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2.
Medicina (Kaunas) ; 58(11)2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2116272

ABSTRACT

Background and Objectives: Aspirin (ASA) is a commonly used antithrombotic drug that has been demonstrated to reduce venous thromboembolism. The aim was to analyze if geriatric COVID-19 patients undergoing a 100 mg/day Aspirin (ASA) treatment prior to hospitalization differ in hospital outcome compared to patients without previous ASA therapy. Materials and Methods: An observational retrospective study was carried out using an anonymized database including geriatric COVID-19 patients (March to April 2020) admitted to Madrid Hospitals Group. A group of COVID-19 patients were treated with low ASA (100 mg/day) prior to COVID-19 infection. Results: Geriatric ASA-treated patients were older (mean age over 70 years; n = 41), had higher frequency of hypertension and hyperlipidemia, and upon admission had higher D-dimer levels than non-ASA-treated patients (mean age over 73 years; n = 160). However, patients under ASA treatment did not show more frequent pulmonary thromboembolism (PE) than non-ASA-treated patients. ASA-treated geriatric COVID-19-infected patients in-hospital < 30 days all-cause mortality was more frequent than in non-ASA-treated COVID-19 patients. In ASA-treated COVID-19-infected geriatric patients, anticoagulant therapy with low molecular weight heparin (LMWH) significantly reduced need of ICU care, but tended to increase in-hospital < 30 days all-cause mortality. Conclusions: Prior treatment with a low dose of ASA in COVID-19-infected geriatric patients increased frequency of in-hospital < 30 days all-cause mortality, although it seemed to not increase PE frequency despite D-dimer levels upon admission being higher than in non-ASA users. In ASA-treated geriatric COVID-19-infected patients, addition of LMWH therapy reduced frequency of ICU care, but tended to increase in-hospital < 30 days all-cause mortality.


Subject(s)
Aspirin , COVID-19 , Humans , Aged , Aspirin/therapeutic use , COVID-19/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Retrospective Studies , Hospitals
3.
J Laryngol Otol ; 136(12): 1309-1313, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2076940

ABSTRACT

OBJECTIVE: Rhino-orbito-cerebral mucormycosis is a rapidly progressive disease with high mortality rates of about 60 per cent. The increasing incidence of rhino-orbito-cerebral mucormycosis in coronavirus disease 2019 patients in India and worldwide has become a matter of concern owing to the case fatality rate. This study explored the use of low dose aspirin in decreasing the mortality rate of coronavirus disease 2019 associated mucormycosis. METHOD: This was a retrospective observational study. Patients suffering from post-coronavirus disease 2019 mucormycosis were included in the study. Each patient was treated with surgical debridement and systemic amphotericin B. Low dose aspirin was added, and mortality rates were compared with the patients who did not receive aspirin. RESULTS: The demographic data and rhino-orbito-cerebral mucormycosis staging between the two groups were not significantly different. There was a statistically significant difference in mortality outcomes between the two groups (p = 0.029) and a 1.77 times higher risk of dying for patients not receiving aspirin. Kaplan-Meier survival indicated that patients receiving aspirin had better survival rates (p = 0.04). CONCLUSION: Low dose aspirin improves survival rates in coronavirus disease 2019 associated mucormycosis.


Subject(s)
COVID-19 , Mucormycosis , Orbital Diseases , Humans , Mucormycosis/drug therapy , Retrospective Studies , Aspirin/therapeutic use , Antifungal Agents/therapeutic use , Debridement
4.
Arch Bronconeumol ; 58(11): 746-753, 2022 Nov.
Article in English, Spanish | MEDLINE | ID: covidwho-2007445

ABSTRACT

INTRODUCTION: The goal of this investigation is to assess the association between prehospital use of aspirin (ASA) and patient-centered outcomes in a large global cohort of hospitalized COVID-19 patients. METHODS: This study utilizes data from the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) Registry. Adult patients hospitalized from February 15th, 2020, to September 30th, 2021, were included. Multivariable regression analyses were utilized to assess the association between pre-hospital use of ASA and the primary outcome of overall hospital mortality. RESULTS: 21,579 patients were included from 185 hospitals (predominantly US-based, 71.3%), with 4691 (21.7%) receiving pre-hospital ASA. Patients receiving ASA, compared to those without pre-admission ASA use, were generally older (median 70 vs. 59 years), more likely to be male (58.7 vs. 56.0%), caucasian (57.4 vs. 51.6%), and more commonly had higher rates of medical comorbidities. In multivariable analyses, patients receiving pre-hospital ASA had lower mortality (HR: 0.89, 95% CI 0.82-0.97, p=0.01) and reduced hazard for progression to severe disease or death (HR: 0.91, 95% CI 0.84-0.99, p=0.02) and more hospital free days (1.00 days, 95% CI 0.66-1.35, p=0.01) compared to those without pre-hospital ASA use. The overall direction and significance of the results remained the same in sensitivity analysis, after adjusting the multivariable model for time since pandemic. CONCLUSIONS: In this large international cohort, pre-hospital use of ASA was associated with a lower hazard for death in hospitalized patients with COVID-19. Randomized controlled trials may be warranted to assess the utility of pre-hospital use of ASA.


Subject(s)
COVID-19 , Virus Diseases , Adult , Humans , Male , Female , COVID-19/epidemiology , Aspirin/therapeutic use , SARS-CoV-2 , Pandemics , Hospitalization , Hospital Mortality
5.
Int J Mol Sci ; 23(13)2022 Jun 21.
Article in English | MEDLINE | ID: covidwho-1963996

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease-19 (COVID-19) is still challenging healthcare systems and societies worldwide. While vaccines are available, therapeutic strategies are developing and need to be adapted to each patient. Many clinical approaches focus on the repurposing of approved therapeutics against other diseases. However, the efficacy of these compounds on viral infection or even harmful secondary effects in the context of SARS-CoV-2 infection are sparsely investigated. Similarly, adverse effects of commonly used therapeutics against lifestyle diseases have not been studied in detail. Using mono cell culture systems and a more complex chip model, we investigated the effects of the acetylsalicylic acid (ASA) salt D,L-lysine-acetylsalicylate + glycine (LASAG) on SARS-CoV-2 infection in vitro. ASA is commonly known as Aspirin® and is one of the most frequently used medications worldwide. Our data indicate an inhibitory effect of LASAG on SARS-CoV-2 replication and SARS-CoV-2-induced expression of pro-inflammatory cytokines and coagulation factors. Remarkably, our data point to an additive effect of the combination of LASAG and the antiviral acting drug remdesivir on SARS-CoV-2 replication in vitro.


Subject(s)
COVID-19 , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Aspirin/pharmacology , Aspirin/therapeutic use , COVID-19/drug therapy , Glycine/pharmacology , Glycine/therapeutic use , Humans , Lysine
6.
Saudi Med J ; 43(7): 715-722, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1955133

ABSTRACT

OBJECTIVES: To assess the effect of different thromboprophylaxis regimens on clinical outcomes and mortality of critical ill patients with coronavirus disease -19 (COVID-19). METHODS: We investigated the medical records of patients with positive COVID-19 (using polymerase chain reaction test) who were admitted to the intensive care unit (ICU) at Sakarya University Hospital, Sakarya, Turkey, from March 2020 to January 2021. We included patients under anticoagulant therapy in the clinical course. The patients were allocated to 3 groups: Group A - low-dose (prophylactic) low-molecular-weight-heparin (LMWH) therapy, Group B - high-dose (therapeutic) LMWH therapy, and patients that received aspirin additional to the high-dose (therapeutic) LMWH as Group C. Primary outcomes were overall mortality rates and length of stay (LOS) in ICU. Secondary outcomes were rates of major hemorrhagic and thrombotic events. RESULTS: Records of 475 patients were reviewed and 164 patients were included. No significant difference was detected in mortality rates between groups (p=0.135). Intensive care unit stay was 13 (9-24.5) days in Group A, 11 (8.75-23) days in Group B, and 13 (9-17) days in Group C without a significant difference (p=0.547). No significant difference was detected between groups in terms of thrombotic (p=0.565) and hemorrhagic events (p=0.615). CONCLUSION: A high-dose anticoagulation therapy and addition of aspirin to LMWH therapy did not decrease the mortality rates and LOS in ICU in critical ill COVID-19 patients. In addition, it did not increase the incidence of major hemorrhage and major thrombotic events.


Subject(s)
COVID-19 , Thrombosis , Venous Thromboembolism , Anticoagulants/adverse effects , Aspirin/therapeutic use , Critical Illness/therapy , Hemorrhage/chemically induced , Hemorrhage/drug therapy , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Retrospective Studies , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control
7.
BMC Infect Dis ; 22(1): 606, 2022 Jul 09.
Article in English | MEDLINE | ID: covidwho-1928161

ABSTRACT

BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).


Subject(s)
COVID-19 , Clinical Deterioration , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aspirin/therapeutic use , Atorvastatin/therapeutic use , COVID-19/drug therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Interleukin-6 , SARS-CoV-2 , Treatment Outcome
8.
J Am Heart Assoc ; 11(13): e024530, 2022 07 05.
Article in English | MEDLINE | ID: covidwho-1902160

ABSTRACT

Background COVID-19 is an infectious illness, featured by an increased risk of thromboembolism. However, no standard antithrombotic therapy is currently recommended for patients hospitalized with COVID-19. The aim of this study was to evaluate safety and efficacy of additional therapy with aspirin over prophylactic anticoagulation (PAC) in patients hospitalized with COVID-19 and its impact on survival. Methods and Results A total of 8168 patients hospitalized for COVID-19 were enrolled in a multicenter-international prospective registry (HOPE COVID-19). Clinical data and in-hospital complications, including mortality, were recorded. Study population included patients treated with PAC or with PAC and aspirin. A comparison of clinical outcomes between patients treated with PAC versus PAC and aspirin was performed using an adjusted analysis with propensity score matching. Of 7824 patients with complete data, 360 (4.6%) received PAC and aspirin and 2949 (37.6%) PAC. Propensity-score matching yielded 298 patients from each group. In the propensity score-matched population, cumulative incidence of in-hospital mortality was lower in patients treated with PAC and aspirin versus PAC (15% versus 21%, Log Rank P=0.01). At multivariable analysis in propensity matched population of patients with COVID-19, including age, sex, hypertension, diabetes, kidney failure, and invasive ventilation, aspirin treatment was associated with lower risk of in-hospital mortality (hazard ratio [HR], 0.62; [95% CI 0.42-0.92], P=0.018). Conclusions Combination PAC and aspirin was associated with lower mortality risk among patients hospitalized with COVID-19 in a propensity score matched population compared to PAC alone.


Subject(s)
COVID-19 , Anticoagulants/adverse effects , Aspirin/therapeutic use , Cohort Studies , Humans , Propensity Score , Registries , Retrospective Studies
9.
Inflammopharmacology ; 30(4): 1475-1476, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1899225

ABSTRACT

In this commentary, we make a case that the mechanism of COVID pathogenesis is related to virus-induced endothelial injury resulting in platelet activation and the formation of microthrombi both systemically and in cardiac and pulmnonary circulation which result in major causes of COVID morbidity and mortality. Aspirin by virtue of its irreversible inhibition of platelet COX-1, should reverse these platelet-induced pathogenic changes associated with COVID infection for the 6-9 day lifetime of the platelet. We also cite recent findings of a retrospective analysis that supports the use of low-dose (81 mg) aspirin to treat the symptoms associated with the early stages of COVID infection.


Subject(s)
Aspirin , COVID-19 , Aspirin/pharmacology , Aspirin/therapeutic use , Blood Platelets , COVID-19/drug therapy , Humans , Platelet Activation , Retrospective Studies
10.
Eur J Clin Pharmacol ; 78(9): 1403-1420, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1899135

ABSTRACT

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has shown unprecedented impact world-wide since the eruption in late 2019. Importantly, emerging reports suggest an increased risk of thromboembolism development in patients with COVID-19. Meanwhile, it is found that aspirin reduced mortality in critically ill patients with non-COVID-19 acute respiratory distress syndrome. Therefore, a meta-analysis was performed to investigate the effects of aspirin on COVID-19 mortality. METHODS: A systematic literature search was conducted in 10 electronic databases and 4 registries. Random effects models were used to calculate pooled relative risks (RRs) with 95% confidence intervals (Cis) to estimate the effect of aspirin on COVID-19 mortality. Relevant subgroup analyses and sensitivity analyses were also performed. RESULTS: The results showed that aspirin use was associated with a reduction in COVID-19 mortality (adjusted RR 0.69; 95% CI 0.50-0.95; P < 0.001). Subgroup analysis found that the low-dose group was associated with a reduced COVID-19 mortality (adjusted RR 0.64; 95% CI 0.48-0.85; P < 0.01). Aspirin use was associated with reduced COVID-19 mortality in Europe and America (crude RR 0.71; 95% CI 0.52-0.98; P = 0.04), and results from cohort studies suggested that aspirin use was a protective factor for COVID-19 mortality (adjusted RR 0.73; 95% CI 0.52-0.99; P = 0.04). Meanwhile, aspirin use was not associated with bleeding risk (crude RR 1.22; 95% CI 0.80-1.87; P = 0.96). CONCLUSIONS: This meta-analysis found that aspirin use was associated with a reduction in mortality in patients with COVID-19 and not with an increased risk of bleeding.


Subject(s)
Aspirin , COVID-19 , Aspirin/therapeutic use , COVID-19/drug therapy , Critical Illness , Hemorrhage/chemically induced , Humans , Pandemics
11.
Drug Metab Pers Ther ; 37(1): 35-40, 2021 07 08.
Article in English | MEDLINE | ID: covidwho-1855056

ABSTRACT

OBJECTIVES: To mitigate the incidence of recurrent stroke in patients, dual antiplatelet therapy comprising aspirin and clopidogrel is usually administered. Clopidogrel is a prodrug and its bioactivation is catalyzed by cytochrome P450 (CYP)2C19. The main objective of this work was to determine the prevalence of CYP2C19*2 carriers in Saudi ischemic stroke patients and assess the suitability of using genotyping to guide antiplatelet therapy in a university hospital setup. METHODS: This prospective (2018-2019) study was conducted on 256 patients (age 61 ± 12.5) clinically diagnosed with ischemic stroke who were genotyped using Spartan RX CYP2C19 assay. RESULTS: From the total patient group (256), upon admission, 210 patients were prescribed either aspirin, clopidogrel or dual antiplatelet therapy. Of the 27 patients with the CYP2C19*2 allele who were prescribed clopidogrel (18) or dual antiplatelet therapy (9), only 21 patients could be followed up for a period of six months post stroke event, in addition to 21 age- and sex-matched patients with the normal allele. The CYP2C19*2 allele carriers had a statistically significant increased risk of recurrent stroke compared to patients carrying the normal allele. CONCLUSIONS: This study shows the suitability of using genotyping to guide antiplatelet therapy in ischemic stroke patients in a clinical setting.


Subject(s)
Cytochrome P-450 CYP2C19 , Ischemic Stroke , Platelet Aggregation Inhibitors , Aged , Aspirin/therapeutic use , Clopidogrel/therapeutic use , Cytochrome P-450 CYP2C19/genetics , Genotype , Hospitals , Humans , Ischemic Stroke/drug therapy , Ischemic Stroke/genetics , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Prevalence , Prospective Studies , Saudi Arabia/epidemiology
12.
Chest ; 161(5): 1275-1284, 2022 05.
Article in English | MEDLINE | ID: covidwho-1828073

ABSTRACT

BACKGROUND: There is no pharmacologic treatment for ARDS. Platelets play an important role in the pathophysiology of ARDS. Preclinical, observational, and clinically relevant models of ARDS indicate aspirin as a potential therapeutic option. RESEARCH QUESTION: Is enteral aspirin (75 mg, once daily) safe and effective in improving surrogate outcomes in adult patients with ARDS? STUDY DESIGN AND METHODS: This randomized, double-blind (patient and investigator), allocation-concealed, placebo-controlled phase 2 trial was conducted in five UK ICUs. Patients fulfilling the Berlin definition of ARDS were randomly assigned at a 1:1 ratio to receive enteral aspirin (75 mg) or placebo, for a maximum of 14 days, using a computer-generated randomization schedule, with variable block size, stratified by vasopressor requirement. The primary end point was oxygenation index (OI) on day 7. Secondary outcomes included safety parameters and other respiratory physiological markers. Analyses were by intention to treat. RESULTS: The trial was stopped early, due to slow recruitment, after 49 of a planned 60 patients were recruited. Twenty-four patients were allocated to aspirin and 25 to placebo. There was no significant difference in day 7 OI [aspirin group: unadjusted mean, 54.4 (SD 26.8); placebo group: 42.4 (SD 25); mean difference, 12.0; 95% CI, -6.1 to 30.1; P = .19]. Aspirin did not significantly impact the secondary outcomes. There was no difference in the number of adverse events between the groups (13 in each; OR, 1.04; 95% CI, 0.56-1.94; P = .56). INTERPRETATION: Aspirin was well tolerated but did not improve OI or other physiological outcomes; a larger trial is not feasible in its current design. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02326350; URL: www. CLINICALTRIALS: gov.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Adult , Aspirin/therapeutic use , Double-Blind Method , Humans , Intensive Care Units , Respiration, Artificial , Respiratory Distress Syndrome/drug therapy , Treatment Outcome
13.
J Intensive Care Med ; 37(9): 1238-1249, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1808050

ABSTRACT

BACKGROUND: Aspirin is widely used as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. The literature has assessed and evaluated its role in hospitalized COVID-19 patients. However, no data are available regarding its role in COVID-19 critically ill patients. This study aimed to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in critically ill patients with COVID-19. METHOD: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to intensive care units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay. The primary outcome was in-hospital mortality, and other outcomes were considered secondary. Propensity score matching was used (1:1 ratio) based on the selected criteria. RESULTS: A total of 1033 patients were eligible, and 352 patients were included after propensity score matching. The in-hospital mortality (HR 0.73 [0.56, 0.97], p = 0.03) was lower in patients who received aspirin during stay. Conversely, patients who received aspirin had a higher odds of major bleeding than those in the control group (OR 2.92 [0.91, 9.36], p = 0.07); however, this was not statistically significant. Additionally, subgroup analysis showed a possible mortality benefit for patients who used aspirin therapy prior to hospitalization and continued during ICU stay (HR 0.72 [0.52, 1.01], p = 0.05), but not with the new initiation of aspirin (HR 1.22 [0.68, 2.20], p = 0.50). CONCLUSION: Continuation of aspirin therapy during ICU stay in critically ill patients with COVID-19 who were receiving it prior to ICU admission may have a mortality benefit; nevertheless, it may be associated with an increased risk of significant bleeding. Appropriate evaluation for safety versus benefits of utilizing aspirin therapy during ICU stay in COVID19 critically ill patients is highly recommended.


Subject(s)
COVID-19 , Adult , Aspirin/therapeutic use , Critical Illness/therapy , Hemorrhage , Humans , Intensive Care Units , Propensity Score , Retrospective Studies , SARS-CoV-2
14.
JAMA ; 327(13): 1247-1259, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1801957

ABSTRACT

Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participants: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Interventions: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Results: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified criterion for futility was met for the pooled antiplatelet group compared with control. Among the 1557 critically ill patients randomized, 8 patients withdrew consent and 1549 completed the trial (median age, 57 years; 521 [33.6%] female). The median for organ support-free days was 7 (IQR, -1 to 16) in both the antiplatelet and control groups (median-adjusted OR, 1.02 [95% credible interval {CrI}, 0.86-1.23]; 95.7% posterior probability of futility). The proportions of patients surviving to hospital discharge were 71.5% (723/1011) and 67.9% (354/521) in the antiplatelet and control groups, respectively (median-adjusted OR, 1.27 [95% CrI, 0.99-1.62]; adjusted absolute difference, 5% [95% CrI, -0.2% to 9.5%]; 97% posterior probability of efficacy). Among survivors, the median for organ support-free days was 14 in both groups. Major bleeding occurred in 2.1% and 0.4% of patients in the antiplatelet and control groups (adjusted OR, 2.97 [95% CrI, 1.23-8.28]; adjusted absolute risk increase, 0.8% [95% CrI, 0.1%-2.7%]; 99.4% probability of harm). Conclusions and Relevance: Among critically ill patients with COVID-19, treatment with an antiplatelet agent, compared with no antiplatelet agent, had a low likelihood of providing improvement in the number of organ support-free days within 21 days. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707.


Subject(s)
COVID-19 , Critical Illness , Platelet Aggregation Inhibitors , Venous Thromboembolism , Adult , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Aspirin/adverse effects , Aspirin/therapeutic use , Bayes Theorem , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , COVID-19/therapy , Critical Illness/mortality , Critical Illness/therapy , Female , Hemorrhage/chemically induced , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Purinergic P2Y Receptor Antagonists/adverse effects , Purinergic P2Y Receptor Antagonists/therapeutic use , Respiration, Artificial , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology
15.
Eur J Pediatr ; 181(7): 2563-2573, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1782803

ABSTRACT

Key aspects of the medical management of Kawasaki disease (KD) are not yet supported by a high evidence level, thus making room for individual recommendations. We performed a structured comparison of existing international KD guidelines to analyze potential differences in the implementation of evidence-based KD recommendations regarding diagnosis and therapy. To identify country-specific guidelines, we took a multilateral approach including a comprehensive PubMed literature, online research, and directly contacting national pediatric associations. We then ran a structured guidelines' analysis and evaluated the diagnostic and therapeutic differences in the context of evidence-based medicine. In this structured guideline analysis, we identified nine national and one European guidelines. According to them all, the diagnosis of KD still relies on its clinical presentation with no reliable biomarker recommended. First-line treatment consistently involves only intravenous immunoglobulin (IVIG) therapy. Recommendations in terms of acetylsalicylic acid, corticosteroids, and additional therapeutic options vary considerably. CONCLUSION: According to all guidelines, KD is diagnosed clinically with some variance in defining incomplete KD and being a non-responder to treatment. First-line treatment consistently includes IVIG. Recommendations for additional therapeutic strategies are more heterogeneous. WHAT IS KNOWN: • The diagnosis of KD relies on the clinical presentation, entailing challenges in timely diagnosis. • Other treatment options then IVIG are not supported by a high evidence level, making room for individual recommendations. WHAT IS NEW: • Definition of incomplete KD and being non-responsive to an initial treatment vary to some extent between the national guidelines. • Only IVIG is consistently proposed throughout all guidelines, further therapeutic recommendations vary between the national recommendations.


Subject(s)
Mucocutaneous Lymph Node Syndrome , Aspirin/therapeutic use , Biomarkers , Child , Evidence-Based Medicine , Humans , Immunoglobulins, Intravenous/therapeutic use , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/therapy
16.
Cardiovasc Hematol Agents Med Chem ; 20(3): 189-196, 2022.
Article in English | MEDLINE | ID: covidwho-1775543

ABSTRACT

INTRODUCTION: Thromboembolic events are one of the important complications in COVID-19 patients, especially in severe cases. Aspirin affects platelet function by irreversibly inhibiting cyclooxygenase activity, reducing the risk of thrombosis. The current systematic review aimed to evaluate aspirin's effectiveness in preventing pro-thrombotic states in COVID-19 hospitalized patients. METHODS: The systematic search was done in PubMed/Medline, EMBASE, and Medrxiv until September 27, 2021. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019 Novel Coronavirus", "Aspirin," and "Acetylsalicylic Acid." RESULTS: Twelve studies were included. In COVID-19 patients, aspirin can reduce CRP, IL-6 levels, and platelet aggregation by inhibiting thromboxane A2. It can also improve antiviral immunity by hindering the biosynthesis of prostaglandins and lipoxin. Eight out of twelve articles indicated that aspirin provided a beneficial effect on COVID-19. Most studies consider lowered mechanical ventilation needs, ICU admission, illness severity, overt thrombosis, and clinical outcomes in COVID-19 patients receiving aspirin. CONCLUSION: Aspirin as an antiplatelet and anti-inflammatory agent may reduce the mortality rates in hospitalized patients with severe COVID-19. Further observational studies are necessary to determine the effect of aspirin on the prevention of pro-thrombotic states in hospitalized COVID- 19 patients.


Subject(s)
COVID-19 , Lipoxins , Thrombosis , Antiviral Agents/therapeutic use , Aspirin/therapeutic use , COVID-19/drug therapy , Humans , Interleukin-6 , Platelet Aggregation Inhibitors/therapeutic use , Prostaglandin-Endoperoxide Synthases , Prostaglandins , SARS-CoV-2 , Thrombosis/drug therapy , Thrombosis/prevention & control , Thromboxane A2
18.
JAMA Netw Open ; 5(3): e223890, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1756516

ABSTRACT

Importance: Prior observational studies suggest that aspirin use may be associated with reduced mortality in high-risk hospitalized patients with COVID-19, but aspirin's efficacy in patients with moderate COVID-19 is not well studied. Objective: To assess whether early aspirin use is associated with lower odds of in-hospital mortality in patients with moderate COVID-19. Design, Setting, and Participants: Observational cohort study of 112 269 hospitalized patients with moderate COVID-19, enrolled from January 1, 2020, through September 10, 2021, at 64 health systems in the United States participating in the National Institute of Health's National COVID Cohort Collaborative (N3C). Exposure: Aspirin use within the first day of hospitalization. Main Outcome and Measures: The primary outcome was 28-day in-hospital mortality, and secondary outcomes were pulmonary embolism and deep vein thrombosis. Odds of in-hospital mortality were calculated using marginal structural Cox and logistic regression models. Inverse probability of treatment weighting was used to reduce bias from confounding and balance characteristics between groups. Results: Among the 2 446 650 COVID-19-positive patients who were screened, 189 287 were hospitalized and 112 269 met study inclusion. For the full cohort, Median age was 63 years (IQR, 47-74 years); 16.1% of patients were African American, 3.8% were Asian, 52.7% were White, 5.0% were of other races and ethnicities, 22.4% were of unknown race and ethnicity. In-hospital mortality occurred in 10.9% of patients. After inverse probability treatment weighting, 28-day in-hospital mortality was significantly lower in those who received aspirin (10.2% vs 11.8%; odds ratio [OR], 0.85; 95% CI, 0.79-0.92; P < .001). The rate of pulmonary embolism, but not deep vein thrombosis, was also significantly lower in patients who received aspirin (1.0% vs 1.4%; OR, 0.71; 95% CI, 0.56-0.90; P = .004). Patients who received early aspirin did not have higher rates of gastrointestinal hemorrhage (0.8% aspirin vs 0.7% no aspirin; OR, 1.04; 95% CI, 0.82-1.33; P = .72), cerebral hemorrhage (0.6% aspirin vs 0.4% no aspirin; OR, 1.32; 95% CI, 0.92-1.88; P = .13), or blood transfusion (2.7% aspirin vs 2.3% no aspirin; OR, 1.14; 95% CI, 0.99-1.32; P = .06). The composite of hemorrhagic complications did not occur more often in those receiving aspirin (3.7% aspirin vs 3.2% no aspirin; OR, 1.13; 95% CI, 1.00-1.28; P = .054). Subgroups who appeared to benefit the most included patients older than 60 years (61-80 years: OR, 0.79; 95% CI, 0.72-0.87; P < .001; >80 years: OR, 0.79; 95% CI, 0.69-0.91; P < .001) and patients with comorbidities (1 comorbidity: 6.4% vs 9.2%; OR, 0.68; 95% CI, 0.55-0.83; P < .001; 2 comorbidities: 10.5% vs 12.8%; OR, 0.80; 95% CI, 0.69-0.93; P = .003; 3 comorbidities: 13.8% vs 17.0%, OR, 0.78; 95% CI, 0.68-0.89; P < .001; >3 comorbidities: 17.0% vs 21.6%; OR, 0.74; 95% CI, 0.66-0.84; P < .001). Conclusions and Relevance: In this cohort study of US adults hospitalized with moderate COVID-19, early aspirin use was associated with lower odds of 28-day in-hospital mortality. A randomized clinical trial that includes diverse patients with moderate COVID-19 is warranted to adequately evaluate aspirin's efficacy in patients with high-risk conditions.


Subject(s)
Aspirin , COVID-19 , Adult , Aspirin/therapeutic use , Cohort Studies , Hospital Mortality , Hospitalization , Humans , Middle Aged , United States/epidemiology
19.
Bosn J Basic Med Sci ; 22(5): 826-832, 2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-1727053

ABSTRACT

The COVID-19 pandemic has caused a global public health emergency. Nutritional status is suggested to be related to the severity of COVID-19 infection. Herein, we aimed to explore the impact of using vitamin and mineral supplements prior to COVID-19 infection on disease severity and hospitalization. In addition, the prior use of aspirin as an anticoagulant on the disease severity was investigated. A cross-sectional, self-administered survey was conducted between March and July 2021. Recovered COVID-19 individuals (age ≥ 18 years, n = 2148) were recruited in the study. A multivariate logistic regression was used to evaluate the associations of supplements and aspirin use with COVID-19 disease severity and hospitalization status. Among the participants, 12.1% reported symptoms consistent with severe COVID-19, and 10.2% were hospitalized due to COVID-19. After adjustment for confounding variables (age, gender, BMI, cigarette smoking status, and the number of comorbidities), the multivariate logistic regression model showed that the consumption of vitamin D supplements prior to COVID-19 infection was associated with a significant decrease in disease severity (OR = 0.68, 95% CI 0.50 - 0.92; P = 0.01), and a lower risk of hospitalization (OR = 0.64, 95% CI 0.45 - 0.89; P = 0.01). On the other hand, there were no significant differences in the frequencies of severe illness and hospitalizations with the consumption of vitamin A, folic acid, vitamin B12, vitamin B complex, vitamin C, zinc, iron, selenium, calcium, magnesium, omega 3, and aspirin before COVID-19 infection. Among the investigated nutrients, the use of vitamin D prior to COVID-19 infection was associated with reduced disease severity and hospitalization. However, more studies are required to confirm this finding.


Subject(s)
COVID-19 , Selenium , Vitamin B Complex , Adolescent , Anticoagulants , Ascorbic Acid/therapeutic use , Aspirin/therapeutic use , Calcium , Cross-Sectional Studies , Dietary Supplements , Folic Acid , Hospitalization , Humans , Iron , Magnesium , Pandemics , Severity of Illness Index , Vitamin A , Vitamin B 12 , Vitamin D/therapeutic use , Zinc
20.
Adv Exp Med Biol ; 1327: 205-214, 2021.
Article in English | MEDLINE | ID: covidwho-1718516

ABSTRACT

The exaggerated host response to Sars-CoV-2 plays an important role in COVID-19 pathology but provides a therapeutic opportunity until definitive virus targeted therapies and vaccines become available. Given a central role of endothelial dysfunction and systemic inflammation, repurposing ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), statins, and aspirin has been of interest. In this retrospective, single-center study, we evaluated the primary outcomes of mortality and ICU admission in 587 hospitalized patients with documented COVID-19 with or without ACEIs, ARBs, statins, and aspirin. Atorvastatin was associated with reduced mortality, which persisted after adjusting for age, lockdown status, and other medications (OR: 0.18. 95% CI: 0.06-0.49, P = 0.001). ACEIs were also associated with reduced mortality in the crude model (OR: 0.20, CI: 0.06-0.66, P = 0.008), as ACEIs and ARBs were combined as a single group (OR: 0.35, CI: 0.16-0.75, P = 0.007), although ARBs alone did not reach statistical significance. There was no association between any medications and risk of ICU admission. Aspirin only achieved a significant association of reduced mortality in a subgroup of patients with diabetes in the crude model (OR: 0.17, CI: 0.04-0.80, P = 0.02). The reduced mortality observed with atorvastatin is consistent with other literature, and consideration should be given to atorvastatin as a COVID-19 treatment. While there was suggested benefit of ACEIs and ARBs in the present study, other studies are varied and further studies are warranted to recommend employing these medications as a treatment strategy. Nevertheless, this study combined with others continues to give credibility that ACEIs and ARBs are safe to continue in the setting of COVID-19.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypertension , Aldosterone , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Angiotensins , Aspirin/therapeutic use , COVID-19/drug therapy , Communicable Disease Control , Hospitals , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intensive Care Units , Renin , Retrospective Studies , SARS-CoV-2
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