The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection

Author:

Melton, Alexandra [ORCID]

Rowe, Lori A [ORCID]

Penney, Toni

Krzykwa, Clara

Goff, Kelly

Scheuermann, Sarah E [ORCID]

Melton, Hunter J [ORCID]

Williams, Kelsey [ORCID]

Golden, Nadia

Green, Kristyn Moore

Smith, Brandon [ORCID]

Russell-Lodrigue, Kasi [ORCID]

Dufour, Jason P

Doyle-Meyers, Lara A

Schiro, Faith

Aye, Pyone P

Lifson,Jeffrey

Beddingfield, Brandon J [ORCID]

Blair, Robert V [ORCID]

Bohm, Rudolf P

Kolls, Jay K [ORCID]

Rappaport, Jay

Hoxie, James A

Maness, Nicholas J [ORCID]
Author Address

Tulane National Primate Research Center, Covington, LA 70433, USA., Biomedical Science Training Program, Tulane University School of Medicine, New Orleans, LA 70112, USA., Department of Statistics, Florida State University, Tallahassee, FL 32306, USA., Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA., AIDS and Cancer Viruses Program, Frederick National Laboratory, Frederick, MD 21701, USA., Department of Microbiology and Immunology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Departments of Medicine and Pediatrics, Center for Translational Research in Infection and Inflammation, Tulane University School of Medicine, New Orleans, LA 70112, USA., Department of Pulmonary Critical Care and Environmental Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA., Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.,

Abstract:

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-na 239;ve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-na 239;ve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.

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