Exhausting T Cells During HIV Infection May Improve the Prognosis of Patients with COVID-19

Abstract

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/μl (IQR = 96-289 cells/μl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/μl) and AIDS (median CD4 = 97 cells/μl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19.

Keywords: COVID-19; HIV; T cells; T-cell exhaustion; lymphocyte redistribution.

Figure 1

Imaging lung manifestations of coronavirus disease 2019 (COVID-19) patients with HIV/AIDS. (A–C) Representative chest CT of three patients with the most severe imaging in the non-AIDS group. (A) A 42-year-old woman had fever, cough, and sputum with a body temperature of 37.4°C. The CD4 T-cell count of this patient, who has received antiretroviral treatment (ART), was 263 cells/μl. Chest CT on the first day after admission demonstrated bilateral peripheral ground-glass opacities with linear opacities. The total severity score (TSS) was 5. (B) A 36-year-old woman had cough with a body temperature of 36.4°C. The CD4 T-cell count of this patient, who has not received ART, was 695 cells/μl. Chest CT on the first day after admission demonstrated peripheral ground-glass opacities with minimal consolidation in the left lung. The TSS was 3. (C) A 39-year-old woman had cough with a body temperature of 36.7°C. The CD4 T-cell count of this patient, who has not received ART, was 227 cells/μl. Chest CT on the first day after admission demonstrated peripheral minimal ground-glass opacities in the left lung. The TSS was 1. (D–F) Representative chest CT of three patients with the worst imaging in the AIDS group. (D) A 48-year-old man had cough and dyspnea with a body temperature of 36.4°C. The CD4 T-cell count of this patient, who refused any ART, was 85 cells/μl. Chest CT on the first day after admission demonstrated bilateral peripheral ground-glass opacities with minimal consolidation. The TSS was 12. (E) A 64-year-old woman had fever and cough with a body temperature of 37.6°C. The CD4 cell count of this patient, who received ART, was 95 cells/μl. Chest CT on the first day after admission demonstrated bilateral peripheral ground-glass opacities with minimal consolidation, mixed with HIV-infected lung imaging manifestations (nonspecific interstitial pneumonitis feature). The TSS was 10. (F) A 41-year-old woman had mild cough with a body temperature of 36.4°C. The CD4 T-cell count of this patient, who received ART, was 64 cells/μl. Chest CT on the first day after admission demonstrated bilateral peripheral ground-glass opacities, mixed with HIV-infected lung imaging manifestations (nonspecific interstitial pneumonitis feature). The TSS was 4. (G, H) Comparison of the TSS on admission (Ba) and on the day of follow-up (FL) after 20 days in hospital among non-AIDS and AIDS patients. Wilcoxon signed-rank tests were performed for each analyte.

Figure 2

Lymphocyte subset counts and C-reactive protein (CRP) and interleukin 6 (IL-6) levels compared between AIDS and non-AIDS patients (A–F). One patient had no lymphocyte subset data on admission and 12 patients lacked lymphocyte subset data at follow-up (FL) (G–I). The Mann–Whitney test was performed for different group comparisons and Wilcoxon signed-rank test was performed for follow-up analysis. Mean values are shown in green for this study. Orange and blue dotted lines indicate the mean values reported by others for common patients or severe COVID-19 patients without HIV/AIDS (Qin et al., 2020).