The Development of Indoor Natural Elements Had Relaxing Psychophysiological Effects on Older Adults in Taiwan During the COVID-19 Pandemic (preprint)

While the COVID-19 pandemic has affected all types of people, older adults have been disproportionately affected. Therefore, during this period we developed an indoor program inspired by art and natural elements (plant essential oils [EOs]) intended to create a relaxing effect akin to a forest atmosphere to enhance their psychophysiological health. There are for 30 Taiwanese older adults (range, 59-79 years) participated in the study. We combined art activity (still-life painting of vegetables) with breathing Pseudotsuga menziesii and Lavandula angustifolia EOs during a 100-minute experiment involving still-life painting and the inhalation of 2.5% diffused EOs. The research shows physiological measures (heart rate, normalized low-frequency heart oscillations, ratio of low- to high-frequency heart oscillations, high-beta waves, and gamma waves) decreased;correspondingly, an increased standard deviation of normal-to-normal intervals, normalized high-frequency heart oscillations, and high-alpha waves were observed, indicating relaxation physiological state. Subjective psychological assessments using the State-Trait Anxiety Inventory–Stateyielded lower post-test scores, further supporting relaxation effects. The psychophysiological data from this study provide important scientific evidence for the physical and mental health benefits of indoor nature-based activity programs for older adults, thereby improving their quality of life.

Impact of Comorbidity on Mortality in COVID-19 Patients: A Single- Center Retrospective Study (preprint)

The global spread of COVID-19 has had a profound impact on human health, with millions of people infected and a significant death. Comorbidities play a pivotal role in the prognosis of COVID-19 patients. The aim of this study was to assess the impact of the comorbidity on mortality in COVID-19 patients in a Single-Centre Retrospective Study. The characteristics and results of patients with COVID-19 admitted to KLE's Hospital in Belgaum, Karnataka, India, were examined through retrospective research. 642 participants having COVID-19 diagnoses between October 1, 2020, and September 30, 2021 were enrolled in the research. Data such as, patients' clinical features, vital signs, demographic information and patients' outcomes (survived or deceased) were collected. The findings of this study showed that out of 642 patients, 256 patients had co morbidities, 62.8% of them had poly morbidity and most prevalent underlying medical conditions were hypertension, diabetes, and heart disease which affected 30.7%, 29.1, and 7.9%, respectively. Only diabetes and renal disease reported strong associations (P.value: 0.011, aOR: 1.852 95% CI: 1.148–2.988), (p.value: 0.000, aOR: 6.491 (95% CI: 2.613–16.124), respectively. Furthermore, Comorbidities such kidney disease, and diabetes mellitus can lead to more serious complications and death in COVID-19 patients. Understanding the impact of these comorbidities on COVID-19 mortality is essential for more effective patient care and resource allocation.

Beyond the Virus: QTc Interval Changes in COVID-19 Survivors (preprint)

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting enzyme-2 receptors on host cells to enter the cells. These receptors are expressed on heart muscle tissue and the tissues of other major organs, which supports the primary accepted theory for the direct cardiac cell injury of coronavirus disease 2019 (COVID-19) and the associated cardiorespiratory manifestations. The SARS-CoV-2 infection leads to unstable myocardial cell membranes due to hypoxia, myocarditis, myocardial ischemia, and abnormal host immune response. This is the main reason behind arrhythmia and electrocardiogram (ECG) changes during COVID-19. However, the specific effect on QTc after Covid 19 infection has not been studied well. Therefore, this study aimed to examine the association between post COVID-19 infection and QTc changes.Objectives: Examine the association between post COVID-19 infection and QTc changes.Materials and Methods: This is a case control study conducted on middle age of either sex involves 50 adult patients with post-COVID-19 infections (eight were defaulted from the study because they were not cooperative), 23 females and 19 males with mean age (36.98 ± 12.2 years) who were non-vaccinated against Covid 19 after one month to two years of an acute episode of COVID-19 (confirmed by positive real-time reverse-transcription polymerase chain reaction (RT-PCR)) test according to the World Health Organization (WHO) selected randomly from those attending to the adult Holter and Echocardiography lab in Al-Zahraa Hospital/ Al-Hussein Medical City/ Karbala Province after being referred by Internist during the period from the 12th of October 2022 to the end of January 2024 and divided in to three groups : non hospitalize, hospitalize and admitted to intensive care while control group consisted of 40 healthy persons 23 females and 17 males with mean age (33.28 ± 9.58 years), whom referred by Internist for ECG with no Hx of the previous infection of covid 19. All of them have electrocardiographic evaluation by taking ECG.Conclusion That post COVID-19 patients had prolonged QT and QTc intervals increase the risk for cardiac arrhythmias.

SERVAL: Synergy Learning between Vertical Models and LLMs towards Oracle-Level Zero-shot Medical Prediction (preprint)

Recent development of large language models (LLMs) has exhibited impressive zero-shot proficiency on generic and common sense questions. However, LLMs' application on domain-specific vertical questions still lags behind, primarily due to the humiliation problems and deficiencies in vertical knowledge. Furthermore, the vertical data annotation process often requires labor-intensive expert involvement, thereby presenting an additional challenge in enhancing the model's vertical capabilities. In this paper, we propose SERVAL, a synergy learning pipeline designed for unsupervised development of vertical capabilities in both LLMs and small models by mutual enhancement. Specifically, SERVAL utilizes the LLM's zero-shot outputs as annotations, leveraging its confidence to teach a robust vertical model from scratch. Reversely, the trained vertical model guides the LLM fine-tuning to enhance its zero-shot capability, progressively improving both models through an iterative process. In medical domain, known for complex vertical knowledge and costly annotations, comprehensive experiments show that, without access to any gold labels, SERVAL with the synergy learning of OpenAI GPT-3.5 and a simple model attains fully-supervised competitive performance across ten widely used medical datasets. These datasets represent vertically specialized medical diagnostic scenarios (e.g., diabetes, heart diseases, COVID-19), highlighting the potential of SERVAL in refining the vertical capabilities of LLMs and training vertical models from scratch, all achieved without the need for annotations.

Cardioprotective effects of vaccination in hospitalized patients with COVID-19 (preprint)

Background COVID-19 vaccination has been shown to prevent and reduce the severity of COVID-19 disease. Aim The aim of this study was to explore the cardioprotective effect of COVID-19 vaccination in hospitalized COVID-19 patients. Methods In this retrospective, single-center cohort study, we included hospitalized COVID-19 patients with confirmed vaccination status from July 2021 to February 2022. We assessed outcomes such as acute cardiac events and cardiac biomarker levels through clinical and laboratory data. Results Our analysis covered 167 patients (69% male, mean age 58 years, 42% being fully vaccinated). After adjustment for confounders, vaccinated hospitalized COVID-19 patients displayed a reduced relative risk for acute cardiac events (RR: 0.33, 95% CI [0.07; 0.75]) and showed diminished troponin T levels (Cohen’s d: -0.52, 95% CI [-1.01; -0.14]), compared to their non-vaccinated peers. Type 2 diabetes (OR: 2.99, 95% CI [1.22; 7.35]) and existing cardiac diseases (OR: 4.31, 95% CI [1.83; 10.74]) were identified as significant risk factors for the emergence of acute cardiac events. Conclusion Our findings suggest that COVID-19 vaccination may confer both direct and indirect cardioprotective effects in hospitalized COVID-19 patients.

COVID-related Constrictive Pericarditis Requiring Pericardiectomy: A Case Report (preprint)

Background The COVID-19 pandemic was primarily considered a respiratory malady in the early phases of the outbreak. However, as more patients suffer from this illness, a myriad of symptoms emerge in organ systems separate from the lungs. Among those patients with cardiac involvement, myocarditis, pericarditis, myocardial infarction, and arrhythmia were among the most common manifestations. Pericarditis with pericardial effusion requiring medical or interventional treatments has been previously reported in the acute setting. Notably, chronic pericarditis with pericardial thickening resulting in constriction requiring sternotomy and pericardiectomy has not been published to date.Case Presentation A patient with COVID-19-associated constrictive pericarditis three years after viral infection requiring pericardiectomy was reported. The COVID-19 infection originally manifested as anosmia and ageusia. Subsequently, the patient developed dyspnea, fatigue, right-sided chest pressure, bilateral leg edema, and abdominal fullness. Following recurrent right pleural effusions and a negative autoimmune work-up, the patient was referred for cardiothoracic surgery for pericardiectomy when radiographic imaging and hemodynamic assessment were consistent with constrictive pericarditis. Upon median sternotomy, the patient’s pericardium was measured to be 8 mm thick. Descriptions of the clinical, diagnostic, and therapeutic features are provided. Within the first week after the operation, the patient’s dyspnea resolved; one month later, leg edema and abdominal bloating were relieved.Conclusions Although an association between COVID-19 and cardiac complications has been established, this case adds another element of virus severity and chronic manifestations. The need for sternotomy and pericardiectomy to treat COVID-19-related constrictive pericarditis is believed to be the first reported diagnosis.

Treadmill Exercise Stress Echocardiography Exposes Impaired Left Ventricular Function in Patients Recovering from Hospitalization with COVID-19 Without Overt Myocarditis Versus Historical Controls (preprint)

Background: Usual clinical testing rarely reveals cardiac abnormalities persisting after hospitalization for COVID-19. Such testing may overlook residual changes responsible for increased adverse cardiac events post-discharge. Methods: To further elucidate long-term status, we performed exercise stress echocardiography (ESE) in 15 patients age 30-63 without myocarditis 3 to 31 months after hospital discharge. We compared patient outcomes to published data in healthy comparisons (HC) exercising according to the same protocol. Results: Patients' treadmill exercise (Bruce protocol), averaging 8.2 min, was halted by dyspnea or fatigue. Pre-stress baselines in recovering patients (RP) matched HC except for higher heart rate: mean 81 bpm for RP and 63 for HC (p<0.0001). At peak stress, RP had significantly lower mean left ventricular (LV) ejection fraction (67% vs 73%, p<0.0017) and higher peak early mitral inflow velocity/early mitral annular velocity (E/e', 9.1 vs 6.6, p<0.006) compared with HC performing equal exercise (8.5 min). Thus, when stressed, patients without known cardiac impairment showed modest but consistently diminished systolic contractile function and diastolic LV compliance during recovery vs HC. Peak HR during stress was significantly elevated in RP vs HC; peak SBP also trended higher. Average pulmonary artery systolic pressures among RP remained normal. Conclusions: Our measurements during ESE uniquely identified residual abnormality in cardiac contractile function not evident in the unstressed condition. This finding exposes a previously-unrecognized residual influence of COVID-19, possibly related to underlying autonomic dysfunction, microvascular disease, or diffuse interstitial changes after subclinical myocarditis; it may have long-term implications for clinical management and later prognosis.

Comparative study to understand the clinically efficiency of Vigo Smart Heart (VSH) against traditional holter in Indian Arrhythmia patients (preprint)

Arrhythmia is an irregular hertbeat which leads to severe heart complications and it is the most common action of Cardio Vascular Diseases. India represents 31% of global deaths and need for accurate diagnosis and monitoring of Arrhythmia has not been addressed. In view, we developed a novel device Vigo Holter (VSH) that is connected to cloud and IoT based platform designed as an easy wearable for the patient. It records continuous ECG and HR to predict the changes in the heart. Compared a Vigo Holter against the traditional holter monitoring in 51 volunteers for 24 hrs with asymptomatic and symptomatic subjects. We evaluated patient compliance, analyzable signal time interval to arrhythmia detection, and diagnostic yield. In total 51 participants we found 46 reports with equivalent result where as the conditions (Second Degree Mobitz Type I block, First Degree AV block, IVCD and SVT episodes) identified by VSH . Importantly, ECG wave quality in reports with differences is same in both recordings and the total diagnostic yield was 39%. Total Noise in Traditional Holter was 1301 minutes whereas in Vigo Holter was 990 minutes. Total Analyzable time in Vigo Holter was 99.3% whereas in Traditional Holter was 90.22%. VSH reports clearly explained that no lead detachments and noise resultant from the wire entanglements leading to low noise and highly analyzable time. We demonstrated that VSH is very much needed and useful for people and doctors to detect arrythmia with highest accuracy and to avoid physical interaction with the patient during COVID-19

SARS-CoV-2 RNA-dependent RNA Polymerase is Linked to Mitochondrial Dysfunction in Mouse Heart (preprint)

Little is known about specific viral factors responsible for the pathogenesis and pathophysiology of long COVID. Here we describe a conditional knock-in (cKI) mouse strain inducibly expressing Nsp12, an essential component of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Induction of Nsp12 translation was dependent on co-treatment with inhibitors of the integrated stress response in vitro and in vivo. We show that Nsp12 has a biologically significant link to mitochondrial dysfunction in vivo. In vitro, ectopic Nsp12 expression suppressed mitochondrial function in primary lung epithelial cells isolated from Nsp12 cKI mice. This functionality was physiologically relevant because, although ectopic Nsp12 expression in mouse lungs did not induce pneumonia, it did decrease mitochondrial activity in the hearts of Nsp12 cKI mice over the short and long terms. Administration in vivo of an RdRp inhibitor, EIDD-2801, restored mitochondrial function in cardiomyocytes of Nsp12 cKI mice. Our data demonstrate that SARS-CoV-2 RdRp activity in the lungs leads to cardiac mitochondrial dysfunction in vivo, generating a phenotype resembling aspects of long COVID in humans. Therapeutic targeting of SARS-CoV-2 RdRp may thus represent a novel means of preventing or mitigating intense fatigue and/or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-like disease caused by mitochondrial dysfunction in long COVID patients.

Cryptococcosis in the Immunocompetent Host: Incidence and Outcomes (preprint)

Cryptococcosis is an invasive fungal infection that typically affects immunocompromised individuals. There is limited research comparing the incidence and clinical outcomes of cryptococcosis in immunocompetent versus immunocompromised patients. Retrospective analysis was performed on patients with a confirmed positive CSF PCR, CSF antigen, or serum cryptococcal antigen tests from 5 hospitals in New York from 2017–2022. Patients were classified as immunocompromised if they had a diagnosis of HIV or active cancer, received an organ transplant, or were on immunosuppressive medications at the time of diagnosis. Baseline demographic information, comorbidities, and clinical outcomes were analyzed. 29 cases of cryptococcosis were identified with 8 cases (27.6%) occurring in immunocompetent patients. Immunocompetent patients with cryptococcosis were more likely to have a prior history of cardiac disease compared to immunocompromised patients (25% vs. 4.76%, p = 0.02). After the beginning of the COVID-19 pandemic, the proportion of immunocompetent cases increased (12% vs 35%, p = 0.03). Despite presenting with meningitis more frequently (75% vs 47.6% p = 0.08), immunocompetent patients demonstrated decreased rates of fungemia (25% vs. 33.3%, p = 0.06) and a significant decrease in mortality (12.5% vs. 23.8%, p = 0.04). Immunocompetent patients presented with meningitis more frequently and demonstrated better outcomes with decreased mortality. The proportion of immunocompetent patients increased over the study period after the beginning of the COVID-19 pandemic. Additional information about cryptococcosis in immunocompetent patients, as well as the role of cardiac disease, diabetes and COVID-19 infection as potential risk factors, warrants further study. Cryptococcosis in the Immunocompetent Host: Incidence and Outcomes

Multimorbidity characteristics in elderly inpatients and their associated factors in complex networks: a cross-sectional study (preprint)

Background Multimorbidity of chronic diseases has become an increasingly serious public health problem. However, the research on the current situation of multimorbidity in the elderly in Jiangsu, China is relatively lacking. Methods We surveyed a total of 229,926 inpatients aged above 60 and with two or more chronic diseases in the First Affiliated Hospital with Nanjing Medical University from January 1, 2015 to December 31, 2021. The Apriori algorithm was used to analyze the association rules of the multimorbidity patternsin old adults. Results The mean age of these patients was 72.0±8.7 years, and the male-to-female ratio was 1:1.53. These patients during the COVID-19 period(from 2020 to 2021) displayed younger, higher male rate, shorter median length of hospital stay, higher ≥6 multimorbidities rate and lower median cost than those not during the COVID-19 period (from 2015 to 2019). In all of these patients, the top 5 chronic diseases were "Hypertensive diseases(I10-I15)", "Other forms of heart disease(I30-I52)", "Diabetes mellitus(E10-E14)", "lschaemic heart diseases(I20-I25)" and "Cerebrovascular diseases(I60-I69)". The complex networks of multimorbidity showed that Hypertensive diseases had a higher probability of co-occurrence with multiple diseases in all these patients, followed by Diabetes mellitus, Other forms of heart disease, and lschaemic heart diseases(I20-I25). Conclusion In conclusion, the patterns of multimorbidity among the aged varied by COVID-19. Our results highlighted the importance of control of hypertensive diseases, diabetes, and heart disease in gerontal patients. More efforts to improve the understanding of multimorbidity patterns would help us develop new clinical and family care models.

Innate Immune Activation and Mitochondrial ROS Invoke Persistent Cardiac Conduction System Dysfunction after COVID-19 (preprint)

BackgroundCardiac risk rises during acute SARS-CoV-2 infection and in long COVID syndrome in humans, but the mechanisms behind COVID-19-linked arrhythmias are unknown. This study explores the acute and long term effects of SARS-CoV-2 on the cardiac conduction system (CCS) in a hamster model of COVID-19. MethodsRadiotelemetry in conscious animals was used to non-invasively record electrocardiograms and subpleural pressures after intranasal SARS-CoV-2 infection. Cardiac cytokines, interferon-stimulated gene expression, and macrophage infiltration of the CCS, were assessed at 4 days and 4 weeks post-infection. A double-stranded RNA mimetic, polyinosinic:polycytidylic acid (PIC), was used in vivo and in vitro to activate viral pattern recognition receptors in the absence of SARS-CoV-2 infection. ResultsCOVID-19 induced pronounced tachypnea and severe cardiac conduction system (CCS) dysfunction, spanning from bradycardia to persistent atrioventricular block, although no viral protein expression was detected in the heart. Arrhythmias developed rapidly, partially reversed, and then redeveloped after the pulmonary infection was resolved, indicating persistent CCS injury. Increased cardiac cytokines, interferon-stimulated gene expression, and macrophage remodeling in the CCS accompanied the electrophysiological abnormalities. Interestingly, the arrhythmia phenotype was reproduced by cardiac injection of PIC in the absence of virus, indicating that innate immune activation was sufficient to drive the response. PIC also strongly induced cytokine secretion and robust interferon signaling in hearts, human iPSC-derived cardiomyocytes (hiPSC-CMs), and engineered heart tissues, accompanied by alterations in electrical and Ca2+ handling properties. Importantly, the pulmonary and cardiac effects of COVID-19 were blunted by in vivo inhibition of JAK/STAT signaling or by a mitochondrially-targeted antioxidant. ConclusionsThe findings indicate that long term dysfunction and immune cell remodeling of the CCS is induced by COVID-19, arising indirectly from oxidative stress and excessive activation of cardiac innate immune responses during infection, with implications for long COVID Syndrome.

Clinical, laboratory, and imaging findings of stage 3-5 chronic kidney disease patients suffering from COVID-19 in Bangladesh: a prospective cross-sectional study (preprint)

Background: Chronic kidney disease (CKD) patients were susceptible to morbidity and mortality once they affected by COVID-19. These patients were more likely to develop severe disease, requiring dialysis, admission to intensive care unit. The aim of this study was to evaluate the presentations and outcomes of COVID-19 in stage 3-5 CKD patients not on dialysis. Methods This prospective observational study was conducted in the COVID-19 unit, at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from September 2020 to August 2021. Hospitalized RT-PCR positive COVID-19 patients with pre-existing CKD having eGFR <60 ml/min/1.73 m 2 but not yet on dialysis were enrolled. Clinical and laboratory parameters were recorded. Outcomes were observed till discharge from the hospital and followed up after 3 months of survived patients. Results Out of 109 patients, the mean age was 58.1(SD: 15.4) years where 61.5% were male. Common co-morbid conditions were hypertension (89.0%), diabetes mellitus (58.7%) and ischemic heart disease (24.8%). Fever, cough, shortness of breath and fatigue were common presenting features. Most of the patients had moderate (41.3%) and severe (41.3%) COVID-19. Sixty-six patients (60.6%) developed AKI on CKD. Twenty patients (30.3%) required dialysis. Death occurred in 16 patients (14.7%) and 12 patients (11%) required ICU admission and 6 patients (9.1%) achieved baseline renal function at discharge. We identified risk factors like low haemoglobin, lymphopenia, high CRP, high procalcitonin, high LDH and low SpO 2 in patients who did not survive. Seventy-six patients were followed up at 3rd month where 17 patients were lost. Ten patients (27.0%) achieved baseline renal function who had persistent AKI at discharge and 34 patients (87.1%) remained stable who had stable renal function at discharge. Conclusion The stage 3-5 chronic kidney patients with COVID-19 are vulnerable to severe to critical morbidity and mortality with higher incidence of AKI which demands a special attention to this group of patients.

Emerging Links Between COVID-19 and Cardiovascular & Cerebrovascular Thromboembolic Events: A Systematic Review (preprint)

COVID-19, caused by the SARS-CoV-2 virus, initially identified as a respiratory illness, has increasingly been linked to a broader range of organ complications. This systematic review explores the impact of COVID-19 on cardiovascular and cerebrovascular health, focusing on thromboembolic events in post-COVID patients. A comprehensive literature search was conducted in PubMed and Google Scholar databases up to July 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies meeting eligibility criteria were analyzed for outcomes and associations between COVID-19 and cardiovascular and cerebrovascular events. The review includes 6 studies involving over 12 million patients, demonstrating a strong connection between COVID-19 and elevated risks of cardiovascular and cerebrovascular thromboembolic events. The risk of these events is evident in conditions such as ischemic heart disease, stroke, and cardiac arrhythmias. The burden of these events beyond the acute phase of the disease is concerning, warranting further exploration of long-term implications. Variability in event rates among different cohorts and healthcare settings underscores the need for understanding underlying factors influencing these differences. Potential mechanisms behind these events include endothelial dysfunction, systemic inflammation, and viral invasion. Implications for public health policies, clinical guidelines, and future research directions are discussed. This review serves as a valuable resource for healthcare providers, policymakers, and researchers to enhance patient care, outcomes, and preparedness for future waves of COVID-19 infections. However, there remain unexplored aspects of the COVID-19 and thromboembolic events relationship, urging further investigations into mechanistic insights and potential therapeutic interventions.

Self-assembly vascularized human cardiac organoids model cardiac diseases in petri dishes and in mice (preprint)

In this study, we generated self-assembly cardiac organoids (COs) from human pluripotent stem cells by dual-phase modulation of Wnt/{beta}-catenin pathway, utilizing CHIR99021 and IWR-1-endo. The resulting COs exhibited a diverse array of cardiac-specific cell lineages, cardiac cavity-like structures and demonstrated the capacity of spontaneous beating and vascularization in vitro. We further employed these complex and functional COs to replicate conditions akin to human myocardial infarction and SARS-CoV-2 induced fibrosis. These models accurately captured the pathological characteristics of these diseases, in both in vitro and in vivo settings. In addition, we transplanted the COs into NOD SCID mice and observed that they survived and exhibited ongoing expansion in vivo. Impressively, over a span of 75-day transplantation, these COs not only established blood vessel-like structures but also integrated with the host mice's vascular system. It is noteworthy that these COs developed to a size of approximately 8 mm in diameter, slightly surpassing the dimensions of the mouse heart. This innovative research highlighted the potential of our COs as a promising avenue for cardiovascular research and therapeutic exploration.

Heart-on-a-chip model of immune-induced cardiac dysfunction reveals the involvement of free mitochondrial DNA and therapeutic effects of endothelial exosomes (preprint)

Cardiovascular disease continues to take more human lives than all cancer combined, prompting the need for improved research models and treatment options. Despite a significant progress in development of mature heart-on-a-chip models of fibrosis and cardiomyopathies starting from induced pluripotent stem cells (iPSCs), human cell-based models of myocardial inflammation are lacking. Here, we bioengineered a vascularized heart-on-a-chip system with circulating immune cells to model SARS-CoV-2-induced acute myocarditis. Briefly, we observed hallmarks of COVID-19-induced myocardial inflammation in the heart-on-a-chip model, as the presence of immune cells augmented the expression levels of proinflammatory cytokines, triggered progressive impairment of contractile function and altered intracellular calcium transient activities. An elevation of circulating cell-free mitochondrial DNA (ccf-mtDNA) was measured first in the in vitro heart-on-a-chip model and then validated in COVID-19 patients with low left ventricular ejection fraction (LVEF), demonstrating that mitochondrial damage is an important pathophysiological hallmark of inflammation induced cardiac dysfunction. Leveraging this platform in the context of SARS-CoV-2 induced myocardial inflammation, we established that administration of human umbilical vein-derived EVs effectively rescued the contractile deficit, normalized intracellular calcium handling, elevated the contraction force and reduced the ccf- mtDNA and chemokine release via TLR-NF-kB signaling axis.

Epigenetic liquid biopsies reveal elevated vascular endothelial cell turnover and erythropoiesis in asymptomatic COVID-19 patients (preprint)

The full spectrum of tissues affected by SARS-CoV-2 infection is crucial for deciphering the heterogenous clinical course of COVID-19. Here, we analyzed DNA methylation and histone modification patterns in circulating chromatin to assess cell type-specific turnover in severe and asymptomatic COVID-19 patients, in relation to clinical outcome. Patients with severe COVID-19 had a massive elevation of circulating cell-free DNA (cfDNA) levels, which originated in lung epithelial cells, cardiomyocytes, vascular endothelial cells and erythroblasts, suggesting increased cell death or turnover in these tissues. The immune response to infection was reflected by elevated B cell and monocyte/macrophage cfDNA levels, and by evidence of an interferon response in cells prior to cfDNA release. Strikingly, monocyte/macrophage cfDNA levels (but not monocyte counts), as well as lung epithelium cfDNA and vascular endothelial cfDNA, predicted clinical deterioration and duration of hospitalization. Asymptomatic patients had elevated levels of immune-derived cfDNA but did not show evidence of pulmonary or cardiac damage. Surprisingly, these patients showed elevated levels of vascular endothelial cell and erythroblast cfDNA, suggesting that sub-clinical vascular and erythrocyte turnover are universal features of COVID-19, independent of disease severity. Epigenetic liquid biopsies provide non-invasive means of monitoring COVID-19 patients, and reveal sub-clinical vascular damage and red blood cell turnover.

A Novel Deep Network Approach for Ecg Classification System Aided on Gsm (preprint)

The prevalence of heart-related diseases and heart attacks has significantly risen, particularly in recent times, largely attributed to the Covid-19 pandemic, thereby increasing the burden on healthcare professionals. Electrocardiogram (ECG)-based approaches are widely employed for the detection of heart diseases due to their reliability and non-invasive nature. With the advancements in technology, numerous novel devices and methods, including machine learning and artificial intelligence (ML-AI) techniques, have been developed to address heart diseases, playing a crucial role in enhancing human well-being. This study introduces a GSM-based approach supported by deep learning, enabling remote monitoring of heart signals, aiming to alleviate the workload of doctors.The purpose of this investigation is to develop a wireless surveillance framework for ECG signals, with the goal of improving patient safety and reducing the workload of healthcare providers. Our research centers on implementing a portable, real-time, and cost-efficient ECG monitoring system that utilizes the GSM network, specifically the GSM Shield Sim900l.

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.