新型冠状病毒感染及其疫苗接种相关的眼科疾病

由新型冠状病毒(严重呼吸综合征-冠状病毒-2型,SARS-CoV-2)引起的新型冠状病毒肺炎(COVID-19),因其极高的传染致病性,严重威胁人类的生命健康,同时也给目前的医疗模式带来全新挑战。已有众多文献资料显示SARS-CoV-2感染不仅可以造成肺脏、肾脏、肠道等全身损害,而且也能累及眼组织,从较为常见的眼表疾病如角膜、结膜、巩膜炎症,到相对少见的旁中心急性中层黄斑病变和急性黄斑神经视网膜病变。对以眼部症状为首发或伴随症状的SARS-CoV-2感染患者而言,眼科医生如何甄别眼部表现与SARS-CoV-2感染之间的相关性无疑面临严峻的挑战。本文将结合近年相关文献,探讨由SARS-CoV-2感染和接种新型冠状病毒肺炎疫苗所引起的相关眼部病变,涵盖了眼表、葡萄膜、视网膜和黄斑以及颅神经等病理改变。     

SARS-CoV和SARS-CoV-2两种高致病性冠状病毒眼部感染的研究进展

COVID-19的全球大流行使冠状病毒再次引起重视。在本世纪大流行的三种高致病性冠状病毒（SARS-CoV、MERS-CoV、SARS-CoV-2）研究中,已有直接证据证明SARS-CoV及SARS-CoV-2可引起人眼部感染。冠状病毒感染除引起眼部症状外,也可通过眼部感染引发全身多种临床表现。两种高致病性冠状病毒（SARS-CoV和SARS-CoV-2）具有更强的流行性及更高的病死率,两种病毒眼部症状相似,病毒结构及眼部感染过程也具有相似性,主要是通过其特异性S蛋白与细胞表面相关受体结合,使其核酸进入细胞内并借用细胞内的蛋白合成通路对自身蛋白进行转录、组装、折叠并通过其受体蛋白激发多种细胞因子表达。本文就2003年流行的SARS-CoV以及2019年末流行的SARS-CoV-2两种高致病性冠状病毒的特点、眼部感染通路的研究进展及病毒眼部感染相关的研究现状进行综述,阐述眼部病毒防护及患者眼部检查的必要性。（国际眼科纵览,2020, 45：374-379）     

冠状病毒眼部感染及检测

自严重急性呼吸综合征冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)感染爆发以来,冠状病毒病原体研究和宿主生物鉴定一直是医学界的重要任务。2019年出现的新型冠状病毒(SARS-CoV-2)传染性和致病能力更强,迅速引起了全球的关注。目前已有临床报道冠状病毒感染患者可出现以结膜炎为主的眼部感染症状,并提出将眼部核酸检测等作为病毒早期鉴定的辅助手段。本文综述冠状病毒的眼部感染及其检测相关进展,以期为冠状病毒的进一步研究和防护提供参考。     

充分认识COVID-19相关眼部损害, 努力提高诊疗水平

由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的新型冠状病毒感染(COVID-19)在全球持续大流行, 给全球医疗模式带来了深刻影响, 更多积累的、新的医学资料提示SARS-CoV-2感染会侵犯患者多个器官, 但对其引起的眼部相关病变特征及其危害仍缺乏足够认识。已有的临床资料发现, COVID-19相关眼病主要包括眼表炎性病变和眼后节的视网膜、脉络膜病变, 疾病不仅表现为急性炎性反应过程, 还可导致视网膜和脉络膜的微血管栓塞性病理过程, 给患者, 尤其是首诊为眼科的患者视力预后可能带来长期影响, 准确诊断COVID-19相关眼病是眼科医生面临的挑战。眼科医生应深入了解SARS-CoV-2感染者眼病相关疾病的发生机制和发展规律, 利用目前的眼科多模式影像检查以减少患者相关眼部疾病的漏诊和误诊, 及时采取针对性治疗措施, 尽可能降低疾病对视功能损害的风险。建议眼科临床工作者开展相关疾病的发病机制研究及多学科临床研究, 以降低COVID-19相关眼病患者的致盲率, 改善患者的生活质量。     

SARS-CoV-2对眼部的影响及其经眼途径传播的可能性

SARS-CoV-2引起的新型冠状病毒肺炎（COVID-19）已对全球构成重大的公共卫生威胁。SARS-CoV-2和SARS-CoV均属于人冠状病毒（HCoVs）β属,两者的基因组相似性高达79.6%,且均通过血管紧张素转换酶2（ACE-2）感染宿主细胞。目前已有研究表明,SARS-CoV-2感染与结膜炎具有一定相关性,SARS-CoV-2是否能经眼感染或传播的问题也备受关注,但目前尚缺乏其通过眼部组织感染的临床确诊病例和实验室证据。本文就SARS-CoV-2的病原学特点、流行病学特征、眼部表现及结膜囊病毒感染率作一综述,并对SARS-CoV-2经眼途径传播的可能性进行探讨。     

关注新型冠状病毒肺炎与眼表传播问题

自2019年岁末以来,新型冠状病毒感染的肺炎(COVID-19)疫情在中国武汉快速传播并引起中国和国际社会的广泛关注。目前已有尚未确认的线索认为结膜可能是新型冠状病毒(SARS-CoV-2)感染的通道之一,因此关于COVID-19感染方式以及SARS-CoV-2是否通过眼表组织进行传播的问题也成为新的关注点。由于目前尚缺乏SARS-CoV-2在眼部感染的临床观察资料和实验室研究证据,因此对引起流行性疾病的病毒引起眼部病变的部分文献进行回溯和分析则更有助于我们在COVID-19疫情防控过程中对眼部及相应的工作环境和器械采取合理的防护措施。     

警惕冠状病毒经眼传播

目前新型冠状病毒肺炎(COVID-19)疫情在中国湖北武汉快速传播,并引起了国际社会的广泛关注。目前有线索认为结膜可能是新型冠状病毒(SARS-CoV-2)感染的入口之一。但目前缺乏SARS-CoV-2眼部感染的临床观察资料,因此了解冠状病毒经眼传播的机制和细胞受体,了解其他同源病毒感染眼部的传播特征,有助于眼科医生在COVID-19防控工作中采取合理防护措施并及时识别与眼部体征并存的COVID-19。     

新型冠状病毒疫苗相关眼部病变的研究进展

2019年以来,新型冠状病毒(SARS-CoV-2)感染在世界范围内广泛流行,造成约7.7亿人感染和690万人死亡。目前针对SARS-CoV-2感染的疫苗已经成为预防重症SARS-CoV-2发生的主要方法。SARS-CoV-2疫苗对于预防重症SARS-CoV-2感染具有实质性保护作用,但使用SARS-CoV-2疫苗后会出现全身多处的不良反应。越来越多的研究表明SARS-CoV-2疫苗可引起眼部结膜、角膜、巩膜、葡萄膜、视网膜、视神经组织的病变,造成视觉功能的损害。文章主要回顾分析了SARS-CoV-2疫苗的分类和特性及其与眼部组织病变的相关研究,期望能更加深刻地认识SARS-CoV-2疫苗引起的眼部不良反应,为防治其造成的眼组织损伤和视功能损害提供一些理论性指导。     

新型冠状病毒肺炎的眼部表现

新型冠状病毒肺炎(coronavirus disease 2019,COVID-19,新冠肺炎)是由新型冠状病毒(novel coronavirus,SARS-CoV-2,新冠病毒)引起的一种具有高度传染性的疾病,目前在世界各地广泛流行,并引起全球性恐慌。研究表明,新冠病毒可以通过眼部黏膜传播,因此眼科医务人员更容易受到感染。新冠肺炎患者眼部表现主要累及结膜、角膜、巩膜、前房、瞳孔、视网膜、视神经和视皮层、眼外肌及其颅神经支配、眼眶和泪器系统等。病毒性结膜炎是新冠肺炎患者最常见的眼部表现。新冠肺炎流行期间,为了眼科医务人员免受感染,安全地开展临床工作,本文依据近年来相关文献报道总结了新冠肺炎的眼部表现,主要包括流行病学、病理生理、临床表现等方面。     

新型冠状病毒受体血管紧张素转化酶2在眼组织表达及分布的研究进展

2019年以来,新型冠状病毒(2019-nCoV,也被称为SARS-CoV-2)在全世界范围内引起了数亿人感染,造成数百万人死亡,对人类健康及社会经济带来了极大的威胁。随着对SARS-CoV-2不断深入的研究,血管紧张素转化酶2(ACE2)被认为是SARS-CoV-2入侵人体的重要功能受体。ACE2在人体多个组织部位都有分布,不仅表达于肺、心血管、肾脏组织,而且也表达于眼部的结膜、角膜、葡萄膜、视网膜和视神经等组织。越来越多的研究发现SARS-CoV-2通过眼部感染的病例,然而眼部ACE2是否在SARS-CoV-2感染过程中发挥作用尚不完全明确,因此探讨ACE2在眼组织中的表达及分布,不但可以深入了解SARS-CoV-2感染的机制,也可以全面认识ACE2在眼组织的作用机制。本文综述关于ACE2在眼组织表达及分布的研究进展,期望能更好地理解ACE2在眼组织病理生理过程中的作用机制。     

Insights on the possibility of SARS-CoV-2 transmission through the eyes

A novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCOV), causing coronavirus disease 2019 (COVID-19), has rapidly spread to most countries and regions worldwide since it broke out at the end of 2019. Epidemic of the virus produces a tremendous pressure on the global health systems. With progressive insight into SARS-CoV-2, the role of eye tissue has attracted wide attention in the spread of COVID-19. Whether SARS-CoV-2 can enter the human body through eyes and cause infection? The fact that unprotected exposure of the eyes to 2019-nCoV might have allowed the virus to infect the body implies that 2019-nCOV can invade eye tissue and set foot in organism. Facing the severe challenge of preventing spread of the COVID-19, combined with the high-risk environment of ophthalmology, it is crucial to investigate ocular tropism of coronavirus. This paper explores the possibility of coronavirus transmission through the eye from aspects of probable mechanisms, clinical cases, detection of coronavirus; and puts forward precautions for ophthalmologists and nurses. Consequently, this review reveals our understanding of ocular tropism of coronavirus and contributes to determining risk of ocular transmission, raising awareness of necessary eye protection among medical workers and reducing further prevalence of SARS-CoV-2.     

Retinal vein occlusion in COVID-19: A novel entity

Coronavirus disease 2019 (COVID-19) is a form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been declared a pandemic by the World Health Organization (WHO). Ocular manifestations related to COVID-19 are uncommon with conjunctivitis being reported in a few cases. We report a unique case of vasculitic retinal vein occlusion (RVO) secondary to COVID-19 in a 52-year-old patient who presented with the diminution of vision in the left eye 10 days after he tested positive for SARS-CoV-2. All investigations for vasculitis were negative. This case supports the mechanism of thrombo-inflammatory state secondary to the “cytokine-storm” as the pathogenesis for systemic manifestations of COVID-19.     

SARS-CoV-2经结膜感染与结膜炎研究述评

当前因新型冠状病毒(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2)引起的新型冠状病毒感染的肺炎(corona virus disease 2019,COVID-19)在我国传播乃至全球爆发,快速蔓延至世界各国,严重威胁世界人民的生命安全与健康。由于特效药物的缺失,积极预防仍是目前抵御COVID-19的有效方法。临床观察发现COVID-19患者可并发结膜炎,动物实验也证实结膜是SARS-CoV-2传播的途径之一。但已有的研究结果存在明显差异性,SARS-CoV-2感染与结膜炎发生的关系也未阐明。所以本文结合目前最新的研究和报道,通过各项分析研究结果,进一步阐述SARS-CoV-2感染与结膜及结膜炎的关系,探讨结膜作为SARS-CoV-2传播途径之一对于该病防护的意义,为该病与眼表关系的研究和临床判读提供帮助。     

Lysozyme Protects Against Severe Acute Respiratory Syndrome Coronavirus 2 Infection and Inflammation in Human Corneal Epithelial Cells

PurposeThe purpose of this study was to investigate the effects of lysozyme, an antimicrobial enzyme found in tears that protects the eye against pathogens, on pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through corneal epithelial cells.MethodsThe expression of the angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease (TMPRSS2) in human corneal epithelial cells (HCECs) was measured by RT-PCR and Western blotting. The altered expression of the pro-inflammatory molecules induced by spike protein and lysozyme was analyzed by RT-PCR. Cell toxicity was tested by CCK8 assay. The cell entry of SAR-CoV-2 in HCECs and primary rabbit corneal epithelial cells (RbCECs) was detected by luciferase assay.ResultsACE2 and TMPRSS2 were highly expressed in HCECs. The spike proteins of SARS-CoV-2 stimulated a robust inflammatory response in HCECs, characterized by increased secretion of pro-inflammatory molecules, including IL-6, TNF-α, iNOS, and MCP-1, and pretreatment with lysozyme in HCECs markedly decreased the production of proinflammatory molecules induced by spike proteins. In addition, the inflammatory cytokine TNF-α enhanced the entry of SARS-CoV-2 into HCECs, which can be mitigated by pretreatment with lysozyme.ConclusionsIn this study, we analyzed the susceptibility of human corneal epithelial cells to SARS-CoV-2 infection and suggested the protective effects of lysozyme on SARS-CoV-2 infection.     

Nasal vein occlusion after COVID-19: A case report

To present a case of nasal vein occlusion that has not been reported after the coronavirus disease 2019 (Covid-19) pandemic. A 53-year-old patient reported a complaint of floaters after a recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. His best corrected visual acuity (BCVA) was 20/20 for both the eyes. On examination, a flame-shaped hemorrhage was observed in the left eye around the infero-nasal area adjacent to the optic disc. Temporal branch vein occlusion has been widely reported in association with SARS-CoV-2 infection. We emphasize that nasal vein occlusions triggered by Covid-19, which do not cause vision loss, should also be considered.     

Dry eye disease among patients infected with the SARS-CoV-2 Omicron variant: a cross-sectional study

AIM: To investigate the incidence of dry eye disease (DED) and relevant risk factors among patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: This cross-sectional, observational analysis included 993 patients with corona virus disease 2019 (COVID-19) treated at the National Exhibition and Convention Center (Shanghai) Fangcang Shelter Hospital, from April 10 to May 26, 2022. Totally 944 uninfected control participants were recruited. All participants completed ocular surface disease index (OSDI) questionnaires, and DED symptoms were determined using OSDI scores. The demographic characteristics, length of hospital stay and in nasopharyngeal swabs were performed using questionnaires. SARS-CoV-2 Omicron variant infection was confirmed by nucleic acid-based detection in nasopharyngeal swabs using a 2019-nCoV nucleic acid detection kit. The risk factors for DED symptoms among patients with COVID-19 and control participants were determined by logistic regression analysis. RESULTS: Patients with COVID-19 showed a higher incidence of DED than controls (64.9% vs 55.1%, P<0.001). SARS-CoV-2 infection [odds ratios (ORs) (95%CI): 1.271 (1.038, 1.556)], use of contact lenses [ORs (95%CI): 9.350 (3.676, 23.783)], history of corneal refractive surgery [ORs (95%CI): 2.047 (1.494, 2.804)], poor sleep quality [ORs (95%CI): 2.657 (2.029, 3.480)], and video display terminal (VDT) use for more than 8h per day [ORs (95%CI): 6.348 (4.720, 8.538)] were found to be risk factors for DED symptoms in patients with COVID-19 as well as controls. For patients with COVID-19, the length of hospital stay [ORs (95%CI): 1.196 (1.134, 1.262)], use of contact lenses [ORs (95%CI): 20.423 (2.680, 155.632)], history of corneal refractive surgery [ORs (95%CI): 2.166 (1.321, 3.553)], poor sleep quality [ORs (95%CI): 3.650 (2.381, 5.597)], and VDT use for more than 8h per day [ORs (95%CI): 7.740 (4.918, 12.180)] were significant risk factors for DED symptoms. CONCLUSION: Patients with COVID-19 are more prone to develop symptomatic DED. SARS-CoV-2 infection and length of hospital stay are important risk factors for DED symptoms.