Dysregulation of immune response in patients with COVID-19 in Wuhan, China.

Original Article: Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, Xie C, Ma K, Shang K, Wang W, Tian DS. Dysregulation of immune response in patients with COVID-19 in Wuhan, China. Clin Infect Dis. 2020 Mar 12. pii: ciaa248.

Author of Summary: Carmela Iosco; Reviewer:  Francesca La Cava

Original Article Published on March 12th, 2020

This article shows the data of 452 COVID-19 patients hospitalized at Tongji Hospital from 01/10/2020 to 02/12/2020. 286 patients (63.3%) received a diagnosis of severe infection (Defined by: 1. Respiratory distress with RR> 30 / min; 2. sO2 <= 93% at rest; 3. PaO2 / FiO2 <= 300 mmHg on arterial blood). Median age was 58 years (range 22 – 95) of which 235 (52%) were men. 201 (44%) patients had a chronic disease (high blood pressure, diabetes, COPD, etc.); of these, 51% of severe cases compared to 33.1% of non-severe cases. The most common symptoms reported are fever (92.6%), dyspnoea (50.8%), sputum (41.4%), asthenia (46.4%), dry cough (33.3%), myalgia (21, 4%). Patients with severe infection showed a higher incidence of dyspnoea and asthenia and a higher median age (61 vs 53 years).

The most serious cases showed a higher white blood cell count (5,600 vs 4,900/mmc) and neutrophilic (4,300 vs 3,200/mmc), lymphopenia (800 vs 1,000/mmc), higher neutrophil/lymphocyte ratio N / L (5.5 vs 3.2) and reduced monocytes (6.6% vs 8.4%). Severe cases showed a greater increase in procalcitonin (0.1 vs 0.05 ng/ml), ferritin (800.4 vs 523.6 ng/ml) and C-reactive protein (57.9 vs 33.2 mg/L) compared to less severe cases, in addition to a marked increase in IL-2R, IL-6, IL-8, IL-10 and TNF-a.

The study of lymphocyte populations showed a reduction in the total number of B, T and NK lymphocytes, more evident in severe cases. T lymphocytes were reduced to a greater extent in severe cases (461.6 vs 663.8 cell/mL). The functionality of CD4+, CD8+ and NK lymphocytes analyzed after stimulation with IFN-gamma was within normal limits.

Both CD4+ and CD8+ T lymphocytes (helper and suppressor) were reduced in COVID-19 patients, especially CD4+ T lymphocytes in severe cases compared to non-serious cases (285.1 vs. 420.5/mL). There was an increase in naive T helper cells (CD3+ CD+ CD45RA+) and a reduction in memory helper T cells (CD3+ CD4+ CD45RO+) in severe cases compared to non-serious cases. Suppressor cytotoxic T cells (CD3+ CD8+ CD28+) were reduced in severe cases. COVID-19 patients showed reduced levels of regulatory T lymphocytes (CD3+ CD4+ CD25+ CD127+ low).

The most severe cases showed a greater increase in both inflammation biomarkers and neutrophil/lymphocyte ratio (N/L), already known in the literature as a predictive value of bacterial infection (especially in the case of pneumonia). In this study, the high N/L ratio was indicative of greater criticality. In addition, the increase in pro-inflammatory cytokines and chemokines suggests a key role of the pro-inflammatory response in the pathogenesis of COVID-19.

Differentiation of naive CD4+ lymphocytes is the most important phenomenon of T-cellular immunity. The results on COVID-19 patients show an imbalance between naive T cells (excess) and reduced effector T cells, indicative of reduced development of the immune response. A reduction of regulatory T lymphocytes, fundamental in regulating inflammation at the mucosal level, has also been reported. These observations, together with the marked increase in proinflammatory cytokines and the consumption of CD4+ and CD8+ T cells, suggest a disease pathogenesis linked to the failure of regulating hyper-inflammation.

The N/L ratio and the increase in procalcitonin suggest that some of the COVID-19 patients may have contracted bacterial superinfection or co-infection, which could influence further the immune response.

The analysis conducted suggests that SARS-CoV-2 virus can act on T lymphocytes and induce a “cytokine storm” capable of generating hyper-inflammation with tissue damage. Surveillance of the N/L ratio and lymphocyte subtypes can be an aid in screening for severe cases and guide the treatment of COVID-19 patients.

N° enrolled patiens: 452

Methods: respiratory rate, Oxygen saturation, Oxygen partial pressure on arterial blood, white cell count by hemocytometer and flow-cytometry, white cell functional analysis by PMA/ionomycin, Real Time RT-PCR, immunoelectrophoresis

Be the first to comment on "Dysregulation of immune response in patients with COVID-19 in Wuhan, China."

Leave a comment

Your email address will not be published.