Repurposing existing medications for coronavirus disease 2019: protocol for a rapid and living systematic review.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has no confirmed specific treatments. However, there might be in vitro and early clinical data as well as evidence from severe acute respiratory syndrome and Middle Eastern respiratory syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and 4 groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. TRIAL REGISTRATION: PROSPERO 2020 CRD42020175648.

Risk factors for systemic and venous thromboembolism, mortality and bleeding risks in 1125 patients with COVID-19: relationship with anticoagulation status.

AIM: Coronavirus disease 2019 (COVID-19) has been associated with increased mortality and morbidity from thromboembolism, especially venous thromboembolism. There are more limited data for systemic thromboembolism. The present study aimed to investigate the prevalence of systemic and venous thromboembolism as well as major bleeding and mortality in relation to underlying risk factors and the impact of anticoagulation use in hospitalized patients with COVID-19. METHODS AND RESULTS: Patients with COVID-19 admitted to Union Hospital, Wuhan, Hubei, China between January 08, 2020 and April 7, 2020 were enrolled in this retrospective study. Cox proportional hazard models were utilized to determine associated risk factors for clinical events, adjusting for the severity of COVID-19 infection, drug therapies, comorbidities, surgery, and use of antithrombotic drugs. There were 1125 patients (49.9% male; mean age 58 years (standard deviation, SD, 15 years)) with a mean follow-up of 21 (SD 13) days. Approximately 25 (30%) patients with thromboembolism also suffered bleeding events. Age was an independent risk factor for thromboembolism, bleeding events, and death (all p<0.05). After adjusting for the severity of COVID-19 infection, comorbidities, surgery, antiviral drugs, immunomodulators, Chinese herbs, and antithrombotic drugs, low lymphocyte counts (hazard ratio, HR, 95% confidence interval (CI), 1.03, 1.01-1.05, p=0.01) and surgery (HR 2.80, 1.08-7.29, p=0.03) independently predicted the risk for major bleeding, whereas liver dysfunction (HR 4.13, 1.30-13.1, p=0.02) was an independent risk factor for patients with both thromboembolism and bleeding events. CONCLUSIONS: Patients with COVID-19 were at high risk for thromboembolic and bleeding events as well as mortality. The use of anticoagulants, especially parenteral anticoagulants, significantly reduced the risk for composite outcomes of thromboembolism, bleeding events, and death. The presence of AF was a contributor to systemic thromboembolism in COVID-19 patients.

Characteristics and Outcomes in Patients With COVID-19 and Acute Ischemic Stroke: The Global COVID-19 Stroke Registry.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.