The paradoxical problem with COVID-19 ocular infection: Moderate clinical manifestation and potential infection risk

Shen, Jiawei; Wu, Jian; Yang, Yang; Wang, Pengcheng; Luo, Tao; Guo, Yanju; Zhao, Jun; Dai, Wei; Han, Ying; Zhu, Peiran; Wu, Qiuyue; Li, Weiwei; Chen, Andrew; Xue, Cong; Xia, Xinyi

doi:10.1016/j.csbj.2021.01.039

Cited by 9 publications

(10 citation statements)

References 47 publications

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“…Confirming previous reports, we noticed a striking expression of CK18 in the optical nerve and in the retinal pigment epithelium of the retina (RPE; Figure 1 d); this was also found in the different secretary glands, such as in the cells composing the Harderian ( Figure 1 g) and intraorbital lacrimal glands ( Figure 1 h) [ 62 , 63 ]. Interestingly, we observed that the expression of ACE2 was highly correlated with the expression of CK18, as we found its expression to be mainly restricted to the RPE layer of the retina ( Figure 1 d), to the lumen of the tubular alveoli of the Harderian glands ( Figure 1 g), to the lumen of the acini cells composing the intraorbital lacrimal glands [ 64 ] ( Figure 1 h), as well as to the optical nerve ( Figure 1 d); this confirmed recent evidence of SARS-CoV-2 tropism in humanized mice [ 61 ]. Background signals were assessed by negative controls, and they demonstrated the specificity of our CK18/ACE2 stainings ( Figure 1 f,i).…”

Section: Resultsmentioning

confidence: 99%

Ocular Symptoms Associated with COVID-19 Are Correlated with the Expression Profile of Mouse SARS-CoV-2 Binding Sites

Brechbühl

Ferreira

Lópes

et al. 2023

Viruses

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The COVID-19 pandemic has engendered significant scientific efforts in the understanding of its infectious agent SARS-CoV-2 and of its associated symptoms. A peculiar characteristic of this virus lies in its ability to challenge our senses, as its infection can lead to anosmia and ageusia. While ocular symptoms, such as conjunctivitis, optic neuritis or dry eyes, are also reported after viral infection, they have lower frequencies and severities, and their functional development is still elusive. Here, using combined technical approaches based on histological and gene profiling methods, we characterized the expression of SARS-CoV-2 binding sites (Ace2/Tmprss2) in the mouse eye. We found that ACE2 was ectopically expressed in subtissular ocular regions, such as in the optic nerve and in the Harderian/intraorbital lacrimal glands. Moreover, we observed an important variation of Ace2/Tmprss2 expression that is not only dependent on the age and sex of the animal, but also highly heterogenous between individuals. Our results thus give new insight into the expression of SARS-CoV-2 binding sites in the mouse eye and propose an interpretation of the human ocular-associated symptoms linked to SARS-CoV-2.

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Section: Resultsmentioning

confidence: 99%

Ocular Symptoms Associated with COVID-19 Are Correlated with the Expression Profile of Mouse SARS-CoV-2 Binding Sites

Brechbühl

Ferreira

Lópes

et al. 2023

Viruses

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“…On the basis of previous experimental [29,30] and human [31] studies one can consider a secondary conjunctival infection due to spreading of infection along mucus membranes. Also, human studies have shown that ACE2 and other SARS-CoV-2 co-receptors are expressed in human ocular tissues [31] and that certain diseases can change protein expressions.…”

Section: Discussionmentioning

confidence: 99%

Presence of SARS-CoV-2 on the conjunctival mucosa in patients hospitalized due to COVID-19: Pathophysiological considerations and therapeutic implications

Végh

Csorba

Koller

et al. 2022

PhysInt

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IntroductionCoronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide pandemic, due to its great capacity to invade the human body. Previous studies have shown that the primary route of invasion of this virus is the human respiratory tract via the co-expression of ACE2 receptor and TMPRSS2, a serine protease on the cellular surface. Interestingly, this condition is present not only on the respiratory epithelium but on the conjunctival mucosa, as well. Thus, we hypothesized that SARS-CoV-2 is present on the conjunctival mucosa.AimTo prove that SARS-CoV-2 can be detected in the conjunctiva.MethodsPreviously nasopharyngeal swab-sample based real-time polymerase chain reaction (PCR) positive COVID-19 infected patients were selected at the COVID Care Centers of Semmelweis University, Budapest, Hungary. The study was approved by the ethical committee of Semmelweis University. During their recovery, both nasopharyngeal and conjunctival swab-samples were taken and PCR method was used to detect the presence of SARS-CoV-2 RNA. Appropriate statistical analysis was performed.ResultsThe study population consisted of 97 patients, 49 females (50.5%) and 48 males (49.5%), with a mean age of 67.2 ± 11.9 years. During recovery, with nasopharyngeal swabs, the PCR test was positive in 55 cases (56.70%), whereas with conjunctival swabs it was positive in 8 cases (8.25%). Both tests were positive in 5 cases (5.15%). In some patients, ocular symptoms were observed as well. The rest of the patients (29 cases) had negative nasopharyngeal PCR tests during recovery.ConclusionsAlthough only in few cases, the data of the present study provides a proof of concept that SARS-CoV-2 can be present on the conjunctival mucosa even in nasopharyngeal negative patients, a finding, which can have clinical importance. Also, on the basis of these findings one can hypothesize that - in addition to the respiratory tract – the conjunctiva can be an entrance route for SARS-CoV-2 to the human body. Thus, in high-risk conditions, in addition to covering the mouth and nose with mask, the protection of the eyes is also strongly recommended.

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“…Another investigation reported that coexpression of ACE2, TMPRSS2, and mitochondrial genes could make cornea a potential and important contributor for the viral infection [49]. It seemed that, despite having a considerable concentration of proteases, SARS-CoV-2-associated conjunctivitis is rare while conjunctiva and cornea can be responsible for the transmission of the virus [50]. On the other hand, different types of cells express TMPRSS2 gene in the olfactory epithelium [30].…”

Section: Ocular and Olfactory Systemmentioning

confidence: 99%

A Review on Expression, Pathological Roles, and Inhibition of TMPRSS2, the Serine Protease Responsible for SARS-CoV-2 Spike Protein Activation

et al. 2021

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SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, uses the host cell membrane receptor angiotensin-converting enzyme 2 (ACE2) for anchoring its spike protein, and the subsequent membrane fusion process is facilitated by host membrane proteases. Recent studies have shown that transmembrane serine protease 2 (TMPRSS2), a protease known for similar role in previous coronavirus infections, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS), is responsible for the proteolytic cleavage of the SARS-CoV-2 spike protein, enabling host cell fusion of the virus. TMPRSS2 is known to be expressed in the epithelial cells of different sites including gastrointestinal, respiratory, and genitourinary system. The infection site of the SARS-CoV-2 correlates with the coexpression sites of ACE2 and TMPRSS2. Besides, age-, sex-, and comorbidity-associated variation in infection rate correlates with the expression rate of TMPRSS2 in those groups. These findings provide valid reasons for the assumption that inhibiting TMPRSS2 can have a beneficial effect in reducing the cellular entry of the virus, ultimately affecting the infection rate and case severity. Several drug development studies are going on to develop potential inhibitors of the protease, using both conventional and computational approaches. Complete understanding of the biological roles of TMPRSS2 is necessary before such therapies are applied.

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The paradoxical problem with COVID-19 ocular infection: Moderate clinical manifestation and potential infection risk

Cited by 9 publications

References 47 publications

Ocular Symptoms Associated with COVID-19 Are Correlated with the Expression Profile of Mouse SARS-CoV-2 Binding Sites

Ocular Symptoms Associated with COVID-19 Are Correlated with the Expression Profile of Mouse SARS-CoV-2 Binding Sites

Presence of SARS-CoV-2 on the conjunctival mucosa in patients hospitalized due to COVID-19: Pathophysiological considerations and therapeutic implications

A Review on Expression, Pathological Roles, and Inhibition of TMPRSS2, the Serine Protease Responsible for SARS-CoV-2 Spike Protein Activation

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