Statins reduce mortality in patients with COVID-19: an updated meta-analysis of 147 824 patients

Diaz‐Arocutipa, Carlos; Melgar-Talavera, Beatriz; Alvarado-Yarasca, Ángel; Saravia-Bartra, María M.; Cazorla, Pedro; Belzusarri, Iván; Hernandez, Adrián V.

doi:10.1016/j.ijid.2021.08.004

Cited by 53 publications

(43 citation statements)

References 38 publications

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“…Statins have been reported to have pleiotropic and protective effects on endothelial cells [ 205 ]. A meta-analysis of 25 cohort studies involving 147,824 participants reported that the use of statin was associated with a lower risk of mortality in COVID-19 patients [ 206 ]. Randomized clinical trials are under way to further investigate the impact of statin use on clinical outcomes in COVID-19.…”

Section: Therapeutic Approaches Targeting Thromboinflammation and Endothelial Injury In Covid-19mentioning

confidence: 99%

Pathogenic Basis of Thromboinflammation and Endothelial Injury in COVID-19: Current Findings and Therapeutic Implications

Higashikuni

Liu

Obana

et al. 2021

IJMS

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic with a great impact on social and economic activities, as well as public health. In most patients, the symptoms of COVID-19 are a high-grade fever and a dry cough, and spontaneously resolve within ten days. However, in severe cases, COVID-19 leads to atypical bilateral interstitial pneumonia, acute respiratory distress syndrome, and systemic thromboembolism, resulting in multiple organ failure with high mortality and morbidity. SARS-CoV-2 has immune evasion mechanisms, including inhibition of interferon signaling and suppression of T cell and B cell responses. SARS-CoV-2 infection directly and indirectly causes dysregulated immune responses, platelet hyperactivation, and endothelial dysfunction, which interact with each other and are exacerbated by cardiovascular risk factors. In this review, we summarize current knowledge on the pathogenic basis of thromboinflammation and endothelial injury in COVID-19. We highlight the distinct contributions of dysregulated immune responses, platelet hyperactivation, and endothelial dysfunction to the pathogenesis of COVID-19. In addition, we discuss potential therapeutic strategies targeting these mechanisms.

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Section: Therapeutic Approaches Targeting Thromboinflammation and Endothelial Injury In Covid-19mentioning

confidence: 99%

Pathogenic Basis of Thromboinflammation and Endothelial Injury in COVID-19: Current Findings and Therapeutic Implications

Higashikuni

Liu

Obana

et al. 2021

IJMS

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“…In several other retrospective studies, the benefits of antecedent use of statins before admission were equivocal [8] , [9] , [10] , [11] , [12] , [13] , [14] . Moreover, despite the favorable results of using statin on survival in recent meta-analyses, the studies exposures included in these meta-analyses were heterogenous: some studied the effect of antecedent use of statins while others studied in-hospital use of statins [15] , [16] , [17] . However, it remains unclear whether statin use during or prior to hospitalization or continuous use of statins from the period antecedent to hospital admission through hospitalization period is beneficial to COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

The association of statins use with survival of patients with COVID-19

Kuno

Iwagami

et al. 2022

Journal of Cardiology

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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 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.

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“…Atorvastatin was co-prescribed 23.21% of the time and Simvastatin 9.49% of the time. Due to these high prescription rates and reports describing an association between statin use and reduced mortality from COVID-19 14,15 we included statins in Model 2.…”

Section: Resultsmentioning

confidence: 99%

Folic Acid and Methotrexate Use and Their Association With Covid-19 Diagnosis and Mortality: An Analysis From the Uk Biobank

Topless

Green

Morgan

et al. 2022

Preprint

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Importance: Folate metabolism is implicated in SARS-CoV-2 infectivity. Medication affecting folate metabolism may influence the risk of COVID-19 diagnosis and outcomes. Objective: to determine if methotrexate (an antifolate) or folic acid prescription were associated with differential risk, for COVID-19 diagnosis or mortality. Design, Setting, and Participants: Case-control analysis of COVID-19 from the population-based UK Biobank (UKBB) cohort. Updated medical information was retrieved on the 13th December 2021. Data from 380,380 UKBB participants with general practice prescription data for 2019 to 2021 were used. Criteria for COVID-19 diagnosis were 1) a positive SARS-CoV-2 test or 2) ICD-10 code for confirmed COVID-19 (U07.1) or probable COVID-19 (U07.2) in hospital records, or death records. By these criteria 26,003 individuals were identified with COVID-19 of whom 820 were known to have died from COVID-19. Logistic regression statistical models were adjusted for age sex, ethnicity, Townsend deprivation index, BMI, smoking status, presence of rheumatoid arthritis, sickle cell disease, use of anticonvulsants, statins and iron supplements. Exposures: Prescription of folic acid and/or methotrexate. Main outcomes and measures: The outcomes of COVID-19 diagnosis and COVID-19 related mortality were analyzed by multivariable logistic regression. The odds ratios from different exposures were compared. Results: Compared with people prescribed neither folic acid nor methotrexate, people prescribed folic acid supplementation had increased risk of diagnosis of COVID-19 (OR 1.51 [1.42 ; 1.61]). The prescription of methotrexate with or without folic acid was not associated with COVID-19 diagnosis (P≥0.18). People prescribed folic acid supplementation had positive association with death after a diagnosis of COVID-19 (OR 2.64 [2.15 ; 3.24]) in a fully adjusted model. The prescription of methotrexate in combination with folic acid was not associated with an increased risk for COVID-19 related death (1.07 [0.57 ; 1.98]). Conclusions and Relevance: We report increased risk for COVID-19 diagnosis and COVID-19-related death for people prescribed folic acid supplementation. Prescription and use of supplemental folic acid may confer increased risk of infection with SARS-CoV-2 and increased risk of death resulting from COVID-19. Our results indicate that methotrexate attenuates an increased risk for COVID-19 diagnosis and death conferred by folic acid.

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Statins reduce mortality in patients with COVID-19: an updated meta-analysis of 147 824 patients

Cited by 53 publications

References 38 publications

Pathogenic Basis of Thromboinflammation and Endothelial Injury in COVID-19: Current Findings and Therapeutic Implications

Pathogenic Basis of Thromboinflammation and Endothelial Injury in COVID-19: Current Findings and Therapeutic Implications

The association of statins use with survival of patients with COVID-19

Folic Acid and Methotrexate Use and Their Association With Covid-19 Diagnosis and Mortality: An Analysis From the Uk Biobank

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