Table 1.
Characteristics of included studies
| Study | Country | Design | Total number of patients | Age (mean [SD]/median [IQR]) | Type of statin | Mortality | Severe illnessa | Adjustment | NOS | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Statin users (n/N; %) | Non-statin users (n/N; %) | Adjusted estimate (95% confidence interval) | Statin users (n/N; %) | Non-statin users (n/N; %) | Adjusted estimate (95% confidence interval) | ||||||||
| Yan et al. [11] | China | Retrospective, multicenter, case–control study | 610 | 48.8 (14.2) | N/A | – | – | – | 5/15; 31.3 | 123/578; 20.7 | OR = 1.78 (0.54–5.13) | Age, sex, body mass index | 5/9 |
| Zhang et al. [12] | China | Retrospective, multicenter, cohort study | 4305 |
Statin: 66.0 (59.0–72.0) Non-statin: 57.0 (45.0–67.0) |
Atorvastatin, rosuvastatin, simvastatin, pravastatin, fluvastatin, pitavastatin | 45/861; 5.2 | 325/3444; 9.4 | HR = 0.58 (0.43–0.80) | N/A | N/A | HR = 0.69 (0.56–0.85) |
Mortality: AGE, gender, and oxygen saturation at admission Severity: Age, gender, blood pressure, pre-existing comorbidities, indicators of disease severity and organ injuries, LDL-C increase, total cholesterol increase |
8/9 |
| Rodriguez-Nava et al. [13] | USA | Retrospective, single-center, cohort study | 87 | 68 (58–75) | Atorvastatin | N/A | N/A | HR = 0.38 (0.18–0.77) | – | – | – | Age, hypertension, cardiovascular disease, invasive mechanical ventilation, severity according to the National Institutes of Health criteria, number of comorbidities, and adjuvant therapies | 7/9 |
| Grasselli et al. [14] | Italy | Retrospective, multicenter, cohort study | 3988 | 63 (56–69) | N/A | N/A | N/A | HR = 0.98 (0.81–1.20) | – | – | – | Age, gender, type of respiratory support, comorbidities, ACEi use, ARB use, diuretic use, positive end-expiratory pressure at admission, fraction of inspired oxygen at admission, arterial partial pressure of oxygen/fraction of inspired oxygen at admission | 7/9 |
| De Spiegeleer et al. [15] | Belgium | Retrospective, multicenter, cohort study | 154 | 85.9 (7.2) | N/A | – | – | – | 6/31 | 31/123 | OR = 0.86 (0.25–2.50) | Age, sex, functional status, diabetes mellitus, hypertension, diagnosis method | 7/9 |
| Gupta et al. [16] | USA | Retrospective, multicenter, cohort study | 2626 |
Statin users: 70 (63–79) Non-statin users: 62 (49–76) |
N/A | N/A | N/A | OR = 0.56 (0.44–0.72) | N/A | N/A | OR = 0.80 (0.64–1.02) | Age, sex, body mass index, ethnicity, insurance, New York City borough of residence, comorbidities, outpatient use of beta-blockers, ACEis, ARBs, oral anticoagulants, and P2Y12 receptor inhibitors | 8/9 |
| Song et al. [17] | USA | Retrospective, multicenter, cohort study | 249 |
Statin users: 71.0 (60.0–79.0) Non-statin users: 54.5 (42.0–67.0) |
N/A | N/A | N/A | OR = 0.88 (0.37–2.08) | N/A | N/A |
ICU admission: OR = 0.90 (0.49–1.67) Intubation: OR = 0.45 (0.20–0.99) |
Age, sex, race, comorbidities | 7/9 |
| Mallow et al. [18] | USA | Retrospective database review | 21676 | 64.9 (17.2) | Atorvastatin, rosuvastatin, simvastatin, pravastatin, pitavastatin | N/A | N/A | OR = 0.54 (0.49–0.60) | – | – | – | Age, sex, primary payer, Medicaid, comorbidities, use of ACEis, use of ARBs, bed size, hospital teaching status, geographic region | 8/9 |
| Cariou et al. [19] | France | Retrospective, multicenter, cohort study | 2449 |
Statin users: 71.7 (10.8) Non-statin users: 70.2 (13.9) |
N/A | 229/1192; 19.2 | 248/1257; 19.7 | OR = 0.92 (0.63–1.35) | 283/1192; 23.7 | 229/1257; 18.2 | OR = 0.92 (0.63–1.35) | Age, sex, ethnicity, body mass index, comorbidities, macrovascular complications, use of co-medications | 6/9 |
| Saeed et al. [20] | USA | Retrospective, single-center, cohort study | 2266 |
Statin users: 69 (11) Non-statin users: 67 (14) |
Atorvastatin, rosuvastatin, simvastatin, pravastatin | N/A | N/A | HR = 0.87 (0.83–0.91) | – | – | – | Age, sex, body mass index, days of symptoms prior to admission, history of atherosclerotic heart disease, Charlson Comorbidity Index, presenting diastolic blood pressure, respiratory rate, pulse oximetry measurement, heart rate, laboratory measurements, use of co-medications, troponin level and intravenous antibiotics during hospitalization | 6/9 |
| Nicholson et al. [21] | USA | Retrospective, multicenter, cohort study | 1042 | 64 (53–75) | N/A | 122/511; 23.9 | 88/531; 16.6 | OR = 0.47 (0.24–0.92) | N/A | N/A | N/A | Age, sex, comorbidities, oxygen saturation to fraction of inspired oxygen ratio, body mass index, neutrophil to lymphocyte ratio, platelet count, procalcitonin level | 8/9 |
| Daniels et al. [22] | USA | Retrospective, single-center, cohort study | 170 | 59 (19) | N/A | – | – | – | 20/46; 43.4 | 70/124; 56.5 | OR = 0.29 (0.11–0.71) | Age, sex, comorbidities, use of ACEis, use of ARBs | 8/9 |
| Bifulco et al. [23] | Italy | Retrospective, single-center, cohort study | 541 |
Statin users: 72.9 (10.9) Non-statin users: 63.0 (14.5) |
N/A | N/A | N/A | OR = 0.75 (0.26–2.17) | – | – | – | Age, sex, smoking habit, comorbidities, indicators of disease severity, organ injuries, blood biomarkers | 7/9 |
| Masana et al. [24] | Spain | Retrospective, multicenter, cohort study | 1162 |
Statin users: 73 (65–80) Non-statin users: 74 (64–84) |
N/A | 115/581; 19.8 | 148/581; 25.4 | HR = 0.58 (0.39–0.89) | – | – | – | Age, sex, smoking habit, comorbidities, use of co-medications, lipid profile before admission | 7/9 |
| Philipose et al. [25] | UK | Retrospective, single-center, cohort study | 466 |
Discharged: 67 (26) Died: 77 (17) |
N/A | 79/164; 48.1 | 120/302 39.7 | OR = 1.03 (0.71–1.45) | – | – | – | Age, sex | 8/9 |
| Butt et al. [26] | Denmark | Retrospective database review | 4842 |
Statin users: 73 (63–79) Non-statin users: 50 (37–65) |
Atorvastatin, rosuvastatin, simvastatin, pravastatin | 311/3999; 7.8 | 177/843; 21.0 | HR = 0.96 (0.78–1.18) | 419/3999; 10.5 | 204/843; 24.2 | HR = 1.16 (0.95–1.41) | Age, sex, ethnicity, education, income, use of comorbidities, co-medications | 7/9 |
| Fan et al. [27] | China | Retrospective, multicenter, cohort study | 412 |
Statin users: 64 (57–72) Non-statin users: 66 (57–73) |
N/A | 3/206; 1.5 | 10/206; 4.9 | HR = 0.25 (0.07–0.92) | 9/206; 4.4 | 17/206; 8.3 | HR = 0.38 (0.16–0.92) | Age, sex, comorbidities, type of hospital, use of ACEis/ARBs, use of glucocorticoids, neutrophil count, D-dimer level, total cholesterol level, triglyceride level, LDL-C level, procalcitonin level, creatine kinase-MB level, troponin level, brain natriuretic peptide level | 8/9 |
| Mitacchione et al. [28] | Italy | Retrospective, multicenter, cohort study | 290 |
Statin users: 71 (64–79) Non-statin users: 72 (61–80) |
Atorvastatin, rosuvastatin, simvastatin | 38/145; 26.2 | 41/145; 28.3 | OR = 0.90 (0.54–1.51) | 6/145; 4.1 | 11/145; 7.6 | OR = 0.53 (0.19–1.46) | Age, sex, comorbidities | 8/9 |
| Rosenthal et al. [29] | USA | Retrospective database review | 64781 | 56.1 (19.9) | N/A | 2426/12233; 19.8 | 4929/52548; 9.4 | OR = 0.60 (0.56–0.65) | – | – | – | Age, sex, race, ethnicity, payer type, type of admission, admission point of origin, geographic region, geographic size, rural/urban status, teaching status, comorbidities, complications, co-medications, use of supplements during index hospitalization | 8/9 |
| Xiang et al. [30] | UK | Prospective, multicenter, cohort study | 3858 | 68.1 (8.1) | N/A | N/A | N/A | OR = 2.48 (0.99–6.19) | – | – | – | Age, sex, ethnicity, comorbidities, blood measurement, number of medications taken, number of non-cancer illnesses, body mass index, Townsend Deprivation Index, smoking status | 7/9 |
| Peymani et al. [31] | Iran | Retrospective, single-center, cohort study | 150 |
Statin users: 63.6 (13.2) Non-statin users: 61.7 (15.8) |
Atorvastatin, rosuvastatin, simvastatin | N/A | N/A | HR = 0.76 (0.16–3.72) | N/A | N/A | OR = 0.96 (0.61–2.49) | Age, comorbidities, disease stage, disease duration, co-medications, blood pressure, oxygen saturation, lymphocyte count, international normalized ratio, serum creatinine level, hematocrit, requirement of mechanical ventilation | 8/9 |
| Byttebier et al. [32] | Belgium | Retrospective, multicenter, case–control study | 959 | 69.2 | N/A | 47/297; 15.8 | 103/662; 15.6 | OR = 0.56 (0.39–0.93) | – | – | – | Age, sex, hospital size, comorbidities | 8/9 |
| Ramachandran et al. [33] | USA | Retrospective, single-center, cohort study | 295 |
PPI users = 67.0 (57.3–76.5) Non-PPI users = 65.0 (54.0–74.0) |
N/A | N/A | N/A | OR = 1.59 (0.84–3.02) | – | – | – | Charlson Comorbidity Index, body mass index, use of PPI | 8/9 |
| Yetmar et al. [34] | USA | Retrospective database review | 1295 |
Statin users: 65 (57–73) Non-statin users: 55 (43–65) |
N/A | 35/500; 7.0 | 24/795; 3.0 | OR = 1.14 (0.64–2.03) | – | – | – | Charlson Comorbidity Index, sex, clinical trial enrollment, aspirin use | 8/9 |
| Torres-Peña et al. [35] | Spain | Retrospective database review | 1868 |
Statin users: 72 (10) Non-statin users: 73 (11) |
N/A | 192/934; 20.6 | 258/934; 27.6 | OR = 0.67 (0.54–0.83) | 333/934; 35.7 | 407/934; 43.6 | OR = 0.78 (0.69–0.89) | Age, sex, comorbidities, treatment with ACEis and ARBs, quick Sequential Organ Failure Assessment category, C-reactive protein, D-dimer, lymphocyte count, serum creatinine | 7/9 |
| Memel et al. [36] | USA | Retrospective, single-center, cohort study | 1179 |
Statin users: 69 Non-statin users: 52 |
Atorvastatin, rosuvastatin, and other statins | 108/777; 13.9 | 46/402; 11.4 | HR = 0.57 (0.37–0.86) | N/A | N/A | HR = 0.85 (0.60–1.19) | Age, sex, race, active smoker, comorbidities, ACEi use at presentation to care, number of days from March 1st, 2020 to the date of hospitalization to account for era effect, prior statin usage | 7/9 |
| Greco et al. [37] | Italy | Retrospective, multicenter, cohort study | 501 |
Statin users: 76 (10) Non-statin users: 71 (17) |
N/A | 15/51; 29.4 | 140/450; 31.1 | OR = 0.63 (0.29–1.35) | 16/51; 31.4 | 113/450; 25.1 | OR = 1.00 (0.47–2.14) | Age, sex, Charlson Comorbidity Index, comorbidities | 8/9 |
| Ahlström et al. [38] | Sweden | Retrospective database review | 1544 | 61 (52–69) | N/A | 110/275; 40 | 236/923; 25.6 | OR = 0.95 (0.81–1.12) | – | – | – | Comorbidities, use of co-medications | 7/9 |
| Oh et al. [39] | Korea | Retrospective database review | 7780 | N/A | N/A | N/A | N/A | OR = 0.74 (0.52–1.05) | – | – | – | Age, sex, income level, area of residence, disability, comorbidities, use of co-medications | 7/9 |
| Aparisi et al. [40] | Spain | Retrospective, multicenter, cohort study | 840 |
Statin users: 73.5 (10.1) Non-statin users: 65.7 (15.9) |
N/A | 64/295; 21.7 | 107/545; 19.6 | OR = 0.48 (0.30–0.77) | – | – | – | Age, sex, comorbidities, use of co-medications | 8/9 |
| Chacko et al. [41] | USA | Retrospective, single-center, cohort study | 255 |
Statin users: 69.0 (10.6) Non-statin users: 62.4 (17.7) |
N/A | 21/116; 18.1 | 32/139; 23.0 | OR = 0.14 (0.03–0.61) | – | – | – | Age, sex, comorbidities, neutrophil to lymphocyte ratio, use of mechanical ventilation, body mass index, serum creatinine at admission, use of ACEis/ARBs, use of antiplatelets | 8/9 |
| Luo et al. [42] | China | Retrospective, single-center, cohort study | 283 |
Metformin users: 63.0 (55.8–68.3) Non-metformin users: 65.0 (57.5–71.0) |
N/A | N/A | N/A | OR = 2.98 (0.65–13.76) | – | – | – | Use of co-medications | 7/9 |
| Lohia et al. [43] | USA | Retrospective, single-center, cohort study | 1014 |
Statin users: 67 (60–74) Non-statin users: 61 (47–72) |
Atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin | 138/454; 30.4 | 159/560; 28.4 | OR = 0.64 (0.47–0.87) |
ICU admission: 163/454; 35.9 Intubation: 120/454; 26.4 |
ICU admission: 174/560; 31.1 Intubation: 130/560 23.2 |
ICU admission: OR = 0.92 (0.66–1.29) Intubation: OR = 0.80 (0.55–1.15) |
Age, sex, race, body mass index, insurance, comorbidities | 8/9 |
| Terlecki et al. [44] | Poland | Retrospective, single-center, cohort study | 1729 | 63 (50–75) | N/A | 32/269; 11.9 | 191/1460; 13.1 | OR = 0.54 (0.33–0.84) | – | – | – | Age, sex, comorbidities, use of co-medications | 8/9 |
| Lala et al. [45] | USA | Retrospective, multicenter, cohort study | 2736 | 66.4 | N/A | N/A | N/A | HR = 0.57 (0.47–0.69) | – | – | – | Age, sex, body mass index, race, ethnicity, comorbidities, use of ACEis/ARBs, CURB-65 score at hospital admission | 8/9 |
ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, HR hazard ratio, ICU intensive care unit, IQR interquartile range, LDL-C low-density lipoprotein cholesterol, N/A not available, NOS Newcastle–Ottawa Scale, OR odds ratio, PPI proton pump inhibitor, SD standard deviation, USA United States of America
aThe definition of severe illness varied across 15 studies: in the study by Yan et al. [11], the definition is based on that given in the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia by the Chinese National Health Commission; in the studies by Zhang et al. [12], Butt et al. [26], Fan et al. [27], Mitacchione et al. [28], and Greco et al. [37] respectively, the definition is based on admission into an ICU or pulmonology department; in the study by De Spiegeleer et al. [15], the definition is based on long-stay hospital admission or death; in the studies by Gupta et al. [16], Cariou et al. [19], and Peymani et al. [31] respectively, the definition is based on the requirement of intubation/mechanical ventilation; in the studies by Song et al. [17] and Lohia et al. [43] respectively, the definition is based on admission into an ICU or the requirement of intubation; in the studies by Daniels et al. [22] and Memel et al. [36] respectively, the definition is based on admission into an ICU or death; in the study by Torres-Peña et al. [35], the definition is based on development of acute respiratory distress syndrome