Multi-dimensional Assessment of IPF Across a Wide Range of Disease Severity

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

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Hidradenitis suppurativa: Wie die Partner von Betroffenen psychosozial beeinträchtigt werden

Karger Kompass Dermatologie ◽

10.1159/000516079 ◽

2021 ◽

pp. 1-3

Author(s):

Uwe Gieler

Keyword(s):

Disease Severity ◽

Social Life ◽

Hidradenitis Suppurativa ◽

Life Quality ◽

Psychosocial Burden ◽

Wide Range ◽

The Family ◽

The Mean ◽

Moderate Effect

Background: Hidradenitis suppurativa is a debilitating disease related to a great psychosocial burden in affected patients and subsequently also people around them. Patients’ partners as caregivers may indirectly experience wide range of devastating effects of the disease on their emotional and social life. Objective: The purpose of this study was to determine the QoL impairment in HS patients’ partners and to identify its aspects that are affected the most. Correlation between QoL burden and disease severity, duration, sex, age and smoking was also assessed. Methods: A total of 50 HS sufferers were assessed according to disease severity and their partners’ QoL was determined using the Family Dermatology Life Quality Index questionnaire. Results: The mean FDLQI for patients’ partners was 8.7 ± 6.8 points, indicating generally a moderate effect of HS on their life. Quality of partners’ life correlated significantly with disease severity but no correlation was found according to other factors. Conclusion: Hidradenitis suppurativa is a highly psychologically devastating disease not only for patients but also for their partners. It occurred to diminish partners’ QoL mostly by increasing daily expenditure but also other problems were often reported. Clinicians should be aware of these psychosocial implications, in order to provide optimal therapy of HS affected families by a multidisciplinary specialized management addressing both, patients and their cohabitants simultaneously.

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Development of a rapid functional assay that predicts GLUT1 disease severity

Neurology Genetics ◽

10.1212/nxg.0000000000000297 ◽

2018 ◽

Vol 4 (6) ◽

pp. e297 ◽

Cited By ~ 3

Author(s):

Sasha M. Zaman ◽

Saul A. Mullen ◽

Slavé Petrovski ◽

Snezana Maljevic ◽

Elena V. Gazina ◽

...

Keyword(s):

Glucose Uptake ◽

Disease Severity ◽

Glucose Transport ◽

Reference Sequence ◽

Functional Assay ◽

Clinical Assessments ◽

Missense Variants ◽

Wide Range ◽

Glut1 Deficiency ◽

Severe Group

ObjectiveTo examine the genotype to phenotype connection in glucose transporter type 1 (GLUT1) deficiency and whether a simple functional assay can predict disease outcome from genetic sequence alone.MethodsGLUT1 deficiency, due to mutations in SLC2A1, causes a wide range of epilepsies. One possible mechanism for this is variable impact of mutations on GLUT1 function. To test this, we measured glucose transport by GLUT1 variants identified in population controls and patients with mild to severe epilepsies. Controls were reference sequence from the NCBI and 4 population missense variants chosen from public reference control databases. Nine variants associated with epilepsies or movement disorders, with normal intellect in all individuals, formed the mild group. The severe group included 5 missense variants associated with classical GLUT1 encephalopathy. GLUT1 variants were expressed in Xenopus laevis oocytes, and glucose uptake was measured to determine kinetics (Vmax) and affinity (Km).ResultsDisease severity inversely correlated with rate of glucose transport between control (Vmax = 28 ± 5), mild (Vmax = 16 ± 3), and severe (Vmax = 3 ± 1) groups, respectively. Affinities of glucose binding in control (Km = 55 ± 18) and mild (Km = 43 ± 10) groups were not significantly different, whereas affinity was indeterminate in the severe group because of low transport rates. Simplified analysis of glucose transport at high concentration (100 mM) was equally effective at separating the groups.ConclusionsDisease severity can be partly explained by the extent of GLUT1 dysfunction. This simple Xenopus oocyte assay complements genetic and clinical assessments. In prenatal diagnosis, this simple oocyte glucose uptake assay could be useful because standard clinical assessments are not available.

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Baseline characteristics of idiopathic pulmonary fibrosis: analysis from the Australian Idiopathic Pulmonary Fibrosis Registry

European Respiratory Journal ◽

10.1183/13993003.01592-2016 ◽

2017 ◽

Vol 49 (2) ◽

pp. 1601592 ◽

Cited By ~ 70

Author(s):

Helen E. Jo ◽

Ian Glaspole ◽

Christopher Grainge ◽

Nicole Goh ◽

Peter M.A. Hopkins ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Disease Severity ◽

Large Population ◽

Underlying Disease ◽

National Registry ◽

Hazard Ratio ◽

Wide Range ◽

Baseline Characteristics

The prevalence of idiopathic pulmonary fibrosis (IPF), a fatal and progressive lung disease, is estimated at 1.25–63 out of 100 000, making large population studies difficult. Recently, the need for large longitudinal registries to study IPF has been recognised.The Australian IPF Registry (AIPFR) is a national registry collating comprehensive longitudinal data of IPF patients across Australia. We explored the characteristics of this IPF cohort and the effect of demographic and physiological parameters and specific management on mortality.Participants in the AIPFR (n=647, mean age 70.9±8.5 years, 67.7% male, median follow up 2 years, range 6 months–4.5 years) displayed a wide range of age, disease severity and co-morbidities that is not present in clinical trial cohorts. The cumulative mortality rate in year one, two, three and four was 5%, 24%, 37% and 44% respectively. Baseline lung function (forced vital capacity, diffusing capacity of the lung for carbon monoxide, composite physiological index) and GAP (gender, age, physiology) stage (hazard ratio 4.64, 95% CI 3.33–6.47, p<0.001) were strong predictors of mortality. Patients receiving anti-fibrotic medications had better survival (hazard ratio 0.56, 95% CI 0.34–0.92, p=0.022) than those not on anti-fibrotic medications, independent of underlying disease severity.The AIPFR provides important insights into the understanding of the natural history and clinical management of IPF.

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Temperature and Wetness-Duration Requirements for Grape Leaf and Cane Infection by Phomopsis viticola

Plant Disease ◽

10.1094/pdis.2003.87.7.832 ◽

2003 ◽

Vol 87 (7) ◽

pp. 832-840 ◽

Cited By ~ 21

Author(s):

O. Erincik ◽

L. V. Madden ◽

D. C. Ferree ◽

M. A. Ellis

Keyword(s):

Disease Severity ◽

Correlation Coefficients ◽

Phomopsis Viticola ◽

Average Temperature ◽

Growing Seasons ◽

Wide Range ◽

Maximum Temperatures ◽

Rain Events ◽

Grape Leaf ◽

The Relationship

In 1998 and 1999, controlled-environment studies were conducted in growth chambers to determine the temperature and wetness-duration parameters required for leaf and cane infection of grape by Phomopsis viticola. Greenhouse-grown ‘Catawba’ (Vitis labrusca) and ‘Seyval’ (French hybrid) grapes were inoculated with P. viticola and incubated at constant temperatures of 5, 10, 15, 20, 25, 30, and 35°C and at wetness durations of 5, 10, 15, and 20 h for each temperature. Data from each cultivar were analyzed by nonlinear regression analysis to determine the relationship between disease severity and temperature and wetness duration. A generalized form of the Analytis Beta model was found to provide the best fit to the data. Disease severity on leaves and canes increased with increasing wetness duration at most temperatures. Minimum and maximum temperatures for infection were around 5 and 35.5°C, respectively. Optimum temperatures for leaf and cane infection were between 16 and 20°C. In the 2000 and 2001 growing seasons, the generalized Beta model was validated in ‘Catawba’ and ‘Seyval’ vineyards by inoculating vines during natural rain events. Average temperature and hours of wetness for each event and inoculation were recorded and used in the model equation to predict disease severity on leaves and internodes. Correlation coefficients between observed disease severities following field inoculations and predicted disease severities for both cultivars were between 0.71 and 0.81 and always significant (P < 0.01). These results indicate that the model reliably predicted leaf and cane infection on both cultivars over a wide range of wetness durations and temperatures. The model may be useful in developing disease-forecasting systems for Phomopsis cane and leaf spot on grapes.

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Efficacy of Variable Tetraconazole Rates Against Cercospora beticola Isolates with Differing In Vitro Sensitivities to DMI Fungicides

Plant Disease ◽

10.1094/pdis-03-12-0255-re ◽

2012 ◽

Vol 96 (12) ◽

pp. 1749-1756 ◽

Cited By ~ 17

Author(s):

Melvin D. Bolton ◽

Viviana Rivera-Varas ◽

Luis E. del Río Mendoza ◽

Mohamed F. R. Khan ◽

Gary A. Secor

Keyword(s):

Sugar Beet ◽

Disease Severity ◽

Cercospora Beticola ◽

In Planta ◽

Sensitivity Testing ◽

In Vitro Sensitivity ◽

Wide Range ◽

Fungicide Efficacy ◽

Dmi Fungicides

Cercospora leaf spot (CLS) of sugar beet is caused by the fungus Cercospora beticola. CLS management practices include the application of the sterol demethylation inhibitor (DMI) fungicides tetraconazole, difenoconazole, and prothioconazole. Evaluating resistance to DMIs is a major focus for CLS fungicide resistance management. Isolates were collected in 1997 and 1998 (baseline sensitivity to tetraconazole, prothioconazole, or difenoconazole) and 2007 through 2010 from the major sugar-beet-growing regions of Minnesota and North Dakota and assessed for in vitro sensitivity to two or three DMI fungicides. Most (47%) isolates collected in 1997–98 exhibited 50% effective concentration (EC50) values for tetraconazole of <0.01 μg ml–1, whereas no isolates could be found in this EC50 range in 2010. Since 2007, annual median and mean tetraconazole EC50 values have generally been increasing, and the frequency of isolates with EC50 values >0.11 μg ml–1 increased from 2008 to 2010. In contrast, the frequency of isolates with EC50 values for prothioconazole of >1.0 μg ml–1 has been decreasing since 2007. Annual median difenoconazole EC50 values appears to be stable, although annual mean EC50 values generally have been increasing for this fungicide. Although EC50 values are important for gauging fungicide sensitivity trends, a rigorous comparison of the relationship between in vitro EC50 values and loss of fungicide efficacy in planta has not been conducted for C. beticola. To explore this, 12 isolates exhibiting a wide range of tetraconazole EC50 values were inoculated to sugar beet but no tetraconazole was applied. No relationship was found between isolate EC50 value and disease severity. To assess whether EC50 values are related to fungicide efficacy in planta, sugar beet plants were sprayed with various dilutions of Eminent, the commercial formulation of tetraconazole, and subsequently inoculated with isolates that exhibited very low, medium, or high tetraconazole EC50 values. The high EC50 isolate caused significantly more disease than isolates with medium or very low EC50 values at the field application rate and most reduced rates. Because in vitro sensitivity testing is typically carried out with the active ingredient of the commercial fungicide, we investigated whether loss of disease control was the same for tetraconazole as for the commercial product Eminent. The high EC50 isolate caused more disease on plants treated with tetraconazole than Eminent but disease severity was not different between plants inoculated with the very low EC50 isolate.

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COVID-19 :Correlation Between CRP and LDH to Disease Severity and Mortality In Hospitalized COVID-19 Patients

Medica Hospitalia : Journal of Clinical Medicine ◽

10.36408/mhjcm.v7i1a.467 ◽

2020 ◽

Vol 7 (1A) ◽

pp. 144-149

Author(s):

Rizal Muldani Tjahyadi ◽

Triwahju Astuti ◽

Aditya Sri Listyoko

Keyword(s):

Statistical Analysis ◽

Respiratory Failure ◽

Disease Severity ◽

Retrospective Cohort ◽

Pearson Correlation ◽

Lung Lesion ◽

Strong Positive Correlation ◽

Intensive Care Patients ◽

Wide Range ◽

Severe Group

Background and Objective:COVID–19 is a newly emerging disease and considered an emergency health problem, worldwide.It has a wide range of clinical features, from mild fever to severe respiratory failure that leads to a higher mortality rate. Previous studies state that CRPhas a very strong positive correlation with the diameter of the lung lesion, and in intensive care patients had a higher level of LDH. This study aims to determine the correlation between CRP, LDH and disease severity and mortality in hospitalized COVID-19 patients. Methods: We conducted a retrospective cohort, a single-center study including 69 laboratory-confirmed patients in our hospital in Malang City, Indonesia from April - June 2020. Result: Subjects consisted of 26 patients (37.7%) in the mild-moderate group and 43 patients in severe group (62.3%).Statistical analysis showed CRP and LDH associated with disease severity (p=0.011 and p<0.001). Analysis of CRPand LDH in survivor and non-survivior group showed that CRP and LDH also asscociated with mortality in hospitalized COVID-19 patients (p=0.034 and 0.002). We also evaluate CRP and LDH with degrees of hypoxemia by assessed P/F ratio. Statistical analysis showed that CRP did not correlate with degrees of hypoxemia (p=0.079) but LDH inverse correlate with degrees of hypoxemia (p<0.001, pearson correlation = -0,489) Conclusion: In our retrospective cohort study demonstrated LDH and CRP can be a crucial indicator to predict severity and mortality for hospitalized COVID-19 patients and LDH may usefull test for predict early identification of patients who become respiratory failure or ARDS. Keywords: COVID-19, LDH, CRP, P/F Ratio

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Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study

PLoS Medicine ◽

10.1371/journal.pmed.1003868 ◽

2021 ◽

Vol 18 (12) ◽

pp. e1003868

Author(s):

Shelly Karuna ◽

Shuying Sue Li ◽

Shannon Grant ◽

Stephen R. Walsh ◽

Ian Frank ◽

...

Keyword(s):

United States ◽

Disease Severity ◽

Disease Onset ◽

Clinical Manifestations ◽

The United States ◽

Immune Defense ◽

Severe Illness ◽

Pseudotyped Virus ◽

Wide Range ◽

Over Time

Background People infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) experience a wide range of clinical manifestations, from asymptomatic and mild illness to severe illness and death, influenced by age and a variety of comorbidities. Neutralizing antibodies (nAbs) are thought to be a primary immune defense against the virus. Large, diverse, well-characterized cohorts of convalescent individuals provide standardized values to benchmark nAb responses to past SARS-CoV-2 infection and define potentially protective levels of immunity. Methods and findings This analysis comprises an observational cohort of 329 HIV–seronegative adults in the United States (n = 167) and Peru (n = 162) convalescing from SARS-CoV-2 infection from May through October 2020. The mean age was 48 years (range 18 to 86), 54% of the cohort overall was Hispanic, and 34% identified as White. nAb titers were measured in serum by SARS-CoV-2.D614G Spike-pseudotyped virus infection of 293T/ACE2 cells. Multiple linear regression was applied to define associations between nAb titers and demographic variables, disease severity and time from infection or disease onset, and comorbidities within and across US and Peruvian cohorts over time. nAb titers peaked 28 to 42 days post-diagnosis and were higher in participants with a history of severe Coronavirus Disease 2019 (COVID-19) illness (p < 0.001). Diabetes, age >55 years, male sex assigned at birth, and, in some cases, body mass index were also independently associated with higher nAb titers, whereas hypertension was independently associated with lower nAb titers. nAb titers did not differ by race, underlying pulmonary disease or smoking. Two months post-enrollment, nAb ID50 (ID80) titers declined 3.5 (2.8)-fold overall. Study limitations in this observational, convalescent cohort include survivorship bias and missing early viral loads and acute immune responses to correlate with the convalescent responses we observed. Conclusions In summary, in our cohort, nAb titers after SARS-CoV-2 infection peaked approximately 1 month post-diagnosis and varied by age, sex assigned at birth, disease severity, and underlying comorbidities. Our data show great heterogeneity in nAb responses among people with recent COVID-19, highlighting the challenges of interpreting natural history studies and gauging responses to vaccines and therapeutics among people with recent infection. Our observations illuminate potential correlations of demographic and clinical characteristics with nAb responses, a key element for protection from COVID-19, thus informing development and implementation of preventative and therapeutic strategies globally. Trial registration ClinicalTrials.gov NCT04403880.

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Novel Coronavirus Infection: A Review on Haematological Markers of Disease Severity

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2020/45253.14036 ◽

2020 ◽

Author(s):

Angela Ogechukwu Ugwu ◽

Theresa Ukamaka Nwagha

Keyword(s):

Respiratory Failure ◽

Disease Severity ◽

White Cell Count ◽

Strong Relationship ◽

Ventilator Support ◽

Increased Risk ◽

Wide Range ◽

Coronavirus Infection ◽

Novel Coronavirus ◽

Prophylactic Anticoagulation

The Corornavirus Disease (COVID-19) virus infection has a wide range of presentation- asymptomatic, mild, severe and critical forms that often lead to death from respiratory failure. There is a strong relationship between the severity of COVID-19 infection and some haematological parameters. Patients often present with lymphocytopenia at diagnosis despite having a normal total white cell count. The degree of lymphocytopenia could predict the progression to pneumonia and subsequent need for ventilator support due to respiratory failure. Apart from lymphocytopenia, thrombocytopenia has been linked with increased severity of COVID-19 symptoms. The lymphocyte-platelet ratio has been found to a better marker for disease severity than isolated lymphocytopenia or thrombocytopenia. COVID-19 patients have been found to be at increased risk of Venous Thromboembolism (VTE). There is elevation of D-dimers, abnormalities of the Prothrombin Time (PT) and activated Partial Thromboplastin Time (aPTT) among hospitalised COVID-19 patients. This has necessitated the use of prophylactic anticoagulation even in the early phases of the infection.

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Variation in virulence and pathogenic specialization of Colletotrichum gloeosporioides isolates from Stylosanthes scabra cvv. Fitzroy and Seca

Australian Journal of Agricultural Research ◽

10.1071/ar9840653 ◽

1984 ◽

Vol 35 (5) ◽

pp. 653 ◽

Cited By ~ 14

Author(s):

RD Davis ◽

JAG Irwin ◽

DF Cameron

Keyword(s):

Disease Severity ◽

Direct Relationship ◽

Linear Growth ◽

Colletotrichum Gloeosporioides ◽

Linear Growth Rate ◽

Wide Range ◽

Rapid Spread ◽

Physiologic Races ◽

Stylosanthes Scabra ◽

Highly Virulent

A survey of anthracnose of Stylosanthes scabra cvv. Fitzroy and Seca, caused by Colletotrichurn gloeosponoides, at 31 sites in Queensland found a wide range of disease severity. Disease was present at each of the 26 sites surveyed for Fitzroy, and inoculation experiments with an isolate from each site indicated that the isolates varied markedly in their virulence on Fitzroy. Some of the variation in disease severity between sites could be explained by differences In virulence of the isolates. Disease was observed In only one of the five fields of Seca surveyed. When nine of the isolates from Fitzroy were tested on SIX genotypes of S. scabra, there was no evidence of pathogenic specialization, and all isolates were avirulent on Seca. The isolate from Seca, when tested on the same genotypes, was moderately virulent on Seca and highly virulent on Fitzroy, indicating further pathogenic specialization within the Type A forms of C. gloeosporioides in Australia. There was a direct relationship between mean linear growth rate of isolates from Fitzroy in pure culture, and virulence on Fitzroy. The recovery of highly virulent Isolates from pods of a Fitzroy seed crop is discussed in relation to the rapid spread of highly virulent physiologic races.

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