scholarly journals Characterization of the Immune Response during Infection Caused by Clostridioides difficile

2019 ◽  
Vol 7 (10) ◽  
pp. 435 ◽  
Author(s):  
Hamo ◽  
Azrad ◽  
Nitzan ◽  
Peretz

The high risk of complications and death following Clostridioides difficile infection (CDI) requires identifying patients with severe disease and treating them accordingly. We characterized the immune response of CDI patients in relation to infection severity. Concentrations of 28 cytokines and chemokines were measured in serum samples, obtained from 54 CDI patients within a median timeframe of 24–48 h after laboratory confirmation of C. difficile infection. Demographic and clinical data were retrospectively collected from medical records. Disease severity score was determined by “Score indices for Clostridioides difficile infection severity”. Of 54 patients (mean age, 76.6 years, 61.1% female), 38 (70.4%) had mild disease and 16 (29.6%) had moderate disease. Seven cytokines were associated with a more severe CDI: granulocyte-macrophage colony-stimulating factor (p = 0.0106), interleukin (IL)-1β (p = 0.004), IL-8 (p = 0.0098), IL-12p70 (p = 0.0118), interferon-α (p = 0.0282), IL-15 (p = 0.0015), and IL-2 (p = 0.0031). Additionally, there was an increased T-helper 1 response in more severe cases of CDI. Cytokines may serve as biomarkers for early prediction of CDI severity. Better and earlier assessment of illness severity will contribute to the adjustment of medical treatment, including monitoring and follow-up.

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 631
Author(s):  
Dor Gotshal ◽  
Maya Azrad ◽  
Zohar Hamo ◽  
Orna Nitzan ◽  
Avi Peretz

Clostridioides difficile infection (CDI) is associated with a high risk for complications and death, which requires identifying severe patients and treating them accordingly. We examined the serum level of six cytokines and chemokines (IL-16, IL-21, IL-23, IL-33, BCA-1, TRAIL) and investigated the association between them and patients’ disease severity. Concentrations of six cytokines and chemokines were measured using the MILLIPLEX®MAP kit (Billerica, MA, USA) in serum samples attained from CDI patients within 24–48 h after laboratory confirmation of C. difficile presence. Demographic and clinical data were collected from medical records. The disease severity score was determined according to guidelines of the “Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America” (SHEA-IDSA). Out of 54 patients, 20 (37%) had mild to moderate disease and 34 (63%) had severe disease. IL-16 (p = 0.005) and BCA-1 (p = 0.012) were associated with a more severe disease. In conclusion, IL-16 and BCA-1, along with other cytokines and chemokines, may serve as biomarkers for the early prediction of CDI severity in the future. An improved and more accessible assessment of CDI severity will contribute to the adjustment of the medical treatment, which will lead to a better patient outcome.


2021 ◽  
Author(s):  
Tsogtsaikhan Sandag ◽  
Enkhsaikhan Lkhagvasuren ◽  
Munkhundrakh Batmunkh ◽  
Oyungerel Ravjir

SARS-CoV-2 disturbs the normal immune responses causing an uncontrolled inflammatory response in patients with severe COVID-19. The pattern of the immune response to the SARS-CoV-2 in individuals may fluctuate. Some have a virus-dependent protective immune response resulting in asymptomatic or mild disease with elimination of the virus within 7-10 days after onset of infection. Others develop virus non-dependent uncontrolled hyper-inflammation in the later period, leading to severe disease with cytokine storm, acute respiratory distress syndrome, disseminated intravascular coagulation and multi-organ failure. Methods: The serum of 72 patients was investigated for titers of 15 cytokines and chemokines using Enzyme-linked immunosorbent assay (ELISA) kits in the serum of peripheral blood samples. The means of groups were compared using ANOVA followed by Tukey multiple post hoc comparisons if the ANOVA p-value was <0.05. Results: Patients with pulmonary infiltrates on CT demonstrated a lower percentage of eosinophils (1.38±1.46%) and elevated level of serum CRP (8.57±19.10 mg/dL) compared to patients without pulmonary infiltrates (2.52±1.47% and 1.96±3.02 mg/dL respectively; p<0.05). ROC analysis for patients aged ≥35 years showed patients with mild disease (n=3) had a significantly higher titer of IL-1α and MCP-1 (AUC, 0.958 and 0.917 respectively, p<0.05) compared to patients with moderate disease (n=7).


2020 ◽  
Author(s):  
Dor Gotshal ◽  
Maya Azrad ◽  
Zohar Hamo ◽  
Orna Nitzan ◽  
Avi Peretz

Abstract Background: Clostridioides difficile infection (CDI) have a high risk for complications up to death which requires identifying patients with severe disease and treating them accordingly. We examined the serum level of 6 cytokines and chemokines (IL-6, IL-21, IL-23, IL-33, BCA-1, TRAIL) and we checked the correlation between them to the patients' clinical characteristics and the bacterial strain.Methods: Concentrations of 6 cytokines and chemokines were measured using the MILLIPLEX®MAP kit (Billerica, USA) based on the Luminex xMAP® technology, in serum samples, attained from 54 CDI patients within a median time of 24-48 hours after laboratory confirmation of C. difficile presence. The demographic and clinical data were retrospectively collected from medical records. Disease severity score was determined according to the guidelines of the "Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America" (SHEA-IDSA).Results: Out of 54 patients (mean age, 76.6 years, 61.1% female), 20 (37%) had mild to moderate disease and 34 (63%) had severe disease. Two immunological markers were associated with a more severe disease: IL-16 (p = 0.005) and BCA-1 (p = 0.012). The study didn’t show a correlation between the immunological markers to the gender, the type of toxin which produced by the bacteria, in hospital mortality and infection acquisition.Conclusions: cytokines and chemokines may serve as a biomarker for early prediction of CDI severity in the future. Improved and more accessible assessment of CDI severity will contribute to adjustment of the medical treatment which will lead to a better patient outcome and hopefully will reduce the patient's mortality.


BMJ ◽  
2020 ◽  
pp. m1443 ◽  
Author(s):  
Shufa Zheng ◽  
Jian Fan ◽  
Fei Yu ◽  
Baihuan Feng ◽  
Bin Lou ◽  
...  

AbstractObjectiveTo evaluate viral loads at different stages of disease progression in patients infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first four months of the epidemic in Zhejiang province, China.DesignRetrospective cohort study.SettingA designated hospital for patients with covid-19 in Zhejiang province, China.Participants96 consecutively admitted patients with laboratory confirmed SARS-CoV-2 infection: 22 with mild disease and 74 with severe disease. Data were collected from 19 January 2020 to 20 March 2020.Main outcome measuresRibonucleic acid (RNA) viral load measured in respiratory, stool, serum, and urine samples. Cycle threshold values, a measure of nucleic acid concentration, were plotted onto the standard curve constructed on the basis of the standard product. Epidemiological, clinical, and laboratory characteristics and treatment and outcomes data were obtained through data collection forms from electronic medical records, and the relation between clinical data and disease severity was analysed.Results3497 respiratory, stool, serum, and urine samples were collected from patients after admission and evaluated for SARS-CoV-2 RNA viral load. Infection was confirmed in all patients by testing sputum and saliva samples. RNA was detected in the stool of 55 (59%) patients and in the serum of 39 (41%) patients. The urine sample from one patient was positive for SARS-CoV-2. The median duration of virus in stool (22 days, interquartile range 17-31 days) was significantly longer than in respiratory (18 days, 13-29 days; P=0.02) and serum samples (16 days, 11-21 days; P<0.001). The median duration of virus in the respiratory samples of patients with severe disease (21 days, 14-30 days) was significantly longer than in patients with mild disease (14 days, 10-21 days; P=0.04). In the mild group, the viral loads peaked in respiratory samples in the second week from disease onset, whereas viral load continued to be high during the third week in the severe group. Virus duration was longer in patients older than 60 years and in male patients.ConclusionThe duration of SARS-CoV-2 is significantly longer in stool samples than in respiratory and serum samples, highlighting the need to strengthen the management of stool samples in the prevention and control of the epidemic, and the virus persists longer with higher load and peaks later in the respiratory tissue of patients with severe disease.


Author(s):  
Ourania S. Kotsiou ◽  
Dimitrios Papagiannis ◽  
Evangelos C. Fradelos ◽  
Dimitra I. Siachpazidou ◽  
Garifallia Perlepe ◽  
...  

Background: In this work we aimed to evaluate antibody-response longevity to SARS-CoV-2 infection and/or vaccination in one of the Greek communities that was worst hit by the pandemic, Deskati, five months after a previous serosurveillance and nine months after the pandemic wave initiation (October 2020). Methods: The SARS-CoV-2 IgG II Quant method (Architect, Abbott, IL, USA) was used for antibody testing. Results: A total of 69 subjects, who previously tested positive or negative for COVID-19 antibodies, participated in the study. We found that 48% of participants turned positive due to vaccination and 27% of participants were both previously infected and vaccinated. All previously infected participants retained antibodies to the virus, irrespective of their vaccination status. The antibody titers were significantly higher in previously infected participants that had been vaccinated than those who were unvaccinated and in those that had been previously hospitalized for COVID-19 than those with mild disease. Conclusions: Antibody responses to SARS-CoV-2 infection were maintained nine months after the pandemic. Vaccination alone had generated an immune response in almost half of the population. Higher antibody titers were found in the case of vaccination in previously infected subjects and especially in those with severe disease leading to hospitalization


2021 ◽  
Vol 8 ◽  
Author(s):  
Lisa Müller ◽  
Marcel Andrée ◽  
Philipp Niklas Ostermann ◽  
Nathalie Jazmati ◽  
Greta Flüh ◽  
...  

Prophylactic vaccination against SARS-CoV-2 is one of the most important measures to contain the COVID-19 pandemic. Recently, break-through infections following vaccination against this virus have been reported. Here, we describe the humoral immune response of break-through infections in fully vaccinated individuals of old age from an outbreak in a nursing home. In cooperation with the local health authority, blood samples from fully vaccinated and infected as well as fully vaccinated and uninfected residents of the nursing home were collected 4 weeks after the onset of the outbreak. The humoral immune response was determined in a neutralisation assay with replication-competent virus isolates and by a quantitative ELISA. In this outbreak a total of 23 residents and four health care workers were tested positive for SARS-CoV-2. Four residents were unvaccinated, including one with a severe course of disease who later severe disease course who later succumbed to infection. Despite their old age, all vaccinated residents showed no or only mild disease. Comparison of the humoral immune response revealed significantly higher antibody levels in fully vaccinated infected individuals compared to fully vaccinated uninfected individuals (p &lt; 0.001). Notably, although only a minority of the vaccinated uninfected group showed neutralisation capacity against SARS-CoV-2, all vaccinated and infected individuals showed high-titre neutralisation of SARS-CoV-2 including the alpha and beta variant. Large SARS-CoV-2 outbreaks can occur in fully vaccinated populations, but seem to associate with mild disease. SARS-CoV-2 infection in fully vaccinated individuals is a strong booster of the humoral immune response providing enhanced neutralisation capacity against immune evasion variants.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yi-Hsin Lai ◽  
Bo-Yang Tsai ◽  
Chih-Yu Hsu ◽  
Yi-Hsuan Chen ◽  
Po-Han Chou ◽  
...  

BackgroundClostridioides difficile is the leading cause of nosocomial infectious diarrhea. Toll-like receptors (TLRs) are the major components of innate immunity that sense pathogens. The relationship between TLRs and C. difficile infection (CDI) was analyzed in clinical patients and a mouse model.Materials and MethodsA prospective investigation was conducted in medical wards of Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan, from January 2011 to January 2013. Adult patients were followed up for the development of CDI. Single nucleotide polymorphisms (SNPs) of TLR2 and TLR4 were analyzed to assess the relationship between genetic polymorphisms and the development of CDI. A mouse model of CDI was used to investigate the pathogenic role of TLRs in CDI, TLR2 and TLR4 knockout (Tlr2-/- and Tlr4-/-) mice.ResultsIn the prospective study, 556 patients were enrolled, and 6.5% (36) of patients, accounting for 3.59 episodes per 1000 patient-days, developed CDI. Of 539 patients with available blood samples, the TLR2 rs3804099 polymorphism was more often noted in those with CDI than in those without CDI (64.5% vs. 46.1%; P = 0.046) but was not significant in multivariate analysis. Because the TLR2 rs3804099 polymorphism was moderately associated with CDI, the role of TLR2 and TLR4 was further evaluated in a mouse model. Both Tlr2-/- and Tlr4-/- mice showed more severe CDI disease than wild-type mice in terms of body weight change and fecal content five days after oral challenge with C. difficile. Furthermore, Tlr2-/- mice suffered from more severe disease than Tlr4-/- mice, as evidenced by stool consistency, cecum weight, and survival rate.ConclusionThe TLR2 rs3804099 polymorphism is marginally associated with the development of CDI, and the pathogenic role of TLR2 is further supported by a mouse model.


2020 ◽  
Author(s):  
Changfu Yao ◽  
Stephanie A Bora ◽  
Tanyalak Parimon ◽  
Tanzira Zaman ◽  
Oren A Friedman ◽  
...  

Coronavirus disease 2019 (COVID-19) has quickly become the most serious pandemic since the 1918 flu pandemic. In extreme situations, patients develop a dysregulated inflammatory lung injury called acute respiratory distress syndrome (ARDS) that causes progressive respiratory failure requiring mechanical ventilatory support. Recent studies have demonstrated immunologic dysfunction in severely ill COVID-19 patients. To further delineate the dysregulated immune response driving more severe clinical course from SARS-CoV-2 infection, we used single-cell RNA sequencing (scRNAseq) to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) from hospitalized COVID-19 patients having mild disease (n = 5), developing ARDS (n = 6), and recovering from ARDS (n = 6). Our data demonstrated an overwhelming inflammatory response with select immunodeficiencies within various immune populations in ARDS patients. Specifically, their monocytes had defects in antigen presentation and deficiencies in interferon responsiveness that contrasted the higher interferon signals in lymphocytes. Furthermore, cytotoxic activity was suppressed in both NK and CD8 lymphocytes whereas B cell activation was deficient, which is consistent with the delayed viral clearance in severely ill COVID-19 patients. Finally, we identified altered signaling pathways in the severe group that suggests immunosenescence and immunometabolic changes could be contributing to the dysfunctional immune response. Our study demonstrates that COVID-19 patients with ARDS have an immunologically distinct response when compared to those with a more innocuous disease course and show a state of immune imbalance in which deficiencies in both the innate and adaptive immune response may be contributing to a more severe disease course in COVID-19.


2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S50-S50
Author(s):  
Abhishek Verma ◽  
Sanskriti Varma ◽  
Daniel Freedberg ◽  
David Hudesman ◽  
Shannon Chang ◽  
...  

Abstract Background Guidelines recommend testing inflammatory bowel disease (IBD) patients hospitalized with flare for Clostridioides difficile infection (CDI), though little is known about whether a delay in testing for CDI is related to adverse outcomes. We examined the relationship between time-to-C. difficile PCR test order, collection, and result with adverse IBD outcomes. Methods We performed a retrospective cohort study of IBD patients hospitalized with flare through the emergency department (ED) between 2013 and 2020 at an urban academic medical center. The time from ED presentation to C. difficile test order (time-to-order), sample collection (time-to-collection), and test result (time-to-result) were collected. Time-to-result was stratified by within 6 hours, 6–24 hours, and 24 hours or longer. The primary outcome was length of stay (LOS). Secondary outcomes were inpatient anti-TNF administration and surgery. We used hemodynamic and laboratory values at presentation to evaluate disease severity as a confounding variable between length of stay and time-dependent variables. Results We identified 122 IBD patients hospitalized with flare. There were no significant differences in baseline characteristics among time-to-result groups. Despite a shorter time-to-result, the average LOS in the 6 hours group was 7.3 days, longer compared to the 6–24 hours group (4.3 days, p=0.018) and the 24 hours group (4.2 days, p=0.035; Table 1). There were no differences in inpatient anti-TNF administration (p=0.10) or surgery (p=0.08) among time-to-result groups. The markers of disease severity that correlated with longer LOS were C-reactive protein (CRP) (0.28 days, p=0.003), heart rate (0.478 days, p&lt;0.001), diastolic hypotension (0.228 days, p=0.01), and hypoalbuminemia (0.215 days, p=0.02). Higher CRP correlated with earlier time-to-result (-0.218 hours, p=0.02). Patients with more markers of disease severity had earlier times-to-result (12.8 hours vs. 32.2 hours, p=0.014) and had a longer LOS (7.9 vs. 3.4 days, p=0.007) (Table 2). Patients with more severe disease had an earlier time-to-order (4.48 hours) compared to those with less severe disease (17.4 hours), though this difference did not meet statistical significance (p=0.09; Table 2). Conclusion Earlier time-to-result for CDI is associated with longer LOS in IBD patients hospitalized with flare. This inverse relationship is confounded by disease severity at presentation: patients with more severe disease have a shorter time-to-result and a longer LOS. It may be that these patients produce a stool sample more readily; however, the near significance of differences in time-to-order among severity groups suggest a role for provider bias, which must be studied further. Delay in testing was not associated with higher rates of inpatient anti-TNF administration or surgery.


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