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1.
Cell Rep ; 37(12): 110126, 2021 12 21.
Article in English | MEDLINE | ID: covidwho-1556413

ABSTRACT

Previous studies have shown that the high mortality caused by viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus primarily results from complications of a cytokine storm. Therefore, it is critical to identify the key factors participating in the cytokine storm. Here we demonstrate that interferon-induced protein 35 (IFP35) plays an important role in the cytokine storm induced by SARS-CoV-2 and influenza virus infection. We find that the levels of serum IFP35 in individuals with SARS-CoV-2 correlates with severity of the syndrome. Using mouse model and cell assays, we show that IFP35 is released by lung epithelial cells and macrophages after SARS-CoV-2 or influenza virus infection. In addition, we show that administration of neutralizing antibodies against IFP35 considerably reduces lung injury and, thus, the mortality rate of mice exposed to viral infection. Our findings suggest that IFP35 serves as a biomarker and as a therapeutic target in virus-induced syndromes.


Subject(s)
COVID-19/blood , COVID-19/drug therapy , Influenza, Human/blood , Influenza, Human/drug therapy , Intracellular Signaling Peptides and Proteins/blood , Animals , Antibodies, Neutralizing/administration & dosage , Biomarkers/blood , COVID-19/pathology , COVID-19/physiopathology , Disease Models, Animal , Humans , Inflammation/metabolism , Influenza, Human/pathology , Lung/metabolism , Lung/pathology , Macrophages/metabolism , Macrophages/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Patient Acuity , SARS-CoV-2/physiology
2.
Front Immunol ; 12: 681516, 2021.
Article in English | MEDLINE | ID: covidwho-1399136

ABSTRACT

Coronavirus disease 2019 (COVID-19) broke out and then became a global epidemic at the end of 2019. With the increasing number of deaths, early identification of disease severity and interpretation of pathogenesis are very important. Aiming to identify biomarkers for disease severity and progression of COVID-19, 75 COVID-19 patients, 34 healthy controls and 23 patients with pandemic influenza A(H1N1) were recruited in this study. Using liquid chip technology, 48 cytokines and chemokines were examined, among which 33 were significantly elevated in COVID-19 patients compared with healthy controls. HGF and IL-1ß were strongly associated with APACHE II score in the first week after disease onset. IP-10, HGF and IL-10 were correlated positively with virus titers. Cytokines were significantly correlated with creatinine, troponin I, international normalized ratio and procalcitonin within two weeks after disease onset. Univariate analyses were carried out, and 6 cytokines including G-CSF, HGF, IL-10, IL-18, M-CSF and SCGF-ß were found to be associated with the severity of COVID-19. 11 kinds of cytokines could predict the severity of COVID-19, among which IP-10 and M-CSF were excellent predictors for disease severity. In conclusion, the levels of cytokines in COVID-19 were significantly correlated with the severity of the disease in the early stage, and serum cytokines could be used as warning indicators of the severity and progression of COVID-19. Early stratification of disease and intervention to reduce hypercytokinaemia may improve the prognosis of COVID-19 patients.


Subject(s)
COVID-19/immunology , Cytokines/genetics , Cytokines/immunology , SARS-CoV-2/immunology , Severity of Illness Index , Transcriptome/immunology , Adult , Aged , Biomarkers/blood , Chemokines/blood , Chemokines/genetics , Chemokines/immunology , Cytokines/blood , Female , Hospitalization/statistics & numerical data , Humans , Influenza, Human/blood , Influenza, Human/immunology , Male , Middle Aged
3.
Front Immunol ; 12: 720363, 2021.
Article in English | MEDLINE | ID: covidwho-1376702

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.


Subject(s)
C-Reactive Protein/metabolism , COVID-19/blood , COVID-19/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Humans , Inflammation/blood , Influenza A Virus, H1N1 Subtype , Influenza, Human/blood , Influenza, Human/complications , Stroke/blood , Virus Diseases
4.
Front Immunol ; 12: 691879, 2021.
Article in English | MEDLINE | ID: covidwho-1282387

ABSTRACT

Increasing human Adenovirus (HAdV) infections complicated with acute respiratory distress syndrome (ARDS) even fatal outcome were reported in immunocompetent adolescent and adult patients. Here, we characterized the cytokine/chemokine expression profiles of immunocompetent patients complicated with ARDS during HAdV infection and identified biomarkers for disease severity/progression. Forty-eight cytokines/chemokines in the plasma samples from 19 HAdV-infected immunocompetent adolescent and adult patients (ten complicated with ARDS) were measured and analyzed in combination with clinical indices. Immunocompetent patients with ARDS caused by severe acute respiratory disease coronavirus (SARS-CoV)-2, 2009 pandemic H1N1 (panH1N1) or bacteria were included for comparative analyses. Similar indices of disease course/progression were found in immunocompetent patients with ARDS caused by HAdV, SARS-CoV-2 or panH1N infections, whereas the HAdV-infected group showed a higher prevalence of viremia, as well as increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK). Expression levels of 33 cytokines/chemokines were increased significantly in HAdV-infected patients with ARDS compared with that in healthy controls, and many of them were also significantly higher than those in SARS-CoV-2-infected and panH1N1-infected patients. Expression of interferon (IFN)-γ, interleukin (IL)-1ß, hepatocyte growth factor (HGF), monokine induced by IFN-γ (MIG), IL-6, macrophage-colony stimulating factor (M-CSF), IL-10, IL-1α and IL-2Ra was significantly higher in HAdV-infected patients with ARDS than that in those without ARDS, and negatively associated with the ratio of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2). Analyses of the receiver operating characteristic curve (ROC) showed that expression of IL-10, M-CSF, MIG, HGF, IL-1ß, IFN-γ and IL-2Ra could predict the progression of HAdV infection, with the highest area under the curve (AUC) of 0.944 obtained for IL-10. Of note, the AUC value for the combination of IL-10, IFN-γ, and M-CSF reached 1. In conclusion, the "cytokine storm" occurred during HAdV infection in immunocompetent patients, and expression of IL-10, M-CSF, MIG, HGF, IL-1ß, IFN-γ and IL-2Ra was closely associated with disease severity and could predict disease progression.


Subject(s)
Adenovirus Infections, Human/blood , Cytokines/blood , Respiratory Distress Syndrome/blood , Adenovirus Infections, Human/complications , Adenovirus Infections, Human/pathology , Adenoviruses, Human , Adolescent , Adult , Bacteria , Bacterial Infections/blood , Bacterial Infections/complications , Bacterial Infections/pathology , Biomarkers/blood , COVID-19/blood , COVID-19/complications , COVID-19/pathology , Disease Progression , Female , Humans , Influenza A Virus, H1N1 Subtype , Influenza, Human/blood , Influenza, Human/complications , Influenza, Human/pathology , Male , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/pathology , SARS-CoV-2 , Severity of Illness Index , Viremia/blood , Viremia/complications , Viremia/pathology , Young Adult
5.
Front Immunol ; 11: 575074, 2020.
Article in English | MEDLINE | ID: covidwho-1256374

ABSTRACT

Combined cellular and humoral host immune response determine the clinical course of a viral infection and effectiveness of vaccination, but currently the cellular immune response cannot be measured on simple blood samples. As functional activity of immune cells is determined by coordinated activity of signaling pathways, we developed mRNA-based JAK-STAT signaling pathway activity assays to quantitatively measure the cellular immune response on Affymetrix expression microarray data of various types of blood samples from virally infected patients (influenza, RSV, dengue, yellow fever, rotavirus) or vaccinated individuals, and to determine vaccine immunogenicity. JAK-STAT1/2 pathway activity was increased in blood samples of patients with viral, but not bacterial, infection and was higher in influenza compared to RSV-infected patients, reflecting known differences in immunogenicity. High JAK-STAT3 pathway activity was associated with more severe RSV infection. In contrast to inactivated influenza virus vaccine, live yellow fever vaccine did induce JAK-STAT1/2 pathway activity in blood samples, indicating superior immunogenicity. Normal (healthy) JAK-STAT1/2 pathway activity was established, enabling assay interpretation without the need for a reference sample. The JAK-STAT pathway assays enable measurement of cellular immune response for prognosis, therapy stratification, vaccine development, and clinical testing.


Subject(s)
Dengue Virus/immunology , Immunity, Cellular , Orthomyxoviridae/immunology , Respiratory Syncytial Virus, Human/immunology , Rotavirus/immunology , Viral Vaccines/therapeutic use , Virus Diseases/immunology , Yellow fever virus/immunology , Biomarkers/blood , Dengue/blood , Dengue/immunology , Dengue/prevention & control , Dengue/virology , Dengue Vaccines/therapeutic use , Dengue Virus/pathogenicity , Diagnosis, Differential , Host-Pathogen Interactions , Humans , Immunogenicity, Vaccine , Influenza Vaccines/therapeutic use , Influenza, Human/blood , Influenza, Human/immunology , Influenza, Human/prevention & control , Influenza, Human/virology , Oligonucleotide Array Sequence Analysis , Orthomyxoviridae/pathogenicity , Predictive Value of Tests , RNA, Messenger/blood , RNA, Messenger/genetics , Respiratory Syncytial Virus Infections/blood , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Virus, Human/pathogenicity , Rotavirus/pathogenicity , Rotavirus Infections/blood , Rotavirus Infections/immunology , Rotavirus Infections/prevention & control , Rotavirus Infections/virology , Rotavirus Vaccines , Signal Transduction/genetics , Virus Diseases/blood , Virus Diseases/prevention & control , Virus Diseases/virology , Yellow Fever/blood , Yellow Fever/immunology , Yellow Fever/prevention & control , Yellow Fever/virology , Yellow Fever Vaccine/therapeutic use , Yellow fever virus/pathogenicity
6.
Front Immunol ; 12: 593595, 2021.
Article in English | MEDLINE | ID: covidwho-1229174

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1ß, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.


Subject(s)
COVID-19 , Cytokines , Influenza A Virus, H1N1 Subtype , Influenza, Human , Matrix Metalloproteinase 1 , Matrix Metalloproteinase 3 , Receptors, Immunologic , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , Cytokines/blood , Cytokines/immunology , Female , Humans , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H1N1 Subtype/metabolism , Influenza, Human/blood , Influenza, Human/epidemiology , Influenza, Human/immunology , Male , Matrix Metalloproteinase 1/blood , Matrix Metalloproteinase 1/immunology , Matrix Metalloproteinase 3/blood , Matrix Metalloproteinase 3/immunology , Middle Aged , Prospective Studies , Receptors, Immunologic/blood , Receptors, Immunologic/immunology , Th1 Cells/immunology , Th2 Cells/immunology
7.
Eur J Med Res ; 26(1): 45, 2021 May 14.
Article in English | MEDLINE | ID: covidwho-1229005

ABSTRACT

BACKGROUND: Hematological comparison of coronavirus disease (COVID-19) and other viral pneumonias can provide insights into COVID-19 treatment. METHODS: In this retrospective case-control single-center study, we compared the data of 126 patients with viral pneumonia during different outbreaks [severe acute respiratory syndrome (SARS) in 2003, influenza A (H1N1) in 2009, human adenovirus type 7 in 2018, and COVID-19 in 2020]. RESULTS: One of the COVID-19 characteristics was a continuous decline in the hemoglobin level. The neutrophil count was related to the aggravation of COVID-19 and SARS. Thrombocytopenia occurred in patients with SARS and severe COVID-19 even at the recovery stage. Lymphocytes were related to the entire course of adenovirus infection, recovery of COVID-19, and disease development of SARS. CONCLUSIONS: Dynamic changes in hematological counts could provide a reference for the pathogenesis and prognosis of pneumonia caused by respiratory viruses in clinics.


Subject(s)
Adenovirus Infections, Human/blood , COVID-19/blood , Influenza, Human/blood , Pneumonia, Viral/blood , Severe Acute Respiratory Syndrome/blood , Adenovirus Infections, Human/pathology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/pathology , Case-Control Studies , Female , Hemoglobins/analysis , Humans , Influenza, Human/pathology , Lymphocyte Count , Male , Middle Aged , Neutrophils/cytology , Pneumonia, Viral/pathology , Retrospective Studies , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/pathology , Thrombocytopenia/pathology , Young Adult
8.
J Med Virol ; 93(4): 2221-2226, 2021 04.
Article in English | MEDLINE | ID: covidwho-1217374

ABSTRACT

It is difficult to distinguish coronavirus disease-2019 (COVID-19) from other viral respiratory tract infections owing to the similarities in clinical and radiological findings. This study aims to determine the clinical importance of platelet count and platelet indices in the differentiation of COVID-19 from influenza and the value of these parameters in the differential diagnosis of COVID-19. The medical records of the patients and the electronic patient monitoring system were retrospectively analyzed. Demographic characteristics, admission symptoms, laboratory findings, radiological involvement, comorbidities, and mortality of the patients were recorded. Forty-three patients diagnosed with influenza and 54 diagnosed with COVID-19 were included in the study. The average age of the COVID-19 patients was lower than that of the influenza patients (influenza: 60.5 years, COVID-19: 52.4 years; pp = 0.024),.024), and the male gender was predominant in the COVID-19 group (influenza: 42%, COVID-19: 56%). According to laboratory findings, the mean platelet volume (MPV) and MPV/platelet ratio were statistically significantly lower, whereas the eosinophil count and platelet distribution width levels were significantly higher (p < 0.05) in the COVID-19 group. It was found that the most common symptom in both groups was dyspnea and that the symptom was more prevalent among influenza patients. In the diagnosis of COVID-19, the platelet count and platelet indices are easily accessible, inexpensive, and important parameters in terms of differential diagnosis and can help in the differentiation of COVID-19 from influenza during seasonal outbreaks of the latter.


Subject(s)
Blood Platelets/pathology , COVID-19/blood , Influenza, Human/blood , Adult , Aged , COVID-19/virology , Female , Humans , Male , Middle Aged , Platelet Count , Pneumonia, Viral/blood , Pneumonia, Viral/virology , Retrospective Studies , SARS-CoV-2/isolation & purification
9.
J Med Virol ; 93(2): 1029-1037, 2021 02.
Article in English | MEDLINE | ID: covidwho-1196434

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 infection. This study aims to examine the changes in peripheral blood parameters during the early stages of COVID-19 and influenza. We analyzed the peripheral blood parameters of 169 COVID-19 patients and 131 influenza patients during the early-onset stage. Results from the patients with COVID-19 were compared with those from healthy controls and influenza patients. In addition, results from patients with common and severe COVID-19 were further compared. There were significant differences between COVID-19 and influenza patients in terms of age, white blood cell count, platelet count, percentage of neutrophils, percentage of lymphocytes, percentage of monocytes, percentage of eosinophils, percentage of basophils, neutrophil, count and monocyte count. Two parameters (monocyte count and percentage of basophils) were combined to clarify the diagnostic efficacy of COVID-19 and influenza and the area under the curve was found to be 0.772. Comparison of peripheral blood parameters from common COVID-19, severe COVID-19, and influenza patients revealed many differences during the early disease stages. The diagnostic formula developed by this study will be of benefit for physicians in the differentiation of COVID-19 and influenza.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Influenza, Human/blood , Influenza, Human/diagnosis , Adolescent , Adult , Aged , China , Diagnosis, Differential , Female , Humans , Leukocyte Count , Lymphocytes/cytology , Male , Middle Aged , Monocytes/cytology , Neutrophils/cytology , Platelet Count , Young Adult
10.
Front Immunol ; 12: 629193, 2021.
Article in English | MEDLINE | ID: covidwho-1140644

ABSTRACT

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS), is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells activate and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with coronavirus 2019 (COVID-19) for a subgroup of patients. CRS is not unique to the SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, and H7N9). With a comprehensive literature search, we collected changing the cytokine levels from patients upon infection with the viral pathogens mentioned above. We analyzed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. Our curation indicates that the cytokine response induced by SARS-CoV-2 is different compared to other CRS-causing respiratory viruses, as SARS-CoV-2 does not always induce specific cytokines like other coronaviruses or influenza do, such as IL-2, IL-10, IL-4, or IL-5. Comparing the collated cytokine responses caused by the analyzed viruses highlights a SARS-CoV-2-specific dysregulation of the type-I interferon (IFN) response and its downstream cytokine signatures. The map of responses gathered in this study could help specialists identify interventions that alleviate CRS in different diseases and evaluate whether they could be used in the COVID-19 cases.


Subject(s)
COVID-19/immunology , Cytokine Release Syndrome/immunology , Influenza A virus/immunology , Influenza, Human/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , SARS Virus/immunology , SARS-CoV-2/immunology , Severe Acute Respiratory Syndrome/immunology , Severity of Illness Index , COVID-19/blood , COVID-19/pathology , COVID-19/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/virology , Cytokines/blood , Humans , Inflammation/immunology , Influenza, Human/blood , Influenza, Human/virology , Severe Acute Respiratory Syndrome/blood , Severe Acute Respiratory Syndrome/virology
11.
Sci Immunol ; 6(57)2021 03 10.
Article in English | MEDLINE | ID: covidwho-1127535

ABSTRACT

While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.


Subject(s)
COVID-19/blood , Cytokines/blood , Adult , Aged , COVID-19/immunology , Cytokines/immunology , Female , Humans , Inflammation/blood , Inflammation/immunology , Influenza A Virus, H1N1 Subtype , Influenza, Human/blood , Influenza, Human/immunology , Male , Middle Aged , SARS-CoV-2 , Severity of Illness Index
12.
Environ Health Perspect ; 128(12): 127004, 2020 12.
Article in English | MEDLINE | ID: covidwho-1050487

ABSTRACT

BACKGROUND: Environmental cadmium exposure is widespread. In humans, cadmium is poorly excreted, triggers pulmonary inflammation, reduces pulmonary function, and enhances lung injury by respiratory syncytial virus. OBJECTIVES: We examined the association of cadmium burden with mortality related to influenza or pneumonia. METHODS: This prospective analysis of the National Health and Nutrition Examination Survey (NHANES) included 7,173 and 8,678 participants ≥45 years of age enrolled in NHANES-III and NHANES 1999-2006, respectively. Associations were evaluated between cadmium and mortality from influenza or pneumonia during a median follow-up of 17.3 y (NHANES-III, based on creatinine-corrected urine cadmium) and 11.4 y (NHANES 1999-2006, based on blood cadmium). Survey-weighted Cox proportional hazard models were used to compute hazard ratios (HRs) comparing the mortality of individuals at the 80th vs. the 20th percentile of cadmium concentrations. RESULTS: In NHANES-III, after adjustment for sex, race/ethnicity, education, body mass index, serum cholesterol, hypertension, and NHANES phase (or cycle), the HR comparing influenza or pneumonia mortality among participants with creatinine-corrected urinary cadmium in the 80th vs. 20th percentile was 1.15 (95% CI: 1.05, 1.26; p=0.002) in the population as a whole and 1.27 (95% CI: 1.12, 1.43; p=0.002) among never smokers. In NHANES 1999-2006, adjusted HRs for the 80th vs. 20th percentile of blood cadmium were 1.14 (95% CI: 0.96, 1.36; p=0.15) for the overall population and 1.71 (95% CI: 0.95, 3.09; p=0.07) in never smokers. DISCUSSION: Among middle-aged and older adults in the United States, higher cadmium burdens are associated with higher mortality from influenza or pneumonia. This raises the possibility that cadmium may worsen outcomes from COVID-19 infections. https://doi.org/10.1289/EHP7598.


Subject(s)
COVID-19/mortality , Cadmium/blood , Environmental Pollutants/blood , Influenza, Human/mortality , Pneumonia/mortality , SARS-CoV-2 , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/complications , Environmental Exposure , Female , Humans , Influenza, Human/blood , Influenza, Human/complications , Male , Middle Aged , Nutrition Surveys , Pneumonia/blood , Pneumonia/complications , Proportional Hazards Models , Prospective Studies , United States/epidemiology
13.
J Clin Invest ; 131(6)2021 03 15.
Article in English | MEDLINE | ID: covidwho-1045635

ABSTRACT

The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-γ production partly via an arginase 1-dependent (Arg-1-dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response.


Subject(s)
COVID-19/immunology , Myeloid-Derived Suppressor Cells/immunology , Adult , Aged , Aged, 80 and over , Arginase/blood , COVID-19/blood , COVID-19/pathology , Case-Control Studies , Cohort Studies , Female , Humans , Influenza, Human/blood , Influenza, Human/immunology , Influenza, Human/pathology , Interferon-gamma/blood , Interleukin-6/blood , Leukocyte Count , Male , Middle Aged , Myeloid-Derived Suppressor Cells/pathology , Pandemics , Respiratory System/immunology , Respiratory System/pathology , SARS-CoV-2 , Severity of Illness Index , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Young Adult
14.
Medicine (Baltimore) ; 99(44): e23064, 2020 Oct 30.
Article in English | MEDLINE | ID: covidwho-990918

ABSTRACT

Coronavirus disease 2019 (COVID-19) is the most important global public health issue that we currently face. We aimed to explore the clinical features of patients with COVID-19 and compared them with those of hospitalized community-acquired pneumonia (CAP) patients caused by influenza virus during the same period.From Jan 1, to Mar 4, 2020, patients with COVID-19 or CAP caused by influenza virus who were admitted to the First Affiliated Hospital of Xiamen University were consecutively screened for enrollment.A total of 35 COVID-19 patients and 22 CAP patients caused by influenza virus were included in this study. Most of COVID-19 patients had characteristics of familial clustering (63%), however, in the other group, there was no similar finding. The percentages of patients with a high fever (the highest recorded temperature was ≥39.0°C; 11% vs 45% [COVID-19 vs CAP groups, respectively]), dyspnea (9% vs 59%), leukocytosis (3% vs 32%), elevated C-reactive protein concentrations (>10 mg/L, 48% vs 86%), elevated procalcitonin levels (>0.1 ng/ml, 15% vs 73%), PaO2/FiO2 <200 mm Hg (4% vs 22%), and infiltration on imaging (29% vs 68%) in the COVID-19 group were less than those same indices in the hospitalized CAP patients caused by influenza virus. Ground-glass opacity with reticular pattern (63%) and interlobular septal thickening (71%) in chest CT were commonly observed in the COVID-19 group.COVID-19 and CAP caused by influenza virus appear to share some similarities in clinical manifestaions but they definitely have major distinctions. Influenza infection remains a health problem even during COVID-19 pandemic.


Subject(s)
Coronavirus Infections/epidemiology , Influenza, Human/epidemiology , Pneumonia, Viral/epidemiology , Adult , Aged , Aged, 80 and over , COVID-19 , China/epidemiology , Community-Acquired Infections , Coronavirus Infections/blood , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Cross-Sectional Studies , Female , Humans , Influenza, Human/blood , Influenza, Human/diagnostic imaging , Influenza, Human/therapy , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/therapy , Radiography, Thoracic , Retrospective Studies
15.
Epidemiol Infect ; 148: e272, 2020 11 05.
Article in English | MEDLINE | ID: covidwho-960249

ABSTRACT

SARS-CoV-2, the causative agent of coronavirus disease 19 (COVID-19), was identified in Wuhan, China. Since then, the novel coronavirus started to be compared to influenza. The haematological parameters and inflammatory indexes are associated with severe illness in COVID-19 patients. In this study, the laboratory data of 120 COVID-19 patients, 100 influenza patients and 61 healthy controls were evaluated. Lower lymphocytes, eosinophils, basophils, platelets and higher delta neutrophil index (DNI), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were found in COVID-19 and influenza groups compared to healthy controls. The eosinophils, lymphocytes and PLR made the highest contribution to differentiate COVID-19 patients from healthy controls (area under the curves (AUCs): 0.819, 0.817 and 0.716, respectively; P-value is <0.0001 for all). The NLR, the optimal cut-off value was 3.58, which resulted in a sensitivity of 30.8 and a specificity of 100 (AUC: 0.677, P < 0.0001). Higher leucocytes, neutrophils, DNI, NLR, PLR and lower lymphocytes, red blood cells, haemoglobin, haematocrit levels were found in severe patients at the end of treatment. Nonsevere patients showed an upward trend for lymphocytes, eosinophils and platelets, and a downward trend for neutrophils, DNI, NLR and PLR. However, there was an increasing trend for eosinophils, platelets and PLR in severe patients. In conclusion, NLR and PLR can be used as biomarkers to distinguish COVID-19 patients from healthy people and to predict the severity of COVID-19. The increasing value of PLR during follow-up may be more useful compared to NLR to predict the disease severity.


Subject(s)
Blood Cell Count , COVID-19/blood , COVID-19/diagnosis , Influenza, Human/blood , Influenza, Human/diagnosis , SARS-CoV-2 , Adolescent , Adult , Aged , Aged, 80 and over , Area Under Curve , Case-Control Studies , Female , Humans , Male , Middle Aged , Young Adult
16.
Infez Med ; 28(4): 534-538, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-950578

ABSTRACT

Since the most frequent symptoms of novel coronavirus 2019 disease (COVID-19) are common in influenza A/B (FLU), predictive models to distinguish between COVID-19 and FLU using standardized non-specific laboratory indicators are needed. The aim of our study was to evaluate whether a recently dynamic nomogram, established in the Chinese population and based on age, lymphocyte percentage and monocyte absolute count, might apply to a different context. We collected data from 299 patients (243 with COVID-19 and 56 with FLU) at Policlinico Umberto I, Sapienza University of Rome. The nomogram included age, lymphocyte percentage and monocyte absolute count to differentiate COVID-19 from FLU. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all associations. Multivariate logistic regression models were used to adjust for potential confounding. A p-value of less than 0.05 was considered statistically significant. Patients with COVID-19 had higher age, lymphocyte percentage and monocyte absolute count than patients with FLU. Although univariate analysis confirmed that age, lymphocyte percentage and monocyte absolute count were associated with COVID-19, only at multivariate analysis was monocyte count statistically significant as a predictive factor of COVID-19. Using receiver operating characteristic (ROC) curves, we found that a monocyte count >0.35x1000/mL showed an AUC of 0.680 (sensitivity 0.992, specificity 0.368). A dynamic nomogram including age, lymphocyte percentage and monocyte absolute count cannot be applied to our context, probably due to differences in demographic characteristics between Italian and Chinese populations. However, our data showed that monocyte absolute count is highly predictive of COVID-19, suggesting its potential role above all in settings where prompt PCR nasopharyngeal testing is lacking.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , Influenza, Human/diagnosis , Monocytes , SARS-CoV-2 , Adult , Age Factors , Aged , COVID-19/blood , COVID-19/epidemiology , Confidence Intervals , Diagnosis, Differential , Hospitalization , Humans , Influenza, Human/blood , Italy/epidemiology , Leukocyte Count , Lymphocyte Count , Middle Aged , Multivariate Analysis , Nomograms , Odds Ratio , Pandemics , ROC Curve , Retrospective Studies , Sensitivity and Specificity , Symptom Assessment/methods
17.
EBioMedicine ; 62: 103125, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-938894

ABSTRACT

BACKGROUND: The pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19. METHODS: In this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (Ctrough) ≥20 mg/L at all measured time points after the second dose. RESULTS: Sixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir Ctrough decreased significantly over time in both groups (p <0.01). Relative to day 2 (48 hrs), concentrations were 91.7% and 90.3% lower in the 1600/600 mg group and 79.3% and 89.5% lower in the 1800/800 mg group at day 7 and 10, respectively. In contrast, oseltamivir concentrations did not change significantly over time. A 2-compartment disposition model with first-order absorption and elimination described the observed favipiravir concentration-time data well. Modeling demonstrated that less than 50% of patients achieved Ctrough ≥20 mg/L for >80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza. CONCLUSION: The two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.


Subject(s)
Amides , Influenza, Human/drug therapy , Oseltamivir , Pyrazines , Aged , Amides/administration & dosage , Amides/pharmacokinetics , Drug Therapy, Combination , Female , Humans , Influenza, Human/blood , Male , Middle Aged , Oseltamivir/administration & dosage , Oseltamivir/pharmacokinetics , Pyrazines/administration & dosage , Pyrazines/pharmacokinetics , Severity of Illness Index
18.
J Clin Lab Anal ; 35(1): e23657, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-938459

ABSTRACT

BACKGROUND: To evaluate the ability of peripheral blood inflammatory markers in predicating the typing of COVID-19, prognosis, and some differences between COVID-19 and influenza A patients. METHODS: Clinical data on 285 cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. Additional 446 Influenza A outpatients' hematologic data were enrolled for comparison. RESULTS: NLR, SII, RLR, PLR, HsCRP, and IL-6 were significant higher and LMR was lower in severe COVID-19 patients than in mild COVID-19 patients (p < .001). PLR and LMR were lower in the individuals with influenza A than those with COVID-19 (p < .01). COVID-19 patients with higher levels of NLR, SII, RLR, PLR, HsCRP, and IL-6 and lower LMR were significantly associated with the severe type. AUC of NLR (0.76) was larger while the specificity of IL-6 (86%) and sensitivity of HsCRP (89%) were higher than other inflammatory markers in predicating the typing of COVID-19. PT had obvious correlation with all the inflammatory markers except RPR. NLR showed positive correlations with AST, TP, BUN, CREA, PT, and D-dimer. Patients with high IL-6 levels have a relatively worse prognosis (HR = 2.30). CONCLUSION: Peripheral blood inflammatory markers reflected the intensity of inflammation and associated with severity of COVID-19.NLR was more useful to predict severity as well as IL-6 to predict prognosis of COVID-19. PLR and LMR were initially found to be higher in SARS-CoV-2 virus-infected group than in influenza A.


Subject(s)
Biomarkers/blood , COVID-19/blood , Inflammation/blood , Influenza, Human/blood , Aged , Blood Cell Count , COVID-19/complications , COVID-19/epidemiology , Comorbidity , Female , Humans , Interleukin-6/blood , Male , Middle Aged , Neutrophils , Prognosis , Retrospective Studies
19.
Biosens Bioelectron ; 169: 112643, 2020 Dec 01.
Article in English | MEDLINE | ID: covidwho-778506

ABSTRACT

Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. We find that the array is readily able to distinguish uninfected from convalescent COVID-19 subjects, and provides quantitative information about total Ig, as well as IgG- and IgM-specific responses.


Subject(s)
Antibodies, Viral/blood , Coronavirus Infections/blood , Coronavirus/isolation & purification , Influenza A virus/isolation & purification , Influenza, Human/blood , Pneumonia, Viral/blood , Betacoronavirus/isolation & purification , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Equipment Design , HEK293 Cells , Humans , Influenza, Human/diagnosis , Influenza, Human/virology , Middle East Respiratory Syndrome Coronavirus/isolation & purification , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Protein Array Analysis/instrumentation , Protein Array Analysis/methods , SARS Virus/isolation & purification , SARS-CoV-2 , Sensitivity and Specificity
20.
Biomed Environ Sci ; 33(8): 614-619, 2020 Aug 20.
Article in English | MEDLINE | ID: covidwho-771380

ABSTRACT

This study aimed to understand the differences in clinical, epidemiological, and laboratory features between the new coronavirus disease 2019 (COVID-2019) and influenza A in children. Data of 23 hospitalized children with COVID-19 (9 boys, 5.7 ± 3.8 years old) were compared with age- and sex-matched 69 hospitalized and 69 outpatient children with influenza A from a hospital in China. The participants' epidemiological history, family cluster, clinical manifestations, and blood test results were assessed. Compared with either inpatients or outpatients with influenza A, children with COVID-19 showed significantly more frequent family infections and higher ratio of low fever (< 37.3 °C), but shorter cough and fever duration, lower body temperature, and lower rates of cough, fever, high fever (> 39 °C), nasal congestion, rhinorrhea, sore throat, vomiting, myalgia or arthralgia, and febrile seizures. They also showed higher counts of lymphocytes, T lymphocyte CD8, and platelets and levels of cholinesterase, aspartate aminotransferase, lactate dehydrogenase, and lactic acid, but lower serum amyloid, C-reactive protein, and fibrinogen levels and erythrocyte sedimentation rate, and shorter prothrombin time. The level of alanine aminotransferase in children with COVID-19 is lower than that in inpatients but higher than that in outpatients with influenza A. Pediatric COVID-19 is associated with more frequent family infection, milder symptoms, and milder immune responses relative to pediatric influenza A.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Influenza, Human/epidemiology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , COVID-19 , Case-Control Studies , Child , Coronavirus Infections/blood , Coronavirus Infections/immunology , Female , Humans , Influenza, Human/blood , Influenza, Human/immunology , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/immunology , SARS-CoV-2
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