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1.
J Clin Med ; 11(19)2022 Sep 24.
Article in English | MEDLINE | ID: covidwho-2066173

ABSTRACT

Statins exert cholesterol-independent beneficial effects, including immunomodulatory effects. In this study, we attempted to investigate the association between statin therapy and the risk of viral infection. We conducted a retrospective cohort study using data from Taiwan's National Health Insurance Research Database. We identified patients with hyperlipidemia and divided them into two cohorts: statin users and statin nonusers. A 1:1 propensity score matching was conducted between the two cohorts, and a Cox proportional hazards model was used to evaluate the risk of viral infection. Overall, a total of 20,202 patients were included in each cohort. The median follow-up durations were 4.41 and 6.90 years for statin nonusers and users, respectively. The risk of viral infection was 0.40-fold (95% confidence interval = 0.38-0.41) in statin users than in statin nonusers after adjustment for potential confounders. Statin treatment was associated with a significantly lower risk of viral infection in all age groups older than 18 years in both men and women. Moreover, the risk of viral infection substantially reduced as the duration of statin treatment increased. Our findings suggest that statin therapy is associated with a significantly lower risk of viral infection in patients with hyperlipidemia.

2.
J Clin Med ; 11(18)2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-2043802

ABSTRACT

There is mounting evidence that statin use is beneficial for COVID-19 outcomes. We performed a systematic review and meta-analysis to evaluate the association between statin use and mortality, intensive care unit (ICU) admission and mechanical ventilation in COVID-19 patients, on studies which provided covariate adjusted effect estimates, or performed propensity score matching. We searched PubMed, Embase, Web of Science and Scopus for studies and extracted odds or hazard ratios for specified outcome measures. Data synthesis was performed using a random-effects inverse variance method. Risk of bias, heterogeneity and publication bias were analyzed using standard methods. Our results show that statin use was associated with significant reductions in mortality (OR = 0.72, 95% CI: 0.67-0.77; HR = 0.74, 95% CI: 0.69, 0.79), ICU admission (OR = 0.94, 95% CI: 0.89-0.99; HR = 0.76, 95% CI: 0.60-0.96) and mechanical ventilation (OR = 0.84, 95% CI: 0.78-0.92; HR = 0.67, 95% CI: 0.47-0.97). Nevertheless, current retrospective studies are based on the antecedent use of statins prior to infection and/or continued use of statin after hospital admission. The results may not apply to the de novo commencement of statin treatment after developing COVID-19 infection. Prospective studies are lacking and necessary.

3.
Front Public Health ; 10: 877944, 2022.
Article in English | MEDLINE | ID: covidwho-2022931

ABSTRACT

Background: The cardiovascular complications of Coronavirus Disease 2019 (COVID-19) may be attributed to the hyperinflammatory state leading to increased mortality in patients with COVID-19. HMG-CoA Reductase Inhibitors (statins) are known to have pleiotropic and anti-inflammatory effects and may have antiviral activity along with their cholesterol-lowering activity. Thus, statin therapy is potentially a potent adjuvant therapy in COVID-19 infection. This study investigated the impact of statin use on the clinical outcome of critically ill patients with COVID-19. Methods: A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 who were admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on the statin use during ICU stay and were matched with a propensity score based on patient's age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality, while 30 day mortality, ventilator-free days (VFDs) at 30 days, and ICU complications were secondary endpoints. Results: A total of 1,049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality [hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004] and 30-day mortality [hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03] were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin therapy had lower odds of hospital-acquired pneumonia [OR 0.48 (95% CI 0.32, 0.69), P < 0.001], lower levels of inflammatory markers on follow-up, and no increased risk of liver injury. Conclusion: The use of statin therapy during ICU stay in critically ill patients with COVID-19 may have a beneficial role and survival benefit with a good safety profile.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Adult , Cohort Studies , Critical Illness , Humans , Retrospective Studies
4.
Int J Mol Sci ; 23(15)2022 Jul 26.
Article in English | MEDLINE | ID: covidwho-1957350

ABSTRACT

Rhabdomyolysis is a compound disease that may be induced by many factors, both congenital and acquired. Statin therapy is considered one of the most common acquired factors. However, recent scientific reports suggest that serious complications such as rhabdomyolysis are rarely observed. Researchers suggest that, in many cases, side effects that occur with statin therapy, including muscle pain, can be avoided with lower-dose statin therapy or in combination therapy with other drugs. One of the most recent agents discovered to contribute to rhabdomyolysis is COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rhabdomyolysis is defined as a damage to striated muscle cells with escape of intracellular substances into the bloodstream. These substances, including myoglobin, creatine kinase (CK), potassium, and uridine acid, are markers of muscle damage and early complications of rhabdomyolysis. Symptoms may be helpful in establishing the diagnosis. However, in almost 50% of patients, they do not occur. Therefore, the diagnosis is confirmed by serum CK levels five times higher than the upper limit of normal. One of the late complications of this condition is acute kidney injury (AKI), which is immediately life-threatening and has a high mortality rate among patients. Therefore, the prompt detection and treatment of rhabdomyolysis is important. Markers of muscle damage, such as CK, lactate dehydrogenase (LDH), myoglobin, troponins, and aspartate aminotransferase (AST), are important in diagnosis. Treatment of rhabdomyolysis is mainly based on early, aggressive fluid resuscitation. However, therapeutic interventions, such as urinary alkalinization with sodium bicarbonate or the administration of mannitol or furosemide, have not proven to be beneficial. In some patients who develop AKI in the course of rhabdomyolysis, renal replacement therapy (RRT) is required.


Subject(s)
Acute Kidney Injury , COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Rhabdomyolysis , Acute Kidney Injury/therapy , Biomarkers , COVID-19/complications , Creatine Kinase , Humans , Myoglobin , Rhabdomyolysis/complications , Rhabdomyolysis/diagnosis , SARS-CoV-2
5.
Molecules ; 27(10)2022 May 18.
Article in English | MEDLINE | ID: covidwho-1953750

ABSTRACT

Voltage-gated potassium channels of the Kv1.3 type are considered a potential new molecular target in several pathologies, including some cancer disorders and COVID-19. Lipophilic non-toxic organic inhibitors of Kv1.3 channels, such as statins and flavonoids, may have clinical applications in supporting the therapy of some cancer diseases, such as breast, pancreas, and lung cancer; melanoma; or chronic lymphocytic leukemia. This study focuses on the influence of the co-application of statins-simvastatin (SIM) or mevastatin (MEV)-with flavonoids 8-prenylnaringenin (8-PN), 6-prenylnarigenin (6-PN), xanthohumol (XANT), acacetin (ACAC), or chrysin on the activity of Kv1.3 channels, viability, and the apoptosis of cancer cells in the human T cell line Jurkat. We showed that the inhibitory effect of co-application of the statins with flavonoids was significantly more potent than the effects exerted by each compound applied alone. Combinations of simvastatin with chrysin, as well as mevastatin with 8-prenylnaringenin, seem to be the most promising. We also found that these results correlate with an increased ability of the statin-flavonoid combination to reduce viability and induce apoptosis in cancer cells compared to single compounds. Our findings suggest that the co-application of statins and flavonoids at low concentrations may increase the effectiveness and safety of cancer therapy. Thus, the simultaneous application of statins and flavonoids may be a new and promising anticancer strategy.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Neoplasms , Apoptosis , Cell Line , Flavonoids/pharmacology , Flavonoids/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Kv1.3 Potassium Channel/metabolism , Neoplasms/drug therapy , Simvastatin/pharmacology
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.
Clin Appl Thromb Hemost ; 28: 10760296221103864, 2022.
Article in English | MEDLINE | ID: covidwho-1879207

ABSTRACT

PURPOSE: Coagulation abnormalities are one of the most important complications of severe COVID-19, which might lead to venous thromboembolism (VTE). Hypercoagulability with hyperfibrinogenemia causes large vessel thrombosis and major thromboembolic sequelae. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic effect. This study aims to evaluate the effectiveness of statins in reducing the risk of thrombosis among hospitalized critically ill patients with COVID-19. METHODS: 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 categorized based on their usage of statins throughout their ICU stay and were matched with a propensity score. The primary endpoint was the odds of all cases of thrombosis; other outcomes were considered secondary. RESULTS: A total of 1039 patients were eligible; following propensity score matching, 396 patients were included (1:1 ratio). The odds of all thrombosis cases and VTE events did not differ significantly between the two groups (OR 0.84 (95% CI 0.43, 1.66), P = 0.62 and OR 1.13 (95% CI 0.43, 2.98), P = 0.81, respectively. On multivariable Cox proportional hazards regression analysis, patients who received statin therapy had lower 30-day (HR 0.72 (95 % CI 0.54, 0.97), P = 0.03) and in-hospital mortality (HR 0.67 (95 % CI 0.51, 0.89), P = 0.007). Other secondary outcomes were not statistically significant between the two groups except for D-dimer levels (peak) during ICU stay. CONCLUSION: The use of statin therapy during ICU stay was not associated with thrombosis reduction in critically ill patients with COVID-19; however, it has been associated with survival benefits.


Subject(s)
Blood Coagulation Disorders , COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Thrombosis , Venous Thromboembolism , Adult , COVID-19/complications , COVID-19/drug therapy , Cohort Studies , Critical Illness , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Intensive Care Units , Retrospective Studies , Thrombosis/chemically induced , Thrombosis/etiology , Venous Thromboembolism/chemically induced , Venous Thromboembolism/etiology
9.
Am J Health Syst Pharm ; 79(17): 1431-1437, 2022 08 19.
Article in English | MEDLINE | ID: covidwho-1831008

ABSTRACT

PURPOSE: The objective of this review is to detail the utility of statin medications in the prevention and treatment of intensive care unit (ICU) delirium. SUMMARY: Delirium is a syndrome characterized by altered mental status, inattention, and disorganized thinking. It is particularly concerning in the ICU where specific risk factors are much more prevalent. Nonpharmacological therapy is the mainstay of treatment, aimed at increasing patient awareness; pharmacological therapies have also been explored with varying success. The utility of statin medications in this scenario has been investigated because of the numerous pleiotropic effects of these drugs. Although the benefits in terms of treating delirium are uncertain, statins may be good candidates for prevention. The peak anti-inflammatory effect of statins is delayed, so initiating a statin on admission will likely have little protective benefit, whereas continuation of a home regimen seems more likely to exert an effect. CONCLUSION: Statin medications are very commonly used, and, while their role in treating delirium is unclear, continuation of these medications from a home regimen is reasonable to decrease the odds of delirium in the intensive care population.


Subject(s)
Delirium , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Critical Care , Delirium/drug therapy , Delirium/prevention & control , Humans , Intensive Care Units , Risk Factors
10.
Cureus ; 14(3): e23511, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1791846

ABSTRACT

Renal failure secondary to rhabdomyolysis due to statins is quite rare. We present a case of a 57-year-old patient who developed acute renal failure due to rhabdomyolysis secondary to atorvastatin. Interestingly, this patient had a similar presentation 27 years ago requiring dialysis only once resulting in complete resolution of symptoms. He presented to the hospital generally feeling unwell and then developed generalized body ache. He had an extremely elevated creatinine kinase level of 116,000 and it went up to 145,000. His urine dip was negative for nitrites and was positive for blood and protein. He was commenced on intravenous fluids. He also had a computerized tomographic scan of the kidneys, ureters, and bladder, which showed some fat stranding around both kidneys likely inflammatory in origin. His creatinine level continue to rise despite intravenous fluids and was acidotic on blood gases. He also tested positive for COVID-19 on day 7 of admission and eventually needed dialysis. His renal functions improved to baseline post dialysis and kidney functions returned to normal. His autoimmune screen was negative and his renal functions remained normal on a follow-up visit.

11.
Ann Palliat Med ; 11(4): 1297-1307, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1786442

ABSTRACT

BACKGROUND: There currently exist limited and conflicting clinical data on the use of statins in coronavirus disease 2019 (COVID-19) patients. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins. METHODS: We performed a population-based retrospective cohort study using South Korea's nationwide healthcare claim database. We identified consecutive patients hospitalized with COVID-19 and aged 40 years or older. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry to capture patients who are chronic statin users and, therefore, receive statin prescriptions as infrequently as every 8 months. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes [myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke]. We compared the risk of outcomes between statin users and non-users using logistic regression models after inverse probability of treatment weighting (IPTW) adjustment. RESULTS: Of 234,427 subjects in the database, 4,349 patients were hospitalized with COVID-19 and aged 40+ years. In total, 1,115 patients were statin users (mean age =65.9 years; 60% female), and 3,234 were non-users (mean age =58.3 years; 64% female). Pre-hospitalization statin use was not significantly associated with increased risk of the primary endpoint [IPTW odds ratio (OR) 0.82; 95% confidence interval (CI): 0.60-1.11]. Subgroup analysis showed a protective role of antecedent statin use for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, P for interaction: 0.0087). CONCLUSIONS: Pre-hospitalization statin use is not detrimental and may be beneficial amongst hypertensive COVID-19 patients. Further investigation into statin is needed for more conclusive effects of statins for treatment of COVID-19.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Aged , Cohort Studies , Female , Hospitalization , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Retrospective Studies
12.
Cureus ; 14(2): e22273, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1776611

ABSTRACT

Statins are a widely prescribed medication that lowers serum cholesterol by inhibiting the HMG-CoA reductase enzyme, a rate-limiting step in cholesterol synthesis. Myopathy is one of the well-known adverse effects of statins, mainly when prescribed with the fibrates. However, statin-induced autoimmune necrotizing myopathy (SIANM) is an infrequent and severe complication. Hence, all clinicians should be more vigilant regarding this complication and treat it early to prevent acute kidney injury (AKI).

13.
Int J Mol Sci ; 23(6)2022 Mar 16.
Article in English | MEDLINE | ID: covidwho-1765732

ABSTRACT

Formation of neutrophil extracellular traps (NETs) is a two-faced innate host defense mechanism, which, on the one hand, can counteract microbial infections, but on the other hand, can contribute to massive detrimental effects on the host. Cholesterol depletion from the cellular membrane by Methyl-ß-cyclodextrin (MßCD) is known as one of the processes initiating NET formation. Since neutrophils mainly act in an inflammatory environment with decreased, so-called hypoxic, oxygen conditions, we aimed to study the effect of oxygen and the oxygen stress regulator hypoxia-inducible factor (HIF)-1α on cholesterol-dependent NET formation. Thus, murine bone marrow-derived neutrophils from wild-type and HIF-knockout mice or human neutrophils were stimulated with MßCD under normoxic (21% O2) compared to hypoxic (1% O2) conditions, and the formation of NETs were studied by immunofluorescence microscopy. We found significantly induced NET formation after treatment with MßCD in murine neutrophils derived from wild-type as well as HIF-1α KO mice at both hypoxic (1% O2) as well as normoxic (21% O2) conditions. Similar observations were made in freshly isolated human neutrophils after stimulation with MßCD or statins, which block the HMG-CoA reductase as the key enzyme in the cholesterol metabolism. HPLC was used to confirm the reduction of cholesterol in treated neutrophils. In summary, we were able to show that NET formation via MßCD or statin-treatment is oxygen and HIF-1α independent.


Subject(s)
Extracellular Traps , Animals , Cholesterol/metabolism , Hypoxia/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Mice , Neutrophils/metabolism , Oxygen/metabolism
14.
Front Cardiovasc Med ; 9: 820260, 2022.
Article in English | MEDLINE | ID: covidwho-1742209

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) might affect everyone, but people with comorbidities such as hypertension and cardiovascular disease (CVD) may often have more severe complications and worse outcomes. Although vaccinations are being performed worldwide, it will take a long time until the entire population of the world is vaccinated. On the other hand, we are witnessing the emergence of new variants of this virus. Therefore, effective therapeutic approaches still need to be considered. Statins are well-known lipid-lowering drugs, but they have also anti-inflammatory and immunomodulatory effects. This study aimed to investigate the effects of statins on the survival of COVID-19 hospitalized patients. Methods: This retrospective study was performed on 583 patients admitted to a highly referenced hospital in Tabas, Iran, between February 2020 and December 2020. One hundred sixty-two patients were treated with statins and 421 patients were not. Demographic information, clinical signs, and the results of laboratory, and comorbidities were extracted from patients' medical records and mortality and survival rates were assessed in these two groups. Results: The results of the Cox crude regression model showed that statins reduced mortality in COVID-19 patients (HR = 0.56, 95% CI: 0.32, 0.97; p = 0.040), although this reduction was not significant in the adjusted model (HRs=0.51, 95%CI: 0.22, 1.17; p = 0.114). Using a composite outcome comprising intubation, ICU admission, and mortality, both crude (HR = 0.43; 95% CI: 0.26, 0.73; p = 0.002) and adjusted (HR = 0.57; 95% CI: 0.33, 0.99; p = 0.048) models suggested a significant protective effect of statin therapy. Conclusion: Due to anti-inflammatory properties of statins, these drugs can be effective as an adjunct therapy in the treatment of COVID-19 patients.

15.
Am J Med ; 135(7): 897-905, 2022 07.
Article in English | MEDLINE | ID: covidwho-1739511

ABSTRACT

INTRODUCTION: Statins have been commonly used for primary and secondary cardiovascular prevention. We hypothesized that statins may improve in-hospital outcomes for hospitalized patients with Coronavirus disease 2019 (COVID-19) due to its known anti-inflammatory effects. METHODS: We conducted a retrospective study at the largest municipal health care system in the United States, including adult patients who were hospitalized for COVID-19 between March 1 and December 1, 2020. The primary endpoint was in-hospital death. Propensity score matching was conducted to balance possible confounding variables between patients receiving statins during hospitalization (statin group) and those not receiving statins (non-statin group). Multivariate logistic regression was used to evaluate the association of statin use and other variables with in-hospital outcomes. RESULTS: There were 8897 patients eligible for study enrollment, with 3359 patients in the statin group and 5538 patients in the non-statin group. After propensity score matching, both the statin and non-statin groups included 2817 patients. Multivariate logistic regression analysis showed that the statin group had a significantly lower risk of in-hospital mortality (odds ratio 0.71; 95% confidence interval, 0.63-0.80; P < .001) and mechanical ventilation (OR 0.80; 95% confidence interval, 0.71-0.90; P < .001) compared with the non-statin group. CONCLUSION: Statin use was associated with lower likelihood of in-hospital mortality and invasive mechanical ventilation in hospitalized patients with COVID-19.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Adult , Hospital Mortality , Hospitals, Public , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , New York City/epidemiology , Retrospective Studies , United States
16.
Front Immunol ; 13: 820131, 2022.
Article in English | MEDLINE | ID: covidwho-1731776

ABSTRACT

Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In observational clinical studies, statins have been identified as beneficial to hospitalized patients with COVID-19. However, experimental evidence of underlying statins protection against SARS-CoV-2 remains elusive. Here we reported for the first-time experimental evidence of the protective effects of simvastatin treatment both in vitro and in vivo. We found that treatment with simvastatin significantly reduced the viral replication and lung damage in vivo, delaying SARS-CoV-2-associated physiopathology and mortality in the K18-hACE2-transgenic mice model. Moreover, simvastatin also downregulated the inflammation triggered by SARS-CoV-2 infection in pulmonary tissue and in human neutrophils, peripheral blood monocytes, and lung epithelial Calu-3 cells in vitro, showing its potential to modulate the inflammatory response both at the site of infection and systemically. Additionally, we also observed that simvastatin affected the course of SARS-CoV-2 infection through displacing ACE2 on cell membrane lipid rafts. In conclusion, our results show that simvastatin exhibits early protective effects on SARS-CoV-2 infection by inhibiting virus cell entry and inflammatory cytokine production, through mechanisms at least in part dependent on lipid rafts disruption.


Subject(s)
COVID-19/drug therapy , Down-Regulation/drug effects , Inflammation/drug therapy , Membrane Microdomains/drug effects , SARS-CoV-2/pathogenicity , Simvastatin/pharmacology , Animals , COVID-19/virology , Disease Models, Animal , Humans , Inflammation/virology , Lung/virology , Mice , Mice, Transgenic , Virus Replication/drug effects
17.
Curr Diabetes Rev ; 18(9): e090222200945, 2022.
Article in English | MEDLINE | ID: covidwho-1686284

ABSTRACT

BACKGROUND AND AIMS: Diabetes mellitus, cardiovascular diseases, obesity, and dyslipidaemia are considered risk factors for more severe forms of COVID-19 infection. Statins have been widely used in such patients to prevent the occurrence of cardiovascular events and the associated mortality. However, statin use has been suggested to promote a more severe form of infection. This review aims to investigate the association between statin use and poor outcomes in COVID-19 patients with diabetes. METHODS: Literature search was performed in PubMed, CENTRAL, Scopus, and pre-print databases (MedRxiv and BioRxiv), and studies published up to March 6th, 2021 have been reviewed. Selected studies were then assessed for risk of bias with the Newcastle Ottawa Scale. RESULT: Four studies were included in the final analysis; all were retrospective studies. Two studies reported a decreased risk of mortality with statin use, while one study reported opposite findings. The other one did not find a significant association between statin use and poor COVID-19 outcomes. CONCLUSION: Available data suggest that statins may be safely administered to diabetic COVID-19 patients as the majority of evidence signifies statins to confer benefits and improve clinical outcomes in COVID-19 patients.


Subject(s)
COVID-19 , Diabetes Mellitus , Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Diabetes Mellitus/drug therapy , Diabetes Mellitus/epidemiology , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Retrospective Studies
18.
J Cardiol ; 79(4): 494-500, 2022 04.
Article in English | MEDLINE | ID: covidwho-1587219

ABSTRACT

BACKGROUND: Statins are frequently prescribed for patients with dyslipidemia and diabetes mellitus. These comorbidities are highly prevalent in coronavirus disease 2019 (COVID-19) patients. Statin's beneficial effect on mortality in COVID-19 infection has been reported in several studies. However, these findings are still inconclusive. METHODS: We conducted a retrospective observational study among 6,095 patients with laboratory confirmed COVID-19 hospitalized in Mount Sinai Health System between March 1st 2020 and May 7th 2020. Patients were stratified into two groups: statin use prior to or during hospitalization (N = 2,423) versus no statins (N = 3,672). We evaluated in-hospital mortality as a primary outcome using propensity score matching and inverse probability treatment weighted (IPTW) analysis. In additional analysis, we compared continuous use of statins (N = 1,108) with no statins, continuous use of statins with discontinuation of statins (N = 644), and discontinuation of statins with no statins. RESULTS: Among 6,095 COVID-19 patients, statin use prior to or during hospitalization group were older (70.8 ± 12.7 years versus 59.2 ± 18.2 years, p<0.001) and had more comorbidities compared to no statins group. After matching by propensity score (1,790 pairs), there were no significant differences in-hospital mortality between patients with statins and those without [28.9% versus 31.0%, p = 0.19, odds ratio (OR) 95% confidence interval (CI): 0.91 (0.79-1.05)]. This result was confirmed by IPTW analysis [OR (95% CI): 0.96 (0.81-1.12), p = 0.53]. In the additional analysis comparing continuous use of statins with no statins group, in-hospital mortality was significantly lower in continuous use of statins compared to no statins group [26.3% versus 34.5%, p<0.001, OR (95% CI): 0.68 (0.55-0.82)] after matching by propensity score (944 pairs), as well as IPTW analysis [OR (95% CI): 0.77 (0.64-0.94), p = 0.009]. Finally, comparison of continuous use of statins with discontinuation of statins showed lower in-hospital mortality in continuous use of statins group [27.9% versus 42.1%, p<0.001, OR (95% CI): 0.53 (0.41-0.68)]. CONCLUSIONS: Use of statins prior to or during hospitalization was not associated with a decreased risk of in-hospital mortality, however, continuous use of statins was associated with lower in-hospital mortality compared to no statin use and discontinuation of statins.


Subject(s)
COVID-19 , Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hospital Mortality , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Retrospective Studies , SARS-CoV-2
19.
Cardiol Ther ; 11(1): 1-7, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1520518

ABSTRACT

A recent meta-analysis of over 20,000 individuals showed that hospitalized COVID-19 patients with acute myocardial injury had more than fourfold higher mortality than those without such injury. Since the COVID-19 pandemic exacerbates already existing health inequalities, there is an urgent need to create measures to protect the most vulnerable patient groups, including those with a pre-existing increased risk of atherosclerotic cardiovascular disease (ASCVD). A typical example is familial hypercholesterolemia (FH), a common genetic disease affecting over 30 million individuals worldwide. If left untreated or undertreated, FH patients suffer from complications of premature ASCVD, such as acute coronary syndromes, resulting in acute myocardial injury/infarction. A recent population-based analysis provided strong evidence suggesting that COVID-19 poses an even higher risk for myocardial injury in FH patients. From the long-term preventive point of view, it is important to note that, in addition to the acutely elevated risk of myocardial injury, an elevated risk of ASCVD and its complications will persist after COVID-19. The decline in outpatient preventive care during the pandemic is likely to influence ASCVD risk and outcomes, particularly in high-risk patients, such as those with FH. This commentary aims to raise global awareness of the challenges that clinicians treating FH patients continue to face during the COVID-19 pandemic, with two low- to middle-income countries, South Africa and Brazil, serving as examples.

20.
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
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