Analysis of type I IFN response and T cell activation in severe COVID-19/HIV-1 coinfection

Abstract

Rationale: 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. Patient concerns: 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. Diagnoses: 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. Interventions: SARS-CoV-2/HIV-1-coinfected female patient under darunavir/cobicistat regimen received a 7-days hydroxychloroquine therapy. Analysis of IFN α /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. Outcomes: 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 F i O 2 of 30%. MRD values for IFN α /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 IFN α/ 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 IFN α/ β: median 28.45 (range: 15/41.9); T cells: median 10 (range 6/22)]. Lessons: 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.

HIV/SARS-CoV-2 co-infection: T cell profile, cytokine dynamics and role of exhausted lymphocytes

“…Elevated serum concentrations of immunosuppressive cytokines IL-10 and TGFβ in Group 1 and 2 with maximums around four weeks since the COVID-19 onset ( Figure 2 , panels E-F), may have strengthened T cell exhaustion further. IL-10 and TGFβ serum amounts have been reported to be higher in PLWH than in general population ( D’Ettorre et al, 2020 , Ho et al, 2020 , Yarilin, 2010 ). In our study, we observed as well higher pre-COVID amounts of the two cytokines in question as their more pronounced growth during COVID-19 course in Group 1 than in Group 2 or especially Group 3 ( Figure 2 , panels E-F).…”

“…Further, it has been detected that HIV/SARS-CoV-2 co-infection may lead to pneumonia complications oftener than COVID-19 itself ( Madge et al, 2020 , Okoh et al, 2020 ). The ability of HIV/SARS-CoV-2 co-infection to cause excessive T cell activation has been observed in sample sets little in size ( D’Ettorre et al, 2020 , Gao et al, 2020 ). Besides, it has been detected that COVID-19 severe symptomatic manifestations may lead to a more pronounced T cell response than mild symptomatic clinical course ( Ho et al, 2020 , Mondi et al, 2020 ).…”

Relationship of SARS-CoV-2–specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection

“…To date, the immunological impact of HIV on SARS-CoV-2 immune response has been mainly reported in isolated or limited cases of coinfection ( 51 – 53 ). Only 2 studies have measured the effect of HIV-1 infection on the overall profile of T cells in COVID-19 cases: Karim et al showed that viremic HIV-infected COVID-19 patients exhibited lower frequencies of tissue-homing CXCR3 + CD8 + T cells and higher T cell activation compared with HIV-uninfected patients ( 54 ).…”

“…To date, the immunological impact of HIV on SARS-CoV-2 immune response has been mainly reported in isolated or limited cases of co-infection (51)(52)(53). Only two studies have measured the effect of HIV-1 infection on the overall profile of T cells in COVID-19 cases: Karim et al…”

Profile of SARS-CoV-2-specific CD4 T cell response: Relationship with disease severity and impact of HIV-1 and activeMycobacterium tuberculosisco-infection

“…To date, the immunological impact of HIV on SARS-CoV-2 immune response has been mainly reported in isolated or limited cases of co-infection (d’Ettorre et al, 2020; Mondi et al, 2020; Wang et al, 2020). Only two studies have measured the effect of HIV-1 infection on the overall profile of T cells in COVID-19 cases: Karim et al .…”