Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
1.
Theranostics ; 12(1): 290-306, 2022.
Article in English | MEDLINE | ID: covidwho-1579955

ABSTRACT

Coronavirus disease 2019 (COVID19), caused by SARS-CoV-2, is a complex disease, with a variety of clinical manifestations ranging from asymptomatic infection or mild cold-like symptoms to more severe cases requiring hospitalization and critical care. The most severe presentations seem to be related with a delayed, deregulated immune response leading to exacerbated inflammation and organ damage with close similarities to sepsis. Methods: In order to improve the understanding on the relation between host immune response and disease course, we have studied the differences in the cellular (monocytes, CD8+ T and NK cells) and soluble (cytokines, chemokines and immunoregulatory ligands) immune response in blood between Healthy Donors (HD), COVID19 and a group of patients with non-COVID19 respiratory tract infections (NON-COV-RTI). In addition, the immune response profile has been analyzed in COVID19 patients according to disease severity. Results: In comparison to HDs and patients with NON-COV-RTI, COVID19 patients show a heterogeneous immune response with the presence of both activated and exhausted CD8+ T and NK cells characterised by the expression of the immune checkpoint LAG3 and the presence of the adaptive NK cell subset. An increased frequency of adaptive NK cells and a reduction of NK cells expressing the activating receptors NKp30 and NKp46 correlated with disease severity. Although both activated and exhausted NK cells expressing LAG3 were increased in moderate/severe cases, unsupervised cell clustering analyses revealed a more complex scenario with single NK cells expressing more than one immune checkpoint (PD1, TIM3 and/or LAG3). A general increased level of inflammatory cytokines and chemokines was found in COVID19 patients, some of which like IL18, IL1RA, IL36B and IL31, IL2, IFNα and TNFα, CXCL10, CCL2 and CCL8 were able to differentiate between COVID19 and NON-COV-RTI and correlated with bad prognosis (IL2, TNFα, IL1RA, CCL2, CXCL10 and CXCL9). Notably, we found that soluble NKG2D ligands from the MIC and ULBPs families were increased in COVID19 compared to NON-COV-RTI and correlated with disease severity. Conclusions: Our results provide a detailed comprehensive analysis of the presence of activated and exhausted CD8+T, NK and monocyte cell subsets as well as extracellular inflammatory factors beyond cytokines/chemokines, specifically associated to COVID19. Importantly, multivariate analysis including clinical, demographical and immunological experimental variables have allowed us to reveal specific immune signatures to i) differentiate COVID19 from other infections and ii) predict disease severity and the risk of death.


Subject(s)
COVID-19/blood , COVID-19/immunology , Adult , Aged , Aged, 80 and over , Biomarkers/blood , CD8-Positive T-Lymphocytes/virology , COVID-19/mortality , Case-Control Studies , Chemokines/blood , Cytokines/blood , Female , Hospitalization , Humans , Killer Cells, Natural/virology , Logistic Models , Male , Middle Aged , Monocytes/virology , Prospective Studies , Respiratory Tract Infections/blood , Respiratory Tract Infections/immunology , Severity of Illness Index
2.
Sci Rep ; 10(1): 14186, 2020 08 25.
Article in English | MEDLINE | ID: covidwho-1434143

ABSTRACT

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s2; 0.43 ± 0.14%/s2, all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.


Subject(s)
Bacterial Infections/blood , Hemostasis , Partial Thromboplastin Time/methods , Virus Diseases/blood , Aged , Aged, 80 and over , C-Reactive Protein/analysis , Dengue/blood , Disseminated Intravascular Coagulation/blood , Disseminated Intravascular Coagulation/etiology , Elective Surgical Procedures , Female , Humans , Male , Middle Aged , Procalcitonin/blood , Respiratory Tract Infections/blood
3.
Biomed Res Int ; 2021: 9939134, 2021.
Article in English | MEDLINE | ID: covidwho-1301740

ABSTRACT

COVID-19, a severe respiratory disease caused by a new type of coronavirus SARS-CoV-2, has been spreading all over the world. Patients infected with SARS-CoV-2 may have no pathogenic symptoms, i.e., presymptomatic patients and asymptomatic patients. Both patients could further spread the virus to other susceptible people, thereby making the control of COVID-19 difficult. The two major challenges for COVID-19 diagnosis at present are as follows: (1) patients could share similar symptoms with other respiratory infections, and (2) patients may not have any symptoms but could still spread the virus. Therefore, new biomarkers at different omics levels are required for the large-scale screening and diagnosis of COVID-19. Although some initial analyses could identify a group of candidate gene biomarkers for COVID-19, the previous work still could not identify biomarkers capable for clinical use in COVID-19, which requires disease-specific diagnosis compared with other multiple infectious diseases. As an extension of the previous study, optimized machine learning models were applied in the present study to identify some specific qualitative host biomarkers associated with COVID-19 infection on the basis of a publicly released transcriptomic dataset, which included healthy controls and patients with bacterial infection, influenza, COVID-19, and other kinds of coronavirus. This dataset was first analysed by Boruta, Max-Relevance and Min-Redundancy feature selection methods one by one, resulting in a feature list. This list was fed into the incremental feature selection method, incorporating one of the classification algorithms to extract essential biomarkers and build efficient classifiers and classification rules. The capacity of these findings to distinguish COVID-19 with other similar respiratory infectious diseases at the transcriptomic level was also validated, which may improve the efficacy and accuracy of COVID-19 diagnosis.


Subject(s)
COVID-19 Testing/methods , COVID-19/diagnosis , COVID-19/genetics , Biomarkers/analysis , COVID-19/blood , Databases, Genetic , Gene Expression Profiling/methods , Humans , Influenza, Human , Machine Learning , Mass Screening/methods , Models, Theoretical , Respiratory Tract Infections/blood , Respiratory Tract Infections/diagnosis , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Transcriptome/genetics
4.
Eur J Clin Microbiol Infect Dis ; 40(9): 1983-1997, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1263157

ABSTRACT

SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.


Subject(s)
Antibodies, Viral/blood , Bacterial Infections/diagnosis , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Respiratory Tract Infections/diagnosis , Antibodies, Bacterial/blood , Bacterial Infections/blood , COVID-19/blood , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Respiratory Tract Infections/blood , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
5.
Front Immunol ; 12: 634181, 2021.
Article in English | MEDLINE | ID: covidwho-1177976

ABSTRACT

Bacterial respiratory tract infections are the hallmark of primary antibody deficiencies (PADs). Because they are also among the most common infections in healthy individuals, PADs are usually overlooked in these patients. Careful evaluation of the history, including frequency, chronicity, and presence of other infections, would help suspect PADs. This review will focus on infections in relatively common PADs, discussing diagnostic challenges, and some management strategies to prevent infections.


Subject(s)
Bacterial Infections/immunology , Immunocompromised Host , Immunoglobulins/deficiency , Primary Immunodeficiency Diseases/immunology , Respiratory Tract Infections/immunology , Agammaglobulinemia/blood , Agammaglobulinemia/immunology , Agammaglobulinemia/therapy , Animals , Bacterial Infections/blood , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Class I Phosphatidylinositol 3-Kinases/blood , Class I Phosphatidylinositol 3-Kinases/immunology , Common Variable Immunodeficiency/blood , Common Variable Immunodeficiency/immunology , Common Variable Immunodeficiency/therapy , Humans , Immunoglobulins/blood , Primary Immunodeficiency Diseases/blood , Primary Immunodeficiency Diseases/therapy , Prognosis , Respiratory Tract Infections/blood , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/prevention & control , Risk Assessment , Risk Factors
6.
Ann Neurol ; 89(3): 610-616, 2021 03.
Article in English | MEDLINE | ID: covidwho-1044305

ABSTRACT

There is emerging evidence for multifarious neurological manifestations of coronavirus disease 2019 (COVID-19), but little is known regarding whether they reflect structural damage to the nervous system. Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal injury. We measured sNfL concentrations of 29 critically ill COVID-19 patients, 10 critically ill non-COVID-19 patients, and 259 healthy controls. After adjusting for neurological comorbidities and age, sNfL concentrations were higher in patients with COVID-19 versus both comparator groups. Higher sNfL levels were associated with unfavorable short-term outcome, indicating that neuronal injury is common and pronounced in critically ill patients. ANN NEUROL 2021;89:610-616.


Subject(s)
COVID-19/blood , Neurofilament Proteins/blood , Adult , Aged , Aged, 80 and over , COVID-19/physiopathology , COVID-19/therapy , Case-Control Studies , Critical Illness , Female , Glasgow Outcome Scale , Hospital Mortality , Humans , Hyponatremia/blood , Hyponatremia/therapy , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Organ Dysfunction Scores , Pulmonary Edema/blood , Pulmonary Edema/therapy , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/blood , Respiratory Insufficiency/therapy , Respiratory Tract Infections/blood , Respiratory Tract Infections/therapy , SARS-CoV-2 , Shock, Cardiogenic/blood , Shock, Cardiogenic/therapy
7.
Med Sci Monit ; 27: e929783, 2021 Jan 03.
Article in English | MEDLINE | ID: covidwho-1005108

ABSTRACT

BACKGROUND This retrospective study aimed to investigate co-infections with common respiratory pathogens and SARS-CoV-2 and laboratory biochemistry findings in patients with COVID-19 in the Zhuzhou area of China, in order to provide a reference for the disease assessment and clinical treatment of COVID-19. MATERIAL AND METHODS The clinical data of COVID-19 patients admitted to the hospital of Zhuzhou City from January 28 to March 15, 2020, as well as laboratory test results for respiratory pathogens and biochemical indicators, were collected to conduct correlation analyses. All patients were diagnosed based on fluorescence-based PCR assay for SARS-CoV-2. RESULTS Eleven of the 78 patients (14.1%) were co-infected with other respiratory pathogens, among which Mycoplasma pneumoniae (n=5, 45.5%) and respiratory syncytial virus (n=4, 36.4%) were the most frequent. There were 8 patients co-infected with 1 other pathogen and 3 patients co-infected with 2 other pathogens. Compared with mono-infected COVID-19 patients, patients with co-infections had significantly higher levels of procalcitonin (P=0.002). CONCLUSIONS The findings showed that Mycoplasma pneumonia and respiratory syncytial virus were the most common co-infections in patients with COVID-19 pneumonia. Increased levels of PCT in patients with COVID-19 pneumonia were associated with co-infection.


Subject(s)
COVID-19/epidemiology , Coinfection/epidemiology , Pandemics , Respiratory Tract Infections/epidemiology , SARS-CoV-2/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Infective Agents/therapeutic use , Biomarkers , C-Reactive Protein/analysis , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Nucleic Acid Testing , Child , Child, Preschool , China/epidemiology , Creatine Kinase/blood , Cross-Sectional Studies , Female , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Pneumonia, Mycoplasma/blood , Pneumonia, Mycoplasma/epidemiology , Procalcitonin/blood , Respiratory Syncytial Virus Infections/blood , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Tract Infections/blood , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , Retrospective Studies , Severity of Illness Index , Young Adult
8.
Cell ; 183(7): 1901-1912.e9, 2020 12 23.
Article in English | MEDLINE | ID: covidwho-950119

ABSTRACT

Long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding was observed from the upper respiratory tract of a female immunocompromised individual with chronic lymphocytic leukemia and acquired hypogammaglobulinemia. Shedding of infectious SARS-CoV-2 was observed up to 70 days, and of genomic and subgenomic RNA up to 105 days, after initial diagnosis. The infection was not cleared after the first treatment with convalescent plasma, suggesting a limited effect on SARS-CoV-2 in the upper respiratory tract of this individual. Several weeks after a second convalescent plasma transfusion, SARS-CoV-2 RNA was no longer detected. We observed marked within-host genomic evolution of SARS-CoV-2 with continuous turnover of dominant viral variants. However, replication kinetics in Vero E6 cells and primary human alveolar epithelial tissues were not affected. Our data indicate that certain immunocompromised individuals may shed infectious virus longer than previously recognized. Detection of subgenomic RNA is recommended in persistently SARS-CoV-2-positive individuals as a proxy for shedding of infectious virus.


Subject(s)
COVID-19/immunology , Common Variable Immunodeficiency/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , SARS-CoV-2/isolation & purification , Aged , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/complications , COVID-19/virology , Common Variable Immunodeficiency/blood , Common Variable Immunodeficiency/complications , Common Variable Immunodeficiency/virology , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/virology , Respiratory Tract Infections/blood , Respiratory Tract Infections/complications , Respiratory Tract Infections/immunology , Respiratory Tract Infections/virology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity
10.
Influenza Other Respir Viruses ; 14(4): 429-435, 2020 07.
Article in English | MEDLINE | ID: covidwho-827106

ABSTRACT

BACKGROUND: Fever and respiratory symptoms are the major causes of hospitalisation in infants aged 90 days or less. Respiratory viruses (RVs) are detected by multiplex reverse transcriptase-polymerase chain reaction (mRT-PCR) in up to 70% of infants tested in this population. Aminotransferase elevation is not uncommon in RV infections, and repeat laboratory investigations are frequent due to concerns regarding the occurrence of hepatic disease. METHODS: This retrospective observational cohort study included 271 infants aged 8-90 days, with positive RV mRT-PCR results. Data were obtained on demographics, laboratory results and final diagnoses of hepatobiliary disease. RESULTS: Fever (73.1%) and/or respiratory symptoms (75.6%) were the major presentations among the hospitalised infants. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels were elevated in 62 (22.9%) of the 271 infants. Twenty-four of these 62 infants had their first follow-up, and 19 (79.2%) showed persistent elevation. All 10 (100%) infants who had their second follow-up showed persistently elevated aminotransferase levels. Eventually, none of the 10 infants were diagnosed with hepatic disease during the median follow-up of 10 days (range 3-232 days). Among the RVs of interest, parainfluenza virus type 1 was significantly associated with aminotransferase elevation (odds ratio: 2.95; 95% confidence interval [CI]: 1.11-7.83). CONCLUSIONS: RV-related non-specific hepatitis is occasionally observed in infants aged 8-90 days, and ALT elevation is the most common abnormality. However, a final diagnosis of primary hepatobiliary disease appears to be rare. Therefore, regular follow-ups and targeted testing may be recommended in this specific population.


Subject(s)
Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Respiratory Tract Infections/virology , Viruses/genetics , Viruses/isolation & purification , Fever/virology , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Respiratory Tract Infections/blood , Respiratory Tract Infections/diagnosis , Retrospective Studies , Viruses/classification
SELECTION OF CITATIONS
SEARCH DETAIL
...