Sociodemographic characteristics, comorbidity, and baseline functional status of older patients treated in emergency departments during the COVID-19 pandemic and associations with mortality: an analysis based on the EDENCOVID cohort. / Sociodemografía, comorbilidad y situación funcional basal de los pacientes mayores atendidos en urgencias durante la pandemia de COVID y su relación con la mortalidad: análisis a partir de la cohorte EDEN-Covid.

OBJECTIVES: To describe the sociodemographic characteristics, comorbidity, and baseline functional status of patients aged 65 or older who came to hospital emergency departments (EDs) during the first wave of the COVID-19 pandemic, and to compare them with the findings for an earlier period to analyze factors of the index episode that were related to mortality. MATERIAL AND METHODS: We studied data from the EDEN-COVID cohort (Emergency Department and Elder Needs During COVID-19) of patients aged 65 years or older treated in 40 Spanish EDs on 7 consecutive days. Nine sociodemographic variables, 18 comorbidities, and 7 function variables were registered and compared with the findings for the EDEN cohort of patients included with the same criteria and treated a year earlier in the same EDs. In-hospital mortality was calculated in the 2 cohorts and a multivariable logistic regression model was used to explore associated factors. RESULTS: The EDEN-COVID cohort included 6806 patients with a median age of 78 years; 49% were women. The pandemic cohort had a higher proportion of men, patients covered by the national health care system, patients brought from residential facilities, and patients who arrived in an ambulance equipped for advanced life support. Pandemic-cohort patients more often had diabetes mellitus, chronic kidney disease, and dementia; they less often had connective tissue and thromboembolic diseases. The Barthel and Charlson indices were worse in this period, and cognitive decline was more common. Fewer patients had a history of depression or falls. Eight hundred ninety these patients (13.1%) died, 122 of them in the ED (1.8%); these percentages were lower in the earlier EDEN cohort, at 3.1% and 0.5%, respectively. Independent sociodemographic factors associated with higher mortality were transport by ambulance, older age, male sex, and living in a residential facility. Mortalityassociated comorbidities were neoplasms, chronic kidney disease, and heart failure. The only function variable associated with mortality was the inability to walk independently. A history of falls in the past 6 months was a protective factor. CONCLUSION: The sociodemographic characteristics, comorbidity, and functional status of patients aged 65 years or older who were treated in hospital EDs during the pandemic differed in many ways from those usually seen in this older-age population. Mortality was higher than in the prepandemic period. Certain sociodemographic, comorbidity, and function variables were associated with in-hospital mortality.

OBJETIVO: Investigar sociodemografía, comorbilidad y situación funcional de los pacientes de 65 o más años de edad que consultaron a los servicios de urgencias hospitalarios (SUH) durante la primera oleada epidémica de COVID, compararlas con un periodo previo y ver su relación. METODO: Se utilizaron los datos obtenidos de la cohorte EDEN-Covid (Emergency Department and Elder Needs during COVID) en la que participaron 40 SUH españoles que incluyeron todos los pacientes de $ 65 años atendidos durante 7 días consecutivos. Se analizaron 9 características sociodemográficas, 18 comorbilidades y 7 variables de funcionalidad, que se compararon con las de la cohorte EDEN (Emergency Department and Elder Needs), que contiene pacientes con el mismo criterio de inclusión etario reclutados por los mismos SUH un año antes. Se recogió la mortalidad intrahospitalaria y se investigaron los factores asociados mediante regresión logística multivariable. RESULTADOS: La cohorte EDEN-Covid incluyó 6.806 pacientes (mediana edad: 78 años; 49% mujeres). Hubo más varones, con cobertura sanitaria pública, procedentes de residencia y que llegaron con ambulancia medicalizada que durante el periodo prepandemia. Presentaron más frecuentemente diabetes mellitus, enfermedad renal crónica, enfermedad cerebrovascular y demencia y menos conectivopatías y enfermedad tromboembólica, peores índices de Barthel y Charlson, más deterioro cognitivo y menos antecedentes de depresión o caídas previas. Fallecieron durante el episodio 890 pacientes (13,1%), 122 de ellos en urgencias (1,8%), porcentajes superiores al periodo prepandemia (3,1% y 0,5%, respectivamente). Se asociaron de forma independiente a mayor mortalidad durante el periodo COVID la llegada en ambulancia, mayor edad, ser varón y vivir en residencia como variables sociodemográficas, y neoplasia, enfermedad renal crónica e insuficiencia cardiaca como comorbilidades. La única variable funcional asociada a mortalidad fue no deambular respecto a ser autónomo, y la existencia de caídas los 6 meses previos resultó un factor protector. CONCLUSIONES: La sociodemografía, comorbilidad y funcionalidad de los pacientes de 65 o más años que consultaron en los SUH españoles durante la primera ola pandémica difirieron en muchos aspectos de lo habitualmente observado en esta población. La mortalidad fue mayor a la del periodo prepandémico. Algunos aspectos sociodemográficos, de comorbilidad y funcionales se relacionaron con la mortalidad intrahospitalaria.

Sociodemografía, comorbilidad y situación funcional basal de los pacientes mayores atendidos en urgencias durante la pandemia de COVID y su relación con la mortalidad: análisis a partir de la cohorte EDEN-Covid

Objective. To describe the sociodemographic characteristics, comorbidity, and baseline functional status of patients aged 65 or older who came to hospital emergency departments (EDs) during the first wave of the COVID-19 pandemic, and to compare them with the findings for an earlier period to analyze factors of the index episode that were related to mortality. Methods. We studied data from the EDEN-COVID cohort (Emergency Department and Elder Needs During COVID-19) of patients aged 65 years or older treated in 40 Spanish EDs on 7 consecutive days. Nine sociodemographic variables, 18 comorbidities, and 7 function variables were registered and compared with the findings for the EDEN cohort of patients included with the same criteria and treated a year earlier in the same EDs . In-hospital mortality was calculated in the 2 cohorts and a multivariable logistic regression model was used to explore associated factors. Results. The EDEN-COVID cohort included 6806 patients with a median age of 78 years;49% were women. The pandemic cohort had a higher proportion of men, patients covered by the national health care system, patients brought from residential facilities, and patients who arrived in an ambulance equipped for advanced life support. Pandemic-cohort patients more often had diabetes mellitus, chronic kidney disease, and dementia;they less often had connective tissue and thromboembolic diseases. The Barthel and Charlson indices were worse in this period, and cognitive decline was more common. Fewer patients had a history of depression or falls. Eight hundred ninety these patients (13.1%) died, 122 of them in the ED (1.8%);these percentages were lower in the earlier EDEN cohort, at 3.1% and 0.5%, respectively. Independent sociodemographic factors associated with higher mortality were transport by ambulance, older age, male sex, and living in a residential facility. Mortality- associated comorbidities were neoplasms, chronic kidney disease, and heart failure. The only function variable associated with mortality was the inability to walk independently. A history of falls in the past 6 months was a protective factor. Conclusions. The sociodemographic characteristics, comorbidity, and functional status of patients aged 65 years or older who were treated in hospital EDs during the pandemic differed in many ways from those usually seen in this older-age population. Mortality was higher than in the prepandemic period. Certain sociodemographic, comorbidity, and function variables were associated with in-hospital mortality.

Longitudinal survey of humoral and cellular response to SARS-CoV-2 infection in children.

BACKGROUND: Data regarding humoral and cellular response against SARS-CoV-2 in children are scarce. We analysed seroconversion rate, decrease of anti-RBD IgG antibodies over time and T-cell response in paediatric patients who suffered COVID-19. METHODS: Longitudinal study of paediatric patients COVID-19 diagnosed by positive molecular assay in nasopharyngeal swabs. Blood samples were drawn 1-2 months and 6-7 months after acute infection. Anti-RBD IgG were determined using the Alinity® SARS-CoV-2 IgG II Quant assay (Abbott). Cellular immune response was analysed by T-SPOT® SARS-CoV-2 assay kit (Oxford Immunotec Ltd.). RESULTS: 27/39 (69,2%) patients seroconverted. Despite a significant decrease in antibody levels over time (p < 0,01), no children seroreverted between first and second visits. Only 6/16 (37,2%) children under 6 years-old were seropositive compared to 21/23 (91,3%) over 6 years-old (p < 0,01). Highest antibody levels were found in seropositive younger children (p = 0,036). Thirteen (33,3%) children showed T-cell response. Among participants showing humoral response, no cellular response was detected in 14 (51,9%). CONCLUSIONS: Anti-RBD IgG antibodies persistence at 6-7-months after SARS-CoV-2 infection was observed. A different IgG response was found depending on age. As measured by T-SPOT, most patients did not display cellular response 6-7 months after infection.

SARS-CoV-2 Infection in Children and Adolescents Living With HIV in Madrid.

Multicenter study designed to describe epidemiologic and clinical characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive cases registered among children and adolescents living with HIV (CALWH). SARS-CoV-2 infection was confirmed in 13.3% of CALWH, with all patients presenting mild symptoms, and the outcome was good in all patients. None of the HIV- and antiretroviral treatment-related variables studied were associated with greater infection risk or could be considered protective.

COVID-19 and Autoimmune Liver Diseases.

SARS-CoV-2 infection can trigger autoimmune responses, either by a systemic hyperstimulation of the immune system or molecular mimicry (or both). We here summarize the current knowledges about autoimmune liver diseases (AILDs) and COVID-19, focusing on (a) the risk of SARS-CoV-2 infection in patients affected by AILDs and/or under pharmacological treatment with immunosuppressants; (b) the capability of vaccination against SARS-CoV-2 to trigger autoimmune responses in the liver; and (c) the efficacy of vaccines against SARS-CoV-2 in patients with AILDs. Although unconclusive results have been obtained regarding the risk of being infected by SARS-CoV-2, generally indicating that all patients with chronic liver diseases have the same risk, irrespective of the etiology, the use of immunosuppressants in patients with AILDs seems to be correlated to COVID-19 severity. Few cases of autoimmune hepatitis (AIH) after SARS-CoV-2 vaccination have been reported, all characterized by a complete remission upon steroid treatment, but further evidence is needed to demonstrate the causality assessment. Humoral responses have been observed in patients with AILDs upon vaccination. In conclusion, the link between SARS-CoV-2 infection and AILDs is far to be completely elucidated. In these patients, the use of immunosuppressants has been correlated to an increase of disease severity and lower levels of antibodies upon vaccination.

A Prospective Study of the Serological, Clinical, and Epidemiological Features of a SARS-CoV-2 Positive Pediatric Cohort.

BACKGROUND: SARS-CoV-2 was a global pandemic. Children develop a mild disease and may have a different rate of seroconversion compared to adults. The objective was to determine the number of seronegative patients in a pediatric cohort. We also reviewed the clinical-epidemiological features associated with seroconversion. METHODS: A multicenter prospective observational study during September-November 2020, of COVID-19, confirmed by reverse transcription-polymerase chain reaction. Data were obtained 4-8 weeks after diagnosis. Blood samples were collected to investigate the humoral response, using three different serological methods. RESULTS: A total of 111 patients were included (98 symptomatic), 8 were admitted to hospital, none required an Intensive Care Unit visit. Median age: 88 months (IQR: 24-149). Median time between diagnosis and serological test: 37 days (IQR: 34-44). A total of 19 patients were non-seroconverters when using three serological techniques (17.1%; 95% CI: 10.6-25.4); most were aged 2-10 years (35%, p < 0.05). Univariate analysis yielded a lower rate of seroconversion when COVID-19 confirmation was not present amongst household contacts (51.7%; p < 0.05). CONCLUSIONS: There was a high proportion of non-seroconverters. This is more commonly encountered in childhood than in adults. Most seronegative patients were in the group aged 2-10 years, and when COVID-19 was not documented in household contacts. Most developed a mild disease. Frequently, children were not the index case within the family.

Pre-existing T cell immunity determines the frequency and magnitude of cellular immune response to two doses of mRNA vaccine against SARS-CoV-2.

Little is known about the factors associated with lack of T-cell response to mRNA vaccines against SARS-CoV-2. In a prospective cohort of 61 health care workers (HCWs), 21% and 16% after the first dose of mRNA BNT162b vaccine, and 12% and 7% after the second dose, showed lack of CD4+ and CD8+ T-cell response, respectively. Pre-existing T-cell immunity, due to past infection (46%) or cross-reactive cellular response (26%), was significantly associated with T-cell response in frequency (CD4+ T-cell, 100% vs 82% after two doses; p = 0.049) and in the magnitude of T-cell response during follow up. Furthermore, baseline CD4+ T-cell correlated positively with the titer of specific IgG-antibodies after first and second vaccine dose. Our data demonstrate that cross-reactive T-cells correlate with a better cellular response as well as an enhanced humoral response, and we confirm the close correlation of humoral and cellular response after mRNA vaccination.

Characteristics of Post-ICU and Post-COVID Recovery Clinics in 29 U.S. Health Systems

OBJECTIVES: The multifaceted long-term impairments resulting from critical illness and COVID-19 require interdisciplinary management approaches in the recovery phase of illness. Operational insights into the structure and process of recovery clinics (RCs) from heterogeneous health systems are needed. This study describes the structure and process characteristics of existing and newly implemented ICU-RCs and COVID-RCs in a subset of large health systems in the United States. DESIGN: Cross-sectional survey. SETTING: Thirty-nine RCs, representing a combined 156 hospitals within 29 health systems participated. PATIENTS: None. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: RC demographics, referral criteria, and operating characteristics were collected, including measures used to assess physical, psychologic, and cognitive recoveries. Thirty-nine RC surveys were completed (94% response rate). ICU-RC teams included physicians, pharmacists, social workers, physical therapists, and advanced practice providers. Funding sources for ICU-RCs included clinical billing (n = 20, 77%), volunteer staff support (n = 15, 58%), institutional staff/space support (n = 13, 46%), and grant or foundation funding (n = 3, 12%). Forty-six percent of RCs report patient visit durations of 1 hour or longer. ICU-RC teams reported use of validated scales to assess psychologic recovery (93%), physical recovery (89%), and cognitive recovery (86%) more often in standard visits compared with COVID-RC teams (psychologic, 54%;physical, 69%;and cognitive, 46%). CONCLUSIONS: Operating structures of RCs vary, though almost all describe modest capacity and reliance on volunteerism and discretionary institutional support. ICU- and COVID-RCs in the United States employ varied funding sources and endorse different assessment measures during visits to guide care coordination. Common features include integration of ICU clinicians, interdisciplinary approach, and focus on severe critical illness. The heterogeneity in RC structures and processes contributes to future research on the optimal structure and process to achieve the best postintensive care syndrome and postacute sequelae of COVID outcomes.

Incidence, Clinical Characteristics, Risk Factors, and Outcomes of Upper Gastrointestinal Bleeding in Patients With COVID-19: Results of the UMC-19-S12.

OBJECTIVE: The authors investigated the incidence, risk factors, clinical characteristics, and outcomes of upper gastrointestinal bleeding (UGB) in patients with coronavirus disease 2019 (COVID-19), who were attending the emergency department (ED), before hospitalization. METHODS: We retrospectively reviewed all COVID-19 patients diagnosed with UGB in 62 Spanish EDs (20% of Spanish EDs, case group) during the first 2 months of the COVID-19 outbreak. We formed 2 control groups: COVID-19 patients without UGB (control group A) and non-COVID-19 patients with UGB (control group B). Fifty-three independent variables and 4 outcomes were compared between cases and controls. RESULTS: We identified 83 UGB in 74,814 patients with COVID-19 who were attending EDs (1.11%, 95% CI=0.88-1.38). This incidence was lower compared with non-COVID-19 patients [2474/1,388,879, 1.78%, 95% confidence interval (CI)=1.71-1.85; odds ratio (OR)=0.62; 95% CI=0.50-0.77]. Clinical characteristics associated with a higher risk of COVID-19 patients presenting with UGB were abdominal pain, vomiting, hematemesis, dyspnea, expectoration, melena, fever, cough, chest pain, and dysgeusia. Compared with non-COVID-19 patients with UGB, COVID-19 patients with UGB more frequently had fever, cough, expectoration, dyspnea, abdominal pain, diarrhea, interstitial lung infiltrates, and ground-glass lung opacities. They underwent fewer endoscopies in the ED (although diagnoses did not differ between cases and control group B) and less endoscopic treatment. After adjustment for age and sex, cases showed a higher in-hospital all-cause mortality than control group B (OR=2.05, 95% CI=1.09-3.86) but not control group A (OR=1.14, 95% CI=0.59-2.19) patients. CONCLUSIONS: The incidence of UGB in COVID-19 patients attending EDs was lower compared with non-COVID-19 patients. Digestive symptoms predominated over respiratory symptoms, and COVID-19 patients with UGB underwent fewer gastroscopies and endoscopic treatments than the general population with UGB. In-hospital mortality in COVID-19 patients with UGB was increased compared with non-COVID patients with UGB, but not compared with the remaining COVID-19 patients.

A case-control analysis of stroke in COVID-19 patients: Results of unusual manifestations of COVID-19-study 11.

OBJECTIVE: We investigated the incidence, predictor variables, clinical characteristics, and stroke outcomes in patients with COVID-19 seen in emergency departments (EDs) before hospitalization. METHODS: We retrospectively reviewed all COVID-19 patients diagnosed with stroke during the COVID-19 outbreak in 62 Spanish EDs. We formed two control groups: COVID-19 patients without stroke (control A) and non-COVID-19 patients with stroke (control B). We compared disease characteristics and four outcomes between cases and controls. RESULTS: We identified 147 strokes in 74,814 patients with COVID-19 seen in EDs (1.96‰, 95% confidence interval [CI] = 1.66‰ to 2.31‰), being lower than in non-COVID-19 patients (6,541/1,388,879, 4.71‰, 95% CI = 4.60‰ to 4.83‰; odds ratio [OR] = 0.42, 95% CI = 0.35 to 0.49). The estimated that standardized incidences of stroke per 100,000 individuals per year were 124 and 133 for COVID-19 and non-COVID-19 individuals, respectively (OR = 0.93 for COVID patients, 95% CI = 0.87 to 0.99). Baseline characteristics associated with a higher risk of stroke in COVID-19 patients were hypertension, diabetes mellitus, and previous cerebrovascular and coronary diseases. Clinically, these patients more frequently presented with confusion, decreased consciousness, and syncope and higher D-dimer concentrations and leukocyte count at ED arrival. After adjustment for age and sex, the case group had higher hospitalization and intensive care unit (ICU) admission rates (but not mortality) than COVID-19 controls without stroke (OR = 3.41, 95% CI = 1.27 to 9.16; and OR = 3.79, 95% CI = 1.69 to 8.50, respectively) and longer hospitalization and greater in-hospital mortality than stroke controls without COVID-19 (OR = 1.55, 95% CI = 1.24 to 1.94; and OR = 1.77, 95% CI = 1.37 to 2.30, respectively). CONCLUSIONS: The incidence of stroke in COVID-19 patients presenting to EDs was lower than that in the non-COVID-19 reference sample. COVID-19 patients with stroke had greater need for hospitalization and ICU admission than those without stroke and longer hospitalization and greater in-hospital mortality than non-COVID-19 patients with stroke.

Statistical analysis plan for the Surgery for Cancer with Option of Palliative Care Expert (SCOPE) trial: a randomized controlled trial of a specialist palliative care intervention for patients undergoing surgery for cancer.

BACKGROUND: The impact of specialist palliative care intervention in patients undergoing surgery for cancer has not been studied extensively. The SCOPE randomized controlled trial will investigate the effect of specialist palliative care intervention in cancer patients undergoing surgery for selected abdominal malignancies. The study protocol of the SCOPE Trial was published in December 2019. METHODS AND DESIGN: The SCOPE Trial is a single-center, single-blind, prospective, randomized controlled trial that will investigate specialist palliative care intervention for cancer patients undergoing surgery for selected abdominal malignancies. The study plans to enroll 236 patients that will be randomized to specialist palliative care (intervention arm) and usual care (control arm) in a 1:1 ratio. RESULTS: The primary outcome of the study is the Functional Assessment of Cancer Therapy-General (FACT-G) Trial Outcome Index (TOI) at 90 days postoperatively. Secondary outcomes of the study include the total FACT-G score at 90 days postoperatively, days alive at home without an emergency room visit within 90 days of operation, and all-cause mortality at 1 year after operation. Time frames for all outcomes will start on the day of surgery. CONCLUSION: This manuscript serves as the formal statistical analysis plan (version 1.0) for the SCOPE randomized controlled trial. The statistical analysis plan was completed on 6 April 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT03436290 . Registered on 16 February 2018.

Impact of in-hospital discontinuation with angiotensin receptor blockers or converting enzyme inhibitors on mortality of COVID-19 patients: a retrospective cohort study.

BACKGROUND: In the first wave of the COVID-19 pandemic, the hypothesis that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) increased the risk and/or severity of the disease was widely spread. Consequently, in many hospitals, these drugs were discontinued as a "precautionary measure". We aimed to assess whether the in-hospital discontinuation of ARBs or ACEIs, in real-life conditions, was associated with a reduced risk of death as compared to their continuation and also to compare head-to-head the continuation of ARBs with the continuation of ACEIs. METHODS: Adult patients with a PCR-confirmed diagnosis of COVID-19 requiring admission during March 2020 were consecutively selected from 7 hospitals in Madrid, Spain. Among them, we identified outpatient users of ACEIs/ARBs and divided them in two cohorts depending on treatment discontinuation/continuation at admission. Then, they were followed-up until discharge or in-hospital death. An intention-to-treat survival analysis was carried out and hazard ratios (HRs), and their 95%CIs were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators. RESULTS: Out of 625 ACEI/ARB users, 340 (54.4%) discontinued treatment. The in-hospital mortality rates were 27.6% and 27.7% in discontinuation and continuation cohorts, respectively (HR=1.01; 95%CI 0.70-1.46). No difference in mortality was observed between ARB and ACEI discontinuation (28.6% vs. 27.1%, respectively), while a significantly lower mortality rate was found among patients who continued with ARBs (20.8%, N=125) as compared to those who continued with ACEIs (33.1%, N=136; p=0.03). The head-to-head comparison (ARB vs. ACEI continuation) yielded an adjusted HR of 0.52 (95%CI 0.29-0.93), being especially notorious among males (HR=0.34; 95%CI 0.12-0.93), subjects older than 74 years (HR=0.46; 95%CI 0.25-0.85), and patients with obesity (HR=0.22; 95%CI 0.05-0.94), diabetes (HR=0.36; 95%CI 0.13-0.97), and heart failure (HR=0.12; 95%CI 0.03-0.97). CONCLUSIONS: The discontinuation of ACEIs/ARBs at admission did not improve the in-hospital survival. On the contrary, the continuation with ARBs was associated with a trend to a reduced mortality as compared to their discontinuation and to a significantly lower mortality risk as compared to the continuation with ACEIs, particularly in high-risk patients.

Effect and safety of combination of interferon alpha-2b and gamma or interferon alpha-2b for negativization of SARS-CoV-2 viral RNA. Preliminary results of a randomized controlled clinical trial. (preprint)

Abstract Objectives: IFN-alpha2b and IFN-gamma combination has demonstrated favorable pharmacodynamics for genes underlying antiviral activity which might be involved in the defense of the organism from a SARS-CoV-2 infection. Considering this we conducted a randomized controlled clinical trial for efficacy and safety evaluation of subcutaneous IFN-alpha2b and IFN-gamma administration in patients positive to SARS-CoV-2. Methods: We enrolled 19-82 years-old inpatients at the Military Central Hospital Luis Diaz Soto, Havana, Cuba. They were hospitalized after confirmed diagnosis for SARS-CoV-2 RNA by real-time reverse transcription polymerase chain reaction. Patients were randomly assigned in a 1:1 ratio to receive either, subcutaneous treatment with a co-lyophilized combination of 3.0 MIU IFN-alpha2b and 0.5 MIU IFN-gamma (HeberFERON, CIGB, Havana, Cuba), twice a week for two weeks, or thrice a week intramuscular injection of 3.0 MIU IFN-alpha2b (Heberon Alpha R, CIGB, Havana, Cuba). Additionally, all patients received lopinavir-ritonavir 200/50 mg every 12 h and chloroquine 250 mg every 12 h (standard of care). The primary endpoints were the time to negativization of viral RNA and the time to progression to severe COVID-19, from the start of treatment. The protocol was approved by the Ethics Committee on Clinical Investigation from the Hospital and the Center for the State Control of Medicines, Equipment and Medical Devices in Cuba. Informed consent was obtained from each participant. Results: A total of 79 patients with laboratory-confirmed SARS-CoV-2 infection, including symptomatic or asymptomatic conditions, fulfilled the inclusion criteria and underwent randomization. Thirty-three subjects were assigned to the HeberFERON group, and 33 to the Heberon Alpha R group. Sixty-three patients were analyzed for viral negativization, of them 78.6% in the HeberFERON group negativized the virus after 4 days of treatment versus 40.6% of patients in the Heberon Alpha R groups (p=0.004). Time to reach the negativization of the SARS-CoV-2 measured by RT-PCR in real time was of 3.0 and 5.0 days for the HeberFERON and Heberon Alpha R groups, respectively. A significant improvement in the reduction of time for negativization was attributable to HeberFERON (p=0.0027, Log-rank test) with a Hazard Ratio of 3.2 and 95% CI of 1.529 to 6.948, as compared to Heberon Alpha R treated group. Worsening of respiratory symptoms was detected in two (6.6%) and one (3.3%) patients in HeberFERON and IFN-alpha2b groups, respectively. None of the subjects transit to severe COVID-19 during the study or the epidemiological follow-up for 21 more days. RT-PCR on day 14 after the start of the treatment was negative to SARS-CoV-2 in 100% and 91% of patients of the combination of IFNs and IFN-alpha2b, respectively. Negativization for HeberFERON treated patients was related to a significant increase in lymphocytes counts and an also significant reduction in CRP as early as 7 days after commencing the therapeutic schedule. All the patients in both cohorts recover by day 14 and were in asymptomatic condition and laboratory parameters return to normal values by day 14 after treatment initiation. Adverse events were identified in 31.5% of patients, 28.5% in the control group, and 34.4% in the HeberFERON group, and the most frequent were headaches (17.4%). Conclusions: In a cohort of 63 hospitalized patients between 19 to 82 years-old with positive SARS-CoV-2, HeberFERON significantly negativized the virus on day 4 of treatment when comparing with IFN-alpha2b. Heberon Alpha R also showed efficacy for the treatment of the viral infection. Both treatments were safe and positively impact on the resolution of the symptoms. None of the patients developed severe COVID-19. Key words: COVID-19, treatment, drug, virus negativization, antiviral, interferon combination, SARS CoV-2.

Use of renin angiotensin aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study

BackgroundConcerns have been raised about the possibility that inhibitors of the renin?angiotensin?aldosterone system (RAAS) could predispose individuals to severe COVID-19;however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19.

The Elabela-APJ axis: a promising therapeutic target for heart failure.

Heart failure (HF) is a growing epidemic with high morbidity and mortality at an international scale. The apelin-APJ receptor pathway has been implicated in HF, making it a promising therapeutic target. APJ has been shown to be activated by a novel endogenous peptide ligand known as Elabela (ELA, also called Toddler or Apela), with a critical role in cardiac development and function. Activation of the ELA-APJ receptor axis exerts a wide range of physiological effects, including depressor response, positive inotropic action, diuresis, anti-inflammatory, anti-fibrotic, and anti-remodeling, leading to its cardiovascular protection. The ELA-APJ axis is essential for diverse biological processes and has been shown to regulate fluid homeostasis, myocardial contractility, vasodilation, angiogenesis, cellular differentiation, apoptosis, oxidative stress, cardiorenal fibrosis, and dysfunction. The beneficial effects of the ELA-APJ receptor system are well-established by treating hypertension, myocardial infarction, and HF. Additionally, administration of ELA protects human embryonic stem cells against apoptosis and stress-induced cell death and promotes survival and self-renewal in an APJ-independent manner (X receptor) via the phosphatidylinositol 3-kinase/Akt pathway, which may provide a new therapeutic approach for HF. Thus, targeting the ELA-APJ axis has emerged as a pre-warning biomarker and a novel therapeutic approach against progression of HF. An increased understanding of cardiovascular actions of ELA will help to develop effective interventions. This article gives an overview of the characteristics of the ELA-apelin-APJ axis and summarizes the current knowledge on its cardioprotective roles, potential mechanisms, and prospective application for acute and chronic HF.