[Clinical significance of early immunological paralysis in patients with severe H1N1 influenza A].

OBJECTIVE: To analysis the immunological characteristics of patients with severe H1N1 influenza A, and to provide theoretical basis for predicting the prognosis of the disease.

METHODS: A retrospective analysis was conducted. The clinical data of 15 patients diagnosed with severe H1N1 influenza A and admitted to Shanghai General Hospital of Nanjing Medical University from October 2015 to December 2016 were collected. All the patients were divided into survival and death groups according to 28-day survival. Clinical characteristics, treatment algorithm, organ function, inflammatory reaction and immune cell status were compared, and Cox regression was used to decide the risk factors of 28-day death in patients with severe H1N1 infection A.

RESULTS: All 15 patients with severe H1N1 infection A were enrolled, most of who presented with cough (93.3%), fever (86.7%), sputum production (80.0%), shortness of breath (73.3%), myalgia (40.0%) and fatigue (40.0%). All had been received anti-virus, antibiotics, mechanical ventilation and anti-coagulation therapy; some were treated with prone position, neuromuscular blocker and extracorporeal membrane oxygenation (ECMO). The incidences of acute myocardial and kidney injury were high, and the acute physiology and chronic health evaluation II (APACHE II) score (14.1±6.1) and sequential organ failure assessment (SOFA) score (9.6±4.1) implicated the critical condition. Of 15 patients, 4 patients died in 28 days, while 11 were cured and discharged. Compared with survival group, the patients in death group had higher levels of APACHE II score (22.7±3.8 vs. 11.8±3.8), troponin [cTn (μg/L): 0.52 (0.07, 2.02) vs. 0.15 (0.10, 0.45)] and blood urea nitrogen [BUN (mmol/L): 11.9 (6.7, 29.1) vs. 3.9 (2.7, 6.8)] and a lower level of blood platelets count [PLT (×10(9)/L): 76±33 vs. 146±49, all P < 0.05]. The levels of C-reactive protein (CRP) and interleukin-6 (IL-6) within 24 hours of admission in death group were significantly higher than those of survival group [CRP (mg/L): 172.2±88.5 vs. 74.8±33.1, IL-6 (ng/L): 283.3 (140.1, 711.0) vs. 18.5 (12.7, 71.4), both P < 0.01]. Compared with survival group, the expressions of CD3(+), CD4(+), CD8(+) T cells and natural killer cell (NK cell) in death group were significantly decreased (CD3(+) T cell: 0.348±0.119 vs. 0.573±0.106, CD4(+) T cell: 0.135±0.046 vs. 0.344±0.098, CD8(+) T cell: 0.089±0.057 vs. 0.208±0.054, NK cell: 0.124±0.057 vs. 0.252±0.182, all P < 0.05), but there were no significant differences in CD4(+)/CD8(+) ratio and human leucocyte antigen-DR positive (HLA-DR(+)) T cell between death group and survival group (CD4(+)/CD8(+) ratio: 1.57±0.26 vs. 1.83±0.54, HLA-DR(+) T cell: 0.035±0.022 vs. 0.062±0.036, both P > 0.05). B lymphocyte in death group was significantly higher than that of survival group (0.477±0.136 vs. 0.229±0.121, P < 0.01). Cox regression analysis revealed that APACHE II score [risk ratio (RR) = 20.4, 95% confidence interval (95%CI) = 5.3-31.2, P = 0.017], CD4(+) T cell (RR = 11.1, 95%CI = 5.1-20.0, P = 0.048) and CD8(+) T cell (RR = 9.1, 95%CI = 4.3-16.7, P = 0.049) were independently risk factors of 28-day survival of patients with severe H1N1 influenza A.

CONCLUSIONS: Immunological paralysis and severe inflammatory response were early complicated with severe H1N1 influenza A, and these were significantly associated with prognosis.