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OBJECTIVE: To assess the potential therapeutic role of exercise on health-related quality of life, assessed by the Pediatric Outcomes Data Collection Instrument (PODCI), coronary flow reserve (CFR), cardiac function, cardiorespiratory fitness, and inflammatory and cardiac blood markers in multisystemic inflammatory syndrome in children (MIS-C) patients. METHODS: This is a case series study of a 12-wk, home-based exercise intervention in children and adolescents after MIS-C diagnosis. From 16 MIS-C patients followed at our clinic, 6 were included (age: 7-16 years; 3 females). Three of them withdrew before the intervention and served as controls. The primary outcome was health-related quality of life, assessed PODCI. Secondary outcomes were CFR assessed by 13N-ammonia PET-CT imaging, cardiac function by echocardiography, cardiorespiratory fitness, and inflammatory and cardiac blood markers. RESULTS: In general, patients showed poor health-related quality of life, which seemed to be improved with exercise. Additionally, exercised patients showed improvements in coronary flow reserve, cardiac function, and aerobic conditioning. Non-exercised patients exhibited a slower pattern of recovery, particularly in relation to health-related quality of life and aerobic conditioning. CONCLUSIONS: Our results suggest that exercise may play a therapeutic role in the treatment of post-discharge MIS-C patients. As our design does not allow inferring causality, randomized controlled trials are necessary to confirm these preliminary findings.
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BackgroundHuman SARS-CoV-2 infection is responsible for a large variety of clinical manifestations related to Coronavirus disease-19 (COVID-19) [1]. SARS-CoV-2 can induce microvascular damage, that can be safely detected by nailfold videocapillaroscopy (NVC), as recently demonstrated [2-4]. Virus-induced endothelial dysfunction has been implicated in the pathogenesis of both active infection and long-COVID clinical manifestations (the last as persistence of disease symptoms after at least three months from onset) [5]. The study group on capillaroscopy and microcirculation in rheumatic diseases of the Italian Society of Rheumatology (CAPSIR) carried out an internal survey on the interest of the Italian Centers that perform NVC in participating in a detailed capillaroscopic and clinical data collection in long-COVID patients.ObjectivesTo carry out an Italian multicenter cognitive survey on the interest in collecting NVC and clinical data of patients affected by long-COVID with or without previous rheumatological diseases.MethodsThe steering committee of the CAPSIR study group formulated a cognitive questionnaire, entitled "Study on the role of capillaroscopy in patients with long-COVID” (CAPSIR_2 Study), consisting of 27 open or multiple-choice questions. A Google Form of the questionnaire was emailed to all the member of the study group between September and October 2022. Data are reported with a descriptive analysis.ResultsThe online questionnaire was completed by 41 CAPSIR members, belonging to 33 different Italian centers. Of note, 63% of participants had already experienced NVC in patients with long-COVID. The primary indication to perform the NVC was the onset of a new Raynaud's phenomenon (46% of cases) and the requests come mainly from General Practitioners (33% of cases). In 2/3 of the cases, patients with long-COVID and previous rheumatic diseases, who underwent NVC examination, represented less than 20% of the total. It should be noted that always in 2/3 of the cases there was no preferential channel for the study of the microcirculation in patients affected by long-COVID nor a NVC investigation prior to the SARS-CoV-2 infection. According to the previous experience of the participants in the interview, the most important NVC parameters considered to be evaluated in long-COVID patients were number of capillaries per linear millimeter (24% of cases), presence of hemorrhages (34% of cases) and giant capillaries (22% of capillaries). All participants (100%) therefore agreed to participate in a further collection of NVC and clinical data in this cohort of patients.ConclusionThis survey highlighted the interest of Italian Rheumatologists in assessing by NVC the COVID-related microvascular involvement. A consensus has emerged that future research is needed. After this pilot survey, the second part of the CAPSIR_2 Study will concern the collection/analysis before and after the SARS-CoV-2 infection of NVC and clinical data in patients with primary and secondary (to rheumatic diseases) Raynaud's phenomenon and affected by long-COVID versus adequate controls. The aim is to investigate if the presence/severity of the microvascular damage might be involved in the pathogenesis of the clinical manifestations observed in COVID-19 patients after the active infection. CAPSIR_2 Study will be open to all Italian rheumatological centers that participated in the previous national CAPSIR_1 Project [6].References[1]Fernandes Q et al. Ann Med. 2022;54:524-540.[2]Cutolo M et al. Nat Rev Rheumatol. 2021;17:665-677.[3]Sulli A et al. Microvasc Res 2022;142:104361.[4]Natalello G et al. Microvasc Res. 2021;133:104071.[5]Charfeddine S et al. Front Cardiovasc Med. 2021;8:745758.[6]Ingegnoli F et al. Reumatismo. 2022;74.AcknowledgementsAuthors wrote the on behalf of the study group on capillaroscopy and microcirculation in rheumatic diseases of the Italian Society of Rheumatology (SIR) - CAPSIR.CAPSIR Study Group thanks the EULAR Study Group of Microcirculation in Rheumatic Diseases for the continuous cultural support.Dis losure of InterestsNone Declared.
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BackgroundFacing the outburst of the COVID-19 pandemic, we gradually comprehend its pathophysiology as a coagulopathy characterized by increased risks of arterial, venous, and microvascular thrombosis. Antiphospholipid syndrome (APS) is an autoimmune, thrombo-inflammatory disease characterized by thrombosis and/or pregnancy loss in the presence of one or more antiphospholipid antibodies (aPL).ObjectivesTo evaluate the clinical scenario of COVID-19 in the APS population of patients.MethodsThis is a single-center, observational, cross-sectional study. Data regarding the severity of COVID-19 (severe COVID-19 considered if interstitial pneumonia was diagnosed), COVID-19 vaccinal status, and post-vaccinal reactions (divided into mild, consisting of fever, myalgia, nausea, and severe if thrombosis at any point occurred) were collected from 44 APS patients (21 with primary and 23 with APS associated with systemic lupus erythematosus (SLE), 90.1% female). aPL analysis included the detection of aCL (IgG/IgM), ß2GPI (IgG/IgM), and LA Results were compared to the control group consisting of 31 healthy individuals, with no APS, matched to the APS group regarding age and gender.ResultsAt the moment of COVID-19 infection, 75% of the APS group was taking Aspirin, 15.9% warfarin, 2.3% non-vitamin K oral anticoagulant, 59.1% chloroquine, 31.8% corticosteroid, 2.3% methotrexate. None of the above-mentioned medications were taken from a control group. There was no difference regarding the severity of COVID-19 between APS patients and healthy controls: 84.1% of APS had mild and 15.9% severe COVID-19 (p=0.509, p=0.292 respectively). But the difference regarding the need for hospitalization was significant (none of the healthy controls compared to 11.4% APS patients, p=0.0073). Interestingly, COVID-19 occurred in 72.7% of APS patients before the COVID-19 vaccination compared to 35.5% of healthy controls, p=0.001, conversely, a significantly lower percentage of vaccinated APS patients had COVID-19 compared to healthy controls (34.1% to 71.0%, p=0.002). 27% of APS patients had mild post-vaccinal reactions, none with severe.ConclusionDuring the COVID-19 pandemic, APS patients in Serbia were at higher risk for hospitalization. However, there was no difference in the severity of clinical presentation compared to non -the APS population. We can only speculate that APS therapy consisting of Aspirin, Chloroquine, and oral anticoagulant therapy contributed to this finding. Moreover, COVID-19 vaccination in the APS population, followed by a low incidence of mild post-vaccinal reactions, had more benefits in protection than in non-APS individuals.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Introduction: SARS-CoV-2 is responsible for the current global pandemic. SARS-CoV-2 infection underlies the novel viral condition coronavirus disease 2019 (COVID-19). COVID-19 causes significant pulmonary sequelae contributing to serious morbidities. The pathogenesis of COVID-19 is complex with a multitude of factors leading to varying levels of injury numerous extrapulmonary organs. This review of 124 published articles documenting COVID- 19 autopsies included 1,142 patients. Method(s): A PubMed search was conducted for COVID-19 autopsy reports published before March 2021 utilizing the query COVID-19 Autopsy. There was no restriction regarding age, sex, or ethnicity of the patients. Duplicate cases were excluded. Findings were listed by organ system from articles that met selection criteria. Result(s): Pulmonary pathology (72% of articles;866/1142 patients): diffuse alveolar damage (563/866), alveolar edema (251/866), hyaline membrane formation (234/866), type II pneumocyte hyperplasia (165/866), alveolar hemorrhage (164/866), and lymphocytic infiltrate (87/866). Vascular pathology (41% of articles;771/1142 patients): vascular thrombi (439/771)-microvascular predominance (294/439)-and inflammatory cell infiltrates (116/771). Cardiac pathology (41% of articles;502/1142 patients): cardiac inflammation (186/502), fibrosis (131/502), cardiomegaly (100/502), hypertrophy (100/502), and dilation (35/502). Hepatic pathology (33% of articles;407/1142 patients): steatosis (106/402) and congestion (102/402). Renal pathology (30% of articles;427/1142 patients): renal arteries arteriosclerosis (111/427), sepsis-associated acute kidney injury (81/427) and acute tubular necrosis (77/427). Conclusion(s): This review revealed anticipated pulmonary pathology, along with significant extrapulmonary involvement secondary to COVID-19, indicating widespread viral tropism throughout the human body. These diverse effects require additional comprehensive longitudinal studies to characterize short-term and long-term COVID-19 sequelae and inform COVID-19 treatment.
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Cerebral microangiopathy (CMA) is one of the significant causes of depression in the elderly. Close associations of the risk of developing depression with white matter hyperintensity, the presence of lacunar infarcts, and other markers of vascular disease are shown. The available data suggest that various vascular mechanisms, in particular, involvement of small vessels of the brain, generalized microvascular and endothelial dysfunction, metabolic risk factors, - are risk factors for the development of depression. Pathogenetic mechanisms include cerebral hypoperfusion and immune dysregulation. Depression is also a common complication of coronavirus infection, occurring both in the acute and post-COVID periods. The same mechanisms as in vascular depression are involved in the pathogenesis of the development of post-COVID depressive disorders. Given the complexity of the mechanisms of development of depressive disorders in patients with CMA, the presence of severe comorbid vascular pathology, antidepressants with an optimal ratio of efficacy and safety should be preferred. Agomelatine (Valdoxan) is one of such drugs.Copyright © 2023 Ima-Press Publishing House. All rights reserved.
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Globally, hepatitis C (26%), alcohol (24%), and hepatitis B (23%) contribute almost equally to the global burden of cirrhosis. The contribution from nonalcoholic fatty liver disease (8%) is small but increasing. Patients with acutely decompensated cirrhosis have a dismal prognosis and frequently progress to acuteon-chronic liver failure, which is characterised by hepatic and extrahepatic organ failure, Cardiovascular alterations including portal hypertension trigger the formation of portocaval shunts and varices. Systemic under filling and arterial hypotension is compensated by vasoconstriction but might decline into a state of aggravated portal hypertension and cirrhotic cardiomyopathy, leading to a hyperdynamic state, microvascular dysfunction and reduced organ perfusion culminating in decompensation. The immune system is dysfunctional showing a contrary co-existence of immune paralysis and immune overstimulation leading to secondary infections and inflammatory response syndrome aggravating cardiovascular alterations but also initiating tissue injury and metabolic alteration. This transition from compensated to decompensated cirrhosis is characterised by the occurrence of ascites, variceal bleeding and/or hepatic encephalopathy or organ failures (in the case of ACLF. Precipitating events for ACLF vary between Western countries (bacterial infection, alcohol intake) and Eastern countries (flare of HBV, superimposed HAV or HEV). In the majority of patients, systemic inflammation is a major driver of progression from compensated to decompensated cirrhosis. Once the first episode of AD develops, systemic inflammation follows a chronic course, with transient periods of aggravation due to proinflammatory precipitants or bursts of bacterial translocation resulting in repeated episodes of AD. The multistate model describing the clinical outcomes of decompensated cirrhosis has been well validated. State 3 is defined by the occurrence of variceal bleeding alone, state 4 by any single non-bleeding event, state 5 by any 2 or more events and the late decompensate state by any event with organ failures either with or without ACLF. 5-year mortality across states from 3 to 5 is in the order of, respectively: 20%, 30%, 88%. With late decompensation mortality ranges between 60 and 80% at 1 year. Cirrhosis is increasingly common and morbid. Optimal utilisation of therapeutic strategies to prevent and control the complications of cirrhosis are central to improving clinical and patient-reported outcomes. Aetiology-focused therapies that can prevent cirrhosis and its complications. These include anti-viral therapies, psychopharmacological therapy for alcohol-use disorder, management of hepatic encephalopathy (HE), ascites, hepatorenal syndrome, non-pain symptoms of cirrhosis including pruritis, muscle cramps, sexual dysfunction and fatigue, and reduce the risk of hepatocellular carcinoma. New disease-modifying agents are expected to be identified in the next few years by systematic drug repurposing and the development of novel molecules currently undergoing pre-clinical or early clinical testing. COVID-19 continues to pose a significant healthcare challenge throughout the world. Comorbidities including diabetes and hypertension are associated with a significantly higher mortality risk. Cirrhosis is associated with an increased risk of all-cause mortality in COVID-19 infection compared to non-cirrhotic patients. Patients with cirrhosis should be considered for targeted public health interventions to prevent COVID-19 infection, such as shielding and prioritisation of vaccination.
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Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of newonset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARSCOV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link.
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Post-COVID-syndromes have a high impact on incapacity for work: a mean of over 100 days has been reported in Germany [1]. Magnesium deficiency is documented as a riskincreasing factor for fatal outcome of acute covid disease [2, 3]. A first case report of post-COVID treatment with hybrid magnesium parenteral/ oral was presented in February 2021 during the Global Magnesium COVID 19 online conference. As of yet, there is no established explanation for post-COVID or long-COVID syndrome as well as there being no established treatment. In recourse to the hypothesis that magnesiumdepletion might favour microvascular early-aging and so favour neuro- degenerative prozesses [4] now preliminary observations of these parameters in post-covid patients in our primary care office result. This is done in connection with long years documentation of pulsewave-analysis (pwv), magnesium and Mg/Caprofiles in patients who suffered covid- disease. Figure 1 shows an over 6-year series of pulse-wave-analyses in a 59-year-old female patient who suffered from post-COVID syndrome. Her augmentation index (AIX) as an indicator of the actual microvascular condition increased from favorable 8% (2020) to highly pathological 39% in the post-COVID disease period - corresponding with the mean value of an 80-year-old person [5]. Another 67-year-old female post-COVID patient recovered clinically very well and quickly with high-dosed magnesium therapy and showed coincident positive decrease of AIX to 4%. Further case reports in the context of magnesium pretests and AIX are presented. Late controlled studies concerning magnesium supplementation and PWV focus on the other parameter - the (macrovascular determined) pulse-wave-velocity (PWV) and found no association of PWV with several months of magnesium supplementation [6]. Therefore, it must be emphasized that all our observations of the last years where not based on PWV but rather focused on AIX as a volatile but more magnesium-dependent parameter. Furthermore, our patients where mostly supplemented over years and not only 24 weeks. Evident is the overall small number of clinically manifesting post-COVID cases among our COVID patients (n= 10 when writing the ) among actually 470 Corona-context treatment cases. We have two working hypotheses for this. I: Persistently high magnesium levels may contrib- ute to reducing the number of post- COVID cases - and II: In the case of post-COVID syndrome, high-dose possibly hybrid magnesium therapy might favorably influence the course of the disease. The Corona pandemic and its microvascular consequences are possibly and unfortunately a non-intended turbo-experiment for microvascular early aging in a great number of undetected magnesium- depletion patients. Facing the burden of disease for individuals - and society as a whole - this justifies not only controlled studies but also the increased attention of medical doctors to the optimal magnesium status of these patients.
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Purpose of Study Sickle cell disease (SCD) disproportionately affects the Tharu population of Nepal, a marginalized indigenous group concentrated in the Dang district. SCD is a structural hemoglobinopathy resulting in abnormal red blood cells with a tendency to occlude microvasculature. Since 2015, University of British Columbia medical students and a local community partner, Creating Possibilities, have improved access to SCD screening and diagnosis for the Tharu population. However, interviews conducted in 2016- 2017 found that SCD-afflicted community members encounter a number of challenges to obtain treatment once diagnosed. The purpose of this study was to develop a questionnaire on barriers to accessing SCD care in this community. Methods Used The Barriers to Accessing SCD Care Questionnaire was developed from items in existing scales, deductive and inductive item generation, and feedback from expert local partners. Reviewing literature on barriers to accessing healthcare in the Western region of Nepal informed region-specific questionnaire items, while literature on accessing SCD treatment in resource-limited settings informed SCD-specific questionnaire items. We also reviewed the literature on barriers to treatment for various stigmatized chronic health conditions in low-resource settings. Summary of Results Qualitative interviews with SCD-afflicted Tharu individuals in 2016-2017 identified inadequate local medical resources, transportation, financial strain, and limited awareness as barriers to care. Based on the literature review, we organized all survey items under the themes transportation, medical infrastructure, finances, community attitudes, and personal attitudes. The questionnaire includes closed-ended questions using a Likert scale, as well as open-ended interview prompts. It was made in collaboration with local community members to ensure it is culturally appropriate, needs-specific, and easily understandable. The questionnaire received ethics board approval, and interviews will begin once local health authorities lift COVID-19 restrictions. Conclusions Results from the Barriers to Accessing SCD Care questionnaire will guide future community-based interventions.
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It is now widely accepted that SARS-CoV-2 infection can affect long-term health and quality of life. Long COVID, a type of post-acute sequelae of SARS-CoV-2 infection (PASC) characterized by persistent unexplained symptoms, has a major impact on the health of many COVID-19 survivors. Although many individuals (up to 30%) experience some limited symptoms in the weeks and months following COVID-19, the prevalence of severe disabling Long COVID is less common (perhaps <5%). Long COVID syndromes are variable and include general (e.g., fatigue) and organ-system specific symptoms (e.g., shortness of breath, palpitations, neurocognitive symptoms), as well as symptoms resembling other medically unexplained syndromes (e.g., myalgic encephalomyelitis/chronic fatigue syndrome, dysautonomia, post-exertional malaise). For reasons not yet understood, female sex is a strong predictor of Long COVID, as is the presence of certain comorbidities, particularly obesity. Mechanisms that might plausibly contribute to Long COVID include irreversible tissue damage associated with acute infection, persistence of SARS-CoV-2 antigen or possibly a viral reservoir, residual or ongoing immune activation and inflammation, reactivation of other latent human viruses, microvascular dysregulation and thrombotic events, microbial translocation, dysbiosis, and autoimmune phenomena. These mechanisms may act in isolation or in combination to drive Long COVID syndromes. Notably, many if not all of these pathways have been implicated as possible mechanisms for the excess rate of cardiovascular disease and other comorbidities in people living with HIV. Industry engagement in Long COVID research is growing, and NIH funding for clinical trials is emerging through programs such as the RECOVER Initiative. As a result, we are entering an era of experimental medicine, in which potential interventions will be used as tools to probe the biology of the disease. This presentation will provide an overview of the proposed biological mechanisms contributing to Long COVID, with a focus on the current state of evidence, human and animal models, and the emerging therapeutic agenda.
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The immunological reaction that facilitates the cytokine storm in the infection by the new coronavirus facilitates the appearance of microvascular, endothelial and direct cellular damage, which leads to a prothrombotic state and events of thromboembolism to different apparatus and systems as a complication. Therefore, the need to provide adequate prophylactic therapy or anticoagulant management in time and adequate dosage to these patients, as well as an individualized coagulation and hemostasis study. This document is intended to summarize in a practical way the evidence published to date and provide a broader view of the pathophysiological phenomena that occur in this hyperinflammatory state that has taught us a lot since its arrival.Copyright © 2022 Comunicaciones Cientificas Mexicanas S.A. de C.V.. All rights reserved.
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The proceedings contain 23 papers. The topics discussed include: Mg and skeletal system: a link to osteoporosis and osteoarthritis;a putative impact of IL-6 on the expression of magnesiotropic genes through the activation of the JAK/STAT3 pathway;magnesium in pain therapy - historical notes and current aspects;Alzheimer's-associated variant rs708727 might be connected to dementia in Parkinson's disease;effect of magnesium citrate supplementation on the brain tissue of patients with Miyoshi dysferlinopathy measured by 31P magnetic resonance spectroscopy;clinical status of magnesium implants;Ionized magnesium: update 2022;magnesium in the treatment of selected types of muscular dystrophy;magnesium speciation analysis in blood serum;epigenetically-induced modulation of the HPA axis might improve resilience to chronic stress;magnesium status in patients with fibromyalgia syndrome;and post-covid-syndrome and transient microvascular pathology in pulse-wave-analysis - association with Mg/Ca ratio and magnesium therapy-options.
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Background: Multisystem inflammatory syndrome in children (MIS-C)/pediatric inflammatory multisystem syndrome(PIMS) is a rare but severe hyper inflammation following exposure to SARS-CoV-2. The exact pathogenesis is unknown, butSARS-CoV-2 is linked to vascular-endothelial pathology. We therefore longitudinally analyzed endothelial function and microcirculation in children with MIS-C/PIMS. Method(s): Overall 17 pediatric patients with MIS-C/PIMS (mean age: 9.4 +/- 4.5 years;30% female) were included in our study. They were examined during the acute phase and in follow-up visits after 3 and 6 months. We assessed the reactive hyperemia index (RHI) as a surrogate for the endothelial function using the Endo PAT device. The microcirculation was visualized using sublingual sidestream dark field (SDF) imaging, which permits analyzing the microvascular flow index (MFI)(0 = no flow, 1 = intermittent, 2 = sluggish, 3 = continuous). Result(s): During the acute phase of MIS-C/PIMS both, macrovascular and microvascular markers were distinctively restricted. Mean RHI was 1.11 +/- 0.25 indicating limited endothelial function in comparison to a group of healthy controls(mean RHI = 1.36 +/- 0.22;n = 14;mean age: 12.8 +/- 2.2 years;50% female). After 3 months, mean RHI improved to 1.42+/-0.45 and even increased to 1.75 +/- 0.66 after 6 months. SDF imaging revealed an impaired microcirculatory flow during the acute phase (mean MFI: 2.45 +/- 0.28), which surprisingly did not improve after three months (mean MFI: 2.45 +/- 0.33).Six months after the acute phase, the microvascular flow ameliorated toward a more continuous flow (mean MFI: 2.66 +/- 0.29). Conclusion(s): Our preliminary results indicate an impaired microcirculation and endothelial function in children with MIS-C/PIMS. The process of full vascular recovery seems to take several months. More research in this field is necessary to better understand the patho physiology and the time course of this rare new SARS-CoV-2-related syndrome.
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Introduction: Covid-19 infection, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a leading cause of morbidity and mortality worldwide. Myocarditis or pericarditis is a common clinical manifestation reported during the acute illness of Covid-19 infection. However, it is rarely reported during the recovery period or as part of post-Covid 19 conditions. We are reporting a case of a pregnant lady presented with post-covid 19 myocarditis with RVOT VT. Case presentation: A 44-year-old lady, Gravida 7 Para 6, presented to us at 32 weeks POA with the complaint of palpitation of 1 week, which was more frequent and persistent on the day of admission, associated with a presyncopal attack. Otherwise denied chest pain, fever or joint pain, or swelling. She had a history of Covid 19 infection 1 month prior to the onset of palpitation and had received 2 doses of SINOVAC vaccination. Upon presentation in the emergency department, she was tachycardic;however, her BP was normotensive and afebrile. Blood Investigations were unremarkable. ECG showed short run VT which self-reverted to sinus rhythm. Upon admission to CCU, she had multiple episodes of stable VT, which self-reverted to sinus rhythm. Echo showed EF 60% with no regional wall motion abnormality or valvular lesion. Cardiac MRI reported LV function of 46% with suspicion of fibrosis at the mid-septal wall. While in the ward, she had polyarthralgia, which improved with hydrocortisone. Blood investigation showed elevated inflammatory markers;otherwise, blood culture and ASOT were negative. Further investigations sent for connective tissue disease showed a positive result for ANA and ENA;however, it does not fulfill the SLICC criteria. Hence, we diagnosed her post covid 19 related myocarditis. She is currently generally asymptomatic with low-dose prednisolone and has been closely monitored for manifestation that may represent SLE. Discussion(s): The incidence of myocarditis in Covid-19 infection is 0.12%, which is 2-3 folder higher than non- covid 19 infection pneumonia;however, the prevalence in post covid infection is still unknown. It has been demonstrated that infectious causes are a significant initiating event in the pathophysiology of autoimmune disorders. A number of processes, including angiotensin-converting enzyme maladaptation, hypercoagulability, microvascular damage, and direct viral toxicity, may cause the etiology of post Covid-19 infection. Conclusion(s): Myocarditis in post Covid-19 condition is an uncommon but still possible condition that needs to be considered. It can be CTD mimickers;however, the symptoms must be closely monitored.Copyright © 2023
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Introduction: There have been some reports on flare-ups of kidney diseases following COVID-19 vaccines such as IgA nephropathy and minimal change disease. However, there have been few reports on those of IgA vasculitis following the vaccines yet. We report a case of IgA vasculitis with a flare-up of gross hematuria and lower-limb purpura following Moderna COVID-19 vaccines. Method(s): The patient is a 16-year-old female with no previous history of abnormal results of urinalyses before April in 2021. She had developed microscopic hematuria, proteinuria and purpura on both of her lower limbs that emerged and then disappeared repeatedly since then. She received Moderna COVID-19 vaccines in August and September in 2021, both of which were followed by gross hematuria lasting for around 10 days. The lower-limb purpura reemerged at the same time as the hematuria. Microscopic hematuria of around 30-49 RBC/HPF, glomerular hematuria of moderate degree and urine protein-to-creatinine ratio (UPCR) of around 0.8 g/gCr had continuously been detected. Skin and kidney biopsies were performed in December in 2021 and in February in 2022 respectively. Result(s): The skin tissue showed formation of leukocytoclastic vasculitis, and the kidney tissue showed that of cellular and fibrocellular crescents and endocapillary hypercellularity. Immunofluorescence staining of both tissues showed deposition of galactose-deficient IgA1(Gd-IgA1) and C3, and she was diagnosed as IgA vasculitis. She received steroid pulse therapy followed by tonsillectomy. The lower-limb purpura has disappeared after she received three courses of the steroid pulse therapy, but microscopic hematuria and UPCR of around 0.8 g/gCr have still continued. Conclusion(s): IgA vasculitis is leukocytoclastic vasculitis characterized by deposition of Gd-IgA1 on microvessel walls in skin and on glomerular capillaries in kidneys. The detailed mechanism of IgA vasculitis has not been fully elucidated yet. Gross hematuria following an upper respiratory infection is considered as a characteristic clinical symptom of IgA vasculitis as well as IgA nephropathy. Post-vaccination gross hematuria of patients with IgA nephropathy has been reported, and it is believed that innate immunity is related to its mechanism. Moderna COVID-19 vaccines, which the patient received, are mRNA vaccines. We estimate that exposure to the mRNA vaccine triggered excess glomerular deposition of Gd-IgA1-containing immune complexes and subsequent gross hematuria by overactivation of innate immunity such as Toll-like receptors that detect RNA. This case suggests that such immune activation by a mRNA vaccine might be related not only to the mechanism of IgA nephropathy but also to that of IgA vasculitis. No conflict of interestCopyright © 2023
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Introduction: In the natural conditions first and major target for respiratory viruses (RVs) are epithelial cells. Nonetheless, recently we have demonstrated that RVs are able to infect not only epithelium, but also Human Microvascular Lung Endothelial Cells (HMVEC-L) which increased network is observed during severe asthma due to increased angiogenesis. Furthermore, on the surface of HMVEC-L we observed intense expression of aminopeptidase N (AP-N)- an entry receptor for Human Coronavirus 229E (HCoV-229E). Due to the facts, that possibility of being infected by HCoV-229E should be considered and there is no research based on this model the aim of this study was to assess the vulnerability of HMVEC-L to HCoV-229E infection. Method(s): HMVEC-L was incubated with HCoV-229E (MOI 0,1;1,0;3,0) for 3 hours, 3x PBS washed and cultured for 120 hours. In relevant time points (5;24;48;72;96 and 120h) viral copy number and mRNA expression of inflammatory, anti-viral and receptor factors were evaluated in Real-Time PCR. Confocal microscopy (CM) and flow cytometry (FACS) were used to measure AP-N surface expression. Result(s): FACS and CM confirmed intense surface expression of AP-N on HMVEC-L. HCoV-229E efficiently infected HMVEC-L (604 945,5 +/-194 930,2 viral copies/mul) in 48h cultures (MOI 0,1) and induced relatively late (between 72- 96h) mRNA expression of RANTES (1181,12);IL-6 (89,6);IFN-beta (53,7);OAS-1 (64,3);PKR (11,4) and TLR-3 (42,4). Increased mRNA expression was also accompanied by protein release to the supernatants. Conclusion(s): HCoV-229E may efficiently infect HMVEC-L and induce delayed inflammatory and anti-viral response.
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Recent studies showed that post-COVID-19 patients with reduced pulmonary oxygen uptake (VO2p) kinetics, exhibited a lower peripheral oxygen extraction [lower C(a-v) O2 /Ca O2 ] rather than a central cardiac limitation (supernormal predicted exercisepeak cardiac output), opening further questions of what is impacting VO dynamics. We proposed to investigate the dynamic matching of VO2p , increase of heart rate (HR) and muscle deoxygenation (deoxy[Hb + Mb]) at the onset of heavy-exercise in post-COVID-19 patients. We expected to find a slowness of VO unrelated to circulatory impairment. 12 patients (90 days after onset of symptoms) were compared to 10 healthy controls. The VO rate of change, deoxy[Hb + Mb] in vastus lateralis (by near infrared spectroscopy) and HR were analyzed during a constant work-rate exercise test up to limit of tolerance (~70%peak work-rate). Post-COVID-19 patients had significantly slower VO2p kinetics than controls (Tau-VO2p 52+/-9 vs 40+/-11 seconds(s);p=0,001 and MRT-VO 70+/-12 vs 51+/-10 s;p<0,001). In contrast, t1/2 -HR was faster in patients (65+/-28 vs 85+/-20 s, p=0,04). Not only deoxy[Hb + Mb] dynamics were not accelerated compared to controls, suggesting normal muscle microvascular O2 delivery, but significantly slower (MRT-deoxy[Hb + Mb] 25+/-7 vs 20+/-2 s;p=0,02)(Figure 1). In conclusion, a sluggish on-exercise VO2p in these patients seems unrelated to central and peripheral circulatory adjustments. .
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Background Prior Coronavirus Disease 2019 (COVID-19) infection has been associated with endothelial injury and coronary microvascular dysfunction (CMD). We aimed to assess if there was an association between SARS-CoV-2 variants and the magnitude of CMD. Methods A prospective cohort of consecutive patients undergoing clinically indicated positron emission tomography (PET) myocardial perfusion imaging were included. Cases that had a polymerase chain reaction (PCR)-confirmed prior COVID-19 infection matched 1:3 on clinical and cardiovascular risk factors to controls with no prior COVID-19. Variants were estimated by the temporal prevalence at time of diagnosis based national reporting. Myocardial flow reserve (MFR) was determined by PET and CMD was defined as MFR<2. Results A total of 282 cases were matched to 869 controls;mean (+/-SD) age 65 (+/-12), 48% female. Most patients with prior COVID-19 infection were diagnosed when the Alpha/Beta variants were dominant (60.6% Alpha/Beta, 19.9% Omicron, 19.5% Delta). The highest rate of CMD was seen with patients diagnosed during the Delta dominance (56.4% Delta, 50% Omicron, 48.5% Alpha/Beta vs 27.7% controls, P for trend<0.001). Conclusion Our analysis shows the magnitude of COVID-19-associated CMD may differ based on the SARS-CoV-2 variant. [Formula presented]Copyright © 2023 American College of Cardiology Foundation
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Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.
Subject(s)
COVID-19 , Vitronectin , Humans , Blood Platelets/physiology , Platelet Glycoprotein GPIIb-IIIa Complex , MicrovesselsABSTRACT
BACKGROUND: Cardiac injury and inflammation are common findings in COVID-19 patients. Autopsy studies have revealed cardiac microvascular endothelial damage and thrombosis in COVID-19 patients, indicative of microvascular dysfunction in which reactive oxygen species (ROS) may play a role. We explored whether the ROS producing proteins NOX2, NOX4 and NOX5 are involved in COVID-19-induced cardio-microvascular endothelial dysfunction. METHODS: Heart tissue were taken from the left (LV) and right (RV) ventricle of COVID-19 patients (n = 15) and the LV of controls (n = 14) at autopsy. The NOX2-, NOX4-, NOX5- and Nitrotyrosine (NT)-positive intramyocardial blood vessels fractions were quantitatively analyzed using immunohistochemistry. RESULTS: The LV NOX2+, NOX5+ and NT+ blood vessels fractions in COVID-19 patients were significantly higher than in controls. The fraction of NOX4+ blood vessels in COVID-19 patients was comparable with controls. In COVID-19 patients, the fractions of NOX2+, NOX5+ and NT+ vessels did not differ significantly between the LV and RV, and correlated positively between LV and RV in case of NOX5 (r = 0.710; p = 0.006). A negative correlation between NOX5 and NOX2 (r = -0.591; p = 0.029) and between NOX5 and disease time (r = -0.576; p = 0.034) was noted in the LV of COVID-19 patients. CONCLUSION: We show the induction of NOX2 and NOX5 in the cardiac microvascular endothelium in COVID-19 patients, which may contribute to the previously observed cardio-microvascular dysfunction in COVID-19 patients. The exact roles of these NOXes in pathogenesis of COVID-19 however remain to be elucidated.