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

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

Clinical and Experimental Medicine ◽

10.1007/s10238-021-00686-z ◽

2021 ◽

Author(s):

Panagiotis Paliogiannis ◽

Arduino Aleksander Mangoni ◽

Michela Cangemi ◽

Alessandro Giuseppe Fois ◽

Ciriaco Carru ◽

...

Keyword(s):

Systematic Review ◽

Serum Albumin ◽

Disease Severity ◽

Meta Analysis ◽

Severe Disease ◽

Geographic Area ◽

Adverse Outcomes ◽

Poor Outcome ◽

Standard Mean Difference ◽

Meta Regression 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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Renin-angiotensin system blocker and outcomes of COVID-19: a systematic review and meta-analysis

Thorax ◽

10.1136/thoraxjnl-2020-215322 ◽

2021 ◽

pp. thoraxjnl-2020-215322

Author(s):

Hyun Woo Lee ◽

Chang-Hwan Yoon ◽

Eun Jin Jang ◽

Chang-Hoon Lee

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Severe Disease ◽

Renin Angiotensin System ◽

Angiotensin Ii Receptor ◽

Angiotensin System ◽

Risk Of Mortality ◽

Increased Risk ◽

All Cause Mortality ◽

Receptor Blockers

BackgroundThe association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.MethodsWe searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.ResultsACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence).ConclusionsACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.

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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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Active pulmonary tuberculosis and coronavirus disease 2019: A systematic review and meta-analysis

PLoS ONE ◽

10.1371/journal.pone.0259006 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0259006

Author(s):

Ashutosh Nath Aggarwal ◽

Ritesh Agarwal ◽

Sahajal Dhooria ◽

Kuruswamy Thurai Prasad ◽

Inderpaul Singh Sehgal ◽

...

Keyword(s):

Systematic Review ◽

Pulmonary Tuberculosis ◽

Patient Outcomes ◽

Meta Analysis ◽

Severe Disease ◽

Random Effects Models ◽

Tuberculosis Patients ◽

Active Pulmonary Tuberculosis ◽

Risk Of Mortality ◽

Related Mortality

Objective The proportion of COVID-19 patients having active pulmonary tuberculosis, and its impact on COVID-19 related patient outcomes, is not clear. We conducted this systematic review to evaluate the proportion of patients with active pulmonary tuberculosis among COVID-19 patients, and to assess if comorbid pulmonary tuberculosis worsens clinical outcomes in these patients. Methods We queried the PubMed and Embase databases for studies providing data on (a) proportion of COVID-19 patients with active pulmonary tuberculosis or (b) severe disease, hospitalization, or mortality among COVID-19 patients with and without active pulmonary tuberculosis. We calculated the proportion of tuberculosis patients, and the relative risk (RR) for each reported outcome of interest. We used random-effects models to summarize our data. Results We retrieved 3,375 citations, and included 43 studies, in our review. The pooled estimate for proportion of active pulmonary tuberculosis was 1.07% (95% CI 0.81%-1.36%). COVID-19 patients with tuberculosis had a higher risk of mortality (summary RR 1.93, 95% CI 1.56–2.39, from 17 studies) and for severe COVID-19 disease (summary RR 1.46, 95% CI 1.05–2.02, from 20 studies), but not for hospitalization (summary RR 1.86, 95% CI 0.91–3.81, from four studies), as compared to COVID-19 patients without tuberculosis. Conclusion Active pulmonary tuberculosis is relatively common among COVID-19 patients and increases the risk of severe COVID-19 and COVID-19-related mortality.

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Chinese Herbal Medicine (“3 Medicines and 3 Formulations”) for COVID-19: Rapid Systematic Review and Meta-Analysis

10.21203/rs.3.rs-209399/v2 ◽

2021 ◽

Author(s):

Xiao-Yang Hu ◽

Yangzihan Wang ◽

Junqiao Chen ◽

Trisha Greenhalgh ◽

Jon Wardle

Keyword(s):

Systematic Review ◽

Herbal Medicine ◽

Disease Severity ◽

Chinese Herbal Medicine ◽

English Language ◽

Meta Analysis ◽

Chinese Herbal ◽

Clinical Trial Registries ◽

Inverse Variance ◽

Secondary Outcomes

Abstract Background: To evaluate the evidence behind claims that Chinese Herbal Medicine, specifically “three medicines and three formulations” (3M3F, comprising Jinhua Qinggan, Lianhua Qingwen, Xuebijing, Qingfei Paidu, Huashi Baidu and Xuanfei Baidu), is an effective treatment for COVID-19. Methods: We searched PubMed, MEDLINE and CNKI databases, preprint servers, clinical trial registries and supplementary sources for Chinese- or English-language randomised trials or non-randomised studies with comparator groups, which tested the constituents of 3M3F in the treatment of COVID-19 up to September 2020. Primary outcome was change in disease severity. Secondary outcomes included various symptoms. Meta-analysis (using generic inverse variance random effects model) was performed when there were two or more studies reporting on the same symptom. Results: Of 607 articles identified, thirteen primary studies (six RCTs and seven retrospective non-randomised comparative studies) with 1467 participants met our final inclusion criteria. Studies were small and had significant methodological limitations, most notably potential bias in assessment of outcomes. No study convincingly demonstrated a statistically significant impact on change in disease severity. Eight studies reported sufficiently similar secondary outcomes to be included in a meta-analysis. Some statistically significant impacts on symptoms, chest CT manifestations, laboratory variables and length of stay were demonstrated, but such findings were sparse and many remain unreplicated.Conclusions: These findings neither support nor refute the claim that 3M3F alters the severity of COVID-19 or alleviates symptoms. More rigorous studies are required to properly ascertain the potential role of Chinese Herbal Medicine in COVID-19.Systematic review registration: This review was registered on PROSPERO (CRD42020187502) prior to data collection and analysis.

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Pre-arrest and intra-arrest prognostic factors associated with survival after in-hospital cardiac arrest: systematic review and meta-analysis

BMJ ◽

10.1136/bmj.l6373 ◽

2019 ◽

pp. l6373 ◽

Cited By ~ 9

Author(s):

Shannon M Fernando ◽

Alexandre Tran ◽

Wei Cheng ◽

Bram Rochwerg ◽

Monica Taljaard ◽

...

Keyword(s):

Systematic Review ◽

Cardiac Arrest ◽

Prognostic Factors ◽

Systematic Reviews ◽

English Language ◽

Data Extraction ◽

Meta Analysis ◽

Research Strategy ◽

Primary Analysis ◽

Hospital Cardiac Arrest

Abstract Objective To determine associations between important pre-arrest and intra-arrest prognostic factors and survival after in-hospital cardiac arrest. Design Systematic review and meta-analysis. Data sources Medline, PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systematic Reviews from inception to 4 February 2019. Primary, unpublished data from the United Kingdom National Cardiac Arrest Audit database. Study selection criteria English language studies that investigated pre-arrest and intra-arrest prognostic factors and survival after in-hospital cardiac arrest. Data extraction PROGRESS (prognosis research strategy group) recommendations and the CHARMS (critical appraisal and data extraction for systematic reviews of prediction modelling studies) checklist were followed. Risk of bias was assessed by using the QUIPS tool (quality in prognosis studies). The primary analysis pooled associations only if they were adjusted for relevant confounders. The GRADE approach (grading of recommendations assessment, development, and evaluation) was used to rate certainty in the evidence. Results The primary analysis included 23 cohort studies. Of the pre-arrest factors, male sex (odds ratio 0.84, 95% confidence interval 0.73 to 0.95, moderate certainty), age 60 or older (0.50, 0.40 to 0.62, low certainty), active malignancy (0.57, 0.45 to 0.71, high certainty), and history of chronic kidney disease (0.56, 0.40 to 0.78, high certainty) were associated with reduced odds of survival after in-hospital cardiac arrest. Of the intra-arrest factors, witnessed arrest (2.71, 2.17 to 3.38, high certainty), monitored arrest (2.23, 1.41 to 3.52, high certainty), arrest during daytime hours (1.41, 1.20 to 1.66, high certainty), and initial shockable rhythm (5.28, 3.78 to 7.39, high certainty) were associated with increased odds of survival. Intubation during arrest (0.54, 0.42 to 0.70, moderate certainty) and duration of resuscitation of at least 15 minutes (0.12, 0.07 to 0.19, high certainty) were associated with reduced odds of survival. Conclusion Moderate to high certainty evidence was found for associations of pre-arrest and intra-arrest prognostic factors with survival after in-hospital cardiac arrest. Systematic review registration PROSPERO CRD42018104795

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Are Fluoroquinolones or Macrolides Better for Treating Legionella Pneumonia? A Systematic Review and Meta-analysis

Clinical Infectious Diseases ◽

10.1093/cid/ciaa441 ◽

2020 ◽

Cited By ~ 1

Author(s):

Annie S Jasper ◽

Jackson S Musuuza ◽

Jessica S Tischendorf ◽

Vanessa W Stevens ◽

Shantini D Gamage ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Clinical Cure ◽

Data Extraction ◽

Meta Analysis ◽

Length Of Hospital Stay ◽

Legionella Pneumonia ◽

Risk Of Mortality ◽

Cure Time ◽

The Mean

Abstract Background The Infectious Diseases Society of America recommends either a fluoroquinolone or a macrolide as a first-line antibiotic treatment for Legionella pneumonia, but it is unclear which antibiotic leads to optimal clinical outcomes. We compared the effectiveness of fluoroquinolone versus macrolide monotherapy in Legionella pneumonia using a systematic review and meta-analysis. Methods We conducted a systematic search of literature in PubMed, Cochrane, Scopus, and Web of Science from inception to 1 June 2019. Randomized controlled trials and observational studies comparing macrolide with fluoroquinolone monotherapy using clinical outcomes in patients with Legionella pneumonia were included. Twenty-one publications out of an initial 2073 unique records met the selection criteria. Following PRISMA guidelines, 2 reviewers participated in data extraction. The primary outcome was mortality. Secondary outcomes included clinical cure, time to apyrexia, length of hospital stay (LOS), and the occurrence of complications. The review and meta-analysis was registered with PROSPERO (CRD42019132901). Results Twenty-one publications with 3525 patients met inclusion criteria. The mean age of the population was 60.9 years and 67.2% were men. The mortality rate for patients treated with fluoroquinolones was 6.9% (104/1512) compared with 7.4% (133/1790) among those treated with macrolides. The pooled odds ratio assessing risk of mortality for patients treated with fluoroquinolones versus macrolides was 0.94 (95% confidence interval, .71–1.25, I2 = 0%, P = .661). Clinical cure, time to apyrexia, LOS, and the occurrence of complications did not differ for patients treated with fluoroquinolones versus macrolides. Conclusions We found no difference in the effectiveness of fluoroquinolones versus macrolides in reducing mortality among patients with Legionella pneumonia.

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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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Sleep Duration in Relation to Cognitive Function among Older Adults: A Systematic Review of Observational Studies

Neuroepidemiology ◽

10.1159/000442418 ◽

2016 ◽

Vol 46 (1) ◽

pp. 57-78 ◽

Cited By ~ 24

Author(s):

Elizabeth E. Devore ◽

Francine Grodstein ◽

Eva S. Schernhammer

Keyword(s):

Systematic Review ◽

Older Adults ◽

Cognitive Function ◽

Sleep Duration ◽

Observational Studies ◽

English Language ◽

Data Extraction ◽

Meta Analysis ◽

Short Sleep ◽

Sleep Parameters

Context: Increasing evidence suggests that circadian and sleep parameters influence cognitive function with aging. Objective: To evaluate observational studies of sleep duration and cognition in older adults. Data Sources: A systematic review of OVID Medline and PsycINFO through September 2015, and review of bibliographies from studies identified. Study Selection: English-language articles reporting observational studies of sleep duration and cognitive function in older populations. Data Extraction: Data extraction by 2 authors using predefined categories of desired information. Results: Thirty-two studies met our inclusion criteria, with nearly two-thirds published in the past 4 years. One-third of studies indicated that extreme sleep durations were associated with worse cognition in older adults. More studies favored an association with long vs. short sleep durations (35 vs. 26% of studies, respectively). Four studies found that greater changes in sleep duration over time were related to lower cognition. Study design and analytic methods were very heterogeneous across studies; therefore, meta-analysis was not undertaken. Limitations: We reviewed English-language manuscripts only, with a qualitative summary of studies identified. Conclusions and Implications of Key Findings: Observational studies of sleep duration and cognitive function in older adults have produced mixed results, with more studies suggesting that long (rather than short) sleep durations are related to worse cognition. Studies more consistently indicate that greater changes in sleep duration are associated with poor cognition. Future studies should be prospectively designed, with objective sleep assessment and longer follow-up periods; intervention studies are also needed to identify strategies for promoting cognitive health with aging.

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