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Identification of pre-infection markers and differential plasma protein expression following SARS-CoV-2 infection in people living with HIV

eBioMedicine, 2023

Kolossváry M., deFilippi C., McCallum S., Fitch K., Diggs M., Fulda E., Ribaudo H., Fichtenbaum C., Aberg J., Malvestutto C., Currier J., Casado J., Gutiérrez F., Sereti I., Douglas P., Zanni M., Grinspoon S.

Disease areaApplication areaSample typeProducts
Infectious Diseases
Pathophysiology
Patient Stratification
Plasma
Olink Target 96

Olink Target 96

Abstract

Background
Mechanisms contributing to COVID-19 severity in people with HIV (PWH) are poorly understood. We evaluated temporal changes in plasma proteins following SARS-CoV-2 infection and identified pre-infection proteomic markers associated with future COVID-19.

Methods
We leveraged data from the global Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). Antiretroviral therapy (ART)-treated PWH with clinical, antibody-confirmed COVID-19 as of September 2021 were matched on geographic region, age, and sample timing to antibody negative controls. For cases and controls, pre COVID-19 pandemic specimens were obtained prior to January 2020 to assess change over time and relationship to COVID-19 severity, using false-discovery adjusted mixed effects modeling.

Findings
We compared 257 unique plasma proteins in 94 COVID-19 antibody-confirmed clinical cases and 113 matched antibody-negative controls, excluding COVID-19 vaccinated participants (age 50 years, 73% male). 40% of cases were characterized as mild; 60% moderate to severe. Median time from COVID-19 infection to follow-up sampling was 4 months. Temporal patterns of protein changes differed based on COVID-19 disease severity. Among those experiencing moderate to severe disease vs. controls, NOS3 increased whereas ANG, CASP-8, CD5, GZMH, GZMB, ITGB2, and KLRD1 decreased. Higher pre-pandemic levels of granzymes A, B and H (GZMA, GZMB and GZMH) were associated with the future development of moderate-severe COVID-19 and were related to immune function.

Interpretation
We identified temporal changes in proteins closely linked to inflammatory, immune, and fibrotic pathways which may relate to COVID-19-related morbidity among ART-treated PWH. Further we identified key granzyme proteins associated with future COVID-19 in PWH.

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