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1.
Eur Heart J Cardiovasc Pharmacother ; 8(2): 157-164, 2022 02 16.
Article in English | MEDLINE | ID: covidwho-1692232

ABSTRACT

AIM: Assessing the effect of statin therapy (ST) at hospital admission for COVID-19 on in-hospital mortality. METHODS AND RESULTS: Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients [1234 men, 923 women; age: 67 y/o (IQR 54-78)] admitted to the hospital were retrieved from the clinical records in anonymized manner. Three hundred and fifty-three deaths occurred. Five hundred and eighty-one patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on ST than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: P = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared with the GM non-statin group (17.4%; P = 0.045). The Cox model applied to the CSH function [HR = 0.58(CI: 0.39-0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39-0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality. CONCLUSIONS: A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Female , Hospital Mortality , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Male , Pandemics , SARS-CoV-2
3.
Eur Heart J Case Rep ; 5(2): ytaa521, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1334208

ABSTRACT

BACKGROUND: Since the first documented outbreak of a novel severe acute respiratory syndrome inducing Coronavirus in China at the end of 2019 the virus has spread to all continents, leading the WHO to declare a pandemic in March 2020. While this virus primarily targets the alveoli in the lungs, multiple authors have described an increased rate of thrombo-embolic events in affected patients. We present this case of a myocardial infarction with no obstructive coronary atherosclerosis in an otherwise healthy 48-year-old patient. CASE SUMMARY: A 48-year-old female, presenting with chest pain radiating to her left shoulder with no cardiovascular risk factors other than genetic predisposition, was screened for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and tested positive. Although computed tomography angiography excluded obstructive coronary heart disease, cardiac magnetic resonance imaging showed an acute myocardial infarction with no obstructive coronary arteries of the inferior wall. The patient was treated with dual anti-platelet therapy, an angiotensin-converting-enzyme inhibitor and a statin, and assigned to a cardiac rehabilitation program. CONCLUSION: We report a serious thrombo-embolic event during an oligosymptomatic SARS-CoV-2 infection in a healthy, young patient. While these two diseases may have occurred simultaneously, by chance, it is possible that the pro-thrombotic effects of the SARS-CoV-2 infection facilitated the infarction. This case further demonstrates the significant cardiovascular morbidity potentially caused by SARS-CoV-2.

4.
Int J Mol Sci ; 22(8)2021 Apr 17.
Article in English | MEDLINE | ID: covidwho-1298166

ABSTRACT

The virus responsible for the current COVID-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a new virus with high infectivity and moderate mortality. The major clinical manifestation of COVID-19 is interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS). However, the disease causes a potent systemic hyperin-flammatory response, i.e., a cytokine storm or macrophage activation syndrome (MAS), which is associated with thrombotic complications. The complexity of the disease requires appropriate intensive treatment. One of promising treatment is statin administration, these being 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that exert pleiotropic anti-inflammatory effects. Recent studies indicate that statin therapy is associated with decreased mortality in COVID-19, which may be caused by direct and indirect mechanisms. According to literature data, statins can limit SARS-CoV-2 cell entry and replication by inhibiting the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). The cytokine storm can be ameliorated by lowering serum IL-6 levels; this can be achieved by inhibiting Toll-like receptor 4 (TLR4) and modulating macrophage activity. Statins can also reduce the complications of COVID-19, such as thrombosis and pulmonary fibrosis, by reducing serum PAI-1 levels, attenuating TGF-ß and VEGF in lung tissue, and improving endothelial function. Despite these benefits, statin therapy may have side effects that should be considered, such as elevated creatinine kinase (CK), liver enzyme and serum glucose levels, which are already elevated in severe COVID-19 infection. The present study analyzes the latest findings regarding the benefits and limitations of statin therapy in patients with COVID-19.


Subject(s)
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Animals , COVID-19/complications , Endothelium/drug effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Inflammation/complications , Inflammation/drug therapy , Lipid Metabolism/drug effects , Macrophage Activation/drug effects , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , SARS-CoV-2/drug effects , Thrombosis/complications , Thrombosis/drug therapy
5.
Curr Opin Lipidol ; 32(4): 231-243, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1266229

ABSTRACT

PURPOSE OF REVIEW: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. RECENT FINDINGS: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. SUMMARY: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.


Subject(s)
Atherosclerosis/drug therapy , COVID-19/drug therapy , Cardiovascular Diseases/drug therapy , Dyslipidemias/drug therapy , Atherosclerosis/complications , Atherosclerosis/epidemiology , Atherosclerosis/virology , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/virology , Cholesterol, LDL/drug effects , Dyslipidemias/complications , Dyslipidemias/epidemiology , Dyslipidemias/virology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents/therapeutic use , SARS-CoV-2/pathogenicity
6.
Hum Vaccin Immunother ; 17(9): 2841-2850, 2021 09 02.
Article in English | MEDLINE | ID: covidwho-1246659

ABSTRACT

The COVID-19 pandemic has disrupted life throughout the world. Newly developed vaccines promise relief to people who live in high-income countries, although vaccines and expensive new treatments are unlikely to arrive in time to help people who live in low-and middle-income countries. The pathogenesis of COVID-19 is characterized by endothelial dysfunction. Several widely available drugs like statins, ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have immunometabolic activities that (among other things) maintain or restore endothelial cell function. For this reason, we undertook an observational study in four Belgian hospitals to determine whether in-hospital treatment with these drugs could improve survival in 959 COVID-19 patients. We found that treatment with statins and ACEIs/ARBs reduced 28-day mortality in hospitalized COVID-19 patients. Moreover, combination treatment with these drugs resulted in a 3-fold reduction in the odds of hospital mortality (OR = 0.33; 95% CI 0.17-0.69). These findings were in general agreement with other published studies. Additional observational studies and clinical trials are needed to convincingly show that in-hospital treatment with statins, ACEIs/ARBs, and especially their combination saves lives.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypertension , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Belgium/epidemiology , Hospital Mortality , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pandemics , SARS-CoV-2
7.
eNeurologicalSci ; 23: 100344, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1210926

ABSTRACT

There is a continuing need for research about the underlying mechanisms behind ischemic strokes in COVID-19 patients. Pre-existing endothelial dysfunction, especially if it is accompanied by a viral infection of the endothelial cells may present an important mechanism behind the immunothrombotic/thromboembolic complications of the COVID-19 illness. Here we emphasize that pharmacotherapy with statins could partly counteract such pathophysiological scenarios. Accordingly, using familial hypercholesterolemia (FH) as a pertinent example of a lifelong endothelial dysfunction, we aim to make the clinicians and consulting neurologists aware of statins as a possible adjuvant therapy in the context of an increased risk of ischemic stroke in patients with COVID-19. Based on recent clinical evidence, there is a need to encourage clinicians and consulting neurologists to continue or initiate effective statin treatment to prevent an ischemic stroke, particularly when they encounter a hypercholesterolemic COVID-19 patient with FH.

8.
J Clin Pharmacol ; 61(10): 1286-1300, 2021 10.
Article in English | MEDLINE | ID: covidwho-1204756

ABSTRACT

The interaction of coronavirus disease (COVID-19) with the majority of common prescriptions is broadly unknown. The purpose of this study is to identify medications associated with altered disease outcomes in COVID-19. A retrospective cohort composed of all adult inpatient admissions to our center with COVID-19 was analyzed. Data concerning all antecedent prescriptions were collected and agents brought forward for analysis if prescribed to at least 20 patients in our cohort. Forty-two medications and 22 classes of medication were examined. Groups were propensity score matched and analyzed by logistic and linear regression. The majority of medications did not show a statistically significant relationship with altered disease outcomes. Lower mortality was associated with use of pregabalin (hazard ratio [HR], 0.10; 95% confidence interval [CI], 0.01-0.92; P = .049) and inhalers of any type (HR, 0.33; 95%CI, 0.14-0.80; P = .015), specifically beclomethasone (HR, 0.10; 95%CI, 0.01-0.82; P = .032), tiotropium (HR, 0.07; 95%CI, 0.01-0.83; P = .035), and steroid-containing inhalers (HR, 0.35; 95%CI, 0.15-0.79; P = .013). Gliclazide (HR, 4.37; 95%CI, 1.26-15.18; P = .020) and proton pump inhibitor (HR, 1.72; 95%CI, 1.06-2.79; P = .028) use was associated with greater mortality. Diuretic (HR, 0.07; 95%CI, 0.01-0.37; P = .002) and statin (HR, 0.35; 95%CI, 0.17-0.73; P = .006) use was associated with lower rates of critical care admission. Our data lends confidence to observing usual practice in patients with COVID-19 by continuing antecedent prescriptions in the absence of an alternative acute contraindication. We highlight potential benefits in investigation of diuretics, inhalers, pregabalin, and statins as therapeutic agents for COVID-19 and support further assessment of the safety of gliclazide and proton pump inhibitors in the acute illness.


Subject(s)
COVID-19 , Hospitalization/statistics & numerical data , Prescription Drugs , SARS-CoV-2/drug effects , Aged , COVID-19/mortality , COVID-19/therapy , COVID-19 Testing/methods , Critical Care Outcomes , Female , Humans , Male , Prescription Drugs/classification , Prescription Drugs/therapeutic use , Propensity Score , Retrospective Studies , Risk Assessment , Severity of Illness Index , United Kingdom/epidemiology
9.
High Blood Press Cardiovasc Prev ; 28(4): 355-364, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1202877

ABSTRACT

INTRODUCTION: The outbreak by SARS-CoV-2 has rapidly spread worldwide. The need for specific treatments to adequately stop the inflammatory response and its sequelae is day by day more urgent and many therapeutic strategies were performed since COVID-19 burst in the last months. Statins were thought to be effective against this novel coronavirus for their anti-inflammatory properties, even if the real effects on COVID patients are still partially unexplored. METHODS: We retrospectively evaluated 501 adult patients, consecutively admitted to the two COVID-hospitals of Ferrara's territory, and divided them into two groups: ST = patients on statin therapy on admission and NST=patients not on statin therapy on admission. We searched for differences between groups in terms of anamnestic, clinical and laboratory data and then in terms of COVID-19 outcomes. RESULTS: We found significant differences between groups in terms of age, comorbidities, procalcitonin and CPK serum levels: ST patients were older, more comorbid, with lower procalcitonin and higher CPK serum levels. Male sex was, together with the Charlson Comorbidity Index, an independent predictor of needing intensification of care, while age only was a good predictor of in-hospital and 100-day mortality. Differences were also found in the survival functions between the two groups. CONCLUSIONS: After a period of observation of 100 days, ST patients, despite their older age and their greater load of comorbidities, have similar survival functions to NST patients. If adjusted for age and CCI the survival functions of ST group are considerably more favourable than those of the second group.


Subject(s)
COVID-19/drug therapy , Dyslipidemias/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , COVID-19/virology , Comorbidity , Dyslipidemias/diagnosis , Dyslipidemias/mortality , Female , Hospital Mortality , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Italy , Male , Middle Aged , Patient Admission , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young Adult
10.
Elife ; 102021 04 23.
Article in English | MEDLINE | ID: covidwho-1200330

ABSTRACT

Many enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ~6000 drugs and >30 spike variants. Together with quantitative cell biology approaches, the screen reveals an essential role for biophysical aspects of the membrane, particularly cholesterol-rich regions, in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates. Our findings potentially provide a molecular basis for positive outcomes reported in COVID-19 patients taking statins and suggest new strategies for therapeutics targeting the membrane of SARS-CoV-2 and other fusogenic viruses.


Subject(s)
COVID-19/pathology , Giant Cells/pathology , Host-Pathogen Interactions , SARS-CoV-2/physiology , Virus Internalization , A549 Cells , Angiotensin-Converting Enzyme 2/metabolism , Cholesterol , Coculture Techniques , Humans , Lung/pathology , Membrane Fusion , Membrane Lipids/metabolism
11.
Arterioscler Thromb Vasc Biol ; 41(3): e175-e182, 2021 03.
Article in English | MEDLINE | ID: covidwho-1189968

ABSTRACT

OBJECTIVE: Although statins are widely prescribed lipid-lowering drugs, there are concerns about the safety of their use in the context of coronavirus disease 2019 (COVID-19), since statins increase the expression of ACE2 (angiotensin-converting enzyme 2). This study aimed to disclose the association between statins and 60-day COVID-19 mortality. Approach and Results: All patients hospitalized with laboratory-confirmed COVID-19 were enrolled in this study from January 19 to April 16, 2020, in Korea. We evaluated the association between the use of statins and COVID-19-related mortality in the overall and the nested 1:2 propensity score-matched study. Furthermore, a comparison of the hazard ratio for death was performed between COVID-19 patients and a retrospective cohort of patients hospitalized with pneumonia between January and June 2019 in Korea. The median age of the 10 448 COVID-19 patients was 45 years. Statins were prescribed in 533 (5.1%) patients. After adjusting for age, sex, and comorbidities, Cox regression showed a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425-0.953]; P=0.0283). Moreover, on comparing the hazard ratio between COVID-19 patients and the retrospective cohort of hospitalized pneumonia patients, the use of statins showed similar benefits. CONCLUSIONS: The use of statins correlates significantly with lower mortality in patients with COVID-19, consistent with the findings in patients with pneumonia. Graphic Abstract: A graphic abstract is available for this article.


Subject(s)
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pandemics , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/complications , COVID-19/mortality , Child , Child, Preschool , Cohort Studies , Diabetes Complications/drug therapy , Diabetes Complications/mortality , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Infant , Infant, Newborn , Male , Middle Aged , Pneumonia/drug therapy , Pneumonia/mortality , Propensity Score , Proportional Hazards Models , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/mortality , Republic of Korea/epidemiology , Retrospective Studies , Young Adult
12.
Cytokine Growth Factor Rev ; 60: 28-45, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1184922

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicits an interferon (IFN) deficiency state, which aggravates the type I interferon deficiency and slow IFN responses, which associate with e.g. aging and obesity. Additionally, SARS-CoV-2 may also elicit a cytokine storm, which accounts for disease progression and ultimately the urgent need of ventilator support. Based upon several reports, it has been argued that early treatment with IFN-alpha2 or IFN-beta, preferentially in the early disease stage, may prohibit disease progression. Similarly, preliminary studies have shown that JAK1/2 inhibitor treatment with ruxolitinib or baricitinib may decrease mortality by dampening the deadly cytokine storm, which - in addition to the virus itself - also contributes to multi-organ thrombosis and multi-organ failure. Herein, we describe the rationale for treatment with IFNs (alpha2 or beta) and ruxolitinib emphasizing the urgent need to explore these agents in the treatment of SARS-CoV-2 - both as monotherapies and in combination. In this context, we take advantage of several safety and efficacy studies in patients with the chronic myeloproliferative blood cancers (essential thrombocythemia, polycythemia vera and myelofibrosis) (MPNs), in whom IFN-alpha2 and ruxolitinib have been used successfully for the last 10 (ruxolitinib) to 30 years (IFN) as monotherapies and most recently in combination as well. In the context of these agents being highly immunomodulating (IFN boosting immune cells and JAK1/2 inhibitors being highly immunosuppressive and anti-inflammatory), we also discuss if statins and hydroxyurea, both agents possessing anti-inflammatory, antithrombotic and antiviral potentials, might be inexpensive agents to be repurposed in the treatment of SARS-CoV-2.


Subject(s)
COVID-19/drug therapy , Cytokine Release Syndrome/virology , Interferons/deficiency , Interferons/therapeutic use , Janus Kinase 1/antagonists & inhibitors , Janus Kinase 2/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , SARS-CoV-2/pathogenicity , Animals , COVID-19/immunology , COVID-19/pathology , Clinical Trials as Topic , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/pathology , Humans , SARS-CoV-2/immunology
13.
Drugs ; 81(6): 685-695, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1157035

ABSTRACT

BACKGROUND: The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS: This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS: After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS: Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.


Subject(s)
COVID-19/complications , COVID-19/epidemiology , Hospital Mortality/trends , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Aged , Aged, 80 and over , COVID-19/mortality , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Risk Assessment , SARS-CoV-2 , Spain/epidemiology
14.
Wien Klin Wochenschr ; 133(17-18): 958-965, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1155277

ABSTRACT

On 11 March 2020 the World Health Organization (WHO) declared a status of global pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019, COVID-19). The pandemic is currently underway, and to date has caused approximately 2.42 million deaths worldwide. The first vaccines have recently been licensed; however, research continues to identify therapeutic agents to prevent serious complications, such as anti-inflammatory, immunomodulatory, anticoagulant or antiviral agents authorized for other therapeutic indications. Epidemiological evidence shows that advanced age and comorbidities, such as diabetes, heart disease, and dyslipidemia may represent COVID-19 risk factors. In particular, in patients with hypercholesterolemia treated with statins, it is recommended that treatment should not be discontinued if COVID-19 infection occurs. The pleiotropic effects of statins are well known. In this brief review, we propose that the use of statins can potentially protect against SARS-CoV-2-induced tissue damage and improve lung function in COVID-19 patients through several pleiotropic effects. Pleiotropic effects of statins that may be a significant benefit in patients with hypercholesterolemia treated with statins and COVID-19 positive. Recent evidence shows promising results.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Pharmaceutical Preparations , COVID-19/drug therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SARS-CoV-2
15.
J Clin Lipidol ; 15(3): 451-459, 2021.
Article in English | MEDLINE | ID: covidwho-1118495

ABSTRACT

BACKGROUND: Statins have been associated with a reduction in inflammatory markers and improved endothelial function. Whether statins offer any benefit in COVID-19 needs to be elucidated. OBJECTIVE: To determine the association between antecedent statin use and severe disease outcomes among COVID-19 patients. METHODS: A retrospective cohort study on 1014 patients with confirmed COVID-19 diagnosis. Outcomes were mortality, need for mechanical ventilation, and intensive care admission. Patients were classified into statin-users vs statin non-users based on antecedent use of statins. Multivariable regression analysis was performed adjusting for confounders such as age, sex, race, BMI, smoking, insurance, and comorbidities. Propensity score matching was performed to achieve a 1:1 balanced cohort. RESULTS: A total of 1014 patients (Median age 65 (IQR 53-73); 530 (52.3%) males; 753 (74.3%) African Americans; median BMI 29.4 (IQR 25.1-35.9); 615 (60.7%) with Medicare insurance) were included in the study. About 454 patients (44.77%) were using statins as home medication. Antecedent statin use was associated with significant decrease in mortality in the total cohort (OR, 0.66; 95% CI, 0.46 - 0.95; p = 0.03). Among the propensity score matched (PSM) cohort of 466 patients (233 statin users and 233 statin non-users), all the baseline characteristics had similar distribution among the two groups. Statin users had significant reduction in mortality in the PSM cohort as well (OR, 0.56; 95% CI, 0.37 - 0.83; p = 0.004). CONCLUSIONS: Statin use was associated with significant reduction in mortality among COVID-19 patients. These findings support the pursuit of randomized clinical trials to explore the possible benefits of statins in COVID-19.


Subject(s)
COVID-19/drug therapy , Hospital Mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , SARS-CoV-2 , Adolescent , Adult , Aged , COVID-19/mortality , Female , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Risk Assessment
16.
Am J Med Sci ; 361(6): 725-730, 2021 06.
Article in English | MEDLINE | ID: covidwho-1116186

ABSTRACT

BACKGROUND: Coronavirus disease-19 (COVID-19) infection is associated with an uncontrolled systemic inflammatory response. Statins, given their anti-inflammatory properties, may reduce the associated morbidity and mortality. This study aimed to determine the association between statin use prior to hospitalization and in-hospital mortality in COVID-19 patients. METHODS: In this retrospective study, clinical data were collected from the electronic medical records of patients admitted to the hospital with confirmed COVID-19 infection from March 1, 2020 to April 24, 2020. A multivariate regression analysis was performed to study the association of pre-admission statin use with in-hospital mortality. RESULTS: Of 255 patients, 116 (45.5%) patients were on statins prior to admission and 139 (54.5%) were not. The statin group had a higher proportion of end stage renal disease (ESRD) (13.8% vs. 2.9%, p = 0.001), diabetes mellitus (63.8% vs. 35.2%, p<0.001), hypertension (87.9% vs. 61.1%, p < 0.001) and coronary artery disease (CAD) (33.6% vs. 5%, p < 0.001). On multivariate analysis, we found a statistically significant decrease in the odds of in-hospital mortality in patients on statins before admission (OR 0.14, 95% CI 0.03- 0.61, p = 0.008). In the subgroup analysis, statins were associated with a decrease in mortality in those with CAD (OR 0.02, 95% CI 0.0003-0.92 p = 0.045) and those without CAD (OR 0.05, 95% CI 0.005-0.43, p = 0.007). CONCLUSIONS: Our study suggests that statins are associated with reduced in-hospital mortality among patients with COVID-19, regardless of CAD status. More comprehensive epidemiological and molecular studies are needed to establish the role of statins in COVID-19.


Subject(s)
COVID-19 , Dyslipidemias , Hospital Mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Anti-Inflammatory Agents/therapeutic use , COVID-19/mortality , COVID-19/therapy , Comorbidity , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Male , Mortality , Outcome Assessment, Health Care , Retrospective Studies , Risk Factors , SARS-CoV-2 , United States/epidemiology
18.
Front Med (Lausanne) ; 8: 639804, 2021.
Article in English | MEDLINE | ID: covidwho-1094176

ABSTRACT

The severe respiratory illness due to SARS-CoV-2, the virus responsible for coronavirus disease 2019 (COVID-19), is triggered by an intense pro-inflammatory host response. Statins, prescribed primarily for lipid reduction, are known to have anti-inflammatory and immunomodulatory properties and have been associated with a reduced mortality rate among COVID-19 patients taking statins as reported in two recent retrospective studies. However, a meta-analysis that included nine studies showed that statin use did not improve in-hospital outcomes of those with COVID-19. In addition, concerns regarding the use of statins and an increase in COVID-19 infections have been raised, as statins may increase the expression of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the SARS-CoV-2 virus. Our goal was to investigate the effect of statins in COVID-19 patients in a large, diverse patient population across the United States containing nearly 120,000 patients diagnosed with COVID-19. We used propensity score matching of demographics, comorbidities, and medication indication to compare statin-treated patients (N = 2,297) with matched controls (N = 4,594). We observed a small, but statistically significant, decrease in mortality among patients prescribed statins (16.1%) when compared with matched COVID-19-positive controls (18.0 to 20.6%). These results support previous evidence that statins do not increase COVID-19-related mortality and may, in fact, have a mitigating effect on severity of the disease reflected in a slight reduction in mortality. Mixed findings on effects of statins in COVID-19 patients reported in the literature should prompt prospective randomized controlled trials in order to define better who might be advantaged with respect to clinical outcomes.

19.
Pharmacol Rep ; 73(3): 769-780, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1091990

ABSTRACT

BACKGROUND AND AIMS: The idea of treating COVID-19 with statins is biologically plausible, although it is still controversial. The systematic review and meta-analysis aimed to address the association between the use of statins and risk of mortality in patients with COVID-19. METHODS: Several electronic databases, including PubMed, SCOPUS, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords up to 11 November 2020, were used to perform a systematic literature search. This study included research papers containing samples of adult COVID-19 patients who had data on statin use and recorded mortality as their outcome of interest. Risk estimates of mortality in statin users versus non-statin users were pooled across studies using inverse-variance weighted DerSimonian-Laird random-effect models. RESULTS: Thirteen studies with a total of 52,122 patients were included in the final qualitative and quantitative analysis. Eight studies reported in-hospital use of statins; meanwhile, the remaining studies reported pre-admission use of statins. In-hospital use of statin was associated with a reduced risk of mortality (RR 0.54, 95% CI 0.50-0.58, p < 0.00001; I2: 0%, p = 0.87), while pre-admission use of statin was not associated with mortality (RR 1.18, 95% CI 0.79-1.77, p = 0.415; I2: 68.6%, p = 0.013). The funnel plot for the association between the use of statins and mortality were asymmetrical. CONCLUSION: This meta-analysis showed that in-hospital use of statins was associated with a reduced risk of mortality in patients with COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , COVID-19/virology , Evaluation Studies as Topic , Hospitals , Humans , Risk , SARS-CoV-2/pathogenicity
20.
Prog Cardiovasc Dis ; 67: 53-64, 2021.
Article in English | MEDLINE | ID: covidwho-1091673

ABSTRACT

Myocarditis refers to the clinical and histological characteristics of a diverse range of inflammatory cellular pathophysiological conditions which result in cardiac dysfunction. Myocarditis is a major cause of mortality in individuals less than 40 years of age and accounts for approximately 20% of cardiovascular disease (CVD) events. Myocarditis contributes to dilated cardiomyopathy in 30% of patients and can progress to cardiac arrest, which has a poor prognosis of <40% survival over 10 years. Myocarditis has also been documented after infection with SARS-CoV-2. The most commonly used lipid-lowering therapies, HMG-CoA reductase inhibitors (statins), decrease CVD-related morbidity and mortality. In addition to their lipid-lowering effects, increasing evidence supports the existence of several additional beneficial, 'pleiotropic' effects of statins. Recently, several studies have indicated that statins may attenuate myocarditis. Statins modify the lipid oxidation, inflammation, immunomodulation, and endothelial activity of the pathophysiology and have been recommended as adjuvant treatment. In this review, we focus on the mechanisms of action of statins and their effects on myocarditis, SARS-CoV-2 and CVD.


Subject(s)
COVID-19/drug therapy , Cardiovascular Diseases/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocarditis/drug therapy , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Molecular Structure , Myocarditis/etiology
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