Preadmission Statin Therapy and Clinical Outcome in Hospitalized Patients With COVID-19: An Italian Multicenter Observational Study.

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.

Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19.

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the sole causative agent of coronavirus infectious disease-19 (COVID-19). METHODS AND RESULTS: We performed a retrospective single-center study of consecutively admitted patients between March 1st and May 15th, 2020, with a definitive diagnosis of SARS-CoV-2 infection. The primary end-point was to evaluate the association of lipid markers with 30-days all-cause mortality in COVID-19. A total of 654 patients were enrolled, with an estimated 30-day mortality of 22.8% (149 patients). Non-survivors had lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) levels during the entire course of the disease. Both showed a significant inverse correlation with inflammatory markers and a positive correlation with lymphocyte count. In a multivariate analysis, LDL-c ≤ 69 mg/dl (hazard ratio [HR] 1.94; 95% confidence interval [CI] 1.14-3.31), C-reactive protein >88 mg/dl (HR 2.44; 95% CI, 1.41-4.23) and lymphopenia <1000 (HR 2.68; 95% CI, 1.91-3.78) at admission were independently associated with 30-day mortality. This association was maintained 7 days after admission. Survivors presented with complete normalization of their lipid profiles on short-term follow-up. CONCLUSION: Hypolipidemia in SARS-CoV-2 infection may be secondary to an immune-inflammatory response, with complete recovery in survivors. Low LDL-c serum levels are independently associated with higher 30-day mortality in COVID-19 patients.

Association of dyslipidemia with the severity and mortality of coronavirus disease 2019 (COVID-19): a meta-analysis.

BACKGROUND: The numbers of confirmed cases of coronavirus disease 2019 (COVID-19) and COVID-19 related deaths are still increasing, so it is very important to determine the risk factors of COVID-19. Dyslipidemia is a common complication in patients with COVID-19, but the association of dyslipidemia with the severity and mortality of COVID-19 is still unclear. The aim of this study is to analyze the potential association of dyslipidemia with the severity and mortality of COVID-19. METHODS: We searched the PubMed, Embase, MEDLINE, and Cochrane Library databases for all relevant studies up to August 24, 2020. All the articles published were retrieved without language restriction. All analysis was performed using Stata 13.1 software and Mantel-Haenszel formula with fixed effects models was used to compare the differences between studies. The Newcastle Ottawa scale was used to assess the quality of the included studies. RESULTS: Twenty-eight studies involving 12,995 COVID-19 patients were included in the meta-analysis, which was consisted of 26 cohort studies and 2 case-control studies. Dyslipidemia was associated with the severity of COVID-19 (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.11-1.44, P = 0.038, I2 = 39.8%). Further, patients with dyslipidemia had a 2.13-fold increased risk of death compared to patients without dyslipidemia (95% CI 1.84-2.47, P = 0.001, I2 = 66.4%). CONCLUSIONS: The results proved that dyslipidemia is associated with increased severity and mortality of COVID-19. Therefore, we should monitor blood lipids and administer active treatments in COVID-19 patients with dyslipidemia to reduce the severity and mortality.

Role of Statins in Coronavirus-Related Disease (COVID-19): A Retrospective Cohort Study in Northern Italy.

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.

Poor Metabolic Health Increases COVID-19-Related Mortality in the UK Biobank Sample.

Previous studies link obesity and components of metabolic health, such as hypertension or inflammation, to increased hospitalizations and mortality of patients with COVID-19. Here, in two overlapping samples of over 1,000 individuals from the UK Biobank we investigate whether metabolic health as measured by waist circumference, dyslipidemia, hypertension, type 2 diabetes, and systemic inflammation is related to increased COVID-19 infection and mortality rate. Using logistic regression and controlling for confounding variables such as socioeconomic status, age, sex or ethnicity, we find that individuals with worse metabolic health (measured on average eleven years prior to 2020) have an increased risk for COVID-19-related death (adjusted odds ratio: 1.75). We also find that specific factors contributing to increased mortality are increased serum glucose levels, systolic blood pressure and waist circumference.

Statin Use and In-Hospital Mortality in Patients With Diabetes Mellitus and COVID-19.

Background Severe coronavirus disease 2019 (COVID-19) is characterized by a proinflammatory state with high mortality. Statins have anti-inflammatory effects and may attenuate the severity of COVID-19. Methods and Results An observational study of all consecutive adult patients with COVID-19 admitted to a single center located in Bronx, New York, was conducted from March 1, 2020, to May 2, 2020. Patients were grouped as those who did and those who did not receive a statin, and in-hospital mortality was compared by competing events regression. In addition, propensity score matching and inverse probability treatment weighting were used in survival models to examine the association between statin use and death during hospitalization. A total of 4252 patients were admitted with COVID-19. Diabetes mellitus modified the association between statin use and in-hospital mortality. Patients with diabetes mellitus on a statin (n=983) were older (69±11 versus 67±14 years; P<0.01), had lower inflammatory markers (C-reactive protein, 10.2; interquartile range, 4.5-18.4 versus 12.9; interquartile range, 5.9-21.4 mg/dL; P<0.01) and reduced cumulative in-hospital mortality (24% versus 39%; P<0.01) than those not on a statin (n=1283). No difference in hospital mortality was noted in patients without diabetes mellitus on or off statin (20% versus 21%; P=0.82). Propensity score matching (hazard ratio, 0.88; 95% CI, 0.83-0.94; P<0.01) and inverse probability treatment weighting (HR, 0.88; 95% CI, 0.84-0.92; P<0.01) showed a 12% lower risk of death during hospitalization for statin users than for nonusers. Conclusions Statin use was associated with reduced in-hospital mortality from COVID-19 in patients with diabetes mellitus. These findings, if validated, may further reemphasize administration of statins to patients with diabetes mellitus during the COVID-19 era.

A Retrospective Controlled Cohort Study of the Impact of Glucocorticoid Treatment in SARS-CoV-2 Infection Mortality.

Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR], 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR], 0.880 [95% confidence interval, 0.449 to 1.726]; P = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.

A Randomized Clinical Trial of the Efficacy and Safety of Interferon ß-1a in Treatment of Severe COVID-19.

To the best of our knowledge, there is no published study on the use of interferon ß-1a (IFN ß-1a) in the treatment of severe COVID-19. In this randomized clinical trial, the efficacy and safety of IFN ß-1a were evaluated in patients with severe COVID-19. Forty-two patients in the interferon group received IFN ß-1a in addition to the national protocol medications (hydroxychloroquine plus lopinavir-ritonavir or atazanavir-ritonavir). Each 44-µg/ml (12 million IU/ml) dose of interferon ß-1a was subcutaneously injected three times weekly for two consecutive weeks. The control group consisted of 39 patients who received only the national protocol medications. The primary outcome of the study was time to reach clinical response. Secondary outcomes were duration of hospital stay, length of intensive care unit stay, 28-day mortality, effect of early or late administration of IFN on mortality, adverse effects, and complications during the hospitalization. Between 29 February and 3 April 2020, 92 patients were recruited, and a total of 42 patients in the IFN group and 39 patients in the control group completed the study. As the primary outcome, time to the clinical response was not significantly different between the IFN and the control groups (9.7 ± 5.8 versus 8.3 ± 4.9 days, respectively, P = 0.95). On day 14, 66.7% versus 43.6% of patients in the IFN group and the control group, respectively, were discharged (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.05 to 6.37). The 28-day overall mortality was significantly lower in the IFN than the control group (19% versus 43.6%, respectively, P = 0.015). Early administration significantly reduced mortality (OR, 13.5; 95% CI, 1.5 to 118). Although IFN did not change the time to reach the clinical response, adding it to the national protocol significantly increased discharge rate on day 14 and decreased 28-day mortality. (This study is in the Iranian Registry of Clinical Trials under identifier IRCT20100228003449N28.).

Issues for the management of people with diabetes and COVID-19 in ICU.

In the pandemic "Corona Virus Disease 2019" (COVID-19) people with diabetes have a high risk to require ICU admission. The management of diabetes in Intensive Care Unit is always challenging, however, when diabetes is present in COVID-19 the situation seems even more complicated. An optimal glycemic control, avoiding acute hyperglycemia, hypoglycemia and glycemic variability may significantly improve the outcome. In this case, intravenous insulin infusion with continuous glucose monitoring should be the choice. No evidence suggests stopping angiotensin-converting-enzyme inhibitors, angiotensin-renin-blockers or statins, even it has been suggested that they may increase the expression of Angiotensin-Converting-Enzyme-2 (ACE2) receptor, which is used by "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to penetrate into the cells. A real issue is the usefulness of several biomarkers, which have been suggested to be measured during the COVID-19. N-Terminal-pro-Brain Natriuretic-Peptide, D-dimer and hs-Troponin are often increased in diabetes. Their meaning in the case of diabetes and COVID-19 should be therefore very carefully evaluated. Even though we understand that in such a critical situation some of these requests are not so easy to implement, we believe that the best possible action to prevent a worse outcome is essential in any medical act.