Molecular and Clinical Epidemiology of SARS-CoV-2 Infection Among Vaccinated and Unvaccinated Individuals in a Large Healthcare Organization from New Jersey (preprint)

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOC) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5,007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOC, including Alpha (n =714), Delta (n =1,877), and Omicron (n =1,802). Omicron isolates were further sub-typed as BA.1 (n =899), BA.2 (n =853), and BA.4/BA.5 (n =50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1,577/5,007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p <0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p <0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p <0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

DiDang decoction improves mitochondrial function and lipid metabolism via the HIF-1 signaling pathway to treat atherosclerosis and hyperlipidemia.

ETHNOPHARMACOLOGICAL RELEVANCE: DiDang Decoction (DDD) is a traditional classical prescription that has been used to treat atherosclerosis (AS) and hyperlipidemia (HLP) in China. Nevertheless, the underlying mechanism of DDD remains unclear. AIM OF THE STUDY: To validate the mechanism of DDD in AS and HLP based on network pharmacology and in vitro experiments. MATERIALS AND METHODS: The chemical components of DDD were obtained from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) database and literature mining, and the disease targets of AS and HLP were obtained from the Gencards, OMIM, and DisGeNET databases. The intersection genes were imported into the STRING database to construct protein-protein interaction (PPI) network, and the DAVID database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Combined with the results of KEGG pathway analysis, the HIF-1 signaling pathway was selected for further in vitro experiments. RESULTS: The results showed that network pharmacology predicted 112 targets related to DDD treatment of AS and HLP, and the top 10 related pathways are: Lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, Chemical carcinogenesis - receptor activation, Pathways in cancer, Proteoglycans in cancer, Fluid shear stress and atherosclerosis, HIF-1 signaling pathway, Alcoholic liver disease, PPAR signaling pathway, and Coronavirus disease-COVID-19. In vitro experiments showed that DDD effectively reduced lipid accumulation in FFA-treated L02 cells; DDD attenuated mitochondrial damage and reduced ROS content; DDD inhibited ferroptosis and apoptosis; DDD up-regulated the expression of HIF-1α, Glutathione Peroxidase 4(GPX4), and Bcl2 proteins, and down-regulated expression of Bax protein. CONCLUSION: DDD exerts therapeutic effects on AS and HLP through multiple targets and pathways, and improves mitochondrial function, reduces ROS content, inhibits ferroptosis and apoptosis by activating the HIF-1 signaling pathway, which provides reliable theoretical and experimental support for DDD treatment of AS and HLP.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.).

Unusual case of propofol-related infusion syndrome complicating severe COVID-19 ARDS.

An elderly man presenting with shortness of breath and hypoxaemia was admitted with acute hypoxic respiratory failure secondary to COVID-19 pneumonia. Due to worsening hypoxaemia, he was transferred to the intensive care unit and required mechanical ventilation. Propofol was infused at 1.5-4 mg/kg/hour. Within 48 hours of initiation, we noticed worsening metabolic acidosis, acute kidney injury, hyperkalaemia, hyperphosphataemia, hypertriglyceridaemia, elevated creatine kinase and elevated myoglobin levels. Suspecting propofol-related infusion syndrome (PRIS), we discontinued his propofol infusion immediately and initiated supportive measures. In 48 hours, there was a significant improvement in metabolic acidosis, hypertriglyceridaemia, rhabdomyolysis and renal function. The propofol infusion rate and cumulative propofol dosage (under 140 mg/kg) were well below levels associated with PRIS. COVID-19's pathogenesis, still under investigation, may have contributed to this presentation. It is imperative for clinicians to maintain a high degree of suspicion once propofol is initiated, regardless of the cumulative dose or rate of infusion.

Characteristics and outcomes of 7620 Multiple Sclerosis patients admitted with COVID-19 in the United States (preprint)

Background At the start of the COVID-19 pandemic, several experts raised concerns about its impact on Multiple Sclerosis (MS) patients. Several small sample studies were published throughout the pandemic highlighting certain risk factors and outcomes. This study aims to provide a perspective using the biggest inpatient database from the United States. Method We screened for COVID-19 cases between April to December 2020, via the 2020 National Inpatient Sample (NIS). Characteristics of COVID-19 patients with and without MS were studied. The odds of mortality, mechanical ventilation and non-invasive ventilation were also analyzed. Finally, we investigated the risk factors of various outcomes among MS patients. Results We identified 1,628,110 hospitalizations with COVID-19, including 7620 (0.5%) MS patients. 68.6% of MS cases were Whites, and 63.3% were covered by Medicare. Compared to non-MS patients, MS patients with COVID-19 were mostly Females, had depression, peripheral vascular disease, and smoked. However, MS patients had lower cases of alcohol abuse, obesity, hyperlipidemia, diabetes, hypertension, CKD, or maintenance dialysis. MS patients with COVID-19 were also younger (mean age 60.65 years vs. 62.60 years, p<0.01). 8.9% of MS patients with COVID-19 did not survive their hospitalization, and it was lower than non-MS cases (12.9%, aOR 0.783, 95% CI 0.721-0.852, p<0.01). Less MS patients with COVID-19 needed non-invasive ventilation (4.5% vs. 6.4%, aOR 0.790, 95% CI 0.706-0.883, p<0.01) and mechanical ventilation (9.0% vs. 11.2%, aOR 1.017, 95% CI 0.937-1.104, p=0.687). Furthermore, MS patients with COVID-19 reported higher odds of non-invasive ventilation if they were of ages 60 and above (aOR 2.124, p<0.01), had chronic pulmonary disease (aOR 1.691, p<0.01), obesity (aOR 1.69, p<0.01), and diabetes (aOR 1.573, p<0.01). Private insurance beneficiaries showed reduced risk compared to Medicare (aOR 0.523, p<0.01). Similarly, for mechanical ventilation, those ages 60 and above (aOR 1.404, p<0.01), alcohol abuse (aOR 6.404, p<0.01), obesity (aOR 1.417, p<0.01), diabetes (aOR 1.992, p<0.01), hypertension (aOR 1.269, p=0.016), or dialysis (aOR 3.003, p<0.01) had higher odds, while females (aOR 0.700, p<0.01), smokers (aOR 0.588, p<0.01), and those with depression (aOR 0.698, p<0.01) or hyperlipidemia (aOR 0.711, p<0.01) showed reduced odds. Our study further found higher odds of mortality among those of age 60 and above (aOR 3.813, p<0.01), chronic pulmonary disease (aOR 1.739, p<0.01), obesity (aOR 1.425, p<0.01), CKD (aOR 1.982, p<0.01), or a history of old MI (aOR 1.864, p<0.01) while females (aOR 0.610, p<0.01), smokers (aOR 0.770, p<0.01), as well as those with depression (aOR 0.695, p<0.01), and hyperlipidemia (aOR 0.769, p<0.01) showed better outcomes. Blacks had lower odds of dying (aOR 0.636, p<0.01), whereas Hispanics had higher odds of dying (aOR 1.674, p<0.01), compared to Whites. Medicaid and Privately insured patients had lower odds of dying compared to Medicare i.e. (aOR 0.435, p<0.01), and (aOR 0.488, p<0.01), respectively. Conclusion We found several differences in patient characteristics among MS and non-MS patients with COVID-19. MS patients were also less likely to die or require non-invasive ventilation than non-MS patients. Further risk factors influencing the different outcomes among MS patients were also identified.

Update on Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Health.

Twenty percent of deaths in the United States are secondary to cardiovascular diseases (CVD). In patients with hyperlipidemia and hypertriglyceridemia, studies have shown high atherosclerotic CVD (ASCVD) event rates despite the use of statins. Given the association of high triglyceride (TG) levels with elevated cholesterol and low levels of high-density lipoprotein cholesterol, the American Heart Association (AHA)/American College of Cardiology (ACC) cholesterol guidelines recommend using elevated TGs as a "risk-enhancing factor" for ASCVD and using omega 3 fatty acids (Ω3FAs) for patients with persistently elevated severe hypertriglyceridemia. Ω3FA, or fish oils (FOs), have been shown to reduce very high TG levels, hospitalizations, and CVD mortality in randomized controlled trials (RCTs). We have published the largest meta-analysis to date demonstrating significant effects on several CVD outcomes, especially fatal myocardial infarctions (MIs) and total MIs. Despite the most intensive research on Ω3FAs on CVD, their benefits have been demonstrated to cluster across multiple systems and pathologies, including autoimmune diseases, infectious diseases, chronic kidney disease, central nervous system diseases, and, most recently, the COVID-19 pandemic. A review and summary of the controversies surrounding Ω3FAs, some of the latest evidence-based findings, and the current and most updated recommendations on Ω3FAs are presented in this paper.

Study protocol of the PROUD48 study comparing the effects of pemafibrate and omega-3 fatty acid ethyl esters on ApoB-48 in statin-treated patients with dyslipidaemia: a prospective, multicentre, open-label, randomised, parallel group trial in Japan.

INTRODUCTION: This study will compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl esters on fasting apolipoprotein B-48 (apoB-48), a surrogate marker reflecting postprandial hypertriglyceridaemia, which is a residual risk for atherosclerotic cardiovascular disease with statin treatment. METHODS AND ANALYSIS: This is a prospective, multicentre, open-label, randomised, parallel group, comparative trial. Adult Japanese patients with dyslipidaemia receiving statin treatment for more than 4 weeks with a fasting triglyceride level ≥177 mg/dL will be randomly assigned in a 1:1 ratio to receive pemafibrate (0.4 mg orally per day) or omega-3 fatty acid ethyl esters (4 g orally per day) for 16 weeks. The primary endpoint is the percentage change in fasting apoB-48 from baseline to 16 weeks. The key secondary endpoints include the change in fasting apoB-48 from baseline to 16 weeks, the percentage changes in clinical variables from baseline to 16 weeks and the incidence of adverse events. A total sample size of 128 was set by considering the increased drop-out rate due to the COVID-19 pandemic, in addition to estimation based on a two-sided alpha of 0.05 and a power of 0.8 for apoB-48. ETHICS AND DISSEMINATION: The study protocol has been approved by the Certified Review Board of the University of the Ryukyus for Clinical Research Ethics (No. CRB7200001) and will be performed in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results of the study will be disseminated through publications and conference presentations to participants, healthcare professionals and the public. TRIAL REGISTRATION NUMBER: jRCTs071200011.

Effect of Comorbidities on the Infection Rate and Severity of COVID-19: Nationwide Cohort Study With Propensity Score Matching.

BACKGROUND: A vaccine against COVID-19 has been developed; however, COVID-19 transmission continues. Although there have been many studies of comorbidities that have important roles in COVID-19, some studies have reported contradictory results. OBJECTIVE: This study was conducted using real-world data from COVID-19 patients in South Korea and aimed to investigate the impact of patient demographics and comorbidities on the infection rate and severity of COVID-19. METHODS: Data were derived from a nationwide South Korean COVID-19 cohort study with propensity score (PS) matching. We included infected individuals who were COVID-19-positive between January 1, 2020, and May 30, 2020, and PS-matched uninfected controls. PS matching was performed to balance the baseline characteristics of each comorbidity and to adjust for potential confounders, such as age, sex, Charlson Comorbidity Index, medication, and other comorbidities, that were matched with binary variables. The outcomes were the confirmed comorbidities affecting the infection rate and severity of COVID-19. The endpoints were COVID-19 positivity and severe clinical outcomes of COVID-19 (such as tracheostomy, continuous renal replacement therapy, intensive care unit admission, ventilator use, cardiopulmonary resuscitation, and death). RESULTS: The COVID-19 cohort with PS matching included 8070 individuals with positive COVID-19 test results and 8070 matched controls. The proportions of patients in the severe group were higher for individuals 60 years or older (severe clinical outcomes for those 60 years or older, 16.52%; severe clinical outcomes for those of other ages, 2.12%), those insured with Medicaid (Medicaid, 10.81%; other insurance, 5.61%), and those with disabilities (with disabilities, 18.26%; without disabilities, 5.07%). The COVID-19 infection rate was high for patients with pulmonary disease (odds ratio [OR] 1.88; 95% CI 1.70-2.03), dementia (OR 1.75; 95% CI 1.40-2.20), gastrointestinal disease (OR 1.74; 95% CI 1.62-1.88), stroke (OR 1.67; 95% CI 1.23-2.27), hepatobiliary disease (OR 1.31; 95% CI 1.19-1.44), diabetes mellitus (OR 1.28; 95% CI 1.16-1.43), and cardiovascular disease (OR 1.20; 95% CI 1.07-1.35). In contrast, it was lower for individuals with hyperlipidemia (OR 0.73; 95% CI 0.67-0.80), autoimmune disease (OR 0.73; 95% CI 0.60-0.89), and cancer (OR 0.73; 95% CI 0.62-0.86). The severity of COVID-19 was high for individuals with kidney disease (OR 5.59; 95% CI 2.48-12.63), hypertension (OR 2.92; 95% CI 1.91-4.47), dementia (OR 2.92; 95% CI 1.91-4.47), cancer (OR 1.84; 95% CI 1.15-2.94), pulmonary disease (OR 1.72; 95% CI 1.35-2.19), cardiovascular disease (OR 1.54; 95% CI 1.17-2.04), diabetes mellitus (OR 1.43; 95% CI 1.09-1.87), and psychotic disorders (OR 1.29; 95% CI 1.01-6.52). However, it was low for those with hyperlipidemia (OR 0.78; 95% CI 0.60-1.00). CONCLUSIONS: Upon PS matching considering the use of statins, it was concluded that people with hyperlipidemia could have lower infection rates and disease severity of COVID-19.

Utilization of preventive services in a systemic lupus erythematosus population-based cohort: a Lupus Midwest Network (LUMEN) study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a disease that can lead to damage of multiple organs and, along with certain treatments, increase the risk of developing cancer, cardiovascular disease, diabetes, osteoporosis, and infections. Preventive services are particularly important in patients with SLE to mitigate the aforementioned risks. We aimed to evaluate the trends of preventive services utilization in patients with systemic lupus erythematosus, compared with non-SLE population. METHODS: All ≥19-year-old patients in the Lupus Midwest Network (LUMEN) registry, a population-based cohort, with SLE on January 1, 2015, were included and matched (1:1) by sex, age, race, and county to non-SLE comparators. Among both groups, we compared the rates of screenings for breast and cervical cancer, hypertension, hyperlipidemia, diabetes mellitus, and osteoporosis as well as immunizations. RESULTS: We included 440 SLE patients and 430 non-SLE comparators. The probability of breast cancer screening among women with SLE was similar to comparators (hazard ratio [HR] 1.09, 95% CI 0.85-1.39), while cervical cancer screening was lower (HR 0.75, 95% CI 0.58-0.96). Hypertension screening was higher among patients with SLE (HR 1.35, 95% CI 1.13-1.62); however, hyperlipidemia screening was similar to comparators (HR 1.16, 95% CI 0.96-1.41). Diabetes and osteoporosis screenings were more likely to be performed for SLE patients than for comparators (HR 2.46, 95% CI 2.11-2.87; and HR 3.19, 95% CI 2.31-4.41; respectively). Influenza and pneumococcal immunizations were higher among SLE patients (HR 1.31, 95% CI 1.12-1.54; and HR 2.06, 95% CI 1.38-3.09; respectively), while zoster vaccination was similar (HR 1.17, 95% CI 0.81-1.69). CONCLUSIONS: The trends of utilization of preventive services by SLE patients vary according to screening or vaccine compared with the general population. Considering these differences, we demonstrate an opportunity for improvement, particularly in cervical cancer, hyperlipidemia, and osteoporosis screenings and vaccinations.

Risk factors of pulmonary complications in the patients with COVID-19: A case-control study (preprint)

Background Pneumothorax (PTX), pneumomediastinum (PM), and emphysema (EM) are complications of SARS-CoV-2 infections. Studying these situations' risk factors, complications, and prognosis is essential for early diagnosis during a pandemic. Methods We performed a case-control study of patients diagnosed with coronavirus pneumonia complicated with PTX, PM, and EM compared with patients without these complications to evaluate the risk factors for the incidence and prognosis of patients with pulmonary complications of COVID-19. We used parametric, non-parametric, and regression tests to analyze the data. Results We enrolled 162 patients (81 complicated, 81 uncomplicated). A past medical history of diabetes mellitus (DM), hyperlipidemia (HLP), lung disease, and ischemic heart disease (IHD) was not associated with PTX, PM, and EM in COVID 19 pneumonia (p-value > 0.05). The mortality rate was higher in the case group (69% vs. 15%). Among ventilator modes, 46.2% of intubated patients in the case group had synchronized intermittent mandatory ventilation (SIMV) for their ventilation. ESR, CRP, D-dimer, LDH, WBC, and troponin significantly increased, and lymphocytes decreased in complicated COVID compared to control groups (p-value < 0.05). Conclusion The nature of SARS-CoV-2 predisposes patients to PTX and other pulmonary complications. In practice, we could predict the complications and severity of COVID-19 pneumonia from some specific laboratory data.

Annual prevalence of non-communicable diseases and identification of vulnerable populations following the Fukushima disaster and COVID-19 pandemic (preprint)

Disasters, pandemics, and their response measures can have secondary effects on the physical and psychological health of affected populations. Identifying populations vulnerable to these effects is beneficial for promoting effective health and prevention strategies. Using health insurance receipt data from 2009 to 2020, we assessed changes in prevalence of major non-communicable diseases (NCDs), including hypertension, hyperlipidemia, diabetes, and mental disorders, among affected populations before and after the Fukushima disaster and coronavirus disease (COVID-19) outbreak in Japan. Furthermore, age and sex groups with the largest increases in prevalence after these events were identified. The participants of this study were members of the Employees' Health Insurance scheme, including employees of companies and their dependent family members. The dataset was provided by JMDC Inc. The annual age-adjusted prevalence of each disease was used to calculate the ratio of disease prevalence before and after the events. After the Fukushima disaster, hypertension, hyperlipidemia, and diabetes generally increased over a 9-year period in Fukushima Prefecture. The increase in the prevalence rate of these three NCDs and mental disorders were the highest among females aged 40-74 years compared to males and the other age groups. The prevalence of all four diseases increased after the COVID-19 outbreak in Japan, with marked increase in males aged 0-39 years. Populations that have experienced secondary health effects such as NCDs are unique to each disaster or pandemic, and it is important to provide tailor-made public health support among populations in accordance to the type of disasters and pandemic.

Hyperlipidemia, COVID-19 and acute pancreatitis: A tale of three entities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the ongoing pandemic of coronavirus disease 2019 (COVID-19), which presented as not only respiratory symptoms, but various digestive manifestations including pancreatic injury and acute pancreatitis (AP). The underlying mechanism is still unclear. Hypertriglyceridemia has become one of the leading causes of AP in recent years and hyperlipidemia is highly reported in COVID-19 cases. The current narrative review aimed to explore the associations between AP, COVID-19 and hyperlipidemia. Substantial cases of COVID-19 patients complicated with AP were reported, while the incidence of AP in the COVID-19 population was relatively low. Hyperlipidemia was common in COVID-19 patients with a pooled incidence of 32.98%. Hyperlipidemia could be a mediating factor in the pathogenesis of AP in COVID-19 patients. Further studies are warranted to clarify the relationship among AP, lipid metabolism disorders and COVID-19.

Epidemiological topology data analysis links severe COVID-19 to RAAS andhyperlipidemia associated metabolic syndrome conditions (preprint)

The emergence of COVID19 created incredible worldwide challenges but offers unique opportunities to understand the physiology of its risk factors and their interactions with complex disease conditions, such as metabolic syndrome. Epidemiological analysis powered by topological data analysis (TDA) is a novel approach to uncover these clinically relevant interactions. Here TDA utilized Explorys data to discover associations among severe COVID19 and metabolic syndrome, and it explored the probative value of drug prescriptions to capture the involvement of RAAS and hypertension with COVID19 as well as modification of risk factor impact by hyperlipidemia on severe COVID19.

Extensive papulonodular xanthoma: a diagnostic clue to homozygous familial hyperlipidaemia.

A man in his early 30s, presented with multiple soft tissue swellings over the buttocks, around the knees, ankles and dorsum of both the hands since childhood. His father and paternal uncle had similar lesions, and his father had coronary artery disease. One of his sisters had a history of sudden death due to an unknown cause at 14 years. The patient and his parents had very high serum levels of total cholesterol and low-density lipoprotein. Based on the above findings, a clinical diagnosis of familial hyperlipidaemia type II was made. Larger lesions were excised in stages, and histopathological evaluation revealed the lesions to be eruptive xanthoma. A cardiac assessment revealed no significant abnormality. Lipid-lowering agents and low-dose aspirin were started, and the patient was advised for regular cardiology and endocrine evaluation. This case emphasises its rare presentation and the importance of early diagnosis and management to prevent any untoward future incidence.

Association of Periodic Fasting with Lower Severity of COVID-19 Outcomes in the SARS-CoV-2 Pre-Vaccine Era: An Observational Cohort from the INSPIRE Registry (preprint)

Objectives: Intermittent fasting boosts some mechanisms of host defense against infection while modulating the inflammatory response. Lower-frequency periodic fasting is associated with greater survival and lower risk of comorbidities that exacerbate COVID-19. This study evaluated the association of periodic fasting with COVID-19 severity and, secondarily, initial diagnosis of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design: Prospective longitudinal observational cohort study. Setting: Single-center secondary care facility in Salt Lake City, Utah, USA with follow-up across a 24-hospital integrated healthcare system. Participants: Patients enrolled in the INSPIRE registry in 2013-2020 were studied if they had SARS-CoV-2 testing in March 2020-February 2021 and either tested positive (N=205) for the primary outcome evaluation or had a positive or negative test result for evaluation of the secondary outcome (n=1,524). Interventions: No treatment assignments were made; individuals provided information about their personal practice and history of engaging in routine periodic fasting across their lifespan. Main outcome measures: The association of periodic fasting with a composite of mortality or hospitalization as the primary outcome was evaluated by Cox regression through February 2021 and multivariable adjustments considered 36 covariables in INSPIRE patients diagnosed with COVID-19. Secondary analysis evaluated the association of fasting with testing positive for SARS-CoV-2 in INSPIRE patients evaluated for COVID-19 (n=1,524). Results: Subjects engaging in periodic fasting (n=73, 35.6%) did so for 40.4{+/-}20.6 years (max: 81.9 years) prior to COVID-19 diagnosis. The composite outcome occurred in 11.0% of periodic fasters and 28.8% of non-fasters (p=0.013), with HR=0.61 (95% CI=0.42, 0.90) favoring fasting. Multivariable analyses confirmed this association. Other predictors of hospitalization/mortality were age, Hispanic ethnicity, prior MI, prior TIA, and renal failure, with trends for race, smoking, hyperlipidemia, coronary disease, diabetes, heart failure, and history of anxiety, but not alcohol use. In secondary analysis, COVID-19 was diagnosed in 14.3% of fasters and 13.0% of non-fasters (p=0.51). Conclusions: Routine periodic fasting was associated with a lower risk of hospitalization or mortality in patients with COVID-19. Fasting may be a complementary therapy to vaccination that could provide immune support and hyperinflammation control during and beyond the pandemic. Trial registration: clinicaltrials.gov, NCT02450006 (the INSPIRE registry)

Hemolysis and blood gas analysis: it's time for a change!

Modern blood gas analyzers are not able to identify hemolysis, lipemia and icterus; therefore, the aim of this study was to assess the influence of hemolysis on blood gas samples. Blood gas analysis represents an essential part in the diagnosis and treatment of critically ill patients, including those affected by the pandemic coronavirus disease 2019 (COVID-19). Hemolysis, lipemia, and icterus, are causes of clinical misinterpretation of laboratory tests. A total of 1244 blood gas specimens were collected over a one-week period from different clinical wards, including the Emergency Department, and were assessed for serum indices on Cobas C6000 CE (Roche Diagnostics, Mannheim, Germany). The prevalence of hemolysis, lipemia, and icterus were 5%, 12%, and 14%, respectively. Sample storage at room temperature, delivery to central laboratory using pneumatic tube system, as well as small sample size, strongly affected blood gas parameters (p < .01). Hemolysis led to an increase in analytical bias for pH, pO2, and potassium, and a significant decrease for pCO2, HCO3-, sodium, and Ca2+ (p <.01). Currently, hemolysis detection systems are not yet widespread, and a rapid centrifugation of samples after blood gas analysis along with the assessment of serum indices represent the only prompt approach to identify unsuitable results, avoiding pitfalls in clinical decision-making, although it cannot be applied to the Emergency Department routine. Blood gas analyzers manufacturers and suppliers should implement automated built-in serum indices detection systems.

Thrombogenicity markers for early diagnosis and prognosis in COVID-19: a change from the current paradigm?

Standard biomarkers have been widely used for COVID-19 diagnosis and prognosis. We hypothesize that thrombogenicity metrics measured by thromboelastography will provide better diagnostic and prognostic utility versus standard biomarkers in COVID-19 positive patients. In this observational prospective study, we included 119 hospitalized COVID-19 positive patients and 15 COVID-19 negative patients. On admission, we measured standard biomarkers and thrombogenicity using a novel thromboelastography assay (TEG-6s). In-hospital all-cause death and thrombotic occurrences (thromboembolism, myocardial infarction and stroke) were recorded. Most COVID-19 patients were African--Americans (68%). COVID-19 patients versus COVID-19 negative patients had higher platelet-fibrin clot strength (P-FCS), fibrin clot strength (FCS) and functional fibrinogen level (FLEV) (P ≤ 0.003 for all). The presence of high TEG-6 s metrics better discriminated COVID-19 positive from negative patients. COVID-19 positive patients with sequential organ failure assessment (SOFA) score at least 3 had higher P-FCS, FCS and FLEV than patients with scores less than 3 (P ≤ 0.001 for all comparisons). By multivariate analysis, the in-hospital composite endpoint occurrence of death and thrombotic events was independently associated with SOFA score more than 3 [odds ratio (OR) = 2.9, P = 0.03], diabetes (OR = 3.3, P = 0.02) and FCS > 40 mm (OR = 3.4, P = 0.02). This largest observational study suggested the early diagnostic and prognostic utility of thromboelastography to identify COVID-19 and should be considered hypothesis generating. Our results also support the recent FDA guidance regarding the importance of measurement of whole blood viscoelastic properties in COVID-19 patients. Our findings are consistent with the observation of higher hospitalization rates and poorer outcomes for African--Americans with COVID-19.

Association of comorbidities with COVID-19 infection rate and severity: nationwide cohort study with propensity score matching (preprint)

ABSTRACT O bjective To describe the association of comorbidities with coronavirus infection-19 (COVID-19) infection rates and severity of infection through Korean nationwide medical system. D esign Nationwide population-based retrospective cohort study. S etting Korean national health insurance claims database between January 1, 2020, and May 30, 2020. P articipants Patients with positive COVID-19 test and 12 folded controls matched by age, sex and region. M ain O utcomes M easures Outcomes were confirmation of the comorbidities affecting the infection rate and the severity of COVID-19. Patients and outcomes were propensity score matching of factors which may affect COVID-19 infection rate and severity was performed. COVID-19 infections were confirmed through laboratory testing. Severe infection was defined as those who underwent tracheostomy, continuous renal replacement therapy, intensive care unit admission, ventilator use, cardiopulmonary resuscitation, or died. R esults A total of 8070 individuals with positive covid-19 test and 12015 controls were identified. In people aged 60 or older, in those insured with Medicaid, and in the disabled, the proportion corresponding to the severe group of patients showed a tendency to increase. The infection rate of COVID-19 was highest in pulmonary disease (adjusted odds ratio 1.88, 95% confidence interval 1.70 to 2.03), and hyperlipidemia (0.73, 0.67 to 0.80) had a lower infection rate. Disease severity was highest in kidney disease (5.59, 2.48 to 12.63), and lower in hyperlipidemia (0.78, 0.60 to 1.00). C onclusions There is less bias as the government pays for all tests and treatments related to COVID-19 included in the data used in this study. Using propensity matching to reduce statistical bias, we found that most comorbidities increased the infection rate and severity of COVID-19, whereas hyperlipidemia reduced the rate and severity of infection. These results can be utilized to effectively manage COVID-19 infections.

Worldwide association of lifestyle related factors and COVID-19 mortality (preprint)

BackgroundSeveral lifestyle related factors such as obesity and diabetes have been identified as risk factors for Coronavirus disease 2019 (COVID-19) mortality. The objective of this study was to examine the global association between lifestyle related factors and COVID-19 mortality using data from each individual country. MethodsThe association between prevalence of seven lifestyle related factors (overweight, insufficient physical activity, smoking, type 2 diabetes, hypertension, hyperlipidemia, and age over 65) and COVID-19 mortality was assessed by linear and multivariable regression among 186 countries. The cumulative effect of lifestyle related factors on COVID-19 mortality was assessed by dividing countries into four categories according to the number of lifestyle related factors in the upper half range and comparing the mean mortality between groups. ResultsIn linear regression, COVID-19 mortality was significantly associated with overweight, insufficient physical activity, hyperlipidemia, and age [≥]65. In multivariable regression, overweight and age [≥]65 demonstrated significant association with COVID-19 mortality (P = 0.0039, 0.0094). Countries with more risk factors demonstrated greater COVID-19 mortality (P for trend <0.001). ConclusionLifestyle related factors, especially overweight and elderly population, were associated with increased COVID-19 mortality on a global scale. Global effort to reduce burden of lifestyle related factors along with protection and vaccination of these susceptible groups may help reduce COVID-19 mortality.