Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis

AbstractCoronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: − 0.99 g/L; 95% CI, − 1.11 to − 0.88, p < 0.001). In multivariate meta-regression analysis, age (t = − 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t = − 2.77, p = 0.008) and C-reactive protein (t = − 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group.

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Laboratory Tests and Outcome for Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa098 ◽

2020 ◽

Vol 5 (5) ◽

pp. 1038-1049 ◽

Cited By ~ 1

Author(s):

Anne Alnor ◽

Maria B Sandberg ◽

Charlotte Gils ◽

Pernille J Vinholt

Keyword(s):

Systematic Review ◽

Disease Severity ◽

Laboratory Tests ◽

Evidence Synthesis ◽

Meta Analysis ◽

Severe Disease ◽

Risk Of Bias ◽

Mean Difference ◽

Routine Laboratory ◽

Standard Mean Difference

Abstract Background Severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019 (COVID-19) and poses substantial challenges for healthcare systems. With a vastly expanding number of publications on COVID-19, clinicians need evidence synthesis to produce guidance for handling patients with COVID-19. In this systematic review and meta-analysis, we examine which routine laboratory tests are associated with severe COVID-19 disease. Content PubMed (Medline), Scopus, and Web of Science were searched until March 22, 2020, for studies on COVID-19. Eligible studies were original articles reporting on laboratory tests and outcome of patients with COVID-19. Data were synthesized, and we conducted random-effects meta-analysis, and determined mean difference (MD) and standard mean difference at the biomarker level for disease severity. Risk of bias and applicability concerns were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. Summary 45 studies were included, of which 21 publications were used for the meta-analysis. Studies were heterogeneous but had low risk of bias and applicability concern in terms of patient selection and reference standard. Severe disease was associated with higher white blood cell count (MD, 1.28 ×109/L), neutrophil count (MD, 1.49 ×109/L), C-reactive protein (MD, 49.2 mg/L), lactate dehydrogenase (MD, 196 U/L), D-dimer (standardized MD, 0.58), and aspartate aminotransferase (MD, 8.5 U/L); all p < 0.001. Furthermore, low lymphocyte count (MD −0.32 × 109/L), platelet count (MD −22.4 × 109/L), and hemoglobin (MD, −4.1 g/L); all p < 0.001 were also associated with severe disease. In conclusion, several routine laboratory tests are associated with disease severity in COVID-19.

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Serum Albumin Concentrations in Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Journal of Clinical Medicine ◽

10.3390/jcm10020269 ◽

2021 ◽

Vol 10 (2) ◽

pp. 269

Author(s):

Elisabetta Zinellu ◽

Alessandro G. Fois ◽

Elisabetta Sotgiu ◽

Sabrina Mellino ◽

Arduino A. Mangoni ◽

...

Keyword(s):

Systematic Review ◽

Chronic Obstructive Pulmonary Disease ◽

Serum Albumin ◽

Pulmonary Disease ◽

Meta Analysis ◽

Forced Expiratory Volume ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Standard Mean Difference ◽

Copd Patients

Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and lung parenchyma damage. Systemic inflammation and oxidative stress also play a role in the pathogenesis of COPD. Serum albumin is a negative acute-phase protein with antioxidant effects and an important marker of malnutrition. The aim of this meta-analysis was to investigate differences in serum albumin concentrations between patients with stable COPD and non-COPD subjects. Methods: A systematic search was conducted, using the terms “albumin” and “chronic obstructive pulmonary disease” or “COPD”, in the electronic databases PubMed and Web of Science, from inception to May 2020. Results: Twenty-six studies were identified on a total of 2554 COPD patients and 2055 non-COPD controls. Pooled results showed that serum albumin concentrations were significantly lower in COPD patients (standard mean difference, SMD = −0.50, 95% CI −0.67 to −0.32; p < 0.001). No significant differences were observed in SMD of serum albumin concentrations between COPD patients with forced expiratory volume in the 1st second (FEV1) < 50% and those with FEV1 > 50%. Conclusions: Our systematic review and meta-analysis showed that serum albumin concentrations are significantly lower in patients with stable COPD compared to non-COPD controls. This supports the presence of a deficit in systemic anti-inflammatory and antioxidant defense mechanisms in COPD.

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Clinical characteristics, treatment and outcomes of paediatric COVID-19: a systematic review and meta-analysis

Archives of Disease in Childhood ◽

10.1136/archdischild-2020-321385 ◽

2021 ◽

pp. archdischild-2020-321385

Author(s):

Omar Irfan ◽

Fiona Muttalib ◽

Kun Tang ◽

Li Jiang ◽

Zohra S Lassi ◽

...

Keyword(s):

Systematic Review ◽

Disease Severity ◽

World Bank ◽

Low Income ◽

Meta Analysis ◽

Severe Disease ◽

Income Level ◽

Clinical Findings ◽

Middle Income ◽

Middle Income Countries

ObjectiveCompare paediatric COVID-19 disease characteristics, management and outcomes according to World Bank country income level and disease severity.DesignSystematic review and meta-analysis.SettingBetween 1 December 2019 and 8 January 2021, 3350 articles were identified. Two reviewers conducted study screening, data abstraction and quality assessment independently and in duplicate. Observational studies describing laboratory-confirmed paediatric (0–19 years old) COVID-19 were considered for inclusion.Main outcomes and measuresThe pooled proportions of clinical findings, treatment and outcomes were compared according to World Bank country income level and reported disease severity.Results129 studies were included from 31 countries comprising 10 251 children of which 57.4% were hospitalised. Mean age was 7.0 years (SD 3.6), and 27.1% had a comorbidity. Fever (63.3%) and cough (33.7%) were common. Of 3670 cases, 44.1% had radiographic abnormalities. The majority of cases recovered (88.9%); however, 96 hospitalised children died. Compared with high-income countries, in low-income and middle-income countries, a lower proportion of cases were admitted to intensive care units (ICUs) (9.9% vs 26.0%) yet pooled proportion of deaths among hospitalised children was higher (relative risk 2.14, 95% CI 1.43 to 3.20). Children with severe disease received antimicrobials, inotropes and anti-inflammatory agents more frequently than those with non-severe disease. Subgroup analyses showed that a higher proportion of children with multisystem inflammatory syndrome (MIS-C) were admitted to ICU (47.1% vs 22.9%) and a higher proportion of hospitalised children with MIS-C died (4.8% vs 3.6%) compared with the overall sample.ConclusionPaediatric COVID-19 has a favourable prognosis. Further severe disease characterisation in children is needed globally.

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Factors Associated with Disease Severity and Mortality among Patients with Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

10.1101/2020.08.07.20166868 ◽

2020 ◽

Author(s):

Vignesh Chidambaram ◽

Nyan Lynn Tun ◽

Waqas Haque ◽

Marie Gilbert Majella ◽

Ranjith Kumar Sivakumar ◽

...

Keyword(s):

Systematic Review ◽

Disease Severity ◽

English Language ◽

Clinical Decision Making ◽

Clinical Laboratory ◽

Data Extraction ◽

Meta Analysis ◽

Severe Disease ◽

Factors Associated ◽

Risk Of Mortality

Background: Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods: We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Results: Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45; 95%CI 1.23,1.71), dyspnea (RR 2.55; 95%CI 1.88,2.46), diabetes (RR 1.59; 95%CI 1.41,1.78), hypertension (RR 1.90; 95%CI 1.69,2.15). Congestive heart failure (OR 4.76; 95%CI 1.34,16.97), hilar lymphadenopathy (OR 8.34; 95%CI 2.57,27.08), bilateral lung involvement (OR 4.86; 95%CI 3.19,7.39) and reticular pattern (OR 5.54; 95%CI 1.24,24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. Conclusion: Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.

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Cardiovascular drugs and COVID-19 clinical outcomes: a living systematic review and meta-analysis

10.1101/2020.10.07.20208918 ◽

2020 ◽

Author(s):

Innocent G Asiimwe ◽

Sudeep Pushpakom ◽

Richard M Turner ◽

Ruwanthi Kolamunnage-Dona ◽

Andrea Jorgensen ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Disease Severity ◽

Meta Analysis ◽

Severe Disease ◽

Cardiovascular Drugs ◽

Susceptibility To Infection ◽

Drug Classes ◽

All Cause Mortality ◽

Length Of Hospitalization

ABSTRACTOBJECTIVETo continually evaluate the rapidly evolving evidence base on the role of cardiovascular drugs in COVID-19 clinical outcomes (susceptibility to infection, hospitalization, hospitalization length, disease severity, and all-cause mortality).DESIGNLiving systematic review and meta-analysis.DATA SOURCESEligible publications identified from >500 databases indexed through 31st July 2020 and additional studies from reference lists, with planned continual surveillance for at least two years.STUDY SELECTIONObservational and interventional studies that report on the association between cardiovascular drugs and COVID-19 clinical outcomes.DATA EXTRACTIONSingle-reviewer extraction and quality evaluation (using ROBINS-I), with half the records independently extracted and evaluated by a second reviewer.RESULTSOf 23,427 titles screened, 175 studies were included in the quantitative synthesis. The most reported drug classes were angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) with ACEI/ARB exposure being associated with higher odds of testing positive for COVID-19 (pooled unadjusted OR 1.15, 95% CI 1.02 to 1.30). Among patients with COVID-19, unadjusted estimates showed that ACEI/ARB exposure was associated with being hospitalized (OR 2.25, 1.70 to 2.98) and having severe disease (OR 1.50, 1.27 to 1.77) but not with the length of hospitalization (mean difference −0.45, −1.33 to 0.43 days) or all-cause mortality (OR 1.25, CI 0.98 to 1.58). However, after adjustment, ACEI/ARB exposure was not associated with testing positive for COVID-19 (pooled adjusted OR 1.01, 0.93 to 1.10), being hospitalized (OR 1.16, 0.80 to 1.68), having severe disease (1.04, 0.76 to 1.42), or all-cause mortality (0.86, 0.64 to 1.15). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with being hospitalized (OR 0.84, 0.58 to 1.22), disease severity (OR 0.88, 0.68 to 1.14) or all-cause mortality (OR 0.77, 0.54 to 1.12) while it decreased the length of hospitalization (mean difference −0.71, −1.11 to −0.30 days). After adjusting for relevant covariates, other cardiovascular drug classes were mostly not found to be associated with poor COVID-19 clinical outcomes. However, the validity of these findings is limited by a high level of heterogeneity in terms of effect sizes and a serious risk of bias, mainly due to confounding in the included studies.CONCLUSIONOur comprehensive review shows that ACEI/ARB exposure is associated with COVID-19 outcomes such as susceptibility to infection, severity, and hospitalization in unadjusted analyses. However, after adjusting for potential confounding factors, this association is not evident. Patients on cardiovascular drugs should continue taking their medications as currently recommended. Higher quality evidence in the form of randomized controlled trials will be needed to determine any adverse or beneficial effects of cardiovascular drugs.PRIMARY FUNDING SOURCENoneSYSTEMATIC REVIEW REGISTRATIONPROSPERO (CRD42020191283)

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Association Between SARS-CoV-2 Cycle Threshold Values and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab453 ◽

2021 ◽

Vol 8 (9) ◽

Author(s):

Vishal P Shah ◽

Wigdan H Farah ◽

James C Hill ◽

Leslie C Hassett ◽

Matthew J Binnicker ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Disease Severity ◽

Meta Analysis ◽

Severe Disease ◽

Sample Type ◽

Sample Collection ◽

Cycle Threshold ◽

Significant Difference ◽

Polymerase Chain

Abstract Cycle threshold (CT) values are correlated with the amount of viral nucleic acid in a sample and may be obtained from some qualitative real-time polymerase chain reaction tests used for diagnosis of most patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, CT values cannot be directly compared across assays, and they must be interpreted with caution as they are influenced by sample type, timing of sample collection, and assay design. Presently, the correlation between CT values and clinical outcomes is not well understood. We conducted a systematic review and meta-analysis of published studies through April 19, 2021, that reported an association between CT values and hospitalization, disease severity, and mortality in patients ≥18 years old with SARS-CoV-2. A meta-analysis of 7 studies showed no significant difference in mean CT values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with CT values <25 had a high risk of more severe disease and mortality than patients with CT values >30 (odds ratio [OR], 2.31; 95% CI, 1.70 to 3.13; and OR, 2.95; 95% CI, 2.19 to 3.96; respectively). The odds of increased disease severity and mortality were less pronounced in patients with CT values of 25–30 compared with >30.

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Serum Prealbumin Concentrations, COVID-19 Severity, and Mortality: A Systematic Review and Meta-Analysis

Frontiers in Medicine ◽

10.3389/fmed.2021.638529 ◽

2021 ◽

Vol 8 ◽

Author(s):

Angelo Zinellu ◽

Arduino A. Mangoni

Keyword(s):

Systematic Review ◽

Risk Stratification ◽

Meta Analysis ◽

Severe Disease ◽

Severe Illness ◽

Lower Serum ◽

Reactive Protein ◽

Early Risk ◽

Standard Mean Difference ◽

Reporting Data

Excessive inflammation and malnutrition are associated with coronavirus disease 2019 (COVID-19) severity and mortality. Combined biomarkers of malnutrition and inflammation, such as serum prealbumin, might be particularly attractive for early risk stratification. We conducted a systematic review and meta-analysis of studies reporting serum prealbumin in patients with COVID-19. We searched PubMed, Web of Science and Scopus, between January and November 2020, for studies reporting data on serum prealbumin, COVID-19 severity, defined as severe illness, prolonged viral load, receiving mechanical ventilation or admitted to intensive care unit (ICU), and mortality. Nineteen studies in 4,616 COVID-19 patients were included in the meta-analysis. Pooled results showed that serum prealbumin concentrations were significantly lower in patients with severe disease and non-survivors (standard mean difference, SMD, −0.92, 95% CI, −1.10 to −0.74, P < 0.001). Extreme heterogeneity was observed (I2 = 77.9%; P < 0.001). In sensitivity analysis, the effect size was not significantly affected when each study was in turn removed (range between −0.86 and −0.95). The Begg's (P = 0.06) and Egger's t-tests (P = 0.26) did not show publication bias. Pooled SMD values were significantly and negatively associated with age (t = −2.18, P = 0.045) and C-reactive protein (t = −3.85, P = 0.002). In our meta-analysis, lower serum prealbumin concentrations were significantly associated with COVID-19 severity and mortality. This combined marker of malnutrition and inflammation might assist with early risk stratification and management in this group.

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Factors associated with disease severity and mortality among patients with COVID-19: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0241541 ◽

2020 ◽

Vol 15 (11) ◽

pp. e0241541 ◽

Cited By ~ 1

Author(s):

Vignesh Chidambaram ◽

Nyan Lynn Tun ◽

Waqas Z. Haque ◽

Marie Gilbert Majella ◽

Ranjith Kumar Sivakumar ◽

...

Keyword(s):

Systematic Review ◽

Disease Severity ◽

English Language ◽

Clinical Decision Making ◽

Clinical Laboratory ◽

Data Extraction ◽

Meta Analysis ◽

Severe Disease ◽

Factors Associated ◽

Risk Of Mortality

Background Understanding the factors associated with disease severity and mortality in Coronavirus disease (COVID-19) is imperative to effectively triage patients. We performed a systematic review to determine the demographic, clinical, laboratory and radiological factors associated with severity and mortality in COVID-19. Methods We searched PubMed, Embase and WHO database for English language articles from inception until May 8, 2020. We included Observational studies with direct comparison of clinical characteristics between a) patients who died and those who survived or b) patients with severe disease and those without severe disease. Data extraction and quality assessment were performed by two authors independently. Results Among 15680 articles from the literature search, 109 articles were included in the analysis. The risk of mortality was higher in patients with increasing age, male gender (RR 1.45, 95%CI 1.23–1.71), dyspnea (RR 2.55, 95%CI 1.88–2.46), diabetes (RR 1.59, 95%CI 1.41–1.78), hypertension (RR 1.90, 95%CI 1.69–2.15). Congestive heart failure (OR 4.76, 95%CI 1.34–16.97), hilar lymphadenopathy (OR 8.34, 95%CI 2.57–27.08), bilateral lung involvement (OR 4.86, 95%CI 3.19–7.39) and reticular pattern (OR 5.54, 95%CI 1.24–24.67) were associated with severe disease. Clinically relevant cut-offs for leukocytosis(>10.0 x109/L), lymphopenia(< 1.1 x109/L), elevated C-reactive protein(>100mg/L), LDH(>250U/L) and D-dimer(>1mg/L) had higher odds of severe disease and greater risk of mortality. Conclusion Knowledge of the factors associated of disease severity and mortality identified in our study may assist in clinical decision-making and critical-care resource allocation for patients with COVID-19.

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B-Type Natriuretic Peptide Concentrations, COVID-19 Severity, and Mortality: A Systematic Review and Meta-Analysis With Meta-Regression

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.690790 ◽

2021 ◽

Vol 8 ◽

Author(s):

Angelo Zinellu ◽

Salvatore Sotgia ◽

Ciriaco Carru ◽

Arduino A. Mangoni

Keyword(s):

Systematic Review ◽

Natriuretic Peptide ◽

Effect Size ◽

Meta Analysis ◽

Severe Disease ◽

Plasma Concentrations ◽

Cardiac Biomarkers ◽

Survival Status ◽

Meta Regression ◽

Meta Regression Analysis

Alterations in cardiac biomarkers have been reported in patients with coronavirus disease 2019 (COVID-19) in relation to disease severity and mortality. We conducted a systematic review and meta-analysis with meta-regression of studies reporting B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) plasma concentrations in COVID-19. We searched PubMed, Web of Science, and Scopus, between January 2020 and 2021, for studies reporting BNP/NT-proBNP concentrations, measures of COVID-19 severity, and survival status (PROSPERO registration number: CRD42021239190). Forty-four studies in 18,856 COVID-19 patients were included in the meta-analysis and meta-regression. In pooled results, BNP/NT-proBNP concentrations were significantly higher in patients with high severity or non-survivor status when compared to patients with low severity or survivor status during follow up (SMD = 1.07, 95% CI: 0.89–1.24, and p < 0.001). We observed extreme between-study heterogeneity (I2 = 93.9%, p < 0.001). In sensitivity analysis, the magnitude and the direction of the effect size were not substantially modified after sequentially removing individual studies and re-assessing the pooled estimates, (effect size range, 0.99 – 1.10). No publication bias was observed with the Begg's (p = 0.26) and Egger's (p = 0.40) t-tests. In meta-regression analysis, the SMD was significantly and positively associated with D-dimer (t = 2.22, p = 0.03), myoglobin (t = 2.40, p = 0.04), LDH (t = 2.38, p = 0.02), and procalcitonin (t = 2.56, p = 0.01) concentrations. Therefore, higher BNP/NT-proBNP plasma concentrations were significantly associated with severe disease and mortality in COVID-19 patients.

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Corticosteroids Treatment for Patients With Coronavirus Disease-2019 (COVID-19) With Different Disease Severity: a Systematic Review and Meta-analysis Protocol

10.21203/rs.3.rs-138312/v1 ◽

2021 ◽

Author(s):

Shaofei Lou ◽

Kaizhuang Huang ◽

Jiao Jiang ◽

Ningjun Li

Keyword(s):

Systematic Review ◽

Disease Severity ◽

Oxygen Therapy ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Antiviral Agents ◽

Adverse Outcomes ◽

Cochrane Library ◽

Registration Number ◽

Meta Analyses

Abstract Introduction: As the coronavirus disease 2019 (COVID-19) pandemic progresses, identifying effective antiviral agents to treat the COVID-19 is of most urgency. Efficacy and safety of corticosteroids in patients with COVID-19 still are debated. Because high-quality randomized clinical trials (RCTs) on the use of corticosteroids for patients with COVID-19 recently were published recently, we aim to conduct a systematic review and meta-analysis of RCTs on corticosteroids therapy in patients with different disease severity to ascertain the effect on survival. Methods: We will undertake a comprehensive literature search among PubMed, EMBASE, Cochrane Library, medRxiv, and bioRxiv from their inception onwards to identify relevant RCTs. Two reviewers will independently extract data and conduct risk of bias assessments. The primary outcome is all-cause mortality, mortality of mechanically ventilated patients and patients who did not receive oxygen therapy. Secondary outcomes include need for mechanical ventilation or oxygen therapy and incidence of adverse outcomes. Heterogeneity of the estimates across studies will be assessed. Outcomes will be analyzed to pooled risk ratio and pertinent 95% confidence interval. A subgroup analysis will be conducted by disease severity to explore the source of heterogeneity. The systematic review and meta-analysis will be presented according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. Discussion: This systematic review will provide an overview of the current state of evidence concerning the effect of corticosteroids on survival of patients with COVID-19 depended on the disease severity. Also, this systematic review will show the limitations and strengths of the studies available in the literature, as well as recommendations for future avenues of research will be given. PROSPERO registration number: CRD42020227740.

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