Validation of a Prognostic Score to Identify Hospitalized Patients with COVID-19 at Increased Risk for Bleeding.

INTRODUCTION: Hospitalized patients with COVID-19 are at increased risk for venous thromboembolism (VTE), but also for bleeding. We previously derived a prognostic score including four variables (elevated D-dimer, elevated ferritin, critical illness, and therapeutic-dose anticoagulation) that identified those at increased risk for major bleeding. METHODS: We aimed to validate the score in a subsequent cohort of hospitalized patients with COVID-19 receiving standard-, intermediate- or therapeutic doses of VTE prophylaxis. We evaluated its capacity to predict major bleeding, non-major bleeding, and bleeding-related death. RESULTS: The cohort included 972 patients from 29 hospitals, of whom 280 (29%) received standard-; 412 (42%) intermediate-, 157 (16%) therapeutic doses of VTE prophylaxis and 123 (13%) other drugs. Median duration of prophylaxis was 14.7 ± 10.3 days. Major bleeding occurred in 65 patients (6.7%) and non-major bleeding in 67 (6.9%). Thirty patients with major bleeding (46%) died within the first 30 days after bleeding. The prognostic score identified 203 patients (21%) at very low risk, 285 (29%) at low risk, 263 (27%) intermediate-risk and 221 (23%) at high risk for bleeding. Major bleeding occurred in 1.0%, 2.1%, 8.7% and 15.4% of the patients, respectively. Non-major bleeding occurred in 0.5%, 3.5%, 9.5% and 14.2%, respectively. The c-statistics was: 0.74 (95% confidence intervals [CI]: 0.68-0.79) for major bleeding, 0.73 (95% CI: 0.67-0.78) for non-major bleeding and 0.82 (95% CI: 0.76-0.87) for bleeding-related death. CONCLUSIONS: In hospitalized patients with COVID-19, we validated that a prognostic score including 4 easily available items may identify those at increased risk for bleeding.

Impact of comprehensive molecular testing to reduce antibiotic use in community-acquired pneumonia (RADICAP): a randomised, controlled, phase IV clinical trial protocol.

INTRODUCTION: Community-acquired pneumonia (CAP) continues to be a major health problem worldwide and is one of the main reasons for prescribing antibiotics. However, the causative agent is often not identified, resulting in antibiotic overtreatment, which is a key driver of antimicrobial resistance and adverse events. We aim to test the hypothesis that comprehensive molecular testing, compared with routine microbiological testing, would be effective in reducing antibiotic use in patients with CAP. METHODS AND ANALYSIS: We will perform a randomised, controlled, open-label clinical trial with two parallel groups (1:1) at two tertiary hospitals between 2020 and 2022. Non-severely immunosuppressed adults hospitalised for CAP will be considered eligible. Patients will be randomly assigned to receive either the experimental diagnosis (comprehensive molecular testing plus routine microbiological testing) or standard diagnosis (only microbiological routine testing). The primary endpoint will be antibiotic consumption measured as days of antibiotic therapy per 1000 patient-days. Secondary endpoints will be de-escalation to narrower antibiotic treatment, time to switch from intravenous to oral antibiotics, days to reaching an aetiological diagnosis, antibiotic-related side effects, length of stay, days to clinical stability, intensive care unit admission, days of mechanical ventilation, hospital readmission up to 30 days after randomisation and death from any cause by 48 hours and 30 days after randomisation. We will need to include 440 subjects to be able to reject the null hypothesis that both groups have equal days of antibiotic therapy per 1000 patient-days with a probability >0.8. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Ethics Committee of Bellvitge Hospital (AC028/19) and from the Spanish Medicines and Medical Devices Agency, and it is valid for all participating centres under existing Spanish legislation. Results will be presented at international meetings and will be made available to patients, their caregivers and funders. TRIAL REGISTRATION NUMBER: ClinicalTrials: NCT04158492. EudraCT: 2018-004880-29.

Long-term outcomes of patients following hospitalization for coronavirus disease 2019: a prospective observational study.

OBJECTIVES: Few data are available regarding follow up of patients with coronavirus disease 2019 (COVID-19) after their discharge. We aim to describe the long-term outcomes of survivors of hospitalization for COVID-19 followed up first at an outpatient facility and subsequently by telephone. METHODS: Observational prospective study conducted at a tertiary general hospital. Clinical and radiological progression was assessed and data were recorded on a standardized reporting form. Patients were divided into three groups according to Pao2/Fio2 at hospitalization: Pao2/Fio2 >300, Pao2/Fio2 300-200 and Pao2/Fio2 <200. A logistic multivariate regression model was performed to identify factors associated with persistence of symptoms. RESULTS: For facility follow up, 302 individuals were enrolled. Median follow up was 45 days after discharge; 78% (228/294) of patients had COVID-19-related symptoms (53% asthenia, 56% respiratory symptoms) and 40% (122/302) had residual pulmonary radiographic lesions. Pao2/Fio2 <200 was an independent predictor of persistent dyspnoea (OR 1.87, 95% CI 1.38-2.52, p < 0.0001). Pao2/Fio2 >300 was associated with resolution of chest radiographic lesions (OR 0.56, 95% CI 0.42-0.74, p < 0.0001). Fifty per cent of patients required specific medical follow up after the first consultation and were transferred to another physician. A total of 294 patients were contacted for telephone follow up after a median follow-up time of 7 months. Fifty per cent of patients (147/294) still presented symptoms and 49% (145/294) had psychological disorders. Asthenia was identified in 27% (78/294) and dyspnoea in 10% (28/294) of patients independently of Pao2/Fio2. CONCLUSIONS: Patients with COVID-19 require long-term follow up because of the persistence of symptoms; patients with low Pao2/Fio2 during the acute illness require special attention.

Long-term follow-up of patients with venous thromboembolism and COVID-19: Analysis of risk factors for death and major bleeding.

INTRODUCTION: COVID-19 predisposes patients to a higher risk of venous thromboembolism (VTE), although the extent of these implications is unclear and the risk of bleeding has been poorly evaluated. To date, no studies have reported long-term outcomes of patients with COVID-19 and VTE. METHOD: Prospective observational study to evaluate long-term (90 days or more) outcomes of patients diagnosed with VTE (PE, DVT of the extremities, or both) in the setting of COVID-19. The main outcome of the study was a compound of major bleeding and death. RESULTS: The study comprised 100 patients (mean age 65 ± 13.9 years). At the time of VTE diagnosis, 66% patients were hospitalized, 34.8% of them in the ICU. Mean follow-up was 97.9 ± 23.3 days. During the study period, 24% patients died and median time to death was 12 (IQR: 2.25-20.75) days, 11% patients had major bleeding and median time to event was 12 (IQR: 5-16) days. The cause of death was PE in 5% and bleeding in 2% of patients. There were no VTE recurrences. The main study outcome occurred in 29% patients. Risk of death or major bleeding was independently associated with ICU admission (HR 12.2; 95% CI 3.0-48.3), thrombocytopenia (HR 4.5; 95% CI 1.2-16.5), and cancer (HR 21.6; 95% CI 1.8-259). CONCLUSION: In patients with COVID-19 and VTE, mortality and major bleeding were high and almost a third of deaths were VTE-related. The majority of complications occurred in the first 30 days. ICU admission, thrombocytopenia, and cancer are risk factors for poor prognosis.

Widespread sensory neuropathy in diabetic patients hospitalized with severe COVID-19 infection.

AIMS: To characterize the distribution and severity of sensory neuropathy using a portable quantitative sensory testing (QST) device in diabetic patients (DM) hospitalized with severe COVID-19 infection. METHODS: Four patients with diabetes and severe SARS-CoV-2 requiring non-invasive ventilation for a protracted duration underwent clinical, laboratory and radiologic assessment and detailed evaluation of neuropathic symptoms, neurological assessment, QST on the dorsum of the foot and face using NerveCheck Master with assessment of taste and smell. RESULTS: All four subjects developed neuropathic symptoms characterized by numbness in the feet with preserved reflexes. QST confirmed symmetrical abnormality of vibration and thermal thresholds in both lower limbs in all patients and an abnormal heat pain threshold on the face of two patients and altered taste and smell. CONCLUSIONS: Severe COVID-19 infection with hypoxemia is associated with neuropathic symptoms and widespread sensory dysfunction in patients with DM.