Hydroxychloroquine and Mortality in SARS-Cov-2 Infection;the HOPE-Covid-19 Registry

Background: Hydroxychloroquine (HCQ) may be an effective, safe, and affordable treatment for Covid-19 that can be used in selected patients. However, more evidence on its association when it is used in different stages of the disease with clinical outcomes is required. This observational study investigates the association between treatment with HCQ and mortality in patients with Covid-19. Method(s): The data from 6217 patients who died or were discharged from 24 Spanish hospitals were analyzed. Propensity matching scores (PMS) were used. Result(s): 5094 patients received HCQ. Death was recorded for 17.5% of those who had HCQ and 34.1% of those who did not have it. Mortality was lower for those who had HCQ, OR=0.41 (95% CI=0.34-0.48). The PMS analysis also showed that mortality was lower for those receiving HCQ, OR=0.47 (95%CI=0.36-0.62). PMS analysis for categories revealed an association between HCQ and lowered mortality for patients over 65 years of age, with a past medical history of hypertension, for those who were diagnosed during admission with sepsis related organ failure or pneumonia, and for those with lymphocytopenia, raised troponin, LDH, ferritin and D-dimer. No increase in mortality associated with HCQ was observed in any category of any of the variables investigated. Conclusion(s): HCQ could be associated with lower mortality for older patients, those with more severe disease and raised inflammatory markers. Further RCTs, observational studies, and summaries of both types of evidence on this topic are necessary to select the precise profile of patients that may benefit from HCQ.Copyright © 2023 Bentham Science Publishers.

Consensus statement of the Colombian Association of Critical Medicine and Intensive Care (AMCI) for the care and management of the paediatric patient with suspicion or confirmation of severe infection by SARS-CoV-2

A new pandemic was recently declared by the World Health Organisation due to the SARS-CoV-2 virus. This virus is characterised by being highly transmissible, lethal, and affecting all age groups. This declaration led to the activation, in all countries, of emergency mechanisms to deal with this public health crisis that has exposed the weaknesses of the health systems and the deficit of beds in adult intensive care (UCIA) and paediatric intensive care units (PICU). Colombia has a reduced number of PICU beds compared to other low- and middle-income countries. For this reason, we must optimise resources, anticipate severe cases, and understand the behaviour of the disease caused by the SARS-CoV-2 virus (called COVID-19) in paediatrics, especially in severe forms of presentation in children. The severity and degree of involvement by the virus in all countries has been very similar, with a greater severity and frequency of infection in the adult population, particularly in people over 60 years of age, and with comorbidities (obesity, hypertension, diabetes, among others). However, severe cases requiring advanced interventions in intensive care have also been reported in the paediatric population, including a form of presentation with a large inflammatory response in children, called multi-systemic inflammatory syndrome (MIS-C). The Colombian Association of Critical Medicine and Intensive Care (AMCI) convened a multidisciplinary team of experts in paediatric critical medicine to establish a consensus statement of good clinical practice for the care of children with severe COVID-19 requiring care in intermediate care or paediatric intensive care. The objective of this consensus statement is to facilitate and standardise decision making in the most relevant aspects of care and to carry out a comprehensive approach to the paediatric patient based on the best available evidence and the opinion of experts in paediatric intensive care with at least 10 years of work experience in the area. Additionally, it was sought to involve those Paediatric Intensivists who have to directly care for children with COVID-19, and belong to reference or university hospitals and have a proven track record in research and teaching in paediatric critical care. This consensus statement will seek to update, as often as necessary, according to the change in the best available evidence, which will enable physicians who care for critical children with COVID-19 to provide comprehensive and adequate care according to the best available literature. © 2020 Asociación Colombiana de Medicina Crítica y Cuidado lntensivo

BARICITINIB for HIGH-RISK PATIENTS with COVID-19: The PANCOVID RANDOMIZED TRIAL

Background: Recent studies suggest that baricitinib added to dexamethasone may reduce mortality in hospitalized COVID-19 patients requiring supplemental oxygen Methods: In a multicenter open-label, pragmatic, randomized clinical trial in 25 hospitals in Spain we included symptomatic participants with SARS-CoV-2 detected by PCR or antigenic test, with a creatinine clearance >60 mL/min, > 60 years or younger if they had at least two comorbidities (hypertension, obesity, diabetes, cirrhosis, chronic neurologic disease, active cancer, heart failure, coronary heart disease or COPD). Participants were initially randomized to receive or not tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). At any moment during the trial participants with room air 02 saturation < 95% and at least one increased inflammatory biomarker could be randomized to dexamethasone (D) or dexamethasone plus baricitinib (DB). Primary outcome was 28 days mortality. Secondary outcomes were disease progression (increase of O2 requirements, mechanical ventilation or increase in medical therapy: steroid dose, need for starting tocilizumab) Results: Out of the 355 participants included in the trial 287 (80.8%) were randomized to D (n=142) or DB (n=145), 264 (91.9%) simultaneously with the TDF/FTC randomization and 23 (8.1%) later on. Median age 67 years (IQR 62, 73), male (65.5%), with median 8 days of symptoms (IQR 5-10), 28.6% with ≤ 5 days of symptoms, 100% hospitalized, 31.6% with one and 38.7% with ≥ 2 comorbidities (most common: 35.9% hypertension, 9.4% diabetes, 1.7 % obesity), 14.3% receiving remdesivir and 49.1% TDF/FTC. Endpoints in participants treated with D vs. those treated with DB favored DB without achieving statistical significance: mortality 4.9%/2.1%, disease progression 27.5%/24.8%, mechanical ventilation (invasive or noninvasive) 25.4%/23.4%, days since randomization until discharge (median [IQR]) 7 [5, 12]/7 [5, 13.5], discharge before 28 days 89%/94.2%. By Cox regression Hazard Ratio (95% CI) of 28-day mortality was 0.51 (0.13-2.06) for participants treated with DB. Serious adverse events occurred in 9.9%/9.7% of participants treated with D or DB respectively. Adverse events leading to B discontinuation occurred in 3.45% of participants. Conclusion: In this clinical trial of high-risk patients with COVID-19 all disease outcomes favored baricitinb added to dexamethasone but differences did not reach statistical significance. Overall mortality was unexpectedly low.

LINKAGE to CARE and TIME to VIRAL SUPPRESSION in PWH in SPAIN: 2004-2020

Background: For newly diagnosed persons with HIV (PWH), early initiation of ART is essential in reducing morbidity and mortality and decreasing the risk of transmitting HIV. We have previously reported the trends in linkage to HIV medical care within one month of HIV diagnosis (LC-1Mo) and viral suppression within three months of HIV diagnosis (VS-3Mo) among PWH in Spain from 2004 to 2018. We herein update this information up to 2020. Methods: Longitudinal study based on the Cohort of the Spanish AIDS Research Network (CoRIS). VS was defined as ever having an HIV-RNA <200 copies/mL. We used logistic regression to assess differences by sex, age, country of birth, transmission category, and baseline CD4+ cell count. Results: A total of 13,632 PWH were enrolled in CoRIS in the study period: males 85%, men having sex with men (MSM) 62%, median age 35 (IQR: 28-43) years. LC-1Mo increased from 41% (95% CI, 37%-45%) in 2004 to 83% (79%-87%) in 2020 (P trend <0.001) (Figure). Median CD4+ cell counts at ART initiation increased from < 250/mm3 in 2004-2005 to > 350/mm3 since 2012 (P for trend <0.001). The percentage of initial ART regimens based on integrase strand transfer inhibitors (InSTI) increased from 3% in 2004 to > 70% from 2016 onwards (P trend <0.001). VS-3Mo increased from 6% (4%-8%) in 2004 to 43% (40%-47%) in 2019 with a small decrease to 41% (36%-46%) in 2020 (P trend [for the entire period] <0.001) (Figure). The odds of achieving VS-3Mo was higher among females (aOR, 95% CI: 1.30, 1.12-1.51), among non-Spanish Europeans and Latin Americans compared to native-born Spaniards (1.26, 1.11-1.44 and 1.36, 1.21-1.52, respectively), and among those older than 50 years (1.20, 1.03-1.41). Opposite, the odds of achieving VS-3Mo was lower among IDU compared to MSM (0.53, 0.40-0.70) and those with CD4 counts between 200-500 cells/uL (0.78, 0.69-0.89) and CD4 counts >500 cells/uL (0.51, 0.44-0.60) compared to those with CD4 < 200 cells/uL. Conclusion: Indicators of care have improved among newly diagnosed PWH in Spain over the last 16 years. Elimination of CD4 cell count restrictions for ART initiation and increasing use of InSTI-based regimens was decisive for progress. A slight decrease in VS-3Mo in 2020 compared with 2019 was observed, perhaps because of the COVID-19 pandemic.

Learning to teach in mixed-reality simulated virtual environments at a Hispanic Serving Institution (HSI)

As a result of the COVID-19 pandemic, faculty at a Hispanic serving institution shifted from face-to-face to totally online teaching. The authors describe two assignments for teacher candidates that required them to design and deliver lessons that focused on practicing two high-leverage practices utilizing Mursion, a mixed-reality simulation (MRS) software and platform. MRS sessions were delivered through Zoom video conferencing and were delivered asynchronously. Benefits, challenges, and limitations of using MRS in conjunction with Zoom in online courses were identified and discussed. Detailed logistics for planning, preparing, and executing MRS effectively were provided. The authors describe implications for remote learning as it related to teaching at an HSI located in one of the poorest areas of the U.S., with one of the most vulnerable populations. © 2021 by IGI Global. All rights reserved.

Clinical Outcomes of Hospitalized COVID-19 Patients Treated with Remdesivir-NEAT ID 909REM Study

Background. There are few real-world data on the use of remdesivir (RDV) looking at timing of initiation in relation to symptom onset and severity of presenting disease. Methods. We conducted multi-country retrospective study of clinical practice and use of RDV in COVID-19 patients. De-identified medical records data were entered into an e-CRF. Primary endpoints were all-cause mortality at day 28 and hospitalization duration. We assessed time from symptom onset to RDV start and re-admission. We included adults with PCR-confirmed symptomatic COVID-19 who were hospitalized after Aug 31, 2020 and received at least 1 dose of RDV. Descriptive analyses were conducted. Kaplan-Meier methods were used to calculate the mortality rate, LogRank test to compare groups defined by severity of disease. Competing risk regression with discharge and death as competing events was used to estimate duration of hospitalization, and Gray's test to compare the groups. Results. 448 patients in 5 countries (12 sites) were included. Demographics are summarized (table) by 3 disease severity groups at baseline: no supplemental oxygen (NSO), low flow oxygen ≤6 L/min (LFO), and high-flow oxygen > 6L/min (HFO). No demographic differences were found between groups except for the higher percentage of cancer/chemotherapy patients in NSO group. Corticosteroids use was HFO 73.6%, LFO 62.7%, NSO 58.0%. Mortality rate was significantly lower in NSO, and LFO groups compared with HFO (6.2%, 10.2%, 23.6%, respectively;Fig1). Median duration of hospitalization was 9 (95%CI 8-10), 9 (8-9), 13 (10-15) days, respectively (Fig2). Median time from first symptom to RDV start was 7 days in all 3 groups. Patients started RDV on day 1 of hospitalization in HFO and LFO and day 2 on NSO groups. And received a 5 day course (median). Readmission within 28-days of discharge was < 5% and similar across all 3 groups. Conclusion. In this real-world cohort of COVID-19 positive hospitalized patients, RDV use was consistent across countries. RDV was started within a median of 7 days from symptom within 2 days of admission and given for a median of 5 days. Higher mortality rate and duration of hospitalization was seen in the HFO group and similar rates seen in the LFO and NSO groups. Readmission was consistently low across all 3 groups.

Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data Factores pronósticos en pacientes oncológicos con COVID-19 a su llegada a urgencias: Análisis de los datos del registro internacional HOPE

<h4>Background</h4> Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis. <h4>Methods</h4> We aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19). Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19). <h4>Results</h4> 5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65–82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women. The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%). In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85–6.58), heart disease (2.32, 1.47–3.66), liver disease (4.69, 1.94–11.62), partial dependence (2.41, 1.34–4.33), total dependence (7.21, 2.60–21.82), fatigue (1.84, 1.16–2.93), arthromialgias (0.45, 0.26–0.78), SatO2 < 92% (4.58, 2.97–7.17), elevated LDH (2.61, 1.51–4.69) and abnormal decreased Blood Pressure (3.57, 1.81–7.15). Analitical parameters are also significant altered. <h4>Conclusion</h4> In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.

Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data.

BACKGROUND: Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis. METHODS: We aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19).Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19). RESULTS: 5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65-82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women.The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%).In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85-6.58), heart disease (2.32, 1.47-3.66), liver disease (4.69, 1.94-11.62), partial dependence (2.41, 1.34-4.33), total dependence (7.21, 2.60-21.82), fatigue (1.84, 1.16-2.93), arthromialgias (0.45, 0.26-0.78), SatO2 < 92% (4.58, 2.97-7.17), elevated LDH (2.61, 1.51-4.69) and abnormal decreased Blood Pressure (3.57, 1.81-7.15). Analitical parameters are also significant altered. CONCLUSION: In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.

ANTECEDENTES: Trabajos previos parecen coincidir en la mayor mortalidad de los pacientes con cáncer y COVID-19. La identificación de posibles factores pronósticos en el momento del ingreso podría ayudar a identificar a los pacientes con mal pronóstico. MÉTODOS: Nos propusimos explorar las características y la evolución de los pacientes con cáncer y COVID-19 ingresados en un registro internacional multicéntrico (HOPE COVID-19).Nuestro objetivo principal es definir aquellas características que nos permitan identificar a los pacientes con cáncer de peor pronóstico (mortalidad en los 30 días siguientes al diagnóstico de COVID-19). RESULTADOS: En este registro se ha recogido a 5.838 pacientes, de los cuales 770 tenían cáncer entre sus antecedentes. La mortalidad hospitalaria alcanzó a 258 pacientes (33,51%). La mediana fue de 75 años (65-82). En cuanto a la distribución por sexo, el 34,55% de los pacientes eran mujeres (266/770).La distribución por tipo de cáncer: genitourinario 238/745 (31,95%), digestivo 124/745 (16,54%) y hematológico 95/745 (12,75%).En el análisis de regresión multivariante, los factores que se asocian de forma independiente con la mortalidad al ingreso son: insuficiencia renal (OR 3,45; IC 97,5%: 1,85-6,58), cardiopatía (2,32; 1,47-3,66), hepatopatía (4,69; 1,94-11,62), dependencia parcial (2,41; 1,34-4,33), dependencia total (7,21; 2,60-21,82), fatiga (1,84, 1;16-2,93), artromialgias (0,45; 0,26-0,78), SatO2 < 92% (4,58; 2,97-7,17), LDH elevada (2,61; 1,51-4,69) y disminución anormal de la presión arterial (3,57; 1,81-7,15). Los parámetros analíticos también están significativamente alterados. CONCLUSIÓN: En los pacientes con cáncer del registro HOPE, la mortalidad a los 30 días por cualquier causa es elevada y se asocia a factores clínicos fácilmente identificables a su llegada al hospital. La identificación de estos pacientes puede ayudar a iniciar tratamientos más intensivos desde el principio y evaluar el pronóstico de estos pacientes.

Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data.

BACKGROUND: Previous works seem to agree in the higher mortality of cancer patients with COVID-19. Identifying potential prognostic factors upon admission could help identify patients with a poor prognosis. METHODS: We aimed to explore the characteristics and evolution of COVID-19 cancer patients admitted to hospital in a multicenter international registry (HOPE COVID-19). Our primary objective is to define those characteristics that allow us to identify cancer patients with a worse prognosis (mortality within 30 days after the diagnosis of COVID-19). RESULTS: 5838 patients have been collected in this registry, of whom 770 had cancer among their antecedents. In hospital mortality reached 258 patients (33.51%). The median was 75 years (65-82). Regarding the distribution by sex, 34.55% of the patients (266/770) were women. The distribution by type of cancer: genitourinary 238/745 (31.95%), digestive 124/745 (16.54%), hematologic 95/745 (12.75%). In multivariate regression analysis, factors that are independently associated with mortality at admission are: renal impairment (OR 3.45, CI 97.5% 1.85-6.58), heart disease (2.32, 1.47-3.66), liver disease (4.69, 1.94-11.62), partial dependence (2.41, 1.34-4.33), total dependence (7.21, 2.60-21.82), fatigue (1.84, 1.16-2.93), arthromialgias (0.45, 0.26-0.78), SatO2<92% (4.58, 2.97-7.17), elevated LDH (2.61, 1.51-4.69) and abnormal decreased Blood Pressure (3.57, 1.81-7.15). Analitical parameters are also significant altered. CONCLUSION: In patients with cancer from the HOPE registry, 30-day mortality from any cause is high and is associated with easily identifiable clinical factors upon arrival at the hospital. Identifying these patients can help initiate more intensive treatments from the start and evaluate the prognosis of these patients.

Serological Tests in the Detection of SARS-CoV-2 Antibodies

Early detection of SARS-CoV-2 is essential for a timely update of health policies and allocation of resources. Particularly, serological testing may allow individuals with low-risk of being contagious of SARS-CoV-2 to return to daily activities. Both private and academic initiatives have sought to develop serological assays to detect anti-SARS-CoV-2 antibodies. Herein, we compared five different assays in active healthcare personnel exposed to SARS-CoV-2 in a large center in Madrid, Spain, in a retrospective study. Median time lapse between polymerase chain-reaction (PCR) and serological testing was 11 days (7-21). All tests assessed IgM/IgG titers except for Euroimmun (IgA/IgG) and The Binding-Site (IgA/IgM/IgG). The highest concordance rate was observed between Dia.Pro and Euroimmun (75.76%), while it was lowest between The Binding-Site and Euroimmun (44.55%). The Binding-Site assay showed the highest concordance (85.52%) with PCR results. Considering PCR results as reference, Dia.Pro was the most sensitive test, although The Binding-Site assay exhibited the highest area under the curve (AUC;0.85). OrientGene and MAGLUMI tests were performed in a smaller cohort with confirmed infection and thus were not adequate to estimate sensitivity and specificity. The Binding-Site assay presented the best joint sensitivity and specificity among all the tests analyzed in our cohort. Likewise, this serological assay presents a greater repertoire of antibodies and antigen-regions tested, which is why each individual's humoral immunity is more accurately reflected. The better the immunity test, the most adequate the health strategy to take in terms of organization of consultations, surgery, and treatments in vulnerable patients. The three antibody classes (IgG/IgM/IgA) were determined jointly, which translates to an economic impact on healthcare. While their role in the protection status remains elusive, serological tests add a valuable tool in the early management of SARS-CoV-2 after known exposition.

Colombian consensus for the prevention, diagnosis and treatment of thrombotic conditions in adults with COVID-19: applying GRADE Evidence to Decision (EtD) Frameworks

Introduction: recent studies have reported the occurrence of thrombotic phenomena or coagulopathy in patients with COVID-19. There are divergent positions regarding the prevention, diagnosis, and treatment of these phenomena, and current clinical practice is based solely on deductions by extension from retrospective studies, case series, observational studies, and international guidelines developed prior to the pandemic. Objective: to generate a group of recommendations on the prevention, diagnosis and management of thrombotic complications associated with COVID-19. Methods: a rapid guidance was carried out applying the GRADE Evidence to Decision (EtD) frameworks and an iterative participation system, with statistical and qualitative analysis. Results: 31 clinical recommendations were generated focused on: a) Coagulation tests in symptomatic adults with suspected infection or confirmed SARS CoV-2 infection;b) Thromboprophylaxis in adults diagnosed with COVID-19 (Risk scales, thromboprophylaxis for outpatient, in-hospital management, and duration of thromboprophylaxis after discharge from hospitalization), c) Diagnosis and treatment of thrombotic complications, and d) Management of people with previous indication of anticoagulant agents. Conclusions: recommendations of this consensus guide clinical decision-making regarding the prevention, diagnosis, and treatment of thrombotic phenomena in patients with COVID-19, and represent an agreement that will help decrease the dispersion in clinical practices according to the challenge imposed by the pandemic.