Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Annals of Allergy, Asthma and Immunology ; 127(5):S95, 2021.
Article in English | EMBASE | ID: covidwho-1734159


Introduction: Common Variable Immunodeficiency (CVID) is a heterogenous disease causing insufficient activity of the humoral arm of adaptive immunity. It is characterized by a broad paucity of serum immunoglobulins. Patients are not only predisposed to recurrent infections, they also are more likely to develop certain cancers and autoimmune diseases. Case Description: We present a case of a 53 year-old female suffering from recurrent pulmonary infections and a past history of Non-Hodgkin’s Lymphoma who came for evaluation of drug allergies. By eliciting a thorough history, it was found that she had a poor response to the MMR and Varicella vaccines as a child, and was infected with COVID-19 twice in 2020. Additionally, longitudinal chest CT scans demonstrated bilateral pulmonary nodules, indicative of chronic inflammation. Testing of her antibody titers in order to determine suitability for S. Pneumoniae vaccination found an overall decrease in major immunoglobulin classes (IgG, IgM, and IgA). Hematological testing showed B-cells with normal morphology. The diagnosis of CVID was made, and prompt treatment with IVIG (intravenous immunoglobulins) was initiated, bringing her IgG levels from 282 to 680 (mg/dL) within three months. Discussion: Her constellation of symptoms and diseases likely arose as a result of immune dysfunction, highlighting the necessity of keeping immunodeficiencies like CVID on the differential when managing patients with seemingly unrelated medical problems. Early detection of immunopathologies like CVID should therefore be a priority for longitudinal care. This ideally ensures early detection and prompt management of the multi-system dysfunctions that pose a significant lifetime risk to such patients.

PUBMED; 2020.
Preprint in English | PUBMED | ID: ppcovidwho-292827


The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.

Lancet ; 398(10295):118-118, 2021.
Article in English | Web of Science | ID: covidwho-1329593
Mucosal Immunol ; 13(6): 877-891, 2020 11.
Article in English | MEDLINE | ID: covidwho-724735


COVID-19 is causing a major once-in-a-century global pandemic. The scientific and clinical community is in a race to define and develop effective preventions and treatments. The major features of disease are described but clinical trials have been hampered by competing interests, small scale, lack of defined patient cohorts and defined readouts. What is needed now is head-to-head comparison of existing drugs, testing of safety including in the background of predisposing chronic diseases, and the development of new and targeted preventions and treatments. This is most efficiently achieved using representative animal models of primary infection including in the background of chronic disease with validation of findings in primary human cells and tissues. We explore and discuss the diverse animal, cell and tissue models that are being used and developed and collectively recapitulate many critical aspects of disease manifestation in humans to develop and test new preventions and treatments.

Antibodies, Viral/biosynthesis , Antiviral Agents/pharmacology , Betacoronavirus/pathogenicity , Coronavirus Infections/immunology , Disease Models, Animal , Pneumonia, Viral/immunology , Viral Vaccines/biosynthesis , Angiotensin-Converting Enzyme 2 , Animals , Animals, Genetically Modified , Antiviral Agents/chemical synthesis , Betacoronavirus/drug effects , Betacoronavirus/genetics , Betacoronavirus/physiology , COVID-19 , COVID-19 Vaccines , Cats , Chiroptera , Coronavirus Infections/drug therapy , Coronavirus Infections/genetics , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Cricetulus , Female , Ferrets , Haplorhini , Humans , Male , Mice , Organoids/drug effects , Organoids/immunology , Organoids/virology , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/genetics , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index , Species Specificity , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Viral Vaccines/administration & dosage