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1.
Sci Rep ; 11(1): 23874, 2021 12 13.
Article in English | MEDLINE | ID: covidwho-1569277

ABSTRACT

The worsening progress of coronavirus disease 2019 (COVID-19) is attributed to the proinflammatory state, leading to increased mortality. Statin works with its anti-inflammatory effects and may attenuate the worsening of COVID-19. COVID-19 patients were retrospectively enrolled from two academic hospitals in Wuhan, China, from 01/26/2020 to 03/26/2020. Adjusted in-hospital mortality was compared between the statin and the non-statin group by CHD status using multivariable Cox regression model after propensity score matching. Our study included 3133 COVID-19 patients (median age: 62y, female: 49.8%), and 404 (12.9%) received statin. Compared with the non-statin group, the statin group was older, more likely to have comorbidities but with a lower level of inflammatory markers. The Statin group also had a lower adjusted mortality risk (6.44% vs. 10.88%; adjusted hazard ratio [HR] 0.47; 95% CI, 0.29-0.77). Subgroup analysis of CHD patients showed a similar result. Propensity score matching showed an overall 87% (HR, 0.13; 95% CI, 0.05-0.36) lower risk of in-hospital mortality for statin users than nonusers. Such survival benefit of statin was obvious both among CHD and non-CHD patients (HR = 0.30 [0.09-0.98]; HR = 0.23 [0.1-0.49], respectively). Statin use was associated with reduced in-hospital mortality in COVID-19. The benefit of statin was both prominent among CHD and non-CHD patients. These findings may further reemphasize the continuation of statins in patients with CHD during the COVID-19 era.


Subject(s)
COVID-19/drug therapy , Coronary Disease/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Inpatients/statistics & numerical data , Adult , Aged , Aged, 80 and over , COVID-19/mortality , China/epidemiology , Comorbidity , Coronary Disease/mortality , Female , Hospital Mortality/trends , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Retrospective Studies , Treatment Outcome
2.
Pharmacol Res Perspect ; 9(6): e00861, 2021 12.
Article in English | MEDLINE | ID: covidwho-1487514

ABSTRACT

Most but not all observational studies of statin treatment of COVID-19 patients suggest that treatment improves outcomes. However, almost all of these studies fail to consider that withdrawing statins after hospital admission may have detrimental effects, a finding which cardiovascular investigators have known for 15-20 years. Continuing or starting statin treatment after hospital admission consistently improves cardiovascular outcomes. Similarly, inpatient statin treatment of COVID-19 improves survival. For this reason, observational studies of the effectiveness of outpatient-documented statin treatment of COVID-19 patients must consider the negative consequences of statin withdrawal after hospital admission.


Subject(s)
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hospital Mortality , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Meta-Analysis as Topic , Observational Studies as Topic , Patient Admission , Treatment Outcome , Withholding Treatment
3.
Lipids Health Dis ; 20(1): 141, 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1484314

ABSTRACT

The global coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 coronavirus started in March 2020. The conclusions from numerous studies indicate that people with comorbidities, such as arterial hypertension, diabetes, obesity, underlying cardiovascular disease, are particularly vulnerable to the severe course of COVID-19. The available data also suggest that patients with dyslipidemia, the most common risk factor of cardiovascular diseases, are also at greater risk of severe course of COVID-19. On the other hand, it has been shown that COVID-19 infection has an influence on lipid profile leading to dyslipidemia, which might require appropriate treatment. Owing to antiviral, anti-inflammatory, immunomodulatory, and cardioprotective activity, statin therapy has been considered as valuable tool to improve COVID-19 outcomes. Numerous observational studies have shown potential beneficial effects of lipid-lowering treatment on the course of COVID-19 with significant improved prognosis and reduced mortality.


Subject(s)
COVID-19/etiology , Dyslipidemias/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemia Type II/drug therapy , COVID-19/drug therapy , COVID-19/epidemiology , Comorbidity , Dyslipidemias/epidemiology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hyperlipoproteinemia Type II/epidemiology , Hyperlipoproteinemia Type II/metabolism , Lipid Metabolism , Prognosis
4.
PLoS Med ; 18(10): e1003820, 2021 10.
Article in English | MEDLINE | ID: covidwho-1468149

ABSTRACT

BACKGROUND: The relationship between statin treatment and Coronavirus Disease 2019 (COVID-19) mortality has been discussed due to the pleiotropic effects of statins on coagulation and immune mechanisms. However, available observational studies are hampered by study design flaws, resulting in substantial heterogeneity and ambiguities. Here, we aim to determine the relationship between statin treatment and COVID-19 mortality. METHODS AND FINDINGS: This cohort study included all Stockholm residents aged 45 or older (N = 963,876), followed up from 1 March 2020 until 11 November 2020. The exposure was statin treatment initiated before the COVID-19-pandemic, defined as recorded statin dispensation in the Swedish Prescribed Drug Register between 1 March 2019 and 29 February 2020. COVID-19-specific mortality was ascertained from the Swedish Cause of Death Registry. Hazard ratios (HRs) were calculated using multivariable Cox regression models. We further performed a target trial emulation restricted to initiators of statins. In the cohort (51.6% female), 169,642 individuals (17.6%) were statin users. Statin users were older (71.0 versus 58.0 years), more likely to be male (53.3% versus 46.7%), more often diagnosed with comorbidities (for example, ischemic heart disease 23.3% versus 1.6%), more frequently on anticoagulant and antihypertensive treatments, less likely to have a university-level education (34.5% versus 45.4%), and more likely to have a low disposable income (20.6% versus 25.2%), but less likely to reside in crowded housing (6.1% versus 10.3%). A total of 2,545 individuals died from COVID-19 during follow-up, including 765 (0.5%) of the statin users and 1,780 (0.2%) of the nonusers. Statin treatment was associated with a lowered COVID-19 mortality (adjusted HR, 0.88; 95% CI, 0.79 to 0.97, P = 0.01), and this association did not vary appreciably across age groups, sexes, or COVID-19 risk groups. The confounder adjusted HR for statin treatment initiators was 0.78 (95% CI, 0.59 to 1.05, P = 0.10) in the emulated target trial. Limitations of this study include the observational design, reliance on dispensation data, and the inability to study specific drug regimens. CONCLUSIONS: Statin treatment had a modest negative association with COVID-19 mortality. While this finding needs confirmation from randomized clinical trials, it supports the continued use of statin treatment for medical prevention according to current recommendations also during the COVID-19 pandemic.


Subject(s)
COVID-19/mortality , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Aged, 80 and over , COVID-19/prevention & control , Female , Humans , Male , Middle Aged , Registries , Sweden/epidemiology
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.
Biomed Res Int ; 2021: 1901772, 2021.
Article in English | MEDLINE | ID: covidwho-1440845

ABSTRACT

Background: Although vaccine rollout for COVID-19 has been effective in some countries, there is still an urgent need to reduce disease transmission and severity. We recently carried out a meta-analysis and found that pre- and in-hospital use of statins may improve COVID-19 mortality outcomes. Here, we provide an updated meta-analysis in an attempt to validate these results and increase the statistical power of these potentially important findings. Methods: The meta-analysis investigated the effect of observational and randomized clinical studies on intensive care unit (ICU) admission, tracheal intubation, and death outcomes in COVID-19 cases involving statin treatment, by searching the scientific literature up to April 23, 2021. Statistical analysis and random effect modeling were performed to assess the combined effects of the updated and previous findings on the outcome measures. Findings. The updated literature search led to the identification of 23 additional studies on statin use in COVID-19 patients. Analysis of the combined studies (n = 47; 3,238,508 subjects) showed no significant effect of statin treatment on ICU admission and all-cause mortality but a significant reduction in tracheal intubation (OR = 0.73, 95% CI: 0.54-0.99, p = 0.04, n = 10 studies). The further analysis showed that death outcomes were significantly reduced in the patients who received statins during hospitalization (OR = 0.54, 95% CI: 0.50-0.58, p < 0.001, n = 7 studies), with no such effect of statin therapy before hospital admission (OR = 1.06, 95% CI = 0.82-1.37, p = 0.670, n = 29 studies). Conclusion: Taken together, this updated meta-analysis extends and confirms the findings of our previous study, suggesting that in-hospital statin use leads to significant reduction of all-cause mortality in COVID-19 cases. Considering these results, statin therapy during hospitalization, while indicated, should be recommended.


Subject(s)
COVID-19/drug therapy , Hospitalization/trends , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intubation, Intratracheal/trends , COVID-19/mortality , Cause of Death/trends , Hospitalization/statistics & numerical data , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Intensive Care Units , Intubation, Intratracheal/statistics & numerical data , Models, Statistical , Observational Studies as Topic , Randomized Controlled Trials as Topic , Survival Analysis , Treatment Outcome
8.
PLoS One ; 16(9): e0256899, 2021.
Article in English | MEDLINE | ID: covidwho-1403304

ABSTRACT

BACKGROUND: There is an urgent need for novel therapeutic strategies for reversing COVID-19-related lung inflammation. Recent evidence has demonstrated that the cholesterol-lowering agents, statins, are associated with reduced mortality in patients with various respiratory infections. We sought to investigate the relationship between statin use and COVID-19 disease severity in hospitalized patients. METHODS: A retrospective analysis of COVID-19 patients admitted to the Johns Hopkins Medical Institutions between March 1, 2020 and June 30, 2020 was performed. The outcomes of interest were mortality and severe COVID-19 infection, as defined by prolonged hospital stay (≥ 7 days) and/ or invasive mechanical ventilation. Logistic regression, Cox proportional hazards regression and propensity score matching were used to obtain both univariable and multivariable associations between covariates and outcomes in addition to the average treatment effect of statin use. RESULTS: Of the 4,447 patients who met our inclusion criteria, 594 (13.4%) patients were exposed to statins on admission, of which 340 (57.2%) were male. The mean age was higher in statin users compared to non-users [64.9 ± 13.4 vs. 45.5 ± 16.6 years, p <0.001]. The average treatment effect of statin use on COVID-19-related mortality was RR = 1.00 (95% CI: 0.99-1.01, p = 0.928), while its effect on severe COVID-19 infection was RR = 1.18 (95% CI: 1.11-1.27, p <0.001). CONCLUSION: Statin use was not associated with altered mortality, but with an 18% increased risk of severe COVID-19 infection.


Subject(s)
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies
10.
Contemp Clin Trials ; 110: 106547, 2021 11.
Article in English | MEDLINE | ID: covidwho-1372905

ABSTRACT

BACKGROUND: Despite improvement in the standard of care (SOC) for hospitalized COVID-19 patients, rates of morbidity and mortality remain high. There continues to be a need for easily available and cost-effective treatments. Colchicine and rosuvastatin are both safe and well-studied medications with anti-inflammatory and other pleiotropic effects that may provide additional benefits to hospitalized COVID-19 patients. METHODS AND RESULTS: The Colchicine/Statin for the Prevention of COVID-19 Complications (COLSTAT) trial is a pragmatic, open-label, multicenter, randomized trial comparing the combination of colchicine and rosuvastatin in addition to SOC to SOC alone in hospitalized COVID-19 patients. Four centers in the Yale New Haven Health network will enroll a total of 466 patients with 1:1 randomization. The trial will utilize the electronic health record (Epic® Systems, Verona, Wisconsin, USA) at all stages including screening, randomization, intervention, event ascertainment, and follow-up. The primary endpoint is the 30-day composite of progression to severe COVID-19 disease as defined by the World Health Organization ordinal scale of clinical improvement and arterial/venous thromboembolic events. The secondary powered endpoint is the 30-day composite of death, respiratory failure requiring intubation, and myocardial injury. CONCLUSIONS: The COLSTAT trial will provide evidence on the efficacy of repurposing colchicine and rosuvastatin for the treatment of hospitalized COVID-19 patients. Moreover, it is designed to be a pragmatic trial that will demonstrate the power of using electronic health records to improve efficiency and enrollment in clinical trials in an adapting landscape. CLINICAL TRIAL REGISTRATION: NCT04472611 (https://clinicaltrials.gov/ct2/show/NCT04472611).


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Colchicine/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SARS-CoV-2 , Treatment Outcome
11.
J Cardiovasc Pharmacol ; 78(1): e94-e100, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1356725

ABSTRACT

ABSTRACT: Statin therapy has been recently suggested as possible adjuvant treatment to improve the clinical outcome in patients with coronavirus disease 2019 (COVID-19). The aim of this study was to describe the prevalence of preadmission statin therapy in hospitalized patients with COVID-19 and to investigate its potential association with acute distress respiratory syndrome (ARDS) at admission and in-hospital mortality. We retrospectively recruited 467 patients with laboratory-confirmed COVID-19 admitted to the emergency department of 10 Italian hospitals. The study population was divided in 2 groups according to the ARDS diagnosis at admission and in-hospital mortality. A multivariable regression analysis was performed to assess the risk of ARDS at admission and death during hospitalization among patients with COVID-19. A competing risk analysis in patients taking or not statins before admission was also performed. ARDS at admission was reported in 122 cases (26.1%). There was no statistically significant difference for clinical characteristics between patients presenting with and without ARDS. One hundred seven patients (18.5%) died during the hospitalization; they showed increased age (69.6 ± 13.1 vs. 66.1 ± 14.9; P = 0.001), coronary artery disease (23.4% vs. 12.8%; P = 0.012), and chronic kidney disease (20.6% vs. 11.1%; P = 0.018) prevalence; moreover, they presented more frequently ARDS at admission (48.6% vs. 19.4%; P < 0.001). At multivariable regression model, statin therapy was not associated neither with ARDS at admission nor with in-hospital mortality. Preadmission statin therapy does not seem to show a protective effect in severe forms of COVID-19 complicated by ARDS at presentation and rapidly evolving toward death.


Subject(s)
COVID-19/therapy , Dyslipidemias/drug therapy , Hospitalization , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Comorbidity , Disease Progression , Dyslipidemias/diagnosis , Dyslipidemias/mortality , Female , Hospital Mortality , Humans , Italy , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors
12.
Int J Infect Dis ; 110: 374-381, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1347651

ABSTRACT

OBJECTIVES: There is conflicting evidence about the efficacy of statin use in regard to clinical outcomes in patients with coronavirus disease 2019 (COVID-19). A systematic review and meta-analysis was performed to examine the effect of statin use on mortality in COVID-19 patients. METHODS: The electronic databases were searched, from inception to March 3, 2021. Unadjusted and adjusted effect estimates with their 95% confidence intervals (95% CI) were pooled using random-effects models. RESULTS: Twenty-five cohort studies involving 147 824 patients were included. The mean age of the patients ranged from 44.9 to 70.9 years; 57% of patients were male and 43% were female. The use of statins was not associated with mortality when applying the unadjusted risk ratio (uRR 1.16, 95% CI 0.86-1.57; 19 studies). In contrast, meta-analyses of the adjusted odds ratio (aOR 0.67, 95% CI 0.52-0.86; 11 studies) and adjusted hazard ratio (aHR 0.73, 95% CI 0.58-0.91; 10 studies) showed that statins were independently associated with a significant reduction in mortality. Subgroup analyses showed that only chronic use of statins significantly reduced mortality according to the adjusted models. CONCLUSIONS: The use of statins was found to be associated with a lower risk of mortality in COVID-19 patients based on adjusted effects of cohort studies. However, randomized controlled trials are still needed to confirm these findings.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Adult , Aged , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Risk , SARS-CoV-2
14.
Adv Exp Med Biol ; 1327: 205-214, 2021.
Article in English | MEDLINE | ID: covidwho-1316250

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
15.
PLoS One ; 16(7): e0254635, 2021.
Article in English | MEDLINE | ID: covidwho-1311289

ABSTRACT

BACKGROUND: Statins have anti-inflammatory and immunomodulatory effects that may reduce the severity of coronavirus disease 2019 (COVID-19), in which organ dysfunction is mediated by severe inflammation. Large studies with diverse populations evaluating statin use and outcomes in COVID-19 are lacking. METHODS AND RESULTS: We used data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease (CVD) Registry to evaluate the associations between statin use and outcomes. Prior to admission, 42% of subjects (n = 4,449) used statins (7% on statins alone, 35% on statins plus anti-hypertensives). Death (or discharge to hospice) occurred in 2,212 subjects (21%). Outpatient use of statins, either alone or with anti-hypertensives, was associated with a reduced risk of death (adjusted odds ratio [aOR] 0.59, 95% CI 0.50-0.69), adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications by logistic regression. In propensity-matched analyses, use of statins and/or anti-hypertensives was associated with a reduced risk of death among those with a history of CVD and/or hypertension (aOR 0.68, 95% CI 0.58-0.81). An observed 16% reduction in odds of death among those without CVD and/or hypertension was not statistically significant. CONCLUSIONS: Patients taking statins prior to hospitalization for COVID-19 had substantially lower odds of death, primarily among individuals with a history of CVD and/or hypertension. These observations support the continuation and aggressive initiation of statin and anti-hypertensive therapies among patients at risk for COVID-19, if these treatments are indicated based upon underlying medical conditions.


Subject(s)
Antihypertensive Agents/administration & dosage , COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Registries/statistics & numerical data , Adult , Age Factors , Aged , American Heart Association , Antihypertensive Agents/therapeutic use , COVID-19/mortality , Cardiovascular Diseases/drug therapy , Drug Utilization/statistics & numerical data , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Mortality/trends , Population Groups/statistics & numerical data , United States
16.
Cardiovasc Toxicol ; 21(10): 781-789, 2021 10.
Article in English | MEDLINE | ID: covidwho-1306730

ABSTRACT

Since the onset of the global COVID-19 pandemic, there has been much discussion about the advantages and disadvantages of ongoing chronic drug therapies in SARS-CoV-2-positive patients. These discussions include also statins treatment. The statins are among the most widely used drugs in the global population. Statins aim to lower cholesterol, which is essential for many biological processes but can lead to heart disease if levels are too high; however, also the pleiotropic effects of statins are well known. So could the anti-inflammatory or the potential antiviral effects of statins be helpful in avoiding extreme inflammation and severity in COVID-19? To date, there are conflicting opinions on the effects of statins in the course of COVID-19 infection. The aim of this article is to describe the molecular and pharmacological basis of the pleiotropic effects of statins that could be more involved in the fight against COVID-19 infection and to investigate the current epidemiological evidence in the literature on the current and important topic.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Heart Diseases/drug therapy , Heart/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SARS-CoV-2/drug effects , Animals , Anti-Inflammatory Agents/adverse effects , Antiviral Agents/adverse effects , COVID-19/epidemiology , COVID-19/physiopathology , COVID-19/virology , Heart/physiopathology , Heart/virology , Heart Diseases/epidemiology , Heart Diseases/physiopathology , Heart Diseases/virology , Host-Pathogen Interactions , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , SARS-CoV-2/pathogenicity , Treatment Outcome
17.
Cardiovasc Diabetol ; 20(1): 140, 2021 07 10.
Article in English | MEDLINE | ID: covidwho-1304404

ABSTRACT

BACKGROUND: The pleiotropic effects of statins may reduce the severity of COVID-19 disease. This study aims to determine the association between inpatient statin use and severe disease outcomes among hospitalized COVID-19 patients, especially those with Diabetes Mellitus (DM). RESEARCH DESIGN AND METHODS: A retrospective cohort study on hospitalized patients with confirmed COVID-19 diagnosis. The primary outcome was mortality during hospitalization. Patients were classified into statin and non-statin groups based on the administration of statins during hospitalization. Analysis included multivariable regression analysis adjusting for confounders and propensity score matching to achieve a 1:1 balanced cohort. Subgroup analyses based on presence of DM were conducted. RESULTS: In the cohort of 922 patients, 413 had a history of DM. About 27.1% patients (n = 250) in the total cohort (TC) and 32.9% patients (n = 136) in DM cohort received inpatient statins. Atorvastatin (n = 205, 82%) was the most commonly prescribed statin medication in TC. On multivariable analysis in TC, inpatient statin group had reduced mortality compared to the non-statin group (OR, 0.61; 95% CI, 0.42-0.90; p = 0.01). DM modified this association between inpatient statins and mortality. Patients with DM who received inpatient statins had reduced mortality (OR, 0.35; 95% CI, 0.21-0.61; p < 0.001). However, no such association was noted among patients without DM (OR, 1.21; 95% CI, 0.67-2.17; p = 0.52). These results were further validated using propensity score matching. CONCLUSIONS: Inpatient statin use was associated with significant reduction in mortality among COVID-19 patients especially those with DM. These findings support the pursuit of randomized clinical trials and inpatient statin use appears safe among COVID-19 patients.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Hospitalization/trends , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , COVID-19/diagnosis , Cohort Studies , Diabetes Mellitus/diagnosis , Female , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Treatment Outcome
18.
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
19.
Atherosclerosis ; 330: 114-121, 2021 08.
Article in English | MEDLINE | ID: covidwho-1283933

ABSTRACT

BACKGROUND AND AIMS: Statin therapy is administered to patients with high cardiovascular risk. These patients are also at risk for severe course of coronavirus disease 2019 (COVID-19). Statins exhibit not only cardioprotective but also immunomodulatory and anti-inflammatory effects. This study performed a systematic review of published evidence regarding statin treatment and COVID-19 related mortality. METHODS: A systematic PubMed/Embase search was performed from February 10, 2020 until March 05, 2021 for studies in COVID-19 patients that reported adjusted hazard or odds ratio for death in statin users versus non-users. RESULTS: 22 studies fulfilled the inclusion criteria and were included in the systematic review. Meta-analysis of 10 studies (n = 41,807, weighted age 56 ± 8 years, men 51%, hypertension 34%, diabetes 21%, statin users 14%) that reported adjusted hazard ratios for mortality in statin users versus non-users showed pooled estimate at 0.65 (95% confidence intervals [CI] 0.53, 0.81). Meta-analysis of 6 studies that reported continuation of statin therapy during hospitalization (58-100% of patients) revealed a pooled hazard ratio of 0.54 (95% CI 0.47, 0.62). Meta-analysis of 12 studies (n = 72,881, weighted age 65 ± 2 years, men 54%, hypertension 66%, diabetes 43%, statin users 30%) that reported adjusted odds ratios for mortality showed pooled estimate at 0.65 (95% CI 0.55, 0.78). Multivariable meta-regression analysis did not reveal any significant association of hazard or odds ratios with anthropometric characteristics or comorbidities. CONCLUSIONS: This meta-analysis of retrospective observational studies showed that statin therapy was associated with an about 35% decrease in the adjusted risk of mortality in hospitalized COVID-19 patients.


Subject(s)
COVID-19 , Diabetes Mellitus , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Retrospective Studies , SARS-CoV-2
20.
PLoS One ; 16(6): e0253576, 2021.
Article in English | MEDLINE | ID: covidwho-1282304

ABSTRACT

INTRODUCTION: Statins may reduce a cytokine storm, which has been hypothesized as a possible mechanism of severe COVID-19 pneumonia. The aim of this study was to conduct a systematic review and meta-analysis to report on adverse outcomes among COVID-19 patients by statin usage. METHODS: Literatures were searched from January 2019 to December 2020 to identify studies that reported the association between statin usage and adverse outcomes, including mortality, ICU admissions, and mechanical ventilation. Studies were meta-analyzed for mortality by the subgroups of ICU status and statin usage before and after COVID-19 hospitalization. Studies reporting an odds ratio (OR) and hazard ratio (HR) were analyzed separately. RESULTS: Thirteen cohorts, reporting on 110,078 patients, were included in this meta-analysis. Individuals who used statins before their COVID-19 hospitalization showed a similar risk of mortality, compared to those who did not use statins (HR 0.80, 95% CI: 0.50, 1.28; OR 0.62, 95% CI: 0.38, 1.03). Patients who were administered statins after their COVID-19 diagnosis were at a lower risk of mortality (HR 0.53, 95% CI: 0.46, 0.61; OR 0.57, 95% CI: 0.43, 0.75). The use of statins did not reduce the mortality of COVID-19 patients admitted to the ICU (OR 0.65; 95% CI: 0.26, 1.64). Among non-ICU patients, statin users were at a lower risk of mortality relative to non-statin users (HR 0.53, 95% CI: 0.46, 0.62; OR 0.64, 95% CI: 0.46, 0.88). CONCLUSION: Patients administered statins after COVID-19 diagnosis or non-ICU admitted patients were at lower risk of mortality relative to non-statin users.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Cytokine Release Syndrome , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SARS-CoV-2 , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/mortality , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects
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