Relations between the ocular surface and SARS-CoV-2 / Relações entre superfície ocular e SARS-CoV-2

ABSTRACT Introduction: The SARS-CoV-2 pandemic has been a major challenge for the international scientific community. Since its inception, studies aiming to describe pathophysiological aspects and clinical manifestations of the disease have been conducted, raising hypotheses and confirming possible associations. One aspect of this scientific medical production is the role of the ocular surface as a means of transmission and clinical presentation of viral syndrome. Objectives: To analyze the role of the ocular surface in transmission, pathophysiology, and clinical manifestations of SARS-CoV-2, by means of a systematic review. Methods: The search was carried out in three databases: Cochrane, PubMed Central Journals and MEDLINE, using the following descriptors: "COVID-19, ophthalmology". The filters last five years and studies on humans resulted in 32 studies; in that 12 were excluded for not meeting the purpose of the study. Results: There are still few published studies on the relation between SARS-CoV-2 and the ocular route. Most studies showed an association between the presence of nonspecific ocular manifestations and infection by the new coronavirus, with limitations in the number of patients analyzed and the methodology adopted. Hypotheses about the pathophysiological role are largely anchored in the association of SARS-CoV and the ocular surface evaluated in the past. Comments: The results found are still not sufficient to confirm the role of the ocular surface in the pathophysiology of the disease. Most of these preliminary studies are of considerable importance in raising hypotheses based on the medical analysis of the patients studied. However, larger studies with standardized methodology for diagnostic protocol and laboratory analysis of the individuals assessed are required.

RESUMO Introdução: A pandemia da SARS-CoV-2 tem sido um grande desafio para a comunidade científica internacional. Desde seu surgimento, estudos com a intenção de descrever os aspectos fisiopatológicos e as manifestações clínicas da doença vêm sendo conduzidos, levantando hipóteses e confirmando possíveis associações. Um dos temas dessa produção médica científica é o papel da superfície ocular como meio de transmissão e apresentação clínica da síndrome viral. Objetivo: Analisar o papel da superfície ocular na transmissão, na fisiopatologia e nas manifestações clínicas de SARS-CoV-2, através de uma revisão sistemática. Realizou-se a busca em três bancos de dados Cochrane Database, PubMed® e MEDLINE®, utilizando os descritores "COVID-19 e ophthalmology". Foram definidos como filtros o artigo ter sido publicado nos últimos 5 anos e estudo realizado em humanos, tendo sido encontrados 32 artigos. Destes, foram excluídos 12 por não corresponderem ao objetivo do estudo. Resultados: Ainda são poucos os estudos publicados sobre a relação entre o coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2) e a via ocular. A maioria dos estudos mostrou associação entre a presença de manifestações oculares inespecíficas e a infecção pelo novo coronavírus, com limitações no número de pacientes analisados e na metodologia adotada. Hipóteses sobre o papel fisiopatológico se ancoram, em grande parte, na associação estudada entre o SARS-CoV-2 e a superfície ocular no passado. Comentários: Os resultados encontrados ainda não são suficientes para confirmar o papel da superfície ocular na fisiopatologia da doença. Grande parte desses estudos preliminares têm importância considerável ao levantar hipóteses baseadas na análise clínica dos pacientes estudados. No entanto, são necessários estudos maiores e com metodologia padronizada para protocolo diagnóstico e análise laboratorial dos indivíduos avaliados.

Ocular transmissibility of COVID-19: possibilities and perspectives.

Since the initial outbreak of coronavirus disease 2019 (COVID-19), extensive research has emerged from across the globe to understand the pathophysiology of this novel coronavirus. Transmission of this virus is a subject of particular interest as researchers work to understand which protective and preventative measures are most effective. Despite the well understood model of aerosol-respiratory mediated transmission, the exact mechanism underlying the inoculation, infection and spread of COVID-19 is currently unknown. Given anatomical positioning and near constant exposure to aerosolized pathogens, the eye may be a possible gateway for COVID-19 infection. This critical review explores the possibility of an ocular-systemic or ocular-nasal-pulmonic pathway of COVID-19 infection and includes novel insights into the possible immunological mechanisms leading to cytokine surge.

Ocular Assessments of a Series of Newborns Gestationally Exposed to Maternal COVID-19 Infection.

IMPORTANCE: Congenital viral infections leading to ocular abnormalities are frequent and devastating. As ophthalmological manifestations of COVID-19 in newborns are still unknown, it is important to clarify if SARS-CoV-2 could be associated with ocular abnormalities. OBJECTIVE: To determine whether exposure to SARS-CoV-2 is associated with outcomes in the eyes of newborns. DESIGN, SETTING, AND PARTICIPANTS: This case series enrolled newborns from April to November 2020 from 3 different maternity hospitals in São Paulo, Brazil. The diagnosis of COVID-19 in mothers and newborns was based on real-time reverse transcriptase-polymerase chain reaction assays with material obtained from oronasopharyngeal swab sample; positive IGM serology was also considered as a diagnostic test for mothers. Newborns were excluded if they had any evidence of another congenital infection. All infants underwent external ocular examination and binocular indirect ophthalmoscopy. EXPOSURES: Serology test for COVID-19 and detection of SARS-CoV-2 from oronasopharyngeal specimen using a real-time reverse transcriptase-polymerase chain reaction assay on both mothers and newborns. MAIN OUTCOMES AND MEASURES: Screening for ophthalmologic manifestation in newborns after maternal COVID-19 infection. RESULTS: A total of 165 newborns (age range at examination, 1 to 18 days) were evaluated. Of these, 123 (74.5%) were born at full term, and 42 (25.4%) were born preterm. Maternal gestational age at the time of COVID-19-positive test varied from first to 40th gestational weeks. Six newborns (3.6%) had positive polymerase chain reaction findings for SARS-CoV-2. One newborn tested positive within 18 days (horizontal transmission), and 5 newborns tested positive in the first day of life (possible vertical transmission). None had ocular abnormalities. Concerning exposed newborns with negative test results, 1 presented with venous engorgement and vascular tortuosity, 7 had intraretinal hemorrhages, and 2 were diagnosed as having retinopathy of prematurity. CONCLUSIONS AND RELEVANCE: In this uncontrolled case series of Brazilian newborns of mothers with COVID-19 infection, a low rate of COVID-19 infection was found among newborns, and none had ocular abnormalities. Additional controlled studies may be warranted to confirm these findings.

Implications of COVID-19 for Ophthalmologists.

PURPOSE: To describe and explain the implications of coronavirus disease 2019 (COVID-19) for ophthalmologists considering the rapid developments in our understanding of the virology, transmission, and ocular involvement. DESIGN: Evidence-based perspective. METHODS: Review and synthesis of pertinent literature. RESULTS: Retrospective studies highlight that <1% of patients display COVID-19-related conjunctivitis. However, prospective studies suggest the rate is higher (~6%). Viral RNA has been identified in tears and conjunctival secretions in patients with active conjunctivitis as well as asymptomatic cases. Overall, conjunctival swabs are positive in 2.5%. Samples taken earlier in the disease course are more likely to demonstrate positive virus. Viral transmission through ocular tissues has not been substantiated. Ophthalmologists are in the high-risk category for COVID-19 infection for several reasons: high-volume clinics, close proximity with patients, equipment-intense clinics, and direct contact with patients' conjunctival mucosal surfaces. COVID-19 is predominantly contracted through direct or airborne transmission by inhalation of respiratory droplets. Evidence that aerosol transmission occurs is increasing in particularly prolonged exposure to high concentrations in a relatively closed environment. Based on the current evidence, ophthalmologists should consider measures that include social distancing, wearing masks, sterilization techniques, and managing clinic volumes. CONCLUSIONS: A major challenge to containing COVID-19 is that many infected people are asymptomatic. Droplet spread, contaminated environmental surfaces, and shared medical devices are areas that require management by ophthalmologists. More studies are required to explore the role of the conjunctiva and ocular tissues in the transmission of disease.

COVID-19 and the Ocular Surface: A Review of Transmission and Manifestations.

PURPOSE: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached pandemic proportions within an unprecedented span of time. It is controversial whether the virus can be transmitted via tears and its ocular implications have not been widely studied. In this article, the current evidence related to ocular transmission and ocular manifestations is reviewed. RESULTS: Several mechanisms for the ocular transmission of the virus are proposed with highlight on the nasolacrimal system as a conduit between the eye and the respiratory tract, and the role of the lacrimal gland in hematogenous spread. Ocular surface manifestations such as conjunctivitis are more commonly reported. CONCLUSION: The exact pathophysiology of ocular transmission of the virus remains incompletely understood, although there is preliminary evidence of SARS-CoV-2 being detected in ocular secretions. The ocular tropism of the virus and its potential to cause localized ocular disease are worth considering.