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Principal Investigator: Afsar Raza Naqvi
Organization: UNIVERSITY OF ILLINOIS AT CHICAGO
Fiscal Year: 2023
Award: $581,037
Funding agency: National Institute of Dental and Craniofacial Research
Abstract
Coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), infecting non-vaccinated and vaccinated people. Covid-19 clinically affects
multiple organs including oral mucosa where SARS-CoV-2 replication occurs to deposit virion into saliva in
sufficient copies (>1000) to be detected. Public health data reveals Covid-19 and periodontitis disproportionally
affects Non-Hispanic Blacks (NHB) and Hispanics (H). We hypothesize that periodontal disease (PD) pre-
conditions oral mucosa for persistent oral pathology and oral Post-Acute Sequelae of Covid-19 (PASC).
However, the cellular and molecular mechanisms underlying this relationship between Covid-19 and poor oral
health outcomes are unclear. Extending our preliminary dataset of oral examination, and immune assessment
of Black and Hispanic cohort, our Aim 1 involves a comparative analysis of the impact of vaccination on oral
PASC indicators and perturbation in oral immune surveillance. We assessed this relationship before vaccination
was available, which provides an opportunity to compare how periodontal health, Covid-19 infection, and the
vaccination status affects minority population (NHB/H) versus Non-Hispanic White (NHW) with similar variables
and risk for oral PASC. Saliva and gingival crevicular fluid (GCF) will be examined to perform comprehensive
profiling of immune cells (both myeloid and lymphoid compartments) and assess mediators of immune cell
activation, polarization and exhaustion contributing to impaired oral immunity. We will decipher three important
gaps of knowledge in an underserved cohort: (1) whether infectivity of SARS-CoV-2 is affected by poor oral
health?, (2) does Covid-19-induced inflammation worsen pre-existing periodontal health, and (3) does Covid-19
vaccination lessen oral PASC viz. periodontal inflammation? In Aim 2, we will examine whether previous
intracellular periopathogens enhance risk for continual reinfection of SARS-CoV-2 and promote oral PASC. Our
lab has optimized an in vitro infection model of SARS-CoV-2 in primary gingival epithelial cells (GEC) to dissect
the role of periodontal pathogens (both bacteria and herpesviruses) enhancing viral tropism and replication.
Characterizing periodontal microbe-SARS-CoV-2 interaction will unravel novel mechanisms that can be targeted
to mitigate oral PASC. Our findings will support that periodontal pathogens increase host susceptibility to SARS-
CoV-2 infection by providing a conducive microenvironment for viral tropism, and persistence. Next, we will
decipher SARS-CoV-2-mediated mechanisms of impairing periodontal immunity. To this end, we will
characterize the novel role of SARS-CoV-2- open reading frames (ORFs) in modulating oral antiviral and
antibacterial immunity by examining viral entry and replication, expression of Pathogen Recognition Receptor
(PRR) and downstream signaling activation. Successful outcomes of this study will disclose novel relationships
between Covid-19 and PD as well as intracellular periodontal bacteria and viruses viz., SARS-CoV-2 and
herpesviruses. Identification of pathogenic factors that promote SARS-CoV-2 oral tropism could serve as novel
therapeutic targets to suppress oral PASC signs and symptoms.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><A actinomycetemcomitans><A. actinomycetemcomitans><ACE2><Actinobacillus actinomycetemcomitans><Adherence><Affect><Aggregatibacter actinomycetemcomitans><Anti-Bacterial Agents><Antibacterial Agents><Attenuated><Bacteria><Bacterium actinomycetem comitans><Bacterium comitans><Bacteroides gingivalis><Biological Response Modifiers><Biomodulators><Biopsy><Black><Black Populations><Black group><Black individual><Black people><Black race><Blacks><Buccal Mucosa><Burkitt Herpesvirus><Burkitt Lymphoma Virus><CMV><COVID><COVID-19><COVID-19 infection><COVID-19 predisposition><COVID-19 related risk><COVID-19 risk><COVID-19 risk factor><COVID-19 susceptibility><COVID-19 vaccination><COVID-19 virus><COVID-19 virus infection><COVID-19 vulnerability><COVID19><COVID19 infection><COVID19 vaccination><COVID19 virus><CV-19><CV19><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Chronic><Chronic Periodontitis><Clinical><Clinical Research><Clinical Study><CoV disease><CoV-2><CoV2><Coronavirus disease 2019 predisposition><Coronavirus disease 2019 susceptibility><Coronavirus disease 2019 vulnerability><Cytomegalovirus><Data Set><Deposit><Deposition><Diagnostic Findings><Double-Stranded DNA><EB virus><EBV><Epithelial Cells><Epstein Barr Virus><Esteroproteases><Exhibits><Forsythia><Gingiva><Gingival><Gingival Crevicular Fluid><Gingival Exudate><Goldenbells><HCMV><HHV-4><HHV4><Health><Herpesviridae><Herpesviruses><Hispanic><Hispanic Populations><Hispanic group><Hispanic individual><Hispanic people><Hispanics><History><Hospital Admission><Hospitalization><Human><Human Figure><Human Herpesvirus 4><Human body><Immune><Immune Cell Activation><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune Mediators><Immune Mediators/Modulators><Immune Regulators><Immune Surveillance><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immunes><Immunity><Immunochemical Immunologic><Immunodeficiency and Immunosuppression Disorders><Immunologic><Immunologic Diseases><Immunologic Surveillance><Immunologic Surveillances><Immunological><Immunological Diseases><Immunological Dysfunction><Immunological Surveillance><Immunological Surveillances><Immunological System Dysfunction><Immunological response><Immunologically><Immunologics><Immunologist><Immunosurveillance><Impairment><In Vitro><Infection><Infectious Mononucleosis Virus><Inflammation><Inflammatory Infiltrate><Innate Immune Response><Intracellular Communication and Signaling><Knowledge><Lian qiao><Lymphoid><Mediating><Metallopeptidases><Metalloproteases><Metalloproteinases><Microbe><Minority Groups><Minority People><Minority Population><Minority individual><Modeling><Modern Man><Molecular><Mouth Diseases><Mouth Mucosa><Mucosal Immunity><Myelogenous><Myeloid><Non-Hispanic><Nonhispanic><Not Hispanic or Latino><ORFs><Open Reading Frames><Oral><Oral Cavity Disease><Oral Cavity Disorder><Oral Disease><Oral Disorder><Oral Examination><Oral Mucosa><Oral Pathology><Oral health><Oral mucous membrane structure><Organ><Outcome><Outcome Study><P gingivalis><P. gingivalis><PASC><Parodontosis><Pathogenicity Factors><Pathway interactions><Peptidases><Peptide Hydrolases><Periodontal Diseases><Periodontitis><Population><Porphyromonas gingivalis><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Predisposed to COVID-19><Predisposed to SARS-CoV-2><Predisposed to Severe acute respiratory syndrome coronavirus 2><Prevalence><Prospective cohort><Protease Gene><Proteases><Protein Coding Region><Proteinases><Proteolytic Enzymes><Public Health><Receptor Protein><Recording of previous events><Regulatory T-Lymphocyte><Risk><Risk Factors><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 predisposition><SARS-CoV-2 susceptibility><SARS-CoV-2 vaccination><SARS-CoV-2 vulnerability><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><Saliva><Salivary Gland Viruses><Salvia><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 predisposition><Severe acute respiratory syndrome coronavirus 2 susceptibility><Severe acute respiratory syndrome coronavirus 2 vaccination><Severe acute respiratory syndrome coronavirus 2 vulnerability><Severe acute respiratory syndrome related corona virus 2><Signal Transduction><Signal Transduction Systems><Signaling><Signs and Symptoms><Surface><Tooth><Tooth structure><Treg><Tropism><Vaccinated><Vaccination><Vaccinee><Viral><Viral Diseases><Virion><Virulence Factors><Virus><Virus Diseases><Virus Particle><Virus Replication><Work><Wuhan coronavirus><Zoonoses><Zoonotic><Zoonotic Infection><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><anergy><angiotensin converting enzyme 2><angiotensin converting enzyme II><anti-bacterial><antibacterial><attenuate><attenuates><biological signal transduction><chronic COVID-19 sequelae><cohort><comparative><corona virus disease><corona virus disease 2019><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 risk><coronavirus disease 2019 risk factor><coronavirus disease 2019 vaccination><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><cytomegalovirus group><dental health><disparities in race><disparity due to race><ds-DNA><dsDNA><exhaustion><hCoV19><health data><herpes virus><high risk group><high risk individual><high risk people><high risk population><histories><host response><immune activation><immune system response><immunomodulatory biologics><immunoresponse><improved><inequality due to race><inequity due to race><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inflammation marker><inflammatory marker><inhibitor><keratinocyte><leukotoxin><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><mouth disorder><nCoV2><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><non vaccinated><not vaccinated><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><oral condition><oral immunity><oral mucosae><oral mucosal><oral tissue><pathogen><pathway><periodontal disorder><periodontal pathogen><periodontium disease><periodontium disorder><periodontopathogen><periopathogen><periopathogenic><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><pre-pandemic><predisposed to Coronavirus disease 2019><race based disparity><race based inequality><race based inequity><race disparity><race related disparity><race related inequality><race related inequity><racial disparities in health><racial disparity><racial health disparity><racial inequality><racial inequity><racially unequal><receptor><receptor expression><regulatory T-cells><risk associated with COVID-19><risk factor associated with COVID-19><risk factor related to COVID-19><risk related to COVID-19><screening><screenings><social role><susceptible to COVID-19><susceptible to Coronavirus disease 2019><susceptible to SARS-CoV-2><susceptible to Severe acute respiratory syndrome coronavirus 2><synergism><teeth><under served community><underserved community><unvaccinated><vaccinate against COVID-19><vaccinate against COVID19><vaccinate against SARS-CoV-2><vaccinate against coronavirus disease 2019><vaccinate against severe acute respiratory syndrome coronavirus 2><vaccinated individual><vaccinated participant><vaccinated patient><vaccinated person><vaccinated subject><vaccination against COVID-19><vaccination against COVID19><vaccination against SARS-CoV-2><vaccination against Severe acute respiratory syndrome coronavirus 2><vaccination against coronavirus disease 2019><viral infection><viral multiplication><viral replication><virus infection><virus multiplication><virus-induced disease>