Ocular COVID-19: Eyes as a Reservoir to Conceal and Spread SARSCoV- 2.

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.

High expression of SARS-CoV-2 entry factors in human conjunctival goblet cells.

The angiotensin-converting enzyme 2 (ACE2) receptor has been proved for SARS-CoV-2 cell entry after auxiliary cellular protease priming by transmembrane protease serine 2 (TMPRSS2), but the co-effect of this molecular mechanism was unknown. Here, single-cell sequencing was performed with human conjunctiva and the results have shown that ACE2 and TMPRSS2 were highly co-expressed in the goblet cells with genes involved in immunity process. This identification of conjunctival cell types which are permissive to virus entry would help to understand the process by which SARS-CoV-2 infection was established. These finding might be suggestive for COVID-19 control and protection.

The eye as the discrete but defensible portal of coronavirus infection.

Oculo-centric factors may provide a key to understanding invasion success by SARS-CoV-2, a highly contagious, potentially lethal, virus with ocular tropism. Respiratory infection transmission via the eye and lacrimal-nasal pathway elucidated during the 1918 influenza pandemic, remains to be explored in this crisis. The eye and its adnexae represent a large surface area directly exposed to airborne viral particles and hand contact. The virus may bind to corneal and conjunctival angiotensin converting enzyme 2 (ACE2) receptors and potentially to the lipophilic periocular skin and superficial tear film with downstream carriage into the nasopharynx and subsequent access to the lungs and gut. Adenoviruses and influenza viruses share this ocular tropism and despite differing ocular and systemic manifestations and disease patterns, common lessons, particularly in management, emerge. Slit lamp usage places ophthalmologists at particular risk of exposure to high viral loads (and poor prognosis) and as for adenoviral epidemics, this may be a setting for disease transmission. Local, rather than systemic treatments blocking virus binding in this pathway (advocated for adenovirus) are worth considering. This pathway is accessible with eye drops or aerosols containing drugs which appear efficacious via systemic administration. A combination such as hydroxychloroquine, azithromycin and zinc, all of which have previously been used topically in the eye and which work at least in part by blocking ACE2 receptors, may offer a safe, cost-effective and resource-sparing intervention.

Dentistry and Covid-19 pandemic: operative indications post-lockdown.

A new Coronavirus, the seventh member of the Coronaviridae family, identified as SARS-CoV-2, spread in late December 2019 in the territory of Wuhan in China. CoV-2019 can be transmitted directly from person to person by respiratory drops, direct contact and contaminated material. Furthermore, 2019-nCov penetrates cells similarly to the SARS coronavirus, i.e., through the ACE2 receptor. This may promote human-to-human transmission. Patients and dental professionals are exposed daily to pathogenic microorganisms, including viruses and bacteria, which infect the oral cavity and respiratory tract. Dental procedures carry the risk of 2019-nCoV infection due to their specificity. Direct transmission regards the distance between operator and patient, exposure to saliva, blood and other body fluids, the use of sharp instruments and "droplet-generating" rotating instruments, contact with the conjunctival mucosa, and finally the contact with droplets produced by coughing and nasal secretion of an infected individual without mask at short distance, increasing the biological risk for the operator. In light of the pandemic linked to COVID-19, although there is no clear scientific evidence in the literature, it is necessary to identify protections with regard to clothing, operating protocols, disinfection of environments and management of waiting rooms and front offices. This paper is a basis for operative indications for dentists and other health care professionals in phase 2 post lockdown for both private and public structures.

Anti-SARS-Cov-2 IgA Response in Tears of COVID-19 Patients.

The pandemic virus SARS-CoV-2 has been reported to be able to enter the body via the eye conjunctiva, but the presence of antiviral response in the eye remains poorly known. Our study was thus aimed to analyze the presence of secretory mucosal anti-SARS-CoV-2 type A immunoglobulins (IgA) in the conjunctival fluid of COVID-19 patients. The tears of 28 COVID-19 patients and 20 uninfected controls were collected by the Schirmer test and analyzed by a specific ELISA assay detecting anti-spike (S1) virus protein IgA. The results showed that 35.7% of COVID-19 subjects have specific antiviral IgA at the ocular level, persisting till 48 days post disease onset. Most of the IgA positive subjects presented mild symptoms. The collected data indicate a prolonged persistence of anti-SARS-CoV-2 IgA at the eye level and suggest that IgA detection may be extremely helpful in clarifying virus pathology and epidemiology.

Detection of SARS-CoV-2 in the tears and conjunctival secretions of Coronavirus disease 2019 patients.

INTRODUCTION: Current studies suggest that tears and conjunctival secretions may be an important transmission route in coronavirus disease 2019 (COVID-19). The study aims to evaluate the presence of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) virus in tears and conjunctival secretion of patients with COVID-19. METHODOLOGY: A prospective interventional case series study was performed, and 32 patients with COVID-19 were selected at the Pamukkale University Hospital from 15 to 22 May 2020. The tear and conjunctival samples were collected by a conjunctival swab. Each specimen was sent to the laboratory for reverse transcription-polymerase chain reaction (RT-PCR) analyses. To avoid cross-infection, gloves and personal protective equipment were changed after collecting each sample. RESULTS: 32 patients (18 male, 14 female) with Covid-19 were included in this cross-sectional study. The average age of the patients was 52.81 ± 16.76 years. By the time of the first collection of conjunctival-tear samples, the mean time of the onset of complaints was 6.84 ± 6.81 (1-35) days. Tear-conjunctival samples from 5 patients (16%) without conjunctivitis yielded positive PCR results, 3 of whom had positive and 2 negative nasopharyngeal PCR results. CONCLUSIONS: Five of 32 patients (16 %) without conjunctivitis or any eye symptoms had viral RNA in their tear-conjunctival samples. The possibility of transmission via tears and conjunctival secretions should be recognized even in the absence of conjunctivitis or other ocular manifestations.

Possible modes of transmission of Novel coronavirus SARS-CoV-2: a review.

INTRODUCTION: The widespread outbreak of the novel SARS-CoV-2 has raised numerous questions about the origin and transmission of the virus. Knowledge about the mode of transmission as well as assessing the effectiveness of the preventive measures would aid in containing the outbreak of the coronavirus. Presently, respiratory droplets, physical contact and aerosols/air-borne have been reported as the modes of SARS-CoV-2 transmission of the virus. Besides, some of the other possible modes of transmission are being explored by the researchers, with some studies suggesting the viral spread through fecal-oral, conjunctival secretions, flatulence (farts), sexual and vertical transmission from mother to the fetus, and through asymptomatic carriers, etc. Aim: The primary objective was to review the present understanding and knowledge about the transmission of SARS-CoV-2 and also to suggest recommendations in containing and preventing the novel coronavirus. METHODS: A review of possible modes of transmission of the novel SARS-CoV-2 was conducted based on the reports and articles available in PubMed and ScienceDirect.com that were searched using keywords, 'transmission', 'modes of transmission', 'SARS-CoV-2', 'novel coronavirus', and 'COVID-19'. Articles referring to air-borne, conjunctiva, fecal-oral, maternal-fetal, flatulence (farts), and breast milk transmission were included, while the remaining were excluded. RESULT AND CONCLUSION: The modes of transmission linked to SARS-CoV-2 were identified and the available literature on each of these is described in detail in view of the possibilities of viral transmission through various modes of transmission. The review provides updated and necessary information on the possible modes of transmission for the health care workers and the lay public under one umbrella that can also be considered during framing guidelines in order to prevent and control the viral spread.

[A special on epidemic prevention and control: analysis on expression of 2019-nCoV related ACE2 and TMPRSS2 in eye tissues].

This article was published ahead of print on the official website of Chinese Journal of Ophthalmolog on Apirl 22,2020. Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental study. Thirty mice were assigned to male, female, aged, diabetic and non-diabetic groups, with 6 mice in each group. Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. Immunohistochemistry staining was applied to visualize the distribution of the two proteins in different mice tissues, and in human corneal and conjunctival sections. Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed using Mann-Whitney U test. Female mice, aged mice, STZ-induced diabetic mice, diabetic group control mice were also subjected to ACE2 expression analysis. Results were analyzed using Student's t-test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. The expression of these two genes in conjunctiva were lower than that in kidney and lung. ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. The expression levels of ACE2 showed gender difference. Female mice had lower ACE2 in conjunctiva and cornea than male mice, with the expression levels being only 43% (t=3.269, P=0.031) and 63% (t=4.080, P=0.015) of that in the male conjunctiva and cornea, respectively. Diabetic mice expressed more ACE2 in conjunctiva (1.21-fold, P>0.05) and lacrimal gland (1.10-fold, P>0.05) compared with the control group. No significant difference on ACE2 expression was found between the aged and young adult mice. The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea (P=0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:438-446).

The ocular surface, coronaviruses and COVID-19.

The ocular surface has been suggested as a site of infection with Coronavirus-2 (SARS-CoV-2) responsible for the coronavirus disease-19 (COVID-19). This review examines the evidence for this hypothesis, and its implications for clinical practice. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), responsible for the COVID-19 pandemic, is transmitted by person-to-person contact, via airborne droplets, or through contact with contaminated surfaces. SARS-CoV-2 binds to angiotensin converting enzyme-2 (ACE2) to facilitate infection in humans. This review sets out to evaluate evidence for the ocular surface as a route of infection. A literature search in this area was conducted on 15 April 2020 using the Scopus database. In total, 287 results were returned and reviewed. There is preliminary evidence for ACE2 expression on corneal and conjunctival cells, but most of the other receptors to which coronaviruses bind appear to be found under epithelia of the ocular surface. Evidence from animal studies is limited, with a single study suggesting viral particles on the eye can travel to the lung, resulting in very mild infection. Coronavirus infection is rarely associated with conjunctivitis, with occasional cases reported in patients with confirmed COVID-19, along with isolated cases of conjunctivitis as a presenting sign. Coronaviruses have been rarely isolated from tears or conjunctival swabs. The evidence suggests coronaviruses are unlikely to bind to ocular surface cells to initiate infection. Additionally, hypotheses that the virus could travel from the nasopharynx or through the conjunctival capillaries to the ocular surface during infection are probably incorrect. Conjunctivitis and isolation of the virus from the ocular surface occur only rarely, and overwhelmingly in patients with confirmed COVID-19. Necessary precautions to prevent person-to-person transmission should be employed in clinical practice throughout the pandemic, and patients should be reminded to maintain good hygiene practices.

Tropism, replication competence, and innate immune responses of the coronavirus SARS-CoV-2 in human respiratory tract and conjunctiva: an analysis in ex-vivo and in-vitro cultures.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing a respiratory disease (coronavirus disease 2019, COVID-19) of varying severity in Wuhan, China, and subsequently leading to a pandemic. The transmissibility and pathogenesis of SARS-CoV-2 remain poorly understood. We evaluate its tissue and cellular tropism in human respiratory tract, conjunctiva, and innate immune responses in comparison with other coronavirus and influenza virus to provide insights into COVID-19 pathogenesis. METHODS: We isolated SARS-CoV-2 from a patient with confirmed COVID-19, and compared virus tropism and replication competence with SARS-CoV, Middle East respiratory syndrome-associated coronavirus (MERS-CoV), and 2009 pandemic influenza H1N1 (H1N1pdm) in ex-vivo cultures of human bronchus (n=5) and lung (n=4). We assessed extrapulmonary infection using ex-vivo cultures of human conjunctiva (n=3) and in-vitro cultures of human colorectal adenocarcinoma cell lines. Innate immune responses and angiotensin-converting enzyme 2 expression were investigated in human alveolar epithelial cells and macrophages. In-vitro studies included the highly pathogenic avian influenza H5N1 virus (H5N1) and mock-infected cells as controls. FINDINGS: SARS-CoV-2 infected ciliated, mucus-secreting, and club cells of bronchial epithelium, type 1 pneumocytes in the lung, and the conjunctival mucosa. In the bronchus, SARS-CoV-2 replication competence was similar to MERS-CoV, and higher than SARS-CoV, but lower than H1N1pdm. In the lung, SARS-CoV-2 replication was similar to SARS-CoV and H1N1pdm, but was lower than MERS-CoV. In conjunctiva, SARS-CoV-2 replication was greater than SARS-CoV. SARS-CoV-2 was a less potent inducer of proinflammatory cytokines than H5N1, H1N1pdm, or MERS-CoV. INTERPRETATION: The conjunctival epithelium and conducting airways appear to be potential portals of infection for SARS-CoV-2. Both SARS-CoV and SARS-CoV-2 replicated similarly in the alveolar epithelium; SARS-CoV-2 replicated more extensively in the bronchus than SARS-CoV. These findings provide important insights into the transmissibility and pathogenesis of SARS-CoV-2 infection and differences with other respiratory pathogens. FUNDING: US National Institute of Allergy and Infectious Diseases, University Grants Committee of Hong Kong Special Administrative Region, China; Health and Medical Research Fund, Food and Health Bureau, Government of Hong Kong Special Administrative Region, China.

Conjunctivitis can be the only presenting sign and symptom of COVID-19.

Five cases of non-remitting conjunctivitis turned out to be the sole presenting sign and symptom of COVID-19. These patients tested positive on RT-PCR of naso-pharyngeal swabs and developed no fever, malaise, or respiratory symptoms throughout the course of their illness. They all fully recovered. In the current efforts to fight the spread of this virus, authors want to emphasize that atypical clinical presentations of COVID-19 can occur and a high level of suspicion should be maintained. Ocular involvement and transmission of SARS-CoV-2 should never be overlooked. In fact, conjunctival mucosae are susceptible to respiratory viruses and remain an important point of entry. For this reason, eye protection in the form of goggles or a face shield should be considered essential for all healthcare providers, even when taking care of patients who are not showing typical symptoms of COVID-19.