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

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 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.

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 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)].

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.

Figure 1

Panel A. Diagnosis, symptoms, and therapy timeline in the SARS-CoV-2/HIV-1-coinfected patient. Red dotted line: nasopharyngeal swabs. Blue asterisk: Hospital admission; Blue triangle: Hospital discharge. Panel B1-B2. Representative chest High-resolution computed tomography (HRCT) images of the SARS-CoV-2/HIV-1-coinfected patient, detected bilateral ground-glass opacities.

Figure 2

MRDs in IFNα and IFNβ gene expression (Panel A) and T cell immune activation (Panel B) levels between the SARS-CoV-2/HIV-1-coinfected patient and HIV-1-positive female patients (green-filled circle) or healthy women (blue-filled circle). SARS-CoV-2/HIV-1-coinfected patient data are representative of 3 independent experimental replicates and results are provided as median for the entire specimen. Vertical bars indicate the errors. The errors on the MRD are calculated with standard error propagation. The red dotted line (Baseline) markers the case of zero difference between variables measurement in the SARS-CoV-2/HIV-1-coinfected patient and HIV-1-positive female patients or healthy women. The blue dotted line represents bias for MRDs between variables measurement in the SARS-CoV-2/HIV-1-coinfected patient and healthy women, whereas the green continuous line indicates bias for MRDs between variables measurement in the SARS-CoV-2/HIV-1-coinfected patient and HIV-1-positive female patients. HIV-1 = human immunodeficiency virus-1, IFN = interferon, MRD = median relative differences, SARS-CoV-2 = severe acute respiratory syndrome coronavirus-2.