scholarly journals Risk Factors for Severe Disease and Efficacy of Treatment in Patients Infected With COVID-19: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis

2020 ◽  
Vol 71 (16) ◽  
pp. 2199-2206 ◽  
Author(s):  
John J Y Zhang ◽  
Keng Siang Lee ◽  
Li Wei Ang ◽  
Yee Sin Leo ◽  
Barnaby Edward Young

Abstract The coronavirus disease 2019 (COVID-19) pandemic spread globally in the beginning of 2020. At present, predictors of severe disease and the efficacy of different treatments are not well understood. We conducted a systematic review and meta-analysis of all published studies up to 15 March 2020, which reported COVID-19 clinical features and/or treatment outcomes. Forty-five studies reporting 4203 patients were included. Pooled rates of intensive care unit (ICU) admission, mortality, and acute respiratory distress syndrome (ARDS) were 10.9%, 4.3%, and 18.4%, respectively. On meta-regression, ICU admission was predicted by increased leukocyte count (P < .0001), alanine aminotransferase (P = .024), and aspartate transaminase (P = .0040); elevated lactate dehydrogenase (LDH) (P < .0001); and increased procalcitonin (P < .0001). ARDS was predicted by elevated LDH (P < .0001), while mortality was predicted by increased leukocyte count (P = .0005) and elevated LDH (P < .0001). Treatment with lopinavir-ritonavir showed no significant benefit in mortality and ARDS rates. Corticosteroids were associated with a higher rate of ARDS (P = .0003).

BMJ Open ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. e021408 ◽  
Author(s):  
Tetsuro Kamo ◽  
Yoshitaka Aoki ◽  
Tatsuma Fukuda ◽  
Kiyoyasu Kurahashi ◽  
Hideto Yasuda ◽  
...  

IntroductionSeveral systematic reviews and meta-analyses have demonstrated that prolonged (≥16 hours) prone positioning can reduce the mortality associated with acute respiratory distress syndrome (ARDS). However, the effectiveness and optimal duration of prone positioning was not fully evaluated. To fill these gaps, we will first investigate the effectiveness of prone positioning compared with the conventional management of patients with ARDS, regarding outcomes using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Second, if statistical heterogeneity in effectiveness with regard to short-term mortality (intensive care unit death or ≤30-day mortality) is shown, we will conduct a meta-regression analysis to explore the association between duration and effectiveness, and determine the optimal duration of prone positioning.Method and analysisRelevant studies are collected using PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials and the WHO International Clinical Trials Platform Search Portal. Randomised controlled trials comparing prone and supine positioning in adults with ARDS will be included in the meta-analysis. Two independent investigators will screen trials obtained by search eligibility and extract data from selected studies to standardised data recording forms. For each selected trial, the risk of bias and quality of evidence will be evaluated using the GRADE system. Meta-regression analyses will be performed to identify the most important factors associated with short-term mortality, and subgroup analysis will be used to analyse the following: duration of mechanical ventilation in the prone position per day, patient severity, tidal volume and cause of ARDS. If heterogeneity or inconsistency among the studies is detected, subgroup analysis will be conducted on factors that may cause heterogeneity.Ethics and disseminationThis study requires no ethical approval. The results obtained from this systematic review and meta-analysis will be disseminated through international conference presentations and publication in a peer-reviewed journal.PROSPERO registration numberCRD42017078340.


2020 ◽  
Author(s):  
Divyajot Sadana ◽  
Simrat Kaur ◽  
Kesavan Sankaramangalam ◽  
Kinjal Banerjee ◽  
Matthew Siuba ◽  
...  

Abstract Background: Acute respiratory distress syndrome (ARDS) is a common occurrence in an intensive care unit. The reported mortality in studies evaluating acute respiratory distress syndrome is highly variable. The adherence to ventilatory specific and adjunctive therapies is also highly variable. We investigated the mortality of ARDS since the 2009 H1N1 pandemic and examined the adherence to ventilatory specific and adjunctive therapies.Methods: We performed a systematic search in MEDLINE and EMBASE using a highly sensitive criterion from January 2009 to May 2019. We then ran a proportional meta-analysis for mortality and a meta-regression analysis using certain variables to address heterogeneity. Results: We screened 5361 citations, of which 85 fully met inclusion criteria. The weighted pooled mortality of all 85 studies published from 2009 to 2019 was 38% (95% CI 35,40). Mortality was higher in observational studies [40% (95% CI 37, 42)] compared to RCTs [35% (95% CI 30,39)], (p=0.04) Significant variability exists in literature of reported tidal volumes, positive end expiratory pressures, plateau pressures, and use adjunctive therapies. The tidal volumes in our systematic review ranged from 5.8 to 8.9 ml/kg with a mean of 7.2 ml/kg. PEEP ranged from 4.6 to 16.1 cm H2O at the time of enrollment with a mean of 10.2 cm H2O. Reported plateau pressures ranged from 21.0 to 35.1 cm H2O, with a mean of 25.6 cm H2O. Higher reported initial PaO2/FiO2 ratios were associated with decreased mortality. A trend towards decreased mortality was seen with lower reported tidal volumes in the included studies.Conclusions: Over the last decade, the mortality in ARDS has marginally improved and there exists significant heterogeneity in the utilization of low tidal volume strategies, application of PEEP and the adoption of adjunctive therapies in the management of these patients in published literature.


2021 ◽  
Vol 8 ◽  
Author(s):  
Angelo Zinellu ◽  
Salvatore Sotgia ◽  
Ciriaco Carru ◽  
Arduino A. Mangoni

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.


2020 ◽  
Vol 21 (2) ◽  
pp. 147032032092689 ◽  
Author(s):  
Raymond Pranata ◽  
Michael Anthonius Lim ◽  
Ian Huang ◽  
Sunu Budhi Raharjo ◽  
Antonia Anna Lukito

Objective: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. Methods: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. Results: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I2, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I2, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I2,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55). Meta-regression analysis showed that gender ( p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79). Conclusion: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Nathalie Verónica Fernández Villalobos ◽  
Jördis Jennifer Ott ◽  
Carolina Judith Klett-Tammen ◽  
Annabelle Bockey ◽  
Patrizio Vanella ◽  
...  

Abstract Background Comprehensive evidence synthesis on the associations between comorbidities and behavioural factors with hospitalisation, intensive care unit (ICU) admission, and death due to COVID-19 is required for deriving national and international recommendations on primary targets for non-pharmacological interventions (NPI) and vaccination strategies. Methods We performed a rapid systematic review and meta-analysis on studies and publicly accessible data to quantify associations between predisposing health conditions, demographics, behavioural factors on the one hand and hospitalisation, ICU admission, and death from COVID-19 on the other hand. We provide ranges of reported and calculated effect estimates and pooled relative risks derived from a meta-analysis and meta-regression. Results Seventy-five studies were included in qualitative and 74 in quantitative synthesis, with study populations ranging from 19 to 44,672 COVID-19 cases. The risk of dying from COVID-19 was significantly associated with cerebrovascular [pooled relative risk (RR) 2.7 (95% CI 1.7–4.1)] and cardiovascular [RR 3.2 (CI 2.3–4.5)] diseases, hypertension [RR 2.6 (CI 2.0–3.4)], and renal disease [RR 2.5 (CI 1.8–3.4)], with high heterogeneity in pooled estimates, partly but not solely explained by age of study participants. For some comorbidities, our meta-regression showed a decrease in effect on the severity of disease with a higher median age of the study population. Compared to death, associations between several comorbidities and hospitalisation and ICU admission were less pronounced. Conclusions We obtained robust estimates on the magnitude of risk for COVID-19 hospitalisation, ICU admission, and death associated with comorbidities, demographic, and behavioural risk factors and show that these estimates are modified by age of study participants. This interaction is an important finding to be kept in mind for current vaccination strategies and for the protection of individuals with high risk for a severe COVID-19 course.


Author(s):  
Panagiotis Paliogiannis ◽  
Arduino Aleksander Mangoni ◽  
Michela Cangemi ◽  
Alessandro Giuseppe Fois ◽  
Ciriaco Carru ◽  
...  

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.


2021 ◽  
Vol 8 (1) ◽  
pp. e000774
Author(s):  
Fatema Alrashed ◽  
Robert Battat ◽  
Israa Abdullah ◽  
Aline Charabaty ◽  
Mohammad Shehab

BackgroundDuring COVID-19 pandemic, the safety of medical therapies for inflammatory bowel disease (IBD) in relation to COVID-19 has emerged as an area of concern. This study aimed to evaluate the association between IBD therapies and severe COVID-19 outcomes.MethodWe performed a systematic review and meta-analysis of all published studies from December 2019 to August 2021 to identify studies that reported severe COVID-19 outcomes in patients on current IBD therapies including 5-aminosalicylic acid (5-ASA), immunomodulators, corticosteroids, biologics, combination therapy, or tofacitinib.ResultsTwenty-two studies were identified. Corticosteroids (risk ratio (RR) 1.91 (95% CI 1.25 to 2.91, p=0.003)) and 5-ASA (RR 1.50 (95% CI 1.17 to 1.93, p=0.001)) were associated with increased risk of severe COVID-19 outcomes in patients with IBD patients. However, possible confounders for 5-ASA use were not controlled for. Sub-analysis showed that corticosteroids increased the risk of intensive care unit (ICU) admission but not mortality. Immunomodulators alone (RR 1.18 (95% CI 0.87 to 1.59, p=0.28)) or in combination with anti-TNFs ((RR 0.96 (95% CI 0.80 to 1.15, p=0.63)), tofacitinib (RR 0.81 (95% CI 0.49 to 1.33, p=0.40)) and vedolizumab ((RR 1.02 (95% CI 0.79 to 1.31, p=0.89)) were not associated with severe disease. Anti-TNFs (RR 0.47 (95% CI 0.40 to 0.54, p<0.00001)) and ustekinumab (RR 0.55 (95% CI 0.43 to 0.72, p<0.00001)) were associated with decreased risk of severe COVID-19.ConclusionIn patients with IBD, the risk of severe COVID-19 is higher among patients receiving corticosteroids. Corticosteroid use was associated with ICU admission but not mortality. The risk is also higher among patients receiving 5-ASAs. However, patient-level data were lacking and insufficient data existed for meta-regression analyses to adjust for confounding. Vedolizumab, tofacitinib, and immunomodulators alone or in combination with anti-TNF were not associated with severe disease. Anti-TNFs, and ustekinumab were associated with favourable outcomes.


2021 ◽  
Author(s):  
Daniel De-la-Rosa-Martínez ◽  
Marco Antonio Delaye-Martínez ◽  
Omar Yaxmehen Bello-Chavolla ◽  
Alejandro Sicilia-Andrade ◽  
Isaac David Juárez-Cruz ◽  
...  

Background: Post-acute COVID-19 syndrome (PACS) is a multi-system disease comprising persistent symptomatology after the acute phase of infection. Long-term PACS effects significantly impact patient outcomes, but their incidence remains uncharacterized due to high heterogeneity between studies. Therefore, we aimed to summarize published data on PACS, characterizing the clinical presentation, prevalence, and modifiers of prevalence estimates. Method: In this systematic review and meta-analysis, we research MEDLINE for original studies published from January 1st, 2020, to January 31st, 2021, that reported proportions of PACS manifestations. Studies were eligible for inclusion if they included patients aged ≥18 years with confirmed COVID-19 by RT-PCR or antigen testing and a minimum follow-up of 21 days. The prevalence of individual manifestations across studies was pooled using random-effects meta-analysis. For evaluating determinants of heterogeneity, meta-regression analysis was performed. This study was registered in PROSPERO (CRD42019125025). Results: After screening 1,235 studies, we included 29 reports for analysis. Twenty-seven meta-analyses were performed, and 61 long-term manifestations were described. The pooled prevalence of PACS was 56% (95%CI 45-66%), with the most common manifestations being diminished health status, fatigue, asthenia, dyspnea, myalgias, hyposmia and dysgeusia. Most of the included studies presented high heterogeneity. After conducting the meta-regression analysis, we identified that age, gender, number of comorbidities, and reported symptoms significantly modify the prevalence estimation of PACS long-term manifestations. Conclusion: PACS is inconsistently reported between studies, and population characteristics influence the prevalence estimates due to high heterogeneity. A systematized approach for the study of PACS is needed to characterize its impact adequately.


2017 ◽  
Vol 38 (11) ◽  
pp. 1319-1328 ◽  
Author(s):  
Philipp P. Kohler ◽  
Cheryl Volling ◽  
Karen Green ◽  
Elizabeth M. Uleryk ◽  
Prakesh S. Shah ◽  
...  

BACKGROUNDMortality associated with infections caused by carbapenem-resistantEnterobacteriaceae(CRE) is higher than mortality due to carbapenem-sensitive pathogens.OBJECTIVETo examine the association between mortality from bacteremia caused by carbapenem-resistant (CRKP) and carbapenem-sensitiveKlebsiella pneumoniae(CSKP) and to assess the impact of appropriate initial antibiotic therapy (IAT) on mortality.DESIGNSystematic review and meta-analysisMETHODSWe searched MEDLINE, EMBASE, CINAHL, and Wiley Cochrane databases through August 31, 2016, for observational studies reporting mortality among adult patients with CRKP and CSKP bacteremia. Search terms were related toKlebsiella, carbapenem-resistance, and infection. Studies including fewer than 10 patients per group were excluded. A random-effects model and meta-regression were used to assess the relationship between carbapenem-resistance, appropriateness of IAT, and mortality.RESULTSMortality was higher in patients who had CRKP bacteremia than in patients with CSKP bacteremia (15 studies; 1,019 CRKP and 1,148 CSKP patients; unadjusted odds ratio [OR], 2.2; 95% confidence interval [CI], 1.8–2.6; I2=0). Mortality was lower in patients with appropriate IAT than in those without appropriate IAT (7 studies; 658 patients; unadjusted OR, 0.5; 95% CI, 0.3–0.8; I2=36%). CRKP patients (11 studies; 1,326 patients; 8-year period) were consistently less likely to receive appropriate IAT (unadjusted OR, 0.5; 95% CI, 0.3–0.7; I2=43%). Our meta-regression analysis identified a significant association between the difference in appropriate IAT and mortality (OR per 10% difference in IAT, 1.3; 95% CI, 1.0–1.6).CONCLUSIONSAppropriateness of IAT is an important contributor to the observed difference in mortality between patients with CRKP bacteremia and patients with CSKP bacteremia.Infect Control Hosp Epidemiol2017;38:1319–1328


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