Biomarkers Of Disease Severity Research Articles

High Sugar-Sweetened Beverage Consumption Is Associated with Increased Health Care Utilization in Patients with Inflammatory Bowel Disease: A Multiyear, Prospective Analysis

BackgroundDietary factors like sugar-sweetened beverage (SSB) consumption are known to influence disease course in a variety of illnesses; however, long-term outcomes are not well documented for inflammatory bowel disease. ObjectiveDoes high consumption of SSBs lead to high healthcare utilization (ie, hospitalizations and emergency department visits), inflammation, and disease severity in patients with inflammatory bowel disease? DesignA prospective cohort study was conducted from 2015 to 2019. Patients enrolled in the discovery study cohort were followed for 3 years, whereas patients in the validation cohort were followed for 2 years. They underwent nutrition assessment and received routine care. Dietary intakes of SSBs and fiber were quantified by a validated, self-reported questionnaire. Participants/settingFor the discovery study cohort, 1133 adult patients were recruited from the University of Pittsburgh Medical Center Digestive Disease Clinic in Pittsburgh, PA. Eligible patients had a preexisting diagnosis of Crohn’s disease or ulcerative colitis and had at least annual follow-up at this tertiary referral center. High SSB consumption was defined as 7 or more SSBs per week. Moderate was defined as > 2 but < 7 SSBs per week. Low SSB consumption was defined as 2 or fewer SSBs per week. Main outcome measuresPrimary outcome was time to hospitalization and emergency department visits. Secondary outcomes assessed laboratory markers of disease severity and inflammation. Tertiary outcomes assessed time to hospitalization and emergency department visits in a subsequent independent cohort of patients. Statistical analysis performedMultivariable logistic regression, Kaplan-Meier, and Cox proportional hazards modeling ResultsThe discovery cohort included of 1,133 adult patients with inflammatory bowel disease (58% women, 70% with Chron’s disease, 30% with ulcerative colitis, median age 46 years). Low SSB consumption, moderate SSB consumption, and high SSB consumption occurred in 57%, 17%, and 26% in the discovery cohort, respectively. Among patients without active disease at enrollment, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption (hazard ratio 1.55, 95% CI 1.06 to 2.27; and hazard ratio 1.53, 95% CI 1.10 to 2.13). In terms of disease severity and inflammatory biomarkers, high SSB consumption was associated with increase odds of elevated erythrocyte sedimentation rate (odds ratio 2.04, 95% CI 1.31 to 3.18), elevated C-reactive protein level (odds ratio 1.60, 95% CI, 1.07-2.37), eosinophilia (odds ratio 1.88, 95% CI 1.06 to 3.335), and monocytosis (odds ratio 1.81, 95% CI 1.18 to 2.79) when compared with low SSB consumption after adjusting for baseline differences. Lastly, the validation cohort produced similar results to our primary outcome (ie, high SSB consumption was associated with decreased time to hospitalization and emergency department visits when compared with low SSB consumption). ConclusionsHigh SSB consumption was associated with decreased time to hospitalization and emergency department visits. Furthermore, high SSB consumption is associated with disease severity biomarkers and inflammation. Prospective studies assessing the therapeutic influence of nutrition counseling and decreased SSB consumption on long-term inflammatory bowel disease clinical course are warranted.

Identification of Serum Interleukin 6 Levels as a Disease Severity Biomarker in Facioscapulohumeral Muscular Dystrophy

Background:Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common myopathies in adults, displaying a progressive, frequently asymmetric involvement of a typical muscles’ pattern. FSHD is associated with epigenetic derepression of the polymorphic D4Z4 repeat on chromosome 4q, leading to DUX4 retrogene toxic expression in skeletal muscles. Identifying biomarkers that correlate with disease severity would facilitate clinical management and assess potential FSHD therapeutics’ efficacy.Objectives:This study purpose was to analyze serum cytokines to identify potential biomarkers in a large cohort of adult patients with FSHD.Methods:We retrospectively measured the levels of 20 pro-inflammatory and regulatory cytokines in sera from 100 genetically confirmed adult FSHD1 patients. Associations between cytokine concentrations and various clinical scores were investigated. We then measured serum and muscle interleukin 6 (IL-6) levels in a validated FSHD-like mouse model, ranging in severity and DUX4 expression.Results:IL-6 was identified as the only cytokine with a concentration correlating with several clinical severity and functional scores, including Clinical Severity Score, Manual Muscle Testing sum score, Brooke and Vignos scores. Further, FSHD patients displayed overall IL-6 levels more than twice high as control, and patients with milder phenotypes exhibited lower IL-6 serum concentration than those with severe muscular weakness. Lastly, an FSHD-like mouse model analysis confirmed that IL-6 levels positively correlate with disease severity and DUX4 expression.Conclusions:Serum IL-6, therefore, shows promise as a serum biomarker of FSHD severity in a large cohort of FSHD1 adult patients.

Elevated serum globulin fraction as a biomarker of multiyear disease severity in inflammatory bowel disease.

Serum protein reflects albumin and globulin levels, both of which can be altered in inflammatory bowel disease (IBD). The implications of a high globulin fraction in IBD are unknown. We hypothesized that a high globulin fraction may function independently of albumin as a biomarker of disease severity in IBD patients over a multiyear period. This was an observational study from a prospective IBD registry of a tertiary care center. High globulin fraction was defined as an elevated globulin level >4 g/dL. Data collected included patient demographics, medication exposures, quality-of-life scores, disease activity, emergency department visits, telephone calls, hospitalizations, and IBD-related surgeries over a 4-year period. Comparisons between patients with a high globulin fraction and those without were performed using Pearson's chi-squared, Student's and Mann-Whitney tests. Multivariate analyses were used to assess the relationship between high globulin fraction and healthcare utilization. A total of 1767 IBD patients with a 4-year follow up were included: 53.5% female, mean age 48.4±15.1 years, and 65.4% with Crohn's disease. Of these patients, 446 (25.2%) presented with elevated globulin fraction. Patients with a high globulin fraction were more likely to be hospitalized during the study period. This result remained significant after multivariate analysis for both Crohn's disease patients and those with ulcerative colitis. A high globulin fraction is independently associated with greater disease severity and healthcare utilization in IBD patients, and may function as a routinely available biomarker of a more severe future disease trajectory.

Biomarkers of disease severity in patients with visceral leishmaniasis co-infected with HIV.

Visceral leishmaniasis (VL) is caused by the protozoan Leishmania spp, transmitted by sand fly bites. VL is one of the deadliest tropical infection diseases, yet the coinfection with HIV virus drastically increases relapses, treatment failure and mortality. The concomitant action of these two pathogens leads to high cellular activation independently of the progression to AIDS. In addition, microbial translocation and bacterial infections are thought to contribute worsening the clinical picture. Identifying biomarkers associated with disease severity is of interest for clinical management of patients with VL-HIV/AIDS. Thus, we analyzed in the sera several markers including interleukins (IL-1β, IL-6, IL-8, and IL-17), interferon-γ (IFN- γ), tumor necrosis factor (TNF), lipopolysaccharide (LPS), soluble CD14 (sCD14), macrophage migration inhibitory factor (MIF) and intestinal fatty acid-binding protein (IFABP). These markers were compared with disease severity in 24 patients with VL/HIV presenting different clinical outcomes. Disease severity was defined by the probability of death calculated using a score set system derived by the Kala-Cal® software. Probability of death ranged from 3.7% to 97.9%, with median of 28.8%. Five patients died (20%). At the univariate analysis, disease severity was correlated with TNF, IFN-γ and sCD14. LPS was positively correlated with sCD14 specifically in patients with low CD4+ count (CD4+ T-cell <200 cells/mL). Most importantly, the multivariate analysis including LPS, CD4+count and sCD14 showed that sCD14 was the only independent predictor for disease severity and death. Altogether, our results indicated that sCD14 is a powerful marker of pathogenicity and death for patients with VL-HIV/AIDS.

Volatile Organic Compounds in Human Breath.

A comprehensive analysis of volatile organic compounds (VOCs) from the exhaled breath sample is termed as breathomics. Breath samples are a complex mixture composed of a multitude of VOCs and other molecules. The analysis of total VOCs in exhaled breath provides a promising tool for the diagnosis of many diseases because it enables the observation of biochemical processes in the body in a non-invasive way. VOCs are produced in various physiological and pathophysiological conditions thus making it a potential biomarker for several diseases.

Alterations of Blood Immune Cells in Elderly Patients with COVID-19 and with or without Pre-Existing Type 2 Diabetes

Elderly individuals, especially those with pre-existing conditions like type 2 diabetes mellitus (T2DM), have a high risk for developing severe cases of COVID-19. The aim of this work was to characterize the alterations of blood immune cells (BIC) in patients with symptomatic COVID-19 and confirmed SARS-CoV-2 infection, ≥60 years and who needed hospitalization in the Centro de Salud Hospital of Tucuman, Argentina, during the second peak of the pandemic in Argentina. Ten patients were enrolled from December 2020 to May 2021. Blood samples were taken at the time of admission (day 0) and five days after (day 5) for routine laboratory tests and the characterization of BIC by flow cytometry. Most of the patients were men (70%) aged between 60 and 78 years. The 70% of patients had T2DM while 50% had arterial hypertension. At day 0, all the patients had increased neutrophils and inflammatory markers (C reactive protein and D-dimers) and reduced numbers of lymphocytes, HLA-DRhi monocytes, CD16+CD56+ NK cells, CD3+HLA−DR+CD25+ cells, CD4+ and CD8+ T cells in blood. Patients received a standard treatment for COVID-19 care (O2, corticosteroids and antibiotics). The hospital treatment normalized the levels of BIC (day 5) in 30% of patients who were those with no comorbidities. In patients with T2DM, BIC recovery was variable. In T2DM patients who required administration of plasma (30%), prolonged O2 therapy (40%) or referral to the intensive care unit (10%) significant reductions of CD16+CD56+, CD3+HLA−DR+CD25+, CD4+ and CD8+ cells were observed between days 0 and 5. In line with previous studies, our results show that absolute counts of major lymphocyte subsets in blood are significantly and substantially decreased during the course of severe COVID-19 disease in elderly patients. These BIC alterations may persist despite clinical care in elderly patients with T2DM. Further studies are needed to investigate the utility of early lymphocyte subset measurements as prognostic biomarkers of disease severity, mortality, and response to treatment in COVID-19 elderly patients with T2DM.

Association of thrombocytopenia with severity and outcome of COVID-19

Background: Laboratory parameters and their association with clinical outcomes in COVID-19 have been an area of focus of researchworldwide. The role of thrombocytopenia in assessing the disease severity and adverse outcome in patients with COVID-19 is not clearly established. The study aims to find the association of thrombocytopenia with the severity and outcome of COVID-19. Materials and Methods: This is a retrospective study conducted in the Department of Respiratory Medicine at a tertiary Centre. 120 RT-PCR confirmed COVID-19 patients, 40 from each category,&gt;18 years of age, admitted from July-September 2020 were included. Mann Whitney Test was used to compare the mean Platelet count between survivors and non-survivors in each category. Statistical significance was set at P&lt; 0.05. Results: Of 120 COVID-19 patients, 74 were males (61.67%) and the average age in all 3 categories varies from 49.63-to 54.60. There were 87 survivors (72.5%). A statistically significant association was found between low platelet count and the disease severity and mortality in patients with COVID-19 (P&lt; 0.001). The sensitivity of low platelet count at the time of admission in predicting the mortality was 80% in Category C patients with the cut-off value being 1.13 lakh per microliter. Conclusion: The degree of thrombocytopenia was more in patients with severe disease and non-survivors than in survivors of COVID-19. Thus, platelet count may serve as a simple and inexpensive biomarker for disease severity and risk of mortality in patients with COVID-19.

Laboratory Biomarkers Associated with Severity and Mortality of COVID-19.

Corona Virus Disease 2019 (COVID-19) emerged late 2019 and has become a global pandemic. There is an urgent need for identification of biomarkers to predict severity of the disease for early treatment and to avoid mortality especially in high-risk population. Therefore, the aim of this study is to investigate laboratory results in COVID-19 patients in Saudi Arabia to identify potential biomarkers correlated with disease severity. Clinical records of 200 patients diagnosed with COVID-19 from July to August 2020 at Jeddah East Hospital were retrospectively analyzed. Laboratory tests including coagulation parameters, D-dimer, kidney, cardiac, and liver enzymes were statistically investigated in patients admitted to wards and intensive care units (ICU). The majority of patients admitted to ward (156/200) were young (mean 47 years old) compared to those admitted to ICU (mean 60 years old), 14/44 passed away in the ICU. Magnesium was significantly (p < 0.05) elevated in the ICU group while blood urea nitrogen and creatinine level was significantly higher in deceased patients (p < 0.05). Lactate dehydrogenase results were high among all groups, compared to normal range, although its level significantly increased (p > 0.05) in ICU and death groups. Elevated lactate dehydrogenase, blood urea nitrogen and creatinine levels may increase the risk of ICU admission and death from COVID-19, which can be used as potential biomarkers for disease severity. Using these markers could help physicians choose the optimal therapeutical option and provide patients with better treatment.

Medulla oblongata volume as a promising predictor of survival in amyotrophic lateral sclerosis

BackgroundUnconventional magnetic resonance imaging studies of the brainstem have recently acquired a growing interest in amyotrophic lateral sclerosis (ALS) pathology since they provide a unique opportunity to evaluate motor tract degeneration and bulbar lower motor neuron involvement. The aim of this study was to investigate the role of brainstem structures as accurate biomarkers of disease severity and predictors of survival. Materials and MethodsA total of 60 ALS patients and 30 healthy controls subjects (CS) were recruited in this study. Patients were divided in two subgroups according to the onset of the disease: 42 spinal (S-ALS) and 18 bulbar (B-ALS). All subjects underwent 3D-structural MRI. Brainstem volume both of the entire cohort of ALS patients and S-ALS and B-ALS onset were compared with those of CS. In addition the two ALS subgroups were tested for differences in brainstem volumes.Volumetric, vertex-wise, and voxel-based approaches were implemented to assess correlations between MR structural features and clinical characteristics expressed as ALSFRS-r and its bulbar (ALSFSR-r-B) and spinal subscores (ALSFSR-r-S). ROC curves were performed to test the accuracy of midbrain, pons, and medulla oblongata volumes able to discriminate patients dichotomized into long and short survivors by using Two-Steps cluster analysis. Univariate and multivariate survival analyses were carried out to test the prognostic role of brainstem structures’ volume, trichotomized by applying a k-means clustering algorithm. ResultsBoth the entire cohort of ALS patients and B-ALS and S-ALS showed significant lower volumes of both medulla oblongata and pons compared to CS. Furthermore, B-ALS showed a significant lower volume of medulla oblongata, compared to S-ALS. Lower score of ALSFRS-r correlated to atrophy in the anterior compartment of midbrain, pons, and medulla oblongata, as well as in the posterior portion of only this latter region. ALSFSR-r-S positively correlated with shape deformation and density reduction of the anterior portion of the entire brainstem, along the corticospinal tracts. ALSFSR-r-B instead showed a positive correlation with shape deformation of the floor of the fourth ventricle in the medulla oblongata and the crus cerebri in the midbrain. Only medulla oblongata volume demonstrated a significant accuracy to discriminate long and short survivors ALS patients (ROC AUC 0.76, p < 0.001). Univariate and multivariate analysis confirmed the survival predictive role of the medulla oblongata (log rank test p: 0.003). DiscussionsOur findings suggest that brainstem volume may reflect the impairment of corticospinal and corticobulbar tracts as well as lower bulbar motor neurons. Furthermore, medulla oblongata could be used as an early predictor of survival in ALS patients.

Glycolithocholic Acid 3-Sulfate as Serum Biomarker for Disease Severity and Mortality in COVID-19 Patients: Mass Spectrometry Approach

Glycolithocholic Acid 3-Sulfate as Serum Biomarker for Disease Severity and Mortality in COVID-19 Patients: Mass Spectrometry Approach

Multiplex metal-detection based assay (MMDA) for COVID-19 diagnosis and identification of disease severity biomarkers.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 highlights the urgent need to develop sensitive methods for diagnosis and prognosis. To achieve this, multidimensional detection of SARS-CoV-2 related parameters including virus loads, immune response, and inflammation factors is crucial. Herein, by using metal-tagged antibodies as reporting probes, we developed a multiplex metal-detection based assay (MMDA) method as a general multiplex assay strategy for biofluids. This strategy provides extremely high multiplexing capability (theoretically over 100) compared with other reported biofluid assay methods. As a proof-of-concept, MMDA was used for serologic profiling of anti-SARS-CoV-2 antibodies. The MMDA exhibits significantly higher sensitivity and specificity than ELISA for the detection of anti-SARS-CoV-2 antibodies. By integrating the high dimensional data exploration/visualization tool (tSNE) and machine learning algorithms with in-depth analysis of multiplex data, we classified COVID-19 patients into different subgroups based on their distinct antibody landscape. We unbiasedly identified anti-SARS-CoV-2-nucleocapsid IgG and IgA as the most potently induced types of antibodies for COVID-19 diagnosis, and anti-SARS-CoV-2-spike IgA as a biomarker for disease severity stratification. MMDA represents a more accurate method for the diagnosis and disease severity stratification of the ongoing COVID-19 pandemic, as well as for biomarker discovery of other diseases.

Role of Neutrophil Extracellular Traps in COVID-19 Progression: An Insight for Effective Treatment.

The coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has resulted in a pandemic with over 270 million confirmed cases and 5.3 million deaths worldwide. In some cases, the infection leads to acute respiratory distress syndrome (ARDS), which is triggered by a cytokine storm and multiple organ failure. Clinical hematological, biochemical, coagulation, and inflammatory markers, such as interleukins, are associated with COVID-19 disease progression. In this regard, neutrophilia, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-albumin ratio (NAR), have emerged as promising biomarkers of disease severity and progression. In the pathophysiology of ARDS, the inflammatory environment induces neutrophil influx and activation in the lungs, promoting the release of cytokines, proteases, reactive oxygen species (ROS), and, eventually, neutrophil extracellular traps (NETs). NETs components, such as DNA, histones, myeloperoxidase, and elastase, may exert cytotoxic activity and alveolar damage. Thus, NETs have also been described as potential biomarkers of COVID-19 prognosis. Several studies have demonstrated that NETs are induced in COVID-19 patients, and that the highest levels of NETs are found in critical ones, therefore highlighting a correlation between NETs and severity of the disease. Knowledge of NETs signaling pathways, and the targeting of points of NETs release, could help to develop an effective treatment for COVID-19, and specifically for severe cases, which would help to manage the pandemic.

Functional Ex Vivo Testing of Alveolar Monocytes in Patients with Pneumonia-Related ARDS.

Biomarkers of disease severity might help with individualizing the management of patients with acute respiratory distress syndrome (ARDS). During sepsis, a sustained decreased expression of the antigen-presenting molecule human leucocyte antigen-DR (HLA-DR) on circulating monocytes is used as a surrogate marker of immune failure. This study aimed at assessing whether HLA-DR expression on alveolar monocytes in the setting of a severe lung infection is associated with their functional alterations. BAL fluid and blood from immunocompetent patients with pneumonia-related ARDS admitted between 2016 and 2018 were isolated in a prospective monocentric study. Alveolar and blood monocytes were immunophenotyped using flow cytometry. Functional tests were performed on alveolar and blood monocytes after in vitro lipopolysaccharide (LPS) stimulation. Phagocytosis activity and intracellular tumor necrosis factor (TNF) production were quantified using fluorochrome-conjugated-specific antibodies. Ten ARDS and seven non-ARDS control patients were included. Patients with pneumonia-related ARDS exhibited significantly lower HLA-DR expression both on circulating (p < 0.0001) and alveolar (p = 0.0002) monocytes. There was no statistically significant difference observed between patient groups (ARDS vs. non-ARDS) regarding both alveolar and blood monocytes phagocytosis activity. After LPS stimulation, alveolar (p = 0.027) and blood (p = 0.005) monocytes from pneumonia-related ARDS patients had a significantly lower intracellular TNF expression than non-ARDS patients. Monocytes from pneumonia-related ARDS patients have a deactivated status and an impaired TNF production capacity but display potent phagocytic activity. HLA-DR level expression should not be used as a surrogate marker of the phagocytic activity or the TNF production capacity of alveolar monocytes.

Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia

Background: The effects of immunomodulators in patients with Coronavirus Disease 2019 (COVID-19) pneumonia are still unknown. We investigated the cellular inflammatory and molecular changes in response to standard-of-care + pidotimod (PDT) and explored the possible association with blood biomarkers of disease severity. Methods: Clinical characteristics and outcomes, neutrophil-to-lymphocyte ratio (NLR), plasma and cell supernatant chemokines, and gene expression patterns after SARS-CoV-2 and influenza (FLU) virus in vitro stimulation were assessed in 16 patients with mild-moderate COVID-19 pneumonia, treated with standard of care and PDT 800 mg twice daily (PDT group), and measured at admission, 7 (T1), and 12 (T2) days after therapy initiation. Clinical outcomes and NLR were compared with age-matched historical controls not exposed to PDT. Results: Hospital stay, in-hospital mortality, and intubation rate did not differ between groups. At T1, NLR was 2.9 (1.7–4.6) in the PDT group and 5.5 (3.4–7.1) in controls (p = 0.037). In the PDT group, eotaxin and IL-4 plasma concentrations progressively increased (p < 0.05). Upon SARS-CoV-2 and FLU-specific stimulation, IFN-γ was upregulated (p < 0.05), while at genetic transcription level, Pathogen Recognition Receptors (TRLs) were upregulated, especially in FLU-stimulated conditions. Conclusions: Immunomodulation exerted by PDT and systemic corticosteroids may foster a restoration in the innate response to the viral infection. These results should be confirmed in larger RCTs.

Muscle magnetic resonance imaging in myotonic dystrophy type 1 (DM1): Refining muscle involvement and implications for clinical trials.

BackgroundOnly a few studies have reported muscle imaging data on small cohorts of patients with myotonic dystrophy type 1 (DM1). We aimed to investigate the muscle involvement in a large cohort of patients in order to refine the pattern of muscle involvement, to better understand the pathophysiological mechanisms of muscle weakness, and to identify potential imaging biomarkers for disease activity and severity.MethodsOne hundred and thirty‐four DM1 patients underwent a cross‐sectional muscle magnetic resonance imaging (MRI) study. Short tau inversion recovery (STIR) and T1 sequences in the lower and upper body were analyzed. Fat replacement, muscle atrophy and STIR positivity were evaluated using three different scales. Correlations between MRI scores, clinical features and genetic background were investigated.ResultsThe most frequent pattern of muscle involvement in T1 consisted of fat replacement of the tongue, sternocleidomastoideus, paraspinalis, gluteus minimus, distal quadriceps and gastrocnemius medialis. Degree of fat replacement at MRI correlated with clinical severity and disease duration, but not with CTG expansion. Fat replacement was also detected in milder/asymptomatic patients. More than 80% of patients had STIR‐positive signals in muscles. Most DM1 patients also showed a variable degree of muscle atrophy regardless of MRI signs of fat replacement. A subset of patients (20%) showed a ‘marbled’ muscle appearance.ConclusionsMuscle MRI is a sensitive biomarker of disease severity alsofor the milder spectrum of disease. STIR hyperintensity seems to precede fat replacement in T1. Beyond fat replacement, STIR positivity, muscle atrophy and a ‘marbled’ appearance suggest further mechanisms of muscle wasting and weakness in DM1, representing additional outcome measures and therapeutic targets for forthcoming clinical trials.

446. Prognostic Value of Absolute Lymphocyte Count for Disease Severity and Clinical Outcomes in Adult COVID-19 Inpatients

BackgroundLymphopenia has been reported as a relatively frequent finding in patients with coronavirus disease 2019 (COVID-19). This study aimed to assess the use of absolute lymphocyte count (ALC) as a prognostic biomarker for disease severity and clinical outcomes. MethodsA cohort of adult patients with COVID-19 admitted to Memorial Healthcare System, Hollywood, Florida from March 7, 2020 to January 18, 2021 was retrospectively analyzed. An absolute lymphocyte count (ALC) < 1.1 × 109/L was used as cutoff point to define lymphopenia. Correlations of ALC upon admission with age and serum levels of C-reactive protein, interleukin-6, lactate dehydrogenase, and creatinine were analyzed. Univariate and multivariate regression models were developed to assess the association of lymphopenia with the risk of ICU admission and clinical outcomes.Results4,485 hospitalized patients were included in the final analyses. Median age was 61 (interquartile range, 47-73) years and 2,311 (51.5%) were men. Lymphopenia was more frequent in patients admitted to the ICU compared to those that were not admitted to the ICU, with an odds ratio of 2.14 (95% confidence interval [CI], 1.78-2.56, p < .0001) (Figure 1). The actual value of the ALC was negatively correlated with age and serum levels of C-reactive protein, interleukin-6, lactate dehydrogenase, and creatinine (all p < 0.005). Patients with lymphopenia (n=2,409) compared to those without lymphopenia (n=2,076) had multivariable-adjusted odds ratios of 1.85 (95% CI, 1.53-2.24) for ICU admission, 2.08 (95% CI, 1.67-2.58) for intubation, 1.98 (95% CI, 1.31-3.00) for development of acute kidney failure, and 2.23 (95% CI, 1.79-2.79) for in-hospital mortality (Table 1). Analyses were adjusted for age, gender, race, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, malignancy, obesity, and smoking. ConclusionLymphopenia in adult COVID -19 hospitalized patients was associated with increased risk of disease severity (as evidenced by need for ICU admission) and poor clinical outcomes. Absolute lymphocyte count may help with prognostication in individuals hospitalized with COVID-19.Disclosures All Authors: No reported disclosures

Correlation between clinical-functional parameters and number of lobes involved in non-cystic fibrosis bronchiectasis.

BackgroundCurrently, the prognosis of bronchiectasis is based on different prognostic indicators, like BSI and FACED score, founded on clinical-demographic, functional and radiological criteria. Both scoring systems include the number of lobes involved in bronchiectasis, which represents an adverse prognostic index. Our study aimed to investigate the prognostic role of the clinical-functional parameters and the number of involved lobes ratio in adult bronchiectasis.MethodsThe study was conducted on 52 patients diagnosed with non-cystic fibrosis bronchiectasis (NCFB) between 2015 and 2017 who attended the Pneumology Unit of Monaldi Hospital in Naples, Italy. Correlations between clinical- functional parameters (BMI, smoking history, number of exacerbations in the previous year, spirometry, DLCO, ABG test, and 6MWT) and number of involved lobes were investigated.ResultsAt baseline, the number of exacerbations in the previous year had a statistically significant association with the number of involved lobes. Furthermore, at baseline, the radiological criterion was also negatively associated with some functional parameters (FEV1/FVC ratio e FEF25-75%). Statistical significance was lost during the follow up, demonstrating the effectiveness of the therapy.ConclusionsImaging extension represents a promising biomarker of disease severity as well as a helpful follow up tool for non-Cystic Fibrosis bronchiectasis (NCFB).

Anti-SARS-CoV-2 IgG responses are powerful predicting signatures for the outcome of COVID-19 patients

IntroductionThe COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. ObjectivesWe assumed that antibodies may serve as biomarkers for predicting the clinical outcome of hospitalized COVID-19 patients on admission. MethodsBy taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. ResultsNonsurvivors (n = 955) induced higher levels of IgG responses against most of non-structural proteins than survivors (n = 79) on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The area under curves (AUCs) for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. ConclusionsOur findings might have important implications for improving clinical management of COVID-19 patients.

Plasma gp96 is a Novel Predictive Biomarker for Severe COVID-19.

ABSTRACTEarly and effective identification of severe coronavirus disease 2019 (COVID-19) may allow us to improve the outcomes of associated severe acute respiratory illness with fever and respiratory symptoms. This study analyzed plasma concentrations of heat shock protein gp96 in nonsevere (including mild and typical) and severe (including severe and critical) patients with COVID-19 to evaluate its potential as a predictive and prognostic biomarker for disease severity. Plasma gp96 levels that were positively correlated with interleukin-6 (IL-6) levels were significantly elevated in COVID-19 patients admitted to the hospital but not in non-COVID-19 patients with less severe respiratory impairment. Meanwhile, significantly higher gp96 levels were observed in severe than nonsevere patients. Moreover, the continuous decline of plasma gp96 levels predicted disease remission and recovery, whereas its persistently high levels indicated poor prognosis in COVID-19 patients during hospitalization. Finally, monocytes were identified as the major IL-6 producers under exogenous gp96 stimulation. Our results demonstrate that plasma gp96 may be a useful predictive and prognostic biomarker for disease severity and outcome of COVID-19.IMPORTANCE Early and effective identification of severe COVID-19 may allow us to improve the outcomes of associated severe acute respiratory illness with fever and respiratory symptoms. Some heat shock proteins (Hsps) are released during oxidative stress, cytotoxic injury, and viral infection and behave as danger-associated molecular patterns (DAMPs). This study analyzed plasma concentrations of Hsp gp96 in nonsevere and severe patients with COVID-19. Significantly higher plasma gp96 levels were observed in severe than those in nonsevere patients, and its persistently high levels indicated poor prognosis in COVID-19 patients. The results demonstrate that plasma gp96 may be a useful predictive and prognostic biomarker for disease severity and outcome of COVID-19.

High Levels of Circulating IL-6 and IL-8 Signature can Predict COVID-19 Severity

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may trigger a cytokine storm, which is characterized by uncontrolled overproduction of proinflammatory cytokines. Objectives: We aimed to investigate the association between circulating levels of inflammatory cytokines and severity of coronavirus disease 2019 (COVID-19). Methods: This cross-sectional study included 46 severe and 32 mildly symptomatic COVID-19 patients. The serum levels of cytokines and chemokines were determined using the Bio-Plex ProTM Human Cytokine Screening Panel. Results: Out of a total of 78 patients with confirmed COVID-19, 54 (69.2%) were males, and 24 (30.8%) were females. The mean age was 43.1 ± 13.3 and 58.2 ± 15 in mild and severe patients, respectively. Severe patients were characterized by significant laboratory abnormalities, such as increased WBC (P = 0.002) and neutrophil counts (P = 0.001), higher levels of ALT (P = 0.03), AST (P = 0.002), LDH (P &lt; 0.001), urea (P = 0.013), ferritin (P &lt; 0.001), D-dimer (P = 0.042), CRP (P &lt; 0.001), and decreased lymphocyte (P &lt; 0.001) and platelet (P = 0.045) counts. The levels of IL-6, IL-8, IL-13, TNF-α, IFN-γ, MIP-1β, and MCP-1 increased in the severe group compared to the mild group. However, significant differences were observed only for IL-6 (P &lt; 0.001) and IL-8 (P &lt; 0.001) levels. Conclusions: Serum IL-6 and IL-8 levels can be used as potential prognostic biomarkers of disease severity in COVID-19 patients.