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Since December 2019, an outbreak of a novel coronavirus (SARS-CoV-2) infection causing COVID-19 disease has influenced the whole world. Angiotensin converting enzyme 2 (ACE2) receptors on type 2 pneumocytes in humans were determined as the entry for SARSCoV-2. Receptor binding and subsequently endocytosis of ACE2 diminish the cell membrane expression and also the function of ACE2. ACE2 is an enzyme involved in bradykinin metabolism. Lys-des-Arg9-BK occured with enzymatic cleaving of Lys-BK derived from low molecular weight kininogen is inactivated by ACE2 in tissues and it is a vasodilator agent having its own receptor named bradykinin B1. Non-metabolized Lys-des-Arg9-BK can be the reason for tissue vasodilation and increased vascular permeability in the patients with COVID-19. Increased bradykinin levels in patients with hereditary angioedema with C1-INH deficiency (C1-INH-HAE) do not cause increased SARS-CoV-2 infection or more severe disease. Although SARS-CoV-2 infection does not result in increased bradykinin levels, it can increase Lys-des-Arg9-BK levels.Copyright © 2020 Bilimsel Tip Yayinevi. All rights reserved.
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Background: Coronavirus disease 2019 (COVID-19) was suspected to trigger angioedema attacks, or cause more severe COVID-19 disease in patients with Hereditary angioedema (HAE). Our objective was to evaluate the severity of COVID-19 and its impact on disease control in patients with severe HAE in long-term prophylaxis(LTP) with subcutaneous C1-inhibitor( SC C1-INH). Method(s): We p erformed a retrospective s tudy of p atients w ith s evere course of HAE who maintained LTP with SC C1-INH during the pandemic. Date were collected under conditions of daily clinical practice. Patients were evaluated at least 2 times after switching to LTP with SC C1-INH. We analyzed COVID19 vaccine application and tolerance, COVID19 infection, disease control after COVID19 infection and the quality-of- life. Result(s): We evaluated 18 patients(12 female) who switched from LTP with IV C1-INH to LTP with SC C1 INH. Switching was followed by a significant decrease in the number of attacks, visits to the emergency department, and use of rescue dose of IV C1-INH or icatibant, as well as improved disease control (Angioedema Control Test). All patients were vaccinated against COVID19 (37 doses of mRNA vaccine and 4 doses of viral vector vaccine). Nor severe neither moderate adverse reactions were observed. 5 patients were infected with COVID19 (one 30 years-old female patient was infected twice) and had mild symptoms. None of the patients needed a hospital admission. Only one of the patients had worsening of the disease control after COVID19 infection and long -term post COVID repercussion (persistent headache and depressive mood). One of the infected patients was pregnant (7 gestational weeks) and had asymptomatic COVID19 infection with no impact on pregnancy. Conclusion(s): In our cohort of patients LTP with SC C1 INH and correct vaccination against COVID19 have shown that can maintain severe HAE patients with good clinical control even when infected with the virus.
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Background: Hereditary (HAE-C1- INH) and acquired (AAE C1-INH) angioedema with C1 inhibitor (C1 INH) deficiency are rare but potentially life-threatening conditions associated with bradykinin overproduction and recurrent episodes of angioedema without wheals. Increased susceptibility to infections or infection-associated fatal outcomes has not been previously described in this condition. However, in 2020 novel theories suggesting bradykinin as a potential mediator involved in lung injury in COVID-19 disease have been proposed. Therefore, a more severe course of COVID-19 infection in C1 INH deficient should be considered. Method(s): In September 2021, we performed a retrospective analysis of COVID-19 disease courses in HAE C1-INH and AAE C1-INH patients from Czech referral centers for the treatment of hereditary angioedema with C1 INH deficiency. Collected data involved basic demography, comorbidities, previous immunosuppressive treatment, COVID-19 symptoms and treatment, HAE symptoms during infection. Result(s): We identified 17 patients (10 females, 7 males) with C1 INH deficiency with COVID-19 positivity from March 2020 until September 2021 with median age of 45 years (10-80 years). Our cohort consisted of 16 HAE C1-INH patients (94%, HAE-1 15/ 16 -94%, HAE-2 1/16 -6%) and 1 AAE C1-INH patient (6%). Only 8 (47%) of the patients were receiving HAE prophylaxis. Most common comorbidity was obesity (4/17, 24%) followed by autoimmune disease (3/17, 18%), hypertension (3/17, 18%), immunodeficiency (3/ 17, 18%), prior immunosuppressive treatment (3/ 17, 18%) and malignancy (2/17, 12%). COVID-19 infection was asymptomatic in 3 of them (18%). Symptomatic patients reported most commonly fever (10/14, 67%), anosmia and ageusia (8/14, 53%) and headache (3/14, 20%). Only 2 symptomatic patients (14%) had pneumonia treated with antibiotics. None of our patients were treated with monoclonal antibodies or referred to the hospital. All the patients recovered. Two patients reported long-lasting symptoms more than 3 months after infection. Five patients (29%) experienced HAE attacks and in two of them, increased attack frequency lasted several weeks after recovery. Conclusion(s): According to our findings, we do not assume C1 INH deficiency to be a risk factor for a severe course of COVID-19 disease. However, as other infections, COVID-19 might trigger angioedema attacks and may cause increased attack frequency after recovery.
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Background: The pandemic of Coronavirus disease 19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), has become a global challenge in the last two years. SARS-CoV- 2 enters the cells of the infected subjects through angiotensin converting enzyme 2 (ACE-2), leading to its depletion on cell surface. ACE-2 activity is involved in the catabolism of des-Arg( 9)-bradykinin and increases the expression of angiotensin converting enzyme (ACE) in animal models. ACE in turn inactivates bradykinin. The infection has therefore the potential to cause a deregulation of the contact system and its pro-inflammatory activity, which could also contribute to the pathogenesis of COVID-19. Since bradykinin-mediated angioedema is generally thought to be the result of a poorly regulated contact system, it has been speculated that these patients are prone to severe SARS-CoV- 2 infection and that COVID-19 can in turn elicit angioedema attacks. We examined these hypotheses in a large group of bradykinin-mediated angioedema patients. Method(s): W e c onducted a m ulticenter r etrospective s tudy t argeting all the patients with hereditary angioedema (HAE) or acquired angioedema due to C1 inhibitor deficiency followed up by the centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). All accessible patients underwent a telephone interview between January 1st and March 31st 2021;we collected data about demographic and angioedema features, the occurrence of SARS-CoV- 2 positivity and COVID-19 outcomes from the beginning of the pandemic until March 31st 2021. A digital diary of attacks developed by ITACA helped us to collect attacks data. 15 centers participated in the survey. Result(s): 677 patients were included;52/677 reported SARS-CoV- 2 positivity (48 with hereditary and 4 with acquired C1 inhibitor deficiency). The incidence was 7.68% (confidence interval 5,79-9,95%), similar to the general population (6.04%). 4/52 patients (7.7%) reported severe COVID-19;the median disease duration was 15 days. One patient suffered a pulmonary thromboembolism;no deaths were reported. 27/52 patients (51,9%) had angioedema attacks during the infection, with a median of 1 attack per patient;severity of COVID-19 predicted more frequent and more severe angioedema attacks in a multivariate analysis (p < 0.001). Conclusion(s): COVID-19 does not seem more severe in bradykinin-mediated angioedema than in the general population. SARS-CoV- 2 infection can elicit angioedema attacks.
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Case report Background: Hereditary angioedema (HAE) is a rare disease that usually manifests during childhood and is characterized by recurrent swelling episodes in various body tissues. Effective treatment options, including replacement therapy with C1 inhibitor (C1-INH) concentrate, are available for acute attacks and, for patients with high disease burden, for prophylaxis. More convenient than intravenous (IV) injections, and better suitable for patients with difficult venous access, is subcutaneous (SC) administration. However, treatment with SC prophylactic C1-INH is not yet approved in Europe for children < 12 years of age. Case Description: The boy presented to our clinic in 2014 at the age of 3, with a diagnosis of HAE due to C1-INH deficiency. During the last 3 months, he had been given IV C1-INH concentrate on-demand for HAE attacks. During the following year, the boy experienced monthly attacks at different body sites and had to be hospitalized several times for edema of the extremities and face, and abdominal colicky pain. At 5 to 6 years of age, attack frequency increased to once weekly and a first swelling of the trachea with dyspnea occurred. Over time, this led to repeated occurrence of panic attacks and psychological problems, which were exacerbated by social distancing during the coronavirus disease-19 pandemic. To mitigate disease burden, his therapy was switched to weekly prophylaxis with IV C1-INH, and the bradykinin receptor inhibitor icatibant was kept on hand as emergency medicine. Less than half a year later, attack frequency increased again and the regimen was changed to twice weekly. This led to drastic deterioration of venous access, so that a switch to SC prophylaxis became inevitable. The patient, now 10 years old, and his mother were trained in SC injection techniques and since June 2021, they administer twice weekly SC C1-INH (2000 International Units) at home, with no breakthrough attacks and significant improvement of quality of life. Conclusion(s): Because of high disease burden and impairment of quality of life due to high edema frequency, routine prophylaxis was chosen. In patients receiving frequent IV prophylaxis, occurrence of breakthrough attacks and deterioration of venous access warrants a switch to SC treatment. In the present case, this switch was unavoidable, although this treatment option is not approved for children. It allows the boy to self-administer his C1-INH and has improved his quality of life significantly.
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SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Macroglossia is a rare but life-threatening symptom that disrupts a person's ability to talk, swallow, and can also compromise their airway. Although not very well studied, there are several case reports describing a possible association between COVID-19 infection and macroglossia in people with African ancestry. We present an African American man who developed significant macroglossia several days after testing positive for COVID-19. CASE PRESENTATION: A 59 y/o African American male with a history of chronic bronchitis and tobacco use presented with 4 days of dyspnea. Sars-Cov-2 PCR was positive. Chest x-ray revealed bilateral, diffuse lung infiltrates. He had an elevated CRP of 295 and a d-dimer of 265. He became lethargic and hypercapnic requiring intubation which was nontraumatic. He was sedated, paralyzed, and proned. He received steroid therapy, broad spectrum antibiotics and a dose of Sarilumab. About a week later, he developed macroglossia that worsened over the course of days. Side effect profiles of each of his medications did not reveal any increased likelihood of macroglossia. C1Q complement cascade was mildly elevated and C1 esterase inhibitor level was normal. Diagnosis and treatment was necessary at this point as concerns for tongue central necrosis were raised and baseline tongue size would be required for proper evaluation and surgical intervention if necessary. He was given 4 units of FFP for possible angioedema with no improvement. CT Neck W/ contrast revealed edema and protrusion of the tongue without a discrete mass. Workup for acromegaly, sarcoidosis, amyloidosis, and hypothyroidism were negative. A pressure ulcer developed on his tongue due to the endotracheal tube and so he underwent tracheostomy. His tongue was draped in Chlorhexidine soaked gauze as well as Vashe wound solution. As he recovered from COVID-19 pneumonia, his respiratory status improved as well as his macroglossia. His tracheostomy was decannulated and his tongue returned to its baseline size. DISCUSSION: Macroglossia can lead to complications including airway compromise, dysphagia, or speech difficulties. It has been heavily proposed in the literature that COVID-19 infection can lead to postinfectious inflammatory peripheral nerve injury secondary to immune driven mechanisms. It was also previously proposed in literature based on immune-histochemical analysis of a tongue tissue sample taken from a COVID-19 patient that tongue muscle atrophy occurs as well as macrophage infiltration similar to that of nerve injury repair which can eventually lead to macroglossia. CONCLUSIONS: As the effects of COVID-19 are becoming better studied overtime, macroglossia, especially in those with African ancestry, is increasingly coming under the radar. This case report seeks to educate clinicians on this possible sequela and encourage supportive treatment in hopes that the tongue will recover. Reference #1: McCrossan S, Martin S, Hill C. Tongue Reduction for Macroglossia. J Craniofac Surg. 2021;32(5):1856-1859. doi:10.1097/SCS.0000000000007276 Reference #2: Colombo D, Del Nonno F, Nardacci R, Falasca L. May macroglossia in COVID-19 be related not only to angioedema?. J Infect Public Health. 2022;15(1):112-115. doi:10.1016/j.jiph.2021.10.026 Reference #3: Fernandez CE, Franz CK, Ko JH, et al. Imaging Review of Peripheral Nerve Injuries in Patients with COVID-19. Radiology. 2020;298 (3). https://doi.org/10.1148/radiol.2020203116 DISCLOSURES: No relevant relationships by Megan Devine No relevant relationships by Devin Haney No relevant relationships by Es-Haq Hassanin No relevant relationships by Nadim Islam No relevant relationships by Alyssa Weyer
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Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is well described as an etiology to severe acute respiratory distress syndrome (ARDS). However, rare immunologic and allergic manifestations may also occur from this infection. We report a novel case of angioedema occurring in the setting of COVID-19 infection in a fully vaccinated patient. Case Report: A 61-yearold COVID-19 vaccinated female with hypertension presented to the emergency department with tongue and lip swelling, odynophagia, dysphonia, and difficulty breathing. She denied personal or family history of allergies, anaphylaxis, or angioedema. Her home medications included Aspirin, methadone, Seroquel, and Klonopin, with no recent changes reported. Physical exam was notable for significant lip and tongue edema, audible dysphonia, and bilateral end-inspiratory wheezing. She was hypoxemic and placed on nasal cannula. Laboratory findings revealed lymphopenia, elevated inflammatory proteins, including C-reactive protein (57), Lactate dehydrogenase (LDH) (238), and D-dimer (11.52). Functional C1 esterase inhibitor levels (>91) were normal. Nasal PCR swab returned positive for SARS-CoV-2. Ear, nose, and throat specialist was consulted given concern for angioedema, and flexible nasolaryngoscopy was performed revealing uvular, epiglottic, and bilateral arytenoid edema concerning for impending airway compromise. The patient was initiated on intravenous methylprednisolone, epinephrine, antihistamines, tranexamic acid and admitted to the medical intensive care unit (ICU). She was monitored closely in the ICU with subsequent improvement of the angioedema and resolution of the hypoxemia. She was discharged with an oral steroid regimen and scheduled for a follow-up appointment with an allergist. Discussion: There exists only a handful of case reports describing angioedema in patients with COVID-19 infection. In those reports, patients also had normal C1 esterase inhibitor levels and no personal or family history of inherited angioedema. Interestingly, our patient was vaccinated six months prior to her presentation. The association between SARS-CoV-2 and angiotensinconverting enzyme 2 (ACE-2), the primary receptor for viral entry into the epithelial cells of the lungs, could be a potential explanation for the occurrence of angioedema. ACE-2 plays a pivotal role in inhibiting a potent ligand of bradykinin receptor 1, Arginine bradykinin. It has been postulated that SARS-CoV-2 downregulation of ACE-2 leads to elevated angiotensin II levels and subsequent activation of the bradykinin pathway. Excessive bradykinin production generates high levels of nitric oxide and prostaglandins, resulting in vasodilation, increased vascular permeability, and angioedema. This case highlights the importance of recognizing atypical and rare presentations of COVID-19 infection, especially angioedema, given its sudden onset and life-threatening complications.
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Systemic capillary leak syndrome (SCLS or Clarkson's disease) is a rare condition characterized by episodes of vascular hyperpermeability. The extravasation of plasma to the interstitial space results in hemoconcentration, hypoalbuminemia, hypovolemia and compartment syndrome of the extremities. The disease can be idiopathic or secondary to causes including viral infections or chemotherapeutic toxicity. We present a fatal case of idiopathic SCLS which rapidly deteriorated to multiple organ failure despite initial improvement with methylene blue. A 57-year-old male presented for worsening back pain over one month. He described a flulike illness 2 weeks prior. Testing for respiratory viruses including SARS-CoV-2 was negative. He received intravenous crystalloid fluids acutely developed respiratory distress and hypotension requiring emergent intubation and initiation of norepinephrine infusion. CT angiography of the chest demonstrated pulmonary edema. Early during his hospitalization urine output ceased and body weight increased by 10 kg, developing tense anasarca. Hematocrit concentrated from 42.7 to 54.4%. Serum albumin dropped from 4.6 to 2.5 g/dL. C1 esterase inhibitor level and IgM were normal. Ferritin was elevated at 2515 ng/ml. He received cefepime and vancomycin, though infectious workup returned unremarkable. Continuous renal replacement therapy and stress dose steroids were initiated. Vasopressor requirement worsened until he was on three vasopressors at one point. Given the constellation of hemoconcentration, hypoalbuminemia, and shock a diagnosis was made of idiopathic SCLS. Treatment was started with methylene blue, montelukast, and the β-adrenergic agonist terbutaline. Blood pressure improved and patient came off pressors and lactate improved from 13 to 4. However, he later developed rising creatine kinase continued to climb to >40,000 U/L. He developed rhabdomyolysis with concern for compartment syndrome of the extremities due to third spacing of fluids. Orthopedic surgery was consulted;but did not believe a fasciotomy was indicated due to rapid decline. Lactic acidosis rose to 18 mmol/L. His family decided to transition to comfort measures. He passed with family at bedside on Day 4 of hospitalization. There are fewer than 500 cases of SCLS reported since initial discovery in 1960. Given the overlap in presentation with common causes of plasma leakage such as sepsis, it is likely that many cases are unrecognized. Patients are often mismanaged;development of severe hypovolemia despite fluids and compartment syndrome is overlooked. This case builds on our evolving recognition of this disease, and the potential for the use of methylene blue to help acute exacerbations of the disease.
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Background: Coronavirus disease 2019 (COVID19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has varied clinical presentations from mild subclinical to severe disease with high mortality. Our aim was to determine whether examining immune-related gene expression early in infection could predict progression to severe disease. Methods: In subjects of the All Ireland Infectious Diseases Cohort study, we analysed expression of 579 genes with the NanoString nCounter Immunology panel in peripheral blood mononuclear cells in those with confirmed SARS-CoV-2 infection collected within 5 days of symptom onset and matched SARS-CoV-2 negative controls with respiratory infection. Subsequent maximum COVID19 disease severity was classified as mild or severe. Read counts were normalized using panel housekeeping genes. Expression changes in severity groups were estimated against control baseline. Results: Between April and July of 2020, we recruited 120 subjects, 62 with COVID19 and 58 controls, with average age 59 y.o. (IQR 34-88), 66% males and 69% Caucasian ethnicity. Maximal disease severity was used to separate COVID19 cases into mild (n=31) and severe (n=31). We identified 20 significantly deregulated genes between those with COVID19 and controls (;log2 fold;>0.5, p<0.05, Benjamin-Yekutieli p-adjustment). Function of 12 of these genes related to cytokine signaling, 9 upregulated genes to type I interferon signaling (MX1, IRF7, IFITM1, IFI35, STAT2, IRF4, PML, BST2, STAT1), while 7 downregulated genes mapped to innate immune function (IRF7, ICAM2, SERPING1, IFI16, BST2, FCER1A, PTK2). Expression in the severe group showed downregulation of FCER1A (innate immunity regulation), IL1B and TNF (inflammatory cytokines), and PTGS2 (inflammatory mediator) and greater upregulation of TNFSF4 (cytokine signaling) and PTK2 (innate immunity). Mild cases presented higher upregulation of IFIT2 (type I interferon signaling). Conclusion: Observed early downregulation of regulators and mediators of inflammation in those who developed severe COVID19, suggested dysregulation of inflammation. Specifically, IFIT2 upregulation in mild cases and FCER1A downregulation in severe cases, points to early differences in host responses centered on deregulation of the interferon and inflammation responses. Whether these patterns reflect delayed interferon involvement in pathways to control the infection and contribute to pathological inflammation and cytokine storms observed in severe COVID19 requires further research.
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Objective: The aim of this study was to determine the clinical course and treatment outcomes of patients with hereditary angioedema (HAE) after infection with coronavirus disease 2019 (COVID-19). Materials and Methods: Thirty-nine patients with HAE were included in this study. These patients were regularly followed up over phone calls since the first COVID-19 case was seen in our country. Patients were asked to visit the hospital if there was a history of contact with a confirmed COVID-19 patient or if the patient developed clinical symptoms of COVID-19. Results: There were 21 (54%) patients with type I HAE, and 18 (46%) with type II HAE. All patients received treatment for angioedema attacks (C1-inhibitor [C1-INH], icatibant), and seven (20%) received long-term prophylaxis (danazol). Treatment for attacks was continued for all patients during the pandemic. Patients taking danazol were switched to long-term prophylaxis using the C1-INH concentrate. Eleven (28%) patients with HAE developed COVID-19 during this study. Only one patient had severe COVID-19. Six patients (54.5%) were diagnosed with type II HAE, and five (45.5%) were diagnosed with type I HAE. The most common COVID-19 symptoms were fever (7/11;64%) and myalgia (6/11;55%). Mild angioedema attacks were experienced by 36% (4/11) of the HAE patients diagnosed with COVID-19. Icatibant was used in all patients. Conclusion: Agents used for HAE block the kallikrein-kinin system and may be useful in the treatment of COVID-19. Considering their beneficial effects on COVID-19, it is recommended that HAE patients should continue the use of agents blocking the kallikrein-kinin system.
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The proceedings contain 38 papers. The topics discussed include: longitudinal assessment of SARS-CoV-2 nucleocapsid antigenemia in patients hospitalized with COVID-19;machine learning-based automated selection of regions for analysis on bone marrow aspirate smears;direct detection of beta-lactamase mediated antibiotic resistance in clinical specimens;convalescent plasma does not provide adequate replacement of C1-Inhibitor and complements in COVID-19 patients;mapping cell-to-cell mitochondria transfer in obesity using high-dimensional spectral flow cytometry;capture the tag: mitigation of biotin interference in ELISA and automated immunoassays by pre-conjugating biotinylated antibodies to the streptavidin surface;and assessment of coagulation tests in hospitalized COVID19 patients;challenging coagulopathies.
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Background: Endothelial damage caused by COVID-19 may imperil the cardiovascular health of millions. More than a year since WHO declared the COVID-19 pandemic, information on the lasting effects of this infection on the cardiovascular system beyond the acute phase is still lacking. Purpose: To study macrovascular endothelial dysfunction and activation, coagulation and inflammation, 3 months after resolution of acute COVID- 19 symptoms. Methods: A cross-sectional observational cohort study was conducted including 203 patients with PCR confirmed COVID-19 disease, 6-20 weeks after acute COVID-19. The primary endpoint was macrovascular endothelial function, assessed by the carotid artery reactivity (CAR) test. The CAR measures the carotid artery diameter in response to hand in icewater immersion. A historic cohort of 313 subjects served as controls. Propensity score matching was used to correct for baseline differences. Plasma endothelin-1 (ET-1), interleukin (IL)-1ra, IL-6, IL-18 were measured by ELISA. ET-1 levels were also measured in a partially overlapping COVID-19 cohort of which plasma samples were available during the acute phase. Coagulation enzyme:inhibitor complexes for thrombin:antithrombin (TAT), factor (F) IXa:AT, FVIIa:AT, FXIa:AT, FXIa:alpha 1 antitrypsin (a1AT), FXIa:C1 esterase inhibitor (C1inh), kallikrein(PKa):C1inh and von Willebrand Factor:antigen (vWF:Ag), were assessed by in house developed ELISA. Results: After propensity score matching, the prevalence of macrovascular dysfunction did not differ between the COVID-19 (22.5%) versus the historical control cohort (18.6%, RD -3.92%, 95%-CI -15 to 7.19, p=0.49). Plasma concentrations of markers for endothelial activation were elevated (>1 SD above normal);ET-1 (64.9%), and vWF:Ag (80.8%). In controls, ET- 1 levels were significantly lower as compared to COVID-19 patients during the acute phase and after 3 months. ET-1 levels were significantly higher 3 months after COVID-19 as compared to the acute phase. Cytokines were high in a majority of patients: IL-18 (73.9%), IL-6 (51.2%), and IL- 1ra (48.9%). TAT and FIXa:AT, reflecting a prothrombotic state, were high in 48.3% and 29.6% of the patients, respectively. FVIIa:AT, as marker of the extrinsic pathway, was elevated (35%). Markers of contact activation were also increased: PKa:C1inh (16.3%), FXIa:AT (16.3%), FXIa:a1AT (20.7%), and FXIa:C1inh (17.7%) (picture 1). Conclusions: At 3 months after acute COVID-19 there was no indication of macrovascular dysfunction as compared to matched historic controls;there was evidence, however, of sustained thrombo-inflammation, indicated by high circulating concentrations of ET-1, vWF:Ag, proinflammatory cytokines, and markers of coagulation (picture 2). Elevated IL-18 levels could potentially induce arterial inflammation and subsequent atherogenesis. Our data highlight the importance of further studies on SARS-CoV-2 related thrombo-inflammation, as well as longer follow-ups in recovered patients. (Figure Presented).