Department of Infectious Diseases, Laboratory of Microbiology and Virology, Amedeo di Savoia Hospital, Turin, Italy.
Influenza Other Respir Viruses. 2013 Nov;7(6):1416-26. doi: 10.1111/irv.12146. Epub 2013 Aug 9.
In patients with A(H1N1)pdm09 infection, severe lung involvement requiring admission to intensive care units (ICU) has been reported. Mutations at the hemagglutinin (HA) receptor binding site (RBS) have been associated with increased virulence and disease severity, representing a potential marker of critical illness.
To assess the contribution of HA-RBS variability in critically ill patients, A(H1N1)pdm09 virus from adult patients with severe infection admitted to ICU for extracorporeal membrane oxygenation support (ECMO) during influenza season 2009-2011 in Piemonte (4·2 million inhabitants), northwestern Italy, was studied.
We retrospectively analyzed HA-RBS polymorphisms in ICU patients and compared with those from randomly selected inpatients with mild A(H1N1)pdm09 disease and outpatients with influenza from the local surveillance program.
By HA-RBS direct sequencing of respiratory specimens, D222G and D222N viral variants were identified in a higher proportion in ICU patients (n=8/24, 33·3%) than in patients with mild disease (n=2/34, 6%) or in outpatients (n=0/44) (Fisher's exact test P<0·0001; OR 38·5; CI 95% 4·494-329·9). Eleven ICU patients died (42%), three of them carrying the D222G variant, which was associated with RBS mutation S183P in two. D222G and D222N mutants were identified in upper and lower respiratory samples.
A(H1N1)pdm09 HA substitutions D222G and D222N were harbored in a significantly higher proportion by patients with acute respiratory distress for A(H1N1)pdm09 severe infection requiring ICU admission and ECMO. These data emphasize the importance of monitoring viral evolution for understanding virus-host adaptation aimed at the surveillance of strain circulation and the study of viral correlates of disease severity.
在 A(H1N1)pdm09 感染患者中，已报告有严重肺部受累需要入住重症监护病房（ICU）的病例。血凝素（HA）受体结合部位（RBS）的突变与毒力增加和疾病严重程度相关，是重症疾病的潜在标志物。
评估 HA-RBS 变异性在重症患者中的作用，对意大利西北部皮埃蒙特地区（420 万居民）2009-2011 年流感季节期间因体外膜氧合（ECMO）支持而入住 ICU 的严重感染成年 A(H1N1)pdm09 病毒患者的病毒进行研究。
我们回顾性分析了 ICU 患者的 HA-RBS 多态性，并与随机选择的轻症 A(H1N1)pdm09 患者和当地监测计划中的流感门诊患者进行比较。
通过对呼吸道标本的 HA-RBS 直接测序，在 ICU 患者（n=24，33·3%）中鉴定出 D222G 和 D222N 病毒变异株的比例高于轻症患者（n=34，6%）或门诊患者（n=44，0%）（Fisher 精确检验 P<0·0001；OR 38·5；95%CI 4·494-329·9）。11 例 ICU 患者死亡（42%），其中 3 例携带 D222G 变异株，其中 2 例与 RBS 突变 S183P 相关。D222G 和 D222N 突变株在上、下呼吸道样本中均有检出。
在因 A(H1N1)pdm09 严重感染而需要入住 ICU 并接受 ECMO 的急性呼吸窘迫患者中，A(H1N1)pdm09 HA 取代 D222G 和 D222N 的比例明显更高。这些数据强调了监测病毒进化以了解病毒-宿主适应的重要性，目的是监测病毒株的循环和研究疾病严重程度的病毒相关性。
