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.     

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。     

Prevalence of SARS-CoV-2 in human post-mortem ocular tissues

BackgroundSARS-CoV-2 is found in conjunctival swabs and tears of COVID-19 patients. However, the presence of SARS-CoV-2 has not been detected in the human eye to date. We undertook this study to analyze the prevalence of SARS-CoV-2 in human post-mortem ocular tissues.MethodsThe expression of SARS-CoV-2 RNA was assessed by RT-PCR in corneal and scleral tissues from 33 surgical-intended donors who were eliminated from a surgical use per Eye Bank Association of America (EBAA) donor screening guidelines or medical director review or positive COVID-19 test. Ocular levels of SARS-CoV-2 RNA (RT-PCR), Envelope and Spike proteins (immunohistochemistry) and anti-SARS-CoV-2 IgG and IgM antibodies (ELISA) in blood were evaluated in additional 10 research-intent COVID-19 positive donors.FindingsOf 132 ocular tissues from 33 surgical-intended donors, the positivity rate for SARS-CoV-2 RNA was ~13% (17/132). Of 10 COVID-19 donors, six had PCR positive post-mortem nasopharyngeal swabs whereas eight exhibited positive post-mortem anti-SARS-CoV-2 IgG levels. Among 20 eyes recovered from 10 COVID-19 donors: three conjunctival, one anterior corneal, five posterior corneal, and three vitreous swabs tested positive for SARS-CoV-2 RNA. SARS-CoV-2 spike and envelope proteins were detected in epithelial layer of the corneas that were procured without Povidone-Iodine (PVP–I) disinfection.InterpretationsOur study showed a small but noteworthy prevalence of SARS-CoV-2 in ocular tissues from COVID-19 donors. These findings underscore the criticality of donor screening guidelines, post-mortem nasopharyngeal PCR testing and PVP-I disinfection protocol to eliminate any tissue harboring SARS-CoV-2 being used for corneal transplantation.     

ACE2 and TMPRSS2 are expressed on the human ocular surface,suggesting susceptibility to SARS-CoV-2 infection

PurposeConjunctival signs and symptoms are observed in a subset of patients with COVID-19, and SARS-CoV-2 has been detected in tears, raising concerns regarding the eye both as a portal of entry and carrier of the virus. The purpose of this study was to determine whether ocular surface cells possess the key factors required for cellular susceptibility to SARS-CoV-2 entry/infection.MethodsWe analyzed human post-mortem eyes as well as surgical specimens for the expression of ACE2 (the receptor for SARS-CoV-2) and TMPRSS2, a cell surface-associated protease that facilitates viral entry following binding of the viral spike protein to ACE2.ResultsAcross all eye specimens, immunohistochemical analysis revealed expression of ACE2 in the conjunctiva, limbus, and cornea, with especially prominent staining in the superficial conjunctival and corneal epithelial surface. Surgical conjunctival specimens also showed expression of ACE2 in the conjunctival epithelium, especially prominent in the superficial epithelium, as well as weak or focal expression in the substantia propria. All eye and conjunctival specimens also expressed TMPRSS2. Finally, Western blot analysis of protein lysates from human corneal epithelium obtained during refractive surgery confirmed expression of ACE2 and TMPRSS2.ConclusionsTogether, these results suggest that ocular surface cells including conjunctiva are susceptible to infection by SARS-CoV-2, and could therefore serve as a portal of entry as well as a reservoir for person-to-person transmission of this virus. This highlights the importance of safety practices including face masks and ocular contact precautions in preventing the spread of COVID-19 disease.     

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。     

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。     

HIV antibody screening of corneal donors

Because of the risk of transmitting the acquired immune deficiency syndrome through corneal transplantation, health officials have recommended donor screening. We prospectively studied the seropositivity rate for human immunodeficiency virus infection among ocular tissue donors at our eye bank during 1986. Of 1,517 corneal donors, 5 (0.3%) were repeatedly reactive by enzyme immunoassay. For comparison, 131 (0.06%) of 206,415 blood donors in Houston were similarly seropositive during this same 1-year period. Routine serological testing can be successfully implemented by eye banking personnel to potentially reduce the risk of viral transmission by keratoplasty.     

Stromal and endothelial herpes simplex virus keratitis reactivation in the convalescent period of COVID-19 – A case report

A 73-year-old lady presented with a white spot and redness in the left eye for 1 month and had been treated elsewhere as a case of fungal keratitis. She had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection 2 months before. Her past ocular history and examination gave a probable diagnosis of herpetic stromal and endothelial keratitis. She responded to oral acyclovir and topical steroid, leading to resolution of stromal edema and inflammation. Anterior chamber fluid polymerase chain reaction (PCR) confirmed pathogen herpes simplex virus (HSV)-1. HSV ocular reactivation after coronavirus disease 2019 (COVID-19) has been reported currently. The present report will add knowledge about this potential opportunistic ophthalmic infection during the recovery phase of COVID-19 disease.     

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）眼表感染研究进展

严重急性呼吸综合征冠状病毒2型（SARS-CoV-2,又称COVID-19）经眼表传播远较经口鼻传播困难,然而现有证据认为眼表传播仍是一条可能的途径,尤其对于医护人员。本文描述了SARS-CoV-2相关的眼表症状,阐释了眼表SARS-CoV-2入胞的可能机制和与眼表相关的SARS-CoV-2传播机制,并对现有的和未来可能的研究方向进行了剖析,为从眼表考虑临床治疗SARS-CoV-2提供新的思路与方法,帮助人们研发出更多的治疗策略。     

从SARS冠状病毒探讨新型冠状病毒眼途径传播的可能机制

新型冠状病毒(SARS-CoV-2)自2019-12爆发以来,传播速度极快,了解其流行病学特征,尤其是切断传播途径对于控制疾病传播至关重要。在传播途径的研究中,SARS-CoV-2是否通过眼表组织进行传播的问题也引起关注,但目前尚缺乏其通过眼表组织感染的临床确诊病例和实验室证据。最新研究认为SARS-CoV-2与SARS冠状病毒(SARS-CoV)属于同一种属,并且其与SARS-CoV进入细胞的途径是一样的。本文通过回顾SARS-CoV的研究,探讨SARS-CoV-2眼途径传播的可能机制。     

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.     

COVID-19 and Eye: A Review of Ophthalmic Manifestations of COVID-19

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had health implications of unprecedented magnitude. The infection can range from asymptomatic, mild to life threatening respiratory distress. It can affect almost every organ of the body. Ophthalmologists world over are reporting various manifestations of the infection in the eye. This review was undertaken to help ophthalmologists recognize the possible manifestations and the stage of the viral disease when they commonly appear. Literature search was performed for the publications on ophthalmic manifestations of coronavirus disease-19 (COVID-19) between January 1, 2020 and January 31, 2021. 46 case reports, 8 case series, 11 cross sectional/cohort observational studies, 5 prospective interventional studies, 3 animal models/autopsy studies and 6 reviews/meta-analysis were included. Conjunctivitis is the most common manifestation and can develop at any stage of the disease. Direct effect due to virus, immune mediated tissue damage, activation of the coagulation cascade and prothrombotic state induced by the viral infection, the associated comorbidities and drugs used in the management are responsible for the findings in the eye. The viral ribonucleic acid (RNA) has been isolated from ocular tissues but the role of eye as a route for infection is yet to be substantiated. Ophthalmic manifestations may be the presenting feature of COVID-19 infection or they may develop several weeks after recovery. Ophthalmologists should be aware of the possible associations of ocular diseases with SARS-CoV-2 in order to ask relevant history, look for specific signs, advise appropriate tests and thereby mitigate the spread of infection as well as diagnose and initiate early treatment for life and vision threatening complications.     

新型冠状病毒相关眼部疾病的研究进展

2019年新型冠状病毒肺炎(COVID-19)自爆发以来已在短时间内呈现出全球大流行状态,新型冠状病毒(SARS-CoV-2)的多种变异株具有高度传染性和致病性。SARS-CoV-2可能通过血管紧张素转化酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)的介导感染组织细胞从而引发不同疾病。呼吸道、心血管、胃肠道系统的临床疾病较为常见; 也有大部分患者以眼部症状为主诉就诊。相较于严重的全身系统疾病,眼部相关症状很容易被忽视。文章通过对SARS-CoV-2相关多种眼部疾病的发病机制和相关病例进行综述,旨在增强临床医师对SARS-CoV-2相关眼病的重视,避免延误病情,造成视力的不可逆损失,并为眼部疾病的预防和治疗提供新思路。     

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。     

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。     

Current concepts and techniques in keratoprosthesis

PURPOSE OF REVIEW: Diseases affecting the cornea are a major cause of blindness worldwide, second only to cataract in overall importance, with an estimated 10 to 15 million affected people. Although keratoplasty is by far the most successful transplantation surgery, the outcomes in high-risk adult patients, including those with ocular surface diseases and multiple graft rejections, and in pediatric patients with congenital corneal opacities are disappointing. RECENT DEVELOPMENTS: Regrettably, no significant clinical developments have been achieved in the field of corneal transplantation since the introduction of steroids for graft rejection. Furthermore, obtaining donor corneal tissues and eye banking, particularly in the developing countries where corneal blindness is most prevalent, are problematic. Although the postoperative complications may be severe and limit the use of currently available devices, keratoprosthesis--artificial corneal implantation--has a role in the management of corneal blindness in carefully selected patients with complex ocular diseases who are at high risk for graft failure. SUMMARY: This article reviews the recent ophthalmic literature published on the current concepts and techniques of keratoprosthesis surgery.     

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。     

Storage, surgery, outcome, complications, and new developments in corneal and conjunctival grafts

This review covers last year's literature on corneal, limbal, and conjunctival transplantation including tissue storage and eye banking. In this area, the main themes were related to a better evaluation of tissue viability and the exclusion of disease transmission. An analysis of the changing indications for penetrating keratoplasty shows the differences between American and European series. Most efforts in relation to surgical techniques are oriented toward obtaining better refractive results, whereas the study of large series sheds new light on the risk factors for graft failure and other complications. Limbal transplants have acquired the status of a new field in the surgical treatment of ocular surface disease, particularly in relation to corneal stem cell deficiencies.     

Retinal manifestations in patients with SARS-CoV-2 infection and pathogenetic implications: a systematic review

International Ophthalmology - The pandemic of COVID-19 has been caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Apart from respiratory malfunction, COVID-19 causes...