The use of statins was associated with reduced COVID-19 mortality: a systematic review and meta-analysis

Figures & data

Table 1. Basic information of the included studies.

Author, year	Study country	Study sample	Enrolled period	Population	Age	Sex (%, male)	Statin regimen	Statin distribution (%, yes)	Comorbidity	Outcomes
Alamdari et al. (2020) [20]	Iran/Tehran	459	30 January–5 April	Hospitalized patients with COVID-19	Mean ± SD: 6.17 ± 11.89	69.7	Drug history	25.5	BMI >35 kg/m^2, DM, hypertensive disorders, coronary heart disease, CKD, CLD, COPD, malignancy, immunocompromized	Mortality
Argenziano et al. (2020) [21]	USA/New York	1000	1 March–5 April	All patients with COVID-19 who received emergency department or inpatient care	Median (IQR): 63.0 (50.0–75.0)	59.6	Drug history, Inpatient drug treatment	36.1	Hypertension, DM, CAD, CHF, pulmonary disease, asthma, COPD, OSA, interstitial lung disease, renal disease, history of stroke, active cancer, transplant history, rheumatological disease, HIV, viral hepatitis, cirrhosis, obesity (BMI >30 kg/m^2)	ICU admission
Cariou Bertrand et al. (2020) [22]	French	1317	10 March–10 April	Hospitalized patients with COVID-19	Mean ± SD: 69.8 ± 13.0	64.9	Drug history	47.6	HF, NAFLD or liver cirrhosis, active cancer, COPD, Treated OSA, organ graft, end-stage renal failure	Mortality, primary outcome
Cariou et al. (2020) [14]	French	2449	10 March–10 April	Hospitalized patients with COVID-19	Mean ± SD: 70.9 ± 12.5	64.03	Drug history	48.67	HF, NAFLD, liver cirrhosis, active cancer, COPD, treated OSA	IMV, mortality
Daniels et al. (2020) [23]	USA/California	170	10 February–17 June	Hospitalized patients with COVID-19	Mean ± SD: 59 ± 19	58	Drug history	27.1	Obesity, DM, hypertension, CVD, HF, stroke, CKD, asthma, COPD, cancer, HIV	Mortality, severity, ICU admission
Davoudi-Monfared et al. (2020) [24]	Iran/Tehran	81	29 February–3 April	Patients with severe COVID-19	Mean ± SD IFN groups: 56.0 ± 16 control group: 59.5 ± 14	54.3	Inpatient drug treatment	18.52	Any comorbidity, hypertension, DM, ischaemic heart disease, endocrine disorder, malignancy, neuropsychiatric disorders, haematologic disorder, rheumatoid disorder, renal disease, liver disease, rheumatoid arthritis, asthma, transplantation, COPD	IFN
De Spiegeleer et al. (2020) [25]	Belgium	154	1 March–16 April	All (anonymized) residents at 2 care homes with COVID-19	Mean ± SD: 85.9 ± 7.2	33.1	Drug history	21	Hypertension, cardiovascular disease, COPD, DM, renal failure, liver disease, obesity	Severity
Dreher et al. (2020) [26]	Germany/Aachen	50	February–March	Hospitalized patients with COVID-19	Median (IQR): 65 (58–76)	66	Drug history	36	Arterial hypertension, obesity, overweight, DM, prediabetes, COPD, OSA, bronchial asthma, other pulmonary diseases, CKD, nicotine abuse, cerebral arterial occlusive disease, cancer, chronic hepatitis, chronic liver failure, PAD	ARDS
Grasselli et al. (2020) [27]	Italy	3988	20 February–22 April	Patients with confirmed COVID-19 infection admitted to one of the network ICUs	Median (IQR): 63 (56–69)	79.9	Drug history	29.79	Hypertension, hypercholesterolaemia, heart disease, DM, malignant neoplasm, COPD, CKD, liver disease, other disease	Mortality
Gupta et al. (2020) [12]	USA/New York	1296^a	1 February–12 May	COVID-19 positive patients	Median (IQR): 69 (61 − 77)	56.48	Drug history	50	Hypertension, DM, CAD, HF, chronic lung disease, CKD, stroke/TIA, atrial arrhythmias, liver disease	IMV, Mortality
Higuchi et al. (2021) [28]	Japan	57	20 February–10 June	Consecutive hospital- admitted patients with COVID-19	Median (IQR): 52 (35–69.5)	56.1	Drug history	21.1	Hypertension, cardiovascular diseases, COPD, asthma, DM, hyperlipidaemia, CKD, haemodialysis, solid tumour	Disease status
Israel et al. (2020) [29]	Israel	37,212^a	25 September–10 October	Hospital admission and confirmation cases	Mean ± SD hospitalized: 56.8 ± 18.9 not hospitalized: 57.2 ± 18.7	49.11	Drug history	Cohort 1: 4.81	Arrhythmia, asthma, CHF, COPD, DM, hypertension, ischaemic heart disease, malignancy, CKD, obesity	Mortality
Jakob et al. (2021) [30]	Germany	2155	16 March–14 May	COVID-19 positive patients	NA	59.7	Drug history	23.2	Cardiovascular disease, DM, pulmonary disease, haematological and/or oncological disease, neurological disease, kidney disease, connective tissue disease, peptic ulcer disease, CLD, liver cirrhosis, organ transplantation, rheumatic disease, HIV/AIDS	Definition complicated clinical staging
Mallow et al. (2020) [31]	USA	21,676	15 March–30 April	COVID-19 positive patients	Mean ± SD: 64.9 ± 17.2	52.8	Inpatient drug treatment	24.51	Chronic lung disease, moderate-to-severe asthma, severe heart disease, immunocompromized, obesity, diabetes, CKD with dialysis, liver disease, hypertension, CKD (any stage), haemoptysis, hypothyroidism, DNR status, MI, CHF, cerebrovascular disease, dementia, chronic pulmonary disease, connective tissue disease, peptic ulcer disease, mild liver disease, DM without end-organ damage, DM with end-organ damage, hemiplegia, moderate or severe renal disease tumour without metastases, moderate or severe liver disease, metastatic solid tumour, AIDS	CDC risk factors
McCarthy et al. (2020) [32]	USA/Boston	247	7 March–30 March	Hospitalized with confirmed SARS-CoV-2	Median (IQR): 61 (50–76)	57.6	Drug history	75.7	Overweight, obesity, overweight or obesity, asthma, COPD, interstitial lung disease, OSA/OHS, hypertension, hyperlipidaemia, DM, known CAD, prior MI, prior revascularization, HF, PAD, prior stroke/TIA, AF, liver cirrhosis, CKD, CKD on dialysis, history of malignancy, active malignancy, prior organ transplant, rheumatologic or inflammatory disorder requiring immunosuppression	ICU admission
Nguyen et al. (2020) [33]	USA	689	16 March–16 April	COVID-19 positive patients	Median (IQR): 55 (40–68)	43	Drug history	16.7	Obesity, DM, hypertension, stroke/cerebrovascular	Mortality
Nicholson et al. (2021) [34]	USA	1042	19 May– 20 July	Patients with laboratory-confirmed COVID-19 infection	Median (IQR): 64 (53–75)	56.81	Drug history	49.04	DM, CKD (stages III–VI), COPD, asthma, cancer, CAD, HF, AF	IMV, mortality
Pitscheider et al. (2020) [35]	Austria	609	N/A	Hospitalized patients with COVID-19	Median (IQR) SARS-CoV-2 cohort: 68 (54–79)	56.65	Drug history	11.99	CAD, arterial hypertension, DM, COPD	Comparison of COVID-19 patients and influenza patients
Rodriguez-Nava et al. (2020) [36]	USA/Evanston	87	March–May	Laboratory-confirmed COVID-19 admitted to the community hospital ICU	Median (IQR): 68.0 (58.0–75.0)	64.4	Inpatient drug treatment	54	Hypertension, cardiovascular disease	Mortality
Rossi et al. (2020) [37]	Italy	71	29 February–20 May	COVID-19 positive patients	Median (IQR): 71 (64–92)	56.33	Drug history	59.1	DM, CAD, hypertension, hyperlipidaemia, CKD, COPD, cancer	Mortality
Saeed et al. (2020) [38]	USA/New York	4252	1 March–2 May	Hospital admission and confirmation cases	Mean ± SD: 65 ± 16	53.50	Inpatient drug treatment	31.87	DM, hypertension, ASHD, lung disease	Mortality
Song et al. (2020) [39]	USA/Rhode Island	249	17 March–10 April	Patients with laboratory confirmed COVID-19	Median (IQR): 62.0 (51.0–75.0)	57	Drug history	49.4	Hypertension, DM, hypercholesterolaemia, obesity (BMI > 30 kg/m^2), CAD, cerebrovascular disease, aortic or mitral valvulopathy, CHF, History of pulmonary embolism, COPD, chronic renal failure	IMV, ICU admission, mortality
Tan et al. (2020) [40]	Singapore	717	22 January–15 April	Hospitalized patients with COVID-19	Median (IQR): 46 (19–57)	57.18	Drug history	21.06	High cardiovascular risk profile, hypertension, hyperlipidaemia, DM, previous atherosclerotic complications, CHF, lung disease, CKD, history of other malignancy	IMV, ICU admission, mortality
Wang et al. (2020) [41]	USA/New York	58	1 March–30 April	COVID-19 positive patients	Median (IQR): 67 (12.5)	52	Drug history	47	Low function, DM, hypertension	Mortality
Yan et al. (2020) [42]	China/Zhejiang	578	10 January–28 February	COVID-19 positive patients	Mean ± SD: 49.18 ± 14.16	50.7	Drug history	2.6	DM, hypertension, cardiovascular diseases, renal Failure	Severity
Yang et al. (2020) [43]	China/Wuhan	836	1 January–23 March	COVID-19 positive patients	Median (IQR): 73.5 (64.5–86.6)	48.44	Inpatient drug treatment	25.64	HBV, DM, hypertension, cardio- or cerebrovascular, tumour	Mortality
Zenga et al. (2020) [44]	China/Wuhan	1031	27 January–8 March	Hospitalized with COVID-19	Mean ± SD: 60.3 ± 14.3	52.2	Drug history	3.6	Hypertension, DM, cardiovascular disease, nervous system disease, chronic lung disease, tumour	Mortality
Zhang et al. (2020) [11]	China/Hubei	4305^a	30 December 2019–17 April 2020	Hospitalized patients with COVID-19	Median (IQR): 66.0 (59.0–72.0)	48.85	Inpatient drug treatment	8.72	COPD, hHypertension, DM, CHD, stroke, cancer	IMV, ICU admission, mortality

AF: atrial fibrillation; ARDS: acute respiratory distress syndrome; ASHD: arteriosclerotic heart disease; BMI: body mass index; CT: computed tomography; CLD: chronic liver disease; CHD: congenital heart defect; CAD: coronary artery disease; CKD: chronic kidney disease; CHF: congestive heart failure; COPD: chronic obstructive pulmonary disease; DM: diabetes mellitus; HIV: human immunodeficiency virus; HBV: hepatitis B virus; HF: heart failure; IMV: invasive mechanical ventilator; ICU: intensive care unit; IFN: interferon; MI: myocardial infarction; OSA: obstructive sleep apnoea; OHS: obesity hypoventilation syndrome; PAD: peripheral artery disease; RT-PCR: real-time reverse-transcriptase polymerase chain reaction; SD: standard deviation; TIA: transient ischaemic attack; USA: United States of America. ^aNumber of participants after applying propensity score-matching model to minimize differences in baseline characteristics between statin users versus non-statin users.

Figure 1. Forest plot showing the association between statin use and the need for intensive care unit care. The squares and bars represent the mean values and 95% CIs of the effect sizes, the area of the squares reflects the weight of the studies, and diamonds represent the combined effects.

Figure 2. Forest plot showing the association between statins and the need for invasive mechanical ventilator support. The squares and bars represent the mean values and 95% CIs of the effect sizes, the area of the squares reflects the weight of the studies, and diamonds represent the combined effects.

Figure 3. Forest plot showing the association between statins and mortality. The squares and bars represent the mean values and 95% CIs of the effect sizes, the area of the squares reflects the weight of the studies and diamonds represent the combined effects.

Table 2. Subgroup analysis for COVID-19 mortality.

Subgroup	Statin (n)	Paper (n)	Relative risk (95% CI)	I^2	p	p (interaction between groups)	I^2 (heterogeneity between groups)
DM						<.0001	93.6
Enrolled only individuals with DM [14]	1192	1	1.55 (1.07–2.25)	N/A	.02
Enrolled individuals with and without DM [11,12,20,23,29,33,34,36,38,39,41,43,44]	5663	13	0.64 (0.51–0.81)	58	.0002
CFR						.19	40.7
≤20 [11,20,33,39,44]	1229	5	0.58 (0.41–0.83)	26	.003
>20 [12,14,34,36,41,43]	3789	7	0.84 (0.55–1.26)	83	.39
Different statistical methods						.70	0
Crude odds ratio [20,33,36,38,41,43,44]	1684	7	0.77 (0.49–1.20)	56	.24
Adjusted odds ratio [23,34,39]	679	3	0.58 (0.37–0.94)	0	.03
Match [11,12,14,29]	4492	4	0.72 (0.43–1.20)	89	.21
Geographic location of studies						.13	57.3
Asia [11,20,29,43,44]	2817	5	0.57 (0.43–0.75)	14	<.0001
` Non-Asian [12,14,23,33,34,36,38,39,41]	4038	9	0.80 (0.57–1.14)	78	.22
Drug treatment timing						.15	51.9
History of drug treatment [12,14,20,23,29,33,34,38,39,41,44]	5937	11	0.75 (0.55–1.02)	76	.06
Inpatient drug treatment [11,36,43]	918	3	0.55 (0.41–0.73)	0	<.0001

CFR: case fatality rate; DM: diabetes mellitus

The measure of mortality outcome is provided for each subgroup, and the interaction p value and I² are provided for subgroup differences. All analyses were conducted using inverse variance and a random-effects model.

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Data availability statement

The data that support the findings of this study are available from the corresponding author, [Pei-Ling Tang], upon reasonable request.