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1.
preprints.org; 2024.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202402.1267.v1

ABSTRACT

Exposure to vaccine lipid nanoparticles, mRNA, adenoviral DNA, and or Spike protein from one of the approved Covid-19 vaccines, or through secondary exposure, as through blood transfusion, is a potential source of harm. Blood reactions are an acknowledged side-effect of Covid-19 vaccination, not limited to hemolysis, paroxysmal nocturnal hemoglobinuria, chronic cold agglutinin disease, immune thrombocytopenia, haemophagocytosis, hemophagocytic lymphohistiocytosis, and many other blood related conditions. The observation of adverse events has motivated investigation into the cardiovascular mechanisms of harm by Covid-19 vaccines, and the biodistribution of vaccine contents. Biodistribution may not be limited to the body of the vaccine recipient, as a growing body of evidence demonstrates the possibility of secondary exposure to vaccine particles. These can be via bodily fluids and include the following routes of exposure: blood transfusion, organ transplantation, breastfeeding, and possibly other means. As covid-19 vaccines are associated with an increased risk of stroke, the persistence of vaccine artifacts in the blood presents a possible threat to a recipient of a blood donation from a vaccinated donor who suffered from vaccine induced thrombosis or thrombocytopenia. (VITT) We assess the feasibility and significance of these risks through an overview of the case report literature of blood disorders in vaccinated individuals, pharmacovigilance reports from the US Vaccine Adverse Events Reporting System (VAERS) and a meta-analysis of the available literature on organ transplants from vaccinated organ donors. Our analysis establishes biological mechanistic plausibility, a coherent safety signal in pharmacovigilance databases for secondary vaccine contents exposure (for the cases of blood transfusion and breastfeeding) and also an elevated level of adverse events in organ transplants from VITT-deceased donors, echoing increases in organ transplantation related complications seen in national statistics for some countries. Secondary exposure to vaccine artifacts is a potential explanation for some of the cases put forth, and requires a deeper investigation.


Subject(s)
Stroke , Hematologic Diseases , Thrombocytopenia , Lymphohistiocytosis, Hemophagocytic , COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Hemoglobinuria, Paroxysmal , Hemolysis , Thrombosis
2.
researchsquare; 2024.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3877193.v1

ABSTRACT

Various cases of immune thrombocytopenic purpura (ITP) were reported among COVID-19-positive patients in the literature. We used the National Inpatient Sample (NIS) to evaluate the odds of ITP among COVID-19 patients in the United States between April and November 2020. Females (vs. Males), Whites (vs. other races), and the presence of multiple comorbidities such as chronic kidney disease, cirrhosis, prior stroke, HIV, obesity, cachexia, neoplasms, and autoimmune conditions showed higher odds of ITP. Meanwhile, those with diabetes and peripheral vascular disease and covered by private insurance (vs. Medicare) were less likely to experience ITP while being positive for the virus. Events of ITP also led to a higher mortality risk in COVID-19-positive patients.


Subject(s)
Stroke , Diabetes Mellitus , Cachexia , Neoplasms , Obesity , COVID-19 , HIV Infections , Renal Insufficiency, Chronic , Purpura, Thrombocytopenic , Purpura, Thrombocytopenic, Idiopathic , Fibrosis , Peripheral Vascular Diseases
3.
arxiv; 2023.
Preprint in English | PREPRINT-ARXIV | ID: ppzbmed-2312.09611v1

ABSTRACT

Societal change is often driven by shifts in public opinion. As citizens evolve in their norms, beliefs, and values, public policies change too. While traditional opinion polling and surveys can outline the broad strokes of whether public opinion on a particular topic is changing, they usually cannot capture the full multi-dimensional richness and diversity of opinion present in a large heterogeneous population. However, an increasing fraction of public discourse about public policy issues is now occurring on online platforms, which presents an opportunity to measure public opinion change at a qualitatively different scale of resolution and context. In this paper, we present a conceptual model of observed opinion change on online platforms and apply it to study public discourse on Universal Basic Income (UBI) on Reddit throughout its history. UBI is a periodic, no-strings-attached cash payment given to every citizen of a population. We study UBI as it is a clearly-defined policy proposal that has recently experienced a surge of interest through trends like automation and events like the COVID-19 pandemic. We find that overall stance towards UBI on Reddit significantly declined until mid-2019, when this historical trend suddenly reversed and Reddit became substantially more supportive. Using our model, we find the most significant drivers of this overall stance change were shifts within different user cohorts, within communities that represented similar affluence levels, and within communities that represented similar partisan leanings. Our method identifies nuanced social drivers of opinion change in the large-scale public discourse that now regularly occurs online, and could be applied to a broad set of other important issues and policies.


Subject(s)
Stroke , COVID-19
4.
preprints.org; 2023.
Preprint in English | PREPRINT-PREPRINTS.ORG | ID: ppzbmed-10.20944.preprints202312.0791.v1

ABSTRACT

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a frequent, debilitating and still enigmatic disease. There is a broad overlap in the symptomatology of ME/CFS and the Post-COVID Syndrome (PCS). A fraction of the PCS patients develops the full clinical picture of ME/CFS. New observations in microvessels and blood from patients suffering from PCS have appeared and include microclots and malformed pathological blood cells. Capillary blood flow is impaired not only by pathological blood components but also by prothrombotic changes in the vascular wall, endothelial dysfunction, and expression of adhesion molecules in the capillaries. These disturbances can finally cause a low capillary flow and even capillary stasis. A low cardiac stroke volume due to hypovolemia and the inability of the capacitance vessels to adequately constrict to deliver the necessary cardiac preload generate an unfavorable low precapillary perfusion pressure. Furthermore, a predominance of vasoconstrictor over vasodilator influences exists, in which sympathetic hyperactivity and endothelial dysfunction play a strong role, causing constriction of resistance vessels and of precapillary sphincters which leads to a fall in capillary pressure behind the sphincters. The interaction of these two precapillary cardiovascular mechanisms causing a low capillary perfusion pressure is hemodynamically highly unfavorable in the presence of a primary capillary stasis already caused by the pathological blood components and their interaction with the capillary wall, to severely impair organ perfusion. The detrimental coincidence of the microcirculatory with the precapillary cardiovascular disturbances may constitute the key disturbance of the Post-COVID-19 syndrome and finally lead to ME/CFS in pre-disposed patients because the interaction causes a particular kind of perfusion disturbance - capillary ischemia-reperfusion - which has a high potential of causing mitochondrial dysfunction by inducing sodium- and calcium-overload in skeletal muscles. The latter in turns worsens the vascular situation by the generation of reactive oxygen species to close a vicious cycle from which the patient can hardly escape.


Subject(s)
Stroke , Sphincter of Oddi Dysfunction , Ischemia , Hypovolemia , COVID-19 , Hyperkinesis , Cardiovascular Diseases , Fatigue Syndrome, Chronic , Mitochondrial Diseases
5.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.10.12.23296968

ABSTRACT

Introduction The potential association between bivalent COVID-19 vaccination and ischemic stroke remains uncertain, despite several studies conducted thus far. The purpose is to evaluate the risk of ischemic stroke following bivalent COVID-19 vaccination. Methods A self-controlled case series study was conducted among members aged 12 years and older who experienced ischemic stroke between September 1, 2022 and March 31, 2023 in a large California health care system. Ischemic strokes were identified using ICD-10 codes in Emergency Department and inpatient settings. Exposures were Pfizer-BioNTech or Moderna bivalent COVID-19 vaccination. Risk intervals were pre-specified as 1-21 days and 1-42 days after bivalent COVID-19 vaccination; all non-risk-interval person-time served as control interval. We conducted overall and subgroup analyses by age, history of SARS-CoV-2 infection, and co-administration of influenza vaccine. When an elevated risk was detected, we performed chart review of ischemic strokes, and re-evaluated the risk. RESULTS With 4933 cases, we found no increased risk within 21-day risk interval across vaccines and by subgroups. However, an elevated risk emerged within 42-day risk interval among individuals <65 years who received co-administration of Pfizer-BioNTech bivalent vaccine and influenza vaccine on the same day; relative incidence (RI) was 2.14 (95% CI, 1.02-4.49). Among those who also had history of SARS-CoV-2 infection, RI was 3.94 (95% CI, 1.10-14.16). After chart review, RIs were 2.35 (95% CI, 0.98-5.65) and 4.33 (95% CI, 0.98-19.11), respectively. Among individuals <65 years who received Moderna bivalent vaccine and had history of SARS-CoV-2 infection, RI was 2.62 (95% CI, 1.13-6.03) before chart review and 2.24 (95% CI, 0.78-6.47) after chart review. CONCLUSIONS The potential association between bivalent COVID-19 vaccination and ischemic stroke in the 1-42-day analysis warrants further investigation among individuals <65 years with influenza vaccine co-administration and prior SARS-CoV-2 infection.


Subject(s)
Stroke , Ischemia , COVID-19
6.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.10.10.23296624

ABSTRACT

In January 2023, the United States Food and Drug Administration and the Centers for Disease Control and Prevention noted a safety concern for ischemic stroke in adults 65 years of age or older receiving the BNT162b2; WT/OMI BA.4/BA.5 COVID-19 bivalent vaccine. This self-controlled case series analysis evaluated stroke risk among Medicare fee-for-service beneficiaries aged 65 years of age or older receiving: 1) a Pfizer-BioNTech (BNT162b2; WT OMI BA.4 and BA.5) or Moderna (mRNA 1273.222) COVID-19 bivalent vaccine, 2) high-dose/adjuvanted influenza vaccines, and 3) concomitant COVID-19 bivalent vaccines and influenza vaccines, from August 31 to November 6, 2022. The primary analysis did not find elevated stroke risk following COVID-19 bivalent vaccines. In the age subgroup analyses, only the 85+ year age group had a risk of NHS (Incident Rate Ratio (IRR)=1.36, 95% CI 1.09 to 1.69 [1 to 21 days]) and NHS/TIA (IRR=1.28, 95% CI 1.08 to 1.52 [1 to 21 days]) with BNT162b2 Bivalent WT OMI BA.4 and BA.5. Among beneficiaries receiving a concomitant COVID-19 bivalent vaccine and a high-dose/adjuvanted influenza vaccine, an increased risk was observed for NHS (IRR=1.20, 95% CI 1.01 to 1.42 [22 to 42 days]) with BNT162b2 Bivalent WT OMI BA.4 and BA.5 and for TIA (IRR=1.35, 95% CI 1.06 to 1.74 [1 to 21 days]) with mRNA 1273.222. Results of the secondary analyses showed a small increased risk of NHS following high-dose or adjuvanted influenza vaccines (IRR=1.09, 95% CI 1.02 to 1.17 [22 to 42 days]).


Subject(s)
Stroke , COVID-19
7.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.10.11.561925

ABSTRACT

Viral infection severity often varies with host factors such as age and sex. The pathogenesis of infections caused by a broad range of viruses, from neurotropic viruses like Rabies and Zika to respiratory viruses such as influenza and SARS-CoV-2, differ between the sexes and across the lifespan. Typically, older males are more susceptible to severe acute outcomes, while females are more vulnerable to the post-acute sequelae of infections. All of these complications can include neuroinflammation, stroke, cognitive dysfunction, and delirium. While these symptoms can be secondary to infection, recent studies suggest that even peripheral infections can lead to neuropathological changes in the brain. However, few studies have characterized the expression of viral receptors in the human brain or examined age- or sex-related differences in such expression. In this study, we used a publicly accessible transcriptomic database to assess the impact of age and sex on the expression of 67 viral host factor genes, associated with ten virus families. Analyzing data from 15 brain areas (n=33, F=14, M=19, age:4 mo-80 yrs), we determined the lifespan trajectory for each gene in each area via LOESS regressions. We used unsupervised hierarchical clustering to determine if a brain-wide pattern or virus family pattern can be detected. Using Dense-tSNE, a dimension-reduction and visualization technique, we discovered four distinct developmental trajectories, clustering the areas into two mixed-sex subcortical clusters and one each of male and female cortical clusters. Applying Differential Expression Sliding Window Analysis (DeSWAN), we identified the genes driving these age- and sex-related differences. Many sex differences were noted in childhood, potentially impacting the brain\'s susceptibility to viral infections and underscoring a broader dimorphic organization of male and female brains. These insights contribute to our understanding of sex-specific responses to viral infections, offering the potential for more personalized treatment strategies.


Subject(s)
Stroke , Delirium , Virus Diseases , Cognition Disorders
8.
researchsquare; 2023.
Preprint in English | PREPRINT-RESEARCHSQUARE | ID: ppzbmed-10.21203.rs.3.rs-3396574.v1

ABSTRACT

Background Depression and anxiety are prevalent after stroke and associated with poor outcomes. We previously co-developed a stroke-specific self-management intervention, HEADS: UP (Helping Ease Anxiety and Depression after Stroke). The two studies reported here aimed to test the feasibility and acceptability of the HEADS: UP course and supporting materials, and research processes ahead of a definitive trial. Methods We recruited community-dwelling stroke survivors (SS) ≥3 months post-stroke, with symptoms of mood disorder (Hospital Anxiety and Depression Scale ≥8). Participants could ‘enrol’ a family member/‘other’ to take part with them, if desired. Study 1 tested HEADS: UP delivered in-person, and informed optimisation of research processes and intervention delivery and materials. In response to Covid-related socialising restrictions HEADS: UP was then adapted for online delivery; tested in Study 2. The primary outcome (both studies) was feasibility (acceptability, fidelity) of the intervention and of research processes. Quantitative data (including patient reported outcomes measures (PROMs) assessing mood and quality of life), and qualitative data were collected pre-/post-intervention. Descriptive statistics were used to analyse quantitative data; a thematic framework approach was used to analyse qualitative data. Both studies received ethical approval prior to commencement. Results Study 1: Feasibility: 13 (59.1%) of 22 potentially eligible stroke survivors consented; aged 66 (median, IQR 14); male (n=9; 69%); 28 (IQR 34; 13.5-48) months poststroke. Of these n=10 (76.9%) completed PROMS pre-intervention; n=6 (46.2%) post-intervention. Acceptability: Six (85.7%) stroke survivors attended ≥4 core intervention sessions. Aspects of screening and data collection were found to be burdensome. Study 2: Feasibility: SS n=9 (41%) of 22 potentially eligible stroke survivors consented; aged 58 years (median; IR 12); male (n=4; 44.4%); 23 (IQR 34; 10-38) months poststroke. Of these n=5 (55.6%) completed PROMS pre-intervention; n=5 (55.6%) post-intervention. Acceptability: Five (55.6%) stroke survivors attended ≥ 4 core sessions. They found online screening and data collection processes straightforward. Conclusions Stroke survivors found in-person and online HEADS: UP intervention and research processes feasible and acceptable. A pilot RCT is warranted, after making the adaptations to intervention delivery and research processes identified in this feasibility and acceptability research. Trial registration Study 1 (in-person delivery): ClinicalTrials.gov: NCT03956693, registered 20 May 2019, https://www.clinicaltrials.gov/study/NCT03956693 Study 2 (online delivery): ClinicalTrials.gov: NCT04567472, registered 23, September 2020, https://clinicaltrials.gov/study/NCT04567472?tab=results


Subject(s)
Stroke , Mood Disorders , Depressive Disorder , Anxiety Disorders , Head and Neck Neoplasms
9.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.09.11.23295368

ABSTRACT

Abstract: Purpose: What is the absolute occurrence of ischemic stroke and transient ischemic attack after a COVID-19 bivalent vaccination? Methods: We conducted a retrospective cohort study of Kaiser Permanente Northwest (KPNW) patients 18 years and older who were vaccinated with either the Pfizer or Moderna formulation of the COVID19 bivalent vaccine between September 1, 2022 and March 1st 2023. Patients were included in the study if they had KP membership at the time of vaccination and through the 21-day follow up period. We replicated the Vaccine Safety Datalink (VSD) rapid cycle analysis methodology and searched for possible cases of ischemic stroke or TIA in the 21 days following vaccination using ICD10CM diagnosis codes in both the primary position and any position. We waited 90 days from the end of the follow up (March 21, 2023) for complete non KP data accrual before analyzing the data to account for the lag in processing outside hospital insurance claims. Two physicians adjudicated possible cases by reviewing the clinical notes in the electronic health record. The analyses were stratified by age 65 years and older to allow for comparisons with VSDs reporting at the Advisory Committee on Immunization Practices (ACIP) meeting of incidence of ischemic stroke or TIA (VSD reported incidence; 24.6 cases of ischemic stroke or TIA per 100,000 patients vaccinated). Results: The incidence of ischemic stroke or TIA was 34.3 per 100,000 (95% CI, 17.7 to 59.9) in patients 65 years or older who received the bivalent Pfizer vaccine, based on a diagnosis code in the primary position of the emergency department or hospital discharge. The incidence increased to 45.7 per 100,000 (95% CI 26.1 to 74.2) when we expanded the search to a diagnosis in any position and did not adjudicate to confirm. However, most of those additional apparent stroke or TIA diagnoses were false-positive diagnoses based on physicians adjudications. Estimating the incidence based on the primary position agreed closely with estimating the incidence based on any position and physician adjudication: 37.1 per 100,000 (95% CI 19.8 to 63.5). Seventy-nine percent of the ischemic stroke cases were admitted to hospitals that are not owned by the integrated delivery system. Conclusion: We identified a 50% increase in the incidence of ischemic stroke per 100,000 patients ages 65 and older vaccinated with the Pfizer bivalent vaccine, compared to the data presented by the VSD. Seventy-nine percent of the ischemic stroke cases were admitted to hospitals that are not owned by the integrated delivery system and a delay in processing outside hospital insurance claims was likely responsible for the discrepancy in case ascertainment of ischemic stroke. Physician adjudication of all cases in this study allowed accurate absolute incidence estimates of stroke per 100,000 vaccine recipients and is helpful in calculation of net benefit for policy recommendations and shared decision-making.


Subject(s)
Stroke , Ischemia , COVID-19 , Encephalomyelitis, Acute Disseminated
10.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.09.10.23295343

ABSTRACT

Background: The COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people and can result in both immediate and prolonged neurological effects, including severe complications. While numerous studies have explored the occurrence and consequences of neurological issues in COVID-19, they have often involved limited sample sizes. Purpose: This paper aims to determine the overall occurrence of neurological complications in COVID-19, examine their links with patient demographics, and assess their impact on patient outcomes. Additionally, it seeks to provide an overview of the current understanding of the underlying mechanisms. Methodology: Two systematic reviews were conducted to investigate acute and chronic neurological complications associated with COVID-19. A comprehensive search of medical databases was performed, and relevant studies were evaluated following PRISMA guidelines. Meta-analysis was carried out using the Mantel-Haenszel method, with subgroup analysis and meta-regression used to assess heterogeneity. Results: The analysis of acute complications included 20,011 patients with an average age of 58.1 years and a slight male predominance (55.2%). Common neurological symptoms included loss of taste and smell, headaches, acute encephalopathy, and stroke. For the analysis of long-term complications, 2,094 patients were included. Survivors of COVID-19 experienced ongoing neurological issues ranging from sensory impairments to fatigue, headaches, strokes, and even cognitive and psychiatric problems. Conclusion: By examining various neurological symptoms, this study found a significant association between these manifestations and worse overall outcomes, especially in patients over 60 years old. Identifying high-risk individuals and maintaining a high level of suspicion are crucial for enhancing our understanding of the underlying mechanisms, validating biomarkers, and improving the management of these neurological issues.


Subject(s)
Stroke , Headache , COVID-19 , Mental Disorders , Brain Diseases , Fatigue , Central Nervous System Diseases
11.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.09.05.23295067

ABSTRACT

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.


Subject(s)
Stroke , Inflammation , Thromboembolism , Ischemia , Respiratory Insufficiency , Severe Acute Respiratory Syndrome , COVID-19 , Heart Diseases , Arrhythmias, Cardiac
12.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.08.14.553245

ABSTRACT

COVID-19 patients present higher risk for myocardial infarction (MI), acute coronary syndrome, and stroke for up to 1 year after SARS-CoV-2 infection. While the systemic inflammatory response to SARS-CoV-2 infection likely contributes to this increased cardiovascular risk, whether SARS-CoV-2 directly infects the coronary vasculature and attendant atherosclerotic plaques to locally promote inflammation remains unknown. Here, we report that SARS-CoV-2 viral RNA (vRNA) is detectable and replicates in coronary atherosclerotic lesions taken at autopsy from patients with severe COVID-19. SARS-CoV-2 localizes to plaque macrophages and shows a stronger tropism for arterial lesions compared to corresponding perivascular fat, correlating with the degree of macrophage infiltration. In vitro infection of human primary macrophages highlights that SARS-CoV-2 entry is increased in cholesterol-loaded macrophages (foam cells) and is dependent, in part, on neuropilin-1 (NRP-1). Furthermore, although viral replication is abortive, SARS-CoV-2 induces a robust inflammatory response that includes interleukins IL-6 and IL-1{beta}, key cytokines known to trigger ischemic cardiovascular events. SARS-CoV-2 infection of human atherosclerotic vascular explants recapitulates the immune response seen in cultured macrophages, including proatherogenic cytokine secretion. Collectively, our data establish that SARS-CoV-2 infects macrophages in coronary atherosclerotic lesions, resulting in plaque inflammation that may promote acute CV complications and long-term risk for CV events


Subject(s)
Stroke , Acute Coronary Syndrome , Inflammation , Myocardial Infarction , Severe Acute Respiratory Syndrome , COVID-19 , Cardiovascular Diseases , Atherosclerosis
13.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.08.06.552160

ABSTRACT

Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothrombotic state is considered a key factor in the increased risk of stroke, which has been observed clinically during both acute infection and long after symptoms have cleared. Here we developed a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells, pericytes, and smooth muscle cells to recapitulate the vascular pathology associated with SARS-CoV-2 exposure. Our results demonstrate that perivascular cells, particularly smooth muscle cells (SMCs), are a specifically susceptible vascular target for SARS-CoV-2 infection. Utilizing RNA sequencing, we characterized the transcriptomic changes accompanying SARS-CoV-2 infection of SMCs, and endothelial cells (ECs). We observed that infected human SMCs shift to a pro-inflammatory state and increase the expression of key mediators of the coagulation cascade. Further, we showed human ECs exposed to the secretome of infected SMCs produce hemostatic factors that can contribute to vascular dysfunction, despite not being susceptible to direct infection. The findings here recapitulate observations from patient sera in human COVID-19 patients and provide mechanistic insight into the unique vascular implications of SARS-CoV-2 infection at a cellular level.


Subject(s)
Stroke , Thromboembolism , Vascular Diseases , COVID-19 , Coronavirus Infections , Acute Disease
14.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.07.20.23292901

ABSTRACT

Background/ aims: Little is known about the experience of people post-stroke and their informal caregivers during the COVID-19 pandemic. The aim of this study was to understand the challenges faced by people post-stroke and informal caregivers during the pandemic, as well as the impact on their healthcare support, lifestyle, and self-care behaviors. Methods: A multi-perspective qualitative study was undertaken, with semi-structured interviews being carried out to sixteen participants: eight stroke patients and eight informal caregivers, mostly performed online. Reflexive thematic analysis was used, with data being independently coded and categorized before consolidated into themes and subthemes. Findings: Three themes were derived from the data analysis: i) Perceived impact of COVID-19 pandemic, ii) What helped? - strategies to manage the distress provoked by COVID-19, and iii) The value of rehabilitation and physical activity, with findings highlighting the negative psychological impact of the pandemic. In response to the perceived lack of support and access to health and social services, participants highlighted the use of digital approaches and professional support. Conclusions: Findings suggest the importance of self-management support and/or digital content in order to mitigate the impact of COVID-19. The involvement of peers, family members, friends or others seems to be an important strategy to increase motivation in remote rehabilitation and physical activity.


Subject(s)
Stroke , COVID-19
17.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.07.07.23292399

ABSTRACT

Background Nationally representative data demonstrating the impact of the COVID-19 pandemic on hemorrhagic stroke outcomes are lacking. Methods In this pooled cross-sectional analysis, we used the National Inpatient Sample (2016-2020) to identify adults (>=18 years) with primary intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH). We fit segmented logistic regression models to evaluate the differences in the rates of in-hospital outcomes (in-hospital mortality, home discharge, and receiving neurosurgical procedures) between the pre-pandemic (January 2016-February 2020) and pandemic periods (March 2020-December 2020). We used multivariable logistic regression models to evaluate the differences in mortality between patients admitted from April to December 2020, with and without COVID-19, and those admitted during a similar period in 2019. Stratified analyses were conducted among patients residing in low and high-income zip codes and among patients with extreme loss of function (E-LoF) and those with minor to major loss of function (MM-LoF). Results Overall, 309,965 ICH patients (mean age [SD]: 68[14.8], 47% female, 56% low-income) and 112,210 SAH patients (mean age [SD]: 60.2[15.4], 62% female, 55% low-income) were analyzed. Pre-pandemic, ICH mortality was decreasing by {approx}1% per month (adjusted odds ratio, 95% confidence interval: 0.99, 0.99-1.00). However, during the pandemic, the overall ICH mortality rate increased by {approx}2% per month (1.02, 1.00-1.02) and {approx}4% per month among low-income patients (1.04, 1.01-1.07). However, there was no change in trend among high-income ICH patients during the pandemic (1.00, 0.97-1.03). Patients with comorbid COVID-19 in 2020 had significantly higher odds of mortality compared to the 2019 comparison cohort, overall (ICH: 1.83, 1.33-2.51; SAH: 2.76, 1.68-4.54), and among patients with MM-LoF (ICH: 2.15, 1.12-4.16; SAH: 5.77, 1.57-21.17). However, patients with E-LoF and comorbid COVID-19 had similar mortality rates with the 2019 cohort. Conclusion Sustained efforts are needed to address socioeconomic disparities in healthcare access, quality, and outcomes during public health emergencies.


Subject(s)
Stroke , Depressive Disorder, Major , Subarachnoid Hemorrhage , COVID-19 , Cerebral Hemorrhage
18.
ssrn; 2023.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.4499590

ABSTRACT

Background: Diffusion microstructure imaging (DMI) is a novel diffusion magnetic resonance imaging (MRI) technique that provides rich estimates of microscopic tissue properties, such as axon morphologies and fiber configurations. DMI has potential applications in neurology, where various diseases and disorders affect the brain tissue's microstructure and connectivity.Objectives: To investigate the current and future applications of DMI in neurology, covering various diseases and disorders such as brain tumors and metastases, Parkinson's syndromes, COVID-19-related neurological symptoms, temporal lobe epilepsy, and acute ischemic stroke.Methods: The PRISMA 2020 statement was followed. Four electronic databases were searched from inception to May the 5th 2023. Two reviewers independently screened, selected, and extracted data from the eligible studies.Results: Seven studies were included in the review. The studies showed that DMI can differentiate between various neurological diseases or disorders based on alterations in brain tissue microstructure and connectivity. The studies also showed that DMI can be superior to conventional diffusion imaging techniques, such as diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), in detecting subtle differences between pathological conditions.Conclusions: DMI is a powerful diffusion imaging technique that can provide rich estimates of microscopic tissue properties and differentiate between various neurological diseases or disorders. However, more research is needed to compare DMI with other imaging modalities or clinical measures and to evaluate longitudinal changes or treatment effects using DMI in neurological diseases or disorders.


Subject(s)
Stroke , Epilepsy, Temporal Lobe , COVID-19 , Parkinson Disease , Heredodegenerative Disorders, Nervous System , Brain Neoplasms , Nervous System Diseases , Neoplasm Metastasis
19.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.07.05.23292278

ABSTRACT

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.


Subject(s)
Stroke , Acute Coronary Syndrome , COVID-19 , Blood Coagulation Disorders , Heart Arrest , Heart Failure , Thrombosis , Acute Kidney Injury
20.
ssrn; 2023.
Preprint in English | PREPRINT-SSRN | ID: ppzbmed-10.2139.ssrn.4496138

ABSTRACT

Background: Nirmatrelvir/ritonavir is mainly used in patients with normal renal function or with only mild renal impairment (eGFR ³ 30 ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease. We performed a retrospective territory-wide cohort study evaluating the safety and efficacy of nirmatrelvir/ritonavir when compared with molnupiravir.Nirmatrelvir/ritonavir is mainly used in patients with normal renal function or with only mild renal impairment (eGFR ≥ 30 ml/min per 1.73m2). There is limited data regarding its use in advanced kidney disease. We performed a retrospective territory-wide cohort study evaluating the safety and efficacy of nirmatrelvir/ritonavir when compared with molnupiravir.Methods: We performed a retrospective cohort study of hospitalized and non-hospitalized patients with a confirmed diagnosis of COVID-19 in Hong Kong, China, for an observation period from 1 January 2022 to 31 December 2022 (during the omicron BA.2 and BA.5 variant wave). Adult COVID-19 patients (age ≥ 18 years) were selected from medical records held by the Hospital Authority of Hong Kong. We included all patients with COVID-19 regardless of disease severity at baseline having chronic kidney disease (CKD) stage 4 or above (i.e with eGFR < 30 ml/min per 1.73m2) with or without dialysis who receive either nirmatrelvir/ritonavir or molnupiravir. Outcomes at day 90 post-treatment of each treatment arm (nirmatrelvir/ritonavir v.s. molnupiravir) were analyzed and compared. All-cause mortality, respiratory outcomes including mechanical ventilation and non-invasive ventilation, cardiovascular events including myocardial infarction and ischemic stroke, and hepatic complications including elevated liver enzymes were analyzed. Time-to-event analysis was performed for the designated outcomes using univariate and multivariate Cox proportional hazard model regression for unadjusted and adjusted hazard ratios (HR).Findings: We included 454 and 5,880 CKD stage 4 or above patients receiving nirmatrelvir/ritonavir and molnupiravir respectively from public clinics and hospitals managed by the Hospital Authority in Hong Kong during the period. At 90 days, 662 (10.4%) patients of the combined cohort experienced all-cause mortality. Nirmatrelvir/ritonavir group had significant lower all-cause mortality than molnupiravir group (6.82% vs 10.7%) with unadjusted HR of 0.67 (95% CI 0.472 - 0.97, p=0.0337*). After adjusting for sex, age, hypertension, diabetes mellitus, history of myocardial infarction and dialysis in multi-variate analysis, nirmatrelvir/ritonavir group was still associated with superior 90-day survival with adjusted HR of 0.60 (95% CI 0.48 - 0.992, p = 0.0452*). Composites of mechanical and non-invasive ventilation rate were similar in nirmatrelvir/ritonavir and molnupiravir groups (0.96% vs 1.10%, p=0.651). Nirmatrelvir/ritonavir group had higher proportion of patients who received non-invasive ventilation (1.10% vs 0.42%, p = 0.0383*) and trended towards fewer patients requiring mechanical ventilation although statistical significance was not reached (0% vs 0.59%, p = 0.996). There were no significant differences in rate of myocardial infarction (0.88% vs 2.14%, p = 0.0844) and ischemic stroke (0.22% vs 0.61%, p = 0.34) between nirmatrelvir/ritonavir and molnupiravir groups. Hepatic impairment, defined by elevated alanine aminotransferase concentration ≥ 2X upper limit of normal (ULN), was present in 1.45% and 0.94% of patients in nirmatrelvir/ritonavir and molnupiravir groups respectively (p=0.523).Interpretation: Nirmatrelvir/ritonavir is safe and efficacious when compared to molnupiravir in patients with advanced kidney disease.Funding: Health and Medical Research Fund, Health Bureau, The Government of the Hong Kong Special Administrative Region, China and Mr. Lee Won Keung Donation Fund.Declaration of Interest: The authors report no conflict of interest.Ethical Approval: The study was approved by the Institutional Review Board of the University of Hong Kong and Hospital Authority Hong Kong West Cluster. Informed consent from individual patient was waived as the study involved analysis of anonymized data from hospital registry only. The study was performed in compliance with the Declaration of Helsinki.


Subject(s)
Stroke , Diabetes Mellitus , Kidney Diseases , Myocardial Infarction , COVID-19 , Renal Insufficiency, Chronic , Liver Diseases , Hypertension
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