scholarly journals Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission

2021 ◽  
Vol 12 ◽  
Author(s):  
Xianwu Pang ◽  
Pu Li ◽  
Lifeng Zhang ◽  
Lusheng Que ◽  
Min Dong ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Severe Disease ◽  
High Coverage ◽  
Reading Frame ◽  
Treatment And Prevention ◽  
High Prevalence ◽  
Enzyme Mutation ◽  
Editing Enzyme

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease.

scholarly journals Emerging SARS-CoV-2 mutation hotspots associated with clinical outcomes

2021 ◽  
Author(s):  
Xianwu Pang ◽  
Pu Li ◽  
Lifeng Zhang ◽  
Lusheng Que ◽  
Min Dong ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
High Frequency ◽  
Mortality Rates ◽  
Rna Seq ◽  
Related Factors ◽  
High Coverage ◽  
Immunogenic Property ◽  
N Protein ◽  
Mitochondrial Permeability ◽  
Treatment And Prevention

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes and related factors is critical for treatment and prevention. Here, we analyzed 209,551 high-coverage complete virus sequences and 321 RNA-seq samples to mine the mutations associated with clinical outcome in the SARS-CoV-2 genome. Several important hotspot variants were found to be associated with severe clinical outcomes. Q57H variant in ORF3a protein were found to be associated with higher mortality rate, and was high proportion in severe cases (39.36%) and 501Y.V2 strains (100%) but poorly proportional to asymptomatic cases (10.04%). T265I could change nsp2 structure and mitochondrial permeability, and evidently higher in severe cases (20.12%) and 501Y.V2 strains (100%) but lower in asymptomatic cases (1.43%). Additionally, R203K and G204R could decrease the flexibility and immunogenic property of N protein with high frequency among severe cases, VUI 202012/01 and 484K.V2 strains. Interestingly, the SARS-CoV-2 genome was more susceptible to mutation because of the high frequency of nt14408 mutation (which located in RNA polymerase) and the high expression levels of ADAR and APOBEC in severe clinical outcomes. In conclusion, several important mutation hotspots in the SARS-CoV-2 genome associated with clinical outcomes was found in our study, and that might correlate with different SARS-CoV-2 mortality rates.

scholarly journals COVID-19 and COPD: a narrative review of the basic science and clinical outcomes

2020 ◽  
Vol 29 (158) ◽  
pp. 200199 ◽  
Author(s):  
Andrew Higham ◽  
Alexander Mathioudakis ◽  
Jørgen Vestbo ◽  
Dave Singh
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Outcomes ◽  
Basic Science ◽  
Inhaled Corticosteroids ◽  
Older Individuals ◽  
Copd Patients ◽  
High Prevalence ◽  
Key Issues ◽  
Key Questions

The 2019 coronavirus disease (COVID-19) pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Clinical outcomes, including mortality, are worse in males, older individuals and patients with comorbidities. COPD patients are included in shielding strategies due to their susceptibility to virus-induced exacerbations, compromised pulmonary function and high prevalence of associated comorbidities. Using evidence from basic science and cohort studies, this review addresses key questions concerning COVID-19 and COPD. First, are there mechanisms by which COPD patients are more susceptible to SARS-CoV-2 infection? Secondly, do inhaled corticosteroids offer protection against COVID-19? And, thirdly, what is the evidence regarding clinical outcomes from COVID-19 in COPD patients? This up-to-date review tackles some of the key issues which have significant impact on the long-term outlook for COPD patients in the context of COVID-19.

Platelet Dysregulation in the Pathobiology of COVID-19

2021 ◽  
Author(s):  
Rebecca A. Mellema ◽  
Jacob Crandell ◽  
Aaron C. Petrey
Keyword(s):  
Immune Response ◽  
Severe Acute Respiratory Syndrome ◽  
Clinical Outcomes ◽  
Adhesion Molecules ◽  
Broad Spectrum ◽  
Current Knowledge ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Multiple Organs ◽  
Disease Present

AbstractCoronavirus disease 2019 (COVID-19) encompasses a broad spectrum of clinical manifestations caused by infection with severe acute respiratory syndrome coronavirus 2.Patients with severe disease present with hyperinflammation which can affect multiple organs which often include observations of microvascular and macrovascular thrombi. COVID-19 is increasingly recognized as a thromboinflammatory disease where alterations of both coagulation and platelets are closely linked to mortality and clinical outcomes. Although platelets are most well known as central mediators of hemostasis, they possess chemotactic molecules, cytokines, and adhesion molecules that are now appreciated as playing an important role in the regulation of immune response. This review summarizes the current knowledge of platelet alterations observed in the context of COVID-19 and their impact upon disease pathobiology.

Effect of Manipulation under Anesthesia of the First Knee in Staged Bilateral Total Knee Arthroplasty on Clinical Outcome and Satisfaction

2020 ◽  
Author(s):  
Jung-Won Lim ◽  
Yong-Beom Park ◽  
Dong-Hoon Lee ◽  
Han-Jun Lee
Keyword(s):  
Total Knee Arthroplasty ◽  
Patient Satisfaction ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Knee Arthroplasty ◽  
Knee Flexion ◽  
Functional Score ◽  
Manipulation Under Anesthesia ◽  
Total Knee

AbstractThis study aimed to evaluate whether manipulation under anesthesia (MUA) affect clinical outcome including range of motion (ROM) and patient satisfaction after total knee arthroplasty (TKA). It is hypothesized that MUA improves clinical outcomes and patient satisfaction after primary TKA. This retrospective study analyzed 97 patients who underwent staged bilateral primary TKA. MUA of knee flexion more than 120 degrees was performed a week after index surgery just before operation of the opposite site. The first knees with MUA were classified as the MUA group and the second knees without MUA as the control group. ROM, Knee Society Knee Score, Knee Society Functional Score, Western Ontario and McMaster Universities (WOMAC) score, and patient satisfaction were assessed. Postoperative flexion was significantly greater in the MUA group during 6 months follow-up (6 weeks: 111.6 vs. 99.8 degrees, p < 0.001; 3 months: 115.9 vs. 110.2 degrees, p = 0.001; 6 months: 120.2 vs. 117.0 degrees, p = 0.019). Clinical outcomes also showed similar results with knee flexion during 2 years follow-up. Patient satisfaction was significantly high in the MUA group during 12 months (3 months: 80.2 vs. 71.5, p < 0.001; 6 months: 85.8 vs. 79.8, p < 0.001; 12 months: 86.1 vs. 83.9, p < 0.001; 24 months: 86.6 vs. 85.5, p = 0.013). MUA yielded improvement of clinical outcomes including ROM, and patient satisfaction, especially in the early period after TKA. MUA in the first knee could be taken into account to obtain early recovery and to improve patient satisfaction in staged bilateral TKA.

Clinicopathological and Imaging Features Predictive of Clinical Outcome in Metaplastic Breast Cancer

2020 ◽  
Vol 16 (6) ◽  
pp. 729-738
Author(s):  
Ga Young Yoon ◽  
Joo Hee Cha ◽  
Hak Hee Kim ◽  
Hee Jung Shin ◽  
Eun Young Chae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Tumor Size ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Imaging Features ◽  
Peritumoral Edema ◽  
Imaging Findings ◽  
Metaplastic Breast Cancer

Background: Metaplastic breast cancer (MC) is a rare disease, thus it is difficult to study its clinical outcomes. Objective: To investigate whether any clinicopathological or imaging features were associated with clinical outcome in MC. Methods: We retrospectively evaluated the clinicopathological and imaging findings, and the clinical outcomes of seventy-two pathologically confirmed MCs. We then compared these parameters between triple-negative (TNMC) and non-TNMCs (NTNMC). Results: Oval or round shape, and not-circumscribed margin were the most common findings on mammography, ultrasound (US), and magnetic resonance imaging (MRI). It was mostly a mass without calcification on mammography, and revealed complex or hypoechoic echotexture, and posterior acoustic enhancement on US, and rim enhancement, wash-out kinetics, peritumoral edema, and intratumoral necrosis on MRI. Of all 72, 64 were TNMCs, and eight were NTNMCs. Clinicopathological and imaging findings were similar between the two groups, except that MRI showed peritumoral edema more frequently in TNMCs than NTNMCs (p=0.045). There were 21 recurrences and 13 deaths. Multivariable analysis showed that larger tumor size and co-existing DCIS were significantly predictive of Disease free survival (DFS), and larger tumor size and neoadjuvant chemotherapy were significantly predictive of overall survival (OS). Conclusion: MC showed characteristic imaging findings, and some variables associated with survival outcome may help to predict prognosis.

Novel Coronavirus Disease (COVID-19): A Narrative Review Based on Current Status

2020 ◽  
Vol 18 ◽  
Author(s):  
Rina Das ◽  
Dinesh Kumar Mehta ◽  
Meenakshi Dhanawat
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Symptoms ◽  
Virus Disease ◽  
Relevant Literature ◽  
World Health ◽  
Current Status ◽  
Future Research ◽  
Treatment And Prevention ◽  
First Case ◽  
Novel Coronavirus

Abstract:: A novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), appeared and expanded globally by the end of year in 2019 from Wuhan, China, causing severe acute respiratory syndrome. During its initial stage, the disease was called the novel coronavirus (2019-nCoV). It was named COVID-19 by the World Health Organization (WHO) on 11 February 2020. The WHO declared worldwide the SARS-CoV-2 virus a pandemic on March 2020. On 30 January 2020 the first case of Corona Virus Disease 2019 (COVID-19) was reported in India. Now in current situation the virus is floating in almost every part of the province and rest of the globe. -: On the basis of novel published evidences, we efficiently summarized the reported work with reference to COVID-19 epidemiology, pathogen, clinical symptoms, treatment and prevention. Using several worldwide electronic scientific databases such as Pubmed, Medline, Embase, Science direct, Scopus, etc were utilized for extensive investigation of relevant literature. -: This review is written in the hope of encouraging the people successfully with the key learning points from the underway efforts to perceive and manage SARS-CoV-2, suggesting sailent points for expanding future research.

scholarly journals Deep phenotyping classical galactosemia: clinical outcomes and biochemical markers

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Mendy M Welsink-Karssies ◽  
Sacha Ferdinandusse ◽  
Gert J Geurtsen ◽  
Carla E M Hollak ◽  
Hidde H Huidekoper ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Newborn Screening ◽  
Clinical Outcomes ◽  
Movement Disorders ◽  
Brain Mri ◽  
Primary Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Classical Galactosemia ◽  
Intellectual Outcome

Abstract Early diagnosis and dietary treatment do not prevent long-term complications, which mostly affect the central nervous system in classical galactosemia patients. The clinical outcome of patients is highly variable, and there is an urgent need for prognostic biomarkers. The aim of this study was first to increase knowledge on the natural history of classical galactosemia by studying a cohort of patients with varying geno- and phenotypes and second to study the association between clinical outcomes and two possible prognostic biomarkers. In addition, the association between abnormalities on brain MRI and clinical outcomes was investigated. Classical galactosemia patients visiting the galactosemia expertise outpatient clinic of the Amsterdam University Medical Centre were evaluated according to the International Classical Galactosemia guideline with the addition of an examination by a neurologist, serum immunoglobulin G N-glycan profiling and a brain MRI. The biomarkers of interest were galactose-1-phosphate levels and N-glycan profiles, and the clinical outcomes studied were intellectual outcome and the presence or absence of movement disorders and/or primary ovarian insufficiency. Data of 56 classical galactosemia patients are reported. The intellectual outcome ranged from 45 to 103 (mean 77 ± 14) and was &lt;85 in 62%. Movement disorders were found in 17 (47%) of the 36 tested patients. In females aged 12 years and older, primary ovarian insufficiency was diagnosed in 12 (71%) of the 17 patients. Significant differences in N-glycan peaks were found between controls and patients. However, no significant differences in either N-glycans or galactose-1-phosphate levels were found between patients with a poor (intellectual outcome &lt; 85) and normal intellectual outcome (intellectual outcome ≥ 85), and with or without movement disorders or primary ovarian insufficiency. The variant patients detected by newborn screening, with previously unknown geno- and phenotypes and currently no long-term complications, demonstrated significantly lower galactose-1-phospate levels than classical patients (P &lt; 0.0005). Qualitative analysis of the MRI’s demonstrated brain abnormalities in 18 of the 21 patients, more severely in patients with a lower intellectual outcome and/or with movement disorders. This study demonstrates a large variability in clinical outcome, which varies from a below average intelligence, movement disorders and in females primary ovarian insufficiency to a normal clinical outcome. In our cohort of classical galactosemia patients, galactose-1-phosphate levels and N-glycan variations were not associated with clinical outcomes, but galactose-1-phosphate levels did differentiate between classical and variant patients detected by newborn screening. The correlation between brain abnormalities and clinical outcome should be further investigated by quantitative analysis of the MR images. The variability in clinical outcome necessitates individual and standardized evaluation of all classical galactosemia patients.

scholarly journals 688 Pediatric Obstructive Sleep Apnea (OSA) and COVID-19-Related Adverse Clinical Outcomes

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A269-A269
Author(s):  
Vaishal Shah ◽  
Nancy Foldvary-Schaefer ◽  
Lu Wang ◽  
Lara Jehi ◽  
Cynthia Pena Obrea ◽  
...  
Keyword(s):  
High Risk ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Pediatric Patients ◽  
Control Design ◽  
Supplemental Oxygen ◽  
Case Control ◽  
World Health ◽  
Invasive Ventilation ◽  
High Flow Oxygen

Abstract Introduction The relationship of OSA and human coronavirus (COVID-19) in the pediatric population is unknown. We postulate that OSA is associated with SARS-CoV-2 positivity and with adverse COVID-19 outcomes in children. Methods A retrospective review of 120 consecutive patients (&lt;18 years) with prior polysomnogram (PSG) and COVID-19 testing from the Cleveland Clinic COVID-19 registry was conducted. Using a case control design of SARS-CoV-2 positive and negative pediatric patients, we examined COVID-19 and pre-existing OSA (dichotomized AHI≥1) using logistic (OR,95%CI) regression and as continuous measures: AHI, oxygen(SpO2) nadir, %time SpO2&lt;90%) using linear regression(beta+/-SE). In those positive for SARS-CoV-2(cases only), we assessed the association of OSA and World Health Organization(WHO) COVID-19 clinical outcome composite score (hospitalization, requiring supplemental oxygen, non-invasive ventilation/high-flow oxygen, invasive ventilation/ECMO or death) using Wilcoxon rank sum test for ordinal data. Results Cases (n=36) were 11.8±4.4 years, 61% male, 27.8% black and 88.9% with OSA, while 85.7% of controls (n=84) had OSA. OSA was not associated with increased SARS-CoV-2 positivity: OR=1.33(0.40, 4.45,p=0.64). No significant difference between cases and controls for mean AHI 3.7(1.5,6.0) vs 3.5(1.5,7.1),p=0.91,SpO2 nadir 88.6±5.4 vs 89.1±4.4,p=0.58,%time SpO2&lt;90% 0.05[0.00,1.00) vs 0.10 (0.00,1.00, p=0.65) respectively was noted. WHO-7 COVID-19 clinical outcome did not meet statistical significance in relation to OSA due to the low event frequency (p=0.49). Of note, those with OSA vs without OSA had a higher WHO-7 outcome score of 2 vs 0 and prevalence of hospitalization: 12.5 vs 0% respectively. Of hospitalized patients, the following was observed: 23% had moderate/severe OSA vs 4.3% mild OSA, 50% required supplemental oxygen and 25% required intubation/invasive ventilation. No deaths or readmissions were reported. High risk conditions included: 75% obesity, 50% asthma, 25% sickle cell disease and 25% hypoplastic left heart. Conclusion In this first report of which we are aware focused on COVID-19 in pediatric OSA, we use a case control design leveraging COVID-19 and sleep laboratory registries. Albeit not statistically significant, pediatric patients with OSA had a higher percentage of worse clinical outcomes. Larger network studies are needed to clarify whether poorer COVID-19 outcomes may be attributable to OSA or modulated via high risk health conditions. Support (if any):

scholarly journals Anti-phospholipid syndrome and COVID-19 thrombosis: connecting the dots

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Moon Ley Tung ◽  
Bryce Tan ◽  
Robin Cherian ◽  
Bharatendu Chandra
Keyword(s):  
Endothelial Dysfunction ◽  
Severe Acute Respiratory Syndrome ◽  
Potential Role ◽  
Molecular Mimicry ◽  
Thromboembolic Events ◽  
The Past ◽  
High Prevalence ◽  
Connecting The Dots ◽  
Anti Phospholipid Syndrome

Abstract As the coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide, it has emerged as a leading cause of mortality, resulting in &gt;1 million deaths over the past 10 months. The pathophysiology of COVID-19 remains unclear, posing a great challenge to the medical management of patients. Recent studies have reported an unusually high prevalence of thromboembolic events in COVID-19 patients, although the mechanism remains elusive. Several studies have reported the presence of aPLs in COVID-19 patients. We have noticed similarities between COVID-19 and APS, which is an autoimmune prothrombotic disease that is often associated with an infective aetiology. Molecular mimicry and endothelial dysfunction could plausibly explain the mechanism of thrombogenesis in acquired APS. In this review, we discuss the clinicopathological similarities between COVID-19 and APS, and the potential role of therapeutic targets based on the anti-phospholipid model for COVID-19 disease.

Discharge heart rate and clinical outcomes in hospitalized heart failure patients with coexisted atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Xing ◽  
X Bai ◽  
J Li
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Clinical Outcome ◽  
Confidence Interval ◽  
Clinical Outcomes ◽  
Beta Blockers ◽  
Funding Source ◽  
Proportional Hazard ◽  
Cox Proportional Hazard

Abstract Background Whether discharge heart rate for hospitalized heart failure (HF) patients with coexisted atrial fibrillation (AF) is associated with long-term clinical outcomes and whether this association differs between patients with and without beta-blockers have not been well studied. Purpose We investigated the associations between discharge heart rate and clinical outcomes in hospitalized HF patients with coexisted AF, while stratified to beta-blockers at discharge. Methods The study cohort included 1631 HF patients hospitalized primarily with AF, which was from the China PEACE Prospective Heart Failure Study. Clinical outcome was 1-year combined all-cause mortality and HF hospitalization after discharge. We analyzed association between outcome and heart rate at discharge with restricted cubic spline and Cox proportional hazard ratios (HR). Results The median age was 68 (IQR: 60- 77) years, 41.9% were women, discharge heart rate was (median (IQR)) 75 (69- 84) beats per minute (bpm), and 60.2% received beta-blockers at discharge. According to the result of restricted cubic spline plot, the relationship between discharge heart rate and clinical outcome may be nonlinear (P&lt;0.01). Based on above result, these patients were divided into 3 groups: lowest &lt;65 bpm, middle 65–86 bpm and highest ≥87 bpm, clinical outcomes occurred in 128 (64.32%), 624 (53.42%) and 156 (59.32%) patients in the lowest, middle, and highest groups respectively. In the Cox proportional hazard analysis, the lowest and highest groups were associated with increased risks of clinical outcome compared with the middle group (HR: 1.289, 95% confidence interval (CI): 1.056 - 1.573, p=0.013; HR: 1.276, 95% CI: 1.06 - 1.537, p=0.01, respectively). And a significant interaction between discharge heart rate and beta-blocker use was observed (P&lt;0.001 for interaction). Stratified analysis showed the lowest group was associated with increased risks of clinical outcomes in patients with beta-blockers (HR: 1.584, 95% confidence interval (CI): 1.215–2.066, p=0.001). Conclusion There may be a U-curve relationship between discharge heart rate and clinical outcomes in hospitalized HF patients with coexisted AF. They may have the best clinical outcomes with heart rates of 65 - 86 bpm. And strict heart rate control (&lt;65 bpm) may be avoided for patients who discharge with beta-blockers. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the National Key Research and Development Program (2017YFC1310803) from the Ministry of Science and Technology of China; the CAMS Innovation Fund for Medical Science (2017-I2M-B&R-02); the 111 Project from the Ministry of Education of China (B16005).

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