Microvascular lung vessels obstructive thromboinflammatory syndrome in patients with COVID-19: Insights from lung intravascular optical coherence tomography.

Background: Microvascular lung vessels obstructive thromboinflammatory syndrome has been proposed as a possible mechanism of respiratory failure in COVID-19 patients. However, it has only been observed in post-mortem studies and has never been documented in vivo, probably because of a lack of CT scan sensitivity in small pulmonary arteries. The aim of the present study was to assess the safety, tolerability, and diagnostic value of optical coherence tomography (OCT) for the assessment of patients with COVID-19 pneumonia for pulmonary microvascular thromboinflammatory syndrome. Methods: The COVID-OCT trial was a multicenter, open-label, prospective, interventional clinical study. Two cohorts of patients were included in the study and underwent pulmonary OCT evaluation. Cohort A consisted of patients with COVID-19 with a negative CT scan for pulmonary thrombosis and elevated thromboinflammatory markers (D-dimer > 10,000 ng/mL or 5,000 < D-dimer < 10,000 ng/mL and one of: C-reactive Protein > 100 mg/dL, IL-6 > 6 pg/mL, or ferritin > 900 ng/L). Cohort B consisted of patients with COVID-19 and a CT scan positive for pulmonary thrombosis. The primary endpoints of the study were: (i) to evaluate the overall safety of OCT investigation in patients with COVID-19 pneumonia, and (ii) to report on the potential value of OCT as a novel diagnostic tool for the diagnosis of microvascular pulmonary thrombosis in COVID-19 patients. Results: A total of 13 patients were enrolled. The mean number of OCT runs performed in each patient was 6.1 ± 2.0, both in ground glass and healthy lung areas, achieving a good evaluation of the distal pulmonary arteries. Overall, OCT runs identified microvascular thrombosis in 8 patients (61.5%): 5 cases of red thrombus, 1 case of white thrombus, and 2 cases of mixed thrombus. In Cohort A, the minimal lumen area was 3.5 ± 4.6 mm2, with stenosis of 60.9 ± 35.9% of the area, and the mean length of thrombus-containing lesions was 5.4 ± 3.0 mm. In Cohort B, the percentage area obstruction was 92.6 ± 2.6, and the mean thrombus-containing lesion length was 14.1 ± 13.9 mm. No peri-procedural complications occurred in any of the 13 patients. Conclusion: OCT appears to be a safe and accurate method of evaluating the distal pulmonary arteries in hospitalized COVID-19 patients. Here, it enabled the first in vivo documentation of distal pulmonary arterial thrombosis in patients with elevated thromboinflammatory markers, even when their CT angiogram was negative for pulmonary thrombosis. Clinical trial registration: ClinicalTrial.gov, identifier NCT04410549.

A cross-sectional survey study of the impact of COVID-19 pandemic on the training and quality of life of Italian medical residents in the Lombardy region.

INTRODUCTION: The reorganization of the healthcare system prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed unique challenges for Residency Training Programs worldwide. To mitigate its potential negative effects, it is crucial to assess how the pandemic influenced the activity and quality of life of residents. The purpose of this study was to assess the impact of the pandemic on residents' competencies, satisfaction, working load, training patterns and occupational exposure in the clinical, surgical, research and didactic fields and to quantify its effects on quality of life and risk perception. METHODS: An online cross-sectional survey was distributed between 1 June 2020 and 31 July 2020 to 1645 residents enrolled in all Residency Programs of four Universities in northern Italy. The survey included questions about clinical, surgical, and research competencies, educational activity, and quality of life pre- and post-pandemic, and on policies and workplace interventions to reduce exposure to SARS-CoV-2. The main outcome measure was the variation in self-perceived clinical, surgical and research competencies and in specialistic training. Data were analysed using the statistical package R Core Team 4.0.0, estimating mean and standard deviation or median and interquartile range for continuous variables. Variables were compared using chi-square test, Fisher exact tests or McNemar test, as appropriate.A multivariate binary logistic regression analysis was performed to test the effect of different factors on the impact of coronavirus disease-2019 (COVID-19) on self-perceived clinical and research competencies and on didactic training. RESULTS: A total of 498 residents completed the survey (response rate 30.3%). The mean age of respondents was 28.9 years, 62.9% were women, and 52.4% were enrolled in the first two years of Training Programs. On the first pandemic wave, over 60% of residents reported a negative impact of the pandemic on their specialistic training. In contrast, 40% of residents involved in clinical duties perceived an improvement in their clinical competences, especially those involved in COVID-19 care, and 34.5% perceived an improvement in their research competences, particularly junior residents, while only 3.5% reported an improvement in surgical skills. Most surgical residents (88.5%) reported a decrease in surgical activities, mainly due to reduced hospital bed capacity and reduction of elective surgery. Almost 90% of all residents experienced a reduction in their didactic activities, but 80% stated their Residency Program adopted virtual training methods. A statistically significant reduction in all examined quality of life items post-pandemic vs. pre-pandemic was found. Even though most survey participants reported the availability of personal protective equipment for residents, 44% considered themselves to be at higher risk of exposure compared to senior staff. CONCLUSION: COVID-19 pandemic caused a significant disruption in surgical training, but it had a positive impact on clinical competencies among residents involved in COVID-19 and urgent care. The pandemic had a detrimental effect on all quality of life aspects, and most residents considered themselves at higher risk of SARS-CoV-2 infection compared to other healthcare professionals.Key MessagesCoronavirus disease-2019 (COVID-19) pandemic caused a significant disruption in surgical training, but it had a positive impact on clinical competencies among residents involved in COVID-19 and urgent care.Most residents experienced a reduction of didactic activities. Although the majority of training programs implemented virtual training methods to counteract the restrictions imposed by the pandemic, only half of the residents were satisfied of them.A vast proportion of residents had a high occupational exposure to SARS-CoV-2 and considered themselves at higher risk of COVID-19 infection compared to senior staff.The survey highlighted a statistically significant reduction in five key quality of life measures (i.e. sleep, mood, familiar relationships and social relationships quality and employment satisfaction) during the first wave, with mood and social relationships being the most affected. Notably, employment satisfaction was significantly higher in medical compared to surgical residents.

Chronic anticoagulant treatment and risk of mortality in SARS-Cov2 patients: a large population-based study.

BACKGROUND: Hypercoagulability is often seen in Covid-19 patients and thromboembolic events appear frequent; antithrombotic treatment has been proposed therefore as part of standard treatment for Covid-19. Under these premises, prior-to-infection antithrombotic treatment may have a protective effect with respect to Covid-19 related thromboembolic events. Aim of the present work was to evaluate the impact of prior-to-infection anticoagulant or antiplatelet treatment on Covid-19 outcomes. METHODS: Beneficiaries of the Regional Health Service of the Lombardy region of Italy aged ≥40 years with a Covid-19 diagnosis made between February 21st and July 18th, 2020 were included in the present study. The impact on Covid-19 mortality of pre-existing and chronic therapy with anticoagulant drugs (vitamin-K antagonist or New Oral Anticoagulants) was evaluated. Analyses were repeated with antiplatelets drugs. RESULTS: Among 79,934 Sars-cov-2 patients beneficiaries of the Regional Healthcare System of the Lombardy Region who received a diagnosis between February 21st and July 18th, 2020, chronic preexisting anticoagulant assumption was present in 6.0% and antiplatelets in 12.7%. The overall unadjusted mortality rate was 20.6%, with male sex, age category and comorbidity burden being significantly associated to increased mortality risk. Anticoagulant chronic treatment was not associated with a reduction in mortality. Similar results were observed when repeating the analyses for pre-existing oral anti-platelet treatment. CONCLUSIONS: In a large population-based study evaluating more than 79,000 Covid-19 patients, pre-existing antithrombotic therapy was not associated to a benefit in terms of mortality. Further studies are needed to evaluate the role of antithrombotic therapy as standard treatment among Covid-19 patients.

Incidence and characterization of acute pulmonary embolism in patients with SARS-CoV-2 pneumonia: A multicenter Italian experience.

BACKGROUND AND AIMS: Several studies reported a high incidence of pulmonary embolism (PE) among patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, but detailed data about clinical characteristics, risk factors of these patients and prognostic role of PE are still lacking. We aim to evaluate the occurrence of pulmonary embolism among patients with SARS-CoV-2 infection, and to describe their risk factors, clinical characteristics, and in-hospital clinical outcomes. METHODS: This is a multicenter Italian study including 333 consecutive SARS-CoV-2 patients admitted to seven hospitals from February 22 to May 15, 2020. All the patients underwent computed tomography pulmonary angiography (CTPA) for PE detection. In particular, CTPA was performed in case of inadequate response to high-flow oxygen therapy (Fi02≥0.4 to maintain Sp02≥92%), elevated D-dimer (>0.5µg/mL), or echocardiographic signs of right ventricular dysfunction. Clinical, laboratory and radiological data were also analyzed. RESULTS: Among 333 patients with laboratory confirmed SARS-CoV-2 pneumonia and undergoing CTPA, PE was detected in 109 (33%) cases. At CTPA, subsegmental, segmental, lobar and central thrombi were detected in 31 (29%), 50 (46%), 20 (18%) and 8 (7%) cases, respectively. In-hospital death occurred in 29 (27%) patients in the PE-group and in 47 (21%) patients in the non-PE group (p = 0.25). Patients in PE-group had a low rate of traditional risk factors and deep vein thrombosis was detected in 29% of patients undergoing compression ultrasonography. In 71% of cases with documented PE, the thrombotic lesions were located in the correspondence of parenchymal consolidation areas. CONCLUSIONS: Despite a low rate of risk factors for venous thromboembolism, PE is present in about 1 out 3 patients with SARS-CoV-2 pneumonia undergoing CTPA for inadequate response to oxygen therapy, elevated D-dimer level, or echocardiographic signs of right ventricular dysfunction. In most of the cases, the thromboses were located distally in the pulmonary tree and were mainly confined within pneumonia areas.

Mortality and Pre-Hospitalization use of Renin-Angiotensin System Inhibitors in Hypertensive COVID-19 Patients.

Background There has been significant controversy regarding the effects of pre-hospitalization use of renin-angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID-19 patients. Methods and Results We retrospectively assessed 2,297 hospitalized COVID-19 patients at Tongji Hospital in Wuhan, China, from January 10th to March 30th, 2020; and identified 1,182 patients with known hypertension on pre-hospitalization therapy. We compared the baseline characteristics and in-hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non-RAS inhibitors (N=827). Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs. 95/827 (11.5%) patients in the non-RAS inhibitors group (p<0.0001). Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15-0.52, p<0.0001) at 45 days in the RAS inhibitors group compared with non-RAS inhibitors group. Similar findings were observed when patients taking angiotensin receptor blockers (N=289) or angiotensin converting enzyme inhibitors (N=66) were separately compared with non-RAS inhibitors group. The RAS inhibitors group compared with non-RAS inhibitors group had lower levels of C-reactive protein (median 13.5 vs. 24.4 pg/mL; p=0.007) and interleukin-6 (median 6.0 vs. 8.5 pg/mL; p=0.026) on admission. The protective effect of RAS inhibitors on mortality was confirmed in a meta-analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29-0.65, p<0.0001). Conclusions In a large single center retrospective analysis we observed a protective effect of pre-hospitalization use of RAS inhibitors on mortality in hypertensive COVID-19 patients; which might be associated with reduced inflammatory response.

ST-Segment-Elevation Myocardial Infarction During COVID-19 Pandemic: Insights From a Regional Public Service Healthcare Hub.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has led to a fast and radical transformation in social, economic, and healthcare networks. COVID-19 outbreak may thus have profound indirect consequences on clinical presentation and management of patients with ST-segment-elevation myocardial infarction (STEMI). Aim of this study was to assess clinical features of patients with STEMI during COVID-19 pandemic. METHODS: This single-center, prospective study from a regional public service healthcare hub in Milan included all consecutive patients with STEMI admitted to our institute from February 21 to April 1, 2020 (during COVID-19 pandemic). These patients were compared with a historical cohort of patients admitted for STEMI during the analogous time period (February 21 to April 1) in 2018 and 2019, in terms of time from symptoms onset to hospital admission, clinical characteristics, and in-hospital outcomes. RESULTS: A total of 26 patients were admitted for STEMI during the study period, and 7 (26.9%) of these patients tested positive for severe acute respiratory syndrome coronavirus 2. On admission, medical therapy, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers use, was similar between cohorts. Median (interquartile range) time from symptoms onset to hospital admission was significantly longer in 2020 as compared to the historical cohort (15.0 [2.0-48.0] versus 2.0 [1.0-3.0] hours; P<0.01). A higher proportion of patients presenting with late presentation STEMI was observed in 2020 compared with the historical cohort (50.0% versus 4.8%; P<0.01). Primary percutaneous coronary intervention resulted indicated in 80.8% of patients in 2020 compared with 100% in the historical cohort (P=0.06). In-hospital death, thromboembolism, mechanical ventilation, or hemodynamic decompensation needing inotropic or mechanical support were similar between years. CONCLUSIONS: These preliminary results from a cardiovascular regional public service healthcare hub demonstrate a significantly longer time from symptoms onset to hospital admission among patients with STEMI during COVID-19 pandemic compared with the same time period in the previous 2 years.

Cardiovascular Implications of the COVID-19 Pandemic: A Global Perspective

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), represents the pandemic of the century, with approximately 3.5 million cases and 250,000 deaths worldwide as of May 2020. Although respiratory symptoms usually dominate the clinical presentation, COVID-19 is now known to also have potentially serious cardiovascular consequences, including myocardial injury, myocarditis, acute coronary syndromes, pulmonary embolism, stroke, arrhythmias, heart failure, and cardiogenic shock. The cardiac manifestations of COVID-19 might be related to the adrenergic drive, systemic inflammatory milieu and cytokine-release syndrome caused by SARS-CoV-2, direct viral infection of myocardial and endothelial cells, hypoxia due to respiratory failure, electrolytic imbalances, fluid overload, and side effects of certain COVID-19 medications. COVID-19 has profoundly reshaped usual care of both ambulatory and acute cardiac patients, by leading to the cancellation of elective procedures and by reducing the efficiency of existing pathways of urgent care, respectively. Decreased use of health care services for acute conditions by non-COVID-19 patients has also been reported and attributed to concerns about acquiring in-hospital infection. Innovative approaches that leverage modern technologies to tackle the COVID-19 pandemic have been introduced, which include telemedicine, dissemination of educational material over social media, smartphone apps for case tracking, and artificial intelligence for pandemic modelling, among others. This article provides a comprehensive overview of the pathophysiology and cardiovascular implications of COVID-19, its impact on existing pathways of care, the role of modern technologies to tackle the pandemic, and a proposal of novel management algorithms for the most common acute cardiac conditions.

Collateral Damage: Medical Care Avoidance Behavior Among Patients With Myocardial Infarction During the COVID-19 Pandemic.

The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous strain on healthcare systems and society on a global scale. We report a new phenomenon of medical care avoidance among patients with acute coronary syndrome, which is due to concerns about contracting severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during hospital stay, ultimately leading to dire clinical outcomes. (Level of Difficulty: Beginner.).