SARS-Cov-2 immunity in COVID-19 convalescent individuals living with HIV: bulk immune profiling and SARS-CoV-2 specific humoral and cellular immune responses


BACKGROUND: SARS'CoV'2-specific immune response features in PLWHA remain to be fully elucidated. The impact of HIV over the immune profile of lymphocyte populations in PLWHA recovered from COVID-19, as well as the humoral and cellular response secondary to COVID-19 were evaluated.
METHODS: Samples from donors to the Argentinean Biobank of Infectious Diseases with COVID-19 diagnosis: 21 PLWHA on ART and 21 HIV-negative (HIVneg) were included. Plasma and PBMC were obtained. SARS-CoV-2-specific IgG/IgM levels and IgG titers were determined by ELISA (COVIDAR test). Antibody neutralization capacity was evaluated against wild-type SARS-CoV-2. IFN-g-secreting cells were detected by ELISPOT using SARS-CoV-2 Spike, RBD or Nucleocapsid protein (10 mg/mL,) or overlapping peptide pools spanning Spike or Nucleocapsid proteins (1mg/mL). Frequency and phenotype of bulk T, B and NK cells were assessed by flow cytometry.
RESULTS: PLWHA median age was 47 (IQR:39.5-54); LTCD4=513 cells/uL (IQR:351-873). HIVneg median age was 41 (IQR:35-57). All individuals presented mild/moderate COVID-19. Mean time from symptoms onset to donation was 44 days (IQR:29.5-55) for HIVneg and 62 (IQR:35-93) for PLWHA. 75% of PLWHA and 85% of HIVneg had detectable SARS-CoV-2-specific antibodies, with IgG levels not differing between groups. Among PLWHA, neutralization capacity correlated with IgG titers (r:0.90, p<0.001), LTCD4 count (r:0.85, p:0.001), LTCD8 count (r:0.97, p<0.001) and age (r:0.63, p:0.021). All donors, including those with undetectable antibody response, had SARS-CoV2-specific cellular immunity. While HIVneg displayed IFN-g-secreting cells in response to S protein, RBD and S peptide pools, PLWHA responses were detected to S protein and N peptide pool, although with decreased magnitude (both p<0.01). Both groups displayed similar Treg (CD127-CD25+CD4+T) frequency, similar effector/memory and T-helper profile for LTCD4, and comparable exhaustion and memory profiles for LTCD8. No differences on NK, B or antibody-secreting cell proportions were observed. PLWHA presented increased Tfh (CD4+CXCR5+T-cells, p<0.01) and CXCR1+Tfh (p<0.05) cell frequency, enhanced expression of PD1+ on LTCD4 (p<0.05), HLA-DR on LTCD8 (p<0.05), and higher expression of CD95 (p=0.002), CD25 (p=0.004), HLA-DR (p<0.0001), NKp46 (p=0.035) and CD38/HLA-DR (p=0.002) on NK cells.
CONCLUSIONS: Although PLWHA showed an immune profile with enhanced activation and exhaustion, severity of COVID-19 was not exacerbated. Among PLWHA, SARS-CoV-2 infection could exert a significant humoral and cellular response, which could be associated to increased proportions of Tfh cells. Cellular response was lower compared to HIVneg individuals; nevertheless, a preserved LTCD4 count emerged as a key factor to achieve better antibody responses with higher neutralization capacity. This data reinforces the impact of ART not only in HIV control but in the capacity of control other infections.