Document text
Principal Investigator: Ivona Vasile Pandrea
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2023
Award: $397,500
Funding agency: National Institute of Diabetes and Digestive and Kidney Diseases
Abstract
With more than 60 million SARS-CoV-2 -infected patients worldwide and nearly 1.5 million COVID-19-related
deaths recoreded thus far (November 25), the COVID pandemic is one of the most critical global health problem
ever known to humankind, and a major emergency in the US. COVID-19 disproportionately impacts elders or
subjects with pre-existing conditions. Considering that the majority of persons living with HIV and AIDS (PLWHA)
in the US are aged over 50 years and that even the younger PLWHA present with accelerated aging and multiple
comorbidities related to HIV-induced excessive chronic inflammation, it is expected that COVID-19 will be
particularly severe in this risk group. Similar to HIV, SARS-CoV-2 replicates in the gut, and patients with
gastrointestinal symptoms were reported to have a more severe outcome. The exact mechanism through which
SARS-CoV-2 impacts the gut health remains elusive, however it is very likely that the two viruses can potentiate
each other through exacerbation of the gut lesions. Here, we will test the hypothesis that exacerbation of
the gut dysfunction of the SIV-infected PTMs after SARS-CoV-2 superinfection occurs through triggering
excessive mobilization, activation and NETosis of neutrophils at mucosal site and consequent gut
collateral damages. Such a scenario will result not only in an increased risk of the PLWHA to develop more
severe forms of COVID-19, but also to a significant boost of HIV pathogenicity through (i) losing control of HIV
at mucosal sites; (ii) depletion of mucosal and systemic immune effectors; (iii) increases of mucosal and systemic
levels of inflammation; and (iv) enhancement of pre-existent SIV-related comorbidities. This innovative project is
designed to assess pathogenic pathways impacted by SARS-CoV-2 in the gut, to understand the natural history
of COVID-19 related to either triggering or exacerbating HIV-associated gut dysfunction and comorbidities. We
will identify risk factors that could prompt therapy changes in high-risk individuals, such as the PLWH. Our highly
translational project addresses key scientific questions identified as critical by the NIDDK, thus being highly
responsive to RFA 20-021.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><AIDS><AIDS Virus><AIDS/HIV><Acceleration><Acquired Immune Deficiency><Acquired Immune Deficiency Syndrome><Acquired Immune Deficiency Syndrome Virus><Acquired Immuno-Deficiency Syndrome><Acquired Immunodeficiency Syndrome><Acquired Immunodeficiency Syndrome Virus><Acquired Immunologic Deficiency Syndrome><Address><Aging><Agreement><Airway infections><Animals><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><COVID crisis><COVID epidemic><COVID infected patient><COVID pandemic><COVID patient><COVID positive patient><COVID-19><COVID-19 affected><COVID-19 associated death><COVID-19 associated fatality><COVID-19 associated mortality><COVID-19 consequence><COVID-19 crisis><COVID-19 death><COVID-19 effect><COVID-19 epidemic><COVID-19 exposure><COVID-19 fatality><COVID-19 global health crisis><COVID-19 global pandemic><COVID-19 health crisis><COVID-19 impact><COVID-19 impacted><COVID-19 induced death><COVID-19 induced fatality><COVID-19 induced mortality><COVID-19 infected patient><COVID-19 infection><COVID-19 mortality><COVID-19 pandemic><COVID-19 pathogenesis><COVID-19 patient><COVID-19 positive patient><COVID-19 public health crisis><COVID-19 related death><COVID-19 related fatality><COVID-19 related mortality><COVID-19 virus><COVID-19 virus infection><COVID19><COVID19 associated death><COVID19 associated fatality><COVID19 associated mortality><COVID19 crisis><COVID19 death><COVID19 epidemic><COVID19 fatality><COVID19 global health crisis><COVID19 global pandemic><COVID19 health crisis><COVID19 induced death><COVID19 induced fatality><COVID19 induced mortality><COVID19 infection><COVID19 mortality><COVID19 pandemic><COVID19 pathogenesis><COVID19 patient><COVID19 positive patient><COVID19 public health crisis><COVID19 related death><COVID19 related fatality><COVID19 related mortality><COVID19 virus><CV-19><CV19><Cell Body><Cells><Cellular injury><Cessation of life><Chronic><Circulation><Clinical><Co-culture><CoV-2><CoV2><Cocultivation><Coculture><Coculture Techniques><Coronaviridae Infections><Coronavirus Infections><Data><Death><Disease Progression><Dysfunction><Elderly><Emergencies><Emergency Situation><Epithelial Cells><Epithelium><Failure><Functional disorder><GI microbiota><Gastrointestinal microbiota><Goals><Gut Epithelium><HIV><HIV/AIDS><Human Immunodeficiency Viruses><Immune><Immune Cell Activation><Immunes><Immunochemical Immunologic><Immunologic><Immunological><Immunologically><Immunologics><Individual><Infection><Inflammation><Inflammatory><Inflammatory Bowel Diseases><Inflammatory Bowel Disorder><Injury><Intestinal><Intestines><LAV-HTLV-III><Lead><Lesion><Lymphadenopathy-Associated Virus><M nemestrina><M. nemestrina><Macaca><Macaca nemestrina><Macaque><Marrow Neutrophil><Microbial Superinvasion><Modeling><Mononuclear><Morbidity><Morbidity - disease rate><Mucosa><Mucosal Inflammation><Mucosal Tissue><Mucositis><Mucous Membrane><NIDDK><National Institute of Diabetes and Digestive and Kidney Diseases><Natural History><Neutrophil Activation><Neutrophil Infiltration><Neutrophil Recruitment><Neutrophilic Granulocyte><Neutrophilic Infiltrate><Neutrophilic Leukocyte><Organ><Outcome><Pathogenicity><Pathologic><Pathway interactions><Patients><Pb element><Persons><Phagocytes><Phagocytic Cell><Physiopathology><Pigtail Macaque><Pigtail Monkey><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Production><Reporting><Respiratory Infections><Respiratory Tract Infections><Risk><Risk Factors><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 associated death><SARS-CoV-2 associated fatality><SARS-CoV-2 associated mortality><SARS-CoV-2 death><SARS-CoV-2 epidemic><SARS-CoV-2 exposure><SARS-CoV-2 fatality><SARS-CoV-2 global health crisis><SARS-CoV-2 global pandemic><SARS-CoV-2 induced death><SARS-CoV-2 induced fatality><SARS-CoV-2 induced mortality><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 mortality><SARS-CoV-2 pandemic><SARS-CoV-2 patient><SARS-CoV-2 positive patient><SARS-CoV-2 related death><SARS-CoV-2 related fatality><SARS-CoV-2 related mortality><SARS-CoV2><SARS-CoV2 epidemic><SARS-CoV2 exposure><SARS-CoV2 infection><SARS-CoV2 pandemic><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 epidemic><SARS-coronavirus-2 pandemic><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SIV><Seasons><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 CoV 2 epidemic><Severe Acute Respiratory Syndrome CoV 2 pandemic><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 epidemic><Severe acute respiratory syndrome coronavirus 2 exposure><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 pandemic><Severe acute respiratory syndrome related corona virus 2><Simian Immunodeficiency Viruses><Site><System><T4 Cells><T4 Lymphocytes><Testing><Therapeutic><Viral Diseases><Viral Pathogenesis><Virus><Virus Diseases><Virus-HIV><Wuhan coronavirus><advanced age><aged><amebocyte><anti-retroviral therapy><anti-retroviral treatment><antiretroviral therapy><antiretroviral treatment><bowel><cell damage><cell injury><cellular damage><co-infection><co-morbid><co-morbidity><coinfection><comorbidity><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease 2019><coronavirus disease 2019 associated death><coronavirus disease 2019 associated fatality><coronavirus disease 2019 associated mortality><coronavirus disease 2019 consequence><coronavirus disease 2019 crisis><coronavirus disease 2019 death><coronavirus disease 2019 effect><coronavirus disease 2019 epidemic><coronavirus disease 2019 exposure><coronavirus disease 2019 fatality><coronavirus disease 2019 global health crisis><coronavirus disease 2019 global pandemic><coronavirus disease 2019 health crisis><coronavirus disease 2019 impact><coronavirus disease 2019 induced death><coronavirus disease 2019 induced fatality><coronavirus disease 2019 induced mortality><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 mortality><coronavirus disease 2019 pandemic><coronavirus disease 2019 pathogenesis><coronavirus disease 2019 patient><coronavirus disease 2019 positive patient><coronavirus disease 2019 public health crisis><coronavirus disease 2019 related death><coronavirus disease 2019 related fatality><coronavirus disease 2019 related mortality><coronavirus disease 2019 virus><coronavirus disease crisis><coronavirus disease epidemic><coronavirus disease infected patient><coronavirus disease pandemic><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 global pandemic><coronavirus disease-19 impact><coronavirus disease-19 mortality><coronavirus disease-19 pandemic><coronavirus disease-19 pathogenesis><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><cytokine><damage to cells><death due to COVID-19><death due to COVID19><death due to SARS-CoV-2><death due to coronavirus disease 2019><death due to severe acute respiratory syndrome coronavirus 2><death in COVID><death in COVID-19><death in SARS-CoV-2><death in coronavirus disease><death in coronavirus disease 2019><death in severe acute respiratory syndrome coronavirus 2><design><designing><elderly patient><elders><enteric microbial community><enteric microbiota><experience><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><extracellular><fatality due to COVID-19><fatality due to COVID19><fatality due to SARS-CoV-2><fatality due to coronavirus disease 2019><fatality due to severe acute respiratory syndrome coronavirus 2><gastrointestinal epithelium><gastrointestinal microbial flora><gastrointestinal symptom><geriatric><global health><gut commensal><gut community><gut flora><gut health><gut microbe community><gut microbial community><gut microbial composition><gut microbial consortia><gut microbiota><gut microbiotic><gut microflora><hCoV19><heavy metal Pb><heavy metal lead><high risk group><high risk individual><high risk people><high risk population><immune activation><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><inflammatory disease of the intestine><inflammatory disorder of the intestine><inhibitor><injuries><injury to cells><innovate><innovation><innovative><insight><intestinal autoinflammation><intestinal flora><intestinal microbes><intestinal microbiota><intestinal microflora><intestinal tract microflora><late life><later life><life-threatening COVID><life-threatening COVID-19><life-threatening SARS-CoV-2><life-threatening coronavirus disease><life-threatening coronavirus disease 2019><life-threatening severe acute respiratory syndrome coronavirus 2><microbial products><mortality due to COVID-19><mortality due to COVID19><mortality due to SARS-CoV-2><mortality due to coronavirus disease 2019><mortality due to severe acute respiratory syndrome coronavirus 2><mucosal site><nCoV2><neutrophil><non-human primate><nonhuman primate><older adult><older patient><older person><pathogen><pathophysiology><pathway><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><pig-tailed macaque><prevent><preventing><restoration><senior citizen><serious COVID><serious COVID-19><serious SARS-CoV-2><serious coronavirus disease><serious coronavirus disease 2019><serious severe acute respiratory syndrome coronavirus 2><severe COVID><severe COVID-19><severe COVID19><severe SARS-CoV-2><severe acute respiratory syndrome coronavirus 2 associated death><severe acute respiratory syndrome coronavirus 2 associated fatality><severe acute respiratory syndrome coronavirus 2 associated mortality><severe acute respiratory syndrome coronavirus 2 death><severe acute respiratory syndrome coronavirus 2 fatality><severe acute respiratory syndrome coronavirus 2 global health crisis><severe acute respiratory syndrome coronavirus 2 global pandemic><severe acute respiratory syndrome coronavirus 2 induced death><severe acute respiratory syndrome coronavirus 2 induced fatality><severe acute respiratory syndrome coronavirus 2 induced mortality><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 mortality><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><severe acute respiratory syndrome coronavirus 2 related death><severe acute respiratory syndrome coronavirus 2 related fatality><severe acute respiratory syndrome coronavirus 2 related mortality><severe coronavirus disease><severe coronavirus disease 19><severe coronavirus disease 2019><severe severe acute respiratory syndrome coronavirus 2><super infection><superinfection><systemic inflammation><systemic inflammatory response><viral infection><virus infection><virus pathogenesis><virus-induced disease>