Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression.
14 May 2020-Journal of the Renin-Angiotensin-Aldosterone System (SAGE PublicationsSage UK: London, England)-Vol. 21, Iss: 2, pp 1470320320926899-1470320320926899
TL;DR: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression in patients with CO VID-19.
Abstract: 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 sev...
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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: 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 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.
4,408 citations
TL;DR: A systematic review and meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19 and the association between lymphocyte count and composite poor outcome was affected by age.
Abstract: Clinical and laboratory biomarkers to predict the severity of coronavirus disease 2019 (COVID-19) are essential in this pandemic situation of which resource allocation must be urgently prepared especially in the context of respiratory support readiness. Lymphocyte count has been a marker of interest since the first COVID-19 publication. We conducted a systematic review and meta-analysis in order to investigate the association of lymphocyte count on admission and the severity of COVID-19. We would also like to analyze whether patient characteristics such as age and comorbidities affect the relationship between lymphocyte count and COVID-19. Comprehensive and systematic literature search was performed from PubMed, SCOPUS, EuropePMC, ProQuest, Cochrane Central Databases, and Google Scholar. Research articles in adult patients diagnosed with COVID-19 with information on lymphocyte count and several outcomes of interest, including mortality, acute respiratory distress syndrome (ARDS), intensive care unit (ICU) care, and severe COVID-19, were included in the analysis. Inverse variance method was used to obtain mean differences and its standard deviations. Maentel-Haenszel formula was used to calculate dichotomous variables to obtain odds ratios (ORs) along with its 95% confidence intervals. Random-effect models were used for meta-analysis regardless of heterogeneity. Restricted-maximum likelihood random-effects meta-regression was performed for age, gender, cardiac comorbidity, hypertension, diabetes mellitus, COPD, and smoking. There were a total of 3099 patients from 24 studies. Meta-analysis showed that patients with poor outcome have a lower lymphocyte count (mean difference − 361.06 μL [− 439.18, − 282.95], p < 0.001; I2 84%) compared to those with good outcome. Subgroup analysis showed lower lymphocyte count in patients who died (mean difference − 395.35 μL [− 165.64, − 625.07], p < 0.001; I2 87%), experienced ARDS (mean difference − 377.56 μL [− 271.89, − 483.22], p < 0.001; I2 0%), received ICU care (mean difference − 376.53 μL [− 682.84, − 70.22], p = 0.02; I2 89%), and have severe COVID-19 (mean difference − 353.34 μL [− 250.94, − 455.73], p < 0.001; I2 85%). Lymphopenia was associated with severe COVID-19 (OR 3.70 [2.44, 5.63], p < 0.001; I2 40%). Meta-regression showed that the association between lymphocyte count and composite poor outcome was affected by age (p = 0.034). This meta-analysis showed that lymphopenia on admission was associated with poor outcome in patients with COVID-19.
464 citations
TL;DR: Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end‐organ damage are at higher risk of mortality due to COVID‐19 infection and should be managed with greater intensity.
Abstract: Mortality rates of coronavirus disease-2019 (COVID-19) continue to rise across the world. Information regarding the predictors of mortality in patients with COVID-19 remains scarce. Herein, we performed a systematic review of published articles, from 1 January to 24 April 2020, to evaluate the risk factors associated with mortality in COVID-19. Two investigators independently searched the articles and collected the data, in accordance with PRISMA guidelines. We looked for associations between mortality and patient characteristics, comorbidities, and laboratory abnormalities. A total of 14 studies documenting the outcomes of 4659 patients were included. The presence of comorbidities such as hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-3.1; P < .00001), coronary heart disease (OR, 3.8; 95% CI, 2.1-6.9; P < .00001), and diabetes (OR, 2.0; 95% CI, 1.7-2.3; P < .00001) were associated with significantly higher risk of death amongst patients with COVID-19. Those who died, compared with those who survived, differed on multiple biomarkers on admission including elevated levels of cardiac troponin (+44.2 ng/L, 95% CI, 19.0-69.4; P = .0006); C-reactive protein (+66.3 µg/mL, 95% CI, 46.7-85.9; P < .00001); interleukin-6 (+4.6 ng/mL, 95% CI, 3.6-5.6; P < .00001); D-dimer (+4.6 µg/mL, 95% CI, 2.8-6.4; P < .00001); creatinine (+15.3 µmol/L, 95% CI, 6.2-24.3; P = .001); and alanine transaminase (+5.7 U/L, 95% CI, 2.6-8.8; P = .0003); as well as decreased levels of albumin (-3.7 g/L, 95% CI, -5.3 to -2.1; P < .00001). Individuals with underlying cardiometabolic disease and that present with evidence for acute inflammation and end-organ damage are at higher risk of mortality due to COVID-19 infection and should be managed with greater intensity.
444 citations
Cites result from "Hypertension is associated with inc..."
...5‐fold increase in the odds of death from COVID‐19, supporting previous studies.(8,12) The second most prevalent comorbidity we assessed was diabetes, which was observed in approximately a quarter of all patients....
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TL;DR: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19, a critically ill patients critically ill with coronavirus disease-2019.
Abstract: Background:Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investiga...
371 citations
TL;DR: In this paper, the authors reviewed the existing literature and knowledge of ACE2 in COVID-19 setting and focused on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.
Abstract: COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is not only an enzyme but also a functional receptor on cell surfaces through which SARS-CoV-2 enters the host cells and is highly expressed in the heart, kidneys, and lungs and shed into the plasma. ACE2 is a key regulator of the renin-angiotensin-aldosterone system (RAAS). SARS-CoV-2 causes ACE/ACE2 balance disruption and RAAS activation, which leads ultimately to COVID-19 progression, especially in patients with comorbidities, such as hypertension, diabetes mellitus, and cardiovascular disease. Therefore, ACE2 expression may have paradoxical effects, aiding SARS-CoV-2 pathogenicity, yet conversely limiting viral infection. This article reviews the existing literature and knowledge of ACE2 in COVID-19 setting and focuses on its pathophysiologic involvement in disease progression, clinical outcomes, and therapeutic potential.
325 citations
References
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TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
TL;DR: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness, and patients often presented without fever, and many did not have abnormal radiologic findings.
Abstract: Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of...
22,622 citations
TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
20,189 citations
TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Abstract: Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
16,635 citations
TL;DR: It is demonstrated that SARS-CoV-2 uses the SARS -CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming, and it is shown that the sera from convalescent SARS patients cross-neutralized Sars-2-S-driven entry.
15,362 citations