Abstract:
INTRODUCTION : SARS-CoV-2 elicits a hyper-inflammatory response that
contributes to increased morbidity and mortality in patients with COVID-19. In
the case of HIV infection, despite effective anti-retroviral therapy, people living
with HIV (PLWH) experience chronic systemic immune activation, which renders
them particularly vulnerable to the life-threatening pulmonary, cardiovascular
and other complications of SARS-CoV-2 co-infection. The focus of the study
was a comparison of the concentrations of systemic indicators o\f innate
immune dysfunction in SARS-CoV-2-PCR-positive patients (n=174) admitted
with COVID-19, 37 of whom were co-infected with HIV.
METHODS : Participants were recruited from May 2020 to November 2021.
Biomarkers included platelet-associated cytokines, chemokines, and growth
factors (IL-1b, IL-6, IL-8, MIP-1a, RANTES, PDGF-BB, TGF-b1 and TNF-a) and
endothelial associated markers (IL-1b, IL-1Ra, ICAM-1 and VEGF).
RESULTS : PLWH were significantly younger (p=0.002) and more likely to be female
(p=0.001); median CD4+ T-cell count was 256 (IQR 115 -388) cells/mL and the
median HIV viral load (VL) was 20 (IQR 20 -12,980) copies/mL. Fractional inspired
oxygen (FiO2) was high in both groups, but higher in patients without HIV
infection (p=0.0165), reflecting a greater need for oxygen supplementation.
With the exception of PDGF-BB, the levels of all the biomarkers of innate
immune activation were increased in SARS-CoV-2/HIV-co-infected and SARSCoV-
2/HIV-uninfected sub-groups relative to those of a control group of
healthy participants. The magnitudes of the increases in the levels of these
biomarkers were comparable between the SARS-CoV-2 -infected sub-groups, the one exception being RANTES, which was significantly higher in the subgroup
without HIV. After adjusting for age, sex, and diabetes in the multivariable
model, only the association between HIV status and VEGF was statistically
significant (p=0.034). VEGF was significantly higher in PLWH with a CD4+ Tcell
count >200 cells/mL (p=0.040) and those with a suppressed VL (p=0.0077).
DISCUSSION : These findings suggest that HIV co-infection is not associated with
increased intensity of the systemic innate inflammatory response during SARSCoV-
2 co-infection, which may underpin the equivalent durations of hospital
stay, outcome and mortality rates in the SARS-CoV-2/HIV-infected and
-uninfected sub-groups investigated in the current study. The apparent
association of increased levels of plasma VEGF with SARS-CoV-2/HIV coinfection
does, however, merit further investigation.
