novel SARS-CoV-2 variant of interest (B.1.526). Discussion: While breakthrough COVID-19 is rare -reported in <0.001% of the fully vacciniated U.S. population as of 20 Apr 2021 -incidence rates may be higher in specific immunosuppressed subgroups such as ESKD patients. This case illustrates the potential for fully-vaccinated ESKD patients to contract COVID-19, particularly following known exposure(s) or in the setting of viral variants. It is also consistent with accumulating anecdotal clinical experience suggesting that breakthrough infections are generally milder phenotypically than primary infections in vaccine-naïve individuals. As such, high levels of suspicion may be required for identification & proper isolation. Constrained local resources in rural settings may also require different risk mitigation & management strategies for in-center hemodialysis patients with breakthrough COVID-19.

Covid 19: Utility of plain chest radiograph Scoring system to predict disease severity and Outcomes

Introduction Plain chest radiograph (CXR) is the most common imaging modality used to evaluate respiratory symptoms. CXR severity scoring has been shown to be an independent predictor of need for hospital admission and intubation and mechanical ventilation (I&MV) in COVID19 patients, but its role in predicting mortality is yet to be explored. Aim We evaluated the predictive value and prognostic utility of CXRs in adult patients with COVID 19 infections. Methods A retrospective analysis of 200 consecutive patients between March 2020 to May 2020 admitted to our tertiary centre with confirmed COVID 19 infection was conducted. Lung fields on CXRs were divided into 6 zones: Right and left upper, mid and lower zones. Mild changes were defined as unilateral changes zones 1-3;moderate changes were: Bilateral changes zones 2-3;severe changes: Changes zones 4-6. CXRs were reviewed and scored independently by 2 reporters: Thoracic radiologist and acute medical physician who were blinded to baseline patient characteristics and outcomes. Results 200 patients (median age: 79 (IQR 63-86) years) were included, 108 of which were females and 92 males. 61 (30.5%) died and 139 (69.5%) were discharged. During admission, 19 (9.5%) were admitted to ITU, 2 (1%) to the Non-invasive ventilation (NIV) unit and 179 (89.5%) to COVID Medical wards. Of the 61 patients (median age: 82 (IQR 73-89) years;27 (44.3%) male, 34 (55.7%) female) who died: 3 (4.9%) were admitted to ITU, 1 (1.6%) to NIV unit and 57 (93.4%) to COVID medical wards;45 (73.8%) received oxygen up to 15L, 1 (1.6%) received nasal high flow oxygen, 2 (3.3%) received CPAP and 3 (4.9%) received I&MV. CXR changes on admission were not an independent predictor of mortality;no CXR changes (p=0.099), Mild CXR changes (p=0.416), Moderate CXR changes (p=0.283), Severe CXR changes (p=0.994). Severe CXR changes was an independent predictor of I&MV (OR 2.298;95% CI 1.156-4.566;p=0.018). Conclusion We conclude that a CXR severity score is an effective tool to predict risk for hospital admission and the need for I&MV. Further larger studies will help validate this score by following up repeat CXRs to determine disease trajectory.

P11 COVID 19: Utility of plain chest radiograph scoring system to predict disease severity and outcomes

IntroductionPlain chest radiograph (CXR) is the most common imaging modality used to evaluate respiratory symptoms. CXR severity scoring has been shown to be an independent predictor of need for hospital admission and intubation and mechanical ventilation (I&MV) in COVID19 patients, but its role in predicting mortality is yet to be explored.AimWe evaluated the predictive value and prognostic utility of CXRs in adult patients with COVID 19 infections.MethodsA retrospective analysis of 200 consecutive patients between March 2020 to May 2020 admitted to our tertiary centre with confirmed COVID 19 infection was conducted. Lung fields on CXRs were divided into 6 zones: right and left upper, mid and lower zones. Mild changes were defined as unilateral changes zones 1–3;moderate changes were: bilateral changes zones 2–3;severe changes: changes zones 4–6. CXRs were reviewed and scored independently by 2 reporters: thoracic radiologist and acute medical physician who were blinded to baseline patient characteristics and outcomes.Results200 patients (median age: 79 (IQR 63–86) years) were included, 108 of which were females and 92 males. 61 (30.5%) died and 139 (69.5%) were discharged. During admission, 19 (9.5%) were admitted to ITU, 2 (1%) to the Non-invasive ventilation (NIV) unit and 179 (89.5%) to COVID Medical wards. Of the 61 patients (median age: 82 (IQR 73–89) years;27 (44.3%) male, 34 (55.7%) female) who died: 3 (4.9%) were admitted to ITU, 1 (1.6%) to NIV unit and 57 (93.4%) to COVID medical wards;45 (73.8%) received oxygen up to 15L, 1 (1.6%) received nasal high flow oxygen, 2 (3.3%) received CPAP and 3 (4.9%) received I&MV. CXR changes on admission were not an independent predictor of mortality;no CXR changes (p=0.099), Mild CXR changes (p=0.416), Moderate CXR changes (p=0.283), Severe CXR changes (p=0.994). Severe CXR changes was an independent predictor of I&MV (OR 2.298;95% CI 1.156–4.566;p=0.018).ConclusionWe conclude that a CXR severity score is an effective tool to predict risk for hospital admission and the need for I&MV. Further larger studies will help validate this score by following up repeat CXRs to determine disease trajectory.