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      Anemia and iron metabolism in COVID-19: a systematic review and meta-analysis

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          Abstract

          Iron metabolism and anemia may play an important role in multiple organ dysfunction syndrome in Coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to evaluate biomarkers of anemia and iron metabolism (hemoglobin, ferritin, transferrin, soluble transferrin receptor, hepcidin, haptoglobin, unsaturated iron-binding capacity, erythropoietin, free erythrocyte protoporphyrine, and erythrocyte indices) in patients diagnosed with COVID-19, and explored their prognostic value. Six bibliographic databases were searched up to August 3rd 2020. We included 189 unique studies, with data from 57,563 COVID-19 patients. Pooled mean hemoglobin and ferritin levels in COVID-19 patients across all ages were 129.7 g/L (95% Confidence Interval (CI), 128.51; 130.88) and 777.33 ng/mL (95% CI, 701.33; 852.77), respectively. Hemoglobin levels were lower with older age, higher percentage of subjects with diabetes, hypertension and overall comorbidities, and admitted to intensive care. Ferritin level increased with older age, increasing proportion of hypertensive study participants, and increasing proportion of mortality. Compared to moderate cases, severe COVID-19 cases had lower hemoglobin [weighted mean difference (WMD), − 4.08 g/L (95% CI − 5.12; − 3.05)] and red blood cell count [WMD, − 0.16 × 10 12 /L (95% CI − 0.31; − 0.014)], and higher ferritin [WMD, − 473.25 ng/mL (95% CI 382.52; 563.98)] and red cell distribution width [WMD, 1.82% (95% CI 0.10; 3.55)]. A significant difference in mean ferritin levels of 606.37 ng/mL (95% CI 461.86; 750.88) was found between survivors and non-survivors, but not in hemoglobin levels. Future studies should explore the impact of iron metabolism and anemia in the pathophysiology, prognosis, and treatment of COVID-19.

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

            Abstract Objective To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died. Design Retrospective case series. Setting Tongji Hospital in Wuhan, China. Participants Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020. Main outcome measures Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms. Results The median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients. Conclusion Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.
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              Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis

              Highlights • COVID -19 cases are now confirmed in multiple countries. • Assessed the prevalence of comorbidities in infected patients. • Comorbidities are risk factors for severe compared with non-severe patients. • Help the health sector guide vulnerable populations and assess the risk of deterioration.
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                Author and article information

                Contributors
                taulant.muka@ispm.unibe.ch
                Journal
                Eur J Epidemiol
                Eur. J. Epidemiol
                European Journal of Epidemiology
                Springer Netherlands (Dordrecht )
                0393-2990
                1573-7284
                20 August 2020
                20 August 2020
                : 1-11
                Affiliations
                [1 ]GRID grid.10359.3e, ISNI 0000 0001 2331 4764, Public Health Department, Faculty of Medicine, , Bahcesehir University, ; Istanbul, Turkey
                [2 ]GRID grid.418078.2, ISNI 0000 0004 1764 0020, Public Health and Epidemiological Studies Group, , Cardiovascular Foundation of Colombia, ; Floridablanca, Colombia
                [3 ]GRID grid.7122.6, ISNI 0000 0001 1088 8582, Doctoral School of Health Sciences, , University of Debrecen, ; Debrecen, Hungary
                [4 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Institute of Social and Preventive Medicine (ISPM), , University of Bern, ; Mittelstrasse 43, 3012 Bern, Switzerland
                [5 ]GRID grid.11159.3d, ISNI 0000 0000 9650 2179, Institute of Child Health and Human Development (ICHHD), National Institutes of Health, , University of the Philippines Manila, ; Manila, Philippines
                [6 ]GRID grid.419770.c, Swiss Paraplegic Research, ; Nottwil, Switzerland
                [7 ]GRID grid.418078.2, ISNI 0000 0004 1764 0020, Research Group and Development of Nursing Knowledge (GIDCEN-FCV), Research Institute, , Cardiovascular Foundation of Colombia, ; Floriadablanca, Santander, Colombia
                [8 ]GRID grid.4830.f, ISNI 0000 0004 0407 1981, Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, , University of Groningen, ; Groningen, The Netherlands
                [9 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Public Health & Primary Care Library, University Library of Bern, , University of Bern, ; Bern, Switzerland
                [10 ]GRID grid.5734.5, ISNI 0000 0001 0726 5157, Department of Emergency Medicine, Inselspital, Bern University Hospital, , University of Bern, ; Bern, Switzerland
                [11 ]GRID grid.7122.6, ISNI 0000 0001 1088 8582, Public Health Research Institute, , University of Debrecen, ; Debrecen, Hungary
                Author information
                http://orcid.org/0000-0003-3235-3073
                Article
                678
                10.1007/s10654-020-00678-5
                7438401
                32816244
                8816782a-9dc6-4500-afda-f92473087379
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 May 2020
                : 14 August 2020
                Funding
                Funded by: University of Bern
                Categories
                Covid-19

                Public health
                anemia,hemoglobin,ferritin,iron,covid-19,prognosis
                Public health
                anemia, hemoglobin, ferritin, iron, covid-19, prognosis

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