Mielke Dieter, Li Shuying Sue, Schuster Daniel J, Li Xiaohong, Hu Jiani, Karuna Shelly, Seaton Kelly E, Brackett Caroline, Dunn Brooke, Keyes Taylor, Zalaquett Adam, Stanfield-Oakley Sherry, Zhang Lu, Wesley Martina S, Eisel Nathan, Yates Nicole L, Shen Xiaoying, Premkumar Lakshmanane, Germain Russell St, Sholukh Anton M, Cohen Kristen, de Rosa Stephen, Randhawa April Kaur, Hural John A, Corey Lawrence, McElrath M Julianna, Tomaras Georgia D, Hyrien Ollivier, Ferrari Guido
Center for Human Systems Immunology, Duke University, Durham, NC, USA.
Department of Surgery, Duke University, Durham, NC, USA.
Commun Med (Lond). 2025 Apr 23;5(1):132. doi: 10.1038/s43856-025-00839-1.
SARS-CoV-2 infection results in greater disease severity among immunocompromised individuals compared to healthy individuals. However, there is conflicting information about the impact of chronic HIV infection on immune responses to SARS-CoV-2 infection and vaccination.
We used a combination of machine learning approaches and network analysis to explore 56 immune markers and comprehensively profile humoral and cellular immunity in a cross-sectional observational cohort of people without HIV (PWOH; n = 216) and people living with HIV (PLWH; n = 43) who recovered from SARS-CoV-2 infection (13-131 days since SARS-COV-2 diagnosis) early in the pandemic.
PLWH recovered from symptomatic outpatient COVID-19 exhibit lower humoral and B cell responses to SARS-CoV-2 vs. PWOH but, surprisingly, both symptomatic outpatient and hospitalized PLWH have higher anti-endemic coronavirus antibody responses compared to PWOH counterparts and asymptomatic PLWH. The latter observation suggests that this was not strictly due to broadly elevated levels of anti-endemic coronavirus antibodies in PLWH. Moreover, correlation-based analysis reveals that while different compartments of the immune response to SARS-CoV-2 infection are positively correlated in PWOH recovered from symptomatic outpatient COVID-19, these correlations are weaker in PLWH.
Our analyses reveal significant differences in the coordinated immune responses elicited by infection in PLWH compared to PWOH.
与健康个体相比,免疫功能低下的个体感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)后疾病严重程度更高。然而,关于慢性人类免疫缺陷病毒(HIV)感染对SARS-CoV-2感染和疫苗接种免疫反应的影响,存在相互矛盾的信息。
我们采用机器学习方法和网络分析相结合的方式,对56种免疫标志物进行探索,并在疫情早期从SARS-CoV-2感染中康复(自SARS-CoV-2诊断后13 - 131天)的无HIV人群(PWOH;n = 216)和HIV感染者(PLWH;n = 43)的横断面观察队列中,全面分析体液免疫和细胞免疫特征。
从有症状门诊COVID-19中康复的PLWH对SARS-CoV-2的体液免疫和B细胞反应低于PWOH,但令人惊讶的是,与PWOH对应人群和无症状PLWH相比,有症状门诊和住院的PLWH对地方性冠状病毒的抗体反应更高。后一观察结果表明,这并非严格由于PLWH中抗地方性冠状病毒抗体水平普遍升高所致。此外,基于相关性的分析显示,虽然从有症状门诊COVID-19中康复的PWOH对SARS-CoV-2感染的不同免疫反应区室呈正相关,但在PLWH中这些相关性较弱。
我们的分析揭示了与PWOH相比,PLWH感染引发的协调免疫反应存在显著差异。