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1.
Frontiers in cardiovascular medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1824169

ABSTRACT

Background Studies examining outcomes among individuals with COronaVIrus Disease 2019 (COVID-19) have consistently demonstrated that men have worse outcomes than women, with a higher incidence of myocardial injury, respiratory failure, and death. However, mechanisms of higher morbidity and mortality among men remain poorly understood. We aimed to identify mediators of the relationship between sex and COVID-19-associated mortality. Methods Patients hospitalized at two quaternary care facilities, New York Presbyterian Hospital (CUIMC/NYPH) and Massachusetts General Hospital (MGH), for SARS-CoV-2 infection between February and May 2020 were included. Five independent biomarkers were identified as mediators of sex effects, including high-sensitivity cardiac troponin T (hs-cTNT), high sensitivity C-reactive protein (hs-CRP), ferritin, D-dimer, and creatinine. Results In the CUIMC/NYPH cohort (n = 2,626, 43% female), male sex was associated with significantly greater mortality (26 vs. 21%, p = 0.0146) and higher peak hs-cTNT, hs-CRP, ferritin, D-dimer, and creatinine (p < 0.001). The effect of male sex on the primary outcome of death was partially mediated by peak values of all five biomarkers, suggesting that each pathophysiological pathway may contribute to increased risk of death in men. Hs-cTnT, creatinine, and hs-CRP were the strongest mediators. Findings were highly consistent in the MGH cohort with the exception of D-dimer. Conclusions This study suggests that the effect of sex on COVID-19 outcomes is mediated by cardiac and kidney injury, as well as underlying differences in inflammation and iron metabolism. Exploration of these specific pathways may facilitate sex-directed diagnostic and therapeutic strategies for patients with COVID-19 and provides a framework for the study of sex differences in other complex diseases.

2.
Rev Endocr Metab Disord ; 23(2): 293-297, 2022 04.
Article in English | MEDLINE | ID: covidwho-1718863

ABSTRACT

Patients with pre-existing cardiovascular disease (CVD) are at high risk for adverse outcomes with coronavirus disease 2019 (COVID-19). Further, COVID-19 infection is associated with numerous cardiovascular (CV) complications including arrhythmia, myocardial injury, cardiomyopathy, and thrombotic events. Increased susceptibility to COVID-19 and CV complications related to COVID-19 may be in part related to immune dysregulation and inflammation associated with CV disease which is exacerbated with viral infection. Vitamin D plays a major role in immune function and exerts anti-inflammatory effects, which may prove important in the context of CVD and COVID-19. To date, studies have shown minimal benefit for vitamin D supplementation in patients with COVID-19, though there are no studies specific to patients with CVD and related complications. Further, given that vitamin D has important protective effects on the CV system, including augmentation of myocardial contractility and anti-thrombotic effects, it is unknown if supplementation with vitamin D can mitigate CVD complications associated with COVID-19.


Subject(s)
COVID-19 , Cardiovascular Diseases , Vitamin D Deficiency , COVID-19/complications , COVID-19/drug therapy , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Humans , Vitamin D/physiology , Vitamin D/therapeutic use , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy , Vitamins/therapeutic use
3.
Am J Respir Crit Care Med ; 204(11): 1274-1285, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1546620

ABSTRACT

Rationale: Two distinct subphenotypes have been identified in acute respiratory distress syndrome (ARDS), but the presence of subgroups in ARDS associated with coronavirus disease (COVID-19) is unknown. Objectives: To identify clinically relevant, novel subgroups in COVID-19-related ARDS and compare them with previously described ARDS subphenotypes. Methods: Eligible participants were adults with COVID-19 and ARDS at Columbia University Irving Medical Center. Latent class analysis was used to identify subgroups with baseline clinical, respiratory, and laboratory data serving as partitioning variables. A previously developed machine learning model was used to classify patients as the hypoinflammatory and hyperinflammatory subphenotypes. Baseline characteristics and clinical outcomes were compared between subgroups. Heterogeneity of treatment effect for corticosteroid use in subgroups was tested. Measurements and Main Results: From March 2, 2020, to April 30, 2020, 483 patients with COVID-19-related ARDS met study criteria. A two-class latent class analysis model best fit the population (P = 0.0075). Class 2 (23%) had higher proinflammatory markers, troponin, creatinine, and lactate, lower bicarbonate, and lower blood pressure than class 1 (77%). Ninety-day mortality was higher in class 2 versus class 1 (75% vs. 48%; P < 0.0001). Considerable overlap was observed between these subgroups and ARDS subphenotypes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR cycle threshold was associated with mortality in the hypoinflammatory but not the hyperinflammatory phenotype. Heterogeneity of treatment effect to corticosteroids was observed (P = 0.0295), with improved mortality in the hyperinflammatory phenotype and worse mortality in the hypoinflammatory phenotype, with the caveat that corticosteroid treatment was not randomized. Conclusions: We identified two COVID-19-related ARDS subgroups with differential outcomes, similar to previously described ARDS subphenotypes. SARS-CoV-2 PCR cycle threshold had differential value for predicting mortality in the subphenotypes. The subphenotypes had differential treatment responses to corticosteroids.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Latent Class Analysis , Respiratory Distress Syndrome/drug therapy , Aged , COVID-19/complications , Cohort Studies , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/classification , Respiratory Distress Syndrome/etiology , Retrospective Studies
4.
Nat Med ; 27(4): 601-615, 2021 04.
Article in English | MEDLINE | ID: covidwho-1517636

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Acute Disease , COVID-19/epidemiology , COVID-19/ethnology , COVID-19/therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Humans , Patient Advocacy , Syndrome , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/therapy , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control
5.
J Am Coll Cardiol ; 78(16): 1635-1654, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1454219

ABSTRACT

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.


Subject(s)
COVID-19/drug therapy , COVID-19/prevention & control , Fatty Acids, Omega-3/therapeutic use , Fibric Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Niacin/therapeutic use , Amides/pharmacology , Amides/therapeutic use , Esters/pharmacology , Esters/therapeutic use , Fatty Acids, Omega-3/pharmacology , Fibric Acids/pharmacology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Lipid Regulating Agents/pharmacology , Lipid Regulating Agents/therapeutic use , Niacin/pharmacology , Randomized Controlled Trials as Topic , Sulfhydryl Compounds/pharmacology , Sulfhydryl Compounds/therapeutic use
6.
J Clin Endocrinol Metab ; 107(2): e698-e707, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1394502

ABSTRACT

BACKGROUND: Obesity is an established risk factor for severe COVID-19 outcomes. The mechanistic underpinnings of this association are not well-understood. OBJECTIVE: To evaluate the mediating role of systemic inflammation in obesity-associated COVID-19 outcomes. METHODS: This hospital-based, observational study included 3828 SARS-CoV-2-infected patients who were hospitalized February to May 2020 at Massachusetts General Hospital (MGH) or Columbia University Irving Medical Center/New York Presbyterian Hospital (CUIMC/NYP). We use mediation analysis to evaluate whether peak inflammatory biomarkers (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR], D-dimer, ferritin, white blood cell count and interleukin-6) are in the causal pathway between obesity (BMI ≥ 30) and mechanical ventilation or death within 28 days of presentation to care. RESULTS: In the MGH cohort (n = 1202), obesity was associated with greater likelihood of ventilation or death (OR = 1.73; 95% CI = [1.25, 2.41]; P = 0.001) and higher peak CRP (P < 0.001) compared with nonobese patients. The estimated proportion of the association between obesity and ventilation or death mediated by CRP was 0.49 (P < 0.001). Evidence of mediation was more pronounced in patients < 65 years (proportion mediated = 0.52 [P < 0.001] vs 0.44 [P = 0.180]). Findings were more moderate but consistent for peak ESR. Mediation by other inflammatory markers was not supported. Results were replicated in CUIMC/NYP cohort (n = 2626). CONCLUSION: Findings support systemic inflammatory pathways in obesity-associated severe COVID-19 disease, particularly in patients < 65 years, captured by CRP and ESR. Contextualized in clinical trial findings, these results reveal therapeutic opportunity to target systemic inflammatory pathways and monitor interventions in high-risk subgroups and particularly obese patients.


Subject(s)
COVID-19/complications , Obesity/complications , Systemic Inflammatory Response Syndrome/etiology , Adult , Aged , Aged, 80 and over , Aging , Blood Sedimentation , C-Reactive Protein/analysis , COVID-19/mortality , Female , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Interleukin-6/blood , Leukocyte Count , Male , Middle Aged , Obesity/mortality , Risk Factors , Systemic Inflammatory Response Syndrome/mortality , Treatment Outcome , United States/epidemiology
7.
Thromb Haemost ; 122(1): 131-141, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1258614

ABSTRACT

BACKGROUND: Thrombotic complications are considered among the main extrapulmonary manifestations of coronavirus disease 2019 (COVID-19). The optimal type and duration of prophylactic antithrombotic therapy in these patients remain unknown. METHODS: This article reports the final (90-day) results of the Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) study. Patients with COVID-19 admitted to intensive care were randomized to intermediate-dose versus standard-dose prophylactic anticoagulation for 30 days, irrespective of hospital discharge status. The primary efficacy outcome was a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation (ECMO), or all-cause death. The main safety outcome was major bleeding. RESULTS: Of 600 randomized patients, 562 entered the modified intention-to-treat analysis (median age [Q1, Q3]: 62 [50, 71] years; 237 [42.2%] women), of whom 336 (59.8%) survived to hospital discharge. The primary outcome occurred in 132 (47.8%) of patients assigned to intermediate dose and 130 (45.4%) patients assigned to standard-dose prophylactic anticoagulation (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 0.95-1.55, p = 0.11). Findings were similar for other efficacy outcomes, and in the landmark analysis from days 31 to 90 (HR: 1.59, 95% CI: 0.45-5.06). There were 7 (2.5%) major bleeding events in the intermediate-dose group (including 3 fatal events) and 4 (1.4%) major bleeding events in the standard-dose group (none fatal) (HR: 1.82, 95% CI: 0.53-6.24). CONCLUSION: Intermediate-dose compared with standard-dose prophylactic anticoagulation did not reduce a composite of death, treatment with ECMO, or venous or arterial thrombosis at 90-day follow-up.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Enoxaparin/administration & dosage , SARS-CoV-2 , Thrombosis/prevention & control , Aged , Anticoagulants/adverse effects , COVID-19/complications , COVID-19/mortality , Cohort Studies , Critical Care , Dose-Response Relationship, Drug , Enoxaparin/adverse effects , Extracorporeal Membrane Oxygenation , Female , Hemorrhage/chemically induced , Humans , Intensive Care Units , Iran/epidemiology , Kaplan-Meier Estimate , Male , Middle Aged , Pandemics , Thrombosis/etiology , Thrombosis/mortality
8.
JAMA ; 325(16): 1620-1630, 2021 04 27.
Article in English | MEDLINE | ID: covidwho-1239957

ABSTRACT

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/complications , Enoxaparin/administration & dosage , Extracorporeal Membrane Oxygenation , Oxygen Inhalation Therapy/methods , Thrombosis/prevention & control , Aged , Anticoagulants/adverse effects , COVID-19/mortality , Drug Administration Schedule , Enoxaparin/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Intensive Care Units , Iran , Length of Stay/statistics & numerical data , Male , Middle Aged , Odds Ratio , Outcome Assessment, Health Care , Pulmonary Embolism/epidemiology , Thrombocytopenia/chemically induced , Thrombosis/etiology , Thrombosis/mortality , Treatment Outcome , Venous Thrombosis/epidemiology , Venous Thrombosis/mortality
9.
Nat Med ; 27(4): 601-615, 2021 04.
Article in English | MEDLINE | ID: covidwho-1147038

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Acute Disease , COVID-19/epidemiology , COVID-19/ethnology , COVID-19/therapy , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/therapy , Humans , Patient Advocacy , Syndrome , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/therapy , Venous Thromboembolism/epidemiology , Venous Thromboembolism/prevention & control
10.
Braz J Anesthesiol ; 71(3): 292-294, 2021.
Article in English | MEDLINE | ID: covidwho-1144515

ABSTRACT

Catatonic patients may develop deep vein thrombosis (DVT) and pulmonary embolism (PE) due to prolonged periods of immobility. These life-threatening conditions demand prompt recognition and management. We describe the case of a patient with catatonia who presented to anesthesia for electroconvulsive therapy (ECT) at the outset of the current coronavirus disease 2019 pandemic. She complained of breathing difficulty and was suspected to have COVID-19 infection. On further evaluation, she was found to have DVT and PE and required oxygen therapy and intensive care management. The diagnostic delay in our patient would have probably not occurred, had it not been for the existing pandemic situation.


Subject(s)
COVID-19/diagnosis , Catatonia/complications , Delayed Diagnosis , Electroconvulsive Therapy , Pulmonary Embolism/diagnosis , Venous Thrombosis/diagnosis , Anesthesia , Catatonia/therapy , Diagnosis, Differential , Female , Humans , Middle Aged , Oxygen/therapeutic use , Pulmonary Embolism/therapy , Tomography, X-Ray Computed , Venous Thrombosis/therapy
11.
JAMA ; 325(16): 1620-1630, 2021 04 27.
Article in English | MEDLINE | ID: covidwho-1139203

ABSTRACT

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 × 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 ×103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7%) were included in the primary analysis (median [interquartile range] age, 62 [50-71] years; 237 [42.2%] women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% [95% CI, -6.6% to 9.8%]; odds ratio, 1.06 [95% CI, 0.76-1.48]; P = .70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% [1-sided 97.5% CI, -∞ to 3.4%]; odds ratio, 1.83 [1-sided 97.5% CI, 0.00-5.93]), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% [95% CI, 0.4%-3.8%]; P = .01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/complications , Enoxaparin/administration & dosage , Extracorporeal Membrane Oxygenation , Oxygen Inhalation Therapy/methods , Thrombosis/prevention & control , Aged , Anticoagulants/adverse effects , COVID-19/mortality , Drug Administration Schedule , Enoxaparin/adverse effects , Female , Hemorrhage/chemically induced , Hospitalization , Humans , Intensive Care Units , Iran , Length of Stay/statistics & numerical data , Male , Middle Aged , Odds Ratio , Outcome Assessment, Health Care , Pulmonary Embolism/epidemiology , Thrombocytopenia/chemically induced , Thrombosis/etiology , Thrombosis/mortality , Treatment Outcome , Venous Thrombosis/epidemiology , Venous Thrombosis/mortality
12.
Nat Commun ; 12(1): 1325, 2021 02 26.
Article in English | MEDLINE | ID: covidwho-1104490

ABSTRACT

The coronavirus disease 2019 (COVID-19) can result in a hyperinflammatory state, leading to acute respiratory distress syndrome (ARDS), myocardial injury, and thrombotic complications, among other sequelae. Statins, which are known to have anti-inflammatory and antithrombotic properties, have been studied in the setting of other viral infections, but their benefit has not been assessed in COVID-19. This is a retrospective analysis of patients admitted with COVID-19 from February 1st through May 12th, 2020 with study period ending on June 11th, 2020. Antecedent statin use was assessed using medication information available in the electronic medical record. We constructed a multivariable logistic regression model to predict the propensity of receiving statins, adjusting for baseline sociodemographic and clinical characteristics, and outpatient medications. The primary endpoint includes in-hospital mortality within 30 days. A total of 2626 patients were admitted during the study period, of whom 951 (36.2%) were antecedent statin users. Among 1296 patients (648 statin users, 648 non-statin users) identified with 1:1 propensity-score matching, statin use is significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.47, 95% CI 0.36-0.62, p < 0.001). We conclude that antecedent statin use in patients hospitalized with COVID-19 is associated with lower inpatient mortality.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Aged , Female , Hospital Mortality , Hospitalization , Humans , Logistic Models , Male , Middle Aged , New York City/epidemiology , Propensity Score , Retrospective Studies , SARS-CoV-2/isolation & purification
14.
J Am Heart Assoc ; 10(1): e018476, 2021 01 05.
Article in English | MEDLINE | ID: covidwho-917839

ABSTRACT

Background Cardiovascular involvement in coronavirus disease 2019 (COVID-19) is common and leads to worsened mortality. Diagnostic cardiovascular studies may be helpful for resource appropriation and identifying patients at increased risk for death. Methods and Results We analyzed 887 patients (aged 64±17 years) admitted with COVID-19 from March 1 to April 3, 2020 in New York City with 12 lead electrocardiography within 2 days of diagnosis. Demographics, comorbidities, and laboratory testing, including high sensitivity cardiac troponin T (hs-cTnT), were abstracted. At 30 days follow-up, 556 patients (63%) were living without requiring mechanical ventilation, 123 (14%) were living and required mechanical ventilation, and 203 (23%) had expired. Electrocardiography findings included atrial fibrillation or atrial flutter (AF/AFL) in 46 (5%) and ST-T wave changes in 306 (38%). 27 (59%) patients with AF/AFL expired as compared to 181 (21%) of 841 with other non-life-threatening rhythms (P<0.001). Multivariable analysis incorporating age, comorbidities, AF/AFL, QRS abnormalities, and ST-T wave changes, and initial hs-cTnT ≥20 ng/L showed that increased age (HR 1.04/year), elevated hs-cTnT (HR 4.57), AF/AFL (HR 2.07), and a history of coronary artery disease (HR 1.56) and active cancer (HR 1.87) were associated with increased mortality. Conclusions Myocardial injury with hs-cTnT ≥20 ng/L, in addition to cardiac conduction perturbations, especially AF/AFL, upon hospital admission for COVID-19 infection is associated with markedly increased risk for mortality than either diagnostic abnormality alone.


Subject(s)
Atrial Fibrillation/diagnosis , COVID-19/epidemiology , Electrocardiography , Heart Rate/physiology , Risk Assessment/methods , SARS-CoV-2 , Troponin T/blood , Atrial Fibrillation/blood , Atrial Fibrillation/epidemiology , Biomarkers/blood , COVID-19/blood , Comorbidity , Female , Follow-Up Studies , Humans , Male , Middle Aged , New York City/epidemiology , Prognosis , Retrospective Studies , Risk Factors
15.
Thromb Res ; 196: 382-394, 2020 12.
Article in English | MEDLINE | ID: covidwho-791550

ABSTRACT

BACKGROUND: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. METHODS: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 × 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count <20,000/fL) for the anticoagulation hypothesis. In a prespecified secondary analysis for non-inferiority, the study will test for the non-inferiority of intermediate intensity versus standard dose anticoagulation for major bleeding, considering a non-inferiority margin of 1.8 based on odds ratio. Key safety endpoints for the statin hypothesis include rise in liver enzymes >3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. CONCLUSIONS: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19.


Subject(s)
Anticoagulants/administration & dosage , Atorvastatin/administration & dosage , COVID-19/drug therapy , Enoxaparin/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Anticoagulants/adverse effects , Atorvastatin/adverse effects , COVID-19/complications , COVID-19/diagnosis , Critical Illness , Double-Blind Method , Enoxaparin/adverse effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Iran , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Thrombosis/diagnosis , Thrombosis/etiology , Time Factors , Treatment Outcome , Venous Thromboembolism/diagnosis , Venous Thromboembolism/etiology
16.
Mayo Clin Proc ; 95(10): 2099-2109, 2020 10.
Article in English | MEDLINE | ID: covidwho-713288

ABSTRACT

OBJECTIVE: To study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication. METHODS: This study analyzed 1258 adults with coronavirus disease 2019 who were seen at three hospitals in New York in March and April 2020. Electrocardiograms at presentation to the emergency department were systematically read by electrophysiologists. The primary outcome was a composite of mechanical ventilation or death 48 hours from diagnosis. The prognostic value of ECG abnormalities was assessed in a model adjusted for demographics, comorbidities, and vital signs. RESULTS: At 48 hours, 73 of 1258 patients (5.8%) had died and 174 of 1258 (13.8%) were alive but receiving mechanical ventilation with 277 of 1258 (22.0%) patients dying by 30 days. Early development of respiratory failure was common, with 53% of all intubations occurring within 48 hours of presentation. In a multivariable logistic regression, atrial fibrillation/flutter (odds ratio [OR], 2.5; 95% CI, 1.1 to 6.2), right ventricular strain (OR, 2.7; 95% CI, 1.3 to 6.1), and ST segment abnormalities (OR, 2.4; 95% CI, 1.5 to 3.8) were associated with death or mechanical ventilation at 48 hours. In 108 patients without these ECG abnormalities and with normal respiratory vitals (rate <20 breaths/min and saturation >95%), only 5 (4.6%) died or required mechanical ventilation by 48 hours versus 68 of 216 patients (31.5%) having both ECG and respiratory vital sign abnormalities. CONCLUSION: The combination of abnormal respiratory vital signs and ECG findings of atrial fibrillation/flutter, right ventricular strain, or ST segment abnormalities accurately prognosticates early deterioration in patients with coronavirus disease 2019 and may assist with patient triage.


Subject(s)
Arrhythmias, Cardiac/diagnostic imaging , Coronavirus Infections/physiopathology , Electrocardiography/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Pneumonia, Viral/physiopathology , Time-to-Treatment/statistics & numerical data , Adult , Betacoronavirus , COVID-19 , Female , Humans , Male , Middle Aged , Pandemics , Prognosis , SARS-CoV-2
17.
Eur J Endocrinol ; 183(5): R133-R147, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-695333

ABSTRACT

The SARS-CoV-2 virus responsible for the COVID-19 pandemic has generated an explosion of interest both in the mechanisms of infection leading to dissemination and expression of this disease, and in potential risk factors that may have a mechanistic basis for disease propagation or control. Vitamin D has emerged as a factor that may be involved in these two areas. The focus of this article is to apply our current understanding of vitamin D as a facilitator of immunocompetence both with regard to innate and adaptive immunity and to consider how this may relate to COVID-19 disease. There are also intriguing potential links to vitamin D as a factor in the cytokine storm that portends some of the most serious consequences of SARS-CoV-2 infection, such as the acute respiratory distress syndrome. Moreover, cardiac and coagulopathic features of COVID-19 disease deserve attention as they may also be related to vitamin D. Finally, we review the current clinical data associating vitamin D with SARS-CoV-2 infection, a putative clinical link that at this time must still be considered hypothetical.


Subject(s)
Adaptive Immunity/immunology , Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Immunity, Innate/immunology , Immunocompetence/immunology , Lung/immunology , Pneumonia, Viral/immunology , T-Lymphocytes/immunology , Vitamin D/immunology , Antimicrobial Cationic Peptides/immunology , Autophagy/immunology , Betacoronavirus , COVID-19 , Defensins/immunology , Humans , Pandemics , SARS-CoV-2 , T-Lymphocytes, Regulatory/immunology , Th1 Cells/immunology , Th17 Cells/immunology , Th2 Cells/immunology , Vitamin D/analogs & derivatives
18.
Nat Med ; 26(7): 1017-1032, 2020 07.
Article in English | MEDLINE | ID: covidwho-639177

ABSTRACT

Although COVID-19 is most well known for causing substantial respiratory pathology, it can also result in several extrapulmonary manifestations. These conditions include thrombotic complications, myocardial dysfunction and arrhythmia, acute coronary syndromes, acute kidney injury, gastrointestinal symptoms, hepatocellular injury, hyperglycemia and ketosis, neurologic illnesses, ocular symptoms, and dermatologic complications. Given that ACE2, the entry receptor for the causative coronavirus SARS-CoV-2, is expressed in multiple extrapulmonary tissues, direct viral tissue damage is a plausible mechanism of injury. In addition, endothelial damage and thromboinflammation, dysregulation of immune responses, and maladaptation of ACE2-related pathways might all contribute to these extrapulmonary manifestations of COVID-19. Here we review the extrapulmonary organ-specific pathophysiology, presentations and management considerations for patients with COVID-19 to aid clinicians and scientists in recognizing and monitoring the spectrum of manifestations, and in developing research priorities and therapeutic strategies for all organ systems involved.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/pathology , Organ Specificity , Pneumonia, Viral/pathology , Adaptive Immunity/physiology , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/immunology , Coronavirus Infections/therapy , Disease Progression , Endothelium, Vascular/pathology , Endothelium, Vascular/virology , Humans , Inflammation/etiology , Inflammation/pathology , Inflammation/virology , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/immunology , Pneumonia, Viral/therapy , Renin-Angiotensin System/physiology , SARS-CoV-2 , Thrombosis/etiology , Thrombosis/pathology , Thrombosis/virology , Virus Internalization
19.
Thromb Haemost ; 120(7): 1004-1024, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-418767

ABSTRACT

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease. In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis. Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated. Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19. Further, we review other agents, including immunomodulators, that may have antithrombotic properties. It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.


Subject(s)
Coronavirus Infections/immunology , Fibrinolytic Agents/therapeutic use , Inflammation/drug therapy , Pneumonia, Viral/immunology , Thrombosis/drug therapy , Animals , Anti-Inflammatory Agents/therapeutic use , Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Glycosaminoglycans/therapeutic use , Hemostasis , Humans , Inflammation/complications , Inflammation/immunology , Pandemics , Platelet Aggregation Inhibitors/therapeutic use , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2 , Thrombosis/complications , Thrombosis/immunology
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