scholarly journals Complement C5a and Clinical Markers as Predictors of COVID-19 Disease Severity and Mortality in a Multi-Ethnic Population

2021 ◽  
Vol 12 ◽  
Author(s):  
Farhan S. Cyprian ◽  
Muhammad Suleman ◽  
Ibrahim Abdelhafez ◽  
Asmma Doudin ◽  
Ibn Mohammed Masud Danjuma ◽  
...  
Keyword(s):  
Disease Severity ◽  
Complete Blood Count ◽  
Severe Disease ◽  
Clinical Severity ◽  
Classification Model ◽  
Clinical Markers ◽  
Hepatocellular Injury ◽  
Risk Of Death ◽  
Markers Of Inflammation ◽  
Wide Range

Coronavirus disease-2019 (COVID-19) was declared as a pandemic by WHO in March 2020. SARS-CoV-2 causes a wide range of illness from asymptomatic to life-threatening. There is an essential need to identify biomarkers to predict disease severity and mortality during the earlier stages of the disease, aiding treatment and allocation of resources to improve survival. The aim of this study was to identify at the time of SARS-COV-2 infection patients at high risk of developing severe disease associated with low survival using blood parameters, including inflammation and coagulation mediators, vital signs, and pre-existing comorbidities. This cohort included 89 multi-ethnic COVID-19 patients recruited between July 14th and October 20th 2020 in Doha, Qatar. According to clinical severity, patients were grouped into severe (n=33), mild (n=33) and asymptomatic (n=23). Common routine tests such as complete blood count (CBC), glucose, electrolytes, liver and kidney function parameters and markers of inflammation, thrombosis and endothelial dysfunction including complement component split product C5a, Interleukin-6, ferritin and C-reactive protein were measured at the time COVID-19 infection was confirmed. Correlation tests suggest that C5a is a predictive marker of disease severity and mortality, in addition to 40 biological and physiological parameters that were found statistically significant between survivors and non-survivors. Survival analysis showed that high C5a levels, hypoalbuminemia, lymphopenia, elevated procalcitonin, neutrophilic leukocytosis, acute anemia along with increased acute kidney and hepatocellular injury markers were associated with a higher risk of death in COVID-19 patients. Altogether, we created a prognostic classification model, the CAL model (C5a, Albumin, and Lymphocyte count) to predict severity with significant accuracy. Stratification of patients using the CAL model could help in the identification of patients likely to develop severe symptoms in advance so that treatments can be targeted accordingly.

scholarly journals Complement C5a and Clinical Markers to predict COVID-19 Disease Severity and Mortality in a Multi-ethnic Population

2021 ◽  
Author(s):  
Farhan S Cyprian ◽  
Muhammad Suleman ◽  
Ibrahim Abdelhafez ◽  
Asmma Doudin ◽  
Ibn Mohammed Masud Danjuma ◽  
...  
Keyword(s):  
Disease Severity ◽  
Complete Blood Count ◽  
Severe Disease ◽  
Clinical Severity ◽  
Classification Model ◽  
Clinical Markers ◽  
Hepatocellular Injury ◽  
Risk Of Death ◽  
Markers Of Inflammation ◽  
Wide Range

Abstract Coronavirus disease-2019 (COVID-19) was declared as a pandemic by WHO in March 2020. SARS-CoV-2 causes a wide range of illness from asymptomatic to life-threatening. There is an essential need to identify biomarkers to predict disease severity and mortality during the earlier stages of the disease, aiding treatment and allocation of resources to improve survival. The aim of this study was to identify at the time of SARS-COV-2 infection patients at high risk of developing severe disease associated with low survival using blood parameters, including inflammation and coagulation mediators, vital signs, and pre-existing comorbidities. This cohort included 89 multi-ethnic COVID-19 patients recruited between July 14th and October 20th 2020 in Doha, Qatar. According to clinical severity, patients were grouped into severe (n = 33), mild (n = 33) and asymptomatic (n = 23). Common routine tests such as complete blood count (CBC), glucose, electrolytes, liver and kidney function parameters and markers of inflammation, thrombosis and endothelial dysfunction including complement component split product C5a, Interleukin-6, ferritin and C-reactive protein were measured at the time COVID-19 infection was confirmed. Correlation tests suggest that C5a is a novel predictive marker of disease severity and mortality, in addition to 40 biological and physiological parameters that were found statistically significant between survivors and non-survivors. Survival analysis showed that. high C5a levels, hypoalbuminemia, lymphopenia, elevated procalcitonin, neutrophilic leukocytosis, acute anemia along with increased acute kidney and hepatocellular injury markers were associated with a higher risk of death in COVID-19 patients. Altogether, we created a prognostic classification model, the CAL model (C5a, Albumin, and Lymphocyte count) to predict severity with significant accuracy. Stratification of patients using the CAL model could help the identification of patients likely to develop severe symptoms in advance so that treatments can be targeted accordingly.

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

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.

scholarly journals Comparison of three serological chemiluminescence immunoassays for SARS-CoV-2, and clinical significance of antibody index with disease severity

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253889
Author(s):  
Nuri Lee ◽  
Seri Jeong ◽  
Min-Jeong Park ◽  
Wonkeun Song
Keyword(s):  
Disease Severity ◽  
Clinical Significance ◽  
Severe Disease ◽  
Clinical Severity ◽  
Clinical Implications ◽  
Antibody Index ◽  
Clinical Markers ◽  
Strong Correlations ◽  
Igg Antibody ◽  
Molecular Tests

Background The clinical significance of the quantitative value of antibodies in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains mostly unidentified. We investigated the dynamics and clinical implications of the SARS-CoV-2 antibody over time using three automated chemiluminescence immunoassays targeting either nucleocapsids or spikes. Methods A total of 126 specimens were collected from 23 patients with confirmed and indeterminate COVID-19 identified by molecular tests. SARS-CoV-2 antibody index was measured using SARS-CoV2 IgG reagent from Alinity (Abbott) and Access (Beckman Coulter) and SARS-CoV2 Total (IgG + IgM) from Atellica (Siemens). Results Three immunoassays showed strong correlations with each other (range of Pearson’ s correlation coefficient (r) = 0.700–0.854, P < 0.001). Eleven (8.7%) specimens showed inconsistencies. SARS-CoV-2 IgG showed a statistically significantly higher value in patients with severe disease than that in non-severe disease patients (P < 0.001) and was significantly associated with clinical markers of disease severity. Conclusion The quantitative value of the SARS-CoV-2 IgG antibody measured using automated immunoassays is a significant indicator of clinical severity in patients with COVID-19.

scholarly journals Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio and Their Role as Predictors of Disease Severity of Coronavirus Disease 2019 (COVID-19)

2021 ◽  
Author(s):  
Rohit Jain ◽  
Arun Gopal ◽  
Basant Kumar Pathak ◽  
Sourya Sourabh Mohakuda ◽  
TVSVGK Tilak ◽  
...  
Keyword(s):  
Disease Severity ◽  
Complete Blood Count ◽  
Wide Spectrum ◽  
Statistical Significance ◽  
Severe Disease ◽  
Neutrophil To Lymphocyte Ratio ◽  
Screening Tools ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Time Of Admission

Abstract Context Due to the wide spectrum of clinical illness in coronavirus disease 2019 (COVID-19) patients, it is important to stratify patients into severe and nonsevere categories. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been evaluated rapidly by a few studies worldwide for its association with severe disease, but practically none have been conducted in the Indian population. This study was undertaken to examine the role of NLR and PLR in predicting severe disease in Indian patients. Objectives The objective was to study the association of NLR and PLR observed at the time of admission with maximum disease severity during hospitalization and to study their role in predicting disease severity. Material and Methods A total of 229 COVID-19 patients were admitted at the center during the study period. After applying inclusion and exclusion criteria, 191 patients were included in the study. The demographic, clinical, and laboratory (complete blood count, NLR, and PLR) data of all patients were obtained at the time of admission. Maximum disease severity of all patients was assessed during hospitalization. Statistical Analysis Chi-square and Mann–Whitney U tests were used to assess statistical significance. Receiver operating characteristic curve (ROC) was plotted for NLR and PLR to estimate the cutoff values and sensitivity and specificity using Youden’s index for predicting severe disease. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals. Results Mean NLR and PLR were significantly higher in severe patients (NLR = 7.41; PLR = 204) compared with nonsevere patients (NLR = 3.30; PLR = 121). ROC analysis showed that NLR, in comparison to PLR, had a higher area under the curve (AUC) of 0.779, with a larger OR of 1.237 and cutoff of 4.1, and showed 69% sensitivity and 78% specificity in predicting severe disease. Cut off for PLR was 115.3, which showed 79% sensitivity and 62% specificity in predicting severe disease. Conclusion NLR and PLR, both showing acceptable AUCs, can be used as screening tools to predict disease severity. However, NLR was a better predictor of disease severity.

scholarly journals Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
M. Flook ◽  
C. Jackson ◽  
E. Vasileiou ◽  
C. R. Simpson ◽  
M. D. Muckian ◽  
...  
Keyword(s):  
Public Health ◽  
Risk Factors ◽  
Systematic Review ◽  
At Risk ◽  
Risk Factor ◽  
Disease Severity ◽  
Severe Disease ◽  
Public Health Response ◽  
Wide Range ◽  
Multivariable Analyses

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.

Severity of Sickle Cell Disease: Modeling Interrelationships among Hemolysis, Pulmonary Hypertension and Risk of Death.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 786-786
Author(s):  
Paola Sebastiani ◽  
Vikki G. Nolan ◽  
Clinton T. Baldwin ◽  
Maria M. Abad-Grau ◽  
Ling Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Disease Severity ◽  
Hemolytic Anemia ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Risk Of Death

Abstract A single point mutation in the β hemoglobin gene causes sickle cell disease (SCD), but patients have extremely variable phenotypes. Hemolysis-related complications include pulmonary hypertension (PHT), priapism, stroke and leg ulceration; blood viscosity and sickle vasoocclusion are associated with painful episodes, acute chest syndrome and osteonecrosis. Predicting who is at highest risk of death would be useful therapeutically and prognostically. Applying Bayesian network modeling that describes complex interactions among many variables by factorizing their joint probability distribution into modules, to data from 3380 SCD patients, we constructed a disease severity score (DSS: 0, least severe; 1, most severe), defining severity as risk of death within 5 years. A network of 24 variables described complex associations among clinical and laboratory complications of SCD. The analysis was validated in 140 patients whose SCD severity was assessed by expert clinicians and 210 adults where severity was also assessed by the echocardiographic diagnosis of PHT and death. Information about PHT allowed a comparison of the DSS with the tricuspid regurgitant jet velocity (TRJV), an objective marker of PHT and an independent risk factor for death. DSS and three indices of clinical severity (severity ranking of individuals by expert clinicians; objective measurement of the presence and severity of PHT; risk of prospective death) were correlated. Among living subjects, the median score was 0.57 in 135 patients without PHT, 0.64 in 40 patients with mild PHT and 0.86 in 15 patients with severe PHT. The difference in average score between living patients with and without PHT is significant. The same increasing trend was noticeable in the subjects who died during follow-up: 0.60 in subjects without PHT; 0.68 in subjects with mild PHT; 0.79 in subjects with severe PHT. The utility of the DSS is also supported by the ability to assign a score to subjects for whom the TRJV cannot be measured. Surprisingly, besides known risk factors like renal insufficiency and leukocytosis, we identified the intensity of hemolytic anemia and clinical events associated with hemolytic anemia as contributing to risk for death. Priapism, an excellent reflection of the hemolytic anemia-related complications of SCD, is associated with PHT and its association with death was unexpected. Laboratory variables predictive of disease severity included LDH and reticulocytes that reflect the intensity of hemolytic anemia. Elevated systolic blood pressure increased the odds of death by 3.4, consistent with hypertension as a marker of early death in SCD. Subjects with sickle cell anemia are at greatest risk compared with subjects with sickle cell anemia-α thalassemia and with subjects with HbSC disease. Our model suggests that the intensity of hemolytic anemia, estimated by LDH, reticulocyte count and AST, and shown previously to be associated with PHT, priapism, leg ulceration and possibly stroke, is an important contributor to death. This model can be used to compute a personalized measure of disease severity that might be useful for guiding therapeutic decisions and designing clinical trials.

scholarly journals Differential Association of Viral Dynamics With Disease Severity Depending on Patients’ Age Group in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuri Kim ◽  
Shinhyea Cheon ◽  
Hyeongseok Jeong ◽  
Uni Park ◽  
Na-Young Ha ◽  
...  
Keyword(s):  
Viral Load ◽  
Elderly Patients ◽  
Disease Severity ◽  
Acute Phase ◽  
Inflammatory Responses ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
The Elderly ◽  
Clinical Severity ◽  
Younger Patients

Despite a clear association of patient’s age with COVID-19 severity, there has been conflicting data on the association of viral load with disease severity. Here, we investigated the association of viral load dynamics with patient’s age and severity of COVID-19 using a set of respiratory specimens longitudinally collected (mean: 4.8 times/patient) from 64 patients with broad distribution of clinical severity and age during acute phase. Higher viral burden was positively associated with inflammatory responses, as assessed by IL-6, C-reactive protein, and lactate dehydrogenase levels in patients’ plasma collected on the same day, primarily in the younger cohort (≤59 years old) and in mild cases of all ages, whereas these were barely detectable in elderly patients (≥60 years old) with critical disease. In addition, viral load dynamics in elderly patients were not significantly different between mild and critical cases, even though more enhanced inflammation was consistently observed in the elderly group when compared to the younger group during the acute phase of infection. The positive correlation of viral load with disease severity in younger patients may explain the increased therapeutic responsiveness to current antiviral drugs and neutralizing antibody therapies in younger patients compared to elderly patients. More careful intervention against aging-associated inflammation might be required to mitigate severe disease progression and reduce fatality in COVID-19 patients more than 60 years old.

scholarly journals Low FT3 is an independent marker of disease severity in patients hospitalized for COVID-19

2021 ◽  
Author(s):  
Aditya Dutta ◽  
Ganesh Jevalikar ◽  
Rutuja Sharma ◽  
Khalid J. Farooqui ◽  
Shama Mahendru ◽  
...  
Keyword(s):  
Disease Severity ◽  
Cox Regression ◽  
Severe Disease ◽  
Thyroid Stimulating Hormone ◽  
Hospitalized Patients ◽  
Thyroid Function Tests ◽  
Cox Regression Analysis ◽  
Markers Of Inflammation ◽  
Outcome Severity ◽  
Independent Marker

Aim: To study the prevalence of thyroid dysfunction and its association with disease severity in hospitalized patients of coronavirus disease-19 (COVID-19). Methods: In this retrospective cohort study, thyroid function tests (TFT) of 236 hospitalized patients of COVID-19, along with demographic, comorbid, clinical, biochemical, and disease severity records were analysed. Patients were divided into previous euthyroid or hypothyroid status to observe the effect of prior hypothyroidism on severity of COVID-19. Results: TFT abnormalities were common. Low free T3 (FT3), high thyroid stimulating hormone (TSH) and low TSH were seen in 56 (23.7%), 15 (6.4%) and 9 (3.8%) patients, respectively. The median levels of TSH (2.06 vs 1.26 mIU/mL, p=0.001) and FT3 (2.94 vs 2.47 pg/mL, p=0.000) were significantly lower in severe disease. Previous hypothyroid status (n=43) was associated with older age, higher frequency of comorbidities, higher FT4 and lower FT3. TFT did not correlate with markers of inflammation (except lactate dehydrogenase), however, FT3 and TSH negatively correlated with outcome severity score and duration of hospital stay. Cox-regression analysis showed that low FT3 was associated with severe COVID-19 (p=0.032, HR 0.302; CI 0.101-0.904), irrespective of prior hypothyroidism. Conclusions: Functional thyroid abnormalities (low FT3 and low TSH) are frequently seen in hospitalized patients of COVID-19. Although these abnormalities did not correlate with markers of inflammation, this study shows that low FT3 at admission independently predicts severity of COVID-19.

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

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.

The HBG2 rs7482144 (C > T) Polymorphism is Linked to HbF Levels but not to the Severity of Sickle Cell Anemia

2021 ◽  
Author(s):  
Bhaskar V. K. S. Lakkakula ◽  
Smaranika Pattnaik
Keyword(s):  
Disease Severity ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
High Performance ◽  
Complete Blood Count ◽  
Small Sample Size ◽  
Severe Disease ◽  
Small Sample ◽  
Total Leucocyte Count ◽  
Severity Scores

AbstractSickle cell anemia (SCA) is a severe disease characterized by anemia, acute clinical complications, and a relatively short life span. In this disease, abnormal hemoglobin makes the red blood cells deformed, rigid, and sticky. Fetal hemoglobin (HbF) is one of the key modulators of SCA morbidity and mortality. Interindividual HbF variation is a heritable trait that is controlled by polymorphism in genes linked and unlinked to the hemoglobin β gene (HBB). The genetic polymorphisms that determine HbF levels are known to ameliorate acute clinical events. About 190 well-characterized homozygous SCA patients were included in this study. Complete blood count (CBC), high-performance liquid chromatography (HPLC), and clinical investigations were obtained from patient's records. Severity scores were determined by using the combination of anemia, complications, total leucocyte count, and transfusion scores. HBG2 rs7482144 polymorphism was genotyped by using the polymerase chain reaction and restriction fragment length polymorphism. The association between HBG2 rs7482144 polymorphism and HbF levels as well as the disease severity of SCA were assessed. SCA patients carrying TT genotype were found to have higher HbF levels. In addition, SCA patients with increased severity showed significantly lower levels of hemoglobin, HbF, and hematocrit values. However, the genotypes of HBG2 rs7482144 polymorphism were not found to be associated with the risk of disease severity. In summary, this study demonstrated that HBG2 rs7482144 polymorphism is linked with HbF levels, but it does not affect disease severity. The sample sizes used and the pattern of association deduced from our small sample size prevents us from extrapolating our findings further.

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