scholarly journals Impact of Strain Variation of Dichelobacter nodosus on Disease Severity and Presence in Sheep Flocks in England

2021 ◽  
Vol 8 ◽  
Author(s):  
Emma M. Monaghan ◽  
Naomi S. Prosser ◽  
Jessica Witt ◽  
Katharine E. Lewis ◽  
Elizabeth Nabb ◽  
...  
Keyword(s):  
Disease Severity ◽  
Strain Variation ◽  
Disease Expression ◽  
Mild Disease ◽  
Dichelobacter Nodosus ◽  
Interdigital Dermatitis

AprV2 and aprB2 are variants of the apr gene of Dichelobacter nodosus, the cause of footrot in sheep. They are putative markers for severe and mild disease expression. The aim of our study was to investigate the distribution of aprV2 and aprB2 in flocks with and without footrot. Our hypotheses were that both strains are present in endemically affected flocks, with aprB2 and aprV2 associated with mild and virulent phenotypes respectively but that D. nodosus is not present in flocks without footrot. Alternatively, aprB2 persists in flocks without footrot. Despite extensive searching over 3 years only three flocks of sheep without footrot were identified. D. nodosus was not detected in these three flocks. In one further flock, only mild interdigital dermatitis was observed, and only aprB2 was detected. Twenty-four flocks with endemic footrot of all severities were sampled on three occasions and all were positive for D. nodosus and the aprV2 variant; aprB2 was detected in only 11 of these flocks. AprB2 was detected as a co-infection with aprV2 in the 22% of samples positive for aprB2 and was more likely in mild footrot phenotypes than severe. Dichelobacter nodosus serogroups were not associated with footrot phenotype. We conclude that D. nodosus, even aprB2 strains, do not persist in flocks in the absence of footrot. Our results support the hypothesis that aprB2 is associated with mild footrot phenotypes. Finally, we conclude that given the small number of flocks without footrot that were identified, footrot is highly endemic in English sheep flocks.

scholarly journals SARS-CoV-2 viral load is associated with increased disease severity and mortality

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jesse Fajnzylber ◽  
◽  
James Regan ◽  
Kendyll Coxen ◽  
Heather Corry ◽  
...  
Keyword(s):  
Viral Load ◽  
Disease Severity ◽  
Diverse Range ◽  
Viral Loads ◽  
Mild Disease ◽  
Reactive Protein ◽  
Markers Of Inflammation ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Absolute Lymphocyte Counts

Abstract The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

scholarly journals Digestive Symptoms in COVID-19 Patients With Mild Disease Severity

2020 ◽  
Vol 115 (6) ◽  
pp. 916-923 ◽  
Author(s):  
Chaoqun Han ◽  
Caihan Duan ◽  
Shengyan Zhang ◽  
Brennan Spiegel ◽  
Huiying Shi ◽  
...  
Keyword(s):  
Disease Severity ◽  
Mild Disease

scholarly journals Dynamic Alterations of Anti-S-Protein Igg Subclasses and of Th1/Th2 Responses are Hallmarks of Acute Severe COVID-19 Disease

2021 ◽  
Author(s):  
Yun Shan Goh ◽  
Siew-Wai Fong ◽  
Siti Naqiah Amrun ◽  
Cheryl Lee ◽  
Pei Xiang Hor ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Th2 Response ◽  
S Protein ◽  
Th1 Response ◽  
Humoral Immune ◽  
Mild Disease ◽  
Humoral Immune Responses ◽  
Disease Spectrum ◽  
Antibody Levels

Abstract PurposeCOVID-19, caused by Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), has a wide disease spectrum ranging from asymptomatic to severe. While it is widely accepted that specific humoral immune responses are critical in controlling the infection, the relationship between the humoral immune response and disease severity is currently unclear.MethodsUsing a flow cytometry-based assay to detect specific antibodies against full length S protein, we compared the antibody levels between patients from different severity groups. We also analysed the cytokine profiles of patients from different severity groups by multiplex microbead-based immunoassay.ResultsWe found an association between specific IgM, IgA and IgG against the spike protein and disease severity. By comparing the ratio of Th1 IgG1 and IgG3 to Th2 IgG2 and IgG4, we observed that all severity groups exhibited a ratio that was skewed towards a stronger Th1 response over Th2 response. In addition to the strong Th1 response, patients with severe disease also developed a Th2 response, as exemplified by the smaller ratio of IgG1 and IgG3 over IgG2 and IgG4 and the smaller Th1/Th2 cytokine ratios, compared to patients with mild disease severity. ConclusionThe results suggest that acute severity or disease resolution is associated with a specific immunological phenotype. A smaller skew towards a Th1 response over Th2 response, during infection, may contribute to disease progression, while a greater skew towards a Th1 response over Th2 response may contribute to a better disease outcome. This may suggest potential therapeutic approaches to COVID-19 disease management.

scholarly journals Immunophenotyping of circulating mononuclear cells in active pulmonary tuberculosis

2018 ◽  
Vol 12 (12) ◽  
pp. 1073-1078
Author(s):  
Amany Elkholy ◽  
Mirvat El Anany ◽  
Ghada Mohamed Ezzat ◽  
Fadwa Abd El Reheem ◽  
Assem Fouad Elessawy
Keyword(s):  
T Cells ◽  
B Lymphocytes ◽  
Disease Severity ◽  
Defense Mechanisms ◽  
Mononuclear Cells ◽  
Immune Defense ◽  
Skin Tests ◽  
Active Pulmonary Tuberculosis ◽  
Mild Disease ◽  
Regulatory Lymphocytes

Introduction: Interpreting the interactions between M. tuberculosis and the host innate and adaptive immune defense mechanisms is mandatory for understanding the pathogenesis of active pulmonary TB (APTB). The aim was to describe the distribution of mononuclear cells in APTB and their relation to disease severity. Methodology: A case-control study of peripheral blood CD4+ T cells, CD8+ T cells, B-lymphocytes, NK cells, T regulatory lymphocytes (Tregs) and monocytes by flow cytometry. The patients had clinical presentations of APTB, positive tuberculin skin tests, acid-fast bacilli smears and sputum cultures using BACTEC 960. Results: There was a significant decrease in the haemoglobin level and the absolute lymphocytic count (p < 0.01), while both the neutrophil count and erythrocyte sedimentation rate showed significant increase in the APTB patients compared to HC with p-values < 0.001 and < 0.0001 respectively. Both the CD4+/CD8+ ratio and the percentages of CD3−CD19+ cells were significantly lower in APTB patients (p = 0.03 and p = 0.005 respectively). The percentages of CD4+, CD8+, CD3−CD19+, CD14+, and CD3−CD (16+56)+ cells showed no significant differences, when comparing either disease severity groups, or cavitated and non-cavitated groups of APTB patients. There was significant increase in the CD4+25+ lymphocytes in the advanced APTB patients than in the mild disease group (p < 0.05). Conclusions: B-lymphocytes and CD4/CD8 ratios were significantly lower in the APTB patients than controls with no association with disease severity. CD4+ CD25+hi Tregs were significantly higher in the advanced versus mild groups.

scholarly journals Genomic heterogeneity of Dichelobacter nodosus within and between UK sheep flocks and between age groups within a flock

2019 ◽  
Author(s):  
PEERS DAVIES ◽  
Adam Blanchard ◽  
Ceri Staley ◽  
Nikki Bollard ◽  
Tracey Coffey ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Age Groups ◽  
Sequence Type ◽  
Causative Pathogen ◽  
Vaccine Production ◽  
Dichelobacter Nodosus ◽  
Pathogen Dynamics ◽  
High Prevalence ◽  
Age Dependent ◽  
Interdigital Dermatitis

Abstract Footrot and interdigital dermatitis are endemic infectious diseases in all sheep farming regions, impairing welfare and production. The development of efficacious vaccines against the primary causative pathogen has been hampered by the extensive antigenic diversity of Dichelobacter nodosus. Understanding the heterogeneity of the pathogen within and between farms is essential if the feasibility of bespoke vaccine production is to be assessed. In this study 56 ewe and lamb isolates from 9 farms were compared by D. nodosus serogroup and Multi Locus Sequence Type which provides significantly enhanced discriminatory power for molecular epidemiology. . Within farm genomic heterogeneity was significantly lower than between farms. Serogroup heterogeneity between flocks ranged from two to five unique serogroups per flock. Three flocks contained isolates of two serogroups, two flocks contained isolates of three serogroups and one flock included isolates of five serogroups. Analysis of 25 isolates from one flock with high prevalence of lameness, identified that serogroup and sequence type was significantly correlated with age. Significantly higher proportion of lambs were infected with serogroup B (principally ST85) as opposed to serogroup H (principally ST86), which predominated amongst adult sheep. This indicates that host-pathogen dynamics and susceptibility to particular D. nodosus strains may be age dependent.

scholarly journals Treatment Outcomes of Mycobacterium Avium Complex Pulmonary Disease According to Disease Severity

2021 ◽  
Author(s):  
Bo-Guen Kim ◽  
Byung Woo Jhun ◽  
Hojoong Kim ◽  
O Jung Kwon
Keyword(s):  
Pulmonary Disease ◽  
Disease Severity ◽  
Mycobacterium Avium ◽  
Treatment Strategies ◽  
Term Treatment ◽  
Intermittent Therapy ◽  
Mild Disease ◽  
Conversion Rates ◽  
Long Term Treatment ◽  
Culture Conversion

Abstract Mycobacterium avium complex pulmonary disease (MAC-PD) requires long-term treatment. We analyzed the outcomes of 992 MAC-PD patients according to disease severity and compared the outcomes of intermittent and daily therapy for mild disease. Patients were divided into groups according to severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) system, and culture conversion rates were evaluated. We also evaluated the effects of intermittent treatment on the culture conversion rates in mild disease group. Using the BACES, 992 patients were divided into mild (n=331), moderate (n=503), and severe (n=158) disease groups, and culture conversion at the end of treatment was achieved in 85% (282/331), 80% (403/503), and 61% (97/158), respectively. Differences in culture conversion among the severity groups were significant (p<0.001). In patients with mild disease, culture conversion rates were similar between intermittent (84%, 166/198) and daily (87%, 116/133) treatment (p=0.396), and intermittent antibiotic therapy did not negatively impact culture conversion (adjusted hazard ratio 1.08; confidence interval 0.83–1.15; p=0.552). MAC-PD patients with mild disease had higher culture conversion rates. Daily and intermittent therapy yielded similar culture conversion rates for mild disease. Treatment strategies with lower pill burden may be applicable in mild MAC-PD.

scholarly journals Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience

2020 ◽  
Author(s):  
Sarfraz A Saleemi ◽  
Abdulrahman Alrajhi ◽  
Mohammed Alhajji ◽  
Areej Alfattani ◽  
Faisal Albaiz
Keyword(s):  
Disease Severity ◽  
Median Time ◽  
Symptom Onset ◽  
Viral Clearance ◽  
P Value ◽  
Nasopharyngeal Swab ◽  
Multivariate Regression Model ◽  
Mild Disease ◽  
Virus Clearance

Background: The role of hydroxychloroquine (HCQ) and azithromycin in the treatment of COVID-19 and its effect on SARS-CoV-2 viral clearance is not known. Methods: This is a retrospective observational study to assess the effect of HCQ and Azithromycin on duration from symptom onset to negative SARS-CoV-2 PCR using nasopharyngeal swab in hospitalized patient with COVID-19. Eighty-five patients were included in the study, 65 in HCQ (Hydroxychloroquine + Azithromycin) and 20 in non-HCQ group. Measurement of duration from symptom onset to negative PCR and effect of gender, age and disease severity on time to viral clearance was measured. Results: Median time to negative PCR in HCQ group was 23 days (IQR: 9, Mean 24+8, N=65) compared with non-HCQ group, 19 days (IQR: 8, Mean 18+6, N=20), (p <0.05). Forty-one (63%) patients in HCQ group and all patients (100%) in non-HCQ group had mild disease. Multivariate regression model (F=6.8, P<0.002, R2=0.20) shows that being in HCQ group would delay the time to negative PCR by 7 days (95%CI: 2-12) and with every year increase in the age, the time to negative PCR would be delayed by 0.12 days (95%CI: 0.017-0.22). Among HCQ sub-groups, gender and disease severity had no effect on duration (p 0.142 and 0.156 respectively) but older patients >60 year had longer duration compared to patients <60 year of age although p value did not reach significance (p 0.073). Median time to negative PCR in mild-HCQ group (23 days, IQR: 9, Mean 23+8, N=41) was longer when compared with non-HCQ group (p <0.05). On day 28, all patients in non-HCQ group had negative PCR while only 50/65 (77%) were negative in HCQ group. Conclusion: Hydroxychloroquine (HCQ) and azithromycin delay SARS-CoV-2 virus clearance in hospitalized patients with COVID-19 and it is correlated with older age. Larger studies are needed to confirm this finding.

scholarly journals Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19

2020 ◽  
Author(s):  
Aaron J. Wilk ◽  
Madeline J. Lee ◽  
Bei Wei ◽  
Benjamin Parks ◽  
Ruoxi Pi ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Single Cell ◽  
Disease Severity ◽  
Full Range ◽  
Innate Immune ◽  
Mild Disease ◽  
Single Cell Profiling ◽  
Immune Phenotypes ◽  
Emergency Myelopoiesis ◽  
Immune Profiling

ABSTRACTOur understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including a prominent neutrophil hyperactivation signature and monocytes with anti-inflammatory features. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.One Sentence SummarySingle-cell profiling demonstrates multifarious dysregulation of innate immune phenotype associated with COVID-19 severity.

scholarly journals Magnitude and Kinetics of Anti–Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Responses and Their Relationship to Disease Severity

2020 ◽  
Author(s):  
Kara L Lynch ◽  
Jeffrey D Whitman ◽  
Noreen P Lacanienta ◽  
Erica W Beckerdite ◽  
Shannon A Kastner ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Disease Severity ◽  
Dynamic Range ◽  
Vaccine Development ◽  
High Sensitivity ◽  
Immunoglobulin M ◽  
Viral Neutralization ◽  
Mild Disease ◽  
Protein Receptor

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets. Methods Sera (n = 533) from patients with real-time polymerase chain reaction–confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity. Results Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG. Conclusions High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.

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