PurposeThis meta-analysis aimed to evaluate the prognostic performance of elevated lactate dehydrogenase (LDH) in patients with COVID-19.MethodsA systematic literature search was performed using PubMed, Embase and EuropePMC on 19 November 2020. The outcome of interest was composite poor outcome, defined as a combined endpoint of mortality, severity, need for invasive mechanical ventilation and need for intensive care unit care. Severity followed the included studies’ criteria.ResultsThere are 10 399 patients from 21 studies. Elevated LDH was present in 44% (34%–53%) of the patients. Meta-regression analysis showed that diabetes was correlated with elevated LDH (OR 1.01 (95% CI 1.00 to 1.02), p=0.038), but not age (p=0.710), male (p=0.068) and hypertension (p=0.969). Meta-analysis showed that elevated LDH was associated with composite poor outcome (OR 5.33 (95% CI 3.90 to 7.31), p<0.001; I2: 77.5%). Subgroup analysis showed that elevated LDH increased mortality (OR 4.22 (95% CI 2.49 to 7.14), p<0.001; I2: 89%). Elevated LDH has a sensitivity of 0.74 (95% CI 0.60 to 0.85), specificity of 0.69 (95% CI 0.58 to 0.78), positive likelihood ratio of 2.4 (95% CI 1.9 to 2.9), negative likelihood ratio of 0.38 (95% CI 0.26 to 0.55), diagnostic OR of 6 (95% CI 4 to 9) and area under curve of 0.77 (95% CI 0.73 to 0.80). Elevated LDH would indicate a 44% posterior probability and non-elevated LDH would in indicate 11% posterior probability for poor prognosis. Meta-regression analysis showed that age, male, hypertension and diabetes did not contribute to the heterogeneity of the analyses.ConclusionLDH was associated with poor prognosis in patients with COVID-19.PROSPERO registration numberCRD42020221594.

Background This systematic review and meta-analysis aimed to assess whether ventricular longitudinal strain can be used as a prognostication tool in patients with coronavirus disease 2019 (COVID-19). Methods Systematic literature searches of PubMed, Embase, and EuropePMC databases were performed on 16 November 2020. Left ventricular global longitudinal strain (LV-GLS) refers to LV contraction measurement using the speckle tracking-based method refers to the mean of strain values of the RV free wall (three segments) measured using echocardiography. The main outcome was poor outcome, defined as a composite of mortality and severe COVID-19. Results Seven studies comprising of 612 patients were included in meta-analysis. Six studies have mortality as their outcome, and 1 study has severity as their outcome. Patients with poor outcome have lower LV-GLS (SMD 1.15 (0.57, 1.72), p < 0.001; I2 70.4%). Each 1% decrease in LV-GLS was associated with 1.4x increased risk of poor outcome (OR 1.37 (1.12, 1.67), p = 0.002; I2 48.8%). Patients with poor outcome have lower RV-LS (SMD 1.18 (0.91, 1.45), p < 0.001; I2 0%). Each 1% decrease in RV-LS was associated with 1.3x increased risk of poor outcome (OR 1.25 (1.15, 1.35), p < 0.001; I2 11.8%). Subgroup analysis showed that for every 1% decrease in LV-GLS and RV-LS is increased mortality with OR of 1.30 (1.12, 1.50) and OR of 1.24 (1.14, 1.35), respectively. Conclusion This study shows that lower LV-GLS and RV-LS measurements were associated with poor outcome in patients with COVID-19. Trial registration PROSPERO CRD42020221144

Background Cardiac injury is frequently encountered in patients with COVID-19 and is associated with an increased risk of mortality. Elevated troponin may signify myocardial damage and predicts mortality. We aimed to assess the prognostic value of elevated troponin above the 99 th percentile upper reference limit (URL) on mortality and factors affecting their relationship. Methods We performed a comprehensive literature search using PubMed (MEDLINE), Scopus, and Embase from inception of the search databases until 16 th December 2020. The key exposure was elevated serum troponin, defined as troponin (of any type) elevation > 99th percentile URL. The outcome was mortality due to any causes. Results There were a total of 12,262 patients from 13 studies in this systematic review and meta-analysis. Mortality was present in 23% (20-26%) of the patients. Elevated troponin was present in 31% (23-38%) of the patients. Elevated troponin was associated with increased mortality (OR 4.75 [4.07, 5.53], p < 0.001; I 2 : 19.9%). Meta-regression shows that the association did not vary with age (p = 0.218), male gender (p = 0.707), hypertension (p = 0.182), diabetes (p = 0.906), and coronary artery disease (p = 0864). Elevated troponin was associated with sensitivity of 0.55 [0.44, 0.66], specificity of 0.80 [0.71, 0.86], PLR 2.7 of [2.2, 3.3], NLR of 0.56 [0.49, 0.65], DOR of 5 [4, 5], and AUC of 0.73 [0.69, 0.77]. Elevated troponin resulted in a 45% probability for mortality and non-elevated troponin resulted in a 14% probability for mortality. Conclusion Elevated troponin was associated with increased mortality with a 55% sensitivity and 80% specificity.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Background and aims Creatine kinase (CK), a marker of muscle damage, is potentially associated with a more severe COVID-19. In this systematic review and meta-analysis, we aim to evaluate the association between the elevated CK and severity and mortality in COVID-19. Methods We performed a systematic literature search on PubMed, Scopus, and Embase up until January 26, 2020. The main outcome was poor outcome, a composite of mortality and severe COVID-19. Results There are 2471 patients from 14 studies included in this systematic review and meta-analysis. The incidence of elevated CK in this pooled analysis was 17% (11%, 22%) and the incidence of poor outcome in this pooled analysis was 27% (19%, 34%). Elevated CK was associated with poor outcome in patients with COVID-19 (OR 3.01 [2.21, 4.10], p < 0.001; I 2 : 10.2%). The effect estimate did not vary with age (p = 0.610), male (p = 0.449), hypertension (p = 0.490), and diabetes (p = 0.457). Elevated CK has a sensitivity of 0.24 (0.17, 0.32), specificity of 0.91 (0.86, 0.94), PLR of 2.6 (1.9, 3.7), NLR of 0.84 (0.78, 0.90), DOR of 3 (2, 5), and AUC of 0.62 (0.57, 0.66) for predicting poor outcome in patients with COVID-19. In this pooled analysis, elevated CK confers to a 49% probability for poor outcome and a non-elevated CK confers to a 24% probability. Subgroup analysis and univariate meta-regression indicates that the sensitivity and specificity does not vary with age, male, hypertension, and diabetes. Conclusion Elevated CK was associated with increased mortality and severity in patients with COVID-19. PROSPERO CRD42021233435.

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 &lt; 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 &lt; 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.