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Postacute sequelae and adaptive immune responses in people with HIV recovering from SARS-COV-2 infection
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We observed that HIV status was strongly associated with PASC, raising concerns that this condition might be common among PWH recovering from COVID-19. Higher levels of inflammation were associated with PASC. Finally, we observed differences in SARS-CoV-2-specific CD4+ and CD8+ T cells that might have implications for long-term immunity conferred by natural infection. This study adds to the limited data examining SARS-CoV-2-specific immune responses in PWH and underscores the need for larger and more detailed studies of PASC in PWH.
we found that PWH had lower SARS-CoV-2-specific CD8+ T cell responses.
we found that SARS-CoV-2-specific CD4+ T cells in PWH had higher expression of the co-inhibitory receptor PD-1, suggesting they may have impaired functionality upon re-encountering infection. Alternatively, PWH may have more SARS-CoV-2 antigen exposure leading to a more exhausted phenotype. Third, we found that a higher CD4+/CD8+ ratio - which can sometimes be optimized with early ART initiation [39] - was associated with lower expression of PD-1 on SARS-CoV-2-specific CD8+ T cells.
Our analysis provides compelling preliminary evidence suggesting an urgent need to better understand the epidemiology and pathophysiology of PASC within PWH. Such efforts may lead to targeted interventions to prevent or treat PASC among this special population of interest.
PASC may be driven, at least in part, by residual or ongoing inflammation following SARS-CoV-2 infection [9,10]. ART-treated HIV is a chronic inflammatory condition associated with persistent immune activation [15-18]. Further immune perturbations related to COVID-19 may, therefore, lead to a higher prevalence of PASC among PWH. Additional factors could also predispose PWH to PASC, such as autoimmunity [33], localized tissue inflammation [34], human herpesvirus reactivation [13], and microvascular dysfunction [14]. Other comorbidities including substance use and metabolic disorders may further contribute. Regardless of mechanism, our observation suggests that PASC may be especially common in PWH and emphasizes the need for studies of PASC in this population.
A combination of factors might underlie PASC [9-14]. Higher prevalence of certain socioeconomic factors and comorbidities among PWH, along with differences in immune responses to SARS-CoV-2 [6,7] and persistent inflammation and immune dysregulation in the presence of antiretroviral therapy (ART) [15-18], may make PWH selectively vulnerable to developing this condition. For these reasons, examination of PASC in PWH is urgently needed.
Here, we sought to test the hypothesis that PASC would be more prevalent in PWH with a history of COVID-19 prior to vaccination and that these individuals would have reduced SARS-CoV-2-specific immune responses in comparison to HIV-negative individuals recovering from COVID-19.
Markers of systemic inflammation
In PWH compared with HIV-negative individuals, mean IL-6 levels were 1.55-fold higher (95% CI 1.06-2.26; P = 0.02), mean IP-10 levels were 1.31-fold higher (95% CI 1.06-1.62; P = 0.01), and TNFα levels were 1.26-fold higher (95% CI 1.08-1.47; P = 0.003).

Postacute sequelae and adaptive immune responses in people with HIV recovering from SARS-COV-2 infection
Peluso, Michael J.a,∗; Spinelli, Matthew A.a,∗; Deveau, Tyler-Marieb; Forman, Carrie A.a; Munter, Sadie E.b; Mathur, Sujatac; Tang, Alex F.a; Lu, Scottc; Goldberg, Sarah A.c; Arreguin, Mireya I.a; Hoh, Rebeccaa; Tai, Vivaa; Chen, Jessica Y.a; Martinez, Enrique O.a; Yee, Brandon C.d; Chenna, Ahmedd; Winslow, John W.d; Petropoulos, Christos J.d; Sette, Alessandroe,f; Weiskopf, Daniellae; Kumar, Nitashab; Lynch, Kara L.g; Hunt, Peter W.b; Durstenfeld, Matthew S.h; Hsue, Priscilla Y.h; Kelly, J. Danielc; Martin, Jeffrey N.c; Glidden, David V.c; Gandhi, Monicaa; Deeks, Steven G.a; Rutishauser, Rachel L.b,∗; Henrich, Timothy J.b,∗
AIDS Oct 2022

Limited data are available on the long-term clinical and immunologic consequences of SARS-CoV-2 infection in people with HIV (PWH).
We measured SARS-CoV-2-specific humoral and cellular responses in people with and without HIV recovering from COVID-19 (n = 39 and n = 43, respectively) using binding antibody, surrogate virus neutralization, intracellular cytokine staining, and inflammatory marker assays. We identified individuals experiencing postacute sequelae of SARS-CoV-2infection (PASC) and evaluated immunologic parameters. We used linear regression and generalized linear models to examine differences by HIV status in the magnitude of inflammatory and virus-specific antibody and T-cell responses, as well as differences in the prevalence of PASC.
Among PWH, we found broadly similar SARS-CoV-2-specific antibody and T-cell responses as compared with a well matched group of HIV-negative individuals. PWH had 70% lower relative levels of SARS-CoV-2-specific memory CD8+ T cells (P = 0.007) and 53% higher relative levels of PD-1+ SARS-CoV-2-specific CD4+ T cells (P = 0.007). Higher CD4+/CD8+ ratio was associated with lower PD-1 expression on SARS-CoV-2-specific CD8+ T cells (0.34-fold effect, P = 0.02). HIV status was strongly associated with PASC (odds ratio 4.01, P = 0.008), and levels of certain inflammatory markers (IL-6, TNF-alpha, and IP-10) were associated with persistent symptoms.
We identified potentially important differences in SARS-CoV-2-specific CD4+ and CD8+ T cells in PWH and HIV-negative participants that might have implications for long-term immunity conferred by natural infection. HIV status strongly predicted the presence of PASC. Larger and more detailed studies of PASC in PWH are urgently needed.

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