scholarly journals The lineage of coronavirus SARS-CoV-2 of Russian origin: Genetic characteristics and correlations with clinical parameters and severity of coronavirus infection

Author(s):  
O. S. Glotov ◽  
A. N. Chernov ◽  
A. I. Korobeynikov ◽  
R. S. Kalinin ◽  
V. V. Tsai ◽  
...  

The identification of new SARS-CoV-2 and human protein and gene targets, which may be markers of the severity and outcome of the disease, are extremely important during the COVID-19 pandemic. The goal of this study was to carry out genetic analysis of SARS-CoV-2 RNA samples to elucidate correlations of genetic parameters (SNPs) with clinical data and severity of COVID-19 infection.Material and Methods. The study included viral RNA samples isolated from 56 patients with COVID-19 infection who received treatment at the City Hospital No. 40 of St. Petersburg from 04/18/2020 to 04/18/2021. Patients underwent physical examination with the assessments of hemodynamic and respiratory parameters, clinical risk according to National Early Warning Score (NEWS), computed tomography (CT) of the chest, and laboratory studies including clinical blood analysis, assessment of ferritin, C-reactive protein (CRP), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, creatinine, and glucose levels. All patients tested positive for SARS-CoV-2 RNA by polymerase chain reaction (PCR). Single nucleotide polymorphisms (SNPs) in viral RNA were identified through the creation of cDNA libraries by targeted sequencing (MiSeq Illumina). Bioinformatic analysis of viral samples was performed using the viralrecon v2 pipeline with the further annotation via Pangolin and Nextlade. Sampled genomes were visualized using the Integrative Genomics Viewer (IGV) software. Statistical data processing (descriptive statistics and graphical analysis of data relationships from diff erent tables) was performed using a GraphPad device on the Prism 8.01 platform.Results. A comparative analysis of SNP frequencies in the virus genome in samples from deceased and discharged patients was carried out. The SNPs associated with risk of death (OR > 1), neutral SNPs (OR = 1), and protective SNPs (OR < 1) were identifi ed. Patient samples were infected with 14 lines of SARS-CoV-2, fi ve of which (B.1.1.129, B.1.1.407, B.1.1.373, B.1.1.397, and B.1.1.152) were of Russian origin. The SNPs in the samples infected with the strains of non-Russian origin were associated with an increased risk of mortality (OR = 2.267, 95% confi dence interval 0.1594-8.653) compared to the SNPs in the samples obtained from the group of patients infected with the strains of Russian origin. Positive correlations were identifi ed between the average SNP number, nonsynonymous SNPs, and S-protein SNPs with the degree of respiratory failure, total NEWS score, CT-based form of disease, duration of treatment with mechanical ventilation, disease outcome, levels of LDH, glucose, D-dimer, and ferritin, and RNA amount in the PCR test. S-protein SNPs negatively correlated with the leukocyte and neutrophil counts.

2021 ◽  
Vol 12 ◽  
Author(s):  
Sergey G. Shcherbak ◽  
Anna Yu Anisenkova ◽  
Sergei V. Mosenko ◽  
Oleg S. Glotov ◽  
Alexander N. Chernov ◽  
...  

ObjectiveA critical role in coronavirus disease 2019 (COVID-19) pathogenesis is played by immune dysregulation that leads to a generalized uncontrolled multisystem inflammatory response, caused by overproduction of proinflammatory cytokines, known as “a cytokine storm” (CS), strongly associated with a severe course of disease. The aim of this study is to identify prognostic biomarkers for CS development in COVID-19 patients and integrate them into a prognostic score for CS-associated risk applicable to routine clinical practice.Materials and MethodsThe authors performed a review of 458 medical records from COVID-19 patients (241 men and 217 women aged 60.0 ± 10.0) who received treatment in the St. Petersburg State Budgetary Institution of Healthcare City Hospital 40 (City Hospital 40, St. Petersburg), from Apr. 18, 2020 to Nov. 21, 2020. The patients were split in two groups: one group included 100 patients with moderate disease symptoms; the other group included 358 patients with progressive moderately severe, severe, and extremely severe disease. The National Early Warning Score (NEWS) score was used alongside with clinical assessment, chest computed tomographic (CT) scans, electrocardiography (ECG), and lab tests, like ferritin, C-reactive protein (CRP), interleukin (IL)-6, lactate dehydrogenase (LDH), and D-dimer.ResultsThe basic risk factors for cytokine storms in COVID-19 patients are male gender, age over 40 years, positive test result for replicative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, absolute lymphocyte count, dynamics in the NEWS score, as well as LDH, D-dimer, ferritin, and IL-6 levels. These clinical and instrumental findings can be also used as laboratory biomarkers for diagnosis and dynamic monitoring of cytokine storms. The suggested prognostic scale (including the NEWS score dynamics; serum IL-6 greater than 23 pg/ml; serum CRP 50 mg/L or greater; absolute lymphocyte count less than 0.72 × 109/L; positive test result for replicative coronavirus (SARS-CoV-2) RNA; age 40 years and over) is a useful tool to identify patients at a high risk for cytokine storm, requiring an early onset of anti-inflammatory therapy.


Heart ◽  
2020 ◽  
pp. heartjnl-2020-316880 ◽  
Author(s):  
Xiaoyuan Zhang ◽  
Shanjie Wang ◽  
Jinxin Liu ◽  
Yini Wang ◽  
Hengxuan Cai ◽  
...  

ObjectiveD-dimer might serve as a marker of thrombogenesis and a hypercoagulable state following plaque rupture. Few studies explore the association between baseline D-dimer levels and the incidence of heart failure (HF), all-cause mortality in an acute myocardial infarction (AMI) population. We aimed to explore this association.MethodsWe enrolled 4504 consecutive patients with AMI with complete data in a prospective cohort study and explored the association of plasma D-dimer levels on admission and the incidence of HF, all-cause mortality.ResultsOver a median follow-up of 1 year, 1112 (24.7%) patients developed in-hospital HF, 542 (16.7%) patients developed HF after hospitalisation and 233 (7.1%) patients died. After full adjustments for other relevant clinical covariates, patients with D-dimer values in quartile 3 (Q3) had 1.51 times (95% CI 1.12 to 2.04) and in Q4 had 1.49 times (95% CI 1.09 to 2.04) as high as the risk of HF after hospitalisation compared with patients in Q1. Patients with D-dimer values in Q4 had more than a twofold (HR 2.34; 95% CI 1.33 to 4.13) increased risk of death compared with patients in Q1 (p<0.001). But there was no association between D-dimer levels and in-hospital HF in the adjusted models.ConclusionsD-dimer was found to be associated with the incidence of HF after hospitalisation and all-cause mortality in patients with AMI.


2020 ◽  
Author(s):  
Qing Yang ◽  
Ying Zhou ◽  
Xinrong Wang ◽  
Shan Gao ◽  
Yang Xiao ◽  
...  

Abstract Background: Previous studies have shown that Coronavirus Disease 2019 (COVID-19) patients with underlying comorbidities can have worse outcomes. However, the effect of hypertension on outcomes of COVID-19 patients remains unclear.Research Question: The aim of this study was to explore the effect of hypertension on the outcomes of patients with COVID-19 by using propensity score–matching (PSM) analysis.Study Design and Methods: Participants enrolled in this study were patients with COVID-19 who had been hospitalized at the Central Hospital of Wuhan, China. Chronic comorbidities and laboratory and radiological data were reviewed; patient outcomes and lengths of stay were obtained from discharge records. We used the Cox proportional-hazard model (CPHM) to analyze the effect of hypertension on these patients’ outcomes and PSM analysis to further validate the abovementioned effect.Results: A total of 226 patients with COVID-19 were enrolled in this study, of whom 176 survived and 50 died. The proportion of patients with hypertension among non-survivors was higher than that among survivors (26.70% vs. 74.00%; P < 0.001). Results obtained via CPHM showed that hypertension could increase risk of mortality in COVID-19 patients (hazard ratio 3.317; 95% CI [1.709–6.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients’ mortality risk. After matching on propensity score, we still came to similar conclusions. After we applied the same method in critically ill patients, we found that hypertension also increased risk of death in patients with severe COVID-19.Conclusion: Hypertension, increased D-dimer and the ratio of neutrophil to lymphocyte increased mortality in patients with COVID-19, with hypertension in particular.


Author(s):  
Alexander H. Cotter ◽  
Su-Jau T. Yang ◽  
Hedyeh Shafi ◽  
Timothy M. Cotter ◽  
Darryl Erik Palmer-Toy

ABSTRACT Context: Coagulation factor and endothelial injury marker, von Willebrand factor antigen (vWF:Ag), is elevated in coronavirus disease 2019 (COVID-19). Objective: To assess prognostic value of vWF:Ag for COVID-19 inpatients. Design: Citrated plasma samples collected from COVID-19 inpatients for D-dimer measurement were tested for vWF:Ag. Measurements of vWF:Ag and common acute phase reactants (APRs) were correlated with clinical outcomes and length of stay (LOS). Results: We included 333 samples from a diverse group of 120 COVID-19 inpatients. There was a clear association of higher peak measurements of vWF:Ag and other APRs with adverse clinical outcomes. Peak vWF:Ag &gt;300% was associated with a 5-fold increased risk of death (Odds Ratio 5.08, P&lt;.001) and a 30-fold increased risk of prolonged (&gt;4 days) LOS (OR 29.65, P =.001). Peak D-dimer &gt;3.8 FEU mg/L was associated with a 15-fold increase in risk of death (OR 14.73, P &lt;.001) and a 5-fold increased risk of prolonged LOS (OR 4.55, P=.02). Using the earliest paired measurements of vWF:Ag and D-dimer from each patient and the same cut-offs, vWF:Ag was associated with a 3.5-fold increase in risk of death (OR 3.54, P=.004) and a 20-fold risk of prolonged LOS (OR 20.19, P=.004). Yet D-dimer was not significantly associated with either death (OR 1.9, P=.29) or prolonged LOS (OR 1.02, P=.98). Conclusions: Both peak and early post-admission vWF:Ag &gt;300% were highly predictive of death and prolonged length of stay among COVID-19 inpatients. Measurement of vWF:Ag may prove a valuable tool to guide escalation of COVID-19 treatment, particularly anticoagulation.


2020 ◽  
Author(s):  
Shant Ayanian ◽  
Juan Reyes ◽  
Lei Lynn ◽  
Karolyn Teufel

AbstractBackgroundThe global pandemic caused by COVID-19 remains poorly understood by clinicians. Identifying biologic markers associated with prognosis can help clinicians recognize disease severity.ObjectiveTo describe the association between D-dimer, CRP, IL-6, ferritin, LDH, and clinical outcomes in a cohort of COVID-19 patients treated on the inpatient medical service at a university hospital in Washington, DC.DesignIn this retrospective study, we included all adults admitted to the inpatient medicine service at George Washington University Hospital between March 12, 2020 and May 9, 2020 with laboratory confirmed COVID-19. Clinical and laboratory data were extracted from electronic medical records and compared between survivors not requiring ICU transfer, survivors requiring ICU transfer, survivors requiring intubation, and non-survivors.Key Results299 patients were included in our study, of whom 69 required transfer to the ICU, 39 required intubation, and 71 died. Threshold values for IL-6 (≥50 pg/mL), D-dimer (≥3 mcg/mL), ferritin (≥450 ng/mL), CRP (≥100 mg/L), and LDH (1,200 u/L) were found to be statistically significant and independently associated with higher odd of clinical deterioration and death. Hypertension, CVA and heart disease independently had an increased risk of all three outcomes, while CKD had only an increased risk of death. Patient co-morbidities had no effect on the different biomarkers’ significant association with poor patient clinical outcomes, except cancer.ConclusionLaboratory markers of inflammation and coagulopathy can help clinicians identify patients who are at high risk for clinical deterioration, independent of clinically significant medical comorbidities.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Nino Balanchivadze ◽  
Raef Fadel ◽  
Jawad Sheqwara ◽  
Philip Kuriakose

Background As the COVID-19 pandemic spread across the US, the city of Detroit rose as one of the earliest infection epicenters in the nation. Henry Ford Hospital serves a diverse multi ethnic population in the inner city and throughout metropolitan Detroit, and thus provided care to a significant percentage of COVID 19 patients in the state of Michigan. Retrospective reviews have described different hematologic abnormalities in patients with COVID-19. Various markers, such as lymphopenia, neutrophilia, elevated ferritin, and DDimer levels have been identified as predictors of poor outcomes, intensive care unit (ICU) admission, and mortality. The aim of this study was to evaluate the impact of hematologic characteristics on the risk of intubation and mortality in our unique patient population infected with COVID-19 who required ICU admission. Methods: This was a retrospective medical record review of adult patients with laboratory-confirmed COVID-19 requiring admission to adult ICU at Henry Ford Hospital in Detroit, MI, from March 1 to April 15, 2020. The main outcomes assessed were death and need for intubation and mechanical ventilation. Results: A total of 229 patients met the study inclusion criteria. Of the 76 surviving patients analyzed, 40 (53%) were men and 36 (47%) were women, including 59 (78%) Black and 11 (14%) White patients. The mean age at presentation was 61 (SD, 15) years. Hypertension was the most common comorbidity (n=65 patients), followed by diabetes (n=39). Most surviving patients (n=60; 79%) were admitted to general practice units (GPU) and then transferred to ICU, while 49 (64%) patients required intubation. Among the 153 patients who died, 95 (62%) were men and 58 (38%) were women, with 41 (27%) being White and 99 (65%) Black. The mean age at presentation was 69 years (SD, 14.3). Hypertension was the most common presenting co-morbidity (n=118), followed by diabetes (n=72). More non-surviving patients were admitted directly to the ICU (n=71; 46%) and/or required intubation (n=147; 96%). Hematologic laboratory findings of the studied patients are represented in Table 1. Multivariate analysis of variables predictive of death and intubation are summarized in Table 2. Logistic modeling revealed an 18% increase in the odds of death and a 17% increase in odds of intubation for each unit increase in WBC. Also, for each unit increase in ANC, there was a 17% increase in odds of death and 21% increase in odds of intubation. Conclusions: Among patients with COVID-19 who required admission to ICU, Black patients were over-represented. Coronary artery disease (CAD), older age, and a lower oxygen saturation (SpO2) on initial triage in the emergency department were associated with increased mortality. A higher absolute neutrophil count (ANC) and white blood cell count (WBC) was associated with higher risk of intubation and death. Male sex and direct ICU admission were predictors of increased risk of intubation - and these patients were more likely to die. Contrary to other reports, lymphopenia did not increase odds of intubation or death in ICU, and neither the serum ferritin nor DDimer levels on admission were discriminators for death; however, higher peak levels during the hospitalization were linked to increased mortality. Inner city Black populations with advanced age, multiple co-morbidities, and COVID-19 may be at increased risk for ICU admission, and thereby at an increased risk of death. However, not all hematologic characteristics are generalizable with regard to intubation and mortality in ICU. Disclosures No relevant conflicts of interest to declare.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Mary Giltinane ◽  
Karl Boyle ◽  
Grainne O'Kane ◽  
Joseph Harbison

Introduction. The Modified Early Warning Score (MEWS) is a tool for estimating risk of death or poor outcome in the Emergency Department (ED). It is a 0-14 point score based on initial physiological observations including heart rate, respiratory rate, systolic blood pressure, temperature and level of consciousness. In Acute medical patients, a score > 4 has been found to be associated with increased risk of death. The score is being widely adopted for use as a risk stratification tool for patients admitted through EDs and in Acute Medical Assessment Units and has been used in stroke patients but has not been validated for acute stroke. We applied the score to a population of acute stroke patients admitted through ED to determine its utility. Methods. Records on consecutive patients admitted through ED to an acute stroke service of an inner city university teaching hospital over 8 months were identified and MEWS calculated for each. Patients dying within 6 months or with a prolonged hospital stay (>42 days) were identified. Results. 132 subjects (Mean age 71, 59% male) were admitted to the service, 122 were admitted through ED. Median MEWS was 1 (range 0-4) and 18 (17%) died within 6 months. Subjects with a MEWS>2 were significantly more likely to die (10/91 vs 10/31 p=0.006 Chi square. O.R. 3.9 (1.4-10.5)) and those who survived more likely to have a prolonged length of stay (21/81 vs 11/21 p=0.02. Chi square. O.R 3.1 (1.2-8.5)). As a tool for identifying those with acute stroke risk of dying the MEWS performed only moderately well (PPV 0.5, NPV 0.68). Conclusion. As part of a screening test for stroke patients a MEWS>2 at ED admission is associated with worse outcome however it is neither sensitive or specific enough to be used in isolation as a means of triaging stroke patients into risk categories.


2020 ◽  
Vol 11 ◽  
Author(s):  
Jinpeng Li ◽  
Zeming Liu ◽  
Gaosong Wu ◽  
Meilin Yi ◽  
Yongfeng Chen ◽  
...  

Background: D-dimer is a small protein fragment and high levels of D-dimer have been associated with increased mortality in patients presenting to emergency departments with infection. Previous studies have reported increased levels of D-dimer in COVID-19; however, it is unclear whether an increased D-dimer level provides early warning of poor prognosis. Therefore, this study aimed to assess the usefulness of D-dimer as an early indicator of prognosis in patients with coronavirus disease (COVID-19).Methods: We conducted a retrospective study of patients with COVID-19 admitted to Leishenshan Hospital in Wuhan, China, from February 15 to March 30, 2020. The final date of follow-up was April 11, 2020.Results: Of the 1,643 patients with COVID-19, 691 had elevated D-dimer levels. Their median age was 65 years. Of the patients with elevated D-dimer levels, 45% had comorbidities, with cardiovascular disease (205 [29.7%]) being the most common. Patients with elevated D-dimer were more likely to require treatment with high-flow oxygen, anticoagulation, antibiotics, and admission to the intensive care unit They were also more likely to have increased interleukin-6, monocytes, and lymphocytes. Patients with elevated D-dimer levels had significantly higher mortality than those with normal or low D-dimer levels.Conclusion: In patients with COVID-19, elevated D-dimer was associated with abnormal immunity, underlying disease, increased disease severity, and increased mortality. Taken together, D-dimer may be a marker for the early warning of disease severity and increased risk of death. These findings provide insights into the potential risk of elevated D-dimer in patients with COVID-19.


2019 ◽  
Vol 29 (1) ◽  
pp. 39-50
Author(s):  
Rika Mayasari ◽  
Hotnida Sitorus ◽  
Milana Salim ◽  
Surakhmi Oktavia ◽  
Yanelza Supranelfy ◽  
...  

Abstract Dengue hemorrhagic fever is an acute epidemic disease that requires a good and complete clinical examination accompanied by an accurate laboratory examination if clinical symptoms are inadequate. The delays in diagnosis results in an increased risk of death. Hospital facilities and health workers are very influential in the recovery of patients with dengue fever. . This scientific paper presents the characteristics of patients (gender, age, temperature, leukocytes, hematocrit, platelets, hemoglobin) in patient of dengue fever in Prabumulih City Hospital. Data analysis was performed on medical record data of patients with dengue fever who were hospitalized in January-May 2016 at Prabumulih City Hospital. This type of research is descriptive analytic with retrospective design. The data discussed is the result of observing the patient’s clinical condition from the first day to the eighth day. The majority of DHF patients are female with the most age groups at 0-4 years. The body temperature of the highest DHF patients on day 1 was 39.80 C and on the eighth day showed a normal temperature of 36.50 C. The lowest hematological value on day 1 was leukocytes of 1,600 cells/mm3 , hematocrit was 27.9%, platelets were 8,000 cells / mm3 , hemoglobin 9.4 gram / dL. The lowest hematological value on the last six days of treatment is 5,600 cell / mm3 leukocytes, 27.9% hematocrit, 74,000 cell / mm3 platelets, 9.7 gram/dL hemoglobin. Hematological values for normal leukocytes and platelets while platelets and hemoglobin did not approach normal values. Abstrak Demam berdarah dengue (DBD) adalah penyakit epidemik akut yang memerlukan pemeriksaan klinis yang baik dan lengkap disertai pemeriksaan laboratorium yang akurat jika gejala klinis tidak memadai. Keterlambatan dalam diagnosis mengakibatkan peningkatan risiko kematian. Fasilitas rumah sakit dan tenaga kesehatan sangat berpengaruh dalam kesembuhan pasien demam berdarah. Naskah ilmiah ini menyajikan karakteristik pasien (jenis kelamin, umur, suhu, leukosit, hematokrit, trombosit, dan hemoglobin) rawat inap demam berdarah di RSUD Kota Prabumulih. Analisa data dilakukan terhadap data rekam medis pasien demam berdarah yang rawat inap bulan Januari-Mei 2016 di RSUD Kota Prabumulih. Jenis penelitian ini adalah deskriptif analitik dengan desain retrospektif. Data yang dibahas adalah hasil pengamatan keadaan klinis pasien mulai pada hari pertama hingga hari ke delapan. Mayoritas pasien DBD berjenis kelamin perempuan dengan kelompok umur terbanyak pada 0-4 tahun. Suhu tubuh pasien DBD tertinggi pada hari ke 1 adalah 39,80 C dan pada hari ke delapan menunjukkan suhu normal yaitu 36,50 C. Nilai hematologi terendah pada hari ke 1 yaitu leukosit sebesar 1.600 sel/mm3 , hematokrit 27,9%, trombosit 8.000 sel/mm3 , hemoglobin 9,4 gram/dL. Nilai hematologi terendah pada hari ke enam terakhir perawatan yaitu leukosit 5.600 sel/mm3 , hematokrit 27,9%, trombosit 74.000 sel/mm3 , hemoglobin 9,7 gram/dL. Nilai hematologi untuk leukosit dan trombosit normal sedangkan trombosit dan hemoglobin tidak mendekati nilai normal.


Author(s):  
Ljiljana Jovanović ◽  
Vesna Subota ◽  
Milena Rajković ◽  
Bojana Subotić ◽  
Boris Džudović ◽  
...  

Abstract In patients with pulmonary embolism (PE), the D-Dimer assay is commonly utilized as part of the diagnostic workup, but data on D-Dimer for early risk stratification and short-term mortality prediction are limited. The purpose of this study was to determine D-Dimer levels as a predictive biomarker of PE outcomes in younger (<50 years of age) compared to older patients. We conducted retrospective analysis for 930 patients diagnosed with PE between 2015 and 2019 as part of the Serbian University Multicenter Pulmonary Embolism Registry (SUPER).All patients had D-Dimer levels measured within 24 hours of hospital admission. The primary outcome was mortality at 30 days or during hospitalization. Patients were categorized into two groups based on age (≤ 50 and >50 years of age). Younger patients constituted 20.5% of the study cohort. Regarding all-cause mortality, 5.2% (10/191)of patients died in group under the 50 years of age; the short-term all-causemortality was 12.4% (92/739) in older group.We have found that there was significant difference in plasma D-Dimer level between patients ≤ 50 years of age and older group (>50), p= 0.006.D-Dimer plasma level had good predictive value for the primary outcome in younger patients (c-statistics 0.710; 95% CI, 0.640-0.773; p<0.031). The optimal cutoff level for D-Dimer to predict PE-cause death in patients aged > 50 years was found to be 8.8 mg/l FEU(c-statistics 0,580; 95% CI 0.544-0.616; p=0.049). In younger PE patients, D-Dimer levels have good prognostic performance for 30-day all-cause mortalityand concentrations above 6.3 mg/l FEU are associated with increased risk of death. D-Dimer in patients aged over 50 years does not have predictive ability for all-caused short-term mortality. The relationship between D-Dimer and age in patients with PE may need further evaluation.


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