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1.
JAMA ; 327(3): 227-236, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1669289

ABSTRACT

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Heparin/administration & dosage , Inpatients , Purinergic P2Y Receptor Antagonists/administration & dosage , Aged , Aged, 80 and over , Anticoagulants/adverse effects , COVID-19/blood , COVID-19/mortality , Clopidogrel/administration & dosage , Clopidogrel/adverse effects , Comorbidity , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Hemorrhage/chemically induced , Heparin/adverse effects , Hospital Mortality , Humans , Male , Medical Futility , Middle Aged , Outcome Assessment, Health Care , Oxygen Inhalation Therapy/statistics & numerical data , Platelet Activation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Purinergic P2Y Receptor Antagonists/adverse effects , Receptors, Purinergic P2Y12 , Respiration, Artificial/statistics & numerical data , Thrombosis/epidemiology , Ticagrelor/administration & dosage , Ticagrelor/adverse effects , Time Factors , Treatment Outcome
2.
Med Care ; 60(2): 125-132, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1627476

ABSTRACT

BACKGROUND: It is not yet known whether socioeconomic factors (ie, social determinants of health) are associated with readmission following hospitalization for coronavirus disease 2019 (COVID-19). METHODS: We conducted a retrospective cohort study of 6191 adult patients hospitalized with COVID-19 in a large New York City safety-net hospital system between March 1 and June 1, 2020. Associations between 30-day readmission and selected demographic characteristics, socioeconomic factors, prior health care utilization, and relevant features of the index hospitalization were analyzed using a multivariable generalized estimating equation model. RESULTS: The readmission rate was 7.3%, with a median of 7 days between discharge and readmission. The following were risk factors for readmission: age 65 and older [adjusted odds ratio (aOR): 1.32; 95% confidence interval (CI): 1.13-1.55], history of homelessness, (aOR: 2.03 95% CI: 1.49-2.77), baseline coronary artery disease (aOR: 1.68; 95% CI: 1.34-2.10), congestive heart failure (aOR: 1.34; 95% CI: 1.20-1.49), cancer (aOR: 1.68; 95% CI: 1.26-2.24), chronic kidney disease (aOR: 1.74; 95% CI: 1.46-2.07). Patients' sex, race/ethnicity, insurance, and presence of obesity were not associated with increased odds of readmission. A longer length of stay (aOR: 0.98; 95% CI: 0.97-1.00) and use of noninvasive supplemental oxygen (aOR: 0.68; 95% CI: 0.56-0.83) was associated with lower odds of readmission. Upon readmission, 18.4% of patients required intensive care, and 13.7% expired. CONCLUSION: We have found some factors associated with increased odds of readmission among patients hospitalized with COVID-19. Awareness of these risk factors, including patients' social determinants of health, may ultimately help to reduce readmission rates.


Subject(s)
COVID-19/epidemiology , COVID-19/therapy , Hospitalization/statistics & numerical data , Patient Readmission/statistics & numerical data , Safety-net Providers/statistics & numerical data , Adult , Aged , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , New York City/epidemiology , Odds Ratio , Oxygen Inhalation Therapy/statistics & numerical data , Retrospective Studies , Risk Factors , SARS-CoV-2 , Socioeconomic Factors
4.
BMC Anesthesiol ; 21(1): 291, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1528676

ABSTRACT

BACKGROUND: Older adults have an increased risk of mortality from Coronavirus disease 2019 (Covid-19). Despite the high number of publications on the topic of Covid-19 pandemic, few studies have focused on the intensive care treatments of Covid-19 patients aged 80 years and older. The goal of our study is to investigate the effect of the intensive care treatments on the mortality of Covid-19 patients aged 80 years and older based on their clinical features, laboratory findings and the intensive care treatments methods. METHODS: The data of 174 patients aged 80 years and older treated from Covid-19 in intensive care unit were assessed retrospectively. The patients were divided into two groups as survivor and non-survivor. The effects of age, gender, length of stay, comorbid diseases, laboratory values, thoracic computed tomography findings, having invasive mechanical ventilation (IMV), high flow nasal cannula (HFNC) and/or non-invasive mechanical ventilation (NIMV), hemodiafiltration (HDF), anti-cytokines and plasma therapy on mortality have been investigated. RESULTS: The mean age and mean values of CRP, PCT, Ferritin, LDH were statistically significantly high in the non-survivor group. The mortality rate of the patients who had IMV was also statistically significantly higher compared to patients who had HFNC and/or NIMV. Albumin level and the rate of treatment with HFNC and/or NIMV were statistically significantly low in non-survivor group compared to the Survivor group. CONCLUSION: ICU treatments may be beneficial for the Covid-19 patients aged 80 years and older. Increased age, high levels of CRP, PCT, ferritin, and having IMV are detected as poor outcome markers.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Critical Care/methods , Geriatric Assessment/methods , Age Factors , Aged, 80 and over , COVID-19/diagnostic imaging , Female , Geriatric Assessment/statistics & numerical data , Hemodiafiltration/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Male , Oxygen Inhalation Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2 , Sex Factors , Tomography, X-Ray Computed , Turkey
7.
Rheumatology (Oxford) ; 60(1): 399-407, 2021 01 05.
Article in English | MEDLINE | ID: covidwho-1388014

ABSTRACT

OBJECTIVES: The Janus kinase (JAK) inhibitor baricitinib may block viral entry into pneumocytes and prevent cytokine storm in patients with SARS-CoV-2 pneumonia. We aimed to assess whether baricitinib improved pulmonary function in patients treated with high-dose corticosteroids for moderate to severe SARS-CoV-2 pneumonia. METHODS: This observational study enrolled patients with moderate to severe SARS-CoV-2 pneumonia [arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (FiO2) <200 mmHg] who received lopinavir/ritonavir and HCQ plus either corticosteroids (CS group, n = 50) or corticosteroids and baricitinib (BCT-CS group, n = 62). The primary end point was the change in oxygen saturation as measured by pulse oximetry (SpO2)/FiO2 from hospitalization to discharge. Secondary end points included the proportion of patients requiring supplemental oxygen at discharge and 1 month later. Statistics were adjusted by the inverse propensity score weighting (IPSW). RESULTS: A greater improvement in SpO2/FiO2 from hospitalization to discharge was observed in the BCT-CS vs CS group (mean differences adjusted for IPSW, 49; 95% CI: 22, 77; P < 0.001). A higher proportion of patients required supplemental oxygen both at discharge (62.0% vs 25.8%; reduction of the risk by 82%, OR adjusted for IPSW, 0.18; 95% CI: 0.08, 0.43; P < 0.001) and 1 month later (28.0% vs 12.9%, reduction of the risk by 69%, OR adjusted for IPSW, 0.31; 95% CI: 0.11, 0.86; P = 0.024) in the CS vs BCT-CS group. CONCLUSIONS: . In patients with moderate to severe SARS-CoV-2 pneumonia a combination of baricitinib with corticosteroids was associated with greater improvement in pulmonary function when compared with corticosteroids alone. TRIAL REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance, ENCEPP (EUPAS34966, http://www.encepp.eu/encepp/viewResource.htm? id = 34967).


Subject(s)
Azetidines/therapeutic use , COVID-19/drug therapy , Glucocorticoids/therapeutic use , Hypoxia/therapy , Janus Kinase Inhibitors/therapeutic use , Methylprednisolone/therapeutic use , Oxygen Inhalation Therapy/statistics & numerical data , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Aged , Antiviral Agents/therapeutic use , COVID-19/metabolism , COVID-19/physiopathology , Cohort Studies , Drug Combinations , Drug Therapy, Combination , Endothelium, Vascular , Enzyme Inhibitors/therapeutic use , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interferon beta-1b/therapeutic use , Lopinavir/therapeutic use , Lung/blood supply , Male , Middle Aged , Oximetry , Prospective Studies , Ritonavir/therapeutic use , SARS-CoV-2 , Severity of Illness Index
8.
Med Intensiva (Engl Ed) ; 45(6): 325-331, 2021.
Article in English | MEDLINE | ID: covidwho-1343315

ABSTRACT

OBJECTIVE: To describe outcomes of critically ill patients with COVID-19, particularly the association of renal replacement therapy to mortality. DESIGN: A single-center prospective observational study was carried out. SETTING: ICU of a tertiary care center. PATIENTS: Consecutive adults with COVID-19 admitted to the ICU. INTERVENTION: Renal replacement therapy. MAIN VARIABLES OF INTEREST: Demographic data, medical history, illness severity, type of oxygen therapy, laboratory data and use of renal replacement therapy to generate a logistic regression model describing independent risk factors for mortality. RESULTS: Of the total of 166 patients, 51% were mechanically ventilated and 26% required renal replacement therapy. The overall hospital mortality rate was 36%, versus 56% for those requiring renal replacement therapy, and 68% for those with both mechanical ventilation and renal replacement therapy. The logistic regression model identified four independent risk factors for mortality: age (adjusted OR 2.8 [95% CI 1.8-4.4] for every 10-year increase), mechanical ventilation (4.2 [1.7-10.6]), need for continuous venovenous hemofiltration (2.3 [1.3-4.0]) and C-reactive protein (1.1 [1.0-1.2] for every 10mg/L increase). CONCLUSIONS: In our cohort, acute kidney injury requiring renal replacement therapy was associated to a high mortality rate similar to that associated to the need for mechanical ventilation, while multiorgan failure necessitating both techniques implied an extremely high mortality risk.


Subject(s)
Acute Kidney Injury/therapy , COVID-19/complications , Critical Illness/therapy , Renal Replacement Therapy , SARS-CoV-2 , Acute Kidney Injury/etiology , Acute Kidney Injury/mortality , Adrenal Cortex Hormones/therapeutic use , Adult , Age Factors , Aged , C-Reactive Protein/analysis , COVID-19/blood , Comorbidity , Continuous Renal Replacement Therapy , Critical Illness/mortality , District of Columbia/epidemiology , Female , Hospital Mortality , Hospitals, University/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Multiple Organ Failure/etiology , Multiple Organ Failure/mortality , Oxygen Inhalation Therapy/statistics & numerical data , Procedures and Techniques Utilization/statistics & numerical data , Prospective Studies , Renal Replacement Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Risk Factors , Tertiary Care Centers/statistics & numerical data , Treatment Outcome
9.
Arthritis Rheumatol ; 73(9): 1713-1719, 2021 09.
Article in English | MEDLINE | ID: covidwho-1326753

ABSTRACT

OBJECTIVE: COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID-19. We undertook this study to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. METHODS: A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death. RESULTS: The cohort included 65 patients with systemic vasculitis who developed COVID-19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1-14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9-38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes. CONCLUSION: In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision-making relating to the risk of severe COVID-19 in this vulnerable patient group.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Glucocorticoids/therapeutic use , Immunosuppressive Agents/therapeutic use , Oxygen Inhalation Therapy/statistics & numerical data , Respiration, Artificial/statistics & numerical data , Systemic Vasculitis/drug therapy , Aged , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/drug therapy , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/epidemiology , Comorbidity , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Odds Ratio , Registries , Respiratory Tract Diseases/epidemiology , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Systemic Vasculitis/epidemiology
10.
PLoS One ; 16(7): e0254580, 2021.
Article in English | MEDLINE | ID: covidwho-1315888

ABSTRACT

Patients hospitalized with COVID-19 infection are at a high general risk for in-hospital mortality. A simple and easy-to-use model for predicting mortality based on data readily available to clinicians in the first 24 hours of hospital admission might be useful in directing scarce medical and personnel resources toward those patients at greater risk of dying. With this goal in mind, we evaluated factors predictive of in-hospital mortality in a random sample of 100 patients (derivation cohort) hospitalized for COVID-19 at our institution in April and May, 2020 and created potential models to test in a second random sample of 148 patients (validation cohort) hospitalized for the same disease over the same time period in the same institution. Two models (Model A: two variables, presence of pneumonia and ischemia); (Model B: three variables, age > 65 years, supplemental oxygen ≥ 4 L/min, and C-reactive protein (CRP) > 10 mg/L) were selected and tested in the validation cohort. Model B appeared the better of the two, with an AUC in receiver operating characteristic curve analysis of 0.74 versus 0.65 in Model A, but the AUC differences were not significant (p = 0.24. Model B also appeared to have a more robust separation of mortality between the lowest (none of the three variables present) and highest (all three variables present) scores at 0% and 71%, respectively. These brief scoring systems may prove to be useful to clinicians in assigning mortality risk in hospitalized patients.


Subject(s)
COVID-19/mortality , Adult , Age Factors , Aged , C-Reactive Protein/analysis , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Comorbidity , Female , Humans , Male , Middle Aged , Oxygen Inhalation Therapy/statistics & numerical data , Patient Admission/statistics & numerical data , Social Class , Survival Analysis , Survival Rate/trends
11.
Epidemiol Health ; 43: e2021035, 2021.
Article in English | MEDLINE | ID: covidwho-1308497

ABSTRACT

OBJECTIVES: We aimed to examine how comorbidities were associated with outcomes (illness severity or death) among hospitalized patients with coronavirus disease 2019 (COVID-19). METHODS: Data were provided by the National Medical Center of the Korea Disease Control and Prevention Agency. These data included the clinical and epidemiological information of all patients hospitalized with COVID-19 who were discharged on or before April 30, 2020 in Korea. We conducted comorbidity network and multinomial logistic regression analyses to identify risk factors associated with COVID-19 disease severity and mortality. The outcome variable was the clinical severity score (CSS), categorized as mild (oxygen treatment not needed), severe (oxygen treatment needed), or death. RESULTS: In total, 5,771 patients were included. In the fully adjusted model, chronic kidney disease (CKD) (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.19 to 5.61) and chronic obstructive pulmonary disease (COPD) (OR, 3.19; 95% CI, 1.35 to 7.52) were significantly associated with disease severity. CKD (OR, 5.35; 95% CI, 2.00 to 14.31), heart failure (HF) (OR, 3.15; 95% CI, 1.22 to 8.15), malignancy (OR, 3.38; 95% CI, 1.59 to 7.17), dementia (OR, 2.62; 95% CI, 1.45 to 4.72), and diabetes mellitus (OR, 2.26; 95% CI, 1.46 to 3.49) were associated with an increased risk of death. Asthma and hypertension showed statistically insignificant associations with an increased risk of death. CONCLUSIONS: Underlying diseases contribute differently to the severity of COVID-19. To efficiently allocate limited medical resources, underlying comorbidities should be closely monitored, particularly CKD, COPD, and HF.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Adult , Aged , Aged, 80 and over , Comorbidity , Diabetes Mellitus/epidemiology , Female , Heart Failure/epidemiology , Humans , Hypertension/epidemiology , Logistic Models , Male , Middle Aged , Oxygen Inhalation Therapy/statistics & numerical data , Prevalence , Pulmonary Disease, Chronic Obstructive/epidemiology , Renal Insufficiency, Chronic/epidemiology , Republic of Korea/epidemiology , Risk Factors , SARS-CoV-2 , Severity of Illness Index
12.
Nutrients ; 13(7)2021 Jun 30.
Article in English | MEDLINE | ID: covidwho-1288968

ABSTRACT

Background & Aims: SARS-CoV2 infection is associated with an increased risk of malnutrition. Although there are numerous screening and nutritional management protocols for malnutrition, only few studies have reported nutritional evolution after COVID-19. The objectives of this study were to describe the evolution of nutritional parameters between admission and 30 days after hospital discharge, and to determine predictive factors of poor nutritional outcome after recovery in adult COVID-19 patients. Methods: In this observational longitudinal study, we report findings after discharge in 91 out of 114 patients initially admitted for COVID-19 who received early nutritional management. Nutritional status was defined using GLIM criteria and compared between admission and day 30 after discharge. Baseline predictors of nutritional status at day 30 were assessed using logistic regression. Results: Thirty days after discharge, 28.6% of patients hospitalized for COVID-19 were malnourished, compared to 42.3% at admission. Half of malnourished patients (53%) at admission recovered a normal nutritional status after discharge. Weight trajectories were heterogeneous and differed if patients had been transferred to an intensive care unit (ICU) during hospitalization (p = 0.025). High oxygen requirement during hospitalization (invasive ventilation p = 0.016 (OR 8.3 [1.6-61.2]) and/or oxygen therapy over 5 L/min p = 0.021 (OR 3.2 [1.2-8.9]) were strong predictors of malnutrition one month after discharge. Conclusions: With early nutritional management, most patients hospitalized for COVID-19 improved nutritional parameters after discharge. These findings emphasize the importance of nutritional care in COVID-19 patients hospitalized in medicine departments, especially in those transferred from ICU.


Subject(s)
COVID-19/diet therapy , Hospitalization , Malnutrition/epidemiology , Nutritional Status , Adult , Aged , Aged, 80 and over , Female , Humans , Intensive Care Units , Logistic Models , Longitudinal Studies , Male , Middle Aged , Nutrition Assessment , Nutrition Therapy/methods , Oxygen Inhalation Therapy/statistics & numerical data , Patient Discharge , Risk Factors , SARS-CoV-2 , Severity of Illness Index
13.
J Korean Med Sci ; 36(19): e139, 2021 May 17.
Article in English | MEDLINE | ID: covidwho-1232536

ABSTRACT

BACKGROUND: Some coronavirus disease 2019 (COVID-19) patients initially present with early oxygen demand, requiring more medical resources, and some develop severe conditions, while others worsen later in their clinical course. Whether the nature of the two groups is the same but in the spectrum of different diagnostic time points is not certain. METHODS: Hospitalized COVID-19 patients who needed oxygen therapy from February to November 2020 were included in the study. The patients were divided into early and late groups based on the time when the oxygen requirement occurred. Basic and epidemiologic characteristics were compared. Clinical variables were analyzed in both groups. RESULTS: A total of 164 patients needed oxygen therapy, 94 of whom were in the early group and 70 of whom were in the late group. The early and late groups had similar baseline characteristics except age (median age, 73 vs. 67 years), uncertain exposure history (50% vs. 31.4%) and the time from the onset of illness to admission (median, 5 vs. 2 days). Multivariate analysis showed that age > 65 years (OR, 4.65), symptom onset > 5 days (OR, 9.13) and several clinical manifestations, such as febrile sensation (OR, 6.01), dyspnea (OR, 30.0), C-reactive protein > 1 mg/dL (OR, 7.87) and chest X-ray abnormality (OR, 8.15), were predictive factors in the early group. The early group required more intensive care such as mechanical ventilation care, extracorporeal membrane oxygenation and death (29.8% vs. 14.3%, P = 0.002). CONCLUSION: Older age, especially > 65 years, and a delay of over 5 days from the onset of illness to admission were associated with early oxygen demand in COVID-19 patients. Interventions for earlier diagnosis of elderly people may benefit clinical outcomes.


Subject(s)
COVID-19/therapy , Hospitalization , Oxygen Inhalation Therapy , SARS-CoV-2 , Age Factors , Aged , COVID-19/complications , COVID-19/epidemiology , Critical Care/statistics & numerical data , Dyspnea/etiology , Extracorporeal Membrane Oxygenation/statistics & numerical data , Fever/etiology , Hospital Mortality , Humans , Male , Middle Aged , Oxygen Inhalation Therapy/statistics & numerical data , Prognosis , Retrospective Studies , Risk Factors , Time Factors
15.
Trials ; 22(1): 42, 2021 Jan 11.
Article in English | MEDLINE | ID: covidwho-1021412

ABSTRACT

OBJECTIVES: As of December, 1st, 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, resulted in more than 1 472 917 deaths worldwide and death toll is still increasing exponentially. Many COVID-19 infected people are asymptomatic or experience moderate symptoms and recover without medical intervention. However, older people and those with comorbid hypertension, diabetes, obesity, or heart disease are at higher risk of mortality. Because current therapeutic options for COVID-19 patients are limited specifically for this elderly population at risk, Biophytis is developing BIO101 (20-hydroxyecdysone, a Mas receptor activator) as a new treatment option for managing patients with SARS-CoV-2 infection at the severe stage. The angiotensin converting enzyme 2 (ACE2) serves as a receptor for SARS-CoV-2. Interaction between ACE2 and SARS-CoV2 spike protein seems to alter the function of ACE2, a key player in the renin-angiotensin system (RAS). The clinical picture of COVID-19 includes acute respiratory distress syndrome (ARDS), cardiomyopathy, multiorgan dysfunction and shock, all of which might result from an imbalance of the RAS. We propose that RAS balance could be restored in COVID-19 patients through MasR activation downstream of ACE2 activity, with 20-hydroxyecdysone (BIO101) a non-peptidic Mas receptor (MasR) activator. Indeed, MasR activation by 20-hydroxyecdysone harbours anti-inflammatory, anti-thrombotic, and anti-fibrotic properties. BIO101, a 97% pharmaceutical grade 20-hydroxyecdysone could then offer a new therapeutic option by improving the respiratory function and ultimately promoting survival in COVID-19 patients that develop severe forms of this devastating disease. Therefore, the objective of this COVA study is to evaluate the safety and efficacy of BIO101, whose active principle is 20-hydroxyecdysone, in COVID-19 patients with severe pneumonia. TRIAL DESIGN: Randomized, double-blind, placebo-controlled, multi-centre, group sequential and adaptive which will be conducted in 2 parts. Part 1: Ascertain the safety and tolerability of BIO101 and obtain preliminary indication of the activity of BIO101, in preventing respiratory deterioration in the target population Part 2: Re-assessment of the sample size needed for the confirmatory part 2 and confirmation of the effect of BIO101 observed in part 1 in the target population. The study is designed as group sequential to allow an efficient run-through, from obtaining an early indication of activity to a final confirmation. And adaptive - to allow accumulation of early data and adapt sample size in part 2 in order to inform the final design of the confirmatory part of the trial. PARTICIPANTS: Inclusion criteria 1. Age: 45 and above 2. A confirmed diagnosis of COVID-19 infection, within the last 14 days, prior to randomization, as determined by PCR or other approved commercial or public health assay, in a specimen as specified by the test used. 3. Hospitalized, in observation or planned to be hospitalized due to COVID-19 infection symptoms with anticipated hospitalization duration ≥3 days 4. With evidence of pneumonia based on all of the following: a. Clinical findings on a physical examination b. Respiratory symptoms developed within the past 7 days 5. With evidence of respiratory decompensation that started not more than 4 days before start of study medication and present at screening, meeting one of the following criteria, as assessed by healthcare staff: a. Tachypnea: ≥25 breaths per minute b. Arterial oxygen saturation ≤92% c. A special note should be made if there is suspicion of COVID-19-related myocarditis or pericarditis, as the presence of these is a stratification criterion 6. Without a significant deterioration in liver function tests: a. ALT and AST ≤ 5x upper limit of normal (ULN) b. Gamma-glutamyl transferase (GGT) ≤ 5x ULN c. Total bilirubin ≤ 5×ULN 7. Willing to participate and able to sign an informed consent form (ICF). Or, when relevant, a legally authorized representative (LAR) might sign the ICF on behalf of the study participant 8. Female participants should be: at least 5 years post-menopausal (i.e., persistent amenorrhea 5 years in the absence of an alternative medical cause) or surgically sterile; OR a. Have a negative urine pregnancy test at screening b. Be willing to use a contraceptive method as outlined in inclusion criterion 9 from screening to 30 days after last dose. 9. Male participants who are sexually active with a female partner must agree to the use of an effective method of birth control throughout the study and until 3 months after the last administration of the investigational product. (Note: medically acceptable methods of contraception that may be used by the participant and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, each supplemented with a condom, as well as sterilization and vasectomy). 10. Female participants who are lactating must agree not to breastfeed during the study and up to 14 days after the intervention. 11. Male participants must agree not to donate sperm for the purpose of reproduction throughout the study and until 3 months after the last administration of the investigational product. 12. For France only: Being affiliated with a European Social Security. Exclusion criteria 1. Not needing or not willing to remain in a healthcare facility during the study 2. Moribund condition (death likely in days) or not expected to survive for >7 days - due to other and non-COVID-19 related conditions 3. Participant on invasive mechanical ventilation via an endotracheal tube, or extracorporeal membrane oxygenation (ECMO), or high-flow Oxygen (delivery of oxygen at a flow of ≥16 L/min.). 4. Participant is not able to take medications by mouth (as capsules or as a powder, mixed in water). 5. Disallowed concomitant medication: Consumption of any herbal products containing 20-hydroxyecdysone and derived from Leuzea carthamoides; Cyanotis vaga or Cyanotis arachnoidea is not allowed (e.g. performance enhancing agents). 6. Any known hypersensitivity to any of the ingredients, or excipients of the study medication, BIO101. 7. Renal disease requiring dialysis, or known renal insufficiency (eGFR≤30 mL/min/1.73 m2, based on Cockcroft & Gault formula). 8. In France only: a. Non-affiliation to compulsory French social security scheme (beneficiary or right-holder). b. Being under tutelage or legal guardianship. Participants will be recruited from approximately 30 clinical centres in Belgium, France, the UK, USA and Brazil. Maximum patients' participation in the study will last 28 days. Follow-up of participants discharged from hospital will be performed through post-intervention phone calls at 14 (± 2) and 60 (± 4) days. INTERVENTION AND COMPARATOR: Two treatment arms will be tested in this study: interventional arm 350 mg b.i.d. of BIO101 (AP 20-hydroxyecdysone) and placebo comparator arm 350 mg b.i.d of placebo. Administration of daily dose is the same throughout the whole treatment period. Participants will receive the study medication while hospitalized for up to 28 days or until a clinical endpoint is reached (i.e., 'negative' or 'positive' event). Participants who are officially discharged from hospital care will no longer receive study medication. MAIN OUTCOMES: Primary study endpoint: The proportion of participants with 'negative' events up to 28 days. 'Negative' events are defined as respiratory deterioration and all-cause mortality. For the purpose of this study, respiratory deterioration will be defined as any of the following: Requiring mechanical ventilation (including cases that will not be intubated due to resource restrictions and triage). Requiring extracorporeal membrane oxygenation (ECMO). Requiring high-flow oxygen defined as delivery of oxygen at a flow of ≥16 L/min. Only if the primary endpoint is significant at the primary final analysis the following Key secondary endpoints will be tested in that order: Proportion of participants with events of respiratory failure at Day 28 Proportion of participants with 'positive' events at Day 28. Proportion of participants with events of all-cause mortality at Day 28 A 'positive' event is defined as the official discharge from hospital care by the department due to improvement in participant condition. Secondary and exploratory endpoints: In addition, a variety of functional measures and biomarkers (including the SpO2 / FiO2 ratio, viral load and markers related to inflammation, muscles, tissue and the RAS / MAS pathways) will also be collected. RANDOMIZATION: Randomization is performed using an IBM clinical development IWRS system during the baseline visit. Block-permuted randomization will be used to assign eligible participants in a 1:1 ratio. In part 1, randomization will be stratified by RAS pathway modulator use (yes/no) and co-morbidities (none vs. 1 and above). In Part 2, randomization will be stratified by centre, gender, RAS pathway modulator use (yes/no), co-morbidities (none vs. 1 and above), receiving Continuous Positive Airway Pressure/Bi-level Positive Airway Pressure (CPAP/BiPAP) at study entry (Yes/No) and suspicion of COVID-19 related myocarditis or pericarditis (present or not). BLINDING (MASKING): Participants, caregivers, and the study team assessing the outcomes are blinded to group assignment. All therapeutic units (TU), BIO101 b.i.d. or placebo b.i.d., cannot be distinguished in compliance with the double-blind process. An independent data-monitoring committee (DMC) will conduct 2 interim analyses. A first one based on the data from part 1 and a second from the data from parts 1 and 2. The first will inform about BIO101 safety, to allow the start of recruitment into part 2 followed by an analysis of the efficacydata, to obtain an indication of activity. The second interim analysis will inform about the sample size that will be required for part 2, in order to achieve adequate statistical power. Numbers to be randomised (sample size) Number of participants randomized: up to 465, in total Part 1: 50 (to obtain the proof of concept in COVID-19 patients). Part 2: 310, potentially increased by 50% (up to 465, based on interim analysis 2) (to confirm the effects of BIO101 observed in part 1). TRIAL STATUS: The current protocol Version is V 10.0, dated on 24.09.2020. The recruitment that started on September 1st 2020 is ongoing and is anticipated to finish for the whole study by March2021. TRIAL REGISTRATION: The trial was registered before trial start in trial registries: EudraCT , No. 2020-001498-63, registered May 18, 2020; and Clinicaltrials.gov, identifier NCT04472728 , registered July 15, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/drug therapy , Ecdysterone/therapeutic use , Respiratory Insufficiency/drug therapy , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/physiopathology , Disease Progression , Double-Blind Method , Extracorporeal Membrane Oxygenation/statistics & numerical data , Hospitalization , Humans , Hypoxia/physiopathology , Middle Aged , Mortality , Oxygen Inhalation Therapy/statistics & numerical data , Proto-Oncogene Proteins/metabolism , Randomized Controlled Trials as Topic , Receptors, Coronavirus/metabolism , Receptors, G-Protein-Coupled/metabolism , Renin-Angiotensin System , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/physiopathology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Tachypnea/physiopathology , Treatment Outcome
16.
Glob Health Sci Pract ; 8(4): 858-862, 2020 12 23.
Article in English | MEDLINE | ID: covidwho-1000594

ABSTRACT

Oxygen therapy is an essential medicine and core component of effective hospital systems. However, many hospitals in low- and middle-income countries lack reliable oxygen access-a deficiency highlighted and exacerbated by the coronavirus disease (COVID-19) pandemic. Oxygen access can be challenged by equipment that is low quality and poorly maintained, lack of clinical and technical training and protocols, and deficiencies in local infrastructure and policy environment. We share learnings from 2 decades of oxygen systems work with hospitals in Africa and the Asia-Pacific regions, highlighting practical actions that hospitals can take to immediately expand oxygen access. These include strategies to: (1) improve pulse oximetry and oxygen use, (2) support biomedical engineers to optimize existing oxygen supplies, and (3) expand on existing oxygen systems with robust equipment and smart design. We make all our resources freely available for use and local adaptation.


Subject(s)
COVID-19/epidemiology , Developing Countries , Oxygen Inhalation Therapy/methods , Oxygen Inhalation Therapy/statistics & numerical data , Oxygen/supply & distribution , COVID-19/therapy , Health Services Accessibility , Hospital Administration/statistics & numerical data , Humans , Oximetry , Pandemics , SARS-CoV-2
18.
J Am Heart Assoc ; 9(23): e017580, 2020 12.
Article in English | MEDLINE | ID: covidwho-945087

ABSTRACT

Background We sought to assess the impact and predictors of coronavirus disease 2019 (COVID-19) infection and severity in a cohort of patients with congenital heart disease (CHD) at a large CHD center in New York City. Methods and Results We performed a retrospective review of all individuals with CHD followed at Columbia University Irving Medical Center who were diagnosed with COVID-19 between March 1, 2020 and July 1, 2020. The primary end point was moderate/severe response to COVID-19 infection defined as (1) death during COVID-19 infection; or (2) need for hospitalization and/or respiratory support secondary to COVID-19 infection. Among 53 COVID-19-positive patients with CHD, 10 (19%) were <18 years of age (median age 34 years of age). Thirty-one (58%) had complex congenital anatomy including 10 (19%) with a Fontan repair. Eight (15%) had a genetic syndrome, 6 (11%) had pulmonary hypertension, and 9 (17%) were obese. Among adults, 18 (41%) were physiologic class C or D. For the entire cohort, 9 (17%) had a moderate/severe infection, including 3 deaths (6%). After correcting for multiple comparisons, the presence of a genetic syndrome (odds ratio [OR], 35.82; P=0.0002), and in adults, physiological Stage C or D (OR, 19.38; P=0.002) were significantly associated with moderate/severe infection. Conclusions At our CHD center, the number of symptomatic patients with COVID-19 was relatively low. Patients with CHD with a genetic syndrome and adults at advanced physiological stage were at highest risk for moderate/severe infection.


Subject(s)
COVID-19/complications , COVID-19/therapy , Heart Defects, Congenital/complications , Academic Medical Centers , Adult , Aged , Azithromycin/therapeutic use , Cohort Studies , Female , Genetic Diseases, Inborn/complications , Heart Defects, Congenital/classification , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/therapeutic use , Intubation, Intratracheal/statistics & numerical data , Male , New York City , Oxygen Inhalation Therapy/statistics & numerical data , Retrospective Studies , Severity of Illness Index , Young Adult
19.
Sci Rep ; 10(1): 19765, 2020 11 13.
Article in English | MEDLINE | ID: covidwho-927776

ABSTRACT

This systematic review and meta-analysis investigated the comorbidities, symptoms, clinical characteristics and treatment of COVID-19 patients. Epidemiological studies published in 2020 (from January-March) on the clinical presentation, laboratory findings and treatments of COVID-19 patients were identified from PubMed/MEDLINE and Embase databases. Studies published in English by 27th March, 2020 with original data were included. Primary outcomes included comorbidities of COVID-19 patients, their symptoms presented on hospital admission, laboratory results, radiological outcomes, and pharmacological and in-patient treatments. 76 studies were included in this meta-analysis, accounting for a total of 11,028 COVID-19 patients in multiple countries. A random-effects model was used to aggregate estimates across eligible studies and produce meta-analytic estimates. The most common comorbidities were hypertension (18.1%, 95% CI 15.4-20.8%). The most frequently identified symptoms were fever (72.4%, 95% CI 67.2-77.7%) and cough (55.5%, 95% CI 50.7-60.3%). For pharmacological treatment, 63.9% (95% CI 52.5-75.3%), 62.4% (95% CI 47.9-76.8%) and 29.7% (95% CI 21.8-37.6%) of patients were given antibiotics, antiviral, and corticosteroid, respectively. Notably, 62.6% (95% CI 39.9-85.4%) and 20.2% (95% CI 14.6-25.9%) of in-patients received oxygen therapy and non-invasive mechanical ventilation, respectively. This meta-analysis informed healthcare providers about the timely status of characteristics and treatments of COVID-19 patients across different countries.PROSPERO Registration Number: CRD42020176589.


Subject(s)
COVID-19/epidemiology , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/therapy , COVID-19 Testing/statistics & numerical data , Comorbidity , Drug Utilization/statistics & numerical data , Humans , Hypertension/epidemiology , Oxygen Inhalation Therapy/statistics & numerical data , Tomography, X-Ray Computed/statistics & numerical data
20.
Diabetes Metab ; 47(4): 101208, 2021 07.
Article in English | MEDLINE | ID: covidwho-907088

ABSTRACT

AIM: Previous studies have reported inconsistent results regarding the association between metformin use and clinical outcomes in diabetes mellitus (DM) patients with coronavirus disease 2019 (COVID-19). This study aimed to evaluate the association between metformin use and clinical outcomes in DM patients with COVID-19. METHODS: This retrospective study was based on claims data. All diseases, including COVID-19, were defined using International Classification of Diseases 10th Revision (ICD-10) codes. Patients were divided into three groups depending on metformin use: CON (those not taking DM medication); N-MFOM (those taking DM medications other than metformin); and MFOM (those taking metformin for DM). Ultimately, 1865 patients were included; CON, N-MFOM and MFOM groups comprised 1301, 95 and 469 patients, respectively. RESULTS: Kaplan-Meier analyses showed that MFOM patients had poorer survival rates than those in the CON group, but there were no significant differences in survival rates between MFOM and N-MFOM groups. Multivariate Cox regression analyses revealed more favourable survival in CON than in N-MFOM patients, but there was no statistically significant difference in MFOM vs the other groups. Also, there were no significant differences in rates of use of inotropes, extracorporeal membrane oxygenation, conventional oxygen therapy, high-flow nasal cannulas or mechanical ventilators, nor in the rates of acute kidney injury or cardiac events across all study groups. CONCLUSION: No definite association could be found between metformin use and clinical outcomes, including survival. However, given the disproportionate participant numbers in our groups and small number of events, further studies are needed to determine whether the use of metformin has favourable or unfavourable effects in DM patients with COVID-19.


Subject(s)
COVID-19/therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Acute Kidney Injury/epidemiology , Adult , Aged , COVID-19/complications , COVID-19/mortality , Cardiotonic Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Extracorporeal Membrane Oxygenation/statistics & numerical data , Female , Heart Arrest/epidemiology , Heart Failure/epidemiology , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Myocardial Infarction/epidemiology , Oxygen Inhalation Therapy/statistics & numerical data , Prognosis , Proportional Hazards Models , Respiration, Artificial/statistics & numerical data , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index
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