The Impact of the COVID-19 Pandemic on Retrenchment, Vaccinations, and Global Happiness

COVID-19's impacts have spread widely in all directions such as economy, people's lifestyles and well-being. Though existing studies have highlighted such an impact, it remains unclear how the current COVID-19 situation has affected the retrenchment, vaccination and global happiness. In this paper, we present an automated tool enables the public to view various insight. In particular, we integrate and analyze the data from various data sources and show how the COVID19 has impacted Singapore and globally. We employ the regression models to identify the correlation between Human Development Index, Stringency Index, Gross Domestic Product per Capita, Total Deaths from COVID-19, and Total Cases of COVID-19;the rate of vaccination and vaccine hesitancy;and the factors to positively correlate to the global happiness. The insight provided adds values to better fight against the COVID-19 pandemic and future global crisis. © 2023 IEEE.

Identification of key drivers for improving inventory management in pharmaceutical supply chains

Existing literature on optimizing inventory levels in pharmaceutical supply chains has focused on a limited set of drivers. However, the global supply chain disruptions produced by the Covid-19 pandemic demonstrated the need for a more nuanced picture of the inventory management drivers in this sector to identify profitable inventory configurations while fulfilling demands and safety margins. To address this gap in the literature, this paper identifies key drivers impacting inventory levels and develops a framework for assessing inventory configurations in pharmaceutical supply chains. The framework is tested using a single case study approach. The case study showed that while external and downstream supply chain factors were recognized as being critical to pursuing inventory reduction initiatives, internal factors prevailed when making inventory management decisions. The framework developed in this paper may assist practitioners in identifying the most important factors impacting inventory levels within a specific pharmaceutical supply chain configuration and is in use in the industry today. © 2023, The Author(s) under exclusive licence to German Academic Society for Production Engineering (WGP).

Cardiac Manifestations of Post-Acute COVID-19 Infection.

PURPOSE OF REVIEW: There is emerging evidence that the post-acute and chronic phases of COVID-19 infection are associated with various significant cardiovascular sequelae. RECENT FINDINGS: Long COVID has been shown to be associated with multiple cardiovascular sequelae including direct myocardial injury, arrhythmias, and cardiomyopathies. Hypotheses on the mechanism of myocardial injury include direct viral infiltration and autoimmune dysregulation. Long COVID is associated with persistent cardiac ischemia in patients with no previous history of coronary disease, atrial and ventricular arrhythmias, and the development of new-onset heart failure in previously healthy patients. Onset of long COVID may be related to severity of the initial SARS-CoV2 infection. Cardiac MRI is a valuable tool in assessing myocarditis and the development of cardiomyopathies in the setting of long COVID. Both patients with and without pre-existing cardiovascular disease are at risk of developing myocardial injury in the setting of long COVID. Future studies will elucidate both cardiovascular mortality and cardiac rehabilitation in the post-acute and chronic phases of COVID-19.

Refractory right ventricular myocarditis induced by immune checkpoint inhibitor despite therapy cessation and immune suppression.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are currently widely used for treatment of various types of cancers. ICI-induced myocarditis, though uncommon, accounts for high risk of major adverse cardiac events and mortality, which makes appropriate diagnosis important. We here present a unique, challenging case of ICI-induced, refractory and isolated right ventricular (RV) myocarditis. CASE PRESENTATION: A 32-year-old female with breast cancer presented with newly onset chest pain and dyspnea shortly after initiation of Pembrolizumab. Coronary angiography showed normal coronary arteries and a cardiac magnetic resonance (CMR) revealed myocarditis involving the right ventricle with chamber dilation and severe dysfunction. ICI therapy was stopped, and high dose steroid therapy was initiated and symptoms resolved. However, three months after initial presentation, the patient was hospitalized for DKA and decompensated right heart failure, and a repeat cardiac MRI at that time showed recurrent, isolated right ventricular myocardial inflammation/edema without LV involvement. High dose steroid therapy was started again and at 6-month follow up, surveillance CMR continued to show persistent right-sided myocarditis, patient was eventually treated with Abatacept with resolution of HF symptoms, RV dysfunction and biomarkers at 10-month follow up. CONCLUSIONS: We describe a unique case of isolated ICI-induced right ventricular myocarditis leading to right ventricular failure, that was refractory despite ICI therapy cessation and immune suppression by repeated high dose steroids. Co-stimulatory pathway modulation with Abatacept eventually lead to the normalization of RV function and dilation ten months after initial myocarditis onset.

Comparable Public Health Responses to COVID-19 Pandemic

Coronavirus-2 (SARS-CoV-2) is a serious respiratory disorder and has challenged public health organizations everywhere. To effectively target government interventions, the most vulnerable persons to coronavirus disease-19 (COVID-19), the development of serious health indications and mortality must be identified. We conducted a thorough literature review to provide the existing position of technical information in these domains, stressing the necessity for a united worldwide approach, touching forward and learning for upcoming diseases. Medline, Embase and Global Health, and the Web of Science, were searched by the end of August 2021. The search criteria were SARS-CoV-2 and COVID-19-specific. A broad array of descriptions has been recycled regarding the harshness of the condition. Furthermore, multiple countries took various public health steps to control the transmission of COVID-19. In this review, we are enlisting the countries and their short- andlong-term public health responses to combat this pandemic. We also described four key sections of public health responses, i-e, monitoring, public education, crowd control and establishment of health care facilities followed by various countries to prevent the pandemic. Copyright © 2022 Khan et al.

Lipid Nanoparticles With Low Immunogenicity For Nucleic Acid Delivery

Purpose/Objectives: The delivery of nucleic acids to cells has revolutionized medicine and enabled new technologies such as mRNA vaccines and stem cell therapies. These recent advances rely on delivery vehicles to stabilize the genetic payload and increase cellular transfection. While engineered viruses are efficient vectors for ex vivo cellular reprogramming, they are not ideal for in vivo gene therapies as repeated dosing leads to anti-vector immunity. Lipid nanoparticles have thus emerged as the best alternative to viral vectors for in vivo nucleic acid delivery. However, all FDA-approved lipid nanoparticles have been linked to inflammatory responses, undesirable for regenerative medicine applications that require precise immunomodulation. Thus, non-immunogenic delivery materials must be developed to fulfill the immense potential of gene therapy in regenerative medicine. Lipid nanoparticles typically comprise 4 different lipids, with the ionizable amino lipid being the main driver of potency and immunogenicity. A way to reduce immunogenicity is to develop lipid nanoparticles that minimize the amount of lipids per gram of nucleic acids. To do so, we developed a novel class of ionizable amino lipids with high charge density. Our primary objective is to design a lipid nanoparticle that maximizes RNA delivery and minimizes immunogenicity. Methodology: We designed a library of proprietary ionizable lipids based on the structure of a poly(amido amine) dendron. The structure is modular, which allowed us to systematically vary molecular motifs to optimize important physiochemical parameters: Lipid-to-RNA ratio;apparent pKa;surface zeta potential;size distribution;and RNA encapsulation These structures are also designed to include a higher number of amines compared to current ionizable lipids. This improves ionization charge density of the lipid and lowers the amount of lipid required to encapsulate RNA. In this study, lipid nanoparticles contain an ionizable lipid selected from our library, cholesterol, a phospholipid, and a PEG-lipid. The lipids and formulation conditions were selected to mimic Moderna's COVID-19 vaccine (SpikeVax), albeit with different lipid-to-RNA ratios. C57BL/6 mice were injected intramuscularly with nanoparticles co-formulated with a firefly luciferase mRNA and ovalbumin mRNA to simultaneously study transfection efficiency and antigen-specific immune responses. Nanoparticles that comprise SM-102, the ionizable lipid used in SpikeVax, were used as a comparative control due to their high potency and immunogenicity. Luciferase activity was detected using an IVIS Spectrum, and key organs were harvested for immune phenotyping. Results: We have so far determined the effect of hydrophobic motifs on apparent pKa and RNA encapsulation. Our best lipids with optimized tails did not induce IFN-I responses in vitro and demonstrated comparable in vivo efficacy to SM-102. We are currently in the process of collecting immunogenicity data which we expect to complete prior to the conference. Conclusion/Significance: We have produced a novel set of lipid nanoparticles that efficiently transfect cells in vivo. These new particles deliver RNA with half of the lipid mass used in SpikeVax, which can reduce the amount of material-induced immunogenicity. This result opens the door to developing mRNA vaccines with fewer side effects and equitable gene therapies for untreatable diseases such as inflammatory and autoimmune disorders.

Legality of restrictions on human rights and freedoms in a Covid-19 Pandemic: The experience of Ukraine

The purpose of the study is to examine the content of the right to health during the COVID-19 pandemic. The study focused on the legitimacy of restrictions on constitutional rights and freedoms due to mandatory vaccination and other restricition measures in Ukraine. Diversified views of scholars on this issue were established, the legislative basis for establishing restrictions on constitutional rights and freedoms of citizens was determined, and the method of normative establishment of such restrictions during the COVID-19 pandemic adopted by the Government of Ukraine was criticized. The legal positions of the European Court of Human Rights, the Constitutional Court of Ukraine and the Supreme Court of Ukraine on the legality of compulsory vaccination during a pandemic and restrictions on the constitutional rights and freedoms of citizens are presented. To achieve the goal of the research, general scientific research methods were used, such as: analysis, synthesis, modeling and ion. These methods were used to determine the constituent elements of a person's right to health care, to determine their relationship, to give specific examples of solving the problem of vaccination, to draw conclusions on the legality of vaccination and to limit certain constitutional rights of citizens.

Coronavirus disease 2019 and the cardiologist.

PURPOSE OF REVIEW: There continues to be extensive clinical and epidemiological data to suggest that coronavirus disease 2019 (COVID-19) infection is associated with numerous different types of cardiac involvement. RECENT FINDINGS: Myocardial injury has been reported in over 25% of patients hospitalized due to COVID-19 infection and is not only associated with a worse prognosis but with higher mortality, approaching 40%. Currently proposed mechanisms of myocardial injury include direct viral infection, cytokine storm, endothelial inflammation, demand ischemia, interferon-mediated response and stress cardiomyopathy. COVID-19 infection is associated with new-onset arrhythmias and heart failure regardless of history of previous cardiovascular disease. Echocardiographic findings can be useful to predict mortality in COVID-19 patients and cardiac MRI is an effective tool to both assess COVID-19 induced myocarditis and to follow-up on cardiac complications of COVID-19 long-term. Although there is an association between COVID-19 vaccination and myocarditis, pericarditis or arrhythmias, the risk appears lower when compared to risk attributable to the natural infection. SUMMARY: Patients with cardiovascular disease are not only more likely to suffer from severe COVID-19 infection but are at increased risk for further complications and higher mortality. Further data compilation on current and emerging treatments of COVID-19 will have additional impact on cardiovascular morbidity and mortality of COVID-19 infection.

A Django Web Application to Promote Local Service Providers

In the recent years, especially after covid-19 became a thing, people started finding information about Retail On- Demand Services online rather than relying on local contacts. This makes it a lot easier for people to find and book services online, rather than going out and booking them in person. So, a Django-based Web application with a real time database deployed on cloud that provides details of some service providers (Carpenters, Electricians etc.) in region of Kanuru (Vijayawada, India) has been designed. Data are collected from multiple sources using a scraping code that Beautiful Soup framework is used and stored in PostgreSQL database that is later deployed on Cloud platforms. This helps people from this region to access information quickly and help them book these On-Demand Services Faster. © 2022 IEEE.

Global estimates of frequency and outcomes of coronavirus disease 2019 associated stroke and myocardial infarction

Background: We evaluated the frequency and outcomes of Coronavirus Disease 2019 (COVID-19) associated stroke (ischemic and hemorrhagic) and myocardial infarction (MI) in a global research network. Methods: All adult (≥ 18 years) patients with ICD-10 diagnoses of COVID-19 were included and those with a stroke (ischemic stroke, intracerebral hemorrhage [ICH], transient ischemic attach [TIA] or subarachnoid hemorrhage [SAH]) or myocardial infarction (MI) ± 28 days from COVID-19 diagnosis were flagged. Individuals with a prior history of stroke / MI were excluded. COVID-19 associated stroke (CAS) and MI (CAM) frequencies were compared to prior AHA-reported population-based incidences. Severe COVID-19 disease (use of ventilator, intubation, or life support) and 90-day mortality were evaluated among no-stroke/MI and stroke/MI subgroups utilizing general linear models adjusted for age, sex, race/ethnicity, and Charlson Comorbidity Index scores. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. Results: Between Jan 2020 and Jul 2021, we identified 637,820 COVID-19 patients of whom 4,559 (0.71%) had a CAS and 6,972 (1.09%) had a CAM. COVID-19 was associated with significantly higher stroke/MI rates compared to population based reported incidence (ORs, CI for CAS 1.99, 1.93 - 2.05 and CAM 3.09, 3.01 - 3.16). Severe COVID disease was observed among 1.07% of COVID-19 only patients, 11.25% of CAS patients (aOR, CI: 4.82, 4.35 - 5.34), and 14.81% of CAM patients (aOR, CI: 5.77, 5.34 - 5.22). 90-Day mortality was 1.92% for COVID-19 only patients, 14.35% for CAS patients (aOR, CI: 3.16, 2.87 - 3.46), and 20.52% for CAM patients (aOR, CI: 4.12, 3.85 - 4.41). Group specific demographic and outcome proportions are reported (Figure). Conclusion: The COVID-19 pandemic has tremendously exacerbated the burden of cerebrovascular and cardiovascular disease globally. Continued work is needed to understand drivers of poor outcomes among COVID-19 patients.

Higher risk of COVID-19 mortality among patients with preexisting neurological disease

Introduction: Neurotropism of the SARS-CoV-2 has been reported. We evaluated the risk of poor outcomes associated with preexisting neurological disease (PEND) among COVID-19 patients. Methods: We analyzed data from COVID-19 Outcomes Registry (CURATOR) at Houston Methodist. All adult (≥ 18 years) patients tested for SARS-CoV-2 RNA in nasopharyngeal specimens were included. Utilizing ICD-10 diagnoses codes, we classified PEND patients as those with documented history of ischemic or hemorrhagic stroke, transient ischemic attack, mild cognitive impairment, Alzheimer's disease and related dementias including vascular dementia, primary and metastatic brain tumors, epilepsy, motor neuron disease, amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, spinal cord injury, and traumatic brain injury. Logistic regression models were fitted to assess the odds of COVID-19 mortality associated with PEND. Odds ratios (OR) and 95% Confidence Intervals (CI) are reported. Results: Between March 3 and August 10, 2020, 86,614 individuals were tested for SARS-CoV-2, of whom 14,233 (16.4%) tested positive, with 4,473 (31.4%) hospitalizations, and 431 (9.6%) deaths. Overall 11,473 (13.2%) individuals had PEND, of whom 1,458 (12.7%) tested positive, 966 (66.3%) were hospitalized and 165 (17.1%) died. Among positive cases, PEND (vs. non-PEND) patients were older (67.1 vs. 46.4 years) and had a higher overall comorbidity burden (median Charlson Comorbidity Index: 6 vs. 1). The proportion of PEND patients was significantly higher among COVID-19 patients who died (vs. those who were discharged alive) (38.3% vs. 19.8%, crude OR, CI: 2.51, 2.03 - 3.09). In the fully adjusted model for socio-demographic, comorbidity and clinical factors, PEND was independently associated with higher risk of COVID-19 mortality OR (CI): 1.42 (1.04, 1.95) (graphic). Conclusions: Biological mechanisms of higher COVID-19 mortality among patients with PEND need to be evaluated.

Risk of COVID-19 mortality among patients with preexisting cerebrovascular disease

Introduction: COVID-19 is associated with incident cerebrovascular disease (CVD). We evaluated the association between preexisting CVD and COVID-19 mortality. Methods: Utilizing deidentified pooled data from 40 healthcare organizations, adult (≥ 18 years) COVID-19 patients were identified based on ICD-10 diagnostic codes and documentation of laboratory positivity for SARS-CoV-2 RNA or antibodies. Among COVID-19 patients, those with documented ICD-10 diagnoses for cerebral infarction / ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH) and transient ischemic attack (TIA) at least 30- days before the index COVID-19 event were classified as the CVD group. The CVD and non-CVD groups were propensity score (PS) matched on demographic and comorbidity variables. Pre and post-match risk ratios (RR) and 95% confidence intervals (CI) for 30 and 90-day mortality were calculated. Mortality rates for CVD subgroups (ICH, SAH, AIS, TIA) are also reported. Results: Among a total of 140,034 COVID-19 cases, 4,614 (3.3%) had prevalent CVD. CVD patients were significantly older and were predominantly males of either white or black race (vs. other). CVD patients also had a higher comorbidity burden (vs. non-CVD patients) (graphic). A 1:1 PS algorithm yielded an optimally matched sample of 8,218 COVID-19 patients (4,109 CVD and non-CVD patients each). In the matched sample, 30-day mortality was 8.4% among CVD patients and 7.0% among non-CVD patients RR (CI): 1.20 (1.03 - 1.39). 90-day mortality among CVD patients (vs. Non-CVD patients) remained significantly elevated (9.7% vs. 8.2%), RR (CI): 1.20 (1.04 - 1.37). Among CVD subgroups, 30 and 90-day mortality was higher for patients with preexisting ICH (11.8% and 13.7%, respectively) compared to IS (8.7% and 10.2%, respectively). Conclusion: Preexisting CVD significantly increases the mortality risk in COVID-19 patients. Mechanisms for poor COVID-19 outcomes among CVD patients need to be evaluated.

COVID-19 susceptibility and mortality among individuals with mild cognitive impairment, alzheimer's disease and related dementias

Introduction: We evaluated the burden of SARS-CoV-2 susceptibility and COVID-19 mortality associated with Mild Cognitive Impairment (MCI) or Dementia (MCID). Methods: We analyzed data from COVID-19 Outcomes Registry (CURATOR) at Houston Methodist;a tertiary healthcare system in greater Houston. All adult (≥ 18 years) patients tested for SARS-CoV-2 RNA in nasopharyngeal swabs were included. Utilizing validated ICD-10 codes (MCI, Alzheimer's Disease, Vascular and Other Dementias) and use of MCID specific medications, we flagged patients with preexisting MCID. Logistic regression models were fitted to evaluate the odds of SARS-CoV-2 susceptibility and COVID-19 mortality associated with preexisting MCID. Odds ratios (OR) and 95% Confidence Intervals (CI) are reported. Results: Between March 3 and August 10, 2020;86,614 individuals were tested, of whom 14,233 (16.4%) tested positive, with 4,473 (31.4%) hospitalizations, and 431 (9.6%) deaths. Overall 3,069 individuals had preexisting MCID;among whom 518 (16.9%) tested positive. Among all SARS-CoV- 2 positive cases, MCID patients (vs. non MCID group) were older (79.9 vs. 47.3 years) and had higher overall comorbidity burden (median Charlson Comorbidity Index: 6 vs. 0), with higher proportion (%) of hypertension (90.3 vs. 39.0), heart failure (37.8 vs. 7.5), diabetes (69.3 vs. 28.2), and cancer (14.5 vs. 4.8). Mortality among MCID patients (vs. non MCID) was 22.3% vs. 8.6%. In fully adjusted models (demographics, comorbidities, clinical / laboratory parameters, complications, treatment and ICU admission), pre-existing MCID was independently associated with higher SARSCoV- 2 susceptibility, OR (CI) 1.62 (1.46-1.80) and in-hospital mortality OR (CI): 1.79 (1.23-2.61) among COVID-19 patients (graphic). Conclusions: Regardless of age, MCID is a potential risk factor for SARS-CoV-2 infection and COVID-19 mortality. Targeted prevention and management strategies are warranted for this highrisk group.

Sex differences in mortality among patients with COVID-19 related stroke

Introduction: Overall poor COVID-19 outcomes have been reported among males. We evaluated sex differences in mortality among patients with stroke related to COVID-19. Methods: Utilizing pooled deidentified data from 30 healthcare organizations, we identified COVID- 19 patients via ICD-10 diagnosis or documented laboratory confirmation of SARS-CoV-2 RNA or antibodies. Patients with ICD-10 diagnoses of ischemic stroke or intracerebral hemorrhage within 30 days before or after the COVID-19 event were flagged. Male and female patients were propensity score (PS) matched on other demographic and comorbidity variables. Risk Ratio (RR) and 95% Confidence Interval (CI) for association between sex and 90-day mortality is reported. Kaplan-Meier analyses with log rank test (LRT) were conducted for time-to-death. As a sensitivity analysis, we only included a smaller sub-set with first instance of IS or ICH ± 30-days of COVID-19 diagnosis. Results: Among 149,410 COVID-19 patients, 1,618 (1.1%) had a stroke diagnosis ± 30-days of confirmed COVID-19. Of whom, 1,609 patients (847 males and 762 females) were included in primary analyses. Females were older (67.7 vs. 65.7 years) and were more likely to be of black race (34.1% vs. 27.6%). Females had a significantly higher proportion of chronic pulmonary disease (38.8% vs. 28.8%) and obesity (34.2% vs. 24.8%);whereas males had higher proportion of alcohol abuse (8.5% vs. 3.8%). A 1:1 PS algorithm yielded an optimally matched sample of 634 males and females each, balanced on all covariates. In the matched sample, 11.7% of females and 15.8% of males experienced 90-day mortality;RR (CI): 1.35 (1.02 - 1.78), LRT p value 0.04. Higher risk of 90- day mortality among males with COVID-19 and stroke was maintained in the sensitivity analyses, RR (CI): 1.47 (1.06 - 2.00), LRT p value = 0.03 (graphic). Conclusion: Future studies examining the socio-demographic and biological mechanisms for poor stroke outcomes among males with COVID-19 are needed.

A meta-analysis to estimate the incidence of thromboembolism in hospitalized COVID-19 patients

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of venous and arterial thrombosis in patients. Numerous studies have been conducted on COVID-19 and its association with thromboembolism is well known. We conducted a meta-analysis to find out the incidence of thromboembolism in hospitalised patients with COVID-19 to provide more generalized results. A systematic literature search was conducted in PubMed and SCOPUS to find observational studies reporting outcomes of interest. Amongst the studied thromboembolic events, the meta-analysis showed the prevalence of pulmonary embolism (PP: 12.4% [7.2%, 18.6%];12 = 97.23%) to be the highest. It was followed by deep vein thrombosis (PP: 8.6% [4.2%, 14.3%];12 = 97.52%), myocardial infarction (PP: 2.3% [0.2%, 11.2%];12 = 99.3%), and stroke (PP: 1.2% [0.8%, 1.6%];12 = 65.09%). The results of this analysis further warrant the timely and appropriate use of pharmacological thromboprophylaxis and identification of risk factors in hospitalized COVID-19 patients.

Ohio response to covid-19 and its impact on interventional pain management practices

The coronavirus disease 2019 (COVID-19) pandemic has drastically altered daily living and medical care for Ohio residents and the practice of medicine for the interventional pain management physician. As a state, Ohio tends to be demographically representative of the broader US population. Thus, reviewing the efforts deployed by Ohio to flatten the COVID-19 infection curve and reduce the spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important component of determining optimal procedures for mitigating the effects of the COVID-19 pandemic. Over the course of several announcements and orders during the months of March and April, new policies were put into place to prevent COVID-19 transmission, which included efforts to facilitate social distancing and ensure the health care system could manage the number of COVID-19 cases at peak infection rate. Efforts directed toward medical providers included delay of elective procedures, expansion of telehealth options, and new temporary guidance for prescribing controlled substances. The Ohio COVID-19 containment approach resulted in a substantial reduction in COVID-19 cases compared with early models of disease spread, and the state has begun a phased reopening. Continued vigilance in applying social distancing and infection control measures will be a critical component of preventing or reducing the impact of a second wave of COVID-19 in Ohio.