Adjudicated myocarditis and multisystem illness trajectory in healthcare workers post-COVID-19.

BACKGROUND: We investigated the associations of healthcare worker status with multisystem illness trajectory in hospitalised post-COVID-19 individuals. METHODS AND RESULTS: One hundred and sixty-eight patients were evaluated 28-60 days after the last episode of hospital care. Thirty-six (21%) were healthcare workers. Compared with non-healthcare workers, healthcare workers were of similar age (51.3 (8.7) years vs 55.0 (12.4) years; p=0.09) more often women (26 (72%) vs 48 (38%); p<0.01) and had lower 10-year cardiovascular risk (%) (8.1 (7.9) vs 15.0 (11.5); p<0.01) and Coronavirus Clinical Characterisation Consortium in-hospital mortality risk (7.3 (10.2) vs 12.7 (9.8); p<0.01). Healthcare worker status associated with less acute inflammation (peak C reactive protein 48 mg/L (IQR: 14-165) vs 112 mg/L (52-181)), milder illness reflected by WHO clinical severity score distribution (p=0.04) and shorter duration of admission (4 days (IQR: 2-6) vs 6 days (3-12)).In adjusted multivariate logistic regression analysis, healthcare worker status associated with a binary classification (probable/very likely vs not present/unlikely) of adjudicated myocarditis (OR: 2.99; 95% CI (1.01 to 8.89) by 28-60 days postdischarge).After a mean (SD, range) duration of follow-up after hospital discharge of 450 (88) days (range 290, 627 days), fewer healthcare workers died or were rehospitalised (1 (3%) vs 22 (17%); p=0.038) and secondary care referrals for post-COVID-19 syndrome were common (42%) and similar to non-healthcare workers (38%; p=0.934). CONCLUSION: Healthcare worker status was independently associated with the likelihood of adjudicated myocarditis, despite better antecedent health. Two in five healthcare workers had a secondary care referral for post-COVID-19 syndrome. TRIAL REGISTRATION NUMBER: NCT04403607.

COVID-19 disease is associated with a hypofibrinolytic state driven by elevated plasminogen activator inhibitor-1 and its cofactor vitronectin

Background: COVID-19 disease arises from infection with severe acute respiratory cornonavirus-2 (SARS-CoV- 2). Severe disease is associated with a coagulopathy characterised by elevated D-dimer levels, fibrin deposition in the lung, and a thrombotic incidence of approximately 30%, indicating catastrophic derailment of the haemostatic system. Aim(s): To investigate whether SARS-CoV- 2- induced coagulopathy arises due to an imbalance in the fibrinolysis. Method(s): Citrated plasma was collected from 139 patients presenting with symptomatic COVID-19, 24 patients with non-COVID- 19 respiratory infection and 30 healthy controls in a dual-centre study. Fibrinolytic biomarkers were evaluated including plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), plasminogen, vitronectin and thrombin activatable fibrinolysis inhibitor (TAFI). Furthermore, diagnostic biomarkers including, fibrinogen, C-reactive protein (CRP), D-dimer and inflammatory cytokines were quantified. Clot lysis was evaluated using turbidity assays, plasma clot structure visualised by confocal microscopy and plasmin generation quantified by chromogenic substrate. Result(s): PAI-1 antigen, activity, and the cofactor for this serpin, vitronectin, were significantly elevated in patients with COVID-19 compared to healthy controls and non-COVID- 19 respiratory infection. Patients with COVID-19 exhibit attenuated plasmin generation compared to healthy volunteers despite significant elevation in tPA. PAI-1 correlated with inflammatory cytokines (IL-1beta, IL-8 and TNF-alpha). In line with this acute phase proteins, fibrinogen and CRP were high in patients with COVID-19 but only CRP was increased compared to non-COVID- 19 respiratory infections. Levels of PAI-1 and vitronectin were associated with escalating oxygen support and a corresponding decrease in plasminogen. Importantly, patients with COVID-19 disease exhibit resistance to fibrinolytic degradation by Actilyse, however, this could be overcome by the PAI-1 resistant form of tPA, Metalyse. Conclusion(s): We reveal that COVID-19 disease promotes a hypofibrinolytic state due to elevated PAI-1 and its stabilizing cofactor vitronectin. PAI-1 correlates with inflammatory cytokines and disease severity thereby highlighting its potential prognostic power in the development of severe COVID-19 disease.

Pulmonary thromboembolism (PTE) in hospitalised patients with COVID-19: A national study of patients managed incritical care and ward environments

Background : Since the emergence of Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2) in late December 2019, there has been increasing recognition of the pro-thrombotic risk this virus can cause as part of Coronavirus disease 2019 (Covid-19). Aims : To assess if the rate of PTE was increased in those with COVID-19 in both critical care and ward patients. To assess the effect of right heart strain or requirement for critical care on mortality. Methods : We reviewed all computed tomography pulmonary angiograms (CTPA) performed in Scotland between 23 rd March and 31 st May 2020 (1st wave) and identified those inpatients with COVID-19 using either classical radiological appearances, or positive COVID-19 polymerase chain reaction swab. 3401 CTPAs were reviewed. 192 were positive for PTE in patients with evidence of COVID-19 either real-time polymerase chain reaction (RT-PCR) swab positive for SARS-CoV-2 [ n = 104] or having radiological changes consistent with COVID-19 [ n = 88]). The total number of hospital admissions in Scotland between 23 rd March 2020 and 31 st May 2020 with COVID-19 was 5195. The incidence of PTE during this time was 3.7% in all patients admitted to all hospitals in Scotland with COVID-19 during this period. 475 hospitalised patients were managed in critical care (both level 2 and level 3 care), in whom the incidence of PTE was 6% ( n = 29). 4720 patients required ward based care alone and the incidence of PTE was 3.5% ( n = 163). This compares to the national pre-Covid rate of 1%. There was increased risk of death with right heart strain (25/52 vs 128/140[ P < 0.01]) and in critical care (15/29 vs 146/163[ P < 0.01]). Conclusions : In this national study, we have demonstrated an increased risk of pulmonary thromboembolism in both critical care and ward based environments.