Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia

Thorax ◽  
2020 ◽  
Vol 75 (11) ◽  
pp. 974-981 ◽  
Author(s):  
Samir Gautam ◽  
Avi J Cohen ◽  
Yannick Stahl ◽  
Patricia Valda Toro ◽  
Grant M Young ◽  
...  
Keyword(s):  
Viral Infection ◽  
Disease Severity ◽  
Influenza Infection ◽  
Characteristic Curve ◽  
Severe Disease ◽  
Antibiotic Administration ◽  
Underlying Assumption ◽  
Cellular Models ◽  
Interferon Signalling ◽  
Bacterial Coinfection

IntroductionProcalcitonin expression is thought to be stimulated by bacteria and suppressed by viruses via interferon signalling. Consequently, during respiratory viral illness, clinicians often interpret elevated procalcitonin as evidence of bacterial coinfection, prompting antibiotic administration. We sought to evaluate the validity of this practice and the underlying assumption that viral infection inhibits procalcitonin synthesis.MethodsWe conducted a retrospective cohort study of patients hospitalised with pure viral infection (n=2075) versus bacterial coinfection (n=179). The ability of procalcitonin to distinguish these groups was assessed. In addition, procalcitonin and interferon gene expression were evaluated in murine and cellular models of influenza infection.ResultsPatients with bacterial coinfection had higher procalcitonin than those with pure viral infection, but also more severe disease and higher mortality (p<0.001). After matching for severity, the specificity of procalcitonin for bacterial coinfection dropped substantially, from 72% to 61%. In fact, receiver operating characteristic curve analysis showed that procalcitonin was a better indicator of multiple indices of severity (eg, organ failures and mortality) than of coinfection. Accordingly, patients with severe viral infection had elevated procalcitonin. In murine and cellular models of influenza infection, procalcitonin was also elevated despite bacteriologic sterility and correlated with markers of severity. Interferon signalling did not abrogate procalcitonin synthesis.DiscussionThese studies reveal that procalcitonin rises during pure viral infection in proportion to disease severity and is not suppressed by interferon signalling, in contrast to prior models of procalcitonin regulation. Applied clinically, our data suggest that procalcitonin represents a better indicator of disease severity than bacterial coinfection during viral respiratory infection.

scholarly journals Association between incubation period and clinical characteristics of patients with COVID-19

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052095683
Author(s):  
Yeyu Cai ◽  
Jiayi Liu ◽  
Haitao Yang ◽  
Mian Wang ◽  
Qingping Guo ◽  
...  
Keyword(s):  
Incubation Period ◽  
Disease Severity ◽  
Symptom Onset ◽  
Clinical Characteristics ◽  
Characteristic Curve ◽  
Severe Disease ◽  
Receiver Operator Characteristic Curve ◽  
Hunan Province ◽  
Laboratory Findings ◽  
Incubation Periods

Purpose To investigate associations between the clinical characteristics and incubation periods of patients infected with coronavirus disease 2019 (COVID-19) in Wuhan, China. Methods Complete clinical and epidemiological data from 149 patients with COVID-19 at a hospital in Hunan Province, China, were collected and retrospectively analyzed. Results Analysis of the distribution and receiver operator characteristic curve of incubation periods showed that 7 days was the optimal cut-off value to assess differences in disease severity between groups. Patients with shorter (≤7 days) incubation periods (n = 79) had more severe disease, longer durations of hospitalization, longer times from symptom onset to discharge, more abnormal laboratory findings, and more severe radiological findings than patients with longer (>7 days) incubation periods. Regression and correlation analyses also showed that a shorter incubation period was associated with longer times from symptom onset to discharge. Conclusion The associations between the incubation periods and clinical characteristics of COVID-19 patients suggest that the incubation period may be a useful marker of disease severity and prognosis.

scholarly journals Prediction of COVID-19 Patients at High Risk of Progression to Severe Disease

2020 ◽  
Vol 8 ◽  
Author(s):  
Zhenyu Dai ◽  
Dong Zeng ◽  
Dawei Cui ◽  
Dawei Wang ◽  
Yanling Feng ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Disease Severity ◽  
Cox Regression ◽  
Clinical Chemistry ◽  
Characteristic Curve ◽  
Severe Disease ◽  
Bootstrap Sampling ◽  
Orthogonal Projections ◽  
High Risk Factors

In order to develop a novel scoring model for the prediction of coronavirus disease-19 (COVID-19) patients at high risk of severe disease, we retrospectively studied 419 patients from five hospitals in Shanghai, Hubei, and Jiangsu Provinces from January 22 to March 30, 2020. Multivariate Cox regression and orthogonal projections to latent structures discriminant analysis (OPLS-DA) were both used to identify high-risk factors for disease severity in COVID-19 patients. The prediction model was developed based on four high-risk factors. Multivariate analysis showed that comorbidity [hazard ratio (HR) 3.17, 95% confidence interval (CI) 1.96–5.11], albumin (ALB) level (HR 3.67, 95% CI 1.91–7.02), C-reactive protein (CRP) level (HR 3.16, 95% CI 1.68–5.96), and age ≥60 years (HR 2.31, 95% CI 1.43–3.73) were independent risk factors for disease severity in COVID-19 patients. OPLS-DA identified that the top five influencing parameters for COVID-19 severity were CRP, ALB, age ≥60 years, comorbidity, and lactate dehydrogenase (LDH) level. When incorporating the above four factors, the nomogram had a good concordance index of 0.86 (95% CI 0.83–0.89) and had an optimal agreement between the predictive nomogram and the actual observation with a slope of 0.95 (R2 = 0.89) in the 7-day prediction and 0.96 (R2 = 0.92) in the 14-day prediction after 1,000 bootstrap sampling. The area under the receiver operating characteristic curve of the COVID-19-American Association for Clinical Chemistry (AACC) model was 0.85 (95% CI 0.81–0.90). According to the probability of severity, the model divided the patients into three groups: low risk, intermediate risk, and high risk. The COVID-19-AACC model is an effective method for clinicians to screen patients at high risk of severe disease.

scholarly journals Differential Cytokine Signatures of SARS-CoV-2 and Influenza Infection Highlight Key Differences in Pathobiology

2021 ◽  
Author(s):  
Andrew H. Karaba ◽  
Weiqiang Zhou ◽  
Leon L. Hsieh ◽  
Alexis Figueroa ◽  
Guido Massaccesi ◽  
...  
Keyword(s):  
Random Forest ◽  
Disease Severity ◽  
Influenza Infection ◽  
Severe Disease ◽  
Gm Csf ◽  
Cytokines And Chemokines ◽  
Severe Influenza ◽  
Tnf Α ◽  
Relationship Of ◽  
The Relationship

ABSTRACTBackgroundSeveral inflammatory cytokines are upregulated in severe COVID-19. We compared cytokines in COVID-19 versus influenza in order to define differentiating features of the inflammatory response to these pathogens and their association with severe disease. Because elevated body mass index (BMI) is a known risk factor for severe COVID-19, we examined the relationship of BMI to cytokines associated with severe disease.MethodsThirty-seven cytokines and chemokines were measured in plasma from 145 patients with COVID-19, 57 patients with influenza, and 30 healthy controls. Controlling for BMI, age, and sex, differences in cytokines between groups were determined by linear regression and random forest prediction was utilized to determine the cytokines most important in distinguishing severe COVID-19 and influenza. Mediation analysis was utilized to identify cytokines that mediate the effect of BMI on disease severity.ResultsIL-18, IL-1β, IL-6, and TNF-α were significantly increased in COVID-19 versus influenza patients while GM-CSF, IFN-γ, IFN-λ1, IL-10, IL-15, and MCP-2 were significantly elevated in the influenza group. In subgroup analysis based on disease severity, IL-18, IL-6, and TNF-α were elevated in severe COVID-19, but not severe influenza. Random forest analysis identified high IL-6 and low IFN-λ1 levels as the most distinct between severe COVID-19 and severe influenza. Finally, IL-1RA was identified as a potential mediator of the effects of BMI on COVID-19 severity.ConclusionsThese findings point to activation of fundamentally different innate immune pathways in SARS-CoV-2 and influenza infection, and emphasize drivers of severe COVID-19 to focus both mechanistic and therapeutic investigations.SummarySevere COVID-19 is marked by dysregulated inflammation and is associated with elevated BMI. By comparing cytokines and chemokines in patients with either COVID-19 or influenza, we identified distinct inflammatory pathways and a cytokine mediator of the effect of BMI.

Development and initial validation of international severity scoring system for familial Mediterranean fever (ISSF)

2016 ◽  
Vol 75 (6) ◽  
pp. 1051-1056 ◽  
Author(s):  
Erkan Demirkaya ◽  
Cengizhan Acikel ◽  
Philip Hashkes ◽  
Marco Gattorno ◽  
Ahmet Gul ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Disease Severity ◽  
Severity Score ◽  
Characteristic Curve ◽  
Severe Disease ◽  
Clinical Manifestations ◽  
Future Research ◽  
Laboratory Findings ◽  
Therapeutic Decisions ◽  
Mediterranean Fever

ObjectiveTo develop widely accepted international severity score for children and adult patients with familial Mediterranean fever (FMF) that can be easily applied, in research and clinical practice.MethodsCandidate severity criteria were suggested by several FMF expert physicians. After three rounds of Delphi survey, the candidate criteria, defined by the survey, were discussed by experts in a consensus meeting. Each expert brought data of clinical manifestations, laboratory findings and physician's global assessments (PGAs) of minimum 20 patients from their centres. We used the PGAs for disease severity as a gold standard. Logistic regression analysis was used to evaluate the predicting value of each item, and receiver operating characteristic curve analysis was performed to demonstrate the success of the criteria set.ResultsA total of 281 patients consist of 162 children and 119 adults with FMF were enrolled and available for validity analysis: Nine domains were included in the final core set of variables for the evaluation of disease severity in FMF. The International Severity Score for FMF (ISSF) may reach a maximum of 10 if all items are maximally scored. The threshold values to determine: severe disease ≥6, intermediate disease 3–5, mild disease ≤2. Area under the curve was calculated as 0.825 for this set in the whole group.ConclusionsThe initial validity of ISSF both in children and adult with FMF was demonstrated. We anticipate that it will provide a robust tool to objectively define disease severity for clinical trials, future research as well as for therapeutic decisions in managing patients with FMF.

scholarly journals Serum C-Reactive Protein and Interleukin-6 Levels as Biomarkers for Disease Severity and Clinical Outcomes in Patients with Idiopathic Granulomatous Mastitis

2021 ◽  
Vol 10 (10) ◽  
pp. 2077
Author(s):  
Yi-Min Huang ◽  
Chiao Lo ◽  
Chiao-Feng Cheng ◽  
Cheng-Hsun Lu ◽  
Song-Chou Hsieh ◽  
...  
Keyword(s):  
Disease Severity ◽  
Severe Disease ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Serum Biomarkers ◽  
Healthy Controls ◽  
Granulomatous Mastitis ◽  
C Reactive Protein ◽  
Idiopathic Granulomatous Mastitis ◽  
Reactive Protein

Idiopathic granulomatous mastitis (IGM) is a rare inflammatory breast disease mimicking breast cancer. Limited research has been conducted on the application of serum biomarkers. This study aims to investigate the association of serum biomarkers with disease severity in patients with IGM. From November 2011 to March 2020, medical records of patients with IGM were reviewed. Serum cytokine levels were measured in patients and healthy controls between July 2018 and March 2020. A total of 41 patients with histologically proven IGM were found. Serum interleukin (IL)-6 level was significantly higher in patients with IGM (n = 11) than healthy controls (n = 7). Serum IL-6 and C-reactive protein (CRP) levels were significantly higher in patients with severe disease than mild and moderate disease. Serum IL-6 (Spearman’s ρ = 0.855; p < 0.001) and CRP (Spearman’s ρ = 0.838; p = 0.001) levels were associated with time to resolution. A higher serum CRP level was associated with a longer time to resolution (B = 0.322; p < 0.001) in multiple linear regression analysis. Serum IL-6 and CRP levels can be used as biomarkers for the evaluation of disease severity in IGM. IL-6 may play a crucial role in the immunopathology of IGM.

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

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

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

scholarly journals CD169/SIGLEC1 is expressed on circulating monocytes in COVID-19 and expression levels are associated with disease severity

Infection ◽  
2021 ◽  
Author(s):  
Jan-Moritz Doehn ◽  
Christoph Tabeling ◽  
Robert Biesen ◽  
Jacopo Saccomanno ◽  
Elena Madlung ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Disease Severity ◽  
Clinical Studies ◽  
Viral Infections ◽  
Severe Disease ◽  
Type I Interferons ◽  
Type I ◽  
Interferon Signaling ◽  
Expression Levels

AbstractCoronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.

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

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

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

scholarly journals Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis

2021 ◽  
Author(s):  
Panagiotis Paliogiannis ◽  
Arduino Aleksander Mangoni ◽  
Michela Cangemi ◽  
Alessandro Giuseppe Fois ◽  
Ciriaco Carru ◽  
...  
Keyword(s):  
Systematic Review ◽  
Serum Albumin ◽  
Disease Severity ◽  
Meta Analysis ◽  
Severe Disease ◽  
Geographic Area ◽  
Adverse Outcomes ◽  
Poor Outcome ◽  
Standard Mean Difference ◽  
Meta Regression Analysis

AbstractCoronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: − 0.99 g/L; 95% CI, − 1.11 to − 0.88, p < 0.001). In multivariate meta-regression analysis, age (t =  − 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t =  − 2.77, p = 0.008) and C-reactive protein (t =  − 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group.

scholarly journals The interplay between environmental exposures and COVID-19 risks in the health of children

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Peter D. Sly ◽  
Brittany A. Trottier ◽  
Catherine M. Bulka ◽  
Stephania A. Cormier ◽  
Julius Fobil ◽  
...  
Keyword(s):  
Air Pollution ◽  
Air Quality ◽  
Disease Severity ◽  
Research Effort ◽  
Severe Disease ◽  
Environmental Exposures ◽  
Research Strategy ◽  
Lessons Learned ◽  
Research Questions ◽  
The Impact

Abstract Background An unusual feature of SARS-Cov-2 infection and the COVID-19 pandemic is that children are less severely affected than adults. This is especially paradoxical given the epidemiological links between poor air quality and increased COVID-19 severity in adults and that children are generally more vulnerable than adults to the adverse consequences of air pollution. Objectives To identify gaps in knowledge about the factors that protect children from severe SARS-Cov-2 infection even in the face of air pollution, and to develop a transdisciplinary research strategy to address these gaps. Methods An international group of researchers interested in children’s environmental health was invited to identify knowledge gaps and to develop research questions to close these gaps. Discussion Key research questions identified include: what are the effects of SAR-Cov-2 infection during pregnancy on the developing fetus and child; what is the impact of age at infection and genetic susceptibility on disease severity; why do some children with COVID-19 infection develop toxic shock and Kawasaki-like symptoms; what are the impacts of toxic environmental exposures including poor air quality, chemical and metal exposures on innate immunity, especially in the respiratory epithelium; what is the possible role of a “dirty” environment in conveying protection – an example of the “hygiene hypothesis”; and what are the long term health effects of SARS-Cov-2 infection in early life. Conclusion A concerted research effort by a multidisciplinary team of scientists is needed to understand the links between environmental exposures, especially air pollution and COVID-19. We call for specific research funding to encourage basic and clinical research to understand if/why exposure to environmental factors is associated with more severe disease, why children appear to be protected, and how innate immune responses may be involved. Lessons learned about SARS-Cov-2 infection in our children will help us to understand and reduce disease severity in adults, the opposite of the usual scenario.

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