• C-reactive protein
• Coronavirus
• D-dimer
• Ferritin
• Vitamin D

• Humans
• SARS-CoV-2
• C-Reactive Protein
• Tertiary Care Centers
• COVID-19/complications
• Vitamin D
• Calcifediol
• Vitamin D Deficiency/complications
• Vitamins
• Ferritins

• Avian influenza virus
• Biomarker
• Biosensor
• Nanomaterial
• Point-of-care testing

• Animals
• Humans
• Influenza in Birds/diagnosis
• Influenza A virus
• Biosensing Techniques/methods
• Nanostructures
• Nanoparticles

• C-Reactive Protein
• CRP
• algorithm
• biochemical properties
• biomarker
• diagnosis
• diagnostic assays
• false results
• forms
• pathophysiology
• systemic inflammation

• COVID-19
• CRP
• HGF
• biomarkers
• disease severity
• mortality
• s-TREM-1
• suPAR

• Humans
• SARS-CoV-2
• C-Reactive Protein
• COVID-19
• Receptors, Urokinase Plasminogen Activator
• Biomarkers

• Universitatea de Medicina şi Farmacie Grigore T. Popa - Iasi
• Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii

• CXCL10
• Human adenovirus type 7
• Inflammatory cytokine
• Lymphocyte subsets
• Pneumonia
• hypercytokinemia

• 2015ZX09J15105-004 the National Science and Technology Major Project of China

Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing.

We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections.

Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days.

Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850–0.948]; AUC for CRP 0.922 [95%CI 0.879–0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694–0.894]; AUC for CRP 0.807 [95%CI 0.721–0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls.

In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions.

• Biomarkers
• C-Reactive Protein/metabolism
• COVID-19/diagnosis
• Humans
• Interleukin-6
• Pneumonia, Bacterial/diagnosis
• Prospective Studies
• Respiratory Tract Infections

• Schweizerische Herzstiftung
• Cardiovascular Research Institute of Basel
• Roche Diagnostics

• COVID-19
• Immunopathogenesis
• Vitamin D

Avian influenza A (H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. The emergence of H7N9 virus infections is a serious public health threat. To identify virus–host interaction differences between the highly virulent H7N9 and pandemic influenza H1N1 (pdmH1N1), RNA sequencing was performed of normal human bronchial epithelial (NHBE) cells infected with either virus. The transcriptomic analysis of host cellular responses to viral infection enables the identification of potential cellular factors related to infection. Significantly different gene expression patterns were found between pdmH1N1- and H7N9-infected NHBE cells. In addition, the H7N9 virus infection induced strong immune responses, while cellular repair mechanisms were inhibited. The differential expression of specific factors observed between avian H7N9 and pdmH1N1 influenza virus strains can account for variations in disease pathogenicity. These findings provide a framework for future studies examining the molecular mechanisms underlying the pathogenicity of avian H7N9 virus.

• avian influenza A(H7N9) virus
• pandemic influenza H1N1 (pdmH1N1)
• transcriptome

• Animals
• Epithelial Cells
• Humans
• Influenza A Virus, H1N1 Subtype
• Influenza A Virus, H5N1 Subtype/genetics
• Influenza A Virus, H7N9 Subtype/genetics
• Influenza, Human
• Transcriptome/genetics

Through the comparison of the demographic, epidemiological, and clinical characteristics of hospital human influenza (influenza A (H1N1) pdm09, H3N2, and B)-related and hospitalized avian-origin influenza A (H7N9)-related viral pneumonia patients, find the different between them.

A retrospective study was conducted in hospitalized influenza-related viral pneumonia patients.

Human influenza A-related patients in the 35–49-year-old group were more than those with B pneumonia patients (p = 0.027), and relatively less in the ≥ 65-year-old group than B pneumonia patients (p = 0.079). The proportion of comorbid condition to human influenza A pneumonia was 58%, lower than B pneumonia and H7N9 pneumonia patients (78% vs. 77.8%; p = 0.013). The proportion of invasive mechanical ventilation (IMV), lymphocytopenia, elevated lactate dehydrogenase to hospitalized human influenza A-related viral pneumonia patients was higher than B pneumonia patients (p < 0.05), but lower than H7N9 pneumonia patients (p < 0.05). In the multivariate analysis, pulmonary consolidation (odds ratio (OR): 13.67; 95% confidence interval (CI) 1.54–121.12; p = 0.019) and positive bacterial culture (sputum) (OR: 7.71; 95% CI 2.48–24.03; p < 0.001) were independently associated with IMV, while shock (OR: 13.16; 95% CI 2.06–84.07; p = 0.006), white blood cell count > 10,000/mm³ (OR: 7.22; 95% CI 1.47–35.58; p = 0.015) and positive bacterial culture(blood or sputum) (OR: 6.27; 95% CI 1.36–28.85; p = 0.018) were independently associated with death in the three types hospitalized influenza-related viral pneumonia patients.

Hospital influenza B-related viral pneumonia mainly affects the elderly and people with underlying diseases, while human influenza A pneumonia mainly affects the young adults; however, the mortality was similar. The hospitalized human influenza A-related viral pneumonia patients was severer than B pneumonia patients, but milder than H7N9 pneumonia patients. Pulmonary consolidation and positive bacterial culture (sputum) were independently associated with IMV, while shock, white blood cell count > 10,000/mm³, and positive bacterial culture (blood or sputum) were independently associated with death to three types hospitalized influenza-related viral pneumonia patients.

The online version contains supplementary material available at 10.1186/s12879-021-06485-x.

• Avian-origin influenza H7N9
• Human influenza A
• Influenza B
• Severe cases
• Viral pneumonia

• C-reactive protein
• COVID-19
• complication
• inflammation
• viral infection

• COVID-19
• Inflammation
• Liver injury
• Management
• SARS-CoV-2

• COVID-19
• Cytokine storm
• IL-6
• Immunotherapy
• Influenza
• SARS

• COVID-19/immunology
• Coronavirus Infections/immunology
• Cytokine Release Syndrome/immunology
• Cytokines/metabolism
• Humans
• Immunomodulation
• Immunotherapy/methods
• Inflammation
• Influenza, Human/immunology
• Middle East Respiratory Syndrome Coronavirus/physiology
• Orthomyxoviridae/physiology
• Severe acute respiratory syndrome-related coronavirus/physiology
• SARS-CoV-2/physiology
• Severe Acute Respiratory Syndrome/immunology

• C-reactive protein
• influenza in humans
• point-of-care testing
• primary health care
• respiratory tract infections

• Adult
• C-Reactive Protein/analysis
• Child
• Cross-Sectional Studies
• Female
• Humans
• Influenza, Human/blood
• Norway
• Primary Health Care
• Sweden

Many laboratory indicators form a skewed distribution with outliers in critically ill patients with COVID-19, for which robust methods are needed to precisely determine and quantify fatality risk factors.

A total of 192 critically ill patients (142 were discharged and 50 died in the hospital) with COVID-19 were included in the sample. Quantile regression was used to determine discrepant laboratory indexes between survivors and non-survivors and quantile shift (QS) was used to quantify the difference. Logistic regression was then used to calculate the odds ratio (OR) and the predictive power of death for each risk indicator.

After adjusting for multiple comparisons and controlling numerous confounders, quantile regression revealed that the laboratory indexes of non-survivors were significantly higher in C-reactive protein (CRP; QS = 0.835, p < .001), white blood cell counts (WBC; QS = 0.743, p < .001), glutamic oxaloacetic transaminase (AST; QS = 0.735, p < .001), blood glucose (BG; QS = 0.608, p = .059), fibrin degradation product (FDP; QS = 0.730, p = .080), and partial pressure of carbon dioxide (PCO₂), and lower in oxygen saturation (SO₂; QS = 0.312, p < .001), calcium (Ca²⁺; QS = 0.306, p = .073), and pH. Most of these indexes were associated with an increased fatality risk, and predictive for the probability of death. Especially, CRP is the most prominent index with and odds ratio of 205.97 and predictive accuracy of 93.2%.

Laboratory indexes provided reliable information on mortality in critically ill patients with COVID-19, which might help improve clinical prediction and treatment at an early stage.

• COVID-19
• Laboratory Indicator
• Mortality
• Quantile regression
• Risk factor

• COVID-19
• SARS-CoV-2
• aminotransferases
• hepatic injury
• liver enzymes

Approximately 20% of patients infected with SARS-CoV-2 (COVID-19) develop potentially life-threatening pathologies involving hyperinflammation, cytokine storm, septic shock complications, coagulation dysfunction, and multiple organ failure. Blood levels of the prototypic acute phase reactant, C-reactive protein (CRP), which is hepatically synthesized and released in response to interleukin-6 stimulation, is markedly elevated in patients with COVID-19. Markedly high CRP levels correlate with poor prognosis for survival. Insights into CRP structure–function relationships have uncovered both pro- and anti-inflammatory isoforms that may be used to monitor the extent of tissue damage associated with COVID-19 pathologies and prognoses. Herein, rationale is given for interpretation of CRP blood levels as a simple, rapid, and cost-effective way to assess disease severity and help guide therapeutic options in COVID-19 patients.

• fluorescence imaging
• scanning electron microscopy
• cancer screening
• colorectal cancer
• electron microscopy

• Aged
• Bacterial Translocation
• Blood Cells/ultrastructure
• Colorectal Neoplasms/blood
• Dysbiosis/blood
• Dysbiosis/etiology
• Endothelium, Vascular/injuries
• Female
• Gastrointestinal Microbiome
• Humans
• Inflammation/blood
• Lipids/blood
• Lipopolysaccharides/blood
• Male
• Microscopy, Electron, Scanning
• Middle Aged
• Plasma
• Thrombelastography
• Thrombophilia/blood
• Thrombophilia/etiology

• National Research Foundation (NRF)
• South African Medical Research Council (SAMRC)

Background: Avian AIV-H7N9 influenza progresses rapidly and has a high fatality rate. However, it lacks an early effective biomarker to predict disease severity and fatal outcomes successfully. Our study aimed to explore whether the neutrophil-to-lymphocyte ratio (NLR) taken within 24 h after admission can predict disease severity and fatality in AIV-H7N9-infected patients.

Methods: We retrospectively studied 237 AIV-H7N9-infected patients from multiple centers from 2013 to 2015. We used univariate analysis and multivariate analysis to compare clinical variables between the survival and fatal groups to evaluate the prognostic value.

Results: The NLR taken within 24 h after admission in the fatal group was significantly higher than that in the survival group (P<0.01). Our study found that NLR was independently associated with fatality. The area under the curve (AUC) of the NLR was 0.70, and moreover, when the NLR =19.94, the specificity was 100%, and the sensitivity was 28.4%. The fatality in the NLR ≥19.94 group was significantly increased relative to the patients with an NLR <19.94 (P<0.05).

Conclusion: The NLR is potentially a predictive prognostic biomarker in patients infected with the AIV-H7N9 influenza virus.

• AIV-H7N9
• NLR (neutrophil-to-lymphocyte ratio)
• biomarker
• influenza A

Organisms respond in multiple ways to microbial infections. Pathogen invasion tipically triggers an inflammatory response where acute phase proteins (APP) have a key role. Pentraxins (PTX) are a family of highly conserved APP that play a part in the host defense against infection. The larger proteins of the family are simply named pentraxins, while c-reactive proteins (CRP) and serum amyloid proteins (SAA, SAP) are known as short pentraxins. Although high APP levels have been broadly associated with bacterial infections, there is a growing body of evidence revealing increased PTX, CRP and SAP expression upon viral infection. Furthermore, CRP, PTX and SAP have shown their potential as diagnostic markers and predictors of disease outcome. Likewise, the measurement of APP levels can be valuable to determine the efficacy of antiviral therapies and vaccines. From the practical point of view, the ability of APP to reduce viral infectivity has been observed in several virus-host models. This has prompted investigation efforts to assess the role of acute phase response proteins as immunoregulatory molecules and their potential as therapeutic reagents. This work aims to present an overview of the APP response to viral infections reviewing the current knowledge in the field.

• Antiviral therapy
• Biomarker
• C-reactive protein
• Pentraxins
• Vaccine
• Viral disease

• cytokines
• immunopathogenesis
• inflammation
• mice
• nervous system
• pseudorabies virus

• Acute respiratory distress syndrome
• Antivirals
• Avian influenza
• Corticosteroids
• H7N9
• Pneumonia
• Proinflammatory mediators

The emergence of zoonotic strains of avian influenza (AI) that cause high rates of mortality in people has caused significant global concern, with a looming threat that one of these strains may develop sustained human-to-human transmission and cause a pandemic outbreak. Most notable of these viral strains are the H5N1 highly pathogenic AI and the H7N9 low pathogenicity AI viruses, both of which have mortality rates above 30%. Understanding of their mechanisms of infection and pathobiology is key to our preparation for these and future viral strains of high consequence. AI viruses typically circulate in wild bird populations, commonly infecting waterfowl and also regularly entering commercial poultry flocks. Live poultry markets provide an ideal environment for the spread AI and potentially the selection of mutants with a greater propensity for infecting humans because of the potential for spill over from birds to humans. Pathology from these AI virus infections is associated with a dysregulated immune response, which is characterized by systemic spread of the virus, lymphopenia, and hypercytokinemia. It has been well documented that host/pathogen interactions, particularly molecules of the immune system, play a significant role in both disease susceptibility as well as disease outcome. Here, we review the immune/virus interactions in both avian and mammalian species, and provide an overview or our understanding of how immune dysregulation is driven. Understanding these susceptibility factors is critical for the development of new vaccines and therapeutics to combat the next pandemic influenza.

• H5N1
• H7N9
• avian influenza virus
• highly pathogenic avian influenza virus
• zoonosis

Severe influenza diseases with high mortality have been frequently reported, especially in those patients infected with avian influenza A (H5N1, H7N9 or H10N8) or during a pandemic. Respiratory distress, which is attributed to alveolar damage associated with immunopathological lesions, is the most common cause of death. There is a wealth of information on pathogenesis or treatment options. In this study, we showed that high levels of C-reactive protein (CRP) were induced and correlated with complement activation in patients infected with severe influenza A (H5N1, H7N9 or H10N8), and higher levels were induced in fatal patients than in survivors. CRP treatment enhanced the phagocytosis of monocytes THP-1 to H5N1 virus as well as the expression of proinflammatory cytokines or apoptosis-associated genes in THP-1 cells or pneumocytes A-549 respectively. CRP may link to proinflammatory mediators contributing to activation of complement and boosting inflammatory response in severe influenza infections. Compound 1,6-bis(phosphocholine)-hexane improved the severity and mortality of mice infected with lethal influenza virus significantly. These observations showed that CRP is involved in deterioration of severe influenza diseases, and indicated a substantial candidate molecule for immunotherapy of severe influenza diseases.

•

CRP induces exacerbated immunoresponse toward overt pulmonary inflammation in severe influenza infections.

Severe influenza diseases with high mortality have been frequently reported, especially in those patients infected with avian influenza A (H5N1, H7N9, or H10N8) or during a pandemic. Respiratory distress associated with immunopathological lesions is the most common cause of death in patients infected by these viruses. In this study, we found that CRP may be linked to exacerbated immunoresponse toward overt pulmonary inflammation, which led to alveolar damage and respiratory failure in severe influenza infection. Our data identified that CRP stabilizer can be used to alleviate the immunopathological lesions and mortality in mice infected with lethal influenza virus.

• C-reactive protein
• Complement response
• Immunotherapy
• Severe influenza infection