Coffee and tea consumption and the risk of glioma: a systematic review and dose-response meta-analysis.

In this systematic review and dose-response meta-analysis, we aimed to assess whether coffee and tea consumption is related to the risk of glioma. We performed a systematic literature search using PubMed, Embase, Scopus and the EuropePMC from the inception of database up until 1 October 2020. Exposures in the present study were coffee and tea consumption, the main outcome was the incidence of glioma. The present study compares the association between the exposure of coffee and tea with the incidence of glioma, and the results are reported in relative risks (RR). There are 12 unique studies comprising of 1 960 731 participants with 2987 glioma cases. Higher coffee consumption was associated with a statistically non-significant trend towards lower risk of glioma (RR 0·77 (95 % CI 0·55, 1·03), P= 0·11; I2:75·27 %). Meta-regression showed that the association between coffee and glioma was reduced by smoking (P= 0·029). Higher tea consumption was associated with a lower risk of glioma (RR 0·84 (95 % CI 0·71, 0·98), P= 0·030; I2:16·42 %). Sensitivity analysis by removal of case-control studies showed that higher coffee consumption (RR 0·85 (95 % CI 0·72, 1·00), P= 0·046; I2:0 %) and higher tea consumption (RR 0·81 (95 % CI 0·70, 0·93), P= 0·004; I2:0 %, Pnon-linearity = 0·140) were associated with lower risk of glioma. Dose-response meta-analysis showed that every one cup of coffee per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 0·99), P= 0·016, Pnon-linearity = 0·054) and every one cup of tea per day decreases the risk of glioma by 3 % (RR 0·97 (95 % CI 0·94, 1·00), P= 0·048). This meta-analysis showed apparent association between coffee and tea intake and risk of glioma.

Statin and mortality in COVID-19: a systematic review and meta-analysis of pooled adjusted effect estimates from propensity-matched cohorts.

PURPOSE: Statin potentially improved outcome in patients with COVID-19. Patients who receive statin generally have a higher proportion of comorbidities than those who did not, which may introduce bias. In this meta-analysis, we aimed to investigate the association between statin use and mortality in patients with COVID-19 by pooling the adjusted effect estimates from propensity-score matching (PSM) matched studies or randomised controlled trials to reduce bias. METHODS: A systematic literature search using the PubMed, Scopus and Embase databases were performed up until 1 March 2021. Studies that were designed the study to assess statin and mortality using PSM with the addition of Inverse Probability Treatment Weighting or multivariable regression analysis on top of PSM-matched cohorts were included. The effect estimate was reported in term of relative risk (RR). RESULTS: 14 446 patients were included in the eight PSM-matched studies. Statin was associated with decreased mortality in patients with COVID-19 (RR 0.72 (0.55, 0.95), p=0.018; I2: 84.3%, p<0.001). Subgroup analysis in patients receiving statin in-hospital showed that it was associated with lower mortality (RR 0.71 (0.54, 0.94), p=0.030; I2: 64.1%, p<0.025). The association of statin and mortality was not significantly affected by age (coefficient: -0.04, p=0.382), male gender (RR 0.96 (0.95, 1.02), p=0.456), diabetes (RR 1.02 (0.99, 1.04), p=0.271) and hypertension (RR 1.01 (0.97, 1.04), p=0.732) in this pooled analysis. CONCLUSION: In this meta-analysis of PSM-matched cohorts with adjusted analysis, statin was shown to decrease the risk of mortality in patients with COVID-19. PROSPERO REGISTRATION NUMBER: CRD42021240137.

Thrombocytopenia as a prognostic marker in COVID-19 patients: diagnostic test accuracy meta-analysis.

This systematic review and meta-analysis aimed to evaluate thrombocytopenia as a prognostic biomarker in patients with coronavirus disease 2019 (COVID-19). We performed a systematic literature search using PubMed, Embase and EuropePMC. The main outcome was composite poor outcome, a composite of mortality, severity, need for intensive care unit care and invasive mechanical ventilation. There were 8963 patients from 23 studies. Thrombocytopenia occurred in 18% of the patients. Male gender (P = 0.037) significantly reduce the incidence. Thrombocytopenia was associated with composite poor outcome (RR 1.90 (1.43-2.52), P < 0.001; I2: 92.3%). Subgroup analysis showed that thrombocytopenia was associated with mortality (RR 2.34 (1.23-4.45), P < 0.001; I2: 96.8%) and severity (RR 1.61 (1.33-1.96), P < 0.001; I2: 62.4%). Subgroup analysis for cut-off <100 × 109/l showed RR of 1.93 (1.37-2.72), P < 0.001; I2: 83.2%). Thrombocytopenia had a sensitivity of 0.26 (0.18-0.36), specificity of 0.89 (0.84-0.92), positive likelihood ratio of 2.3 (1.6-3.2), negative likelihood ratio of 0.83 (0.75-0.93), diagnostic odds ratio of 3 (2, 4) and area under curve of 0.70 (0.66-0.74) for composite poor outcome. Meta-regression analysis showed that the association between thrombocytopenia and poor outcome did not vary significantly with age, male, lymphocyte, d-dimer, hypertension, diabetes and CKD. Fagan's nomogram showed that the posterior probability of poor outcome was 50% in patients with thrombocytopenia, and 26% in those without thrombocytopenia. The Deek's funnel plot was relatively symmetrical and the quantitative asymmetry test was non-significant (P = 0.14). This study indicates that thrombocytopenia was associated with poor outcome in patients with COVID-19.PROSPERO ID: CRD42020213974.

Effect of heart failure on the outcome of COVID-19 - A meta analysis and systematic review.

BACKGROUND: Several comorbidities have been associated with an increased risk of severity and mortality in coronavirus disease 2019 (COVID-19), including hypertension, diabetes, cerebrovascular disease, chronic kidney disease, and chronic obstructive pulmonary disease. PURPOSE: In this systematic review and meta-analysis, we attempted to investigate the association between heart failure (HF) and poor outcome in patients with COVID-19. METHODS: We performed a systematic literature search from PubMed, EuropePMC, SCOPUS, Cochrane Central Database, and medRxiv with the search terms, "Heart failure" and "COVID-19". The outcome of interest was mortality and poor prognosis (defined by incidence of severe COVID-19 infection, admission to ICU, and use of ventilator) in patients with preexisting heart failure with coronavirus disease. RESULTS: We identified 204 potential articles from our search, and 22 duplicates were removed. After screening of the titles and abstracts of the remaining 182 articles we identified 92 potentially relevant articles. We excluded 74 studies due to the following reasons: four studies were systematic reviews, two studies were meta-analyses, three articles were literature reviews, and 65 articles did not report on the outcome of interest. Finally, we included the remaining 18 studies in our qualitative synthesis and meta-analysis. There were 21,640 patients from 18 studies. HF was associated with hospitalization in COVID19 HR was 2.37 [1.48, 3.79; p < 0.001], high heterogeneity [I2, 82%; p < 0.001]. HF was associated with a poor outcome demonstrated by an OR of 2.86 [2.07; 3.95; p < 0.001] high heterogeneity [I2, 80%; p < 0.001]. Patient with preexisting HF was associated with higher mortality OR of 3.46 [2.52, 4.75; p < 0.001] moderately high heterogeneity [I2, 77%; p < 0.001]. CONCLUSION: Patients with heart failure are at increased risk for hospitalization, poor outcome, and death from COVID-19. A significant difference in mortality between patients with and without heart failure was observed, patients with heart failure having a higher mortality.

Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19-systematic review, meta-analysis, and meta-regression.

BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, and cardiovascular diseases and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database. The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19. RESULTS: A total of 4448 patients were obtained from 16 studies. Cerebrovascular disease was associated with an increased composite poor outcome (RR 2.04 [1.43,2.91], p<0.001; I2: 77%). Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92,2.96], p<0.001; I2: 0%) and showed borderline significance for severe COVID-19 (RR 1.88 [1.00,3.51], p = 0.05; I2: 87%). Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71,2.91], p<0.001; I2: 60%), mortality (RR 2.25 [1.53,3.29], p<0.001; I2: 33%) and severe COVID-19 (RR 2.25 [1.51,3.36], p<0.001; I2: 76%). Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities. Furthermore, the association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa. CONCLUSION: Cerebrovascular and cardiovascular diseases were associated with an increased risk for poor outcome in patients with COVID-19.

Impact of cerebrovascular and cardiovascular diseases on mortality and severity of COVID-19-systematic review, meta-analysis, and meta-regression.

BACKGROUND: We conducted a systematic review and meta-analysis to evaluate the latest evidence on the association between cerebrovascular, and cardiovascular diseases and poor outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: A comprehensive systematic literature search was performed using PubMed, SCOPUS, EuropePMC, and Cochrane Central Database. The outcome of interest was composite poor outcome that comprised of mortality and severe COVID-19. RESULTS: A total of 4448 patients were obtained from 16 studies. Cerebrovascular disease was associated with an increased composite poor outcome (RR 2.04 [1.43,2.91], p<0.001; I2: 77%). Subgroup analysis revealed that cerebrovascular disease was associated with mortality (RR 2.38 [1.92,2.96], p<0.001; I2: 0%) and showed borderline significance for severe COVID-19 (RR 1.88 [1.00,3.51], p = 0.05; I2: 87%). Cardiovascular disease was associated with increased composite poor outcome (RR 2.23 [1.71,2.91], p<0.001; I2: 60%), mortality (RR 2.25 [1.53,3.29], p<0.001; I2: 33%) and severe COVID-19 (RR 2.25 [1.51,3.36], p<0.001; I2: 76%). Meta-regression demonstrate that the association was not influenced by gender, age, hypertension, diabetes, and respiratory comorbidities. Furthermore, the association between cerebrovascular disease and poor outcome was not affected by cardiovascular diseases and vice versa. CONCLUSION: Cerebrovascular and cardiovascular diseases were associated with an increased risk for poor outcome in patients with COVID-19.

Decompression Alone Compared to Decompression With Fusion in Patients With Lumbar Spondylolisthesis: Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: We aimed to synthesize the latest evidence on the efficacy and safety of decompression alone compared to decompression with fusion in patients with lumbar spondylolisthesis. We also aimed to evaluate factors affecting the efficacy and complications. METHODS: A systematic literature search was conducted using PubMed, Scopus, Europe PMC, Cochrane Central Database, and ClinicalTrials.gov. The main outcome was improvement in Oswestry Disability Index (ODI). The secondary outcome was back pain and leg pain improvement, complications, reoperation rate, duration of surgery, length of hospital stay, and blood loss. RESULTS: There were 3993 patients from 13 studies. Decompression with fusion was associated with greater reduction in ODI (mean difference 4.04 [95% CI 0.95, 7.13], P = 0.01) compared to decompression alone. Greater reduction in back (standardized mean difference [SMD] 0.27 [95% CI 0.00, 0.53], P = 0.05) and leg pain (SMD 0.13 [95% CI 0.06, 0.21], P < 0.001) was observed in the decompression with fusion group. Complications were similar in the 2 groups (OR 0.60 [95% CI 0.34, 1.04], P = 0.07). The reoperation rate was similar in both groups (P = 0.54). Decompression alone resulted in shorter duration of surgery (mean difference -85.18 minutes [95% CI -122.79, -47.57], P < 0.001), less blood loss (mean difference -262.65 mL [95% CI -313.45, -211.85], P < 0.001), and shorter hospital stay (mean difference -2.64 days [95% CI -3.58, -1.70], P < 0.001). Empirical Bayes random-effects meta-regression showed that the rate of complication was influenced by age (coefficient 0.172, P = 0.004). CONCLUSION: Decompression with fusion had greater efficacy than decompression alone but was associated with more blood loss, lengthier surgery, and hospitalization. In terms of complications, decompression alone may be beneficial in younger patients. (PROSPERO CRD42020211904) LEVEL OF EVIDENCE: 2A.

Endotheliopathy marked by high von Willebrand factor (vWF) antigen in COVID-19 is associated with poor outcome: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to compare the levels of von Willebrand Factor (vWF) antigen in patients with coronavirus disease 2019 (COVID-19) with a poor outcome compared with those with a good outcome, and explored factors that may affect the difference in terms of vWF antigen between the two groups. METHODS: A comprehensive literature search of PubMed, Embase and Scopus databases was undertaken from inception until 7 April 2021. The primary outcome was poor outcome, which is a composite of mortality and severity of COVID-19. RESULTS: Ten studies including a total of 996 patients were included in this systematic review and meta-analysis. vWF antigen was higher in patients with poor outcomes [standardized mean difference (SMD) 0.84 [0.45-1.23], P<0.001; I2=87.3, P<0.001). For subgroup analysis on studies that reported the vWF antigen level as a percentage, the mean difference was 121.6 [(53.7-189.4), P<0.001; I2=92.0, P<0.001]. Meta-regression showed that the SMD between poor outcome and good outcome was affected by the platelet count (coefficient 0.0061, P=0.001), d-dimer level (coefficient 0.0007, P=0.026) and factor VIII level (coefficient 0.0057, P=0.031), but not by age (coefficient -0.0610, P=0.440), gender (coefficient 0.0135, P=0.698), obesity (coefficient 0.0282, P=0.666), hypertension (coefficient 0.0273, P=0.423), diabetes (coefficient 0.0317, P=0.398) or malignancy (coefficient 0.0487, P=0.608). CONCLUSION: This meta-analysis showed that the level of vWF antigen was significantly higher in patients with COVID-19 with a poor outcome, signalling marked endotheliopathy. Meta-regression showed that the differences became larger as the platelet count, d-dimer level and factor VIII level increased.

Dose response relationship between D-dimer level and mortality in critically ill COVID-19 patients: a retrospective observational study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic. Coagulopathy is one of the most common complications characterized by increased D-dimer level. We aimed to investigate the dose-response relationship between elevated D-dimer level and mortality in critically ill COVID-19 patients. METHODS: This was a retrospective observational study in 259 critically ill COVID-19 patients requiring intensive care unit admission between March and December 2020. We compared the mortality rate between patients with and without elevated D-dimer. Receiver operating characteristic (ROC) curve analysis, Fagan's nomogram, and dose-response relationship were performed to determine the association between D-dimer level and mortality. RESULTS: Overall mortality rate was 40.9% (106 patients). Median D-dimer level was higher in non-survivor group (10,170 ng/mL vs 4,050 ng/mL, p=0.028). The association remained significant after multivariate logistic regression analysis (p=0.046). The optimal cut-off for D-dimer level to predict mortality from ROC curve analysis was 9,020 ng/mL (OR (odds ratio) 3.73 [95% CI (confidence interval) 1.91 - 7.28], p<0.001). D-dimer level >9,020 ng/mL confers 67% posterior probability of mortality and D-dimer level <9,020 ng/mL had 35% probability of mortality. CONCLUSIONS: There was a non-linear dose-response relationship between D-dimer level and mortality with P nonlinearity of 0.004. D-dimer level was associated with mortality in critically ill COVID-19 patients in the non-linear dose-response relationship.

Coronavirus disease 2019 (COVID-19) markedly increased mortality in patients with hip fracture - A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to evaluate the prevalence of coronavirus disease 2019 (COVID-19) and its impact on mortality in patients with hip fracture. METHODS: We performed a systematic literature search in PubMed, Cochrane Central Database, and medRvix from inception up to July 13, 2020 on research articles that enrolled hip fracture patients who had information on COVID-19 and clinically validated definition of death. RESULTS: A total of 984 participants from 6 studies were included in our study. The pooled prevalence of COVID-19 was 9% [95% CI: 7-11%]. The mortality rate in patients with concomitant hip fracture and COVID-19 was found to be 36% (95% CI: 26-47%), whereas the mortality rate in hip fracture without COVID-19 is 2% (95% CI: 1-3%). Meta-analysis showed that COVID-19 was associated with a seven-fold increase in risk (RR 7.45 [95% CI: 2.72, 20.43], p < 0.001; I2: 68.6%) of mortality in patients with hip fracture. Regression-based Harbord's test showed no indication of small-study effects (p = 0.06). CONCLUSION: The present meta-analysis showed that COVID-19 increased the risk of mortality in patients with hip fracture. TRIAL REGISTRATION: This study is registered with PROSPERO, July 21, 2020, number CRD42020199618. Available from https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020199618.

Minimal Invasive Surgery Instrumented Fusion versus Conventional Open Surgical Instrumented Fusion for the Treatment of Spinal Metastases: A Systematic Review and Meta-analysis.

OBJECTIVE: In this study, we aimed to compare the minimally invasive surgery (MIS) instrumented fusion ± decompression versus conventional open surgery (COS) instrumented fusion ± decompression for the treatment of spinal metastases. METHODS: We performed a systematic literature search through PubMed, Scopus, Europe PMC (PubMed Central), and Cochrane Central Database using the keywords "minimal invasive surgery" OR "minimally invasive surgery" OR "mini-open" AND "conventional open surgery" OR "traditional open surgery" OR "open surgery" AND "spinal metastasis". The outcomes of interest were complications, neurologic improvement, length of stay, intraoperative blood loss, transfusion rate, and operative duration. RESULTS: There were a total of 8 studies comprising 486 patients. Complications were less frequent in MIS compared with COS (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.30-0.84; P = 0.01; I2 = 0%). Major complications related to surgery were less in the MIS group (OR, 0.42; 95% CI, 0.21-0.84; P = 0.01; I2 = 0%). The rate of neurologic improvement was similar in both groups (OR, 1.01; 95% CI, 0.64-1.59; P = 0.95; I2 = 0%). MIS was associated with less blood loss (mean difference, -690.00 mL; 95% CI, -888.31 to -491.69; P < 0.001; I2 = 56%), and lower transfusion rate compared with COS (OR, 0.27; 95% CI, 0.11-0.66; P = 0.004; I2 = 50%). Length of surgery was similar in both groups (mean difference, -12.49 minutes; 95% CI, -45.93 to 20.95; P = 0.46; I2 = 86%). MIS resulted in shorter length of stay compared with COS (mean difference -3.58 days; 95% CI, -6.90 to -0.26; P = 0.03; I2 = 89%). CONCLUSIONS: MIS was associated with lower complications, blood loss, transfusion rate, and shorter length of stay with a similar rate of neurologic improvement and length of surgery compared with COS.

Epidemiological pattern of orthopaedic fracture during the COVID-19 pandemic: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed evaluate the 30-day mortality, number and site of fracture, mechanism of injury, and location where injury was sustained during the pandemic compared to pre-pandemic. METHODS: We performed a systematic literature search from PubMed and Embase on original articles, research letters, and short reports which have data about the number of fractures, site of fracture, mechanism of injury, location where injury was sustained, percentage of operative intervention, mortality during the pandemic compared to a specified period of time before the pandemic. The search was finalized in October 14, 2020. RESULTS: A total of 11,936 participants from 16 studies were included in our study. The pooled analysis indicated a higher 30-days mortality associated with fractures during the pandemic (9% vs 4%, OR 1.86 [1.05, 3.27], p = 0.03; I2: 36%, p = 0.15). The number of fractures presenting to hospitals has declined 43% (35-50%) compared to pre-pandemic. Hand fracture was fewer during the pandemic (18% vs 23%, OR 0.75 [0.58, 0.97], p = 0.03; I2: 69%, p = 0.002). Work-related traumas, high-energy falls, and domestic accidents were more common during the pandemic, while sports-related traumas were found to be less. Injuries that occurred in the sports area were lower than before the pandemic. CONCLUSION: The present meta-analysis showed that during the COVID-19 pandemic, the number of fractures has decreased, but there is a higher mortality rate associated with fractures.

The association between triglyceride-glucose index and the incidence of type 2 diabetes mellitus-a systematic review and dose-response meta-analysis of cohort studies.

ABSTARCT: AIMS: We aimed to assess the dose-response relationship between triglyceride-glucose (TyG) index and the incidence of type 2 diabetes mellitus (T2DM). METHODS: We performed a comprehensive systematic literature search using PubMed, Scopus, and Embase for records published from inception until 9 February 2021. The effect estimates were reported as relative risks (RRs). RESULTS: 270,229 subjects from 14 studies were included in this systematic review and meta-analysis. The pooled incidence of T2DM was 9%. Meta-regression analysis indicates that baseline age (coefficient: 0.67, p = 0.026), drinking (coefficient: 0.03, p = 0.035), and HDL (coefficient: -0.89, p = 0.035) affected the incidence of T2DM in future. High TyG index was associated with increased incidence of T2DM in pooled unadjusted (RR 4.68 [3.01, 7.29], p < 0.001; I2: 96.6%) and adjusted model (adjusted RR 3.54 [2.75, 4.54], p < 0.001; I2: 83.7%). Dose-response meta-analysis for the adjusted RR showed that the linear association analysis was not significant per 0.1 increase in TyG index (RR 1.01 [0.99, 1.03], p = 0.223). There is a non-linear trend (p < 0.001) for the association between TyG index and incidence of T2DM. The dose-response curve became increasingly steeper at TyG index above 8.6. CONCLUSIONS: TyG index was associated with the incidence of T2DM in a non-linear fashion.

Tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography and mortality in COVID-19: A systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we assessed the association between tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography and mortality in coronavirus disease 2019 (COVID-19). METHODS: We performed a systematic literature search using PubMed, Embase, and Scopus databases with the keywords "COVID-19" OR "SARS-CoV-2" OR "2019-nCoV" AND "Tricuspid annular plane systolic excursion" OR "TAPSE" until January 20, 2021. The main outcome was mortality. The effect estimate was reported as the hazard ratio (HR), which was pooled from the unadjusted and adjusted effect estimates retrieved from the studies included. Mean differences in TAPSE (in mm) between non-survivors and survivors were pooled. RESULTS: In total, 641 patients from seven studies were included in this systematic review and meta-analysis. TAPSE was lower in non-survivors compared with survivors (mean difference = -3.74 [-5.22, -2.26], p < 0.001; I2: 85.5%, p < 0.001). Each 1 mm decrease in TAPSE was associated with increased mortality (HR = 1.24 [1.18, 1.31], p < 0.001; I2: 0.0%, p = 0.491). In the pooled adjusted model, each 1 mm decrease in TAPSE was associated with increased mortality (HR = 1.21 [1.11, 1.33], p < 0.001; I2: 45.1%, p = 0.156). Meta-regression indicated that the difference in TAPSE between non-survivors and survivors was affected by chronic obstructive pulmonary disease (-0.183, p < 0.001) and pulmonary artery systolic pressure (-0.344, p = 0.039), but not by age (p = 0.668), male gender (p = 0.821), hypertension (p = 0.101), diabetes (p = 0.603), coronary artery disease (p = 0.564), smoking (p = 0.140), and left ventricular ejection fraction (p = 0.452). CONCLUSION: Every 1 mm decrease in TAPSE was associated with an increase in mortality of approximately 20%. PROSPERO ID: CRD42021232194.

Active prescription of low-dose aspirin during or prior to hospitalization and mortality in COVID-19: A systematic review and meta-analysis of adjusted effect estimates.

BACKGROUND: This study aimed to investigate whether the active prescription of low-dose aspirin during or prior to hospitalization affects mortality in patients with coronavirus disease 2019 (COVID-19). Aspirin is often prescribed for secondary prevention in patients with cardiovascular disease and other comorbidities that might increase mortality, and may therefore falsely demonstrate increased mortality. To reduce bias, only studies that performed an adjusted analysis were included in this review. METHODS: A systematic literature search of PubMed, Scopus, Embase and Clinicaltrials.gov was performed, from inception until 16 April 2021. The exposure was active prescription of low-dose aspirin during or prior to hospitalization. The primary outcome was mortality. The pooled adjusted effect estimate was reported as relative risk (RR). RESULTS: Six eligible studies were included in this meta-analysis, comprising 13,993 patients. The studies had low-to-moderate risk of bias based on the Newcastle-Ottawa Scale. The meta-analysis indicated that the use of low-dose aspirin was independently associated with reduced mortality {RR 0.46 [95% confidence interval (CI) 0.35-0.61], P < 0.001; I2 = 36.2%}. Subgroup analysis on in-hospital low-dose aspirin administration also showed a significant reduction in mortality [RR 0.39 (95% CI 0.16-0.96), P < 0.001; I2 = 47.0%]. CONCLUSION: Use of low-dose aspirin is independently associated with reduced mortality in patients with COVID-19, with low certainty of evidence.