PURPOSE

To determine characteristics of conjunctivitis associated with human adenovirus E4 (AdV E4)

METHODS

Samples and outcomes from 500 conjunctivitis patients were obtained from the NVC-422 randomized controlled clinical trial comparing auricloscene to placebo. Molecular typing identified 36 cases associated with AdV E4. Signs and symptoms at presentation and day 18 endpoint were compared with the larger cohort of 262 subjects with conjunctivitis due to AdV D8. Full viral genomes of 22 AdV E4 isolates were reconstructed.

RESULTS

AdV E4 was the most frequently identified adenoviral type in conjunctivitis cases from the US. Signs and symptoms at presentation were comparable to those associated with AdV D8. Viral load at presentation was comparable between groups but resolution was more rapid in the AdV E4 group. Clinical signs were fully resolved by day 18 in 26/36 (72%) patients with AdV E4. Subepithelial infiltrates developed in 12/36 (33%) of patients with AdV E4 compared with 98/215 (45%) of patients with AdV D8 (p = 0.0001). 124 polymorphisms were observed among 22 whole viral genome sequences, which clustered into three clades. Patients in each clade developed subepithelial infiltrates. Neither single nucleotide polymorphism analysis nor machine learning approaches identified specific sequence features predictive of presenting signs or outcome.

CONCLUSIONS

AdV E4 conjunctivitis may be indistinguishable at presentation from AdV D8-associated disease. Resolution of viral load for AdV E4 appears more rapid than for AdV D8, and risk for subepithelial infiltrates appears lower. Multiple substrains of AdV E4 are in circulation but all appeared equivalently pathogenic for conjunctivitis.

中文翻译：

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人腺病毒 E4 相关结膜炎的分子和临床特征

目的

确定与人类腺病毒 E4 (AdV E4) 相关的结膜炎的特征

方法

来自 500 名结膜炎患者的样本和结果是从 NVC-422 随机对照临床试验中获得的，该试验将 auricloscene 与安慰剂进行了比较。分子分型确定了 36 例与 AdV E4 相关的病例。将就诊时和第 18 天终点时的体征和症状与 262 名因 AdV D8 引起的结膜炎受试者的较大队列进行比较。重建了 22 个 AdV E4 分离株的完整病毒基因组。

结果

AdV E4 是美国结膜炎病例中最常见的腺病毒类型。就诊时的体征和症状与 AdV D8 相关。出现时的病毒载量在各组之间具有可比性，但 AdV E4 组的消退速度更快。26/36 (72%) AdV E4 患者的临床症状在第 18 天完全消失。12/36 (33%) AdV E4 患者出现上皮下浸润，而 AdV D8 患者为 98/215 (45%) (p = 0.0001)。在22个全病毒基因组序列中观察到124个多态性，它们聚集成三个进化枝。每个进化枝中的患者出现上皮下浸润。单核苷酸多态性分析和机器学习方法都没有识别出预测出现迹象或结果的特定序列特征。

结论

AdV E4 结膜炎在就诊时可能与 AdV D8 相关疾病无法区分。AdV E4 的病毒载量消退似乎比 AdV D8 更快，并且上皮下浸润的风险似乎更低。AdV E4 的多种亚株在循环中，但都表现出对结膜炎具有同等致病性。