Document text
Principal Investigator: Thomas Nutman
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $1,082,746
Funding agency: National Institute of Allergy and Infectious Diseases
Our research encompasses several key areas: evaluating tuberculosis (TB) treatment outcomes in pulmonary tuberculosis, investigating the impact of helminthic infections on type 2 diabetes mellitus, exploring how coinfections and comorbidities such as undernutrition modulate immune responses in tuberculosis, studying the immune responses and pathogenesis of Multisystem Inflammatory Syndrome in Children (MIS-C), and identifying the determinants of COVID-19 vaccination receipt in rural India.
A. Distinct TB-antigen stimulated cytokine profiles as predictive biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis.
Assessing tuberculosis (TB) treatment outcomes often relies on sputum culture conversion, but identifying non-sputum-based biomarkers could enhance treatment management. Cytokines, frequently studied in TB diagnostics, may offer potential as predictors of unfavorable treatment outcomes. Our study evaluated TB antigen-stimulated cytokine profiles at pre-treatment and 2 months into anti-TB treatment (ATT) in a cohort of newly diagnosed drug-sensitive pulmonary TB patients. The cohort included 27 patients with unfavorable outcomes and 31 patients with favorable, microbiologically cured outcomes. Pre-treatment, the cytokines IL-2, IFN-γ, TNF-α, IL-6, IL-10, IL-17A, IL-18, and GM-CSF were significantly higher in patients with unfavorable outcomes compared to cured controls. At the 2-month, cytokines IL-2, IL-10, IL-13, IFN-γ, IL-6, IL-12p70, IL-17A, and TNF-α continued to differ significantly between the groups. The differences were specifically associated with TB antigens, not mitogens. Patients with unfavorable TB treatment outcomes exhibit a distinct cytokine profile compared to those who are cured, observable even before treatment begins. Cytokine levels at pre-treatment and at 2 months could serve as potential immune markers for predicting unfavorable TB treatment outcomes, with these markers being influenced by TB-specific antigens.
B. Impact of Strongyloides stercoralis infection on complement activation in Type 2 diabetes mellitus: Insights from a clinical and anthelmintic intervention study.
This study explored the impact of the helminth Strongyloides stercoralis on complement activation in individuals with type 2 diabetes mellitus (T2D). Complement proteins play a critical role in immune defense and tissue homeostasis, and their dysregulation is linked to complications in diabetes. By comparing individuals with T2D who were infected with S. stercoralis to those who were not, the study assessed levels of various complement proteins and regulatory components. The researchers found that individuals with both T2D and S. stercoralis infection had significantly reduced levels of several complement proteins, including C1q, C4b, MBL (Lectin), C3, C5a, and C3b/iC3b, as well as regulatory proteins such as Factor B and Factor D, compared to those with T2D alone. This reduction in complement activation suggests a potential protective effect of S. stercoralis against inflammation and tissue damage associated with diabetes. Following anthelmintic treatment, which aimed to eliminate the helminth infection, these complement levels partially returned to baseline values. This indicates that S. stercoralis infection might modulate the immune system in a way that reduces complement activation, potentially mitigating some of the inflammatory processes in T2D. The findings underscore the complex relationship between helminth infections, complement regulation, and diabetes, and suggest that further research into these interactions could reveal new therapeutic approaches for managing diabetes and its complications.
C. Sex-specific differences in systemic immune responses in MIS-C children.
Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but serious condition linked to SARS-CoV-2 infection, leading to increased morbidity and mortality. While there is growing evidence of sex differences in COVID-19 outcomes, there is limited information on how these differences manifest in MIS-C. Our study aimed to examine sex-specific differences in immune parameters among children with MIS-C. Our findings revealed that male children with MIS-C exhibited significantly higher levels of pro-inflammatory cytokines (including IFNγ, IL-2, TNFα, IL-1α, IL-1β, IL-6, IL-12, G-CSF, and GM-CSF), chemokines (such as CCL2, CCL11, CXCL1, CXCL8, and CXCL10), acute phase proteins (like α-2M and CRP), growth factors (VEGF and TGFα), microbial translocation markers (iFABP, LBP, EndoCAb), complement components (C1q, MBL, and C3), and matrix metalloproteinases (MMP-8 and MMP-9) compared to female children with MIS-C. These results suggest that a heightened immune response in males is a notable characteristic of MIS-C. This sex-specific immune response might explain differences in disease pathogenesis between males and females and could enhance our understanding of MIS-C.
D. Hookworm infection induces glycometabolic modulation in South Indian individuals with type 2 diabetes.
This study explores the relationship between hookworm infection and type 2 diabetes mellitus (T2DM). Previous research suggested an inverse relationship between helminth infections and T2DM, but the specific impact of hookworm infection remained underexplored. The study examined biochemical parameters in T2DM individuals with (INF, n = 35) and without (UN, n = 35) hookworm infection, including random blood glucose, glycated hemoglobin, and various pancreatic hormones, incretins, and adipokines. The results showed that INF individuals had significantly lower random blood glucose and glycated hemoglobin levels, along with reduced levels of adiponectin, adipsin, C-peptide, insulin, and glucagon compared to UN individuals. However, INF individuals had elevated levels of visfatin and incretins. These beneficial effects on glycometabolic parameters were not observed after anthelmintic treatment. The study concludes that hookworm infection may have a positive influence on glycometabolic health in individuals with T2DM.
E. Strongyloides stercoralis Coinfection Exacerbates Disease Severity and Adverse Treatment Outcomes in Pulmonary Tuberculosis.
This study investigates the impact of Strongyloides stercoralis (Ss) co-infection on pulmonary tuberculosis (PTB) severity, bacterial loads, and treatment outcomes, particularly in regions where these diseases overlap. The research included 409 PTB patients, assessing lung disease via chest X-rays, bacterial loads through sputum smear grades, and systemic levels of cytokines and pro-fibrotic factors using multiplex ELISA. Ss infection was confirmed through seropositivity.
Key findings include that PTB patients with Ss co-infection had significantly higher bacterial loads, greater risks of bilateral lung lesions and cavitary disease, and an increased likelihood of unfavorable treatment outcomes. The odds ratios (OR) for these risks were notably elevated: bacterial loads (aOR, 8.14), bilateral lung lesions (aOR, 4.37), cavitary disease (aOR, 5.21), and poor treatment outcomes (aOR, 1.2). Additionally, these patients exhibited higher levels of harmful cytokines (IL-4, IL-5, IL-13, IFNα, IFNβ) and pro-fibrotic factors (VEGF, EGF, FGF-2, PDGF-AB/BB), alongside a decrease in protective cytokines (IFNγ, IL-2).
The study underscores the critical link between Ss co-infection and increased PTB severity, suggesting that Ss infection exacerbates PTB by enhancing bacterial burden and worsening lung pathology, thereby leading to poorer treatment outcomes. These findings advocate for integrated management approaches that consider the complex interactions between helminth infections and tuberculosis to improve patient care and outcomes.
Terms: <(IFN) α><(IFN)-α><(IFN)α><(TNF)-α><0-11 years old><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><3-10C><92-kDa Gelatinase><92-kDa Type IV Collagenase><ACRP30 protein><AIDS Virus><AMCF-I><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Acute-Phase Proteins><Acute-Phase Reactants><Address><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Advocate><Alferon><Alternative Pathway Complement Factor B><Ancylostomatidae><Anthelmintics><Antidiabetic Hormone><Antigens><Antihelminthic Agent><Antihelminthic Drugs><Antitubercular Agents><Area><Autoregulation><B Cell Differentiation Factor I><B cell differentiation factor><B cell growth factor><B cell growth factor 2><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-1><B-Cell Differentiation Factor-2><B-Cell Growth Factor-1><B-Cell Growth Factor-I><B-Cell Growth Factor-II><B-Cell Proliferating Factor><B-Cell Stimulating Factor><B-Cell Stimulating Factor-1><B-Cell Stimulation Factor-1><B-Cell Stimulatory Factor-1><B-Cell Stimulatory Factor-2><BCDF><BCDF-1><BCGF><BCGF-1><BCGF-II><BCGF2><BCSF 1><BSF-1><BSF-2><BSF1><BSF2><Basic Fibroblast Growth Factor><Basic Fibroblast Growth Factor Gene><Beta Proprotein Interleukin 1><Bilateral><Binetrakin><Biochemical><Biological Markers><Biotech><Biotechnology><Blood Glucose><Blood Sugar><Body Tissues><C 3-5 Converting Enzyme><C-Peptide><C1 q><C1q><C3 Proactivator><C3 convertase activator><C3PA><C3PA Convertase><C3PAse><C3b><C3bi><C4 b><C4b><C5 a><C5a><CCL11><CCL11 gene><CCL2><CCL2 gene><COVID-19><COVID-19 infection><COVID-19 vaccination><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><CRG-2><CSF3><CSF3 gene><CSIF><CSIF-10><CTLA-8><CTLA-8 Gene><CTLA8><CTLA8 Gene><CV-19><CVFBb><CXCL1><CXCL1 gene><CXCL10><CXCL10 gene><CXCL8><CXR><Cachectin><Characteristics><Chemokine, CC Motif, Ligand 2><Chemotactic Cytokines><Child><Child Youth><Childhood><Children (0-21)><Clinical><Co-Stimulator><CoV-2><CoV2><Collaborations><Communicable Diseases><Complement><Complement 1q><Complement 3 Proactivator><Complement 3b><Complement 4b><Complement 5a><Complement Activation><Complement C1q><Complement C3b><Complement C4b><Complement C5a><Complement Factor B><Complement Factor D><Complement Protein B><Complement Protein D><Complement Protein Factor B><Complement Proteins><Complex><Coronavirus Infectious Disease 2019><Costimulator><Country><Cross-Product Ratio><Cytokine Synthesis Inhibitory Factor><Cytotoxic T-Lymphocyte-Associated Antigen 8><Cytotoxic T-Lymphocyte-Associated Antigen 8 Gene><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8><Cytotoxic T-Lymphocyte-Associated Serine Esterase 8 Gene><D component of complement><Dengue><Developing Countries><Developing Nations><Diabetes Mellitus><Differences between sexes><Differs between sexes><Disease><Disorder><EGF><EGF gene><ELISA><Edodekin Alfa><Elderly><Emerging Communicable Diseases><Emerging Infectious Diseases><Endemic Diseases><Enzyme-Linked Immunosorbent Assay><Eo-CSF><Eosinophil Differentiation Factor><Epidemiology><Epidermal Growth Factor-Related Transforming Growth Factor><Epidermal Thymocyte Activating Factor><Exhibits><FGF-2><FGF2><FGF2 gene><FGFB><Factor B><Factor D><Family><Female><Fibroblast Growth Factor 2><Fibroblast Growth Factor 2 Gene><Filariasis><Filarioidea Infections><Fostering><Future><G-CSF><GBGase><GCP1><GCSF><GM-CSF><GRO1><GROA><Gelatinase B><Glucagon><Glukagon><Glycated Hemoglobins><Glycosylated Hemoglobin><Goals><Granulocyte-Macrophage Colony-Stimulating Factor><Growth Agents><Growth Factor><Growth Substances><HBGF-2><HG-Factor><HIV><HPGF><Health><Healthcare><Helminths><Hemoglobin concentration result><Heparin-Binding Growth Factor 2><Heparin-Binding Growth Factor Class II><Hepatocyte-Stimulating Factor><Histamine-Producing Cell-Stimulating Factor><Homeostasis><Homologous Chemotactic Cytokines><Hookworm Infections><Hookworms><Hospitals><Human Immunodeficiency Viruses><Humulin R><Hybridoma Growth Factor><Hyperglycemic-Glycogenolytic Factor><IFI10><IFN Alpha><IFN α><IFN-Gamma><IFN-Gamma-Inducing Factor Gene><IFN-beta 2><IFN-g><IFN-gamma-Inducing Factor><IFN-α><IFN-γ><IFNB2><IFNG><IFNa><IFNα><IFNγ><IGIF><IGIF Gene><IL-1 Gamma><IL-1 Gamma Gene><IL-1 alpha><IL-1 beta><IL-1 β><IL-1-a><IL-1-b><IL-10><IL-12><IL-13><IL-17><IL-17 Gene><IL-17A><IL-17A Gene><IL-18><IL-18 Gene><IL-1A><IL-1alpha><IL-1g><IL-1g Gene><IL-1α><IL-1β><IL-2><IL-4><IL-5><IL-6><IL-8><IL1-Alpha><IL1-Beta><IL1-α><IL1-β><IL10><IL10A><IL12><IL13><IL17><IL17 Protein><IL17 gene><IL17A><IL17A Gene><IL18><IL18 Protein><IL18 gene><IL1A Protein><IL1B Protein><IL1F1><IL1F2><IL1F4><IL1F4 Gene><IL1β><IL2 Protein><IL4 Protein><IL6 Protein><IL8><IL8 gene><INP10><IP-10><IgA enhancing factor><Immune><Immune Interferon><Immune Markers><Immune response><Immune system><Immunes><Immunochemical Immunologic><Immunologic><Immunologic Markers><Immunological><Immunological response><Immunologically><Immunologics><Immunology><Immunomodulation><India><Individual><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammation><Inflammatory><Institution><Insulin><Intercrines><Interferon Alfa-n3><Interferon Gamma><Interferon Type II><Interferon alpha><Interferon-Gamma-Inducing Factor Gene><Interferon-gamma-Inducing Factor><Interferon-α><Interleukin 10 Precursor><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8)><Interleukin 17 (Cytotoxic T-Lymphocyte-Associated Serine Esterase 8) Gene><Interleukin 17 Precursor><Interleukin 17 Precursor Gene><Interleukin 18 (Interferon-Gamma-Inducing Factor)><Interleukin 18 (Interferon-Gamma-Inducing Factor) Gene><Interleukin 18 Proprotein><Interleukin 18 Proprotein Gene><Interleukin 1alpha><Interleukin 1beta><Interleukin 2><Interleukin 2 Precursor><Interleukin 5 Precursor><Interleukin II><Interleukin-1 Gamma><Interleukin-1 Gamma Gene><Interleukin-1 alpha><Interleukin-1 beta><Interleukin-10><Interleukin-12><Interleukin-13><Interleukin-17><Interleukin-18><Interleukin-18 Precursor><Interleukin-18 Precursor Gene><Interleukin-1β><Interleukin-2><Interleukin-4><Interleukin-4 Precursor><Interleukin-5><Interleukin-6><Interleukine 2><Interleukine 2 Precursor><Interleukine II><International><Intervention Studies><Investigators><K60><Ketosis-Resistant Diabetes Mellitus><LAV-HTLV-III><Lectin><Less-Developed Countries><Less-Developed Nations><Leukocyte Interferon><Link><Lung><Lung Diseases><Lung Respiratory System><Lung TB><Lung Tuberculosis><Lymphadenopathy-Associated Virus><Lymphoblast Interferon><Lymphoblastoid Interferon><Lymphocyte Mitogenic Factor><Lymphocyte Stimulatory Factor 1><M tuberculosis infection><M. tb infection><M. tuberculosis infection><M.tb infection><M.tuberculosis infection><MCAF><MCGF-2><MCP-1><MCP1><MGC12320><MGC12320 Gene><MGC22554><MGC45931><MGI-2><MGSA><MIS-C><MMP-8><MMP-9><MMP-9 Protein><MMPs><MOB-1><MTB infection><Macrophage Gelatinase><Macrophage-Derived TNF><Malaria><Malnutrition><Mast Cell Growth Factor-2><Matrix Metalloproteinase-8><Matrix Metalloproteinase-9><Matrix Metalloproteinases><Maturity-Onset Diabetes Mellitus><Medical Research><Metabolic Diseases><Metabolic Disorder><Mitogenic Factor><Molgramostin><Monocyte Chemoattractant Protein-1><Monocyte Chemotactic Protein-1><Monocyte Chemotactic and Activating Factor><Monocyte Chemotactic and Activating Protein><Monocyte Chemotactive and Activating Factor><Monocyte Secretory Protein JE><Monocyte-Derived TNF><Morbidity><Morbidity - disease rate><Multiorgan Inflammatory Syndrome in Children><Multisystem Inflammatory Syndrome in Children><Mycobacterium tuberculosis (MTB) infection><Mycobacterium tuberculosis infection><Myeloid Differentiation-Inducing Protein><NIAID><NIDDM><NIH><NKSF><National Institute of Allergy and Infectious Disease><National Institutes of Health><Natural Killer Cell Stimulatory Factor><Neutrophil Collagenase><Newly Diagnosed><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Novolin R><Nutritional Deficiency><Obesity><Odds Ratio><Outcome><PDGF-AB><PMNL Collagenase><Paludism><Pancreatic Hormones><Parasitic Worms><Pathogenesis><Patient Care><Patient Care Delivery><Patient Recruitments><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Physicians><Physiological Homeostasis><Plasmacytoma Growth Factor><Plasmodium Infections><Play><Population><Postdoc><Postdoctoral Fellow><Preinterleukin 1 Alpha><Preinterleukin 1 Beta><Proactivator Convertase><Process><Profibrotic factor><Profibrotic signal><Properdin Factor B><Properdin Factor D><Prostate Epithelial Cell Growth Factor><Proteins Growth Factors><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Pathology><Pulmonary TB><Pulmonary Tuberculosis><Recombinant C5a><Regional Disease><Regular Insulin><Regulation><Regulatory Protein><Relative Odds><Research><Research Associate><Research Institute><Research Personnel><Research Resources><Researchers><Resources><Risk><Risk Ratio><Role><Rural><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 pathogenesis><SARS-CoV-2 vaccination><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SCYA11><SCYA2><SCYB1><SCYB10><SCYB8><SIS cytokines><Scientist><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Sex Differences><Sexual differences><Site><Slow-Onset Diabetes Mellitus><Small Inducible Cytokine A2><Sputum><Stable Diabetes Mellitus><Strongyloides stercoralis><Strongyloidiasis><T cell growth factor><T cell replacing factor><T-Cell Growth Factor><T-Cell Growth Factor 2><T-Cell Replacing Factor><T-Cell Stimulating Factor><T2 DM><T2D><T2DM><TB diagnostics><TB immunity><TB infection><TB therapy><TB treatment><TC-GM-CSF><TGF A><TGF-alpha><TGF-α><TGFalpha><TGFα><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><TSG-1><Thesaurismosis><Third-World Countries><Third-World Nations><Thoracic Radiography><Thymocyte Stimulating Factor><Tissues><Training><Transforming Growth Factor alpha><Treatment outcome><Tuberculosis><Tuberculostatic Agents><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><Tumor-Cell Human GM Colony-Stimulating Factor><Type 2 Diabetes Mellitus><Type 2 diabetes><Type II Diabetes Mellitus><Type II diabetes><Type V Collagenase><Under-Developed Countries><Under-Developed Nations><Undernutrition><United States National Institutes of Health><VEGF><VEGFs><Vaccination><Vascular Endothelial Growth Factors><Vermifuges><Viral Diseases><Virus><Virus Diseases><Virus-HIV><Work><Wuhan coronavirus><adipocyte 28 kDa protein><adipocyte complement-related protein 30-kDa><adipocyte, C1q and collagen domain containing protein><adipocytokines><adipokines><adiponectin><adiposity><adipsin><adult onset diabetes><adulthood><advanced age><age group><anti-TB><anti-tuberculosis><antiTB><antihelminthic><apM-1 protein><apM1 (adipose-specific) protein><b-ENAP><bFGF><bio-markers><biologic marker><biomarker><biomarker discovery><burden of disease><burden of illness><care for patients><care of patients><caring for patients><chemoattractant cytokine><chemokine><chest X ray><chest Xray><chest radiography><clinical research site><clinical site><co-infection><co-morbid><co-morbidity><cohort><coinfection><comorbidity><complement pathway regulation><complementation><connecting peptide><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 vaccination><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><corpulence><cyber infrastructure><cyberinfrastructure><cytokine><developing country><developing nation><diabetes><diabetes management><diabetes mellitus management><diabetic management><dietary deficiency><disease burden><disease of the lung><disease severity><disorder of the lung><disseminated TB><disseminated tuberculosis><drug-sensitive><enzyme linked immunoassay><epidemiologic><epidemiological><filarial disease><filarial infection><gIP-10><genetic regulatory protein><geriatric><granulocyte macrophage colony stimulating factor><hCoV19><health care><helminth infection><helminthic infection><hemoglobin level><host response><iC3b><immune modulation><immune regulation><immune response to vaccination><immune response to vaccines><immune system response><immune-based biomarkers><immunity against M. tuberculosis><immunity against Mtb><immunity against Mycobacterium tuberculosis><immunity against TB><immunity against tuberculosis><immunity in tuberculosis><immunity to TB><immunity to tuberculosis><immunogen><immunologic reactivity control><immunological biomarkers><immunological markers><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><improved><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with helminth><infected with severe acute respiratory syndrome coronavirus 2><infection due to Mycobacterium tuberculosis><insight><interferon beta 2><international center><intervention research><interventional research><interventional study><interventions research><ketosis resistant diabetes><kids><lFN-Gamma><lung disorder><lung lesion><lung pathology><lung radiography><male><malnourished><maturity onset diabetes><metabolism disorder><microbial><mortality><multisystem inflammatory syndrome of children><nCoV2><new therapeutic approach><new therapeutic intervention><new therapeutic strategies><new therapy approaches><new treatment approach><new treatment strategy><novel therapeutic approach><novel therapeutic intervention><novel therapeutic strategies><novel therapy approach><nutrition deficiency><nutrition deficiency disorder><nutritional deficiency disorder><pancreas hormone><participant recruitment><patient oriented outcomes><pediatric><pediatric inflammatory multisystem syndrome><platelet-derived growth factor AB><post-doc><post-doctoral><post-doctoral trainee><predictive biomarkers><predictive marker><predictive molecular biomarker><programs><protective effect><pulmonary><pulmonary lesion><radiographic chest image><radiographic lung image><regulatory gene product><research associates><senior citizen><seropositive><severe acute respiratory syndrome coronavirus 2 pathogenesis><sex><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><social role><student mentoring><student-led learning><thoracic radiogram><thorax radiography><treat M. tuberculosis><treat Mtb><treat Mycobacterium tuberculosis><treat tb><treat tuberculosis><tuberculosis diagnostics><tuberculosis immunity><tuberculosis infection><tuberculosis therapy><tuberculosis treatment><tuberculous spondyloarthropathy><type 2 DM><type II DM><type two diabetes><vaccinate against COVID-19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccination against COVID-19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><vaccine associated immune response><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><viral infection><virus infection><virus-induced disease><welfare><work group><working group><youngster>