Table 1.

Characteristics of included studies.

ICU admission
Author	Statin		Sample	Setting	Study design	Result	Conclusion	Reference
	User	Nonuser
Masana et al.	581	1576	Patients admitted to their hospitals because of SARS-CoV-2 infection	Members of the Lipids and Arteriosclerosis Units Net (XULA) of Catalonia (Spain)	Retrospective observational	N/A	N/A	[30]
	103 (17.7)	233 (14.8)
Zhang et al.	1219	12762	Patients with COVID-19	Hubei Province, China	Retrospective	aHR: 0.69, CI: 0.56-0.85, p = 0.001	Cox model analysis showed statin use associated with lower prevalence ICU admission	[25]
	N/A	N/A
Song et al.	123	126	Patients with COVID-19	“Lifespan” healthcare system hospitals	Retrospective cohort	OR: 0.90, CI: 0.49-1.67, p = 0.756	No significant associations between statin use and hospital death or ICU admission	[31]
	N/A	N/A
Argenziano et al.	325	525	Patients with laboratory-confirmed COVID-19 infection	New York-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center	Retrospective case series	OR = 1.07, CI: 0.79-1.46	N/A	[32]
	93	143
De Spiegeleer et al.	31	123	Residents at two elderly care homes with COVID-19 diagnosis	One of two Belgian nursing homes	Retrospective multicenter cohort	OR: 0.75, CI: 0.24-1.87	Statin use showed nonsignificant benefits	[33]
	6	31
Yan et al.	N/A	N/A	Confirmed COVID-19 diagnosis	Hospitals in Zhejiang Province, China	Case-control	OR: 0.98, CI: 0.32-2.99, p = 0.973	N/A	[34]
	N/A	N/A
Dreher et al.	18	32	COVID-19 patients with and without acute respiratory distress syndrome (ARDS)	Aachen University Hospital	Retrospective cohort	OR: 1.13, CI: 0.36-3.60	N/A	[35]
	9	15
Tan et al.	40	509	717 patients admitted	Tertiary center in Singapore for COVID-19 infection	Retrospective cohort	ATET Coeff: − 0.12, CI: −0.23-0.01, p = 0.028	Statin use independently associated with lower requirement for ICU admission	[36]
	1	N/A
Daniels et al.	46	124	Patients hospitalized for treatment of COVID-19	University of California San Diego Health (UCSDH), ascertained by data capture within system-wide electronic health record (EHR) system (Epic Systems, Verona, WI, USA)	Retrospective cohort	Adjusted OR: 0.29, CI: 0.11-0.71, p < 0.01	Inpatients hospitalized for COVID-19, use of statin medication prior to admission associated with reduced risk of severe disease	[37]
	20	70
Vahedian-Azimi et al.	326	525	Positive for SARS-CoV-2	Baqiyatallah University of Medical Sciences	Prospective observational	OR: 1.00, CI: 0.58-1.74, p = 0.736	Statin use not associated with mortality	[10]
	39	243
Butt et al.	843	3999	Danish citizens had a primary or secondary diagnosis code for COVID-19 infection	A Danish hospital, including inpatient, outpatient, and emergency department visits	Observational cohort study	HR 2.41 (95% CI 2.04 to 2.85)	Statin exposure was associated with a significantly higher risk of severe COVID-19 infection compared with no statin exposure)severe COVID-19 infection, defined as a hospital diagnosis of “COVID-19 severe acute respiratory syndrome” (ICD-10 code: B972A) or admission to an intensive care unit(	[38]
	204 (24.2%)	419 (10.5%)
Fan et al.	250	1897	Patients with COVID-19	Zhongnan Hospital of Wuhan University and Leishenshan Hospital in Wuhan, China	Retrospective study	Adjusted HR, 0.319; 95% CI, 0.270–0.945; p = 0.032	The risk was lower for intensive care unit (ICU) care in the statin group vs. the nonstatin group	[39]
	N/A	N/A
Hippisley-Cox et al.	5616	13870	Patients who had COVID-19 disease	General practices in England contributing to the QResearch database from which current data were available, England	Prospective cohort study	HR = 1.21 (1.02-1.43) OR = 1.55 (1.38-1.75)	For ICU admission, there was no significant associations with the statin	[40]
	487 (8.7%)	799 (5.8%)
McCarthy et al.	107	140	Patients hospitalized with confirmed SARS-CoV-2 infection	Three Partners Healthcare hospitals (Massachusetts General Hospital, Brigham and Women's Hospital, and Newton-Wellesley Hospital)	Retrospective cohort study	Admitted to ICU or died OR: 1.18 (0.71-1.96)	N/A	[41]
	51	61
Mitacchione et al.	179	663	Patients hospitalized for COVID-19	Hospitals include Luigi Sacco Hospital, Milan; Policlinico Umberto I Hospital, Rome; Spedali Civili Hospital, Brescia; Humanitas Gavazzeni Hospital; Bergamo, Italia	Observational multicenter study	p = 0.162	Our results did not confirm the supposed favorable effects of statin therapy on COVID-19 intensive care unit admission	[42]
	6 (3%)	40 (6%)
Ahlström et al.	N/A	N/A	ICU COVID-19 patients	Sweden	Retrospective cohort study	OR = 0.95 (0.81-1.12) p = 0.53	We did not find a protective effect on ICU admission in statin-treated patients	[43]
	518	1466
Izzi-Engbeaya et al.	N/A	N/A	Patients hospitalized with swab-positive COVID-19	ICHNT, which includes three hospitals admitting patients with COVID-19 (Charing Cross Hospital, Hammersmith Hospital, and St. Mary's Hospital), London	Retrospective cohort study	Primary outcome of death/ICU admission Estimate: −0.105 SE: 0.504 p = 0.835 OR = 1.49 (1.12-1.98)	N/A	[44]
	N/A	N/A
Tracheal intubation
Author	Statin		Sample	Setting	Study design	Result	Conclusion
	User	Nonuser
Zhang et al.	1219	12762	Patients with COVID-19	Hubei Province, China	Retrospective	aHR: 0.37, CI: 0.26-0.53, p < 0.001	Cox model analysis showed statin use associated with a lower prevalence of using mechanical ventilation	[25]
	N/A	N/A
Song et al.	123	126	Patients with COVID-19	“Lifespan” healthcare system hospitals	Retrospective cohort	Statin use significantly associated with decreased risk for IMV OR: 0.45, CI: 0.20-0.99, p = 0.048	Data support continued use of statins in patients hospitalized with COVID-19 due to decreased risk for IMV	[31]
	N/A	N/A
Gupta et al.	648	648	Positive for SARS-CoV-2	Columbia University Irving Medical Center (CUIMC) and Allen Hospital sites of the New York-Presbyterian Hospital (NYPH)	Retrospective	No significant difference in invasive mechanical ventilation	N/A	[45]
	130 (20.1%)	158 (24.4%)
Masana et al.	581	1576	Patients admitted to hospitals due to SARS-CoV-2 infection	Members of the Lipids and Arteriosclerosis Units Net (XULA) of Catalonia (Spain)	Retrospective observational	N/A	N/A	[30]
	84 (14.46)	191 (12.12)
Cariou et al.	1192	1257	Patients with diabetes admitted with COVID-19	68 French hospitals	Nationwide observational	OR: 1.13, CI: 0.83-1.53	Routine statin use not significantly associated with increased risk of tracheal intubation/mechanical ventilation	[46]
	19.2%	19.7%
Tan et al.	40	509	Patients admitted for COVID-19	Tertiary center in Singapore for COVID-19 infection	Retrospective cohort	ATET Coeff: −0.08, CI: −0.19-0.02, p = 0.114	No significant differences in intubation	[36]
	1	N/A
Peymani et al.	75	75	Hospitalized COVID-19 patients	Single tertiary hospital in Shiraz, Iran	Retrospective	OR: 0.96, CI: 0.61-2.99, p = 0.942	Nonsignificant association between statin use and reduction in mortality in COVID-19 patients	[47]
	N/A	N/A
Fan et al.	250	1897	Patients with COVID-19	Zhongnan Hospital of Wuhan University and Leishenshan Hospital in Wuhan, China	Retrospective study	N/A	N/A	[39]
	26 (10.4%)	180 (9.4%)
Mitacchione et al.	179	663	Patients hospitalized for COVID-19	Hospitals include Luigi Sacco Hospital, Milan; Policlinico Umberto I Hospital, Rome; Spedali Civili Hospital, Brescia; Humanitas Gavazzeni Hospital; Bergamo, Italia	Observational multicenter study	p = 0.258	Our results did not confirm the supposed favorable effects of statin therapy on COVID-19 mechanical ventilation	[42]
	6 (3%)	36 (5%)
Nicholson et al.	511	531	Adult patients with laboratory-confirmed COVID-19 infection	Five hospitals in the Mass General Brigham healthcare system (Massachusetts General Hospital (MGH), Brigham and Women's Hospital (BWH), Newton Wellesley Hospital (NWH), Brigham and Women's Faulkner Hospital (BWFH), and North Shore Medical Center, NSMC) in Boston, USA	Retrospective cohort	OR = 0.84 (0.65–1.09), p = 0.182	N/A	[48]
	180	224
Mortality
Author	Statin		Sample	Setting	Study design	Result	Conclusion	Statin time
	User	Nonuser
Gupta et al.	648	648	Positive for SARS-CoV-2	Columbia University Irving Medical Center (CUIMC) and Allen Hospital sites of the New York-Presbyterian Hospital (NYPH)	Retrospective	Univariate OR: 0.69, CI: 0.56-0.85. Multivariate adjusted OR: 0.49, CI: 0.38-0.63	Antecedent statin use associated with significantly lower rates of in-hospital mortality within 30 days	[45]
	112 (17.2%)	201 (31.0%)
Masana et al.	581	581	Patients admitted to hospitals due to SARS-CoV-2 infection	Members of the Lipids and Arteriosclerosis Units Net (XULA) of Catalonia (Spain)	Retrospective observational	Significant difference in mortality rate between groups HR: 0.58, CI: 0.39-0.89, p = 0.01	A lower SARS-CoV-2 infection-related mortality observed in patients treated with statin therapy prior to hospitalization	[30]
	115 (19.79)	148 (25.40)
Zhang et al.	1219	12762	Patients with COVID-19	Hubei Province, China	Retrospective	Individuals with statin therapy had a lower crude 28-day mortality (incidence rate ratios (IRR): 0.78, CI: 0.61–1.00, p = 0.046)	Statin use in hospitalized COVID-19 patients associated with lower risk of all-cause mortality and favorable recovery profile	[25]
	0.21%	0.27%
Rossi et al.	42	29	Patients with preexisting chronic cardiovascular disease, with COVID-19	N/A	Observational	Mortality rates of patients taking statins were 21.4% (9/42) and 34.5% (10/29) in those not taking statins (p < 0.05)	Statin use significantly reduced risk of mortality in COVID-19 patients	[19]
	9 (21.4%)	10 (34.5%)
Cariou et al.	1192	1257	Patients with diabetes admitted with COVID-19	68 French hospitals	Nationwide observational	Mortality rates significantly higher in statin users in 28 days (23.9% vs. 18.2%, p < 0.001). OR: 1.46, CI: 1.08-1.95	Routine statin treatment significantly associated with increased mortality in T2DM patients hospitalized for COVID-19	[46]
	23.9%	18.2%
Saeed et al.	983	1283	Patients with diabetes mellitus hospitalized with COVID-19	Montefiore Medical Center, Bronx, New York	Observational retrospective	Patient with diabetes on statins had lower cumulative in-hospital mortality (24% vs. 39%, p < 0.01). HR: 0.51, CI: 0.43-0.61, p < 0.001	Statin use associated with reduced in-hospital mortality from COVID-19 in patients with diabetes	[21]
	24%	39%
Saeed et al.	372	1614	Patients without diabetes mellitus hospitalized with COVID-19	Montefiore Medical Center in Bronx, New York	Observational retrospective	No difference noted in patients without diabetes (20% vs. 21%, p = 0.82)	Statin use associated with reduced in-hospital mortality from COVID-19 inpatients with diabetes	[21]
	20%	21%
Song et al.	123	126	Patients with COVID-19	“Lifespan” healthcare system hospitals	Retrospective cohort	No significant associations between statin use and in-hospital death OR: 0.88, CI: 0.37-2.08, p = 0.781	No significant associations between statin use and hospital death	[31]
	N/A	N/A
De Spiegeleer et al.	31	123	Residents at two elderly care homes with COVID-19 diagnosis	One of two Belgian nursing homes	Retrospective multicenter cohort	Considering death as serious outcome, the effect sizes, OR: 0.61, CI: 0.15-1.71, p = 0.380	Statins not statistically significantly associated with death from COVID-19 in elderly adults in nursing homes	[33]
	N/A	N/A
Rodriguez-Nava et al.	47	40	Laboratory-confirmed COVID-19	Community hospital intensive care unit (ICU) located in Evanston, IL	Retrospective cohort	Multivariable Cox PH regression model showed atorvastatin nonusers had 73% chance of faster progression to death compared with users. HR: 0.38, CI: 0.18-0.77, p = 0.008	Slower progression to death associated with atorvastatin use in patients with COVID-19 admitted to ICU	[26]
	23 (49%)	25 (63%)
Zenga et al.	38	993	COVID-19 inpatients	Tongji Hospital, Tongji Medical College of HUST (Wuhan, China)	Retrospective cohort	OR = 0.79, CI = 0.3-2.05	N/A	[49]
	5	160
Nguyen et al.	90	266	African American population with COVID-19	University of Chicago Medical Center (UCMC), serving south metropolitan Chicago	Retrospective observational	OR = 0.81, CI = 0.39-1.72	N/A	[50]
	10	35
Wang et al.	24	12	Multiple myeloma patients with COVID-19	Mount Sinai Hospital	Retrospective cohort	Statin use significantly associated with mortality. OR: 6.21, CI: 1.37-39.77, p = 0.012	N/A	[49]
	11	3
Grasselli et al.	N/A	N/A	Patients admitted to ICUs in Lombardy with suspected SARS-CoV-2 infection	One of the network ICUs, Milan	Retrospective, observational study	Statins associated with higher mortality in univariate analysis. HR: 0.98, CI: 0.81-1.2, p = 0.87	Long-term treatment with statins, before ICU admission associated with higher mortality unadjusted analysis only. Multivariate analysis did not confirm association between any home therapies and increased mortality	[51]
	N/A	N/A
Ayed et al.	10	93	Intensive care unit- (ICU-) admitted COVID-19 patients	Jaber Al-Ahmad Al Sabah Hospital, Kuwait	Retrospective cohort	OR: 0.49, CI: 0.11-2.08	N/A	[52]
	4	43
Tan et al.	40	509	717 patients admitted	Tertiary center in Singapore for COVID-19 infection	Retrospective cohort	ATET Coeff: −0.04, CI: −0.16-0.08, p = 0.488	No significant differences in mortality	[36]
	2
Peymani et al.	75	75	Hospitalized COVID-19 patients	Single tertiary hospital, Shiraz, Iran	Retrospective	HR: 0.76, CI: 0.16-3.72, p = 0.735	Nonsignificant association between statin use and reduction in mortality in patients with COVID-19	[47]
	N/A	N/A
Nicholson et al.	511	531	1042 people with COVID-19 symptoms admitted	Mass General Brigham Hospitals	Retrospective cohort	OR: 0.50, CI: 0.27-0.93, p = 0.027	Chronic statin use associated with reduced in-hospital mortality	[53]
	N/A	N/A
Lala et al.	984	1752	Hospitalized COVID-19-positive patients	1 of 5 Mount Sinai Health System hospitals in New York City	Multihospital retrospective cohort	HR: 0.57, CI: 0.47-0.69, p < 0.001	Statin use associated with improved survival	[54]
	N/A	N/A
Krishnan et al.	81	71	Consecutive patients requiring mechanical ventilation from March 10 to April 15	St. Joseph Mercy Oakland Hospital	Retrospective observational	OR: 2.44, CI: 1.23-4.76, p = 0.0080	Statin use associated with increased mortality	[55]
	N/A	N/A
Vahedian-Azimi et al.	326	525	Positive for SARS-CoV-2	Baqiyatallah University of Medical Sciences	Prospective observational	OR: 0.18, CI: 0.06–0.49 p = 0.0001	Statin use associated with decreased mortality	[10]
	8	282
Butt et al.	843	3999	Danish citizens had a primary or secondary diagnosis code for COVID-19 infection	A Danish hospital, including inpatient, outpatient, and emergency department visits	Observational cohort study	HR 2.87 (95% CI 2.39 to 3.46)	Statin exposure was associated with a significantly higher risk of mortality compared with no statin exposure	[38]
	177 (21.0%)	311 (7.8%)
Fan et al.	250	1897	Patients with COVID-19	Zhongnan Hospital of Wuhan University and Leishenshan Hospital in Wuhan, China	Retrospective study	Adjusted HR, 0.428; 95% CI, 0.169–0.907; p = 0.029	Statin use was associated with lower mortality	[39]
	6 (2.4%)	70 (3.7%)
Israel et al.	N/A	N/A	Hospitalized COVID-19 patients were assigned to two distinct case-control cohorts. Control patients were taken from the general population	Clalit Health Services (CHS) data warehouse	Retrospective cohort	OR (95%CI) = 0.691 (0.444, 1.037), 0.072	Rosuvastatin has protective effects in this large population analysis	[56]
	N/A	N/A
Israel et al.	N/A	N/A	Hospitalized COVID-19 patients were assigned to two distinct case-control cohorts. Case patients were nonhospitalized SARS-CoV-2-positive patients	Clalit Health Services (CHS) data warehouse	Case-control matched cohort	OR (95% CI) 0.530 (0.360, 0.766) p < 0.001	Rosuvastatin has protective effects in this large population analysis	[56]
	N/A	N/A
Mughal et al.—abstract	44	76	Adult patients who were hospitalized with RT-PCR-confirmed SARS-CoV-2 infection	N/A	Retrospective cohort	N/A	N/A	[57]
	14 (31.8%)	7 (9.2%)
Mallow et al.	5313	16363	COVID-19 patient	Database of inpatient and hospital-based outpatient detailed claims across more than 300 acute care hospitals in the US	Retrospective cohort	OR 0.54, 95% CI, 0.49–0.60; p < 0.001	Our findings suggest that patients administered statins in the hospital had a 46% lower risk of death than those not receiving statins	[28]
	N/A	N/A
McCarthy et al.	107	140	Patients hospitalized with confirmed SARS-CoV-2 infection	Three Partners Healthcare hospitals (Massachusetts General Hospital, Brigham and Women's Hospital, and Newton-Wellesley Hospital)	Retrospective cohort study	Admitted to ICU or died OR: 1.18 (0.71-1.96)	N/A	[41]
	51	61
Alamdari et al.	117	342	COVID-19 patients	Patients who were admitted to Shahid Modarres Hospital, which is a 279-bed tertiary referral center in Tehran, Iran	Retrospective cohort	OR: 0.27 (0.11–0.64)	Statin use history decreased the incidence of mortality dramatically	[58]
	6 (9.5%)	57 (16.7%)
Soleimani et al.	66	188	Patients with COVID-19	Sina Hospital in Tehran, Iran	Retrospective observational study	OR: 0.93 (0.49–1.76)	N/A	[59]
	17 (25%)	51 (27%)
Ayeh et al.	594	3853	Patients with a diagnosis of SARS-CoV-2 infection	Johns Hopkins Hospital and affiliated hospitals, Johns Hopkins Bayview Medical Center, Howard County General Hospital, Sibley Memorial Hospital, and Suburban Hospital, USA	Retrospective study	HR = 0.92, 95% CI (0.53–1.59)	The average treatment effect of statin use on COVID-19-related mortality in the matched groups was not statistically significant	[60]
	N/A	N/A
Ahlström et al.	N/A	N/A	ICU COVID-19 patients	Sweden	Retrospective cohort study	OR = 0.72 (0.53-0.98) p = 0.034	Statins were protective of ICU death	[43]
	110	N/A
An et al.	1074	9160	Patients diagnosed with COVID-19	South Korea	Nationwide cohort	OR: 4.11 (3.07-5.51)	N/A	[61]
	69 (6.4%)	159 (1.7%)
Holman et al.	118995	142710	COVID-19 people with type 1 diabetes	The National Diabetes Audit (NDA), UK	Population-based cohort study	HR = 0.82 (0.65-1.03) p = 0.081	Association of prescription of statins with mortality in type 1 diabetes was not significant	[62]
	338	120
Holman et al.	2099505	752245	COVID-19 people with type 2 diabetes	The National Diabetes Audit (NDA), UK	Population-based cohort study	HR = 0.72 (0.62-0.75) p < 0.001	In people with type 2 diabetes, prescription for statins was associated with reduced mortality	[62]
	7355	3086
Inciardi et al.	25	74	Patients hospitalized for COVID-19 pneumonia	Civil Hospitals of Brescia, Lombardy, Italy	Retrospective cohort	OR = 1.89 (0.71-5.03)	N/A	[63]
	9 (36%)	17 (23%)
Luo et al.	55	228	Patients with confirmed COVID-19	Tongji Hospital in Wuhan, China	Retrospective study	OR = 2.98 (0.65–13.76) p = 0.16	N/A	[27]
	N/A	N/A
Ullah et al.	108	104	Confirmed COVID-19 patients	Primary, secondary, and tertiary electronic healthcare records (EHRs) of HPB patients in East London	Retrospective single-center cohort study	OR = 2.39 (1.25-4.56)	N/A	[64]
	36	18
Ramachandran et al.	114	181	Patients admitted with a principal diagnosis of COVID-19	Tertiary care academic medical center in Brooklyn, New York	Retrospective cohort study	OR = 1.59 (0.84-3.02) p = 0.157	N/A	[65]
	N/A	N/A
Izzi-Engbeaya et al.	N/A	N/A	Patients hospitalized with swab-positive COVID-19	ICHNT, which includes three hospitals admitting patients with COVID-19 (Charing Cross Hospital, Hammersmith Hospital, and St. Mary's Hospital), London	Retrospective cohort study	Primary outcome of death/ICU admission Estimate: −0.105 SE: 0.504 p = 0.835 OR = 1.49 (1.12-1.98)	N/A	[44]
	N/A	N/A
Bifulco et al.	117	424	COVID-19 patients	Patients admitted to Humanitas Clinical and Research Hospital (Rozzano, Milan, Italy)	Retrospective cohort	Adjusted odds ratio (aOR): 0.75; 95% confidence interval (CI): 0.26–2.17; p = 0.593	Deaths were lower, although not significantly, in statin users with respect to nonstatin users	[66]
	N/A	N/A
Oh et al.	N/A	N/A	Patients with COVID-19	NHIS-COVID-19 cohort database, South Korean	Retrospective cohort study	OR (95% CI) 0.74, (0.52, 1.05), p = 0.094	We found that it did not affect the hospital mortality of patients who were diagnosed with COVID-19	[29]
	N/A	N/A
Maric et al.	2297	4594	COVID-19 patients	Cerner's large COVID-19 EHR database, USA	Retrospective cohort study	p = 0.0183	We observed a small, but statistically significant, decrease in mortality among patients prescribed statins (16.1%) when compared with matched COVID-19-positive controls (18.0 to 20.6%)	[67]
	369 (16.1%)	845 (18.39%)
Mitacchione et al.	179	663	Patients hospitalized for COVID-19	Hospitals include Luigi Sacco Hospital, Milan; Policlinico Umberto I Hospital, Rome; Spedali Civili Hospital, Brescia; and Humanitas Gavazzeni Hospital, Bergamo, Italia	Observational multicenter study	p = 0.006	Statin users appeared to show higher mortality rates	[42]
	52 (%29)	130 (%20)

N/A: not available.