R01AI170197

Understanding Co-Morbidities: COVID-19 in Individuals Living with HIV/AIDS - Summary

While COVID-19 continues to be a health challenge, very little is known about how COVID-19 affects people living with HIV (PLHIV). Based on the most recent reports originating from CDC and WHO, however, it appears that people with HIV may have a 30% greater likelihood of developing severe COVID-19 disease when infected with SARS-CoV-2.

We will leverage the established Rhesus macaque models of SARS-CoV-2 infection resulting in COVID-19 and SIV infection to characterize the effects of underlying SIV infection on the manifestation of both acute and post-acute COVID-19 sequelae. Our group was amongst few that established the Rhesus macaque models of COVID-19 infection early on during the pandemic. Our model has been utilized to both study the immunological mechanisms of protection from SARS-CoV-2 infection, as well as for accelerated development of vaccine and therapeutics against COVID-19.

Here we propose to couple this model with the long-standing, highly validated, pathogenic AIDS NHP model in SIV infected Rhesus macaques to study a central hypothesis that underlying SIV infection and the resulting immunodeficiency/immune activation promotes the progression of a more severe COVID-19 presentation due to SARS-CoV-2 infection. As a corollary, we hypothesize that ART does not completely suppress the ill effects of chronic immune activation due to SIV. Therefore, it will not completely prevent the progression of severe COVID-19 due to SARS-CoV-2 infection in the macaque model.

We have the experience in infecting Rhesus macaques with SIV and treating these animals with ART to suppress viral replication and study immune mechanisms. By profiling the differences in dynamics of viral titers, induced tissue pathology, and underlying immunological perturbations, we will provide definitive knowledge on whether SIV infected Rhesus macaques exhibit higher susceptibility to severe COVID-19. Furthermore, our studies will also be able to hint at the specific mechanisms which result in this susceptibility.

Delineating these comorbid immunological factors driving susceptibility will enable better clinical monitoring and informed decisions for patient care. Mechanistic insights developed by this study are also imperative for the development of host-directed immunotherapeutic interventions for combating COVID-19 in PLHIV.

Texas Biomedical Research Institute

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Texas United States

State-Wide

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 294% from $989,774 to $3,900,756.