Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19

Abstract

Background Coronavirus disease 2019 (COVID-19) is pandemic. It is critical to identify COVID-19 patients who are most likely to develop a severe disease. This study was designed to determine the clinical and epidemiological features of COVID-19 patients associated with the development of pneumonia and factors associated with disease progression. Methods Seventy consecutive patients with etiologically confirmed COVID-19 admitted to PLA General Hospital in Beijing, China from December 27, 2019 to March 12, 2020 were enrolled in this study and followed-up to March 16, 2020. Differences in clinical and laboratory findings between COVID-19 patients with pneumonia and those without were determined by the χ2 test or the Fisher exact test (categorical variables) and independent group t test or Mann–Whitney U test (continuous variables). The Cox proportional hazard model and Generalized Estimating Equations were applied to evaluate factors that predicted the progression of COVID-19. Results The mean incubation was 8.67 (95% confidence interval, 6.78–10.56) days. Mean duration from the first test severe acute respiratory syndrome coronavirus 2-positive to conversion was 11.38 (9.86–12.90) days. Compared to pneumonia-free patients, pneumonia patients were 16.5 years older and had higher frequencies of having hypertension, fever, and cough and higher circulating levels of neutrophil proportion, interleukin-6, low count (< 190/µl) of CD8+ T cells, and neutrophil/lymphocyte ratio. Thirteen patients deteriorated during hospitalization. Cox regression analysis indicated that older age and higher serum levels of interleukin-6, C-reactive protein, procalcitonin, and lactate at admission significantly predicted the progression of COVID-19. During hospitalization, circulating counts of T lymphocytes, CD4+ T cells, and CD8+ T cells were lower, whereas neutrophil proportion, neutrophil/lymphocyte ratio, and the circulating levels of interleukin-6, C-reactive protein, and procalcitonin were higher, in pneumonia patients than in pneumonia-free patients. CD8+ lymphocyte count in pneumonia patients did not recover when discharged. Conclusions Older age and higher levels of C-reactive protein, procalcitionin, interleukin-6, and lactate might predict COVID-19 progression. T lymphocyte, especially CD8+ cell-mediated immunity is critical in recovery of COVID-19. This study may help in predicting disease progression and designing immunotherapy for COVID-19.

Human immunodeficiency virus and mortality from coronavirus disease 2019: A systematic review and meta-analysis

“…57 This exhaustion of T-cell lymphocytes was associated with the progression and severe manifestation of COVID-19. 58,59 Limitations Firstly, only a limited number of our included studies reported on CD4 cell counts, viral loads and ART -a fact that is likely to have impacted the precision of the meta-regression analysis of this study. Indeed, most studies focussed on the characteristics of COVID-19 patients rather than its effects on PLWH.…”

Epidemiological feature, viral shedding, and antibody seroconversion among asymptomatic SARS-CoV-2 carriers and symptomatic/presymptomatic COVID-19 patients

“…In a previous prospective study, we have demonstrated that lower circulating counts of T lymphocytes, CD4 + T cells, and CD8 + T cells as well as higher circulating levels of neutrophil proportion, neutrophil/lymphocyte ratio, interleukin-6, CRP, and procalcitonin facilitate the progression of COVID-19. Of those, CD8 + T cell exhaustion plays an important role in the pathogenesis of COVID-19 [18]. Other studies have also shown that disease severity is negatively associated with NK cells and CD3 + , CD4 + , and CD8 + T lymphocyte levels, while intensive expansion of highly cytotoxic effector T cell subsets, such as CD4 + effector-granulysin, CD8 + effector-granulysin, and NKT CD160, is associated with convalescence of COVID-19 patients [19-21].…”

COVID-19 as a mediator of interferon deficiency and hyperinflammation: Rationale for the use of JAK1/2 inhibitors in combination with interferon

“…In the early HIV-era hydroxyurea, was used in the treatment of HIV and demonstrated synergistic effects with e.g nucleoside reverse transcriptase inhibitors [ 187 , 188 ]. Based upon its cytoreductive, anti-inflammatory and antithrombotic capabilities, it may be a highly efficacious agent in the treatment of COVID-19 patients with leukocytosis and imminent ARDS due to a rising potentially life-threatening cytokine storm [ [184] , [185] , [186] , [187] , [188] , [189] ]. In this context, the hydroxyurea-specific myeloid targets - monocytes and macrophages – may be of particular importance.…”

“…As in HIV-infection, hydroxyurea may also in COVID-19 attenuate viral rebound by decreasing CD4 T cell proliferation, as well as preventing the exhaustion of CD8 T cells(for Reviews: 187,188). Indeed, the cytostatic effect of hydroxyurea on both CD4 and CD8 T cells may also prohibit the cytokine storm by reducing COVID-19 induced immune system overactivation, thus preventing both CD8 T cell exhaustion and CD4 T cell depletion and thereby the ultimate collapse of the immune system in COVID-19 [ 189 , 190 ]. Rationales for the potential benefits of hydroxyurea in patients with COVID-19 are summarized in Table 5 .…”