Autoimmune disease and COVID-19- a multicentre observational study in the United Kingdom

Objective To establish the demographic characteristics, laboratory findings and clinical outcomes in patients with autoimmune disease (AD) in comparison to a propensity matched cohort of patients without AD admitted with COVID-19 to hospitals in the UK. Methods This is a multicentre observational study across 26 NHS Trusts. Data were collected both retrospectively and prospectively using a pre-designed standardised case record form. Adult patients (≥18 years) admitted between 1st of April 2020 and 31 July 2020 were included. Results Overall, 6288 patients were included to the study. Of these, 394 patients had AD prior to admission with COVID-19. Of 394 patients, 80 patients with systemic lupus erythematosus, rheumatoid arthritis or antiphospholipid syndrome were classified as severe rheumatologic AD. A higher proportion of those with AD had anaemia: 240(60.91%) vs 206(52.28%), p= 0.015, raised LDH 150(38.08%) vs 43(10.92%), p< 0.001 and raised creatinine 122(30.96%) vs 86(21.83%), p= 0.01 respectively. A significantly higher proportion of patients with severe rheumatologic AD had raised CRP : 77(96.25%) vs 70(87.5%), p= 0.044 and LDH 20(25%) vs 6(7.5%), p= 0.021. Patients with severe rheumatologic AD had significantly higher mortality [32/80(40%)] compared with propensity matched cohort of patients without AD [20/80(25%)], p= 0.043. However, there was no difference in 180-day mortality between propensity matched cohorts of patients with or without AD in general, p= 0.47. Conclusions Patients with severe rheumatologic AD had significantly higher mortality. Anaemia, renal impairment and raised LDH were more frequent in patients with any AD whilst raised CRP and LDH were more frequent in patients with severe rheumatologic AD both of which have been shown to associate with increased mortality in patients with COVID-19

Thombosis, major bleeding, and survival in COVID-19 supported by veno-venous extracorporeal membrane oxygenation in the first vs second wave: a multicenter observational study in the United Kingdom

Background Bleeding and thrombosis are major complications of veno-venous (VV) extracorporeal membrane oxygenation (ECMO). Objectives To assess thrombosis, major bleeding (MB), and 180-day survival in patients supported by VV-ECMO between the first (March 1 to May 31, 2020) and second (June 1, 2020, to June 30, 2021) waves of the COVID-19 pandemic. Methods An observational study of 309 consecutive patients (aged ≥18years) with severe COVID-19 supported by VV-ECMO was performed in 4 nationally commissioned ECMO centers in the United Kingdom. Results Median age was 48 (19-75) years, and 70.6% were male. Probabilities of survival, thrombosis, and MB at 180 days in the overall cohort were 62.5% (193/309), 39.8% (123/309), and 30% (93/309), respectively. In multivariate analysis, an age of >55 years (hazard ratio [HR], 2.29; 95% CI, 1.33-3.93; P = .003) and an elevated creatinine level (HR, 1.91; 95% CI, 1.19-3.08; P = .008) were associated with increased mortality. Correction for duration of VV-ECMO support, arterial thrombosis alone (HR, 3.0; 95% CI, 1.5-5.9; P = .002) or circuit thrombosis alone (HR, 3.9; 95% CI, 2.4-6.3; P < .001) but not venous thrombosis increased mortality. MB during ECMO had a 3-fold risk (95% CI, 2.6-5.8, P < .001) of mortality. The first wave cohort had more males (76.7% vs 64%; P = .014), higher 180-day survival (71.1% vs 53.3%; P = .003), more venous thrombosis alone (46.4% vs 29.2%; P = .02), and lower circuit thrombosis (9.2% vs 28.1%; P < .001). The second wave cohort received more steroids (121/150 [80.6%] vs 86/159 [54.1%]; P < .0001) and tocilizumab (20/150 [13.3%] vs 4/159 [2.5%]; P = .005). Conclusion MB and thrombosis are frequent complications in patients on VV-ECMO and significantly increase mortality. Arterial thrombosis alone or circuit thrombosis alone increased mortality, while venous thrombosis alone had no effect. MB during ECMO support increased mortality by 3.9-fold. Keywords: COVID-19; extracorporeal membrane oxygenation; hemorrhage; mortality; thrombosi

Clinical and biological features of cerebral venous sinus thrombosis following ChAdOx1 nCov-19 vaccination

Vaccines for COVID-19were developed with unprecedented speedand since January 2021, the AstraZeneca/Oxford University ChAdOx1 nCoV-19 vaccine has been administered to over 400 million people globally1. In April 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA)reported a possible association between ChAdOx1 nCoV-19 and a rare syndrome of unusual site thrombosis combined with thrombocytopenia, termed vaccine-induced immune thrombotic thrombocytopenia (VITT).Frequency of VITT varies across age groups. Overall 411 cases of VITT have been reported to Medicine & Healthcare prodcuts Regulatory Agency (MHRA) by 21st of July 2021 with fatality rate of 17.76% (73/411)2

Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH: reply

We thank Dr Desborough and colleagues for their response to the recently published guidance from the SSC of the ISTH on the management of direct oral anticoagulants (DOACs) in women of childbearing potential [1,2]. We have carefully examined their view and seriously considered their proposal regarding the recommendation of this guidance as detailed below. We hereby, provide a detailed response to their letter. This article is protected by copyright. All rights reserve

Rescue therapy with thrombolysis in patients with severe COVID-19 ARDS

Acute respiratory distress syndrome (ARDS) in patients with Coronavirus disease 19 (COVID-19) is associated with an unusually high incidence of pulmonary embolism (PE) and microthrombotic disease, with evidence for reduced fibrinolysis. We describes even patients requiring invasive ventilation for COVID-19 ARDS with pulmonary thromboembolic disease, pulmonary hypertension ± severe right ventricular (RV) dysfunction on echocardiography, who were treated with alteplaseas fibrinolytic therapy. All patients were non-smokers, 6 (86%) were male and median age was 56.7 (50-64) years. They had failed approaches including therapeutic anticoagulation, prone ventilation (n=4), inhaled nitric oxide (n=5) and nebulised epoprostenol (n=2). The median duration of mechanical ventilation prior to thrombolysis was 7 (5-11) days.Systemic alteplase was administered to 6 patients (50mg or 90mg bolus over 120 minutes) at 16 (10-22) days after symptom onset. All received therapeutic heparin pre-and post-thrombolysis, without intracranial haemorrhageor other major bleeding. Alteplase improvedPaO2/FiO2(PF) ratio (from 97.0 (86.3-118.6) to 135.6 (100.7-171.4), p=0.03) and ventilatory ratio (from 2.76 (2.09 -3.49) to 2.36 (1.82 –3.05), p=0.011) at twenty-four hours.Echocardiographic parameters at 2 (1-3) days (n=6) showed RVSP was 63 (50.3-75) then 57 (49-66) mmHgpost-thrombolysis (p=0.26), TAPSE was unchanged (from 18.3 (11.9-24.5) to 20.5 (15.4-24.2) mm, p=0.56)and RV fractional area change (from 15.4 (11.1-35.6) to 31.2 (16.4-33.1) %, p=0.09). At7 (1-13) days after thrombolysis,using DECT imaging(n=3),average relative peripheral lung enhancement increased from 12.6 to 21.6% (p=0.06).Conclusion:Thrombolysis improved PF ratio and ventilatory ratio at 24h as rescue therapy in patients with RV dysfunction due to COVID-19 ARDS despite maximum therapy, as part of a multimodal approach, and requires further study