Do Statins Affect Viral Infections Encountered by International Travelers?
Abstract
:1. Introduction
2. Effect of Statins on Different Viruses
2.1. Respiratory Viruses: COVID-19
2.2. Respiratory Viruses: Influenza
Pathogen | Year | Title of Study | Type of Study | Type of Statin | Key Findings Pertaining to Statins | Category of Evidence |
---|---|---|---|---|---|---|
SARS-CoV-2 | 2022 | Effects of statins on clinical outcomes in hospitalized patients with COVID-19 [85] | Meta-analysis of randomized controlled trials | Multiple statins | There was no evidence of clinical benefits of statin use. | Ia |
2023 | Effects of statin therapy in hospitalized adult COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials [86] | Meta-analysis of randomized controlled trials | Multiple statins | Statin use did not affect the clinical outcomes of patients hospitalized with COVID-19. | Ia | |
2022 | Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: A randomised clinical trial (RESIST trial) [82] | Randomized controlled trial | Atorvastatin 40 mg daily | The use of aspirin, atorvastatin, or both in hospitalized patients with mild to moderate COVID-19 infection did not prevent clinical deterioration. | Ib | |
2022 | Atorvastatin versus placebo in patients with COVID-19 in intensive care: Randomized controlled trial [83] | Randomized controlled trial | Atorvastatin 20 mg daily | Atorvastatin did not affect the rate of thrombosis, treatment with extracorporeal membrane oxygenation, or mortality in patients with COVID-19 admitted to the intensive care unit. | Ib | |
2022 | Survival of the hospitalized patients with COVID-19 receiving atorvastatin: A randomized clinical trial [84] | Randomized controlled trial | Atorvastatin 20 mg daily | Adding atorvastatin to the standard therapy for COVID-19 worsened the clinical outcomes of hospitalized patients. | Ib | |
2020 | Meta-analysis of effect of statins in patients with COVID-19 [62] | Meta-analysis | Multiple statins (Atorvastatin, rosuvastatin, simvastatin, pravastatin, fluvastatin, pitavastatin) | Statins significantly reduced hazard for fatal or severe disease (HR = 0.70; 95% CI 0.53–0.94) compared to non-use of statins in COVID-19 patients. | IIa | |
2021 | Protective effects of statins administration in European and North American patients infected with COVID-19: A meta-analysis [64] | Meta-analysis | Multiple statins | Statin usage in Western patients hospitalized with COVID-19 was associated with nearly 40% lower odds of progressing toward severe illness or death (odds ratio: 0.59; 95% confidence interval: 0.35–0.99). | IIa | |
2021 | The protective association between statins use and adverse outcomes among COVID-19 patients: A systematic review and meta-analysis [66] | Meta-analysis | Multiple statins | 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). 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). | IIa | |
2021 | Improved COVID-19 ICU admission and mortality outcomes following treatment with statins: A systematic review and meta-analysis [67] | Meta-analysis | Multiple statins (lovastatin OR fluvastatin OR pravastatin OR rosuvastatin OR pitavastatin OR atorvastatin OR simvastatin OR cerivastatin OR lipitor OR lescol OR lecol AND xl OR mevacor OR altoprev OR pravachol OR crestor OR zocor OR livalo.) | There were significant reductions in ICU admission (OR = 0.78, 95% CI: 0.58–1.06; n = 10; I 2 = 58.5%) and death (OR = 0.70, 95% CI: 0.55–0.88; n = 21; I2 = 82.5%) outcomes, with no significant effect on tracheal intubation (OR = 0.79; 95% CI: 0.57–1.11; n = 7; I2= 89.0%). | IIa | |
2021 | The use of statins was associated with reduced COVID-19 mortality: A systematic review and meta-analysis [68] | Meta-analysis | Multiple statins | The use of statins was significantly associated with decreased mortality (odds ratio [OR] = 0.71, 95% confidence interval [CI]: 0.55–0.92) and the need for IMV (OR = 0.81, 95% CI: 0.69–0.95) but was not linked to the need for ICU care (OR = 0.91, 95% CI: 0.55–1.51). | IIa | |
2021 | In-hospital use of statins is associated with a reduced risk of mortality in coronavirus-2019 (COVID-19): Systematic review and meta-analysis [69] | Meta-analysis | Multiple statins (atorvastatin, fluvastatin, pravastatin, simvastatin, rosuvastatin) | In-hospital use of statin was associated with a reduced risk of mortality (RR 0.54, 95% CI 0.50–0.58, p < 0.00001; I2: 0%, p = 0.87), while pre-admission use of statin was not associated with mortality (RR 1.18, 95% CI 0.79–1.77, p = 0.415; I2: 68.6%, p = 0.013). | IIa | |
2021 | Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies [63] | Meta-analysis | Multiple statins | Univariate comparisons of statin users versus non-users found no statistically significant reduction in deaths (OR: 0.97, 95% CI: 0.92–1.03) or severity (OR: 1.09, 95% CI: 0.99–1.22), but multivariable analysis found lower OR in statin users. | IIa | |
2021 | Prior statin use and risk of mortality and severe disease from coronavirus disease 2019: A systematic review and meta-analysis [70] | Meta-analysis | Multiple statins | Prior statin use was associated with a lower risk of mortality (pooled aRR, 0.65 [95% confidence interval 143, 0.56–0.77], I2 = 84.1%) and a reduced risk of severe COVID-19 (pooled aRR, 0.73 [95% CI, 0.57–0.94]. | IIa | |
2021 | Statins reduce mortality in patients with COVID-19: An updated meta-analysis of 147,824 patients [71] | Meta-analysis | Multiple statins (atorvastatin (71%), rosuvastatin (13%), and simvastatin (13%)) | 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. | IIa | |
2021 | Statin use and mortality in COVID-19 patients: Updated systematic review and meta-analysis [73] | Meta-analysis | Multiple statins (Atorvastatin, pitavastatin, simvastatin, rosuvastatin) | The reported adjusted hazard ratios for mortality in statin users versus non-users showed a pooled estimate at 0.65 (95% confidence intervals [CI] 0.53, 0.81). | IIa | |
2021 | Statin use is associated with a decreased risk of mortality among patients with COVID-19 [75] | Meta-analysis | Multiple statins | Statin use was associated with a significantly decreased risk of mortality among patients with COVID-19 (RR adjusted = 0.64; 95% CI: 0.57–0.72, p < 0.001). | IIa | |
2021 | Statin therapy is associated with less ICU admissions in COVID-19 patients [76] | Meta-analysis | Multiple statin | Statin users show a lower risk of ICU admission compared to non-statin users (OR: 0.84, 95% CI: 0.72–0.99, p = 0.004, I2: 39.2%). A further meta-regression, using age as moderator variable, did not reveal any significant correlation, although a positive trend between the outcome and age was observed (β = 0.006, 95% CI: −0.006 to 0.019, Z value: 0.98, p = 0.32). | IIa | |
2021 | Statin and outcomes of coronavirus disease 2019 (COVID-19): A systematic review, meta-analysis, and meta-regression [77] | Meta-analysis | Multiple statins | Statins did not improve COVID-19 outcomes (OR 1.08, 95% CI 0.86–1.35; p = 0.50). | IIa | |
2022 | Statin use and clinical outcomes in patients with COVID-19: An updated systematic review and meta-analysis [65] | Meta-analysis | Multiple statins | The use of statin was found to significantly reduce the risk of adverse outcomes (OR 0.51; 95% CI 0.41 to 0.63, p < 0.0005. | IIa | |
2022 | Statin and mortality in COVID-19: A systematic review and meta-analysis of pooled adjusted effect estimates from propensity-matched cohorts [72] | Meta-analysis | Multiple statins | In patients receiving statin in-hospital, the study showed that it was associated with lower mortality (RR 0.71 (0.54, 0.94), p = 0.030. | IIa | |
2022 | The association between the use of statins and clinical outcomes in patients with COVID-19: A systematic review and meta-analysis [74] | Meta-analysis | Multiple statins (atorvastatin, rosuvastatin, simvastatin, pravastatin, pitavastatin) | The use of statins was associated with a significantly lower risks of all-cause mortality (HR = 0.70, 95% CI 0.58–0.84, n = 21,127, and OR = 0.63, 95% CI 0.51–0.79, n = 115,097) and the composite endpoint of severe illness (OR = 0.80, 95% CI 0.73–0.88, n = 10,081) in patients with COVID-19, compared to non-use of statins. | IIa | |
2021 | Statins and SARS-CoV-2 infection: Results of a population-based prospective cohort study of 469 749 adults from 2 Canadian provinces [53] | Prospective cohort | Multiple statins | Patients younger than 75 years on statin had the same incidence and outcomes of SARS-CoV-2; however, patients older than 75 years using statins had increased hospitalizations but lower 30-day all-cause mortality. | IIb | |
2021 | Pharmacological predictors of morbidity and mortality in COVID-19 [30] | Retrospective cohort | Multiple statins (rosuvastatin, atorvastatin) | Statin use was associated with lower rates of critical care admission (HR, 0.35; 95% CI, 0.17–0.73; p = 0.006). | IIb | |
2021 | Association between antecedent statin use and severe disease outcomes in COVID-19: A retrospective study with propensity score matching [35] | Retrospective cohort | Multiple statins (rosuvastatin, atorvastatin, simvastatin, pravastatin, lovastatin) | Statin users had significant reduction in mortality in the PSM cohort as well (OR, 0.56; 95% CI, 0.37–0.83; p = 0.004). | IIb | |
2021 | Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19 [36] | Retrospective cohort | Multiple statins | Statin use was significantly associated with lower odds of the primary endpoint in the propensity-matched cohort (OR 0.47, 95% CI 0.36–0.62, p < 0.001). | IIb | |
2021 | Association of pre-admission statin use with reduced in-hospital mortality in COVID-19 [43] | Retrospective cohort | Multiple statins | There was a statistically significant decrease in the odds of in-hospital mortality in patients on statins before admission (OR 0.14, 95% CI 0.03–0.61, p = 0.008). | IIb | |
2021 | Beneficial effect of statins in COVID-19-related outcomes—brief report: A national population-based cohort study [44] | Retrospective cohort | Multiple statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) | There was a significant decrease in hazard ratio associated with the use of statins (hazard ratio, 0.637 [95% CI, 0.425–0.953]; p = 0.0283). | IIb | |
2021 | Prior treatment with statins is associated with improved outcomes of patients with COVID-19: Data from the SEMI-COVID-19 Registry [45] | Retrospective cohort | Multiple statins | Continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54–0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76, 0.6–0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69–0.89, p < 0.001), and sepsis (4.82% vs. 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs. 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. | IIb | |
2021 | Association of in-hospital use of statins, aspirin, and renin-angiotensin-aldosterone inhibitors with mortality and ICU admission due to COVID-19 [46] | Retrospective cohort | Atorvastatin | 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). | IIb | |
2021 | Identification of drugs associated with reduced severity of COVID-19—a case-control study in a large population [47] | Retrospective cohort | Rosuvastatin | Rosuvastatin is associated with significantly reduced odds for COVID-19 hospitalization (OR = 0.673, 95% CI [0.596 to 0.758], p < 0.001). | IIb | |
2021 | Promising effects of atorvastatin on mortality and need for mechanical ventilation in patients with severe COVID-19: A retrospective cohort study [48] | Retrospective cohort | Atorvastatin | In-hospital use of atorvastatin was associated with decrease in mortality (HR = 0.679, p = 0.005) and lower need for invasive mechanical ventilation (HR = 0.602, p = 0.014). | IIb | |
2021 | Statins in patients with COVID-19: A retrospective cohort study in Iranian COVID-19 patients [56] | Retrospective cohort | Three different types of statin were used among the 75 patients on statins: atorvastatin (94.7%), rosuvastatin (2.7%), and simvastatin (2.7%) | After propensity score matching, statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), p = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), p = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61–2.99), p = 0.942], and patients on statins showed a more normal computed tomography scan result [OR = 0.41, 95% CI = (0.07–2.33), p = 0.312]. | IIb | |
2021 | Impact of prior statin use on clinical outcomes in COVID-19 patients: Data from tertiary referral hospitals during COVID-19 pandemic in Italy [60] | Retrospective cohort | Multiple statins | Statin use was associated with more severe disease (OR 1.7, 95% CI 1.067–2.71; p = 0.026) but not mortality. | IIb | |
2022 | Effect of statin therapy on SARS-CoV-2 infection-related mortality in hospitalized patients [25] | Retrospective cohort | Categorized as high intensity (80 mg/day atorvastatin and 20 mg/day rosuvastatin) or low-moderate intensity | A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization (19.8% vs. 25.4%, χ2 with Yates continuity correction: p = 0.027). | IIb | |
2022 | Effects of statins on outcomes in Hispanic patients with COVID-19 [27] | Retrospective cohort | Multiple statins (rosuvastatin-atorvastatin-simvastatin) | In patients who had myocardial infarction and stroke with COVID-19, association was found between statin use and a reduced risk of mortality (aRR = 0.61, p = 0.005), mechanical ventilation (aRR = 0.53, p = 0.012), and ICU transfers (aRR = 0.81, p = 0.005). | IIb | |
2022 | The effect of statins on clinical outcome among hospitalized patients with COVID-19: A multi-centric cohort study [28] | Retrospective cohort | Multiple statins (rosuvastatin-atorvastatin-simvastatin) | Statin use was associated with lower odds of mortality in the propensity-matched cohort (OR 0.52, 95% CI 0.33–0.64, p < 0.001). | IIb | |
2022 | Association of statins and 28-day mortality rates in patients hospitalized with severe acute respiratory syndrome coronavirus 2 infection [33] | Retrospective cohort | Multiple statins (rosuvastatin-atorvastatin) | Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality rates (HR, 0.566; p = 0.008). | IIb | |
2022 | Statins and risk of thrombosis in critically ill patients with COVID-19: A multicenter cohort study [41] | Retrospective cohort | Multiple statins (atorvastatin (81.8%), rosuvastatin (16%) | 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. | IIb | |
2022 | The impact of HMG-CoA reductase inhibitors use on the clinical outcomes in critically ill patients with COVID-19: A multicenter, cohort study [42] | Retrospective cohort | Multiple statins (atorvastatin (81.3%), rosuvastatin (14.1%) | 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 and had lower odds of hospital-acquired pneumonia [OR 0.48 (95% CI 0.32, 0.69), p < 0.001]. | IIb | |
2022 | Associations of statin use with 30-day adverse outcomes among 4 801 406 US Veterans with and without SARS-CoV-2: An observational cohort study [55] | Retrospective cohort | Multiple statins | Statin use was associated with lower odds of death at 30 days (OR 0.81 (95% CI 0.77 to 0.85)) but not with hospitalization or ICU admission. Associations were similar comparing use of each specific statin to no statin. Compared with low–moderate-intensity statin use, high-intensity statin use was not associated with lower odds of ICU admission or death. | IIb | |
2022 | A historical cohort study to investigation of statins safety in COVID-19 hospitalized patients [57] | Retrospective cohort | Multiple statins with most common atorvastatin and rosuvastatin. | Following adjustment of odds ratio based on multiple variables (age, sex, diabetes, hypertension status, stroke, dyslipidemia, cardiovascular diseases, chronic kidney disease (CKD), corticosteroids, renin-angiotensin-aldosterone axis inhibitors and proton pump inhibitors (PPIs)), it was shown that statins did not change mortality (95% CI, OR 0.71 (0.41–1.22), p = 0.22), ICU admission (95% CI, OR 1.05 (0.66–1.66), p = 0.835), or length of hospitalization (95% CI, OR 1.30 (0.78–2.17), p = 0.311). | IIb | |
2022 | Association between statin use and outcomes in patients with coronavirus disease 2019 (COVID-19): A nationwide cohort study [58] | Retrospective cohort | Simvastatin, atorvastatin, rosuvastatin | After adjustment for age, sex, ethnicity, socioeconomic status, and comorbidities, statin exposure was not associated with a significantly different risk of mortality (HR 0.96 (95% CI 0.78 to 1.18); severe COVID-19 infection (HR 1.16 (95% CI 0.95 to 1.41); or the composite outcome of all-cause mortality or severe COVID-19 infection (HR 1.05 (95% CI 0.89 to 1.23). | IIb | |
2023 | Statin therapy may protect against acute kidney injury in patients hospitalized for interstitial SARS-CoV2 pneumonia [54] | Prospective cohort | Multiple statins | Statin use did not affect critical care admission and mortality but significantly lowered the risk of developing acute kidney injury (OR 0.47, 95% CI 0.23–0.95; p = 0.036) and C-reactive protein (CRP) levels (p = 0.048). | IIb | |
2023 | Association of statin use with outcomes of patients admitted with COVID-19: An analysis of electronic health records using superlearner [49] | Retrospective cohort | Multiple statins | Statin users still had lower rates of the composite outcome (adjusted risk difference: −3.4%; 95% CI: −4.6% to −2.1%), ICU admissions (−3.3%; −4.5% to −2.1%), and intubation (−1.9%; −2.8% to −1.0%) but comparable inpatient deaths (0.6%; −1.3% to 0.1%). | IIb | |
2023 | Survival impact of previous statin therapy in patients hospitalized with COVID-19 [31] | Retrospective cohort | Multiple statins (rosuvastatin, atorvastatin, simvastatin, pravastatin, pitavastatin, fluvastatin- lovastatin). | Significant association between previous treatment with statins and lower mortality in hospitalized patients with COVID-19 (HR: 0.76; 95% CI: 0.59–0.97). | IIb | |
2023 | The impact of statin therapy on in-hospital prognosis and endothelial function of patients at high-to-very high cardiovascular risk admitted for COVID-19 [38] | Retrospective cohort | Multiple statins | Preadmission statin therapy was independently associated with a 75% risk reduction of intensive care unit admission/in-hospital death (adjusted hazard ratio 0.252, 95% confidence interval 0.122–0.521, p < 0.001). | IIb | |
2023 | Role of statins in clinical evolution of octogenarian patients admitted due to COVID-19 [39] | Retrospective cohort | Multiple statins (rosuvastatin, atorvastatin, pravastatin) | Pre-admission treatment with statins was associated with lower in-hospital mortality (RR 0.58 95% CI [0.41–0.83]; p = 0.003). | IIb | |
2023 | Routine statins use is associated with less adverse outcome in patients above 70 years of age admitted to hospital with COVID-19 [40] | Retrospective cohort | Multiple statins | After adjustment for potential confounders, prior statin use was associated with decreased risk for an adverse outcome (odds ratio = 0.4, 95% confidence interval 0.18–0.92, p = 0.03). | IIb | |
2020 | In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19 [26] | Retrospective cohort | Multiple statins (atorvastatin—83.2%, rosuvastatin 15.6%) | Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. | III | |
2020 | Relation of statin use prior to admission to severity and recovery among COVID-19 inpatients [34] | Retrospective cohort | Multiple statins | Statin use prior to admission was associated with reduced risk of severe COVID-19 (adjusted OR 0.29, 95% CI 0.11 to 0.71, p < 0.01) and faster time to recovery among those without severe disease (adjusted HR for recovery 2.69, 95% CI 1.36 to 5.33, p < 0.01). | III | |
2020 | Statin use is associated with lower disease severity in COVID-19 infection [37] | Retrospective cohort | Multiple statins | Logistic treatment models showed a lower chance of ICU admission for statin users when compared to non-statin users (ATET: Coeff (risk difference): −0.12 (−0.23, −0.01); p = 0.028). | III | |
2020 | Risk Factors associated with in-hospital mortality in a US national sample of patients with COVID-19 [50] | Retrospective cohort | Multiple statins | Receipt of statins (OR, 0.60; 95% CI, 0.56–0.65; p < 0.001) was associated with decreased odds of death. | III | |
2020 | Protective role of statins in COVID 19 patients: Importance of pharmacokinetic characteristics rather than intensity of action [79] | Retrospective cohort | Multiple statins (18/42 on high-intensity statin, 24/42 on low or moderate-intensity statin) | Simvastatin and atorvastatin reduced mortality in COVID-19 patients, unlike pravastatin and rosuvastatin, which did not. | III | |
2021 | Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: Updated results from the nationwide CORONADO study [59] | Observational study | Multiple statins | In patients with diabetes hospitalized for COVID-19, statin use was associated with a higher risk of death (OR 1.42, 95% CI 1.00–2.02). | III | |
2021 | Association of lipid-lowering drugs with COVID-19 outcomes from a Mendelian randomization study [51] | Mendelian randomization study | Multiple statins | Higher expressions of HMG-CoA reductase (HMGCR) and HMGCR-mediated LDL cholesterol were associated with a higher risk of COVID-19 hospitalization (OR 1.38, 95% CI 1.06–1.81 and OR 1.32, 95% CI 1.00–1.74, respectively). | III | |
2021 | The role of lovastatin in the attenuation of COVID-19 [24] | Retrospective cohort | Lovastatin | There is a potential use of lovastatin to mitigate the inflammatory response induced by SARS-CoV-2 infection. | III | |
2021 | Decreased mortality rate among COVID-19 patients prescribed statins: Data from electronic health records in the US [32] | Retrospective cohort | Multiple statins (atorvastatin (Lipitor), cerivastatin (Baycol), fluvastatin (Lescol), lovastatin (Mevacor), pitavastatin (Zypitamag, Livalo or Nikita), pravastatin (Pravachol), rosuvastatin (Ezallor or Crestor), simvastatin (FloLipid or Zocor) | Statins do not increase COVID-19-related mortality and may, in fact, have a mitigating effect on the severity of the disease reflected in a slight reduction in mortality. | III | |
2022 | Critical influenza and COVID-19—a comparative nationwide case-control study [29] | Retrospective cohort | Multiple statins (rosuvastatin, atorvastatin, simvastatin) | Premorbid use of statin medication was associated with a reduced risk of ICU admission for both diseases. | III | |
2022 | The association of statins use with survival of patients with COVID-19 [52] | Retrospective cohort | Multiple statins | Continuous statin use was associated with lower in-hospital mortality compared to no statin use and discontinuation of statins. | III | |
2020 | Statins and SARS-CoV-2 disease: Current concepts and possible benefits [23] | Narrative review | Multiple statins (rosuvastatin- atorvastatin- simvastatin) | Early international retrospective observations suggested a beneficial effect of statin use before and during hospitalization on the clinical outcomes of COVID-19, notably critical care admission and mortality. | IV | |
2021 | COVID-19 and lipids. The role of lipid disorders and statin use in the prognosis of patients with SARS-CoV-2 infection [61] | Narrative review | Multiple statins | 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. | IV | |
2021 | Investigating lipid-modulating agents for prevention or treatment of COVID-19: JACC State-of-the-Art Review [81] | Narrative review | Multiple statins | Statins’ impact on COVID-19 outcomes was also studied through randomized controlled clinical trials (RCT), reportedly seventeen in 2021. | IV |
Pathogen | Year | Title of Study | Type of Study | Type of Statin | Key Findings Pertaining to Statins |
---|---|---|---|---|---|
SARS-CoV-2 | 2023 | Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients [80] | Cell culture | Simvastatin | Simvastatin was a potent direct inhibitor of SARS-CoV-2 infected cells in vitro, unlike most other statins being less effective. |
Influenza | 2009 | Evaluation of the efficacy and safety of a statin/caffeine combination against H5N1, H3N2, and H1N1 virus infection in BALB/c mice [87] | Animal study | Statin 50 μg/caffeine 200 μg | The combination of statins and caffeine was first proven to decrease lung damage and viral replication as effectively as oseltamivir and ribavirin, notably when administered preventatively. |
2012 | The effect of rosuvastatin in a murine model of influenza A infection [88] | Animal study | Rosuvastatin | Statins did not affect the clearance of the influenza A virus from the lung and did not decrease the severity of the induced lung injury or related mortality. | |
2012 | Effect of statin treatments on highly pathogenic avian influenza H5N1, seasonal, and H1N1pdm09 virus infections in BALB/c mice [103] | Animal study | Multiple statins (simvastatin, lovastatin, mevastatin, pitavastatin, atorvastatin, or rosuvastatin) at various concentrations | The statins administered intraperitoneally or orally at any dose did not significantly enhance the total survivors relative to untreated controls. | |
2013 | Simvastatin treatment showed no prophylactic effect in influenza virus-infected mice [90] | Animal study | Simvastatin | Results showed that simvastatin failed to protect mice against influenza virus infection. | |
2013 | Simvastatin and oseltamivir combination therapy does not improve the effectiveness of oseltamivir alone following highly pathogenic avian H5N1 influenza virus infection in mice [89] | Animal study | Simvastatin | In mice infected with influenza, simvastatin did not decrease the morbidity, mortality, or viral titers and its addition to oseltamivir was no more efficient than oseltamivir alone. | |
2014 | Protective effect of fluvastatin on influenza virus infection [91] | Cell culture | Fluvastatin | Fluvastatin had an anti-inflammatory activity that minimally inhibited influenza virus infection. | |
Yellow fever | 2021 | Inhibition of orbivirus replication by fluvastatin and identification of the key elements of the mevalonate pathway involved [104] | Cell culture and animal study | Fluvastatin | Fluvastatin reduces replication of orbiviruses (bluetongue virus (BTV) and Great Island virus (GIV)) in cell culture. Pre-treatment of IFNAR(-/-) mice with fluvastatin promoted their survival upon challenge with live BTV, although only limited protection was observed. |
Dengue | 2009 | Cholesterol biosynthesis modulation regulates dengue viral replication [105] | Cell culture | Lovastatin | Lovastatin could inhibit DEN-2 New Guinea C live virus replication in human peripheral blood mononuclear cells. |
2014 | Lovastatin delays infection and increases survival rates in AG129 mice infected with dengue virus serotype 2 [106] | Animal study | Lovastatin | Mice pre-treated with lovastatin had lower dengue 2 viremia levels and increased survival. Effect was dose dependent. | |
2019 | Lipophilic statins inhibit Zika virus production in Vero cells [16] | Cell culture | Lipophilic statins (atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, and simvastatin) | Lipophilic statins (atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, and simvastatin) could reduce ZIKV production in vitro and result in smaller foci of infection. Early treatment with statins is more beneficial than late treatment; however, statins could not completely inhibit the entry stage of ZIKV infection. Fluvastatin was the most efficient at low concentrations in terms of anti-ZIKV capacity. | |
2022 | Effects of statin combinations on Zika virus infection in Vero cells [107] | Cell culture | Multiple statins | In a previous study, they found that lipophilic statins can inhibit ZIKV production in Vero cells; therefore, they looked at combinations. They found that certain combinations of atorvastatin or fluvastatin with simvastation or mevastatin may be synergistic. | |
2023 | Cholesterol-lowering drugs as potential antivirals: A repurposing approach against flavivirus Infections [108] | Cell culture and animal study | Atorvastatin | The combination of atorvastatin and ezetimibe had a synergistic effect against dengue 2, an additive effect against dengue 4 and Zika, and an antagonistic effect against yellow fever virus. In mice infected with dengue 2, monotherapy with atorvastatin or ezetimibe had significantly increased survival but not with the combination of both drugs. | |
Norovirus | 2009 | Role of cholesterol pathways in norovirus replication [109] | Cell culture | Simvastatin and lovastatin | Statins enhance LDL receptor expression, aiding cholesterol uptake in cells, potentially increasing norovirus susceptibility. Unlike statins, zaragozic acid and 6-fluoromevalonate, which block cholesterol biosynthesis via different pathways, did not affect virus replication. This raises concerns about statins’ role in norovirus infections and merits further study. |
2012 | The effects of simvastatin or interferon-α on infectivity of human norovirus using a gnotobiotic pig model for the study of antivirals [110] | Animal study | Simvastatin | Simvastatin treatment elevated HuNoV infectivity in Gn pig model, likely by suppressing innate immunity and reducing cholesterol levels, aligning with previous reports. These results offer insight into the heightened HuNoV disease observed in statin-treated individuals. | |
2013 | Median infectious dose of human norovirus GII.4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age [111] | Animal study | Simvastatin | Simvastatin increased susceptibility to infection and more importantly the incidence of diarrhoea in Gn pigs inoculated with a GII.4 NoV variant. | |
2021 | Simvastatin reduces protection and intestinal T-cell responses induced by a norovirus P particle vaccine in gnotobiotic pigs [112] | Animal study | Simvastatin | In a pig model of human NoV infection, simvastatin, a cholesterol-lowering agent, was observed to impede T-cell immunity and annul the protective efficacy of P particles, shedding light on the potential impact of statins on NoV pathogenesis. | |
Hepatitis B and C | 2012 | Atorvastatin inhibits proliferation and apoptosis but induces senescence in hepatic myofibroblasts and thereby attenuates hepatic fibrosis in rats [113] | Cell culture | Atorvastatin | Atorvastatin inhibited the activation of hepatic stellate cells to myofibroblasts (MFB) and decreased cytokine and collagen production in MFB in vitro, thereby reduced MFB turnover and fibrogenesis. |
2013 | The transcription factor KLF2 mediates hepatic endothelial protection and paracrine endothelial-stellate cell deactivation induced by statins [114] | Cell culture | Four different statins (atorvastatin, mevastatin, simvastatin, and lovastatin) | Upregulation of hepatic endothelial KLF2-derived transcriptional programs by statins confers vasoprotection and stellate cells deactivation, reinforcing the therapeutic potential of these drugs for liver diseases that course with endothelial dysfunction. | |
Measles | 2009 | Impaired cholesterol biosynthesis in a neuronal cell line persistently infected with measles virus [115] | Cell culture | Simvastatin | Simvastatin leads to reduction in number of giant cells and virus plaques; however, it was dose-dependent. This suggested that cholesterol synthesis and raft integrity are important factors for successful budding and production of infectious MV progeny. |
2.3. Select Travel-Related Flavivirus Concerns: Yellow Fever, Dengue, Zika, Tick-Borne Encephalitis
2.4. Haemorrhagic Fever Viruses
2.5. GI Viruses: Norovirus
2.6. Blood/Body Fluid-Transmitted Viruses: Hepatitis B, Hepatitis C
2.7. Other Viruses: Measles and Herpesvirus
3. Limitations
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Abbreviations
aHR | adjusted hazard ratio |
APC | antigen-presenting cells |
CAD | coronary artery disease |
CCR-5 | C-C chemokine receptor type 5 |
CDC | Centers for Disease Control and Prevention |
CI | confidence interval |
CRP | C-reactive protein |
DENV | dengue virus |
DHS | dengue hemorrhagic fever |
DS | severe dengue |
DSSL | dengue shock syndrome |
EIP | Emerging Infections Program |
HBV | hepatitis B Virus |
HCC | hepatocellular carcinoma |
HCV | hepatitis C virus |
HMG-CoA | hydroxymethylglutaryl-CoA |
HMG-CoAR | HMG-CoA reductase |
HR | hazard ratio |
ICU | intensive care unit |
LDL | low-density lipoprotein |
OR | odds ratio |
RCT | randomized controlled trials |
US | United States |
YFV | yellow fever virus |
ZKV | Zika virus |
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Pathogen | Year | Title of Study | Type of Study | Type of Statin | Key Findings Pertaining to Statins | Category of Evidence |
---|---|---|---|---|---|---|
Influenza | 2011 | Pre-admission statin use and in-hospital severity of 2009 pandemic influenza A(H1N1) disease [94] | Retrospective cohort | Multiple statins | No statistically significant association between pre-admission statin use and severity of outcome after adjustment for age and sex [adjusted OR: 0.81 (95% CI 0.46–1.38); n = 571]. | IIb |
2012 | Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: A multistate study [96] | Retrospective cohort | Multiple statins | In a multivariable logistic regression model, administration of statins prior to or during hospitalization was associated with protective odds of death (adjusted odds ratio, 0.59 [95% confidence interval, 0.38–0.92]) when adjusting for age; race; cardiovascular, lung, and renal disease; influenza vaccination; and antiviral administration. | IIb | |
2022 | The effect of statins on the prevalence and mortality of influenza virus infection: A systematic review and meta-analysis [100] | Meta-analysis | Multiple statins | In flu-vaccinated and unvaccinated subjects, the regular use of statins significantly decreased influenza prevalence (OR 0.85, 95% CI 0.73–0.99; p = 0.04), 30-day mortality (OR 0.61, 95% CI 0.47, 0.80; p < 0.001), and 90-day mortality after the diagnosis (OR 0.74, 95% CI 0.55, 1.00; p = 0.042). | IIb | |
2022 | Statins and influenza mortality: Systematic review and meta-analysis [101] | Meta-analysis | Multiple statins | Statin therapy was associated with decreased mortality (OR 0.66; 95% CI 0.51–0.85; p < 0.01). | IIb | |
2009 | Influenza morbidity and mortality in elderly patients receiving statins: A cohort study [93] | Retrospective cohort | Multiple statins: atorvastatin, cerivastatin, fluvastatin, lovastatin, pravastatin, and simvastatin | An analysis of over 10 influenza seasons (1996 to 2006) in Canada showed that the minimal statistically significant protective effect of statin against influenza morbidity was probably due to confounding variables. | III | |
2015 | Statin treatment and mortality: Propensity score-matched analyses of 2007–2008 and 2009–2010 laboratory-confirmed influenza hospitalizations [95] | Retrospective cohort | Data on statin dose or frequency of administration were not collected | A propensity score-matched analysis of influenza hospitalization data from two seasons suggested a protective effect of statins against mortality in 2007–2008 but not during the 2009 pandemic, with sensitivity analysis indicating potential influence from unmeasured confounders. This analysis does not support using statins as an adjunct treatment for preventing death among persons hospitalized for influenza. | III | |
2017 | The effect of statins on influenza-like illness morbidity and mortality [99] | Retrospective cohort | Multiple statins | The potentially beneficial effect of statins on influenza-related adverse outcomes may be explained by a healthy user bias. | III | |
2018 | Statin use and risks of influenza-related outcomes among older adults receiving standard-dose or high-dose influenza vaccines through Medicare during 2010–2015 [98] | Retrospective cohort | Multiple statins | Statin use around the time of vaccination did not affect the risk of influenza-related medical encounters in older adults. | III | |
2019 | Statins and outcomes of hospitalized patients with laboratory-confirmed 2017–2018 influenza [97] | Retrospective cohort | Multiple statins | Statin use was not associated with mortality benefit in patients with influenza. | III | |
2022 | Critical influenza and COVID-19—A comparative nationwide case-control study [29] | Case-control study | Multiple statins | The premorbid use of statin was associated with a reduced risk of intensive care unit (ICU) admission with an odds ratio (OR) of 0.74 (95% confidence interval (CI) 0.62–0.89; p-value 0.002). | III | |
2013 | Adjunctive therapies and immunomodulatory agents in the management of severe influenza [92] | Narrative review | Multiple statins | Epidemiologic studies on the impact of statin use in influenza patients have shown mixed results. While some studies suggest a small protective effect against pneumonia hospitalization and mortality, others found no significant association after adjusting for confounding factors. | IV |
Pathogen | Year | Title of Study | Type of Study | Type of Statin | Key Findings Pertaining to Statins | Category of Evidence |
---|---|---|---|---|---|---|
Dengue | 2015 | Lovastatin for the treatment of adult patients with dengue: A randomized, double-blind, placebo-controlled trial [116] | Randomized controlled trial | Lovastatin | RCT of lovastatin in patients with Dengue with the primary outcome being safety. Lovastatin was safe and well tolerated in adults with dengue. However, although the study was not powered to address efficacy, they found no evidence of a beneficial effect on any of the clinical manifestations or on dengue viremia. | Ib |
2023 | Hyperlipidemia, statin use and dengue severity [117] | Retrospective cohort | Multiple statins | Compared dengue patients with hyperlipidemia on the basis of statin use. Outcomes were development of dengue hemorrhagic fever (DHF) or shock syndrome (DSS) and severe dengue (SD). A total of 257 dengue patients were included; 191 (74.3%) were statin users and 66 (25.7%) were non-users. No significant difference detected in risk of DHF/DSS (adjusted risk ratio [aRR] = 0.66, 95% confidence interval [CI]: 0.41–1.08, p = 0.10) or SD (aRR = 1.43, 95% CI: 0.84–2.43, p = 0.19). | IIb | |
Tick-borne encephalitis | 2018 | Impact of pre-existing treatment with statins on the course and outcome of tick-borne encephalitis [118] | Retrospective cohort | Multiple statins | A total of 700 adult patients with tick-borne encephalitis of whom 77 (11%) were being treated with statins, along with 410 other patients, of whom 53 (13%) were receiving statins. Multivariable analyses found no statistically significant association between statin usage and having a milder acute illness, prognosis, or long-term symptoms. | III |
Ebola | 2015 | Treating the host response to Ebola virus disease with generic statins and angiotensin receptor blockers [119] | Narrative review | Atorvastatin 40 mg/day | In Sierra Leone, approximately 100 Ebola patients were treated with this combination, and reports indicate that survival was greatly improved. Unfortunately, supervising physicians and health officials in Sierra Leone have not released reports of the treatment results, although they exchanged letters and memoranda describing their experience, with one letter noting “remarkable improvement” on treatment. | IV |
2015 | Treating Ebola patients: A ‘bottom up’ approach using generic statins and angiotensin receptor blockers [120] | Narrative review | Atorvastatin 40 mg/day | Atorvastatin and irbesartan reduced Ebola mortality in Sierra Leone. The treatment was also safe and restored endothelial barrier integrity. | IV | |
Norovirus | 2010 | Norovirus disease associated with excess mortality and use of statins: A retrospective cohort study of an outbreak following a pilgrimage to Lourdes [121] | Retrospective cohort | Multiple statins | A retrospective cohort study identified statin use as a risk factor for norovirus disease, underscoring the necessity for further investigations to assess the ramifications of statins in NoV infection. | III |
Hepatitis B and C | 2004 | Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis [122] | Randomized controlled trial | Simvastatin | Simvastatin administration increases the hepatosplanchnic output of nitric oxide products and decreases hepatic resistance in patients with cirrhosis. | Ib |
2017 | Statin use and risk of cirrhosis and related complications in patients with chronic liver diseases: A systematic review and meta-analysis [123] | Meta-analysis | Multiple statins | In patients with cirrhosis, statin use was associated with 46% lower risk of hepatic decompensation (four studies; RR, 0.54; 95% CI, 0.46–0.62; I2 = 0%; moderate-quality evidence), and 46% lower mortality (5 studies; RR, 0.54; 95% CI, 0.47–0.61; I2 = 10%; moderate-quality evidence). | Ib | |
2019 | Comprehensive evaluation of effects and safety of statin on the progression of liver cirrhosis: A systematic review and meta-analysis [124] | Meta-analysis | Multiple statins | For a long-term follow-up, statin treatment surprisingly decreased mortality rate (HR = 0.782, 95% CI: 0.718–0.846, I2 > 50%) and lowered the occurrence of hepatocellular carcinoma (HR = 0.75, 95% CI: 0.64–0.86, I2 > 50%) in liver cirrhosis. | Ib | |
2021 | Statin therapy in chronic viral hepatitis: A systematic review and meta-analysis of nine studies with 195,602 participants [125] | Meta-analysis | Multiple statins | In a meta-analysis of statin effects on liver health in CVH patients, long-term statin use did not show overall mortality reduction. However, mortality risk dropped by 39% in statin users followed for over three years. Additionally, statin therapy was associated with significant reductions in hepatocellular carcinoma risk by 53%, fibrosis by 45%, and cirrhosis by 41%. | Ib | |
2016 | Statins reduce the risk of cirrhosis and its decompensation in chronic hepatitis B patients: A nationwide cohort study [126] | Retrospective cohort | Multiple statins | CHB patients using statins had a significantly lower cumulative incidence of cirrhosis (relative risk = 0.433; 95% confidence interval (CI) = 0.344–0.515; modified log-rank test, p < 0.001) and decompensated cirrhosis (relative risk = 0.468; 95% CI = 0.344–0.637; p < 0.001) compared with patients not using statins (after adjustment for competing mortality). | IIb | |
2017 | Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: A population-based study [127] | Retrospective cohort | Multiple statins | Among patients with cirrhosis, statin use decreased the risk of decompensation, mortality, and HCC in a dose-dependent manner (p for trend <0.0001, <0.0001, and 0.009, respectively). Regression analysis revealed a lower risk of decompensation among statin users with cirrhosis due to chronic HBV (adjusted hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.25–0.62) or HCV infection (HR, 0.51; 95% CI, 0.29–0.93). | IIb | |
2021 | Statins associate with better clinical outcomes in chronic hepatitis B patients with HBsAg seroclearance [128] | Retrospective cohort | Simvastatin, atorvastatin, and rosuvastatin | Statins were associated with lower cirrhosis/HCC risk in HbsAg seroclearance patients (adjusted hazard ratio [aHR]: 0.44; 95% CI 0.20–0.96; aHR for every 1-year increase in use: 0.85; 95% CI 0.75–0.97). Statin users had no hepatic decompensation or liver-related death/transplantation (vs 18/778 [2.3%] and 18/784 [2.3%] cases in statin non-users, respectively). Statins were also associated with lower all-cause mortality risk (aHR: 0.21; 95% CI 0.08–0.53). | IIb | |
2022 | Statins in hepatitis B or C patients is associated with reduced hepatocellular carcinoma risk: A systematic review and meta-analysis [129] | Meta-analysis | Multiple statins | Statin users had a significantly lower risk of hepatocellular carcinoma (relative risk = 0.47, 95% CI = 0.38–0.56) with significant heterogeneity. In seven hepatitis studies, using statin was associated with a 53% reduction in the incidence of hepatocellular carcinoma (relative risk = 0.47, 95% CI = 0.43–0.50) with substantial heterogeneity. In three cirrhosis studies, the incidence of hepatocellular carcinoma in statin users was significantly reduced by 55% (relative risk = 0.45, 95% CI = 0.30–0.61) with no heterogeneity. | IIb | |
2022 | Can statins lessen the burden of virus mediated cancers? [130] | Narrative review | Multiple statins | Studies of populations with HBV and HCV suggest a protective, dose-dependent effect of statins on hepatocellular carcinoma risk and support the theory that statins may offer clinical benefit if used as chemoprophylactic agents to reduce liver cancer incidence. | IV | |
Herpes simplex | 2005 | Statins lower the risk of developing Alzheimer’s disease by limiting lipid raft endocytosis and decreasing the neuronal spread of herpes simplex virus type 1 [131] | Narrative review | Multiple statins | Long-term statin therapy protects individuals from Alzheimer’s disease by reducing the neuronal spread of HSV-1 via lipid raft domain pathways. | IV |
Varicella-Zoster | 2014 | Statins and the risk of herpes zoster: A population-based cohort study [132] | Retrospective cohort | Multiple statins | A population-based retrospective cohort study conducted over 13 years identified that older patients treated with statins had a small but notably increased risk of herpes zoster with a (hazard ratio) HR of 1.13. This association persisted even within a subgroup of patients with diabetes (HR—1.18) | IIb |
2009 | High serum cholesterol levels are associated with herpes zoster infection after heart transplantation [133] | Case-control study | Multiple statins | A case-control analysis has indicated a link between elevated blood cholesterol levels and the occurrence of herpes zoster infection in individuals who had undergone heart transplantation. This study also found that cholesterol could trigger the reactivation and dissemination of VZV in vivo. | III |
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Jani, C.T.; Mouchati, C.; Abdallah, N.; Jani, R.; Kakoullis, L.; Chen, L.H. Do Statins Affect Viral Infections Encountered by International Travelers? Trop. Med. Infect. Dis. 2025, 10, 73. https://doi.org/10.3390/tropicalmed10030073
Jani CT, Mouchati C, Abdallah N, Jani R, Kakoullis L, Chen LH. Do Statins Affect Viral Infections Encountered by International Travelers? Tropical Medicine and Infectious Disease. 2025; 10(3):73. https://doi.org/10.3390/tropicalmed10030073
Chicago/Turabian StyleJani, Chinmay T., Christian Mouchati, Nour Abdallah, Ruchi Jani, Loukas Kakoullis, and Lin H. Chen. 2025. "Do Statins Affect Viral Infections Encountered by International Travelers?" Tropical Medicine and Infectious Disease 10, no. 3: 73. https://doi.org/10.3390/tropicalmed10030073
APA StyleJani, C. T., Mouchati, C., Abdallah, N., Jani, R., Kakoullis, L., & Chen, L. H. (2025). Do Statins Affect Viral Infections Encountered by International Travelers? Tropical Medicine and Infectious Disease, 10(3), 73. https://doi.org/10.3390/tropicalmed10030073