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1.
J Vet Intern Med ; 36(2): 532-540, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1799262

ABSTRACT

BACKGROUND: Infection with Bartonella species is common in cats but reported effects of bacteremia on laboratory variables differ. OBJECTIVES: Evaluate for associations between Bartonella bacteremia and CBC and serum biochemical changes in sick and healthy cats throughout the United States. ANIMALS: A total of 3964 client-owned cats. METHODS: Retrospective cohort study using submissions to a commercial laboratory between 2011 and 2017. Serum biochemistry and CBC abnormalities (categorized as above or below reference intervals), age, and location (high- or low-risk state for Ctenocephalides felis) in presumed healthy and sick cats were evaluated for associations with presence of Bartonella spp. DNA, detected by PCR. Univariate and multivariable logistic regression analyses were performed. RESULTS: Bartonella spp. DNA was amplified from 127 (3.2%) of 3964 cats; 126 (99.2%) of 127 were from high flea risk states and 121 (95.3%) of 127 were presumed sick. Fever of unknown origin was the most common PCR panel requested. In the multivariable analysis, neutrophilia, decreased ALP activity, clinical status (presumed sick), and young age (≤2 years) each were positively associated whereas neutropenia and hyperproteinemia both were negatively associated with Bartonella spp. bacteremia. Presence of Bartonella spp. DNA had no association with test results for other infectious disease agents. CONCLUSIONS AND CLINICAL IMPORTANCE: In both healthy and sick cats, active Bartonella infections had minimal association with clinically relevant laboratory abnormalities. However, based on these results, in areas considered high risk for C. felis, active infection with Bartonella spp. is a reasonable differential diagnosis for cats presented with unexplained fever and neutrophilia, particularly if the cat is young.


Subject(s)
Bartonella Infections , Bartonella , Cat Diseases , Animals , Bartonella/genetics , Bartonella Infections/veterinary , Blood Cell Count/veterinary , Cats , DNA , Humans , Retrospective Studies
2.
Mech Ageing Dev ; 204: 111674, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1783626

ABSTRACT

To reduce the mortality of COVID-19 older patients, clear criteria to predict in-hospital mortality are urgently needed. Here, we aimed to evaluate the performance of selected routine laboratory biomarkers in improving the prediction of in-hospital mortality in 641 consecutive COVID-19 geriatric patients (mean age 86.6 ± 6.8) who were hospitalized at the INRCA hospital (Ancona, Italy). Thirty-four percent of the enrolled patients were deceased during the in-hospital stay. The percentage of severely frail patients, assessed with the Clinical Frailty Scale, was significantly increased in deceased patients compared to the survived ones. The age-adjusted Charlson comorbidity index (CCI) score was not significantly associated with an increased risk of death. Among the routine parameters, neutrophilia, eosinopenia, lymphopenia, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, procalcitonin, IL-6, and NT-proBNP showed the highest predictive values. The fully adjusted Cox regressions models confirmed that high neutrophil %, NLR, derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte count, eosinophil %, and lymphocyte-to-monocyte ratio (LMR) were the best predictors of in-hospital mortality, independently from age, gender, and other potential confounders. Overall, our results strongly support the use of routine parameters, including complete blood count, in geriatric patients to predict COVID-19 in-hospital mortality, independent from baseline comorbidities and frailty.


Subject(s)
COVID-19 , Frailty , Aged , Aged, 80 and over , Blood Cell Count , COVID-19/diagnosis , Hospital Mortality , Humans , Prognosis , Retrospective Studies
4.
Front Immunol ; 13: 794006, 2022.
Article in English | MEDLINE | ID: covidwho-1742215

ABSTRACT

To rapidly prognosticate and generate hypotheses on pathogenesis, leukocyte multi-cellularity was evaluated in SARS-CoV-2 infected patients treated in India or the United States (152 individuals, 384 temporal observations). Within hospital (<90-day) death or discharge were retrospectively predicted based on the admission complete blood cell counts (CBC). Two methods were applied: (i) a "reductionist" one, which analyzes each cell type separately, and (ii) a "non-reductionist" method, which estimates multi-cellularity. The second approach uses a proprietary software package that detects distinct data patterns generated by complex and hypothetical indicators and reveals each data pattern's immunological content and associated outcome(s). In the Indian population, the analysis of isolated cell types did not separate survivors from non-survivors. In contrast, multi-cellular data patterns differentiated six groups of patients, including, in two groups, 95.5% of all survivors. Some data structures revealed one data point-wide line of observations, which informed at a personalized level and identified 97.8% of all non-survivors. Discovery was also fostered: some non-survivors were characterized by low monocyte/lymphocyte ratio levels. When both populations were analyzed with the non-reductionist method, they displayed results that suggested survivors and non-survivors differed immunologically as early as hospitalization day 1.


Subject(s)
Blood Cell Count/methods , COVID-19/immunology , SARS-CoV-2/physiology , Adult , COVID-19/diagnosis , COVID-19/mortality , Diagnostic Tests, Routine , Female , Humans , India , Male , Middle Aged , Precision Medicine , Retrospective Studies , Software , Survival Analysis , United States
5.
J Virol ; 96(3): e0082621, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1691430

ABSTRACT

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV-1. However, its primary receptor portfolio remains controversial, potentially including sialic acid, coxsackie and adenovirus receptor (CAR), integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned on the basis of the inability to cocrystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infection in vitro and in vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domain CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild-type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (i.m.) injection but not after intranasal (i.n.) administration. Ad26 transduction was 10-fold lower than Ad5 transduction after intratumoral (i.t.) injection of CD46-expressing tumors. Ad26 transduction of liver was 1,000-fold lower than that ofAd5 after intravenous (i.v.) injection. These data demonstrate the use of CD46 by Ad26 in certain situations but also show that the receptor has little consequence by other routes of administration. Finally, i.v. injection of high doses of Ad26 into CD46 mice induced release of liver enzymes into the bloodstream and reduced white blood cell counts but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during coronavirus disease 2019 (COVID-19) vaccination with this serotype of adenovirus. IMPORTANCE The human species D Ad26 is being investigated as a low-seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection and its role in virus biology, vaccine efficacy, and, importantly, vaccine safety.


Subject(s)
Adenovirus Infections, Human/metabolism , Adenovirus Infections, Human/virology , Adenoviruses, Human/classification , Adenoviruses, Human/physiology , Coxsackie and Adenovirus Receptor-Like Membrane Protein/metabolism , Host-Pathogen Interactions , Membrane Cofactor Protein/metabolism , Adenoviruses, Human/ultrastructure , Animals , Biomarkers , Blood Cell Count , CHO Cells , Cell Line , Coxsackie and Adenovirus Receptor-Like Membrane Protein/chemistry , Cricetulus , Disease Models, Animal , Gene Expression , Humans , Membrane Cofactor Protein/chemistry , Membrane Cofactor Protein/genetics , Mice, Transgenic , Models, Biological , Models, Molecular , Mutagenesis , Protein Binding , Protein Conformation , Serogroup , Sialic Acids/metabolism , Sialic Acids/pharmacology , Structure-Activity Relationship
6.
Viruses ; 14(2)2022 01 20.
Article in English | MEDLINE | ID: covidwho-1649018

ABSTRACT

While numerous studies have already compared the immune responses against SARS-CoV-2 in severely and mild-to-moderately ill COVID-19 patients, longitudinal trajectories are still scarce. We therefore set out to analyze serial blood samples from mild-to-moderately ill patients in order to define the immune landscapes for differently progressed disease stages. Twenty-two COVID-19 patients were subjected to consecutive venipuncture within seven days after diagnosis or admittance to hospital. Flow cytometry was performed to analyze peripheral blood immune cell compositions and their activation as were plasma levels of cytokines and SARS-CoV-2 specific immunoglobulins. Healthy donors served as controls. Integrating the kinetics of plasmablasts and SARS-CoV-2 specific antibodies allowed for the definition of three disease stages of early COVID-19. The incubation phase was characterized by a sharp increase in pro-inflammatory monocytes and terminally differentiated cytotoxic T cells. The latter correlated significantly with elevated concentrations of IP-10. Early acute infection featured a peak in PD-1+ cytotoxic T cells, plasmablasts and increasing titers of virus specific antibodies. During late acute infection, immature neutrophils were enriched, whereas all other parameters returned to baseline. Our findings will help to define landmarks that are indispensable for the refinement of new anti-viral and anti-inflammatory therapeutics, and may also inform clinicians to optimize treatment and prevent fatal outcomes.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , COVID-19/physiopathology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Acute Disease , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , Blood Cell Count , Chemokine CXCL10/blood , Chemokine CXCL10/immunology , Cytokines/blood , Cytokines/immunology , Female , Humans , Inflammation , Longitudinal Studies , Male , Middle Aged , Neutrophils/immunology , T-Lymphocytes, Cytotoxic/immunology , Young Adult
7.
Microvasc Res ; 140: 104303, 2022 03.
Article in English | MEDLINE | ID: covidwho-1568955

ABSTRACT

Systemic inflammatory response, as observed in sepsis and severe COVID-19, may lead to endothelial damage. Therefore, we aim to compare the extent of endothelial injury and its relationship to inflammation in both diseases. We included patients diagnosed with sepsis (SEPSIS group, n = 21), mild COVID-19 (MILD group, n = 31), and severe COVID-19 (SEVERE group, n = 24). Clinical and routine laboratory data were obtained, circulating cytokines (INF-γ, TNF-α, and IL-10) and endothelial injury markers (E-Selectin, Tissue Factor (TF) and von Willebrand factor (vWF)) were measured. Compared to the SEPSIS group, patients with severe COVID-19 present similar clinical and laboratory data, except for lower circulating IL-10 and E-Selectin levels. Compared to the MILD group, patients in the SEVERE group showed higher levels of TNF-α, IL-10, and TF. There was no clear relationship between cytokines and endothelial injury markers among the three studied groups; however, in SEVERE COVID-19 patients, there is a positive relationship between INF-γ with TF and a negative relationship between IL-10 and vWF. In conclusion, COVID-19 and septic patients have a similar pattern of cytokines and endothelial dysfunction markers. These findings highlight the importance of endothelium dysfunction in COVID-19 and suggest that endothelium should be better evaluated as a therapeutic target for the disease.


Subject(s)
COVID-19/pathology , Endothelium, Vascular/pathology , SARS-CoV-2 , Sepsis/pathology , Systemic Inflammatory Response Syndrome/blood , Aged , Aged, 80 and over , Biomarkers , Blood Cell Count , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/complications , COVID-19/physiopathology , E-Selectin/blood , Female , Humans , Interferon-gamma/blood , Interleukin-10/blood , Male , Middle Aged , Retrospective Studies , Sepsis/blood , Sepsis/complications , Sepsis/physiopathology , Severity of Illness Index , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/physiopathology , Thromboplastin/analysis , Tumor Necrosis Factor-alpha/analysis , von Willebrand Factor/analysis
8.
Hematology ; 26(1): 1007-1012, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1555722

ABSTRACT

BACKGROUND: Haematological markers such as absolute lymphopenia have been associated with severe COVID-19 infection. However, in the literature to date, the cohorts described have typically included patients who were moderate to severely unwell with pneumonia and who required intensive care stay. It is uncertain if these markers apply to a population with less severe illness. We sought to describe the haematological profile of patients with mild disease with COVID-19 admitted to a single centre in Singapore. METHODS: We examined 554 consecutive PCR positive SARS-COV-2 patients admitted to a single tertiary healthcare institution from Feb 2020 to April 2020. In all patients a full blood count was obtained within 24 h of presentation. RESULTS: Patients with pneumonia had higher neutrophil percentages (66.5 ± 11.6 vs 55.2 ± 12.6%, p < 0.001), lower absolute lymphocyte count (1.5 ± 1.1 vs 1.9 ± 2.1 x109/L, p < 0.011) and absolute eosinophil count (0.2 ± 0.9 vs 0.7 ± 1.8 × 109/L, p = 0.002). Platelet counts (210 ± 56 vs 230 ± 61, p = 0.020) were slightly lower in the group with pneumonia. We did not demonstrate significant differences in the neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in patients with or without pneumonia. Sixty-eight patients (12.3%) had peripheral eosinophilia. This was more common in migrant workers living in dormitories. CONCLUSION: Neutrophilia and lymphopenia were found to be markers associated with severe COVID-19 illness. We did not find that combined haematological parameters: neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio, had any association with disease severity in our cohort of patients with mild-moderate disease. Migrant workers living in dormitories had eosinophilia which may reflect concurrent chronic parasitic infection.


Subject(s)
Blood Cell Count , COVID-19/blood , Pandemics , SARS-CoV-2 , Adult , Anthelmintics/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Dyslipidemias/epidemiology , Eosinophilia/epidemiology , Eosinophilia/etiology , Female , Fever/epidemiology , Fever/etiology , Housing , Humans , Hypertension/epidemiology , Hypoxia/epidemiology , Hypoxia/etiology , Male , Middle Aged , Neutrophils , Parasitic Diseases/drug therapy , Parasitic Diseases/epidemiology , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Singapore/epidemiology , Tertiary Care Centers/statistics & numerical data , Transients and Migrants/statistics & numerical data , Travel-Related Illness , Young Adult
9.
Clin Lab ; 67(12)2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1538779

ABSTRACT

BACKGROUND: Coronavirus disease, which initially appeared in Wuhan, China during the month of December 2019, very quickly spread and became a worldwide pandemic. The African continent was not spared. The poor health system and low socioeconomic status in some regions has raised concern on the risk of an epidemic disaster due to the rapid transmission of the virus. This study therefore aims to determine the relationship between the modifications of complete blood count parameters, CRP, and the severity and outcome of SARS-CoV2 infection in the first patients hospitalized at the Centre Hospitalier Universitaire de Libreville (Libreville University Hospital Center) in Gabon. METHODS: This is a prospective study led from April to July 2020 in the COVID infectious department (SICov) of the Centre Hospitalier Universitaire de Libreville (CHUL). RESULTS: In total, 184 patients participated in the study. The median age was 47 (37 - 54) years. Male subjects predominated. The median number of leucocytes was 5.6 (4.4 - 7.45) x 109/L. It was significantly higher in patients with acute respiratory distress syndrome (ARDS) and in intensive care units (ICU) compared to pauci-symptomatic cases (p < 0.01). Factors associated with death were leukocytosis (crude OR 37.1 (8.3 - 98.4) p < 0.01), neutrophilia (OR 20.1 (4.6 - 89.0) p < 0.01), NRL ≥ 9 (OR 13.5 (2.7 - 67.4); p < 0.01) and CRP > 100 mg/L (OR 17.8 (2.0 - 154.0) p = 0.02). CONCLUSIONS: The hematological profile of patients with COVID-19 varies according to the severity of the disease. Leukocytosis, neutrophilia, a NLR above 6 and a CRP higher than 100 mg/L were associated with the severity of the infection and death in Gabonese patients.


Subject(s)
C-Reactive Protein , COVID-19 , Receptors, Immunologic , Blood Cell Count , Humans , Male , Middle Aged , Patient Acuity , Prospective Studies , RNA, Viral , Receptors, Immunologic/analysis , SARS-CoV-2
10.
Biochem Med (Zagreb) ; 31(3): 030501, 2021 Oct 15.
Article in English | MEDLINE | ID: covidwho-1534569

ABSTRACT

Coronavirus disease 2019 (COVID-19) pandemic represents a scientific and social crisis. One of the main unmet needs for coronavirus disease 2019 is its unpredictable clinical course, which can rapidly change in an irreversible outcome. COVID-19 patients can be classified into mild, moderate, and severe. Several haematological parameters, such as platelets, white blood cell total count, lymphocytes, neutrophils, (together with neutrophil-lymphocyte and platelet-lymphocyte ratio), and haemoglobin were described to be associated with COVID-19 infection and severity. The purpose of these review is to describe the current state of the art about complete blood count alterations during COVID-19 infection, and to summarize the crucial role of some haematological parameters during the course of the disease. Decreased platelet, lymphocyte, haemoglobin, eosinophil, and basophil count, increased neutrophil count and neutrophil-lymphocyte and platelet-lymphocyte ratio have been associated with COVID-19 infection and a worse clinical outcome. Our study adds some novelty about the identification of effective biomarkers of progressive disease, and might be helpful for diagnosis, prevention of complications, and effective therapy.


Subject(s)
COVID-19 , Blood Cell Count , Humans , Leukocyte Count , Lymphocytes , Neutrophils , Retrospective Studies , SARS-CoV-2
11.
Biomed Res Int ; 2021: 1676914, 2021.
Article in English | MEDLINE | ID: covidwho-1533104

ABSTRACT

OBJECTIVES: This study screened for factors affecting coronavirus disease 2019 (COVID-19) incidence in type 1 diabetes mellitus (T1DM) patients, appraised vitamin D's efficacy in preventing COVID-19, and assessed the effects of clinical characteristics, glycemic status, vitamin D, and hydroxychloroquine administration on COVID-19's progression and severity in T1DM patients. METHODS: This retrospective research on 150 adults was conducted at Security Forces Hospital, Riyadh, KSA. Participants were allocated to three groups (50/group): control, T1DM, and T1DM with COVID-19. Participants' fasting blood glucose (FBG), glycated hemoglobin (HbA1c), complete blood count, vitamin D, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, lactate dehydrogenase (LDH), prothrombin time, activated partial thromboplastin time, D-dimer, liver and kidney function, and hydroxychloroquine treatment were retrieved and analyzed. RESULTS: The percentages of comorbidities and not taking hydroxychloroquine were significantly higher among T1DM patients with COVID-19 than patients with T1DM only. Mean vitamin D level was significantly lower in T1DM with COVID-19 patients than in the other two groups. Vitamin D showed a significant negative correlation with LDH, CRP, ESR, ferritin, and D-dimer, which was the most reliable predictor of COVID-19 severity in T1DM patients. CONCLUSION: Comorbidities and vitamin D deficiency are risk factors for COVID-19 in patients with T1DM. Patients who do not take hydroxychloroquine and have higher FBG and HbA1c levels are vulnerable to COVID-19. Vitamin D may be useful for preventing COVID-19 in T1DM patients. Comorbidities, higher FBG and HbA1c levels, not taking hydroxychloroquine, and vitamin D inadequacy elevate COVID-19 progression and severity in patients with T1DM.


Subject(s)
Biomarkers/blood , COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 1/epidemiology , Hydroxychloroquine/therapeutic use , Vitamin D/therapeutic use , Adult , Blood Cell Count , Blood Glucose/metabolism , Blood Sedimentation , C-Reactive Protein/metabolism , COVID-19/blood , Comorbidity , Cross-Sectional Studies , Diabetes Mellitus, Type 1/blood , Disease Progression , Female , Glycated Hemoglobin A/metabolism , Humans , Incidence , Male , Retrospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology , Severity of Illness Index
13.
Future Microbiol ; 16: 1389-1400, 2021 12.
Article in English | MEDLINE | ID: covidwho-1528783

ABSTRACT

Background: We aimed to compare the clinical, laboratory and radiological findings of confirmed COVID-19 and unconfirmed patients. Methods: This was a single-center, retrospective study. Results: Overall, 620 patients (338 confirmed COVID-19 and 282 unconfirmed) were included. Confirmed COVID-19 patients had higher percentages of close contact with a confirmed or probable case. In univariate analysis, the presence of myalgia and dyspnea, decreased leukocyte, neutrophil and platelet counts were best predictors for SARS-CoV-2 RT-PCR positivity. Multivariate analyses revealed that only platelet count was an independent predictor for SARS-CoV-2 RT-PCR positivity. Conclusion: Routine complete blood count may be helpful for distinguishing COVID-19 from other respiratory illnesses at an early stage, while PCR testing is unique for the diagnosis of COVID-19.


Subject(s)
COVID-19/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Blood Cell Count , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/virology , Female , Humans , Male , Middle Aged , Radiography , Retrospective Studies , SARS-CoV-2/classification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Thorax/diagnostic imaging , Tomography, X-Ray Computed , Young Adult
14.
J Virol ; 96(3): e0082621, 2022 02 09.
Article in English | MEDLINE | ID: covidwho-1522911

ABSTRACT

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV-1. However, its primary receptor portfolio remains controversial, potentially including sialic acid, coxsackie and adenovirus receptor (CAR), integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned on the basis of the inability to cocrystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infection in vitro and in vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domain CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild-type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (i.m.) injection but not after intranasal (i.n.) administration. Ad26 transduction was 10-fold lower than Ad5 transduction after intratumoral (i.t.) injection of CD46-expressing tumors. Ad26 transduction of liver was 1,000-fold lower than that ofAd5 after intravenous (i.v.) injection. These data demonstrate the use of CD46 by Ad26 in certain situations but also show that the receptor has little consequence by other routes of administration. Finally, i.v. injection of high doses of Ad26 into CD46 mice induced release of liver enzymes into the bloodstream and reduced white blood cell counts but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during coronavirus disease 2019 (COVID-19) vaccination with this serotype of adenovirus. IMPORTANCE The human species D Ad26 is being investigated as a low-seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection and its role in virus biology, vaccine efficacy, and, importantly, vaccine safety.


Subject(s)
Adenovirus Infections, Human/metabolism , Adenovirus Infections, Human/virology , Adenoviruses, Human/classification , Adenoviruses, Human/physiology , Coxsackie and Adenovirus Receptor-Like Membrane Protein/metabolism , Host-Pathogen Interactions , Membrane Cofactor Protein/metabolism , Adenoviruses, Human/ultrastructure , Animals , Biomarkers , Blood Cell Count , CHO Cells , Cell Line , Coxsackie and Adenovirus Receptor-Like Membrane Protein/chemistry , Cricetulus , Disease Models, Animal , Gene Expression , Humans , Membrane Cofactor Protein/chemistry , Membrane Cofactor Protein/genetics , Mice, Transgenic , Models, Biological , Models, Molecular , Mutagenesis , Protein Binding , Protein Conformation , Serogroup , Sialic Acids/metabolism , Sialic Acids/pharmacology , Structure-Activity Relationship
15.
BMJ Case Rep ; 14(11)2021 Nov 11.
Article in English | MEDLINE | ID: covidwho-1515267

ABSTRACT

Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/µL of blood. Nitrofurantoin has been associated with haematological adverse events, but few agranulocytosis cases worldwide have been reported. We present a case of a 68-year-old woman who presented with fever and agranulocytosis following treatment with nitrofurantoin. Extensive workup for agranulocytosis, including a bone marrow aspirate, was unremarkable. Treatment with nitrofurantoin was discontinued, which led to a complete recovery of the complete blood count. This case stresses the importance of monitoring treatments, given that widely used drugs are not free from severe adverse reactions.


Subject(s)
Neutropenia , Nitrofurantoin , Aged , Blood Cell Count , Female , Humans , Leukocyte Count , Neutrophils , Nitrofurantoin/adverse effects
16.
Saudi Med J ; 42(4): 370-376, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1513257

ABSTRACT

OBJECTIVES: To assess the neutrophil-to-lymphocyte ratio (NLR) diagnostic and prognostic value in the context of Coronavirus disease-2019 (COVID-19) infection in Saudi Arabia. METHODS: A case-control study in which 701 confirmed COVID-19 patients (of which 41 were intensive care unit [ICU]-admitted) and 250 control subjects were enrolled. The study was conducted retrospectively in October on patients admitted to 3 separate hospitals in Saudi Arabia namely: King Abdullah Bin Abdulaziz University Hospital (Riyadh), Ohud Hospital (Madinah), and Nojood Medical Center (Madinah) between May and September 2020. Neutrophil-to-lymphocyte ratio was calculated based on absolute neutrophil and lymphocyte count. Institutional ethical approval was obtained prior to the study. RESULTS: Patients (median age 35 years), of which 54.8% were females, were younger than the control cohort (median age 48 years). Patients had significantly higher NLR compared to the control group. Intensive care unit admitted patients had significantly higher platelet, WBC and neutrophil counts. The ICU patients' NLR was almost twice as of the non-intensive patients. The NLR value of 5.5 was found to be of high specificity (96.4%) and positive predictive value (91.4%) in diagnosing COVID-19. Furthermore, it had a very good sensitivity (86.4%) in predicting severe forms of disease, such as, ICU admission. CONCLUSION: Neutrophil-to-lymphocyte ratio is an important tool in determining the COVID-19 clinical status. This study further confirms the prognostic value of NLR in detecting severe infection, and those patients with high NLR should be closely monitored and managed.


Subject(s)
COVID-19/diagnosis , Lymphocyte Count , Neutrophils , Adult , Blood Cell Count , COVID-19/blood , Case-Control Studies , Female , Hospitalization , Humans , Intensive Care Units , Leukocyte Count , Male , Middle Aged , Platelet Count , Predictive Value of Tests , Prognosis , Retrospective Studies , SARS-CoV-2 , Saudi Arabia , Sensitivity and Specificity , Severity of Illness Index
17.
J Clin Lab Anal ; 35(12): e24100, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1508785

ABSTRACT

OBJECTIVES: This study aimed to explore clinical indexes for management of severe/critically ill patients with COVID-19, influenza A H7N9, and H1N1 pneumonia by comparing hematological and radiological characteristics. METHODS: Severe/critically ill patients with COVID-19, H7N9, and H1N1 pneumonia were retrospectively enrolled. The demographic data, clinical manifestations, hematological parameters, and radiological characteristics were compared. RESULTS: In this study, 16 cases of COVID-19, 10 cases of H7N9, and 13 cases of H1N1 who met severe/critically ill criteria were included. Compared with COVID-19, H7N9 and H1N1 groups had more chronic diseases (80% and 92.3% vs. 25%, p < 0.05), higher APACHE Ⅱ scores (16.00 ± 8.63 and 15.08 ± 6.24, vs. 5.50 ± 2.58, p < 0.05), higher mortality rates (40% and 46.2% vs. 0%, p < 0.05), significant lymphocytopenia (0.59 ± 0.31 × 109 /L and 0.56 ± 0.35 × 109 /L vs. 0.97 ± 0.33 × 109 /L, p < 0.05), and elevated neutrophil-to-lymphocyte ratio (NLR; 14.67 ± 6.10 and 14.64 ± 10.36 vs. 6.29 ± 3.72, p < 0.05). Compared with the H7N9 group, ground-glass opacity (GGO) on chest CT was common in the COVID-19 group (p = 0.028), while pleural effusion was rare (p = 0.001). CONCLUSIONS: The NLR can be used as a clinical parameter for the predication of risk stratification and outcome in COVID-19 and influenza A pneumonia. Manifestations of pleural effusion or GGO in chest CT may be helpful for the identification of different viral pneumonia.


Subject(s)
COVID-19/blood , COVID-19/diagnostic imaging , Influenza, Human/blood , Influenza, Human/diagnostic imaging , Aged , Aged, 80 and over , Blood Cell Count , COVID-19/etiology , Chronic Disease , Critical Illness , Female , Humans , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H7N9 Subtype , Influenza, Human/etiology , Influenza, Human/virology , Male , Middle Aged , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Retrospective Studies , Sex Factors
18.
Sci Rep ; 11(1): 21136, 2021 10 27.
Article in English | MEDLINE | ID: covidwho-1493228

ABSTRACT

The COVID-19 pandemic is impressively challenging the healthcare system. Several prognostic models have been validated but few of them are implemented in daily practice. The objective of the study was to validate a machine-learning risk prediction model using easy-to-obtain parameters to help to identify patients with COVID-19 who are at higher risk of death. The training cohort included all patients admitted to Fondazione Policlinico Gemelli with COVID-19 from March 5, 2020, to November 5, 2020. Afterward, the model was tested on all patients admitted to the same hospital with COVID-19 from November 6, 2020, to February 5, 2021. The primary outcome was in-hospital case-fatality risk. The out-of-sample performance of the model was estimated from the training set in terms of Area under the Receiving Operator Curve (AUROC) and classification matrix statistics by averaging the results of fivefold cross validation repeated 3-times and comparing the results with those obtained on the test set. An explanation analysis of the model, based on the SHapley Additive exPlanations (SHAP), is also presented. To assess the subsequent time evolution, the change in paO2/FiO2 (P/F) at 48 h after the baseline measurement was plotted against its baseline value. Among the 921 patients included in the training cohort, 120 died (13%). Variables selected for the model were age, platelet count, SpO2, blood urea nitrogen (BUN), hemoglobin, C-reactive protein, neutrophil count, and sodium. The results of the fivefold cross-validation repeated 3-times gave AUROC of 0.87, and statistics of the classification matrix to the Youden index as follows: sensitivity 0.840, specificity 0.774, negative predictive value 0.971. Then, the model was tested on a new population (n = 1463) in which the case-fatality rate was 22.6%. The test model showed AUROC 0.818, sensitivity 0.813, specificity 0.650, negative predictive value 0.922. Considering the first quartile of the predicted risk score (low-risk score group), the case-fatality rate was 1.6%, 17.8% in the second and third quartile (high-risk score group) and 53.5% in the fourth quartile (very high-risk score group). The three risk score groups showed good discrimination for the P/F value at admission, and a positive correlation was found for the low-risk class to P/F at 48 h after admission (adjusted R-squared = 0.48). We developed a predictive model of death for people with SARS-CoV-2 infection by including only easy-to-obtain variables (abnormal blood count, BUN, C-reactive protein, sodium and lower SpO2). It demonstrated good accuracy and high power of discrimination. The simplicity of the model makes the risk prediction applicable for patients in the Emergency Department, or during hospitalization. Although it is reasonable to assume that the model is also applicable in not-hospitalized persons, only appropriate studies can assess the accuracy of the model also for persons at home.


Subject(s)
COVID-19/mortality , Machine Learning , Pandemics , SARS-CoV-2 , Aged , Aged, 80 and over , Blood Cell Count , Blood Chemical Analysis , COVID-19/blood , Cohort Studies , Female , Hospital Mortality , Humans , Male , Middle Aged , Models, Statistical , Multivariate Analysis , Oxygen/blood , Pandemics/statistics & numerical data , ROC Curve , Risk Factors , Rome/epidemiology
19.
Int J Lab Hematol ; 43(6): 1334-1340, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1443280

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV2 can present from mild flu-like symptoms to acute respiratory distress syndrome. There is multi-organ involvement; particularly, hematopoietic system can be associated with morphological changes in blood cells of COVID-19 patients. METHOD: We conducted a cross-sectional study on a cohort of 50 COVID-19 patients, confirmed on RT-PCR with documented cycle threshold (Ct) value. Peripheral blood sample of these patients was collected and examined for complete blood counts (CBC) on automated haematological analyser as well as Leishman-stained blood smears to look for morphological changes in blood cells. Morphological changes were evaluated with reference to clinical severity and Ct value. Additionally, association between Ct value and clinical severity was also performed. Statistical tests were performed, and P value <.05 was considered significant. RESULTS: Mean age of our study group was 42.16 ± 15.55 years, with male preponderance. Most commonly observed peripheral blood changes were hypolobation (P value = .002) and toxic granules (P value = .005) in neutrophils, atypical granules with nucleolar prominence in lymphocytes, cytoplasmic granulation with clumped nuclear chromatin in monocytes, giant platelets and thrombocytopenia and normocytic normochromic anaemia. CONCLUSION: No association was found between clinical severity and Ct value as well as peripheral blood morphological changes with Ct value. We conclude that examination of peripheral smear coupled with complete blood count (CBC) is only partially supportive of disease pathogenesis and to assess the viral load other parameters should be utilised instead of relying solely on Ct value.


Subject(s)
Blood Cells/ultrastructure , COVID-19 Nucleic Acid Testing/methods , COVID-19/blood , SARS-CoV-2/isolation & purification , Viral Load , Viremia/blood , Adult , Aged , Aged, 80 and over , Blood Cell Count , COVID-19/virology , Cell Shape , Cell Size , Cross-Sectional Studies , Cytoplasmic Granules/ultrastructure , Female , Hematopoiesis , Humans , Male , Middle Aged , Nasopharynx/virology , Oropharynx/virology , Prospective Studies , RNA, Viral/blood , Severity of Illness Index , Young Adult
20.
Comput Methods Programs Biomed ; 211: 106444, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1439955

ABSTRACT

BACKGROUND: As blood testing is radiation-free, low-cost and simple to operate, some researchers use machine learning to detect COVID-19 from blood test data. However, few studies take into consideration the imbalanced data distribution, which can impair the performance of a classifier. METHOD: A novel combined dynamic ensemble selection (DES) method is proposed for imbalanced data to detect COVID-19 from complete blood count. This method combines data preprocessing and improved DES. Firstly, we use the hybrid synthetic minority over-sampling technique and edited nearest neighbor (SMOTE-ENN) to balance data and remove noise. Secondly, in order to improve the performance of DES, a novel hybrid multiple clustering and bagging classifier generation (HMCBCG) method is proposed to reinforce the diversity and local regional competence of candidate classifiers. RESULTS: The experimental results based on three popular DES methods show that the performance of HMCBCG is better than only use bagging. HMCBCG+KNE obtains the best performance for COVID-19 screening with 99.81% accuracy, 99.86% F1, 99.78% G-mean and 99.81% AUC. CONCLUSION: Compared to other advanced methods, our combined DES model can improve accuracy, G-mean, F1 and AUC of COVID-19 screening.


Subject(s)
COVID-19 , Blood Cell Count , Cluster Analysis , Humans , Machine Learning , SARS-CoV-2
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