COVID-19 may be more severe in people with HIV (PWH), but the mechanisms contributing to this are poorly understood. A team from Massachusetts General Hospital in Boston used three Olink® Target 96 panels for targeted protein biomarker discovery to undertake a longitudinal proteomics study in PWH undergoing anti-retroviral therapy. Leveraging data from the REPRIEVE clinical trial cohort, they compared protein profiles between matched cases and controls who did or did not develop COVID-19 during the course of the study. Among the COVID cases, 40% were characterized as mild and 60% moderate to severe, and median time from SARS-CoV-2 infection to follow-up sampling was 4 months.
The longitudinal analysis revealed some interesting temporal patterns of protein changes linked to disease severity. In patients with moderate/severe COVID, NOS3 was significantly increased over time, while levels of ANG, CASP-8, CD5, GZMH, GZMB, ITGB2 & KLRD1 decreased. Pathway analysis was used to interpret these data as relevant adaptive and maladaptive changes in inflammatory, immune, and fibrotic pathways underlying moderate-to-severe COVID-19 in PWH.
Also of potential importance, pre-infection levels of the three granzyme proteins, GZMA, GZMB & GZMH were shown to be an independent risk factor for the development of subsequent moderate-to-severe COVID-19 among these patients. This observation is of significant interest since granzymes are serine proteases produced by cytotoxic T-cells and NK cells that induce apoptosis in virus-infected cells.