Combined Indexes of Serum NLR, CRP, LDH, IL-6 and D-Dimer Levels are a Biomarker of Disease Severity and Prognostic Predictor in Patients with Coronavirus Disease 2019

Abstract Background: Coronavirus disease-2019 (COVID-19) has become a worldwide emergency and has had a severe impact on human health. Inflammatory factors have the potential to either enhance the efficiency of host immune responses or damage the host organs with immune overreaction in COVID-19. Therefore, there is an urgent need to investigate the functions of inflammatory factors and serum markers that participate in disease progression. Methods: In total, 54 COVID-19 patients were enrolled in this study. Disease severity was evaluated by clinical evaluation, laboratory tests, and computed tomography (CT) scans. Data were collected at: admission, 3–5 days after admission, when severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection became negative, and composite endpoint. Results: We found that the positive rate in sputum was three times higher than that in throat swabs. Higher levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer (D-D), interleukin-6 (IL-6) and neutrophil-to-lymphocyte (NLR) or lower lymphocyte counts suggested more severe disease, and the levels of cytokines and serum markers were intrinsically correlated with disease progression. When SARS-CoV-2 RNA detection became negative, the receiver operating characteristic (ROC) curve demonstrated that LDH had the highest sensitivity independently, and four indicators (NLR, CRP, LDH, and D-D) when combined had the highest sensitivity in distinguishing critically ill patients from mild ones. Conclusions: Monitoring dynamic changes in NLR, CRP, LDH, IL-6, and D-D levels, combined with CT imaging and viral RNA detection in sputum, could aid in severity evaluation and prognosis prediction and facilitate COVID-19 treatment.

Download Full-text

Clinical Characteristic of Thoracic Malignancy Patients with Coronavirus Disease 2019 Related to Mitigation Strategy in Dharmais National Cancer Center Hospital, Indonesia

Open Access Macedonian Journal of Medical Sciences ◽

10.3889/oamjms.2021.6525 ◽

2021 ◽

Vol 9 (B) ◽

pp. 692-697

Author(s):

Arif Hanafi ◽

Noorwati Soetandyo ◽

Achmad Mulawarman Jayusman ◽

Leovinna Widjaja ◽

Fifi Dwijayanti ◽

...

Keyword(s):

Cancer Patients ◽

Disease Severity ◽

Poor Prognosis ◽

Severe Disease ◽

Mitigation Strategy ◽

Cancer Center ◽

P Value ◽

Lymphocyte Ratio ◽

Thoracic Malignancy ◽

D Dimer

Aim: To describe the clinical data and disease severity of thoracic malignancy patients with COVID-19 and its relation to the mitigation process at the Dharmais National Cancer Center, Indonesia. Methods: Total 5256 cancer patients registered from May 2020 to March 2021. There were 681 cancer patients diagnosed with COVID-19. Forty-five thoracic malignancy patients were enrolled. Data from medical records were obtained at the Dharmais Cancer Hospital, then analyzed using SPSS version 25. Comparative result was considered significant, as p-value < 0.05. Results: There were 12.9% of total patients registered infected by COVID-19, which 6% with thoracic malignancy dominated by Non-small cell lung carcinoma (57.8%). Patients who have asymptomatic (31.1%), mild (13.3%), and moderate COVID-19 disease (8.9%) were alive. Patient with severe disease (46.7%) tend to deteriorate. Neutrophilia (mean 78.0%), lymphopenia (mean 13.0%), high neutrophil to lymphocyte ratio (mean 13.1), hyperuricemia (mean 31.6 mg/dL), high fibrinogen (mean 521.7 mg/dL), and high d-dimer (mean 3821.6 ng/mL) were significantly associated with disease severity (p-value < 0.05). Conclusions: Only small number of cancer patients affected by COVID-19 and mostly do not progress to severe disease, showing the strict mitigation strategy was successful. Severe disease patients have a poor prognosis, with neutrophilia, lymphopenia, high neutrophil to lymphocyte ratio, hyperuricemia, high fibrinogen, and high d-dimer may be valuable for predicting poor prognosis.

Download Full-text

Establishment of a clinical nomogram model to predict the progression of COVID-19 to severe disease

10.21203/rs.3.rs-44136/v1 ◽

2020 ◽

Author(s):

changli tu ◽

Guojie Wang ◽

Cuiyan Tan ◽

Meizhu Chen ◽

Zijun Xiang ◽

...

Keyword(s):

Disease Progression ◽

Selection Process ◽

Severe Disease ◽

Area Under The Curve ◽

Training Dataset ◽

Validation Dataset ◽

Efficient Manner ◽

And Performance ◽

Sensitivity Specificity ◽

D Dimer

Abstract Background Coronavirus disease 2019 (COVID-19) is a worldwide public health pandemic with a high mortality rate, among severe cases. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. It is important to ensure early detection of the virus to curb disease progression to severe COVID-19. This study aimed to establish a clinical-nomogram model to predict the progression to severe COVID-19 in a timely, efficient manner. Methods This retrospective study included 202 patients with COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University and Shiyan Taihe Hospital from January 17 to April 30, 2020. The patients were randomly assigned to the training dataset (n = 163, with 43 progressing to severe COVID-19) or the validation dataset (n = 39, with 10 progressing to severe COVID-19) at a ratio of 8:2. The optimal subset algorithm was applied to filter for the clinical factors most relevant to the disease progression. Based on these factors, the logistic regression model was fit to distinguish severe (including severe and critical cases) from non-severe (including mild and moderate cases) COVID-19. Sensitivity, specificity, and area under the curve (AUC) were calculated using the R software package to evaluate prediction performance. A clinical nomogram was established and performance assessed with the discrimination curve. Results Risk factors, including demographics data, symptoms, laboratory and image findings were recorded for the 202 patients. Eight of the 52 variables that were entered into the selection process were selected via the best subset algorithm to establish the predictive model; they included gender, age, BMI, CRP, D-dimer, TP, ALB, and involved-lobe. Sensitivity, specificity and AUC were 0.91, 0.84 and 0.86 for the training dataset, and 0.87, 0.66, and 0.80 for the validation dataset. Conclusions We established an efficient and reliable clinical nomogram model which showed that gender, age, and initial indexes including BMI, CRP, D-dimer, involved-lobe, TP, and ALB could predict the risk of progression to severe COVID-19.

Download Full-text

D Dimer – Prognostic indicator for disease severity in patients hospitalised with COVID 19

Indian Journal of Pathology and Oncology ◽

10.18231/j.ijpo.2021.096 ◽

2021 ◽

Vol 8 (4) ◽

pp. 461-464

Author(s):

Vineet Banga ◽

Stuti Jain

Keyword(s):

Retrospective Study ◽

Disease Severity ◽

Severe Disease ◽

Prognostic Indicator ◽

Clinical Severity ◽

Care Hospital ◽

Severity Of Disease ◽

Management Protocol ◽

Severity Levels ◽

D Dimer

Patients of Covid 19 infections present with different severity. Levels of D Dimer in these patients can be correlated with disease severity for management and prognosis. To evaluate the usefulness of D-Dimer levels in blood to correlate with disease severity in COVID 19 patients. Retrospective study was done in Department of Pathology of Secondary Care hospital that became designated covid hospital from May 2021 to June 2021 on 60 COVID 19 positive admitted patients. D dimer levels were analysed and correlated with clinical severity of disease. Out of total 60 patients, 33 were in mild, 23 in moderate and 4 were in severe category. In mild cases D Dimer varies from 43 ng/ml to 183 ng/ml. In moderate cases D Dimer varies from 270 ng/ml to 991 ng/ml. In severe cases D Dimer varies from 1043 ng/ml to 2463 ng/ml. The study suggests cut off levels for D Dimer as up to 200 ng/ml for mild, 200-1000 ng/ml for moderate and more than 1000 ng/ml for severe category in COVID 19 patients. D dimer helps in identifying severe disease and can be used as an essential biomarker in developing the management protocol for COVID 19 patients.

Download Full-text

The (AAT)n repeat of the cannabinoid CB1 receptor gene influences disease progression in relapsing multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510388680 ◽

2010 ◽

Vol 17 (3) ◽

pp. 281-288 ◽

Cited By ~ 16

Author(s):

Silvia Rossi ◽

Fabio Buttari ◽

Valeria Studer ◽

Caterina Motta ◽

Paolo Gravina ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Progression ◽

Disease Severity ◽

Receptor Gene ◽

Severe Disease ◽

Autoimmune Encephalomyelitis ◽

Homozygous Genotype ◽

Relapsing Remitting ◽

Risk Of Progression ◽

Cnr1 Gene

Background: Genetic and pharmacological inactivation of cannabinoid CB1 receptors (CB1Rs) exacerbates disease course in experimental autoimmune encephalomyelitis, suggesting that CB1Rs might play a role in the neurodegenerative damage associated with multiple sclerosis (MS). Objectives: To see whether CNR1 gene polymorphism could influence disease progression in relapsing–remitting MS. Methods: The genotype of 350 patients for the number of AAT repeats was characterized and correlation studies were performed with measures of disease severity and progression. Results: MS patients with the homozygous genotype for long AAT repeats in the CNR1 gene had more severe disease and higher risk of progression. These subjects had significantly higher scores on both the progression index and the MS severity scale. Furthermore, the percentage of patients with MS functional composite score progression or Bayesian Risk Estimate for MS (BREMS) score ≥2 (considered at very high risk of secondary progression) was significantly higher in the AAT long group than in the short group, while the frequency of patients with BREMS score ≤−0.63 (very likely to remain progression-free) was not significantly different between the two groups, although lower in the long group. Finally, the frequency of patients prescribed a second-line treatment was significantly higher among subjects of the AAT long group, providing a further, indirect indication of higher disease severity. Conclusions: The results of the present investigation point to CB1R as an important modulator of disease severity in relapsing MS subjects.

Download Full-text

Rotational Thromboelastometry Reveals Distinct Coagulation Profiles for Patients With COVID-19 Depending on Disease Severity

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211027653 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110276

Author(s):

Mehmet Gökhan Gönenli ◽

Zeynep Komesli ◽

Said İncir ◽

Özlem Yalçın ◽

Olga Meltem Akay

Keyword(s):

Disease Severity ◽

Complete Blood Count ◽

Severe Disease ◽

Clinical Severity ◽

Therapeutic Approaches ◽

Thrombotic Risk ◽

Rotational Thromboelastometry ◽

Coagulation Parameters ◽

Positive Correlations ◽

D Dimer

Identifying a hypercoagulable state in patients with COVID-19 may help identify those at risk for virus–induced thromboembolic events and improve clinical outcomes using personalized therapeutic approaches. Herein, we aimed to perform a global assessment of the patients’ hemostatic system with COVID-19 using rotational thromboelastometry (ROTEM) and to describe whether patients with different disease severities present different coagulation profiles. Together with 37 healthy volunteers, a total of 65 patients were included and then classified as having mild, moderate, and severe disease depending on clinical severity. Peripheral blood samples were collected and analyzed using a ROTEM Coagulation Analyzer. Also, complete blood count and coagulation parameters including prothrombin time, activated partial thromboplastin time, fibrinogen levels, and D-dimer levels were measured at admission. EXTEM and INTEM MCF ( P < 0.001) values were significantly higher and the EXTEM CFT ( P = 0.002) value was significantly lower in patients with COVID-19 when compared with controls. In particular, patients with the severe disease showed a significant decrease in CFT ( P < 0.001) and an increase in MCF ( P < 0.001) in both INTEM and EXTEM assays compared with patients with the non-severe disease. Correlation analysis revealed significant correlations between ROTEM parameters and other coagulation parameters. There were significant positive correlations between fibrinogen, D-dimer, platelet count, and MCF in both EXTEM and INTEM assays. Our data demonstrate thromboelastographic signs of hypercoagulability in patients with COVID-19, which is more pronounced in patients with increased disease severity. Therefore, ROTEM analysis can classify subsets of patients with COVID-19 at significant thrombotic risk and assist in clinical decisions.

Download Full-text

A Composite study of Coagulation Milieu in Covid-19: Experience from a Tertiary Care Centre from India

Cardiovascular & Haematological Disorders - Drug Targets ◽

10.2174/1871529x21666211201110007 ◽

2021 ◽

Vol 21 ◽

Author(s):

Gopal Krishana Bohra ◽

Abhishek Purohit ◽

Deepak Kumar ◽

Mahendra Kumar Garg ◽

Naresh Kumar Midha ◽

...

Keyword(s):

Factor Viii ◽

Disease Severity ◽

Inflammatory Markers ◽

Severe Disease ◽

Advanced Age ◽

P Value ◽

Coagulation Parameters ◽

Inflammatory Parameters ◽

Hs Crp ◽

D Dimer

Background:: The understanding of pathogenesis is necessary for the development of effective treatment for COVID-19. Various studies have postulated that there is a complex interplay of mediators of coagulation and inflammation responsible for the pathogenesis of COVID-19. We did this study on coagulation parameters and inflammatory markers and their effect on outcome in patients with COVID-19. Methods: This was a single centre observational cross-sectional study. Procoagulants [Prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, lupus anticoagulant (LA), fibrinogen, factor-VIII (F-VIII)]; anticoagulants [protein-C (PC), protein-S (PS), antithrombin] and inflammatory markers [interleukin-6 (IL-6) and highly sensitive – C-reactive protein (hs-CRP)] were measured at the time of hospitalization and correlated with the severity of the disease. Results: A total of 230 patients were enrolled, of which 61.3%, 20.0%, and 18.7% had asymptomatic/ mild, moderate, or severe disease, respectively. COVID-19 disease severity was associated with rising trends with coagulation parameters (PT, APTT, D-Dimer; p value 0.01, <0.0001, <0.0001, respectively). Falling trends of anticoagulant (PC, Antithrombin; p value <0.0001, 0.003 respectively) and rising trends of procoagulant (fibrinogen, F-VIII; p value 0.004, <0.0001 respectively) were observed with increasing COVID-19 disease severity. Multivariate logistic regression analysis found that advanced age, D-Dimer, and hs-CRP (p value 0.035, 0.018, <0.0001 respectively) were independent predictors of mortality in COVID-19. Procoagulant parameters (D-dimer, APTT, Factor VIII) were positively correlated with anticoagulant parameters (PC and PS) and inflammatory parameters (hs-CRP). Conclusions: This study revealed increased levels of coagulation and inflammatory parameters, which correlated with the severity of COVID-19. Age, D-dimer, IL-6, hs-CRP, APTT, fibrinogen, and Factor VIII were significantly higher in patients with moderate and severe disease as compared to asymptomatic/mild disease. Advanced age, D dimer, and hs-CRP were significantly associated with poor outcomes.

Download Full-text

Diverse Functional Autoantibodies in Patients with COVID-19

10.1101/2020.12.10.20247205 ◽

2020 ◽

Cited By ~ 1

Author(s):

Eric Y. Wang ◽

Tianyang Mao ◽

Jon Klein ◽

Yile Dai ◽

John D. Huck ◽

...

Keyword(s):

Disease Severity ◽

Healthcare Workers ◽

Immune Cell ◽

Wide Spectrum ◽

Severe Disease ◽

Surface Proteins ◽

Complement Components ◽

Host Immune Responses ◽

High Prevalence ◽

The Impact

COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–8. While pathological innate immune activation is well documented in severe disease1, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody discovery technique called Rapid Extracellular Antigen Profiling (REAP) to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.

Download Full-text

Gender‐based disparities in COVID-19 patient outcomes

Journal of Investigative Medicine ◽

10.1136/jim-2020-001641 ◽

2021 ◽

pp. jim-2020-001641

Author(s):

Paul Ellis Marik ◽

Sarah E DePerrior ◽

Qamar Ahmad ◽

Sunita Dodani

Keyword(s):

Disease Severity ◽

Patient Outcomes ◽

Demographic Data ◽

Severe Disease ◽

Experimental Studies ◽

Men And Women ◽

Reactive Protein ◽

Male Patients ◽

Gender Based ◽

D Dimer

Studies reported to date suggest that men with COVID-19 have more severe disease and worse outcomes when compared with women. The explanation for this finding is not entirely clear. The goal of this study was to compare clinical characteristics, inflammatory biomarkers and clinical outcome between men and women. This retrospective study included patients with COVID-19 admitted to 10 Virginia hospitals from January 1, 2020, to June 15, 2020. Demographic data, comorbidities, and inflammatory markers, including C reactive protein (CRP), D-dimer, ferritin, and the neutrophil:lymphocyte ratio, as well as patient outcomes, were compared between men and women. During the study period, 701 patients with PCR-confirmed COVID-19 infection were admitted. The patient’s mean age was 61±17 years. There were 370 men (52.8%). There was no difference in age, racial distribution, and comorbidities in the male patients compared with the female patients. However, both the baseline and peak levels of CRP and ferritin were significantly higher in men as compared with women. While the baseline D-dimer was similar between the sexes, men had a significantly higher maximal D-dimer. Men had evidence of greater disease severity, with a significantly greater admission to the intensive care unit and borderline higher hospital mortality. Our study supports the observation that COVID-19 causes more severe disease in men. The greater disease severity in men was not due to the effect of age or comorbidities; however, in keeping with experimental studies, men had evidence of a heightened inflammatory response, likely contributing to disease severity.

Download Full-text

802. Proton Pump Inhibitors Increase Clostridioides difficile Disease Severity Controlling for Infecting Strains

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.992 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S444-S444

Author(s):

Saad Fallatah ◽

Masaad Almutairi ◽

Faris S Alnezary ◽

Anne J Gonzales-Luna ◽

Kevin W Garey

Keyword(s):

Disease Severity ◽

Proton Pump Inhibitors ◽

Clinical Data ◽

Proton Pump ◽

Multicenter Study ◽

Severe Disease ◽

Composite Endpoint ◽

Hospitalized Patients ◽

Clostridioides Difficile ◽

Poor Outcomes

Abstract Background Proton pump inhibitors (PPI) display pleotropic properties that increase the risk of poor outcomes in patients with C. difficile infection (CDI). However, clinical data on PPI and CDI outcomes is controversial perhaps due to lack of knowledge of infecting strain. The purpose of this study was to assess CDI outcomes in hospitalized patients infected with known C. difficile ribotypes based on use of PPI. Methods This was a multicenter study (20 hospitals) of hospitalized patients infected with one of three C. difficile ribotypes (RT027, RT106, and RT014-020). Electronic medical records were reviewed by investigators blinded to RT that collected data on PPI use along with other clinical data. A composite endpoint of disease severity, mortality and 90-day CDI recurrence was assessed based on receipt of PPI and ribotype using multivariate logistic regression. Results A total of 380 patients with CDI aged 66±17 years (Female: 59.5%; White: 70.5%) infected with RT 106 (115/380; 30.3%), RT027 (116/380; 30.5%), and RT014-020 (149/380; 39.2%) were included. One hundred and ninety-nine patients (52.4%) were given a PPI at the time of CDI diagnosis and 129 patients (66.1%) experienced either severe disease or CDI recurrence. Disease severity differed significantly between ribotypes (p< 0.05) and increased in patients given PPI (p=0.08). CDI recurrence also differed significantly among ribotypes (p< 0.05) and increased in patients given PPI. Using the composite endpoint, receipt of PPIs significantly increased the likelihood of poor outcomes (OR:1.78; 95% CI: 1.17-2.73; p=0.007) after controlling for infecting ribotype. Conclusion In this multicenter study, receipt of PPIs increased the likelihood of poor outcomes in CDI patients after controlling for infecting ribotype. Disclosures Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)

Download Full-text