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2.
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
3.
Mol Neurobiol ; 58(9): 4575-4587, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1263176

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 or COVID-19 has been declared as a pandemic disease by the World Health Organization (WHO). Globally, this disease affected 159 million of the population and reported ~ 3.3 million deaths to the current date (May 2021). There is no definitive treatment strategy that has been identified, although this disease has prevailed in its current form for the past 18 months. The main challenges in the (SARS-CoV)-2 infections are in identifying the heterogeneity in viral strains and the plausible mechanisms of viral infection to human tissues. In parallel to the investigations into the patho-mechanism of SARS-CoV-2 infection, understanding the fundamental processes underlying the clinical manifestations of COVID-19 is very crucial for designing effective therapies. Since neurological symptoms are very apparent in COVID-19 infected patients, here, we tried to emphasize the involvement of redox imbalance and subsequent mitochondrial dysfunction in the progression of the COVID-19 infection. It has been articulated that mitochondrial dysfunction is very apparent and also interlinked to neurological symptoms in COVID-19 infection. Overall, this article provides an in-depth overview of redox imbalance and mitochondrial dysfunction involvement in aggravating COVID-19 infection and its probable contribution to the neurological manifestation of the disease.


Subject(s)
COVID-19/complications , Mitochondria/physiology , SARS-CoV-2/pathogenicity , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/metabolism , Central Nervous System/virology , Drug Repositioning , Endothelium, Vascular/physiopathology , Endothelium, Vascular/virology , Humans , Mice , Mitochondria/drug effects , Mitochondria/pathology , Models, Biological , Olfactory Nerve/virology , Organ Specificity , Oxidation-Reduction , Oxidative Stress/drug effects , Pandemics , SARS-CoV-2/physiology , Viral Proteins/physiology , Viral Tropism , Viremia/complications , Virulence , Virus Internalization
4.
BMJ Case Rep ; 14(2)2021 Feb 04.
Article in English | MEDLINE | ID: covidwho-1066845

ABSTRACT

COVID-19 is a biphasic illness with an initial viraemia phase and later effective adaptive immune phase, except in a minority of people who develop severe disease. Immune regulation is the key target to treat COVID illness. In anticipation, an elderly man self-medicated himself with dexamethasone on the day of symptom onset of a flu-like illness, took other symptomatic measures and was tested positive for SARS-CoV-2. His condition deteriorated with each passing day resulting in hospitalisation. He demanded oxygen and declared as severe COVID. With supportive treatment, he recovered after the 20th day of illness. Immunosuppression and anti-inflammation are likely to benefit when the immune response is dysregulated and turning into a cytokine storm. A medication that has saved many could be the one predisposing to severity if taken as a preventive measure, too early in the disease course, especially the viraemia phase.


Subject(s)
Anti-Inflammatory Agents/adverse effects , COVID-19/drug therapy , Dexamethasone/adverse effects , Viremia/drug therapy , Aged , Anti-Infective Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Dexamethasone/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Male , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , SARS-CoV-2/isolation & purification , Self Medication/methods , Steroids/adverse effects , Steroids/therapeutic use , Treatment Outcome , Viremia/complications
7.
J Infect Chemother ; 26(11): 1220-1223, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-654302

ABSTRACT

Coronavirus disease 2019 (COVID-19) is spreading worldwide and poses an imminent threat to public health. We encountered 2 cases of COVID-19 with progression resulting in severe respiratory failure and improvement without any specific treatment. To examine the course of infection, we performed reverse-transcription (RT) polymerase chain reaction assay with serum specimens, and serum SARS-CoV-2 RNA was detected in both cases when body temperature increased and respiratory status deteriorated. We, then examined, retrospectively and prospectively, the clinical course during hospitalization by performing serial examinations of serum SARS-CoV-2 RNA status. The findings from our cases suggest that not only is detection of viremia useful as a predictive marker of severity, but also serial serum SARS-CoV-2 RNA results can be helpful for predicting the clinical course.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Pneumonia, Viral/complications , RNA, Viral/blood , Respiratory Insufficiency/diagnosis , Viremia/diagnosis , Adult , Aged , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Humans , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , RNA, Viral/isolation & purification , Respiratory Insufficiency/blood , Respiratory Insufficiency/virology , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Severity of Illness Index , Time Factors , Viremia/complications , Viremia/virology
8.
Transpl Infect Dis ; 22(6): e13367, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-596059

ABSTRACT

The clinical course and outcomes of immunocompromised patients, such as transplant recipients, with COVID-19 remain unclear. It has been postulated that a substantial portion of the disease burden seems to be mediated by the host immune activation to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, we present a simultaneous heart-kidney transplant (SHKT) recipient who was hospitalized for the management of respiratory failure from volume overload complicated by failure to thrive, multiple opportunistic infections, and open non-healing wounds in the setting of worsening renal dysfunction weeks prior to the first case of SARS-CoV-2 being detected in the state of Connecticut. After his third endotracheal intubation, routine nucleic acid testing (NAT) for SARS-CoV-2, in anticipation of a planned tracheostomy, was positive. His hemodynamics, respiratory status, and ventilator requirements remained stable without any worsening for 4 weeks until he had a negative NAT test. It is possible that the immunocompromised status of our patient may have prevented significant immune activation leading up to clinically significant cytokine storm that could have resulted in acute respiratory distress syndrome and multisystem organ failure.


Subject(s)
COVID-19/immunology , Cardiomyopathy, Dilated/surgery , Heart Transplantation , Immunocompromised Host/immunology , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Malnutrition/immunology , Opportunistic Infections/immunology , Antibiotics, Antineoplastic/adverse effects , BK Virus , Bacteremia/complications , Bacteremia/immunology , COVID-19/complications , COVID-19 Nucleic Acid Testing , Cardiomyopathy, Dilated/chemically induced , Cardiomyopathy, Dilated/complications , Cardiotoxicity , Doxorubicin/adverse effects , Graft Rejection/prevention & control , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/immunology , Humans , Incidental Findings , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , Malnutrition/complications , Methicillin-Resistant Staphylococcus aureus , Middle Aged , Mycophenolic Acid/therapeutic use , Opportunistic Infections/complications , Polyomavirus Infections/complications , Polyomavirus Infections/immunology , Postoperative Complications/therapy , Prednisone/therapeutic use , Renal Dialysis , SARS-CoV-2 , Staphylococcal Infections/complications , Staphylococcal Infections/immunology , Surgical Wound Infection/complications , Surgical Wound Infection/immunology , Tacrolimus/therapeutic use , Tracheostomy , Tumor Virus Infections/complications , Tumor Virus Infections/immunology , Vancomycin-Resistant Enterococci , Viremia/complications , Viremia/immunology , Water-Electrolyte Imbalance/complications , Water-Electrolyte Imbalance/therapy
9.
Clin Immunol ; 215: 108410, 2020 06.
Article in English | MEDLINE | ID: covidwho-38673

ABSTRACT

Infection caused by SARS-CoV-2 can result in severe respiratory complications and death. Patients with a compromised immune system are expected to be more susceptible to a severe disease course. In this report we suggest that patients with systemic lupus erythematous might be especially prone to severe COVID-19 independent of their immunosuppressed state from lupus treatment. Specifically, we provide evidence in lupus to suggest hypomethylation and overexpression of ACE2, which is located on the X chromosome and encodes a functional receptor for the SARS-CoV-2 spike glycoprotein. Oxidative stress induced by viral infections exacerbates the DNA methylation defect in lupus, possibly resulting in further ACE2 hypomethylation and enhanced viremia. In addition, demethylation of interferon-regulated genes, NFκB, and key cytokine genes in lupus patients might exacerbate the immune response to SARS-CoV-2 and increase the likelihood of cytokine storm. These arguments suggest that inherent epigenetic dysregulation in lupus might facilitate viral entry, viremia, and an excessive immune response to SARS-CoV-2. Further, maintaining disease remission in lupus patients is critical to prevent a vicious cycle of demethylation and increased oxidative stress, which will exacerbate susceptibility to SARS-CoV-2 infection during the current pandemic. Epigenetic control of the ACE2 gene might be a target for prevention and therapy in COVID-19.


Subject(s)
Coronavirus Infections/genetics , Epigenesis, Genetic , Genetic Predisposition to Disease , Lupus Erythematosus, Systemic/genetics , Pandemics , Peptidyl-Dipeptidase A/genetics , Pneumonia, Viral/genetics , Viremia/genetics , Angiotensin-Converting Enzyme 2 , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , CD11a Antigen/genetics , CD11a Antigen/immunology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Cytokines/genetics , Cytokines/immunology , DNA Methylation , Disease Progression , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Interferon Regulatory Factors/genetics , Interferon Regulatory Factors/immunology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/immunology , NF-kappa B/genetics , NF-kappa B/immunology , Oxidative Stress/genetics , Oxidative Stress/immunology , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Protein Binding , Receptors, KIR/genetics , Receptors, KIR/immunology , SARS-CoV-2 , Signal Transduction , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Viremia/complications , Viremia/epidemiology , Viremia/immunology
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