COVID-19 in Ultramarathon Runners: Findings of The Ultrarunner Longitudinal TRAcking Study

Purpose: Ultramarathon runners are a unique patient population who have been shown to be free of nearly all severe chronic medical conditions. The effect that COVID-19 infection has on this population and their running behavior is unknown. Method(s): The Ultrarunner Longitudinal TRACking Study (ULTRA Study) is the largest known longitudinal study of ultramarathon runners. Questions on general health status, running behavior, performance, and COVID-19 infection were included. Result(s): Six hundred sixty-two ultramarathon runners participated in the study. This group exercised an average of 10.0 hours per week, including running an average of 26.8 miles per week;52.1% of ultramarathon runners reported ever being symptomatic from a COVID-19 infection with 6.3% testing positive multiple times. Severe infection occurred in 0.3% (2 patients) requiring a total of 3 days of hospitalization. Of those who were infected, 84% were fully vaccinated at the time of their infection;67% of infections effected running for a mean of 33.1 days. The most common other symptoms included fever (73.3%), fatigue (68.7%), sore throat (67.5%), runny nose (67.0%), and cough (66.7%). Cardiovascular symptoms, which are of particular interest in the running population, included shortness of breath (46.4%), increased heart rate (45.2%), chest pain (34.2%), and wheezing (32.5%). Of 662, 48 (7.3%) of ultrarunners reported Long COVID (symptoms lasting more than 12 weeks). Conclusion(s): Severe COVID-19 infection is rare in ultramarathon runners, although symptomatic infection that affects running is common. These rates, along with Long COVID, are lower than is reported in the literature for the population on average. Significance: Ultrarunners are at very low risk of COVID- 19 symptoms requiring hospital care but significant risk of infection that effects running. Cardiovascular symptoms are common, and the long-term significance of these symptoms in runners is unknown.

Complex breathlessness in postural tachycardia syndrome and autonomic dysfunction

Breathlessness can occur in a number of autonomic conditions, often in the form of dysfunctional breathing. The exact mechanism remains uncertain, but reduced perfusion of blood pressure receptors and chemoreceptors in the carotid sinus and carotid body, leading to hyperventilation, is postulated. This is recognised to occur in vasovagal syncope and in cases of significant autonomic dysfunction. It also occurs in PoTS, a condition predominantly affecting young women and often precipitated by another illness and increasingly by coronavirus disease 2019. It is characterised by cardiovascular and respiratory symptoms when upright, is relieved by recumbency and is associated with a significant heart rate increase. Other autonomic symptoms of organ dysfunction can occur, in the gastrointestinal and genitourinary system for example. There are guidelines and therapies that can produce significant symptomatic improvements, but maintaining a high level of suspicion for the diagnosis is important, as it can easily be overlooked.Copyright © ERS 2021.

Anxiety and depression among ambulatory and hospitalized patients with cardiovascular long-COVID-19 presentation referred to cardiology consultation after COVID-19 infection

Introduction: COVID-19 is connected with varying degrees of emotional stress. Patients (pts) who are hospitalized with severe COVID-19 (C19) are located in single rooms without a permanent attendant to prevent contamination. All personnel serving these pts come into contact with patients with personal full-body protective garment. Ambulatory C19 pts, usually with less severe presentation, are treated in more comfortable conditions. Purpose(s): To evaluate the impact of the psychosocial changing conditions on individuals' psyche and to analyse the differences in terms of experienced anxiety and depression among the ambulatory and hospital patients referred to post-C19 cardiology consultation. Method(s): The study involved 388 pts with persistent cardiovascular symptoms, including 198 ambulatory patients (130 females and 68 males) and 190 hospital patients (128 females and 62 males) referred to the cardiology consultation (mean age 4.9+/-12.9 and 50.5+/-14.4 years, respectively). The data were collected using the specially designed questionnaire related to descriptive characteristics of the patients and to standardized questionnaires: The State-Trait Anxiety Inventory (STAI) and Beck's Depression Inventory (BDI). Result(s): Abnormal psychological metrics was common in the study pts. Indicators of anxiety were lower in the ambulatory than in hospitalized pts (p<0.001). Depression level was also lower in the ambulatory pts (p<0.001). The same differences were statistically significant in both female and male pts subsets. However, anxiety and depression were more pronounced among female than male pts. Very strong positive correlation was observed between anxiety - state and depression among ambulatory patients, both females and males (p<0.05). Conclusion(s): C19 convalescents with persistent symptoms of presumed cardiovascular origin present with abnormal psychological traits including increased anxiety and depression especially in individuals requiring hospital treatment. For this reason, it is necessary to plan the interventions particularly in hospitalized pts to reduce their anxiety and depression levels and to create psychological support programs.

Clinical observation on safety of chloroquine phosphate treatment in patients with novel coronavirus pneumonia.

Objective: To explore the safety of chloroquine phosphate treatment in patients with novel coronavirus pneumonia (COVID-19) and provide references for clinical safety medication. Method(s): Active monitoring for adverse events (AE) was carried out in the Third People's Hospital of Shenzhen from February to March 2020 during the treatment with chloroquine phosphate in patients with COVID-19. The causal relationship between AE and chloroquine phosphate was evaluated. Result(s): A total of 33 patients were entered in the study, including 16 males and 17 females, aged (43+/-13) years. The clinical types of COVID-19 in 26 patients (78.8%) were mild, in 7 patients (21.2%) were common. There were 7 patients (21.2%) with basic diseases, including 6 with hypertension and 1 with hypothyroidism. The treatment course of chloroquine phosphate was (8+/-3) days. During the treatment, a total of 28 cases of AE in 24 (72.7%) of the 33 patients which were probably or possibly related to chloroquine phosphate were detected. The clinical manifestations of AE included abnormal liver function (8/33, 24.2%), gastrointestinal reactions (8/33, 24.2%), neuropsychiatric system reactions (8/33, 24.2%), cardiovascular system reactions (5/33, 15.2%), eye and vision abnormality (2/33, 6.1%), and skin injury (1/33, 3.0%). The severity of AE was grade 1 or grade 2. After drug withdrawal or symptomatic treatments, all the patients' symptoms were improved and the laboratory tests results returned to normal. Conclusion(s): The adverse effects of chloroquine phosphate in the treatment of patients with COVID-19 are mild, but it is still necessary to strengthen the monitoring.Copyright © 2020 by the Chinese Medical Association.

The arrhythmic events and short-term cardiovascular outcomes in patients hospitalized with COVID-19 infection in Taiwan

Objective: The aim of this study is to investigate the arrhythmic events and short-term cardiovascular (CV) outcomes in patients hospitalized with COVID-19 infection in a single Taiwan tertiary center. Method(s): A retrospective study was carried out on 186 confirmed COVID-19 infection patients admitted to our hospital between May, 2021 and September, 2021. We investigate their CV symptoms, vital signs, laboratory examinations, arrhythmic events, and major adverse cardiovascular events (MACE), including ischemic stroke or systemic embolism, myocardial infarction, CV death, and heart failure (HF) during hospitalization. Result(s): During the hospitalization, 29.6% of patients had an elevation of cardiac enzymes, 67.2% had an elevation of d-dimer level, and 7.5% had abnormal NT-pro BNP level. The most common recorded arrhythmia is sinus tachycardia (22%), followed by atrial arrhythmia (12.4%, including atrial fibrillation 7.0%), sinus bradycardia (3.2%), ventricular arrhythmia (1.6%), and paroxysmal supraventricular tachycardia (1.1%). A total of 68 patients (36.6%) had arrhythmic events during hospitalization. During the mean follow-up of 2.8 months, 17 patients (9.1%) developed MACE, including 6 ischemic strokes, one pulmonary embolism, one peripheral artery occlusive disease, 3 HF, and 7 CV death. The total mortality rate is 19.9%. The hospitalized patients with arrhythmic events were associated with a higher incidence of intubation (32% vs 15%, p = 0.0062), MACE (22% vs 2%, p < 0.001), and mortality (37% vs 10%, p < 0.001) than those without arrhythmic events. Conclusion(s): The patients hospitalized with COVID-19 infection were associated with higher CV manifestations and arrhythmic events in Taiwan. Those patients with arrhythmic events were associated with higher morbidity and mortality.

Covid-19 vaccination status and adverse events following sars-cov- 2 vaccine in autoimmune inflammatory rheumatic disease (AIRD) patients: A single center experience

Background: Autoimmune inflammatory rheumatic diseases (AIRD) were associated with an increased risk for COVID-19 infection, worse clinical outcomes, and COVID-19- related deaths. Vaccines carry the potential benefit of reducing disease transmission and disease severity. Issues on vaccine safety, trigger of an autoimmune reaction or disease flares has been a long issue. Thus this study describes the COVID-19 vaccination status and adverse events following SARS-COV 2 vaccine in a tertiary hospital in Manila, Philippines. Method(s): This retrospective cross-sectional study included patients diagnosed with AIRD and seen in the clinics over 12 months (March 2021-March 2022).We collected data from patients' clinic records and analyzed the clinicodemographic profile, vaccination status, adverse events and development of new onset autoimmune reaction and disease flares post vaccination and those who developed COVID-19 infection even after vaccination. Result(s): There were 204 respondents included in this study: 174 (85%) were female and 30 (14%) were male;63.2 % with SLE, 10.8% rheumatoid arthritis, 8.3% psoriatic arthritis, 6.4% ankylosing spondylitis and other systemic autoimmune disease. Others included were scleroderma and inflammatory arthritis and myopathies. The median age is 38.4 years. 100% of the respondents were fully vaccinated;87 (42.6%) received inactivated vaccine, 63 (30.8%) viral vector vaccine and 54 (26.4%) mRNA vaccine. 133 (65.2%) reported no adverse events while 71 (34.8%) experienced constitutional symptoms, musculoskeletal, cutaneous, respiratory, gastrointestinal and cardiovascular symptoms after vaccination. There were 9 (4.4%) of the respondents who developed new onset autoimmune reaction and disease flares 7-28 days post vaccination;1 patient had new onset amyopathic dermatomyositis;3 SLE patients developed severe hematologic, cutaneous and renal flare;2 rheumatoid arthritis, 1 spondyloarthritis, and 1 inflammatory arthritis patients in long remission had disease flares and 1 patient with henoch schonlein purpura developed flare. Twenty two (10.8%)of the respondents developed COVID-19 infection after 30-120 days post vaccination;19 (86.4%) had mild symptoms, 2 (9.1%) moderate infection and 1 (4.5%) had severe infection and all of the patients recovered. Conclusion(s): This study showed that patients with AIRD experienced varied organ system adverse events following vaccination ranging from mild side effects, disease flares and new onset autoimmune reactions. The development of an autoimmune reaction following SARS-COV 2 vaccination is of scientific and public importance and still needs to be investigated. Even after a complete vaccination, some patients still had COVID-19 infection, however preventing them from worse complications, hospitalization and mortality.

Effect of the Covid-19 Pandemic on Neuroinflammatory Diseases

In December of 2019, SARS-CoV-2 surfaced and the global COVID-19 pandemic began. The pandemic has had far-reaching effects, socially, economically, and especially for healthcare, presenting challenges to patients with neuroinflammatory disorders. Apart from the well-known respiratory, pulmonary, and cardiovascular symptoms that COVID-19 is responsible for, studies continue to show its role in generating neuroinflammation and the different neurological effects that can arise. This review summarizes the relationship between the COVID-19 pandemic and neuroinflammatory diseases, with an emphasis on the effects on patients with neuroinflammatory disorders. Copyright © 2022, Biolife s.a.s.. All rights reserved.

Effect of the Covid-19 Pandemic on Neuroinflammatory Diseases

In December of 2019, SARS-CoV-2 surfaced and the global COVID-19 pandemic began. The pandemic has had far-reaching effects, socially, economically, and especially for healthcare, presenting challenges to patients with neuroinflammatory disorders. Apart from the well-known respiratory, pulmonary, and cardiovascular symptoms that COVID-19 is responsible for, studies continue to show its role in generating neuroinflammation and the different neurological effects that can arise. This review summarizes the relationship between the COVID-19 pandemic and neuroinflammatory diseases, with an emphasis on the effects on patients with neuroinflammatory disorders. Copyright © 2022, Biolife s.a.s.. All rights reserved.

COVID-19 and Cardiac Complication: what is new?

Coronavirus disease 2019 (COVID-19) has been reported to cause cardiovascular complications such as myocardial injury, thromboembolic events, arrhythmia, and heart failure. Multiple mechanisms-some overlapping, notably the role of inflammation and IL-6-potentially underlie these complications. The reported cardiac injury may be a result of direct viral invasion of cardiomyocytes with consequent unopposed effects of angiotensin II, increased metabolic demand, immune activation, or microvascular dysfunction. Thromboembolic events have been widely reported in both the venous and arterial systems that have attracted intense interest in the underlying mechanisms. These could potentially be due to endothelial dysfunction secondary to direct viral invasion or inflammation. Additionally, thromboembolic events may also be a consequence of an attempt by the immune system to contain the infection through immunothrombosis and neutrophil extracellular traps. Cardiac arrhythmias have also been reported with a wide range of implicated contributory factors, ranging from direct viral myocardial injury, as well as other factors, including at-risk individuals with underlying inherited arrhythmia syndromes. Heart failure may also occur as a progression from cardiac injury, precipitation secondary to the initiation or withdrawal of certain drugs, or the accumulation of des-Arg9-bradykinin (DABK) with excessive induction of pro-inflammatory G protein coupled receptor B1 (BK1). The presenting cardiovascular symptoms include chest pain, dyspnoea, and palpitations. There is currently intense interest in vaccine-induced thrombosis and in the treatment of Long COVID since many patients who have survived COVID-19 describe persisting health problems. This review will summarise the proposed physiological mechanisms of COVID-19-associated cardiovascular complications. Copyright © 2022, Anka Publishers. All rights reserved.

Updated Review about Liver Cirrhosis in the COVID-19 Era

Background: The clinical manifestations in patients with COVID-19 may be nonspecific, but most have fever, cough, followed by dyspnea, fatigue, or sputum production. approximately 14% to 53% of patients experience various degrees of liver damage, although most of these injuries are mild and transient, with a satisfactory prognosis in patients without prior liver disease. In contrast, COVID-19 in patients with pre-existing liver disease has been reported to result in higher hospitalization and mortality rates. Among these pre-existing liver diseases, cirrhosis is a chronic liver disease that involves the collapse of the structure of the liver and distortion of the vascular architecture. Cirrhosis is associated with inherent immune dysfunction and an altered gut-liver axis;patients with cirrhosis are particularly at elevated risk of infections and the associated complications. It remains uncertain whether immunocompromised patients with COVID-19 have a higher risk of adverse outcomes. Patients with cancer or solid organ transplant recipients may have an elevated risk of more severe COVID-19;whereas patients taking biologic therapies may not have a greater risk of developing severe COVID-19. No additional risk of death was observed in cancer patients receiving active treatment except in those undergoing chemotherapy. Whether patients with human immunodeficiency virus infection are at higher risk of mortality due to COVID-19 is unclear.Limited evidence has shown that the clinical manifestations in cirrhotic patients with COVID-19 are similar to those in the general population with COVID-19, with fever and cough remaining the most common symptoms, followed by shortness of breath and sputum production. Interestingly, whereas similar proportions of cirrhotic and noncirrhotic patients developed respiratory and cardiovascular symptoms, cirrhotic patients were less likely to develop gastrointestinal symptoms (e.g., diarrhea, nausea, vomiting). Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Single-centre study: MIS-C impact on blood pressure, coronary arteries and left ventricular function

Background and Aim: MIS-C is a hyperinflammatory syndrome caused by Sars-CoV-2 virus. Cardiovascular system impairment is observed up to 100 % of all MIS-C patients with a wide spectrum and severity of symptoms. It is important to identify the course of the disease and its outcome, which could significantly improve public health. Method(s): A single-centre study, prospective cohort study, con-ducted in the Children's Clinical University hospital in Latvia from January to December 2021. Patients between the ages of one to seventeen years who met the MIS-C criteria were included in the study. We evaluated blood pressure, left ventricular heart func-tion, size of coronary arteries and hospital course. Result(s): Thirty-one patients were included who met the MIS-C criteria. The median age was 8.0 years, 52% were boys. Of all patients 77% initially presented with hypotension of whom 42% required inotropic support. Treatment in PICU was required in 58% of all patients. Reduced left ventricular ejection fraction was observed in 35% of all patients. Mildly decreased ventricular ejection fraction (lt;55%) was observed in 19% of cases but mod-erate dysfunction (ejection fraction lt;45%) was observed in 16% of patients. Twelve percent of patients received milrinone to improve left heart function. Left heart function significantly improved in all patients during the hospitalisation. In 6 % of all patients coronary artery dilations was observed. All patients had dilations resolution at the time of discharge. Median length of hospitalisation was twelve days and median length of PICU stay was three days. Conclusion(s): All patients cardiovascular symptoms had resolved at the time of discharge. Whether patients will have chronic cardiac impairment is unknown therefore it is crucial to perform long-term follow-up.

Evolution of echocardiographic and cardiac MRI abnormalities during follow-up in patients with previous MIS-C diagnosis

Background and Aim: Growing evidence has documented a severe systemic hyperinflammation syndrome affecting children previ-ously exposed to SARS-CoV-2, known as Multisystem Inflammatory Syndrome in Children (MIS-C). Cardiovascular manifestations in MIS-C are frequent (34%-82%). The aim of our study was to describe the early and late cardiac abnormalities in patients with MIS-C, assessed by standard echocardiography, speckle tracking echocardiography (STE), and cardiac MRI (CMR). Method(s): 32 consecutive patients (21M, 11F), mean age 8.25 +/- 4years (range 1.3-17.7), with confirmed MIS-C diagnosis were enrolled in this study. Clinical, laboratory and microbiological data were collected. At disease onset, all children underwent standard transthoracic echocardiography, STE with analysis of left ventricle global longitudinal strain (GLS) and 23 (75%) of them performed CMR. Patients underwent complete cardiological evaluation, including echocardiography and STE at two months (T1) and six months (T2) after diagnosis. CMR was repeated at six months after diagnosis. Result(s): Cardiovascular symptoms were present in 45.8% of cases. Thirteen children (40.6%) shared Kawasaki Disease-like symp-toms, and 5 (15.6%) needed ICU admission. Early survival was 100%. All patients showed an hyperinflammatory state. Tn-I was elevated in 20 (62.5%) and BNP in 28 (87.5%) patients. Mean LVEF at baseline was 58.8 +/- 10% with 10 patients (31%) below 55%. STE showed reduced mean LV GLS (-17.4 +/- 4%). On CMR, LGE with nonischemic pattern was evident in 8/23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 +/- 7.5 vs. 58.8 +/- 10.6%, p value 0.044) with only three patients (10%) below <= 55% at T1 and one (4%) at T2. LV GLS remained impaired at T1 (-17.2 +/- 2.7 vs.-17.4 +/- 4, p value 0.71), and significantly improved at T2 (-19 +/- 2.6% vs.-17.4 +/- 4%, p value 0.009). LV GLS was impaired (gt;-18%) in 53% of patients at baseline and T1, while only 13% showed persistent LV GLS reduc-tion at T2. Follow-up CMR showed LGE persistence in 33.4% of cases. Conclusion(s): Even though, early cardiac involvement significantly improves during follow-up, subclinical myocardial damage seems to be still detectable 6 months follow up in one third of MIS-C patients.

THAT BLOODY CLOT DOES NOT ALWAYS NEED A TUNNEL TO MIGRATE: A CASE OF MULTIPLE ARTERIAL AND VENOUS THROMBOSIS IN A COVID-19 PATIENT

SESSION TITLE: Rare Cases of Nervous System and Thrombotic Complication Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Covid 19 virus has impacted nearly 450 million people across the globe;ranging from an asymptomatic carrier state to respiratory symptoms, cardiovascular symptoms, hematologic manifestations and multiorgan failure to death. Thrombotic events are one of its devastating complications. CASE PRESENTATION: A 66 year old man with a history of diabetes mellitus, hypertension and 30 pack years smoking history presented to the emergency room with hypoxia and altered mental status. On exam, his GCS was 8/15 and oxygen saturation was 85% on room air. He was subsequently intubated. CTA chest demonstrated bilateral diffuse ground glass opacities and left pulmonary embolism (PE). CT abdomen and pelvis showed multifocal infarcts in the right kidney with findings suggestive of renal artery thrombosis. Initial platelet count was 80,000/ul with creatinine of 3.9 mg/dl and creatine kinase (CK) of 3977 u/l. His INR was 1.4. Patient was not a candidate for thrombolysis given his thrombocytopenia. He was started on intravenous (IV) heparin and given IV hydration. On day 3 of his admission, he developed dry gangrene of the toes. Ankle brachial index of the right lower extremity (LE) was 1.16 and left LE was 0. Duplex ultrasonography of left LE showed mid to distal popliteal artery thrombus occluding below knee popliteal and tibial arteries. Echocardiogram showed ejection fraction of 55% and bubble study was negative for any intra atrial or pulmonary shunting. On day 4 of his admission, he developed oliguria and his gangrene got worse. His platelet counts decreased to 36,000/ul. Other pertinent labs showed INR 1.2, PT 15.3, PTT 34, D dimer 14.82, fibrinogen 498, CK 6434 mg/dl, hemoglobin 13.2 g/dl, haptoglobin 243 mg/dl and LDH 1041 U/l. Given his poor prognosis in the setting of ventilator dependent respiratory failure, multiple thrombosis and kidney failure requiring hemodialysis, the family decided to withdraw care. DISCUSSION: There are multiple hypotheses of thrombus formation in Covid 19 infection such as interleukin 6 and other cytokines induced endothelial injury, angiogenesis and elevated prothrombotic factors such as factor VIII and fibrinogen. Our patient had PE, renal artery thrombosis and popliteal artery thrombosis. Despite being on full dose anticoagulation, he developed gangrene of the toes. His lab results were not consistent with disseminated intravascular coagulation, thrombotic thrombocytopenic purpura and he was not known to have any baseline hypercoagulable disorder. He did not have any intra cardiac shunts. Hence, it is most likely Covid 19 induced multiple arterial and venous thrombosis. CONCLUSIONS: The treatment of Covid 19 related thrombosis has become very challenging especially in the setting of multiple clots. It is crucial to have large multicenter studies to investigate vascular complications of Covid-19 and to formulate management strategies to ensure good patient outcomes. Reference #1: https://www.nejm.org/doi/full/10.1056/nejmoa2015432 Reference #2: https://journal.chestnet.org/article/S0012-3692(21)01126-0/fulltext DISCLOSURES: No relevant relationships by Devashish Desai No relevant relationships by Swe Swe Hlaing no disclosure on file for Jean Marie Koka;No relevant relationships by Hui Chong Lau No relevant relationships by Subha Saeed No relevant relationships by Anupam Sharma No relevant relationships by Muhammad Moiz Tahir

Study of Extrapulmonary Manifestations of COVID-19 patients

Aim: To study extrapulmonary manifestations in COVID-19 patients. Material and methods: The present retrospective study was conducted among 200 COVID positive patients in the department of medicine, CSS Hospital, Subharti Medical College, Meerut. COVID-19 was diagnosed on the basis of the WHO interim guidance. Patients' diagnosis was identified along with the co-morbidity (if present). Laboratory investigations comprised of CBC and serum albumin detection. Extrapulmonary manifestations were defined as patients having predominantly neurological, gastrointestinal (GI), cardiovascular, cutaneous, and uncommon respiratory symptom such as hemoptysis either concomitant with typical respiratory symptoms or as the sole manifestation. Results: Fever was most frequent complain (n=97, 48.5%), followed by cough (n=76, 38%) and dyspnea was present in 51 subjects (25.5%). The most common respiratory symptoms was dyspnea (n=64, 32%). The most common cardiovascular symptoms was Dyspnea on exertion (n=54, 27%), followed by Palpitations (n=29, 14.5%). The most common GIT Symptoms was diarrhea (n=34, 17%), followed by Vomiting (n=13, 6.5%) and only 8 subjects (4%) reported abdominal pain. Dermatological symptoms were shown in 5 (2.5%) subjects. The most common musculoskeletal Symptoms was fatigue (n=103, 51.5%), followed by Myalgias (n=11, 5.5%) and Joint/Back Pain (n=4, 2%). Conclusion: Patients with COVID-19 require long-term follow-up even after recovery for observation and management of their post-COVID ailments. During the ongoing COVID-19pandemic, most health facilities are overloaded. Hence, arranging follow-up for patients can be a challenge. Therefore, a comprehensive rehabilitation program is essential for such patients during hospitalization and discharge.

Multisystem Inflammatory Syndrome in Children (MIS-C) with COVID-19: A Single-Center Experience

Objective: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory syndrome associated with multiorgan damage that occurs following coronavirus disease 2019 (COVID-19). Research on clinical and laboratory findings, and imaging studies, aiming to predict the progression to severe disease state is limited. This study recruited patients with MIS-C who presented with mild or severe symptoms from a single center in Turkey and evaluated factors related to their symptoms. Methods: This retrospective study included 25 pediatric patients with mild and severe presentations of MIS-C. We explored the differences in demographic and clinical data on clinical severity to understand their possible diagnostic and prognostic values. Results: Patients with MIS-C had cardiovascular symptoms (68%), gastrointestinal symptoms (64%), dermatologic/mucocutaneous findings (64%), lung involvement (36%), and neurological symptoms (16.0%). About 45.1% of patients with MIS-C had manifestations that overlapped with Kawasaki disease. Eleven patients (44%) were admitted to the intensive care unit, and one (4%) patient died. Grouping based on clinical severity did not differ statistically in terms of gender, age, height, weight, body mass index, and duration of hospital stay. Procalcitonin and ferritin levels correlated with disease severity. The receiver operating characteristic curve for D-dimer gave the highest value of area under the curve, among other biomarkers. The cutoff value for D-dimer was determined as more than 6780. Conclusions: Although COVID-19 is usually mild in children, some can be severely affected, and clinical severity in MIS-C can differ from mild to severe multisystem involvement. This study shows that procalcitonin, ferritin, and D-dimer levels may give us information about disease severity.

Association of COVID-19 with impaired endothelial glycocalyx, vascular function and myocardial efficiency four months after infection

Aims: SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers four months after COVID-19 infection. Methods: In a case-control prospective study, we included 100 patients four months after COVID-19 infection, 50 age- and sex-matched healthy individuals. We measured a) pulse wave velocity (PWV), b) flow-mediated dilation (FMD) of brachial artery, c) coronary Flow Reserve (CFR) by Doppler echocardiography d) left ventricular (LV) global longitudinal strain (GLS), e) left ventricular myocardial work index, constructive work, wasted work and work efficiency and e) von-Willenbrand factor and thrombomodulin as endothelial biomarkers. Results: COVID-19 patients had lower CFR and FMD values than controls (2.39 ± 0.39 vs 3.31 ± 0.59, p = 0.0122, 5.12 ± 2.95% vs 8.12 ± 2.23%, p = 0.006 respectively). Compared to controls, COVID-19 patients had higher PWV (PWVc-f 12.32 ± 2.44 vs 10.11 ± 1.85 m/sec, p = 0.033) and impaired LV GLS (-19.11 ± 2.14% vs -20.41 ± 1.61%, p = 0.001). Compared to controls, COVID-19 patients had higher myocardial work index, and wasted work (2067.7 ± 325.9 mmHg% vs 1929.4 ± 312.7 mmHg%, p = 0.026, 104.6 ± 58.9 mmHg% vs 75.1 ± 52.6 mmHg%, p = 0.008, respectively), while myocardial efficiency was lower (94.8 ± 2.5% vs 96.06 ± 2.3%, p = 0.008). and thrombomodulin were higher in COVID-19 patients than controls (3716.63 ± 188.36 vs 2590.02 ± 156.51pg/ml, p < 0.001). MDA was higher in COVID-19 patients than controls (10.55 ± 2.45 vs 1.01 ± 0.50 nmole/L, p = 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress markers. Myocardial work efficiency was related with PWV (F=-0.309, p = 0.016) and vWillenbrand (F=-0.541, p = 0.037). Myocardial wasted work was related with PWV (F = 0.255, p = 0.047) and vWillenbrand (F = 0.610, p = 0.016). Conclusions: SARS-CoV-2 may cause vascular dysfunction, followed by a waste of cardiac work, in order to compensate for increased arterial stiffness 4 months after infection.

Association of COVID-19 with impaired endothelial glycocalyx, coronary flow and longitudinal strain four months after infection

Aims: SARS-CoV-2 infection may lead to endothelial and vascular dysfunction. We investigated alterations of arterial stiffness, endothelial coronary and myocardial function markers four months after COVID-19 infection. Methods: In a case-control prospective study, we included 100 patients four months after COVID-19 infection, 50 age- and sex-matched healthy individuals. We measured a) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), b) flow-mediated dilation (FMD), c) coronary Flow Reserve (CFR) by Doppler echocardiography d) pulse wave velocity (PWV) e) global left (LV) and right (RV) ventricular longitudinal strain (GLS), f) malondialdehyde (MDA), an oxidative stress marker, von-Willenbrand factor and thrombomodulin as endothelial biomarkers. Results: COVID-19 patients had lower CFR and FMD values than controls (2.39 ± 0.39 vs 3.31 ± 0.59, p = 0.0122, 5.12 ± 2.95% vs 8.12 ± 2.23%, p = 0.006 respectively). Compared to controls, COVID-19 had greater PBR5-25 (2.11 ± 0.14μm vs 1.87 ± 0.16μm, p = 0.002), higher PWV (PWVc-f 12.32 ± 2.44 vs 10.11 ± 1.85 m/sec, p = 0.033) and impaired LV and RV GLS (-19.11 ± 2.14% vs -20.41 ± 1.61%, p = 0.001 and -16.45 ± 3.33% vs -20.11 ± 2.48%, p < 0.001). MDA and thrombomodulin were higher in COVID-19 patients than controls (10.55 ± 2.45 vs 1.01 ± 0.50 nmole/L, p = 0.001 and 3716.63 ± 188.36 vs 2590.02 ± 156.51pg/ml, p < 0.001). Residual cardiovascular symptoms at 4 months were associated with oxidative stress and endothelial dysfunction markers. Conclusions: SARS-CoV-2 may cause endothelial and vascular dysfunction linked to.

Impaired coronary flow reserve in athletes with long-term cardiovascular symptoms after COVID-19

Introduction: Cardiovascular symptoms post-acute sequelae of SARS-CoV-2 infection (CV-PASC) have been increasingly recognized, but the underlying pathobiology is unclear. Endothelial and cardiac pericyte ACE2 receptors are important targets of SARS-CoV-2, resulting in virally-induced endothelial activation, which may adversely affect the coronary microvasculature and impair myocardial performance. We hypothesized that athletes with CV-PASC have microvascular and subclinical myocardial dysfunction. Methods: We compared 15 athletes with CV-PASC with 7 control athletes without prior COVID-19 using regadenoson stress cardiac magnetic resonance (CMR). All athletes participated in >6 hours of endurance activities per week. We analyzed CMR volumes, function, global circumferential strain (GCS), late gadolinium enhancement (LGE), and coronary flow reserve (CFR) by coronary sinus method. Values presented as median [IQR]. Results: CMR in CV-PASC athletes occurred 102 [66,123] days post-SARS-CoV-2 infection. There were no differences in chamber volumes, function, or LGE between groups. One CV-PASC athlete had acute myocarditis (7%). CVPASC athletes had decreased CFR compared with control athletes (Figure 1). Multiple CV-PASC participants had CFR below the 95% CI of the controls and reported normal values from the literature (2.9 and 2.5, respectively). GCS was worse in CV-PASC athletes at the base (-23.7% [-21.6,-26.4] vs -31.1% [-27.3,-33.0], p=0.01), mid-LV (-21.5% [-18.5,-22.8] vs -28.5 [-25.4,-29.9], p=0.008), and apex (-27.1% [-24.1,-29.9] vs -30.6% [-27.8,-38], p=0.07), though the apex did not reach statistical significance. Conclusions: This pilot case-control study found CV-PASC athletes had reduced CFR and associated subclinical myocardial dysfunction as assessed by GCS compared to control athletes. These findings suggest coronary microvascular dysfunction related to endothelial injury may mediate CV-PASC symptoms.

Early echocardiographic and cardiac MRI findings in multisystem inflammatory syndrome in children (MIS-C)

Introduction: Multisystem Inflammatory Syndrome in Children (MISC) is a known severe condition affecting children previously exposed to SARS-CoV-2. Cardiovascular manifestations in MIS-C are quite common and include myocardial dysfunction, coronary artery dilation or aneurysms, arrhythmias, conduction abnormalities, pericarditis and valvulitis. Severe cases can present even with cardiogenic shock. To date, little is known about the very early myocardial abnormalities in pediatric patients with MIS-C. The Speckle Tracking Echocardiography (STE) and cardiac MRI (cMRI) have shown to be potential candidate for identifying regional ventricular dysfunctions in early stages of inflammatory COVID-related conditions [1,2]. Objectives: To describe the early cardiac findings in patients with MIS-C, evaluated by two advanced cardiovascular imaging, STE and cMRI. Methods: Consecutive patients with MIS-C underwent standard transthoracic echocardiography (TTE), speckle-tracking echocardiography (STE) with analysis of left ventricle (LV) global longitudinal strain (GLS) and cardiac MRI (cMRI). Clinical and laboratory data, including markers of systemic inflammation, Troponin I (TnI) and Brain Natriuretic Peptide (BNP) were also collected at onset and during follow up. All patients received intravenous immunoglobulins (IVIGs), intravenous corticosteroids (methylprednisolone) and antiplatelet therapy (aspirin). The use of biological agents (Anakinra) was reserved to patients with severe or critical illness. The need for Intensive Care Unit (ICU) was based on clinical and hemodynamic status at presentation. Results: Twenty-three patients (13M, 10F), mean age 8.1±4years (range 5.4-15.7), all with positive clinical and/or serological evidence of previous SARS-COV2 infection, entered the study. The majority (78.2%) was caucasian. All presented high degree fever, gastrointestinal symptoms and rash. Conjunctivitis and cardiovascular symptoms, as hypotension, thoracic pain or dysrhythmia, were present in 10 (43.5%). Nine children (39.1%) shared Kawasaki Disease-like symptoms. Four patients (17.4%) needed ICU admission and 3 required inotropic support. Short-term survival was 100%. All patients showed an hyperinflammatory state with elevated CRP, ESR, and D-Dimer. Tn- I was abnormal (>34 ng/L) in 15 patients (65.2%), BNP was significantly elevated in 20 (86.9%). Median time to STE evaluation was 8 days and to cMRI was 18 days since fever onset. Mean LVEF and RVEF were respectively 59±10% and 45±7%. Coronary dilation was observed in 6 (26.1%) patients. STE showed reduced mean LVGLS (-17±4.3%). LVEF on cMR was 60±13%, LGE with non-ischemic pattern was evident in 6/16 patients (37.5%) and pericardial effusion in 2 (12.5%). Conclusion: MIS-C can occur in a small but not negligible proportion of children previously affected by COVID-19 and affects the heart in a significant proportion of them. STE and cMRI were shown to be very sensitive tools to evaluate and monitor the early cardiac dysfunctions in patients with MIS-C. The elevation of myocardial necrosis markers, the myocardial injury confirmed by reduced LVGLS and presence of LGE on cMR in about a quarter of the patients support the pathogenetic hypothesis of a post-viral immuno-mediated myocarditis.

Cardio-COVID clinic-a one-center experience

Background: Persistent symptoms affect a relatively large portion of coronavirus disease (COVID) survivors. Hence, specific clinics had been established in order to better characterize and manage this emerging entity of Post-COVID, among them our Cardio-COVID Clinic, which is dedicated to the cardiovascular (CV) aspects of the phenomenon. Aim: To present the experience of our Cardio-COVID Clinic. Methods: Included in this report are 76 adult patients seen at the clinic between June 2020 and March 2021, who have recovered from a polymerase chain reaction (PCR)-confirmed COVID, and who were suspected by their referring physicians to experience ongoing cardiac sequelae. All participants underwent a structured assessment by a single cardiologist, which consisted of history taking, physical examination (PE), electrocardiogram (ECG), trans-thoracic echocardiogram (TTE), and further tests as deemed appropriate, including any combination of Holter, ischemic provocation test, cardiopulmonary exercise test (CPET), cardiac magnetic resonance (CMR), and cardiac computed tomography (CCT). Results: Initial visits occurred within a median of 131 days after diagnosis. Most participants (83%) were referred from our general Long-COVID Clinic. About half were males, and the mean age was 53 years. 18% of participants had prior CV conditions, and the majority (72%) had at least one CV risk factor, mostly dyslipidemia. Nearly all participants experienced a symptomatic acute illness, which was graded according to the National Institutes of Health (NIH) criteria as severe in 23% of the study cohort. As for Post-COVID, late symptoms were present in 97% of patients, the most common being dyspnea (57%). While PE was unremarkable in all but 3 patients who exhibited murmurs, ECG findings were revealed in 45%-mostly non-specific ST-T changes (31%) and conduction abnormalities (14%)-and TTE aberrations were discovered in 28%-including pericardial effusion (24%), reduced left ventricular ejection fraction (LVEF) (5%), grade 2 diastolic dysfunction (3%), moderate and up valvular dysfunction (1%), and systolic pulmonary hypertension (1%);right ventricular function was universally normal. Upon conclusion of the work-up, CV diagnoses were made in 8 (11%) patients-including myocarditis (4), myopericarditis (1), inappropriate sinus tachycardia (1), chronotropic incompetence (1), and an aberrant coronary (1). Of note, CPET and CMR had the highest diagnostic yield, in light of 57% positive results on each-followed by CCT, Holter, and provocation test. Interesting as well, among those with abnormal CMR findings, 40% had normal ECG's and TTE's. Also, none of the CV restraints on CPET translated to provocation test anomalies. Conclusion: CV symptoms of Post-COVID are highly prevalent, but signify actual CV disease only in a minority of patients. Further research is needed that will help identify predictors for CV morbidity and define optimal clinical pathways.