ABSTRACT
Although COVID-19 has been reported to be associated with high rates of venous thromboembolism (VTE), the risk of VTE and bleeding after hospitalization for COVID-19 remains unclear, and the optimal hospital VTE prevention strategy is not known. We collected retrospective observational data on thrombosis and bleeding in 303 consecutive adult patients admitted to the hospital for at least 24 hours for COVID-19. Patients presenting with VTE on admission were excluded. Data were collected until 90 days after admission or known death by using medical records and an established national VTE network. Maximal level of care was ward based in 78% of patients, with 22% requiring higher dependency care (12% noninvasive ventilation, 10% invasive ventilation). Almost all patients (97.0%) received standard thromboprophylaxis or were already receiving therapeutic anticoagulation (17.5%). Symptomatic image-confirmed VTE occurred in 5.9% of patients during index hospitalization, and in 7.2% at 90 days after admission (23.9% in patients requiring higher dependency care); half the events were isolated segmental or subsegmental defects on lung imaging. Bleeding occurred in 13 patients (4.3%) during index hospitalization (1.3% had major bleeding). The majority of bleeds occurred in patients on the general ward, and 6 patients were receiving treatment-dose anticoagulation, highlighting the need for caution in intensifying standard thromboprophylaxis strategies. Of 152 patients discharged from the hospital without an indication for anticoagulation, 97% did not receive thromboprophylaxis after discharge, and 3% received 7 days of treatment with low molecular weight heparin after discharge. The rate of symptomatic VTE in this group at 42 days after discharge was 2.6%, highlighting the need for large prospective randomized controlled trials of extended thromboprophylaxis after discharge in COVID-19.
Subject(s)
COVID-19/complications , COVID-19/epidemiology , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Aged , Aged, 80 and over , Biomarkers , Blood Coagulation Tests , COVID-19/virology , Diagnostic Imaging/methods , Disease Management , Disease Susceptibility , England/epidemiology , Female , Follow-Up Studies , Hospitalization , Humans , Incidence , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Symptom Assessment , Time Factors , Venous Thromboembolism/diagnosis , Venous Thromboembolism/prevention & controlABSTRACT
BACKGROUND: This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults. METHODS: We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (nâ¯=â¯6; ChAdOx1 85A alone), high dose groups; Group A (nâ¯=â¯12; ChAdOx1 85A), Group B (nâ¯=â¯12; ChAdOx1 85A prime - MVA85A boost) or Group C (nâ¯=â¯12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs). Immunogenicity was measured by antigen-specific ex-vivo IFN-γ ELISpot, IgG serum ELISA, and antigen-specific intracellular IFN-γ, TNF-α, IL-2 and IL-17. RESULTS: AEs were mostly mild/moderate, with no Serious Adverse Events. ChAdOx1 85A induced Ag85A-specific ELISpot and intracellular cytokine CD4+ and CD8+ T cell responses, which were not boosted by a second dose, but were boosted with MVA85A. Polyfunctional CD4+ T cells (IFN-γ, TNF-α and IL-2) and IFN-γ+, TNF-α+ CD8+ T cells were induced by ChAdOx1 85A and boosted by MVA85A. ChAdOx1 85A induced serum Ag85A IgG responses which were boosted by MVA85A. CONCLUSION: A ChAdOx1 85A prime - MVA85A boost is well tolerated and immunogenic in healthy UK adults.