d'Ettorre Gabriella, Recchia Gregorio, Ridolfi Marco, Siccardi Guido, Pinacchio Claudia, Innocenti Giuseppe Pietro, Santinelli Letizia, Frasca Federica, Bitossi Camilla, Ceccarelli Giancarlo, Borrazzo Cristian, Antonelli Guido, Scagnolari Carolina, Mastroianni Claudio Maria
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155.
Laboratory of Virology, Department of Molecular Medicine, affiliated to Istituto Pasteur Italia - Cenci Bolognetti Foundation, Sapienza University.
Medicine (Baltimore). 2020 Sep 4;99(36):e21803. doi: 10.1097/MD.0000000000021803.
Complex immune dysregulation in interferon (IFN) and T cell response has been observed in human immunodeficiency virus (HIV-1)-infected patients as well as in coronavirus disease-2019 (COVID-19) patients. However, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)/HIV-1 coinfection has been described in only few cases worldwide and no data are available on immunological outcomes in HIV-1-patients infected with SARS-CoV-2. Hence, this study aims to compare type I IFN response and T cell activation levels between a SARS-CoV-2/HIV-1-coinfected female patient and age-matched HIV-1-positive or uninfected women.
A 52-year-old woman diagnosed with SARS-CoV-2/HIV-1 coinfection, ten HIV-1-positive women and five age-matched-healthy individuals were enrolled in this study.
SARS-CoV-2 infection caused severe pneumonia in the second week of illness in HIV-1-positive patient under protease inhibitors. Chest high-resolution computed tomography images of the SARS-CoV-2/HIV-1-coinfected patient showed bilateral ground-glass opacities.
SARS-CoV-2/HIV-1-coinfected female patient under darunavir/cobicistat regimen received a 7-days hydroxychloroquine therapy. Analysis of IFNα/β mRNA levels and CD4 and CD8 T cell (CD38, human leukocyte antigen-DR [HLA-DR], CD38 HLA-DR) frequencies were performed by RT/real-time PCR assays and flow cytometry, respectively. Median relative difference (MRD) was calculated for each immunological variable. For values greater than reference, MRD should be a positive number and for values that are smaller, MRD should be negative.
The severe pneumonia observed in SARS-CoV-2/HIV-1-positive patient under protease inhibitors was reversed by a 7-days hydroxychloroquine therapy. At the end of treatment, on day 7, patient reported resolution of fever, normalization of respiratory rate (14 breaths/min), and improved oxygen arterial pressure with a FiO2 of 30%. MRD values for IFNα/β and CD4 and CD8 T cells expressing CD38 and/or HLA-DR found in SARS-CoV-2-/HIV-1-coinfected woman were approximatively equal to 0 when refereed respectively to HIV-1-positive female patients [MRDs IFNα/β: median -0.2545 (range: -0.5/0.1); T cells: median -0.11 (range: -0.8/1.3)] and ≥ 6 when referred to healthy individuals [MRDs IFNα/β: median 28.45 (range: 15/41.9); T cells: median 10 (range 6/22)].
These results indicate that SARS-CoV-2 infection in HIV-1-positive female patient was associated with increased levels of IFNα/β-mRNAs and T cell activation compared to healthy individuals.
在人类免疫缺陷病毒（HIV-1）感染患者以及2019冠状病毒病（COVID-19）患者中，均观察到干扰素（IFN）和T细胞反应存在复杂的免疫失调。然而，全球仅报道了少数严重急性呼吸综合征冠状病毒2（SARS-CoV-2）/HIV-1合并感染的病例，且尚无关于感染SARS-CoV-2的HIV-1患者免疫结局的数据。因此，本研究旨在比较一名SARS-CoV-2/HIV-1合并感染的女性患者与年龄匹配的HIV-1阳性或未感染女性之间的I型干扰素反应和T细胞活化水平。
本研究纳入了一名诊断为SARS-CoV-2/HIV-1合并感染的52岁女性、十名HIV-1阳性女性和五名年龄匹配的健康个体。
在接受蛋白酶抑制剂治疗的HIV-1阳性患者中，SARS-CoV-2感染在发病第二周导致严重肺炎。SARS-CoV-2/HIV-1合并感染患者的胸部高分辨率计算机断层扫描图像显示双侧磨玻璃样混浊。
接受达芦那韦/考比司他治疗方案的SARS-CoV-2/HIV-1合并感染女性患者接受了7天的羟氯喹治疗。分别通过RT/实时PCR检测和流式细胞术分析IFNα/β mRNA水平以及CD4和CD8 T细胞（CD38、人类白细胞抗原-DR [HLA-DR]、CD38 HLA-DR）频率。计算每个免疫变量的中位数相对差异（MRD）。对于大于参考值的值，MRD应为正数；对于较小的值，MRD应为负数。
接受蛋白酶抑制剂治疗的SARS-CoV-2/HIV-1阳性患者出现的严重肺炎通过7天的羟氯喹治疗得到缓解。在治疗结束时，即第7天，患者报告发热消退、呼吸频率恢复正常（14次/分钟），且在FiO2为30%时动脉血氧压力改善。与HIV-1阳性女性患者相比，SARS-CoV-2/HIV-1合并感染女性患者中IFNα/β以及表达CD38和/或HLA-DR的CD4和CD8 T细胞的MRD值分别约为0 [MRD IFNα/β：中位数-0.2545（范围：-0.5/0.1）；T细胞：中位数-0.11（范围：-0.8/1.3）]；与健康个体相比，MRD≥6 [MRD IFNα/β：中位数28.45（范围：15/41.9）；T细胞：中位数10（范围6/22）]。
这些结果表明，与健康个体相比，HIV-1阳性女性患者感染SARS-CoV-2与IFNα/β mRNA水平和T细胞活化水平升高有关。
