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1.
Viruses ; 14(7)2022 06 30.
Article in English | MEDLINE | ID: covidwho-1917791

ABSTRACT

Infectious diseases of the conjunctiva and cornea usually leave behind both broad local and systemic immunity. Case reports of SARS-CoV-2-positive conjunctivitis with subsequent systemic immunity suggest a new route of immunization preventing the primary infection of the airways. MATERIAL AND METHODS: A total of 24 Syrian field hamsters were treated. In systematic animal experiments, we infected the eyes of n = 8 animals (group 1) and the airways of another n = 8 animals (group 2) with SARS-CoV-2 (Wuhan type); n = 8 hamsters served as controls (group 3). The weight development of the animals was recorded. After two weeks of observation of disease symptoms, all animals were re-exposed to SARS-CoV-2 in the respiratory tract (challenge) to determine whether immunity to the virus had been achieved. RESULTS: The epi-ocularly infected animals (group 1) showed no clinically visible disease during the ocular infection phase. At most, there was a slightly reduced weight gain compared to the control group (group 3), while the respiratory infected animals (group 2) all lost weight, became lethargic, and slowly recovered after two weeks. After the challenge, none of the animals in groups 1 and 2 became ill again. The animals in the negative control (group 3) all became ill. Cytotoxic antibodies were detectable in the blood of the infected groups before and after challenge, with higher titers in the epi-ocularly infected animals. CONCLUSION: By epi-ocular infection with SARS-CoV-2, the development of systemic immunity with formation of cytotoxic antibodies without severe general disease could be observed in the experimental animals, which did not induce any more disease upon a second infection in the respiratory tract. Therefore, it can be concluded that a purely epi-ocular infection with SARS-CoV2 only induces a weak disease pattern followed by systemic immunity.


Subject(s)
COVID-19 , Eye Infections , Animals , COVID-19/prevention & control , Conjunctiva , Cricetinae , Immunization , Mesocricetus , RNA, Viral , SARS-CoV-2
2.
Sci Rep ; 12(1): 7225, 2022 05 04.
Article in English | MEDLINE | ID: covidwho-1890252

ABSTRACT

Tear fluid cytokine levels may serve as biomarkers of innate immune system response against SARS-CoV-2 infection. Therefore, our aim was to analyze panel of selected inflammatory cytokines in tears of COVID-19 patients in relation to presence of SARS-CoV-2 viral load in conjunctival secretions. In this study concentrations of TNF-α, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p70, GM-CSF, and IFN-γ were determined by a magnetic bead assay in tear film collected from 232 symptomatic COVID-19 patients. SARS-CoV-2 ocular infection was confirmed based on positive conjunctival swab-based RT-PCR testing. Viral RNA in conjunctival sac was detected in 21 patients (9%). No relation between presence and the duration of ophthalmic symptoms and SARS-CoV-2 infection detected in conjunctival secretions was found. The tear film concentrations of IFN-γ, TNF-α, IL-5, IL-8 and GM-CSF were found to be significantly greater among patients with positive conjunctival swab results as compared to the group negative for SARS-CoV-2 in conjunctival sac. Our current data depict a group of inflammatory mediators in human tears, which may play a significant role in ocular pathology of SARS-CoV-2 conjunctival infection.


Subject(s)
COVID-19 , Conjunctiva , Cytokines , Granulocyte-Macrophage Colony-Stimulating Factor , Humans , Interleukin-5 , Interleukin-8 , SARS-CoV-2 , Tears , Tumor Necrosis Factor-alpha
4.
Graefes Arch Clin Exp Ophthalmol ; 260(5): 1789-1797, 2022 May.
Article in English | MEDLINE | ID: covidwho-1787813

ABSTRACT

PURPOSE: To detect SARS-CoV-2 RNA in post-mortem human eyes. Ocular symptoms are common in patients with COVID-19. In some cases, they can occur before the onset of respiratory and other symptoms. Accordingly, SARS-CoV-2 RNA has been detected in conjunctival samples and tear film of patients suffering from COVID-19. However, the detection and clinical relevance of intravitreal SARS-CoV-2 RNA still remain unclear due to so far contradictory reports in the literature. METHODS: In our study 20 patients with confirmed diagnosis of COVID-19 were evaluated post-mortem to assess the conjunctival and intraocular presence of SARS-CoV-2 RNA using sterile pulmonary and conjunctival swabs as well as intravitreal biopsies (IVB) via needle puncture. SARS-CoV-2 PCR and whole genome sequencing from the samples of the deceased patients were performed. Medical history and comorbidities of all subjects were recorded and analyzed for correlations with viral data. RESULTS: SARS-CoV-2 RNA was detected in 10 conjunctival (50%) and 6 vitreal (30%) samples. SARS-CoV-2 whole genome sequencing showed the distribution of cases largely reflecting the frequency of circulating lineages in the Munich area at the time of examination with no preponderance of specific variants. Especially there was no association between the presence of SARS-CoV-2 RNA in IVBs and infection with the variant of concern (VOC) alpha. Viral load in bronchial samples correlated positively with load in conjunctiva but not the vitreous. CONCLUSION: SARS-CoV-2 RNA can be detected post mortem in conjunctival tissues and IVBs. This is relevant to the planning of ophthalmologic surgical procedures in COVID-19 patients, such as pars plana vitrectomy or corneal transplantation. Furthermore, not only during surgery but also in an outpatient setting it is important to emphasize the need for personal protection in order to avoid infection and spreading of SARS-CoV-2. Prospective studies are needed, especially to determine the clinical relevance of conjunctival and intravitreal SARS-CoV-2 detection concerning intraocular affection in active COVID-19 state and in post-COVID syndrome.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , Conjunctiva , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Tears/chemistry
5.
Trends Mol Med ; 26(6): 529-531, 2020 06.
Article in English | MEDLINE | ID: covidwho-1720652

ABSTRACT

The current coronavirus disease 2019 (COVID-19) pandemic is rapidly spreading around the world. The first doctor to report this new disease was an ophthalmologist: this exemplifies the role of ophthalmologists in an infectious disease pandemic. Here we review how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects the eye and discuss implications for ophthalmologists.


Subject(s)
Betacoronavirus/isolation & purification , Conjunctiva/virology , Conjunctivitis, Viral/virology , Coronavirus Infections/complications , Pneumonia, Viral/complications , COVID-19 , Conjunctivitis, Viral/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Eye/virology , Humans , Ophthalmologists , Ophthalmology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , SARS-CoV-2
6.
Int Ophthalmol ; 42(3): 723-727, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1681275

ABSTRACT

PURPOSE: Upon the outbreak of 2019, novel coronavirus (COVID-19) pandemic confirmed the cases surpassed 20 million. Despite a few reports identified the association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ocular manifestations, it may assess the ocular symptoms of patients with the COVID-19 by ophthalmologists facilitate the diagnosis and prevent transmission. METHODS: A total of 60 patients with the COVID-19 admitted to Baghiatallah hospital from March 2020 to May 2020 were retrospectively reviewed and analyzed for the ocular manifestations, blood tests, and reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2 using nasopharyngeal and conjunctival swabs. RESULTS: Among 60 included patients with clinically confirmed COVID-19, the median age 58.36 years (IQR: 30-88 years), 27 (45%) were male. Furthermore, 29 (48%) and 5 (8%) patients yielded positive for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs and conjunctival specimens, respectively. Among 60 patients, 10 (16%) and 3 (5%), respectively, had the ocular manifestations and positive results for SARS-CoV-2 on RT-PCR from conjunctival and nasopharyngeal swabs. CONCLUSION: Although the positive rate of tear RT-PCR rate is not noticeable as nasopharyngeal swabs yet, COVID-19 transmission through the eyes is biologically plausible.


Subject(s)
COVID-19 , COVID-19/diagnosis , Conjunctiva , Humans , Intensive Care Units , Male , Middle Aged , RNA, Viral/analysis , Retrospective Studies , SARS-CoV-2 , Tears/chemistry
7.
Ophthalmologie ; 119(8): 807-812, 2022 Aug.
Article in German | MEDLINE | ID: covidwho-1653449

ABSTRACT

BACKGROUND: There are only few reports on ocular symptoms and manifestations in association with coronavirus disease 2019 (COVID-19). OBJECTIVE: The aim of this study is to describe ocular manifestations in the anterior and posterior segments of the eye and to analyze viral prevalence in tears of patients with COVID-19. METHODS: Hospitalized COVID-19 patients treated from 16 April 2020 to 7 January 2021 at this hospital were screened for ocular manifestations in the anterior and posterior segments. Conjunctival swabs were analyzed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. RESULTS: A total of 37 patients were enrolled in this study. In the anterior segment we found chemosis of the conjunctiva (5), hyposphagma (2) and conjunctivitis (1). In 11 patients vascular alterations and potentially disease-specific manifestations of the fundus were found in one or both eyes: retinal hemorrhages (5), cotton wool spots (5) and tortuosity (5). One patient demonstrated branch artery occlusion, one had branch retinal vein occlusion and two patients had positive conjunctival swab results in one or both eyes. CONCLUSION: Our findings of the anterior segment are commonly known, although not specific for COVID-19. Various vascular fundus abnormalities were found in the study; however, it is unclear whether these were correlated to systemic comorbidities or whether they were caused or exacerbated by COVID-19. This study suggests that the risk of viral transmission via tears is low.


Subject(s)
COVID-19 , COVID-19/epidemiology , Conjunctiva , Humans , RNA, Viral , SARS-CoV-2 , Tears
8.
Vestn Oftalmol ; 137(6): 142-148, 2021.
Article in Russian | MEDLINE | ID: covidwho-1599970

ABSTRACT

Conjunctivitis may appear as the first symptom of the coronavirus infection (COVID-19). In isolated cases, the lesion of the conjunctiva evokes a systemic infectious process. Currently, the conjunctiva is not considered as an area of long-term reproduction of coronavirus, and its damage is caused by hyperproduction of pro-inflammatory cytokines (especially IL-6); development of iridocyclitis and keratoconjunctivitis is also possible. Most often, local corticosteroids are used to treat these processes, although their use requires caution due to the risk of activating secondary infection (herpetic bacterial, fungal), which often develops as a result of immunodeficiency caused both by COVID-19 and the massive corticosteroid and antibiotic therapy employed when the course of the disease is severe. The severe condition of patients, the lung ventilation, and the prone position all contribute to corneal erosions, exposure keratopathy, pseudomonas aeruginosa keratitis and angle-closure glaucoma attacks. The risk of transmission of coronavirus infection during keratoplasty is estimated as minimal.


Subject(s)
COVID-19 , Conjunctivitis , Keratoconjunctivitis , Conjunctiva , Humans , SARS-CoV-2
9.
J Ocul Pharmacol Ther ; 38(1): 56-65, 2022.
Article in English | MEDLINE | ID: covidwho-1565952

ABSTRACT

Purpose: Recent studies have shown the presence of SARS-CoV-2 entry factors on the ocular surface, identifying the eye as an additional entry route for the virus. Moreover, the coexpression of angiotensin-converting enzyme 2 (ACE2) with other SARS-CoV-2 entry factors [transmembrane protease serine 2 (TMPRSS2), transmembrane protease serine 4 (TMPRSS4), and dipeptidyl peptidase-4 (DPP4)] facilitates the virus infection. Methods: Here, we performed a study over 10 adult corneal and limbal tissues from human donors, both male and female between 58 and 85 years of age. Some of the main virus entry factors were analyzed and their expression was quantified and correlated with the age and sex of the donors through western blot. The receptors' localization was investigated through immunofluorescence. Results: Immunofluorescence confirmed the localization of ACE2 and TMPRSS2 on the ocular surface and showed, for the first time, the localization of TMPRSS4 and DPP4 in limbal and corneal epithelial superficial cells. The quantitative analysis showed that the expression of SARS-CoV-2 entry factors on corneal and limbal cells is likely to be modulated in an age-dependent manner, in agreement with the increased susceptibility to COVID-19 in the elderly. Moreover, we found a relationship between the expression of TMPRSS proteases with the activation state of limbal cells in 80-year-old donors. Conclusion: This study provides information on the expression of SARS-CoV-2 entry factors on the ocular surface of 10 adult human donors and is a first observation of a possible age-dependent modulation on corneal and limbal tissues. Our data pave the way to further investigate the susceptibility to the infection through the ocular surface in the elderly.


Subject(s)
Conjunctiva/metabolism , Conjunctiva/virology , Cornea/metabolism , Cornea/virology , SARS-CoV-2/metabolism , Virus Internalization , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , Female , Gene Expression Regulation, Viral/physiology , Humans , Male , Middle Aged , Serine Endopeptidases/metabolism
10.
Cornea ; 41(2): 238-242, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1546065

ABSTRACT

PURPOSE: The purpose of this study was to evaluate the prevalence of SARS-CoV-2 in human postmortem ocular tissues of asymptomatic donors and its implications on our eye banking protocols. METHODS: The expression of SARS-CoV-2 RNA was assessed by reverse transcription-polymerase chain reaction in corneal rims and conjunctival tissues from 100 donors who were found suitable for transplantation as per the donor screening guidelines of the Global Alliance of Eye Bank Associations. The donor's clinical history and cause of death were assessed for secondary analysis. RESULTS: Of 200 ocular tissues (100 corneal and 100 conjunctival) from the same 1 eye of 100 surgical-intended donors, between September 2020 and April 2021, the overall positivity rate for SARS-CoV-2 was ∼1% (2/200). Both the ocular samples that tested positive were conjunctival biopsies (2/100, 2%), whereas corneal samples were negative (0/100, 0%) in both donors. The causes of donor death were trauma in 51 donors, suicide in 33, cardiac arrest in 7, electric shock in 5, metabolic cause in 2, malignancy in 1, and snake bite in 1. None of the donors had a medical history suggestive of COVID infection or possible contact. None of the recipients from the donors were reported to have any systemic adverse event after keratoplasty until the follow-up of 6 weeks. CONCLUSIONS: The overall prevalence of SARS-CoV-2 was 1% (2% for conjunctival and 0% for corneal samples, P value = 0.5) in the donors who were found suitable for cornea recovery and transplantation. The findings of exceptionally low positive rates in our samples validate the criticality of history-based donor screening and do not support the necessity of postmortem PCR testing as a criterion for procurement and subsequent use for corneal transplantation.


Subject(s)
COVID-19 Nucleic Acid Testing/statistics & numerical data , COVID-19/epidemiology , Conjunctiva/virology , Cornea/virology , Keratoplasty, Penetrating , SARS-CoV-2/isolation & purification , Tissue Donors/statistics & numerical data , Adult , COVID-19 Testing , Cause of Death , Donor Selection , Eye Banks/statistics & numerical data , Female , Humans , India/epidemiology , Keratoplasty, Penetrating/statistics & numerical data , Male , Middle Aged , Prevalence , RNA, Viral/genetics , SARS-CoV-2/genetics
11.
Indian J Ophthalmol ; 69(12): 3636-3637, 2021 12.
Article in English | MEDLINE | ID: covidwho-1538667
12.
Indian J Ophthalmol ; 69(12): 3633-3636, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1538655

ABSTRACT

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.


Subject(s)
COVID-19 , RNA, Viral , Comorbidity , Conjunctiva , Cross-Sectional Studies , Hospitals , Humans , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , SARS-CoV-2
13.
Exp Eye Res ; 214: 108864, 2022 01.
Article in English | MEDLINE | ID: covidwho-1531248

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen for coronavirus disease 2019 (COVID-19) pandemic. Its infection depends on the binding of spike protein to the host cell receptor angiotensin-converting enzyme 2 (ACE2), type II transmembrane serine protease (TMPRSS2) and neuropilin-1 (NRP1). Hydroxychloroquine has been applied as one of the COVID-19 treatment strategies. Here we aimed to evaluate hydroxychloroquine treatment on SARS-CoV-2 receptor expression in human primary pterygium and conjunctival cells and its potential influences. Expression of ACE2, TMPRSS2 and NRP1 proteins were found in the epithelial layer of both primary pterygium and conjunctiva tissues as well as in their isolated fibroblasts. High concentration of hydroxychloroquine treatment significantly reduced the viability of both primary pterygium and conjunctival cells. ACE2 protein expression was significantly decreased in both pterygium and conjunctival cells after hydroxychloroquine treatment. Hydroxychloroquine also reduced NRP1 protein expression in conjunctival cells. In contrast, TMPRSS2 protein expression showed slightly increased in conjunctival cells. Notably, ROS production and SOD2 expression was significantly elevated in both pterygium and conjunctival cells after hydroxychloroquine treatment. In summary, this study revealed the reduction of ACE2 and NRP1 expression by hydroxychloroquine in human primary pterygium and conjunctival fibroblasts; yet with the increase in TMPRSS2 expression and oxidative stress and decrease in cell viability. Implementation of hydroxychloroquine for COVID-19 treatment should be carefully considered with its potential side effects and in combination with TMPRSS2 inhibitor.


Subject(s)
Angiotensin-Converting Enzyme 2/biosynthesis , COVID-19/drug therapy , Conjunctiva/abnormalities , Hydroxychloroquine/therapeutic use , Neuropilin-1/biosynthesis , Pterygium/drug therapy , SARS-CoV-2 , Serine Endopeptidases/biosynthesis , Biomarkers/metabolism , COVID-19/metabolism , COVID-19/virology , Comorbidity , Humans , Pandemics , Pterygium/diagnosis , Pterygium/epidemiology
14.
Int J Mol Sci ; 22(21)2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-1512378

ABSTRACT

Autoimmune epithelitis and chronic inflammation are one of the characteristic features of the immune pathogenesis of Sjögren's syndrome (SS)-related dry eye disease. Autoimmune epithelitis can cause the dysfunction of the excretion of tear fluid and mucin from the lacrimal glands and conjunctival epithelia and meibum from the meibomian glands. The lacrimal gland and conjunctival epithelia express major histocompatibility complex class II or human leukocyte antigen-DR and costimulatory molecules, acting as nonprofessional antigen-presenting cells for T cell and B cell activation in SS. Ocular surface epithelium dysfunction can lead to dry eye disease in SS. Considering the mechanisms underlying SS-related dry eye disease, this review highlights autoimmune epithelitis of the ocular surface, chronic inflammation, and several other molecules in the tear film, cornea, conjunctiva, lacrimal glands, and meibomian glands that represent potential targets in the treatment of SS-related dry eye disease.


Subject(s)
B-Lymphocytes/immunology , Conjunctiva/immunology , Lacrimal Apparatus/immunology , Lymphocyte Activation , Meibomian Glands/immunology , Sjogren's Syndrome/immunology , T-Lymphocytes/immunology , B-Lymphocytes/pathology , Chronic Disease , Conjunctiva/pathology , Humans , Lacrimal Apparatus/pathology , Meibomian Glands/pathology , Mucins/immunology , Sjogren's Syndrome/pathology , T-Lymphocytes/pathology
15.
Cornea ; 41(2): 252-253, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1505854

ABSTRACT

PURPOSE: The purpose of this study was to report a case of acute corneal epithelial rejection of living-related conjunctival limbal allograft (LR-CLAL) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. OBSERVATIONS: A 27-year-old woman developed acute epithelial rejection of LR-CLAL 2 weeks after receiving the SARS-CoV-2 vaccine. She received the LR-CLAL transplant 4 years and 7 months previously and had a stable clinical course with no history of rejection. She had an ABO blood group and human leukocyte antigen compatible donor, no systemic comorbidities, and no rejection risk factors. CONCLUSIONS: The novel SARS-CoV-2 vaccine upregulates the immune system to produce an adaptive immune response. The SARS-CoV-2 vaccine may potentially be associated with increased risk of rejection in those with ocular surface transplants.


Subject(s)
/adverse effects , Epithelium, Corneal/pathology , Graft Rejection/etiology , Limbus Corneae/cytology , Living Donors , Stem Cell Transplantation , Vaccination/adverse effects , Acute Disease , Administration, Ophthalmic , Administration, Oral , Adult , Allografts , COVID-19/prevention & control , Conjunctiva/cytology , Female , Glucocorticoids/therapeutic use , Graft Rejection/diagnosis , Graft Rejection/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Mycophenolic Acid/therapeutic use , Ophthalmic Solutions , Slit Lamp Microscopy , Tacrolimus/therapeutic use , Visual Acuity/physiology
16.
J AAPOS ; 25(4): 230-231, 2021 08.
Article in English | MEDLINE | ID: covidwho-1486297

ABSTRACT

The most common ocular manifestation of SARS-CoV-2 in adults and children is acute conjunctivitis. We report the case of a 4-day-old infant who presented with acute-onset mucopurulent discharge of the left eye as well as subconjunctival hemorrhage and palpebral injection, without corneal findings. A diagnosis of ophthalmia neonatorum was established, for which ocular cultures and Gram staining were performed. No bacterial growth was noted, and polymerase chain reaction (PCR) testing for Chlamydia trachomatis, Neisseria gonorrhea, and herpes simplex were negative. Nasopharyngeal and conjunctival SARS-CoV-2 PCR were positive. Given the identification of SARS-CoV-2 illness, lack of other underlying bacterial or viral etiology on testing, and the well-documented ability for SARS-CoV-2 to cause conjunctivitis, the clinical picture was supportive of ophthalmia neonatorum secondary to SARS-CoV-2. The infant was treated with ceftriaxone and azithromycin prior to culture results. During admission, no systemic findings of Covid-19 illness were observed.


Subject(s)
COVID-19 , Conjunctivitis , Gonorrhea , Ophthalmia Neonatorum , Adult , Child , Conjunctiva , Humans , Infant , Infant, Newborn , Ophthalmia Neonatorum/diagnosis , Ophthalmia Neonatorum/drug therapy , SARS-CoV-2
17.
Ophthalmic Res ; 64(5): 785-792, 2021.
Article in English | MEDLINE | ID: covidwho-1443682

ABSTRACT

INTRODUCTION: In December 2019, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic broke out. The virus rapidly spread globally, resulting in a major world public-health crisis. The major disease manifestation occurs in the respiratory tract. However, further studies documented other systemic involvement. This study investigates histopathologic eye changes in postmortem material of coronavirus disease 2019 (COVID-19) patients. METHODS: Sections of formalin-fixed, paraffin-embedded eyes from 5 patients (10 eyes) who died of COVID-19 at the University Hospital in Basel were included. Gross examination and histological evaluation were performed by 3 independent ophthalmopathologists. Immunohistochemical staining was performed using antibodies against fibrin, cleaved caspase 3, and ACE-2. Five enucleated eyes of patients not infected with SARS-CoV-2 served as control group. All cases have been studied for presence of SARS-CoV-2 RNA by means of reverse transcription PCR and RNA in situ hybridization (ISH). The choroidal vessels of one case were analyzed with electron microscope. RESULTS: Ophthalmopathologically, 8 eyes from 4 patients displayed swollen endothelial cells in congested choroidal vessels. No further evidence of specific eye involvement of SARS-CoV-2 was found in any of the patients. In the 8 eyes with evidence of changes due to SARS-CoV-2, immunohistochemical staining demonstrated fibrin microthrombi, apoptotic changes of endothelial and inflammatory cells. In control eyes, ACE-2 was detectable in the conjunctiva, cornea, retina, and choroidea and displayed significantly lower amounts of stained cells as in COVID-19 eyes. SARS-CoV-2 RNA was detectable in both bulbi of 2/5 patients, yet ISH failed to visualize viruses. Electron microscopy showed no significant results due to the artifacts. DISCUSSION/CONCLUSION: As already described in other organs of COVID-19 patients, the ophthalmological examination revealed-microthrombi, that is, hypercoagulation and vasculopathy most probably due to endothelial damage. A possible viral spread to the endothelial cells via ACE-2 provides one pathophysiological explanation. The expression of ACE-2 receptors in the conjunctiva hints toward its susceptibility to infection. To what extend eyes, function is disrupted by SARS-CoV-2 is subject to further studies, especially in the clinic.


Subject(s)
COVID-19/pathology , Choroid Diseases/pathology , Eye Infections, Viral/pathology , RNA, Viral/genetics , Retinal Diseases/pathology , SARS-CoV-2/genetics , Aged , Aged, 80 and over , Angiotensin-Converting Enzyme 2/metabolism , COVID-19 Nucleic Acid Testing , Caspase 3/metabolism , Choroid/blood supply , Choroid/pathology , Choroid Diseases/virology , Ciliary Body/blood supply , Ciliary Body/pathology , Conjunctiva/metabolism , Cornea/metabolism , Endothelial Cells/metabolism , Eye Infections, Viral/virology , Female , Fibrin/metabolism , Humans , Immunohistochemistry , In Situ Hybridization , Male , Real-Time Polymerase Chain Reaction , Retinal Diseases/virology , Retinal Vessels/pathology , Thrombosis/metabolism , Thrombosis/pathology
18.
Sci Rep ; 11(1): 19140, 2021 09 27.
Article in English | MEDLINE | ID: covidwho-1440481

ABSTRACT

Despite the reported low expression of the primary SARS-CoV-2 receptor ACE2 in distinct ocular tissues, some clinical evidence suggests that SARS-CoV-2 can infect the eye. In this study, we explored potential entry sites for SARS-CoV-2 by viral S protein histochemistry on various ocular tissues and compared the staining patterns with RNA and protein expression of TMPRSS2 and ACE2. Potential viral entry sites were investigated by histochemistry using tagged recombinant viral S protein on 52 ocular tissue samples including specimens of the cornea, conjunctiva, lid margin, lacrimal gland tissue, retina, choroid, and RPE. In addition, ACE2 and TMPRSS2 immunohistochemistry were performed on the same ocular tissue, each with distinct antibodies binding to different epitopes. Lung tissue samples were used as positive controls. Finally, bulk RNA sequencing (RNA-Seq) was used to determine the expression of ACE2 and its auxiliary factors in the tissues mentioned above. S protein histochemistry revealed a positive staining in lung tissue but absent staining in the cornea, the conjunctiva, eye lid samples, the lacrimal glands, the retina and the optic nerve which was supported by hardly any immunoreactivity for ACE2 and TMPRSS2 and scarce ACE2 and TMPRSS2 RNA expression. Negligible staining with antibodies targeting ACE2 or TMPRSS2 was seen in the main and accessory lacrimal glands. In contrast, ocular staining (S protein, ACE2, TMPRSS2) was distinctly present in pigmented cells of the RPE and choroid, as well as in the ciliary body and the iris stroma. S protein histochemistry revealed hardly any SARS-CoV-2 entry sites in all ocular tissues examined. Similarly, no significant ACE2 or TMPRSS2 expression was found in extra- and intraocular tissue. While this study suggest a rather low risk of ocular infection with SARS-CoV-2, it should be noted, that potential viral entry sites may increase in response to inflammation or in certain disease states.


Subject(s)
COVID-19/prevention & control , Conjunctiva/metabolism , Cornea/metabolism , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Conjunctiva/virology , Cornea/virology , Gene Expression Profiling/methods , Humans , Immunohistochemistry/methods , RNA-Seq/methods , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Virus Internalization
19.
Infect Disord Drug Targets ; 21(4): 480-483, 2021.
Article in English | MEDLINE | ID: covidwho-1435869

ABSTRACT

Ocular tissues can serve as a reservoir for the SARS-CoV-2 virus which can not only cause conjunctivitis but also serve as a source of infection transmission to others. Additionally, the eye and its tear drainage apparatus can track the SARS-CoV-2 from the eye into the respiratory tract of the patient. The potential ocular presence of the SARS-CoV-2 in the eye of a patient can target ACE2 receptors in the endothelium of the conjunctival vessels and use the lacrimal sac a potential space to evade immune detection and clinical isolation. The recently reported case of COVID-19 after the acquisition of SARS-CoV-2 from a COVID-19 patient should alert the healthcare professionals dealing with COVID-19 patients that wearing masks alone cannot guarantee protection against infection transmission. Further studies, like isolation of SARS-CoV-2 from the eyes of patients with COVID-19, are needed to identify the eyes as a potential source of SARS-CoV-2 infection transmission.


Subject(s)
COVID-19 , Conjunctiva , Humans , Masks , SARS-CoV-2
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