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.     

Scar sarcoidosis with systemic involvement after blepharoplasty

AIM: To explore the ocular features of COVID-19 and SARS-CoV-2 detection in tears and conjunctival scrapes in non-severe COVID-19 patients. METHODS: This is a multicenter observational clinical study with no intervention conducted from Jan 28th to March 1st 2020. Clinical data and samples of tears and conjunctival scraping were collected in consecutive laboratory-confirmed, non-severe COVID-19 patients from three hospitals. COVID-19 virus was analyzed by real-time RT-PCR kits. RESULTS: Totally 255 laboratory-confirmed, non-severe COVID-19 patients were recruited for ocular manifestation investigation. Of them, 54.9% were females, with a median age of 49.4y. None of the patients has evidence of uveitis, 11 patients (4.3%) complained of mild asthenopia, 2 (0.8%) had mild conjunctival congestion and serous secretion. Twenty-five of them had performed tears and conjunctival scrape for COVID-19 virus detection, with 4 yield possible positive results in the N gene. One of them were asymptomatic with normal chest CT and positive pharyngeal swab result. CONCLUSION: Ocular manifestations are neither common nor specific in non-severe COVID-19 patients. Meanwhile, COVID-19 virus nucleotides can be detected in the tears and conjunctival scrape samples, warranting further research on the transmissibility by the ocular route.     

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。     

Preoperative COVID-19 testing for elective vitreoretinal surgeries: Experience from a major tertiary care institute in South India

Purpose:To study the prevalence of asymptomatic SARS-CoV-2 virus infection (COVID-19) among patients undergoing elective vitreoretinal surgeries at a tertiary care eye hospital.Methods:This cross-sectional, observational study was performed between July 16, 2020 and August 31, 2020, in the retina clinic of a tertiary care eye hospital in south India. All patients undergoing elective retinal surgical procedures underwent RT-PCR testing for SARS-CoV-2 before being posted for surgery and after obtaining informed consent. Patients planned for surgery under general anesthesia underwent additional computed tomography of the chest. Testing strategies and outcomes were documented.Results:Out of a total of 413 patients who were given appointments for surgery during this period, nine patients (2.2%) were found to have positive RT-PCR for SARS-CoV-2, and their surgeries were postponed. The test positivity (prevalence) rate of asymptomatic COVID-19 infection among all elective vitreoretinal surgical patients in our hospital was 2.2%. None of the patients were symptomatic for COVID-19.Conclusion:Our results showed that among patients visiting high volume ophthalmic centers in the near future, approximately 1 in 45 patients may be asymptomatic, SARS-CoV-2 RT-PCR positive. Asymptomatic COVID-19 patients may lead to chances of transmission of the virus inside healthcare facilities among other visiting patients and healthcare workers.     

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.     

Ophthalmic manifestations in the COVID-19 clinical spectrum

Purpose:The aim of this study was to determine the frequency and various types of ophthalmic manifestation of patients with COVID-19.Methods:This is a prospective observational study conducted on patients with SARS-Co-V-2 infection, at a dedicated tertiary COVID-19 hospital in South India from April 1 to July 31, 2020. At the time of their admission to the COVID hospital, demographic data such as name, age, sex was recorded. A thorough history regarding the onset, duration, progression, nature of symptoms and its associated factors, medication history, treatment history were elicited and documented. Ocular examination was performed under torchlight by an ophthalmologist posted for COVID duty. Further investigations including imaging were sought for, depending on clinical indications. Serial follow-up examinations of all patients were carried out every 72 hours or when patients complained of any ocular symptoms whichever earlier, until discharge. All relevant data were compiled and statistically analyzed.Results:A total of 2742 patients were examined. Of them, 1461 (53.28%) were males and 1281 (46.72%) were females. The mean age (±SD) was 39.46 ± 17.63 years. None of the patients in our study had any ocular symptoms or signs as the presenting complaint at the time of their admission. On subsequent follow-up, only 20 (0.72%) developed ocular manifestations, of which 19 (95%) had features suggestive of Bilateral viral conjunctivitis. However, 1 (5%) patient had orbital cellulitis secondary to pansinusitis.Conclusion:Ophthalmic manifestations in the clinical spectrum of COVID-19 infection are uncommon and unlikely to be the presenting clinical impression. However, it has broadened our view to a wider spectrum of COVID-19 presentations enhancing our clinical acumen for staunch detection of COVID-19 suspects in our daily practice, augmenting early diagnosis and management and also break the chain of transmission for the greater good of humanity.     

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。     

Evaluating the presence of SARS-CoV-2 in the intraocular fluid of COVID-19 patients

Purpose:To detect the presence of SARS-CoV-2 in aqueous and vitreous humor of COVID-19 patients in a pilot study.Methods:Consecutive patients planned for emergency ophthalmic surgeries after ocular trauma were subjected to naso-oropharyngeal RT-PCR test for SARS-CoV-2. Laboratory-confirmed cases were enrolled for the study. During surgery, 0.1 mL aqueous and vitreous each was aspirated. The vitreous tap was collected on clinical suspicion of endophthalmitis. RT-PCR test was used to detect SARS-COV-2 nucleotide in the samples. Cycle threshold (Ct) for E gene of ≤35 along with confirmatory results on one of the two target genes (RdRp or ORF1b) was considered as positive.Results:One hundred and thirty two patients were found positive on naso-oropharyngeal RT-PCR test for SARS-CoV-2 preoperatively. Seven patients with ocular trauma were studied. The mean age was 31.8 years. There were six male and one female patient. Two patients had symptoms of mild COVID-19 disease and the rest were asymptomatic. The mean Ct value of the E gene on naso-oropharyngeal RT-PCR was 23.14 ± 4.7. Corneal and corneoscleral laceration repair was done in five patients, intracorneal wooden foreign body was removed in one patient, and injection of intravitreal antibiotics was done in one patient. Aqueous and vitreous tap was collected in 7 and 5 patients, respectively. None of the aqueous or vitreous samples was found positive for SARS-CoV-2.Conclusion:SARS-CoV-2 was not detected by RT-PCR in aqueous or vitreous humor in this pilot study. Future studies with a larger sample size are needed to further explore the presence of SARS-CoV-2 in intraocular fluids.     

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。     

Detection of SARS-CoV-2 RNA in a conjunctival swab sample in real-time-polymerase chain reaction positive COVID-19 patients and its association with comorbidity and severity at a designated COVID-19 hospital in Central India

Purpose:To evaluate the presence of SARS-CoV-2 RNA in the conjunctival swab sample of positive confirmed COVID-19 patients and to find out its association with comorbidity and severity of COVID-19 disease.Methods:We conducted an observational cross-sectional study at a dedicated tertiary COVID-19 hospital in central India for a period of 8 weeks from February 2021to March 2021. We included patients who tested positive for SARS-CoV-2 RNA through nasopharyngeal swab and were above 18 years of age. Swab samples have been collected within 48 h of admission. Conjunctival swab was taken from the lower fornix of both eyes and sent to microbiology laboratory for real-time- polymerase chain reaction (RT-PCR).Results:Out of 150 patients, conjunctival swab RT-PCR was positive in five patients (3.33%). Two patients had conjunctival manifestations in the form of conjunctivitis but conjunctival swab RT-PCR was negative in those patients. Among the RT-PCR positive patients, two (40%) were from mild, one (20%) was from moderate, and two (40%) were from severe category. No association could be established between conjunctival swab RT-PCR positivity and severity of the disease or associated comorbidity.Conclusion:Our study provides evidence that SARS-CoV-2 RNA could be detected in conjunctival secretions, and though the risk is relatively low, the eye may act as source of transmission. Extra caution should be taken by healthcare workers, and use of proper precautions like face shields and goggles should be encouraged.     

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。     

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.     

Ocular manifestations and SARS-CoV-2 detection in tears and conjunctival scrape from non-severe COVID-19 patients

AIM: To investigate whether the axial length (AL)/total corneal refractive power (TCRP) ratio is a sensitive and simple factor that can be used for the early diagnosis of Marfan syndrome (MFS) in children. METHODS: The relationship between the AL/TCRP ratio and the diagnosis of MFS for 192 eyes in 97 children were determined. The biological characteristics, including age, sex, AL, and TCRP, were collected from medical records. Receiver operating characteristic (ROC) curve analysis was performed to investigate whether the AL/TCRP ratio effectively distinguishes MFS from other subjects. The Youden index was used to re-divide the whole population into two groups according to an AL/TCRP ratio of 0.59. RESULTS: Of 96 subjects evaluated, 56 (110 eyes) had a definite diagnosis of MFS in childhood based on the revised Ghent criteria, 41 (82 eyes) with diagnosis of congenital EL were included as a control group. AL was negatively correlated with TCRP, with a linear regression coefficient of -0.3566 (r=0.081). A significant correlation was found between age and the AL/TCRP ratio (P=0.023). ROC curve analysis showed that the AL/TCRP ratio distinguished MFS from the other subjects at a threshold of 0.59. MFS patients were present in 24/58 (41.38%) subjects with an AL/TCRP ratio of <0.6 and in 34/39 (87.18%) subjects with an AL/TCRP ratio of ≥0.6.CONCLUSIONS: An AL/TCRP ratio of ≥0.59 is significantly associated with the risk of MFS. The AL/TCRP ratio should be measured as a promising marker for the prognosis of children MFS. Changes in the AL/TCRP ratio should be monitored over time.     

Impacto de la infección por el nuevo coronavirus en los pacientes con uveítis asociada a una enfermedad autoinmune: resultado de la encuesta COVID-19-GEAS pacientes

IntroductionThe objetive of these study is to know the characteristics of COVID-19 in patients with uveitis associated with Systemic Autoimmune Disease (SAD) through telematic survey.Material and methodsInternal Medicine Society and Group of Systemic Autoimmune disease conducted a telematic survey of patients with SAD to learn about the characteristics of COVID-19 in this population.ResultsA total of 2,789 patients answered the survey, of which 28 had a diagnosis of uveitis associated with SAE. The majority (82%) were female and caucasian (82%), with a mean age of 48 years. The most frequent SAEs were Behçet's disease followed by sarcoidosis and systemic lupus erythematosus. 46% of the patients were receiving corticosteroid treatment at a mean prednisone dose of 11 mg/day. Regarding infection, 14 (50%) patients reported symptoms compatible with SARS-CoV-2 infection. RT-PCR was performed on the nasopharyngeal smear in two patients and in one of them (4%) it was positive.ConclusionsBoth asymptomatic and symptomatic COVID-19 patients with ASD-associated UNI had received similar immunosuppressive treatment.     

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）     

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.     

Cilioretinal artery occlusion with paracentral acute middle maculopathy associated with COVID-19

The purpose of the study is to describe cilioretinal artery (CILRA) occlusion that is presumed to be associated with COVID-19 without severe respiratory distress and inform ophthalmologists of unusual ocular presentations of COVID-19. Here, we present the first case of a patient with isolated CILRA occlusion and paracentral acute middle maculopathy (PAMM) after recently polymerase chain reaction-proven COVID-19. A 26-year-old female patient presented with a visual field defect in her left eye for 2 days and decreased vision compared to her right eye. It was learned that the patient had a laboratory-proven COVID-19 infection with mild respiratory symptoms that did not require hospitalization 2 weeks ago. Fundus examination revealed retinal edema in the left eye area supplied by the CILRA. Spectral-domain optical coherence tomography revealed a prominent hyperreflective band at the inner nuclear layer level. These findings led us to the diagnosis of isolated CILRA occlusion and PAMM associated with recent COVID-19. CILRA occlusion and PAMM could be associated with the inflammatory and procoagulant condition caused by the SARS-CoV-2 infection.