Fibrosis-4 index and mortality in coronavirus disease 2019: a meta-analysis.

BACKGROUND/AIMS: In this meta-analysis, we aimed to evaluate the prognostic value of fibrosis-4 index (FIB-4) in COVID-19. METHODS: We performed a comprehensive literature search of PubMed, Embase, and Scopus databases on 26 November 2020. FIB-4 was calculated by [age (years) × AST (IU/L)]/[platelet count (109/L) × âˆšALT (U/L)]. A value above cutoff point was considered high and a value below cutoff point was considered low. The main outcome was mortality, the association between high FIB-4 and mortality was reported in odds ratio (OR). Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic OR (DOR), area under the curve (AUC) were generated. RESULTS: There were 963 patients from five studies included in this systematic review and meta-analysis. Meta-analysis showed that high FIB-4 was associated with increased mortality [OR 3.96 (2.16-7.27), P < 0.001; I2: 41.3%]. High FIB-4 was associated mortality with a sensitivity of 0.56 (0.40-0.70), specificity of 0.80 (0.72-0.86), PLR 2.8 (1.8-4.2), NLR 0.55 (0.39-0.78), DOR 5 (2-10), and AUC of 0.77 (0.73-0.81). Fagan's nomogram indicated that for a pre-test probability (mortality) of 30%, a high FIB-4 was associated with 54% post-test probability and a low FIB-4 was associated with 19%, respectively. The funnel-plot analysis was asymmetrical, trim-and-fill analysis by imputation of a study on the left side using linear estimator resulted in an OR of 3.48 (1.97-6.14). Egger's test showed no indication of small-study effects (P = 0.881). CONCLUSION: High FIB-4 was associated with mortality in patients with COVID-19.

Managing Covid-19 in patients with heart failure: current status and future prospects.

INTRODUCTION: COVID-19 may contribute to decompensation of previously stable chronic HF or cause a de-novo heart failure, which may come from the hyperinflammatory response and subsequent increase in metabolic demand. AREAS COVERED: Two independent investigators searched MEDLINE (via PubMed), Europe PMC, and ScienceDirect databases with the following search terms: COVID-19, heart failure, COVID-19 drugs, heart failure drugs, and device therapy. All of the included full-text articles were rigorously evaluated by both authors in case there was disagreement about whether research should be included or not. In total, 157 studies were included and underwent extensive reading by the authors. EXPERT OPINION: The World Health Organization (WHO) and the National Institute of Health (NIH) have published COVID-19 drug recommendations, although recommendations for HF-specific drug choices in COVID-19 are still lacking. We hope that this review can answer the void of comprehensive research data regarding the management options of HF in the COVID-19 condition so that clinicians can at least choose a more beneficial therapy or avoid combination therapies that have a high burden of side effects on HF; thus, morbidity and mortality in COVID-19 patients with HF may be reduced.

Elevated De Ritis Ratio Is Associated With Poor Prognosis in COVID-19: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis aims to assess whether elevated De Ritis ratio is associated with poor prognosis in patients with coronavirus 2019 (COVID-19). Methods: A systematic literature search was performed using PubMed, Embase, and EuropePMC databases up until September 17, 2021. De Ritis ratio is also known as Aspartate aminotransferase/alanine transaminase (AST/ALT) ratio. The main outcome was poor prognosis, a composite of mortality, severity, the need for ICU care, and intubation. The effect measure was odds ratios (ORs) and mean differences. We generated sensitivity and specificity, negative and positive likelihood ratio (NLR and PLR), diagnostic odds ratio (DOR), and area under curve (AUC). Results: There were eight studies with 4,606 patients. De Ritis ratio was elevated in 44% of the patients. Patients with poor prognosis have higher De Ritis ratio [mean difference 0.41 (0.31, 0.50), p < 0.001; I 2: 81.0%] and subgroup analysis showed that non-survivors also have higher De Ritis Ratio [mean difference 0.47 (0.46, 0.48), p < 0.001; I 2: 0%]. Elevated De Ritis ratio was associated with poor prognosis [OR 3.28 (2.39, 4.52), p < 0.001; I 2: 35.8%]. It has a sensitivity of 55% (36-73), specificity of 71% (52-85), PLR 1.9, NLR.63, DOR of 3 (2-4), and AUC of.67 (0.63-0.71). The posterior probability of poor prognosis was 38% if De Ritis is elevated, while 17% if De Ritis is not elevated. Conclusion: Elevated De Ritis ratio is associated with poor prognosis in patients with COVID-19. Systematic Review Registration: PROSPERO ID: CRD42020216634.

Elevated De Ritis Ratio Is Associated With Poor Prognosis in COVID-19: A Systematic Review and Meta-Analysis

Objective: This meta-analysis aims to assess whether elevated De Ritis ratio is associated with poor prognosis in patients with coronavirus 2019 (COVID-19). Methods: A systematic literature search was performed using PubMed, Embase, and EuropePMC databases up until September 17, 2021. De Ritis ratio is also known as Aspartate aminotransferase/alanine transaminase (AST/ALT) ratio. The main outcome was poor prognosis, a composite of mortality, severity, the need for ICU care, and intubation. The effect measure was odds ratios (ORs) and mean differences. We generated sensitivity and specificity, negative and positive likelihood ratio (NLR and PLR), diagnostic odds ratio (DOR), and area under curve (AUC). Results: There were eight studies with 4,606 patients. De Ritis ratio was elevated in 44% of the patients. Patients with poor prognosis have higher De Ritis ratio [mean difference 0.41 (0.31, 0.50), p < 0.001;I2: 81.0%] and subgroup analysis showed that non-survivors also have higher De Ritis Ratio [mean difference 0.47 (0.46, 0.48), p < 0.001;I2: 0%]. Elevated De Ritis ratio was associated with poor prognosis [OR 3.28 (2.39, 4.52), p < 0.001;I2: 35.8%]. It has a sensitivity of 55% (36–73), specificity of 71% (52–85), PLR 1.9, NLR.63, DOR of 3 (2–4), and AUC of.67 (0.63–0.71). The posterior probability of poor prognosis was 38% if De Ritis is elevated, while 17% if De Ritis is not elevated. Conclusion: Elevated De Ritis ratio is associated with poor prognosis in patients with COVID-19. Systematic Review Registration: PROSPERO ID: CRD42020216634.

Corrigendum: Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fnut.2021.660420.].

Repurposing FIB-4 index as a predictor of mortality in patients with hematological malignancies and COVID-19.

BACKGROUND: In this study, we aimed to investigate whether FIB-4 index is useful in predicting mortality in patients with concurrent hematological malignancies and COVID-19. We also aimed to determine the optimal cut-off point for the prediction. METHODS: This is a single-center retrospective cohort study conducted in Dharmais National Cancer Hospital, Indonesia. Consecutive sampling of adults with hematological malignancies and COVID-19 was performed between May 2020 and January 2021. COVID-19 screening test using the reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal samples were performed prior to hospitalization for chemotherapy. FIB-4 index is derived from [age (years) × AST (IU/L)]/[platelet count (109/L) × âˆšALT (U/L)]. The primary outcome of this study is mortality, defined as clinically validated death/non-survivor during a 3-months (90 days) follow-up. RESULTS: There were a total of 70 patients with hematological malignancies and COVID-19 in this study. Median FIB-4 Index was higher in non-survivors (13.1 vs 1.02, p<0.001). FIB-4 index above 3.85 has a sensitivity of 79%, specificity of 84%, PLR of 5.27, and NLR of 0.32. The AUC was 0.849 95% CI 0.735-0.962, p<0.001. This cut-off point was associated with OR of 16.70 95% CI 4.07-66.67, p<0.001. In this study, a FIB-4 >3.85 confers to 80% posterior probability of mortality and FIB-4 <3.85 to 19% probability. FIB-4 >3.85 was associated with shorter time-to-mortality (HR 9.10 95% CI 2.99-27.65, p<0.001). Multivariate analysis indicated that FIB-4 >3.85 (HR 4.09 95% CI 1.32-12.70, p = 0.015) and CRP> 71.57 mg/L (HR 3.36 95% CI 1.08-10.50, p = 0.037) were independently associated with shorter time-to-mortality. CONCLUSION: This study indicates that a FIB-4 index >3.85 was independent predictor of mortality in patients with hematological malignancies and COVID-19 infection.

Decrease in the Number of Patients Presenting With ST-Segment Elevation Myocardial Infarction Across Catheterization Centers in Indonesia During the Coronavirus Disease 2019 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has become a global problem, put a heavy burden on the health care system, and resulted in many fatalities across the globe. A reduction in the number of cardiac emergencies, especially ST-segment elevation myocardial infarction (STEMI), is observed worldwide. In this study, we aimed to analyze the trends of cases and presentation of STEMI across several cardiac catheterization centers in Indonesia. Method: This retrospective study was performed by combining medical record data from five different hospitals in Indonesia. We compared data from the time period between February to June 2019 with those between February and June 2020. Patients who were diagnosed with STEMI and underwent primary percutaneous coronary intervention (PPCI) procedures were included in the study. Results: There were 41,396 emergency department visits in 2019 compared with 29,542 in 2020. The number of patients with STEMI declined significantly from 338 in 2019 to 190 in 2020. Moreover, the total number of PPCI procedures reduced from 217 in 2019 to 110 in 2020. The proportion of PPCI was not significantly reduced (64.2 vs. 57.9%). The majority of the patients were men, with a mean age of 54 years in 2019 and 55 years in 2020. We observed a significantly longer door-to-balloon time in 2020 than in 2019 (p < 0.001). We also observed a difference in the door-to-balloon time and ischemic time between the two periods. Conclusion: We observed a decline in the number of patients presenting with STEMI to our centers. However, we observed no significant decline in the percentage of PPCI performed across our centers during this pandemic.

In-depth review of cardiopulmonary support in COVID-19 patients with heart failure.

Coronavirus disease 2019 infection has spread worldwide and causing massive burden to our healthcare system. Recent studies show multiorgan involvement during infection, with direct insult to the heart. Worsening of the heart function serves as a predictor of an adverse outcome. This finding raises a particular concern in high risk population, such as those with history of preexisting heart failure with or without implantable device. Lower baseline and different clinical characteristic might raise some challenge in managing either exacerbation or new onset heart failure that might occur as a consequence of the infection. A close look of the inflammatory markers gives an invaluable clue in managing this condition. Rapid deterioration might occur anytime in this setting and the need of cardiopulmonary support seems inevitable. However, the use of cardiopulmonary support in this patient is not without risk. Severe inflammatory response triggered by the infection in combination with the preexisting condition of the worsening heart and implantable device might cause a hypercoagulability state that should not be overlooked. Moreover, careful selection and consideration have to be met before selecting cardiopulmonary support as a last resort due to limited resource and personnel. By knowing the nature of the disease, the interaction between the inflammatory response and different baseline profile in heart failure patient might help clinician to salvage and preserve the remaining function of the heart.

Candesartan as a tentative treatment for COVID-19: A prospective non-randomized open-label study.

BACKGROUND: This study aimed to investigate whether the addition of candesartan to the standard care regimen improved the outcome in patients with coronavirus 2019 (COVID-19). METHODS: A prospective non-randomized open-label study was undertaken from May to August 2020 on 75 subjects (aged 18-70 years) hospitalized in Siloam Kelapa Dua Hospital. Uni- and multi-variable Cox regression analyses were performed to obtain hazard ratios (HRs). The primary outcomes were: (1) length of hospital stay; (2) time to negative swab; and (3) radiological outcome (time to improvement on chest X ray). RESULTS: None of the 75 patients with COVID-19 required intensive care. All patients were angiotensin-receptor-blocker naïve. In comparison with the control group, the candesartan group had a significantly shorter hospital stay [adjusted HR 2.47, 95% confidence interval (CI) 1.16-5.29] after adjusting for a wide range of confounders, and no increased risk of intensive care. In the non-obese subgroup, the candesartan group had a shorter time to negative swab (unadjusted HR 2.11, 95% CI 1.02-4.36; adjusted HR 2.40, 95% CI 1.08-5.09) and shorter time to improvement in chest x ray (adjusted HR 2.82, 95% CI 1.13-7.03) compared with the control group. CONCLUSION: Candesartan significantly reduces the length of hospital stay after adjustment for covariates. All primary outcomes improved significantly in the non-obese subgroup receiving candesartan.

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.

The Prognostic Value of Hyponatremia for Predicting Poor Outcome in Patients With COVID-19: A Systematic Review and Meta-Analysis.

Background: This meta-analysis aimed to assess the prognostic value of hyponatremia in patients with COVID-19. Methods: We performed a systematic literature search on PubMed, Scopus, ScienceDirect, and Wiley up until January 26, 2021. The key exposure was hyponatremia, defined as sodium level below the reference level. The outcome of interest was poor outcome, which was a composite of mortality, severe COVID-19, and prolonged hospitalization. Severe COVID-19 was defined severe CAP or needing ICU care or IMV. The pooled effect estimate was odds ratio (OR). Sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic OR (DOR), and area under curve (AUC) were generated. Results: There were 11,493 patients from eight studies included in this systematic review and meta-analysis. The incidence of hyponatremia was 24%, and incidence of poor outcome was 20%. Hyponatremia was associated with poor outcome in COVID-19 (OR 2.65 [1.89, 3.72], p < 0.001; I2: 67.2%). Meta-regression analysis showed that the association between hyponatremia and poor outcome was reduced by age (OR 0.94 [0.90, 0.98], p = 0.006) and hypertension (OR 0.96 [0.93, 0.94], p < 0.001). Hyponatremia has a sensitivity of 0.37 [0.27, 0.48], specificity of 0.82 [0.72, 0.88], PLR of 2.0 [1.5, 2.7], NLR of 0.77 [0.69, 0.87], DOR of 3 [2, 4], and AUC of 0.62 [0.58, 0.66] for predicting poor outcome. In this pooled analysis, hyponatremia has a 33% posttest probability for poor outcome, and absence of hyponatremia confers to a 16% posttest probability. Conclusion: Hyponatremia was associated with poor outcome in patients with COVID-19. Systematic Review Registration: PROSPERO, CRD42021233592.

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.

Ivermectin and mortality in patients with COVID-19: A systematic review, meta-analysis, and meta-regression of randomized controlled trials.

AIMS: This systematic review and meta-analysis aims to investigate the effect of ivermectin on mortality in patients with COVID-19. METHODS: A comprehensive systematic literature search was performed using PubMed, Scopus, Embase, and Clinicaltrials.gov from the inception of databases up until April 9, 2021. The intervention group was ivermectin and the control group was standard of care or placebo. The primary outcome was mortality reported as risk ratio (RR). RESULTS: There were 9 RCTs comprising of 1788 patients included in this meta-analysis. Ivermectin was associated with decreased mortality (RR 0.39 [95% 0.20-0.74], p = 0.004; I2: 58.2%, p = 0.051). Subgroup analysis in patients with severe COVID-19 showed borderline statistical significance towards mortality reduction (RR 0.42 [95% 0.18-1.00], p = 0.052; I2: 68.3, p = 0.013). The benefit of ivermectin and mortality was reduced by hypertension (RR 1.08 [95% CI 1.03-1.13], p = 0.001); but was not influenced by age (p = 0.657), sex (p = 0.466), diabetes (p = 0.429). Sensitivity analysis using fixed-effect model showed that ivermectin decreased mortality in general (RR 0.43 [95% CI 0.29-0.62], p < 0.001) and severe COVID-19 subgroup (RR 0.48 [95% CI 0.32-0.72], p < 0.001). CONCLUSIONS: Ivermectin was associated with decreased mortality in COVID-19 with a low certainty of evidence. Further adequately powered double-blinded placebo-controlled RCTs are required for definite conclusion.

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.

Diabetes and COVID-19: The past, the present, and the future.

Diabetes, one of the most prevalent chronic diseases in the world, is strongly associated with a poor prognosis in COVID-19. Scrupulous blood sugar management is crucial, since the worse outcomes are closely associated with higher blood sugar levels in COVID-19 infection. Although recent observational studies showed that insulin was associated with mortality, it should not deter insulin use in hospitalized patients requiring tight glucose control. Back and forth dilemma in the past with regards to continue/discontinue certain medications used in diabetes have been mostly resolved. The initial fears of consequences related to continuing certain medications have been largely dispelled. COVID-19 also necessitates the transformation in diabetes care through the integration of technologies. Recent advances in health-related technologies, notably telemedicine and remote continuous glucose monitoring, have become essential in the management of diabetes during the pandemic. Today, these technologies have changed the landscape of medicine and become more important than ever. Being a high-risk population, patients with type 1 or type 2 diabetes, should be prioritized for vaccination. In the future, as the pandemic fades, the prevalence of non-communicable diseases is expected to rise due to lifestyle changes and medical issues/dilemma encountered during the pandemic.

Sofosbuvir with daclatasvir and the outcomes of patients with COVID-19: a systematic review and meta-analysis with GRADE assessment.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the effect of sofosbuvir/daclatasvir (SOF/DCV) on mortality, the need for intensive care unit (ICU) admission or invasive mechanical ventilation (IMV) and clinical recovery in patients with COVID-19. METHODS: We performed a systematic literature search through the PubMed, Scopus and Embase from the inception of databases until 6 April 2021. The intervention group was SOF/DCV, and the control group was standard of care. The primary outcome was mortality, defined as clinically validated death. The secondary outcomes were (1) the need for ICU admission or IMV and (2) clinical recovery. The pooled effect estimates were reported as risk ratios (RRs). RESULTS: There were four studies with a total of 231 patients in this meta-analysis. Three studies were randomised controlled trial, and one study was non-randomised. SOF/DCV was associated with lower mortality (RR: 0.31 (0.12, 0.78); p=0.013; I2: 0%) and reduced need for ICU admission or IMV (RR: 0.35 (0.18, 0.69); p=0.002; I2: 0%). Clinical recovery was achieved more frequently in the SOF/DCV (RR: 1.20 (1.04, 1.37); p=0.011; I2: 21.1%). There was a moderate certainty of evidence for mortality and need for ICU/IMV outcome, and a low certainty of evidence for clinical recovery. The absolute risk reductions were 140 fewer per 1000 for mortality and 186 fewer per 1000 for the need for ICU/IMV. The increase in clinical recovery was 146 more per 1000. CONCLUSION: SOF/DCV may reduce mortality rate and need for ICU/IMV in patients with COVID-19 while increasing the chance for clinical recovery. PROTOCOL REGISTRATION: PROSPERO: CRD42021247510.

Colchicine and mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia: A systematic review, meta-analysis, and meta-regression.

OBJECTIVE: This systematic review, with meta-analysis and meta-regression aims to evaluate the effect of colchicine administration on mortality in patients with coronavirus disease 2019 (COVID-19) and factors affecting the association. METHODS: A systematic literature search using the PubMed, Scopus, and Embase databases were performed from inception of databases up until 3 March 2021. We included studies that fulfill all of the following criteria: 1) observational studies or randomized controlled trials (RCTs) that report COVID-19 patients, 2) reporting colchicine use, and 3) mortality within 30 days. There was no restriction on the age, inpatients or outpatients setting, and severity of diseases. The intervention was colchicine administration during treatment for COVID-19. The control was receiving placebo or standard of care. The outcome was mortality and the pooled effect estimate was reported as odds ratio (OR). Random-effects restricted maximum likelihood meta-regression was performed to evaluate factors affecting the pooled effect estimate. RESULTS: Eight studies comprising of 5530 patients were included in this systematic review and meta-analysis. There were three RCTs and five observational studies. Pooled analysis showed that colchicine was associated with lower mortality in patients with COVID-19 (OR 0.47 [0.31, 0.72], p = 0.001; I2: 30.9, p = 0.181). Meta-regression analysis showed that the association between colchicine and mortality was reduced by increasing age (OR 0.92 [0.85, 1.00], p = 0.05), but not gender (reference: male, p = 0.999), diabetes (p = 0.376), hypertension (p = 0.133), and CAD (p = 0.354). CONCLUSION: This meta-analysis indicates that colchicine may reduce mortality in patients with COVID-19. Meta-regression analysis showed that the benefit was reduced as age increases. PROSPERO: CRD42021240609.

Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis.

Background: This systematic review and meta-analysis aimed to assess whether low serum 25-hydroxyvitamin D (25-OHD) level is associated with susceptibility to COVID-19, severity, and mortality related to COVID-19. Methods: Systematic literature searches of PubMed, Scopus, and Embase database up until 9 December 2020. We include published observational prospective and retrospective studies with information on 25-OHD that reported main/secondary outcome. Low serum 25-OHD refers to participants with serum 25-OHD level below a cut-off point ranging from 20 to 30 ng/mL. Other cut-off values were excluded to reduce heterogeneity. The main outcome was mortality defined as non-survivor/death. The secondary outcome was susceptibility and severe COVID-19. Results: There were 14 studies comprising of 999,179 participants. Low serum 25-OHD was associated with higher rate of COVID-19 infection compared to the control group (OR = 2.71 [1.72, 4.29], p < 0.001; I 2: 92.6%). Higher rate of severe COVID-19 was observed in patients with low serum 25-OHD (OR = 1.90 [1.24, 2.93], p = 0.003; I 2: 55.3%), with a sensitivity of 83%, specificity of 39%, PLR of 1.4, NLR of 0.43, and DOR of 3. Low serum 25-OHD was associated with higher mortality (OR = 3.08 [1.35, 7.00], p = 0.011; I 2: 80.3%), with a sensitivity of 85%, specificity of 35%, PLR of 1.3, NLR of 0.44, and DOR of 3. Meta-regression analysis showed that the association between low serum 25-OHD and mortality was affected by male gender (OR = 1.22 [1.08, 1.39], p = 0.002), diabetes (OR = 0.88 [0.79, 0.98], p = 0.019). Conclusion: Low serum 25-OHD level was associated with COVID-19 infection, severe presentation, and mortality.

Prognostic value of fasting hyperglycemia in patients with COVID-19 - Diagnostic test accuracy meta-analysis.

AIMS: This meta-analysis aimed to assess the prognostic value of fasting hyperglycemia in patients with COVID-19. METHODS: A systematic literature search on PubMed, Embase, and Scopus were performed up until February 18, 2021. Fasting hyperglycemia was defined as fasting plasma glucose level above the reference value. The outcome of interest was poor outcome, which was a composite of mortality and severe COVID-19. The effect estimate was in odds ratio (OR). RESULTS: There were 9045 patients from 12 studies included in this systematic review and meta-analysis. The prevalence of fasting hyperglycemia was 29%. The incidence of poor outcome was 15%. Fasting hyperglycemia was associated with poor outcome in COVID-19 (OR 4.72 [3.32, 6.72], p < 0.001; I2: 69.8%, p < 0.001). Subgroup analysis in patients without prior history of diabetes showed that fasting hyperglycemia was associated with poor outcome in COVID-19 (OR 3.387 [2.433, 4.714], p < 0.001; I2: 0, p = 0.90). Fasting hyperglycemia has a sensitivity of 0.57 [0.45, 0.68], specificity of 0.78 [0.70, 0.84], PLR of 2.6 [2.0, 3.3], NLR of 0.55 [0.44, 0.69], DOR of 5 [3, 7], and AUC of 0.74 [0.70, 0.78] for predicting poor outcome. In this pooled analysis, fasting hyperglycemia has a 32% post-test probability for poor outcome, and absence of fasting hyperglycemia confers to a 9% post-test probability. Meta-regression and subgroup analysis showed that the sensitivity and specificity varies by chronic kidney disease but not by age, male (gender), hypertension, and chronic kidney disease. CONCLUSION: Fasting hyperglycemia was associated with mortality in COVID-19 patients, with or without diabetes. PROSPERO: CRD42021237997.

Visceral adiposity, subcutaneous adiposity, and severe coronavirus disease-2019 (COVID-19): Systematic review and meta-analysis.

BACKGROUND AND AIMS: Body mass index (BMI) has previously been shown to increase mortality and disease severity in patients with COVID-19, but the pooled effect estimate was heterogeneous. Although BMI is widely used as an indicator, it cannot distinguish visceral from subcutaneous fat. This systematic review and meta-analysis aimed to investigate the association between visceral adiposity, subcutaneous fat, and severe COVID-19. METHODS: We performed a systematic literature search using the databases: PubMed, Embase, and EuropePMC. Data on visceral fat area (VTA), subcutaneous fat area (SFA), and total fat area (TFA) were collected. The outcome of interest was severe COVID-19. We used a REML random-effects model to pool the mean differences and odds ratio (OR). RESULTS: There were 5 studies comprising of 539 patients. Patients with severe COVID-19 have a higher VTA (mean difference 41.7 cm2 [27.0, 56.4], p < 0.001; I2: 0%) and TFA (mean difference 64.6 cm2 [26.2, 103.1], p = 0.001; I2: 0%). There was no significant difference in terms of SFA between patients with severe and non-severe COVID-19 (mean difference 9.3 cm2 [-4.9, 23.4], p = 0.199; I2: 1.2%). Pooled ORs showed that VTA was associated with severe COVID-19 (OR 1.9 [1.1, 2.2], p = 0.002; I2: 49.3%). CONCLUSION: Visceral adiposity was associated with increased COVID-19 severity, while subcutaneous adiposity was not. PROSPERO ID: CRD42020215876.