Validation of RT-qPCR primers and probes for new and old variants of SARS-CoV-2 in a world scale (preprint)

Introduction: The demand for molecular diagnosis of pathogens has surged dramatically since the onset of the COVID-19 pandemic. In this context, different diagnostic tests have been developed to identify SARS-CoV-2 in patient samples. The emergence of new variants of SARS-CoV-2 raises questions about whether the molecular tests available for diagnosis continue to be effective in detecting the virus in biological samples. Objective: This study analyzed the viability of molecular targets directed to N, E and RdRp genes available against the new variants of SARS-CoV-2. Methodology: For this, we used bioinformatics tools to analyze SARS-CoV-2 genomic data of different variants deposited in GSAID and NCBI virus genomic databases to assess the accuracy of molecular tests available for the diagnosis of COVID-19. We also developed software for analyzing mutation frequencies in different molecular targets from the mutation database. Results: Mutation frequency analysis revealed a high rate of mutations in the N, E and RdRp genes and targets, although the target regions were more conserved. Only three SNPs were recurrent in the sequences of the variants identified in different continents and all in different targets. On the other hand, the registered mutations are not consistent and do not appear frequently in isolates of the same variant in all regions of the world. Conclusion: Our data suggest that the molecular targets designed for the first SARS-CoV-2 variants remain valid for the identification of new virus variants despite the large number of identified haplotypes. However, false negative test failures can be identified by using more than one molecular target for the same sample. Genomic regions that are under evolutive selective pressure should be avoided in the use of the diagnostic, once the emergence of new variants may affect the efficiency of molecular testing on a global scale.

Preoperative COVID-19 Vaccination is Associated with Decreased Perioperative Mortality after Major Vascular Surgery (preprint)

Background: The objective of this study was to examine the effect of COVID-19 vaccination on perioperative outcomes after major vascular surgery. Methods: This is a multicenter retrospective study of patients who underwent major vascular surgery between December 2021 through August 2023. The primary outcome was all-cause mortality within 30 days of index operation or prior to hospital discharge. Multivariable models were used to examine the association between vaccination status and the primary outcome. Results: Of the total 85,424 patients included, 19161 (22.4%) were unvaccinated. Unvaccinated patients were younger compared to vaccinated patients (mean age 68.44 +/- 10.37 years vs 72.11 +/- 9.20 years, p <.001) and less likely to have comorbid conditions, including hypertension (87.2% vs 89.7%, p <.001), congestive heart failure (14.5% vs 15.9%, p <.001), chronic obstructive pulmonary disease (35.7% vs 36.3, p <.001) and renal failure requiring hemodialysis (1.4% vs 1.7%, p = .005). After risk factor adjustment, vaccination was associated with decreased mortality (OR 0.7, 95% CI 0.62 - 0.81, p <.0001). Stratification by procedure type demonstrated that vaccinated patients had decreased odds of mortality after open AAA (OR 0.6, 95% CI 0.42-0.97, p = 0.03), EVAR (OR 0.6, 95% CI 0.43-0.83, p 0.002), CAS (OR 0.7, 95% CI 0.51-0.88, p = 0.004) and infra-inguinal lower extremity interventions (OR 0.7, 95% CI 0.48-0.96, p = 0.03). Conclusions: COVID-19 vaccination is associated with reduced perioperative mortality in patients undergoing vascular surgery. This association is most pronounced for patients undergoing aortic aneurysm repair, carotid stenting and infrainguinal bypass.

Pathways in the brain, heart, and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: an in silico study hinting cancer incidence (preprint)

The influence of SARS-CoV-2 non-structural protein in the host\'s tissue-specific complexities remains a mystery and needs more in-depth attention because of COVID-19 recurrence and long COVID. Here we investigated the influence of SARS-CoV-2 transmembrane protein NSP6 (Non-structural protein 6) in three major organs - the brain, heart, and lung in silico. To elucidate the interplay between NSP6 and host proteins, we analyzed the protein-protein interaction network of proteins interacting with NSP6 interacting proteins. Reported host interacting partners of NSP6 were ATP5MG, ATP6AP1, ATP13A3, and SIGMAR1. Pathway enrichment analyses provided global insights into biological pathways governed by differentially regulated genes in the three tissues after COVID-19 infection. Hub genes of tissue-specific protein interactome were analysed for drug targets and many were found. miRNA-gene network for the tissue-specific regulated proteins was sought. Comparing this list with the gene list targetted by SARS-CoV-2 regulated miRNAs, we found three and two common genes in the brain and lung respectively. Among the five common proteins revealed as potential therapeutic targets across the three tissues, four non-approved drugs and one approved drug could target Galectin 3 (LGALS3) and AIFM1 respectively. Increased expression of LGALS3 (that was upregulated in the heart after COVID-19 infection) is observed in multiple cancers and acts as a modulator for tumor progression. COVID-19 infection also causes myocardial inflammation and heart failure (HF). HF is observed to be increasing cancer incidence. The present scenario of long COVID-19 and recurrent COVID-19 infections warrants in-depth studies to probe the effect of COVID-19 infection on increased cancer incidence.

Prognostic Value of T wave Positivity in Lead aVR in COVID-19 Pneumonia (preprint)

Background: T wave positivity in the lead aVR is a marker of ventricular repolarization abnormality and provides information on short and long-term cardiovascular mortality in patients who have heart failure, anterior myocardial infarction, and receive hemodialysis for various reasons. The aim of this study was to investigate the relationship between T wave positivity in the lead aVR on superficial ECG and mortality from COVID-19 pneumonia. Methods: This study retrospectively included 130 patients who were diagnosed with COVID-19 and treated as an outpatient or in the thoracic diseases ward in a single center between January 2021 and June 2021. All patients included in the study had clinical and radiological features and signs of COVID-19 pneumonia. The COVID-19 diagnosis of all patients was confirmed by polymerase chain reaction (PCR) studied from an oropharyngeal swab Results: A total of 130 patients were included in this study. Patients were divided into 2 groups: survived and deceased. There were 55 patients (with a mean age of 64.76-14.93 years, 58.18% male, 41.12% female) in the survived group, while there were 75 patients (with a mean age of 65-15 years, 58.67% male, 41.33% female) in the deceased group. The univariate and multivariate regression analyses showed that positive TAVR (OR: 5.151, 95% CI: 1.001-26.504, p: 0.0012), lactate dehydrogenase (LDH) (OR: 1.006, 95% CI: 1.001-1.010, p: 0.012) and D-dimer (OR:1.436, 95% CI: 1.115-1.848, p: 0.005) were independent risk factors for mortality Conclusions: positive TAaVR is useful in risk stratification for COVID-19 pneumonia mortality. KEY WORLD:Electrocardıographıa, positive TAaVR, COVID-19 pneumonia, mortality

How phytocannabinoids affect cardiovascular health? An update on the most common cardiovascular diseases. (preprint)

Cardiovascular diseases (CVDs) remain the cause of millions of deaths in the world annually. Despite the great progress in therapies, which are available for patients with CVDs, some limitations including drug complications still exist. Hence, the endocannabinoid system (ECS) was proposed as a new avenue for CVDs treatment. The cardiovascular action of cannabinoids is complex as they not only affect vasculature and myocardium directly via specific receptors but also exert indirect effects through the central and peripheral nervous system. The growing interest in phytocannabinoid studies has been broadened the knowledge about their molecular targets as well as therapeutical properties, nonetheless, some areas of their actions are not yet fully recognized. The purpose of this review is to summarize and update the cardiovascular actions of the most potent phytocannabinoids and the potential therapeutic role of ECS in CVDs, including ischemic reperfusion injury, arrhythmia, heart failure, hypertension as well as cardiac complications associated with the novel coronavirus SARS-CoV-2 infections.

PVT in patients presenting with post-acute sequelae of COVID-19 (preprint)

We investigated performance validity tests (PVTs) in patients presenting with new onset cognitive complaints associated with post-acute sequelae of COVID-19 infection (PASC). Retrospective data were obtained from IRB-approved registries. All patients completed the Victoria Symptom Validity Test (VSVT) in conjunction with a neuropsychological evaluation. A sub-analysis included 7 other PVT measures. The PASC sample was compared to an analogous multiple sclerosis (MS) sample with known PVT failure rates. The PASC sample consisted of 177 patients (49.4 ± 11.2 years), educated (14.7 ± 2.3 years), predominantly female (81.4%), and white, non-Hispanic (85.3%) patients. Seven percent of the PASC sample scored below the established VSVT hard item cut-off, and of those with invalid VSVT over 50% failed 3 or more additional PVTs. In comparison to a MS sample, the PASC sample reported comparable psychological symptoms, but were significantly less likely to produce invalid VSVT scores and seek disability benefits. This study provides a profile of PVTs in patients presenting with PASC. The general infrequence of invalid responding in this PASC sample (7%) is noteworthy compared to an MS sample and highlights the role of additional factors in non-credible response such as elevated psychological symptoms or pursuit of disability.

The impact of Long COVID on Health-Related Quality-of-life using OpenPROMPT (preprint)

Background: Long COVID is a major problem affecting patient health, the health service, and the workforce. To optimise the design of future interventions against COVID-19, and to better plan and allocate health resources, it is critical to quantify the health and economic burden of this novel condition. Methods With the approval of NHS England, we developed OpenPROMPT, a UK cohort study measuring the impact of long COVID on health-related quality-of-life (HRQoL). OpenPROMPT invited responses to Patient Reported Outcome Measures (PROMs) using a smartphone application and recruited between November 2022 and October 2023. We used the validated EuroQol EQ-5D questionnaire with the UK Value Set to develop disutility scores (1-utility) for respondents with and without Long COVID using linear mixed models, and we calculated subsequent Quality-Adjusted Life-Months (QALMs) for long COVID. Results We used data from 6,070 participants where 24.7% self-reported long COVID. In multivariable regressions, long COVID had a consistent impact on HRQoL, showing a high probability of reporting loss in quality-of-life (OR: 22, 95% CI:12.35-39.29) compared with people who did not report long COVID. Reporting a disability was the largest predictor of losses of HRQoL (OR: 60.2, 95% CI: 27.79-130.57) across survey responses. Self-reported long COVID was associated with an 0.37 QALM loss. Conclusions We found substantial impacts on quality-of-life due to long COVID, representing a major burden on patients and the health service. We highlight the need for continued support and research for long COVID, as HRQoL scores compared unfavourably to patients with conditions such as multiple sclerosis, heart failure, and renal disease.

Impact of the COVID-19 Pandemic on Same-day Discharge Adoption Following Percutaneous Coronary Intervention for Stable CAD: A National Time Series Analysis (preprint)

Abstract Background: Elective percutaneous coronary intervention (PCI) historically required hospitalization post procedure. Same day discharge (SDD) has emerged as a safe and cost efficient option, although the impact of the coronavirus disease of 2019 (COVID-19) pandemic on rates of SDD and associated care episode costs remains uncertain. Methods: A national sample of consecutive patients undergoing elective PCI at 42 hospitals (Ascension, St.Louis, MO) between May 2019 to April 2021 were identified using internal registry data and administrative claims data. Rates of SDD before and after the COVID-19 pandemic (March 2020) were compared using multivariable logistic regression adjusted for patient and procedural characteristics. Additionally, an interrupted time series model was used to determine the effect of the pandemic and policy on SDD rates before and after pandemic declaration. Lastly, we estimated total costs per PCI episode in pre and post pandemic periods. Results: In total, 12,740 interventions were performed within 42 Ascension facilities that met study eligibility criteria (5955 PCI prior to the pandemic and 6785 after). Demographic data were similar between both populations although higher rates of dyslipidemia, prior myocardial infarction, and heart failure history were noted in the post pandemic group. Pandemic declaration was associated with a higher likelihood of SDD (OR 2.09, CI 1.93-2.25, p < 0.001). From pre-pandemic to post-pandemic, mean SDD rose from 34% to 45% (p< 0.001) with an accelerated monthly SDD adoption rate after the pandemic (0.1% per month vs 1.0% per month, p=0.02). Total costs per episode were $679.52 (95% CI $476.12 ? $882.92, p < 0.001) higher in the post-pandemic period, driven by increased material costs. SDD was associated with a $2137.05 (95% CI $1925.03 - $2349.07, p < 0.001) reduction in costs relative to non-SDD episodes throughout the study period. Conclusion: Among a large national risk-adjusted sample of consecutive patients, the COVID-19 pandemic accelerated adoption of SDD. As a care strategy, SDD was associated with reduced episode costs during elective PCI in the post-pandemic period .

Interest Rates, Venture Capital, and Financial Stability (preprint)

Following several prominent bank failures and as central banks continue to tighten interest rates to fight inflation, there is increasing interest in the relationship between monetary policy and financial stability. This Article illuminates one path through which the prolonged period of low interest rates from 2009-2021 has impacted financial stability: it traces how yield-seeking behavior in the wake of the Global Financial Crisis and Covid pandemic led to a bubble in the venture capital industry, which in turn spawned a crypto bubble as well as a run on the VC-favored Silicon Valley Bank. This Article uses this narrative to illustrate the importance of proactive financial regulation both in preventing financial crises that invite more accommodative monetary policy, and in preventing accommodative monetary policy from sowing the seeds of future financial stability problems if it is deployed. The Article is primarily a descriptive account, designed to highlight the venture capital industry’s unexpected and underappreciated contribution to financial stability threats in the early 2020s. This Article does, however, suggest several policy implications of this account. It argues for increased monitoring of the venture capital industry by financial stability regulators, given that venture capital is well-positioned to generate asset bubbles now and in the future. More specifically, it argues for more aggressive enforcement of the securities laws to tamp down on the present crypto bubble, as well as for structural separation between crypto and the traditional financial system.

Lung ultrasound score as a predictor of failure to wean COVID-19 patients off mechanical ventilation: a prospective observational study (preprint)

Background The lung ultrasound score was developed for rapidly assessing the extent of lung ventilation, and it can predict failure to wean various types of patients off mechanical ventilation. Whether it is also effective for COVID-19 patients is unclear.Methods This single-center, prospective, observational study was conducted to assess the ability of the 12-region lung ultrasound score to predict failure to wean COVID-19 patients off ventilation. In parallel, we assessed whether right hemidiaphragmatic excursion or previously published predictors of weaning failure can apply to these patients. Predictive ability was assessed in terms of the area under the receiver operating characteristic curve (AUC).Results Among the 35 patients in the study, 12 patients (37%) could not be weaned off mechanical ventilation. The lung ultrasound score predicted these failures with an AUC of 0.885 (95% CI 0.770–0.999, p < 0.001), and a threshold score of 10 provided specificity of 72.7% and sensitivity of 92.3%. AUCs were lower for previously published predictors of weaning failure, and right hemidiaphragmatic excursion did not differ significantly between the two groups.Conclusions The lung ultrasound score can accurately predict failure to wean critically ill COVID-19 patients off mechanical ventilation, whereas assessment of right hemidiaphragmatic excursion does not appear helpful in this regard.Trial registration: https://clinicaltrials.gov/ct2/show/NCT05706441

Human complement Factor H and Properdin act as soluble pattern recognition receptors and differentially modulate SARS-CoV-2 Infection (preprint)

Severe cases of SARS-CoV-2 infection are characterised by an imbalanced immune response, excessive inflammation, and the development of acute respiratory distress syndrome, which can lead to multiorgan failure and death. Several studies have demonstrated dysregulated complement activity as an indicator of immunopathogenesis in the SARS-CoV-2 infection. Notably, the complement alternative pathway has been implicated in driving the excessive inflammation during severe SARS-CoV-2 infection. Reduced levels of factor H (FH), a down-regulator of the alternative pathway, and increased levels of properdin (Factor P/FP), the only known up-regulator of the alternative pathway, have been observed in individuals with severe COVID-19 infection. The present study investigated the complement activation-independent, and a more direct role of FH and FP against SARS-CoV-2 infection. Using direct ELISA, the interactions of FH and FP with the SARS-CoV-2 spike (S) and receptor binding domain (RBD) were assessed. Using S protein expressing lentiviral pseudotypes, the cell binding and luciferase-based virus entry assays were employed to assess the potential modulatory effects of FH, FP, and recombinant thrombospondin repeats 4 and 5 (TSR4+5) on SARS-CoV-2 cell entry. We also evaluated the immunomodulatory functions of FH and FP in the cytokine response triggered by SARS-CoV-2 pseudotypes via RT-qPCR. SARS-CoV-2 S and RBD proteins were found to bind both FH and FP. Treatment of A549 cells expressing human ACE2 and TMPRSS2 with FP or TSR4+5 resulted in increased cell entry and binding of SARS-CoV-2 pseudotypes. In silico studies revealed that FP increases affinity between SARS-CoV-2 and host ACE2. The impact of FP on viral cell entry and binding was reversed by anti-FP antibody treatment in A549-hACE2+TMPRSS2 cells. However, FH treatment reduced the cell entry and binding of SARS-CoV-2 lentiviral pseudotypes. Furthermore, the A549-hACE2+TMPRSS2 cells challenged with SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes pre-treated with FP or TSR4+5, exhibited upregulation of the transcripts of pro-inflammatory cytokines, such as IL-1{beta}, IL-8, IL-6, TNF-, IFN- and RANTES (as well as NF-kB). Conversely, FH pre-treatment downregulated the expression of these pro-inflammatory cytokines. Treatment of A549-hACE2+TMPRSS2 cells with FP increased S protein-mediated NF-kB activation, while FH treatment reduced it. These findings suggest that FH may act as an inhibitor of SARS-CoV-2 cell entry and binding, thereby attenuating the infection-associated inflammatory response in a complement activation-independent manner. FP may contribute to viral cell entry, binding, and exacerbating the immune response. That may result in potentially influencing the severity of the infection.

Intracardiac Thrombus in COVID-19 Inpatients: A Nationwide Study of Incidence, Predictors and Outcomes (preprint)

Background: COronaVIrus Disease 2019 (COVID-19) has been observed to be associated with a hypercoagulable state. Intracardiac thrombosis is a serious complication but has seldom been evaluated in COVID-19 patients. We assessed the incidence, associated factors, and outcomes of COVID-19 patients with intracardiac thrombosis. Methods: COVID-19 inpatients during 2020 were retrospectively identified from the national inpatient sample (NIS) database, and data retrieved regarding clinical characteristics, intracardiac thrombosis, and adverse outcomes. Multivariable logistic regression was performed to identify the clinical factors associated with intracardiac thrombosis and in-hospital mortality and morbidities. Results: A total of 1,683,785 COVID-19 inpatients were identified in 2020 from NIS, with a mean age of 63.8 {+/-} 1.6 years, and 32.2% females. Intracardiac thrombosis was present in 0.001% (1,830) patients. Overall, in-hospital outcomes include all-cause mortality 13.2% (222,695/1,683,785), cardiovascular mortality 3.5%, cardiac arrest 2.6%, acute coronary syndrome (ACS) 4.4%, heart failure 16.1%, stroke 1.3% and acute kidney injury (AKI) 28.3%. The main factors associated with intracardiac thrombosis were a history of congestive heart failure and coagulopathy. Intracardiac thrombosis was independently associated with a higher risk of in-hospital all-cause mortality (OR: 3.32, 95% CI: 2.42-4.54, p<0.001), cardiovascular mortality (OR: 2.95, 95% CI: 1.96-4.44, p<0.001), cardiac arrest (OR: 2.04, 95% CI: 1.22-3.43, p=0.006), ACS (OR: 1.62, 95% CI: 1.17-2.22, p=0.003), stroke (OR: 3.10, 95% CI: 2.11-4.56, p<0.001), and AKI (OR: 2.13 95% CI: 1.68-2.69, p<0.001), but not incident heart failure (p=0.27). Conclusion: Although intracardiac thrombosis is rare in COVID-19 inpatients, its presence was independently associated with higher risks of in-hospital mortality and most morbidities. Prompt investigations and treatments for intracardiac thrombosis are warranted when there is a high index of suspicion and a confirmed diagnosis respectively.

The role of COVID-19 vaccines in preventing post COVID-19 thromboembolic and cardiovascular complications: a multinational cohort study (preprint)

ImportanceThe overall effects of vaccination on the risk of cardiac, and venous and arterial thromboembolic complications following COVID-19 remain unclear. ObjectiveWe studied the association between COVID-19 vaccination and the risk of acute and subacute COVID-19 cardiac and thromboembolic complications. DesignMultinational staggered cohort study, based on national vaccination campaign rollouts. SettingNetwork study using electronic health records from primary care records from the UK, primary care data linked to hospital data from Spain, and national insurance claims from Estonia. ParticipantsAll adults with a prior medical history of [≥]180 days, with no history of COVID-19 or previous COVID-19 vaccination at the beginning of vaccine rollout were eligible. ExposureVaccination status was used as a time-varying exposure. Vaccinated individuals were classified by vaccine brand according to the first dose received. Main OutcomesPost COVID-19 complications including myocarditis, pericarditis, arrhythmia, heart failure (HF), venous (VTE) and arterial thromboembolism (ATE) up to 1 year after SARS-CoV-2 infection. MeasuresPropensity Score overlap weighting and empirical calibration based on negative control outcomes were used to minimise bias due to observed and unobserved confounding, respectively. Fine-Gray models were fitted to estimate sub-distribution Hazard Ratios (sHR) for each outcome according to vaccination status. Random effect meta-analyses were conducted across staggered cohorts and databases. ResultsOverall, 10.17 million vaccinated and 10.39 million unvaccinated people were included. Vaccination was consistently associated with reduced risks of acute (30-day) and subacute post COVID-19 VTE and HF: e.g., meta-analytic sHR 0.34 (95%CI, 0.27-0.44) and 0.59 (0.50-0.70) respectively for 0-30 days, sHR 0.58 (0.48 - 0.69) and 0.71 (0.59 - 0.85) respectively for 90-180 days post COVID-19. Additionally, reduced risks of ATE, myocarditis/pericarditis and arrhythmia were seen, but mostly in the acute phase (0-30 days post COVID-19). ConclusionsCOVID-19 vaccination reduced the risk of post COVID-19 complications, including cardiac and thromboembolic outcomes. These effects were more pronounced for acute (1-month) post COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough vs unvaccinated SARS-CoV-2 infection. RelevanceThese findings highlight the importance of COVID-19 vaccination to prevent cardiovascular outcomes after COVID-19, beyond respiratory disease. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the impact of COVID-19 vaccination to prevent cardiac complications and thromboembolic events following a SARS-CoV-2 infection? FindingsResults from this multinational cohort study showed that COVID-19 vaccination reduced risk for acute and subacute COVID-19 heart failure, as well as venous and arterial thromboembolic events following SARS-CoV-2 infection. MeaningThese findings highlight yet another benefit of vaccination against COVID-19, and support the recommendations for COVID-19 vaccination even in people at high cardiovascular risk.

Long-term outcomes of hospitalized SARS-CoV-2/COVID-19 patients with and without neurological involvement: 3-year follow-up assessment (preprint)

Background and ObjectivesAcute neurological manifestations are a common complication of acute COVID-19 disease. This study investigated the 3-year outcomes of patients with and without significant neurological manifestations during initial COVID-19 hospitalization. MethodsPatients infected by SARS-CoV-2 between March 1 and April 16, 2020 and hospitalized in the Montefiore Health System in the Bronx, an epicenter of the early pandemic, were included. Follow-up data was captured up to January 23, 2023 (3 years post COVID-19). This cohort consisted of 414 COVID-19 patients with significant neurological manifestations and 1199 propensity-matched COVID- 19 patients without neurological manifestations. Primary outcomes were mortality, stroke, heart attack, major adverse cardiovascular events (MACE), reinfection, and hospital readmission post-discharge. Secondary outcomes were clinical neuroimaging findings (hemorrhage, active stroke, prior stroke, mass effect, and microhemorrhage, white-matter changes, microvascular disease, and volume loss). Predictive models were used to identify risk factors of mortality post-discharge. ResultsMore patients in the neurological cohort were discharged to acute rehabilitation (10.54% vs 3.68%, p<0.0001), skilled nursing facilities (30.67% vs 20.78%, p=0.0002) and fewer to home (55.27% vs 70.21%, p<0.0001) compared to the matched controls. Incidence of readmission for any medical reason (65.70% vs 60.72%, p=0.036), stroke (6.28% vs 2.34%, p<0.0001), and MACE (20.53% vs 16.51%, p=0.032) was higher in the neurological cohort post-discharge. Neurological patients were more likely to die post-discharge (58 (14.01%) vs 94 (7.84%), p=0.0001) compared to controls (HR=2.346, 95% CI=(1.586, 3.470), p<0.0001). The major causes of death post-discharge were heart disease (14.47%), sepsis (13.82%), influenza and pneumonia (11.18%), COVID-19 (8.55%) and acute respiratory distress syndrome (7.89%). Factors associated with mortality after leaving the hospital were belonging to the neurological cohort (OR=1.802 (1.237, 2.608), p=0.002), discharge disposition (OR=1.508, 95% CI=(1.276, 1.775), p<0.0001), congestive heart failure (OR=2.281 (1.429, 3.593), p=0.0004), higher COVID-19 severity score (OR=1.177 (1.062, 1.304), p=0.002), and older age (OR=1.027 (1.010, 1.044), p=0.002). There were no group differences in gross radiological findings, except the neurological cohort showed significantly more age-adjusted brain volume loss (p<0.05) compared to controls. DiscussionCOVID-19 patients with neurological manifestations have worse long-term outcomes compared to matched controls. These findings raise awareness and the need for closer monitoring and timely interventions for COVID-19 patients with neurological manifestations.

The Role of the Immune System on the Cardiac Complications Observed in SARS-CoV-2

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.

Heart failure after dengue infection- a population-based self-controlled case-series study.

BACKGROUND: Major cardiovascular events (MACEs) have been described with dengue infection. Among these MACEs, heart failure (HF) is the most common but has not been thoroughly assessed. This study aimed to evaluate the association between dengue and HF. METHODS: Under the self-controlled case-series study design, we used the Notifiable Infectious Disease dataset linkage with the National Health Insurance claims data to obtain the study subjects. All laboratory-confirmed dengue cases who were hospitalized for HF after dengue infection within one year between 2009 and 2015 in Taiwan were included. We identified the first 7 and 14 days after dengue infection as the risk intervals. The incidence rate ratio (IRR) and 95% confidence interval (CI) for HF were estimated by conditional Poisson regression. RESULTS: Among the 65,906 dengue patients, 230 had admission for HF after dengue infection within one year. The IRR of HF admission within the first week after dengue infection was 56.50 (95% C.I. 43.88-72.75). This risk was highest in >60 years (IRR = 59.32, 95% C.I. 45.43-77.43) and lower in 0-40 years (IRR = 25.82, 95% C.I. 2.89-231.02). The risk was nearly nine times higher among admission (for dengue infection) than among nonadmission cases (IRR 75.35 vs. 8.61, p < 0.0001). The risks increased slightly in the second week 8.55 and became less obvious after the third and fourth week. CONCLUSIONS: Patients with dengue infection have a risk of developing acute heart failure within one week, especially in >60 years, men, and dengue admission subjects. The findings emphasize the awareness of diagnosis and further appropriate treatment of HF.

Monitoring Acute Heart Failure Patients Using Internet-of-Things-Based Smart Monitoring System.

With technological advancements, smart health monitoring systems are gaining growing importance and popularity. Today, business trends are changing from physical infrastructure to online services. With the restrictions imposed during COVID-19, medical services have been changed. The concepts of smart homes, smart appliances, and smart medical systems have gained popularity. The Internet of Things (IoT) has revolutionized communication and data collection by incorporating smart sensors for data collection from diverse sources. In addition, it utilizes artificial intelligence (AI) approaches to control a large volume of data for better use, storing, managing, and making decisions. In this research, a health monitoring system based on AI and IoT is designed to deal with the data of heart patients. The system monitors the heart patient's activities, which helps to inform patients about their health status. Moreover, the system can perform disease classification using machine learning models. Experimental results reveal that the proposed system can perform real-time monitoring of patients and classify diseases with higher accuracy.

Improvement of clinical symptoms and cardiac abnormalities detected by cardiac magnetic resonance imaging in patients with long COVID syndrome after guideline-oriented therapy (preprint)

Patients with cardiovascular long COVID syndrome and cardiac magnetic resonance (CMR) scans were included prospectively into the Vienna PostCoV Registry between March 2021 and March 2023 (EC: 1008/2021, clinicaltrials.gov NCT05398952; n=240). Clinical symptoms, age and sex, time between COVID-positivity and vaccination and CMR, as well as CMR findings were recorded. After medical treatment, clinical assessment and CMR was repeated in 67 patients with pathological CMR findings showing myopericarditis, pericardial effusion or cardiac functional abnormalities. Blood pressure and condition-adapted heart failure treatment led to a significant increase in left ventricular ejection fraction. Low-moderate doses of NSAIDs for 3 months significantly reduced pericardial effusion. Clinical symptoms improved markedly with a decrease in CMR abnormalities.  In conclusion, medical treatment of cardiac/cardiovascular long COVID syndrome related to CMR abnormalities led to significant improvement in ejection fraction and decreased pericardial effusion, and were associated with improvements in the cardiovascular long COVID complaints.

Evidence of Autoinflammation as a Principal Mechanism of Myocardial Injury in SARS-CoV-2 PCR-Positive Medical Examiner Cases (preprint)

Background Disease from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains the third leading cause of death in the United States, after cancer and heart disease. Many patients infected with this virus develop later cardiovascular complications including myocardial infarctions, stroke, arrhythmia, heart failure, and sudden cardiac death (20–28%). The purpose of this study is to understand the primary mechanism of myocardial injury in patients infected with SARS-CoV-2.Methods We investigated a consecutive cohort of 48 medical examiner cases who died with PCR-positive SARS-CoV-2 (COVpos) infection in 2020. We compared them to a consecutive cohort of 46 age and sex-matched controls who were PCR-negative for SARS-CoV-2 (COVneg). Clinical information available at postmortem examination was reviewed on each patient. Formalin-fixed sections were examined using antibodies directed against CD42 (platelets), CD15 (myeloid cells), CD68 (monocytes), C4d, Fibrin, CD34 (stem cell antigen), CD56 (natural killer cells), and Myeloperoxidase (MPO) (neutrophils and NETs). We used a Welch 2-sample T-test to determine significance. A cluster analysis of marker distribution was also done.Results We found a significant difference between COVpos and COVneg samples for all markers, all of which were significant at p < 0.001. The most prominent features were neutrophils (CD15, MPO) and MPO positive debris suggestive of NETS. A similar distribution of platelets, monocytes, fibrin and C4d was seen in COVpos cases. Clinical features were similar in COVpos and COVneg cases for age, sex, and body mass index (BMI).Conclusion These findings suggest an autoinflammatory process is likely involved in cardiac damage during these infections.