SciELO - Scientific Electronic Library Online

 
vol.7 número2Pandemia SARS-CoV-2: A Perspetiva do Laboratório de Patologia Clínica do Hospital CUF Infante Santo E tudo o SARS-CoV-2 mudou...COVID-19 em Pediatria: O Muito que Ainda Não se Sabe! índice de autoresíndice de assuntosPesquisa de artigos
Home Pagelista alfabética de periódicos  

Serviços Personalizados

Journal

Artigo

Indicadores

Links relacionados

  • Não possue artigos similaresSimilares em SciELO

Compartilhar


Gazeta Médica

versão impressa ISSN 2183-8135versão On-line ISSN 2184-0628

Gaz Med vol.7 no.2 Queluz jun. 2020  Epub 29-Jun-2021

https://doi.org/10.29315/gm.v7i2.317 

Artigo de Revisão

COVID-19: An Ophthalmologist’s Perspective

COVID-19: A Perspetiva do Oftalmologista

João Paulo Cunha1  2 
http://orcid.org/0000-0002-3162-0531

Nuno Moura-Coelho3  4 

Rita Pinto Proença4  5 

Arnaldo Dias Santos3  4  6 

Joana Tavares Ferreira1  2  6 

1 Ophthalmology, Hospital CUF Cascais, Cascais, Portugal.

2 Instituto Politécnico de Lisboa, Escola Superior de Tecnologia da Saúde de Lisboa, Lisbon, Portugal.

3 NOVA Medical School, Faculdade de Ciências Médicas - Universidade Nova de Lisboa, Lisbon, Portugal.

4 Ophthalmology, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal.

5 Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.

6 Ophthalmology, Hospital CUF Descobertas, Lisbon, Portugal.


Abstract

In just one hundred years, the world has been through five pandemics. Lessons of the past have not prevented a new virus from being responsible for a fifth wave of deaths worldwide, even with scientific advances and the rapid response of societies that, for the most part, anticipated the political and economic response. A century after the end of the Spanish Flu (1918/19), in December 2019, the world has watched the beginning of the second pandemic of the 21st century, coronavirus disease 2019 (COVID-19) caused by a new severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2). The eye can not only be the entry point for coronaviruses, but also a target organ. Conjunctivitis, uveitis, vasculitis, retinitis and optic neuritis have all been documented in animal models studies. In this article, we review the possible roles of the visual system/ocular tissues as an entryway, and the potential ophthalmic manifestations of human SARS-CoV-2 infections. This review article will also highlight the most effective ways for protecting and preventing the spread of the virus.

Keywords: COVID-19; Coronavirus Infections; Disease Outbreaks; Eye Diseases; Eye/virology; Ophthalmology; Pandemics; SARS-CoV-2

Resumo

Em apenas cem anos, o mundo registou 5 pandemias. As lições do passado não evitaram que um novo vírus fosse responsável pela quinta vaga de mortes a nível mundial, mesmo com os avanços científicos e a rapidez de resposta das sociedades que, na sua maioria, se anteciparam à resposta política e económica. Passado um século do final da Gripe Espanhola (1918-19), em dezembro 2019, regista-se o início da segunda pandemia do século XXI, a coronavirus disease 2019 (COVID-19) provocada por um novo coronavírus (CoV), severe acute respiratory syndrome coronavirus - 2 (SARS-CoV-2). O olho poderá ser não só a porta de entrada dos CoV, como também um dos órgãos-alvo do mesmo. Conjuntivite, uveíte, vasculite, retinite e nevrite ótica foram documentadas em modelos animais. Neste artigo, fazemos uma revisão dos possíveis papéis do sistema visual/tecidos oculares como porta de entrada, bem como das possíveis manifestações oftalmológicas da infeção humana por SARS-CoV-2. Este artigo de revisão também destacará as normas mais eficazes de proteção e evicção de propagação do referido vírus.

Palavras-chave: Coronavírus; Doenças dos Olhos; Infeção por Coronavírus; Oftalmologia; Olho/virology; Pandemia; Síndrome Respiratória Aguda Grave; Surtos de Doença

Introduction

Historical background: 100 years of pandemics

The current COVID-19 pandemic is still far from being equated with other global public health crises. However, it worries both the authorities and scientific community, which have long tried to anticipate a new pandemic, and the population, which remains the key to flatten the pandemic’s progression curve.

The H1N1 virus pandemic, widely known as Spanish flu, which began in 1918 and ended in 1919, killed more than 50 million Europeans, North Americans and Asians, taking many more lives than World War I.1 Since then, 4 more deadly pandemics (1957, 1968, 2009 and 2019-20) have been recorded by the World Health Organization (WHO). Asian influenza, caused by an influenza A virus of the subtype H2N2, victimized about 2-4 million people in 1957-58, affecting mainly children of Southeast Asia. The Hong Kong flu (1968-69), caused by another influenza H3N2 virus, currently still in circulation, has a lower mortality rate (due to its genetic similarities to the Asian flu), with around 1 million deaths reported.2 The H1N1 virus again emerged in 2009 as a combination of the swine, avian and human influenza viruses, originating in Mexico. It was responsible for what was initially called the swine flu pandemic and later type A flu. This pandemic made more victims in Argentina, Brazil and Mexico, with two hundred thousand deaths having been reported, and 62% to 85% of those being in people under 65 years.3

A century after the end of the Spanish flu, the second pandemic of the 21st century started in December 2019 in the city of Wuhan, China, due to a new coronavírus responsible for a severe acute respiratory syndrome (SARS). On the 30th of January of 2020, the WHO has declared this disease as the sixth public health emergency of international concern (PHEIC),4 following the 2009 H1N1 pandemic (2009), the 2014 polio outbreak in the Middle East (2014), the Ebola outbreak in West Africa (2014), the Zika outbreak in Brazil/South America (2016), and the 2019 Ebola outbreak in the Democratic Republic of Congo (2019).5

On the 11th of February of 2020, the WHO announced a new name for the epidemic disease caused by 2019-nCoV: coronavirus disease (COVID-19). Regarding the virus itself, the International Committee on Taxonomy of Viruses has renamed the previously provisionally named 2019-nCoV as severe acute respiratory syndrome

coronavirus-2 (SARS-CoV-2).6

One month later, on 11th March 2020, the WHO declared COVID-19 as the second pandemic of 21st century.7

This new pandemic has spread across the globe rapidly, affecting 2 108 897 people in the world as of the 16th of April 2020.8

Methods

We searched the PubMed and Google Scholar databases to identify articles published up to 16th April 2020, using the following key terms: “COVID-19”, “coronavirus”, “pandemic”. In addition, we manually searched the reference lists of most primary articles and reviewed articles.

Coronavirus - virology and proposed pathogenic mechanisms

Coronaviruses (CoV) are enveloped, positive stranded RNA viruses that belong to the Coronaviridae family and the order Nidovirales.9 The CoV have been known to affect birds and mammals.10 Public opinion became aware of CoVs after the outbreak of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003.11 The SARS-CoV outbreak was responsible for more than 8000 infected patients and 774 deaths in 26 countries.12

In 2012, a new CoV variant was detected in Saudi Arabia which was responsible for the coronavirus-related Middle Eastern respiratory syndrome (MERS-CoV). MERS-CoV was isolated in the same year13 and has been responsible for more than 850 deaths.14 Of the 2223 confirmed cases in the MERS-CoV laboratory reported to the WHO, 415 were healthcare professionals, representing more than a third of all secondary transmission15 and a fifth of all cases. Both severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) are caused by coronaviruses.

The entry of SARS-CoV in human host cells is mediated mainly by an angiotensin-converting enzyme 2 receptor (ACE2-R),16 which is expressed in the epithelium of human airways, in the lung parenchyma, vascular endothelium, kidney cells and intestinal cells.17 However, the presence of ACE2-R is neither enough nor necessary to make host cells susceptible to infection. For instance, in some scientific studies, endothelial cells that express ACE2 and human intestinal cell lines were not infected with SARS-CoV,18 while some cells with very low levels of ACE2 expression, such as hepatocytes19 or neuronal cells,20 could also be infected with SARS-CoV.

The respiratory involvement of human CoV has been clearly established since the 1960s. Data reported in scientific literature has also demonstrated that, similar to other human viruses, CoV have naturally neuroinvasive and neurotropic capacities, with potential neuropathological consequences in genetically or otherwise susceptible individuals, with or without additional environmental insults. The presence of CoV in the human central nervous system (CNS) is now a recognized fact, either as a result of hematogenous or transneural spread.21

Increasing evidence shows that CoVs can first invade peripheral nerve endings and then gain access to the CNS. Trans-synaptic transfer has been well documented for other CoVs, such as hepatitis E virus (HEV),22,23 and avian bronchitis virus.24,25

It is known that interleukin 6 (IL-6) has neurotrophic and neuroprotective effects and can increase the permeability of the blood-brain barrier.26 A high level of IL-6 leads to progressive neurological disorders with neurodegeneration and cognitive decline.27 Although elevated serum levels of IL-6, interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in patients infected with SARS and MERS have been illustrated,28-30 there are studies in which there are no significant increases in the serum levels of these cytokines but they become significantly accumulated in the cerebrospinal fluid of patients with CoV infection.31 Moreover, Arbour et al showed that human CoV (HCoV) can infect human astrocytes and microglia in primary cultures and can acutely and persistently infect immortalized human glial cells.32

Severely affected patients are more likely to develop neurological symptoms, including headache, disturbances in consciousness and paresthesia, than patients with mild or moderate disease.33 Autopsy reports have revealed brain tissue edema and partial neuronal degeneration in deceased patients with COVID-19.34 Another study has reported a case of viral encephalitis, caused by a new CoV with confirmation of the presence of SARS-CoV-2 in cerebrospinal fluid by genome sequencing.35 In addition, an increasing number of patients with COVID-19 report a sudden loss of smell or taste. Therefore, anosmia and dysgeusia are likely to be seen in patients with COVID-19.36,37

In addition to hematogenous dissemination, a second form of viral dissemination to the CNS is through the neuronal retrograde pathway.38 After an intranasal infection, both HCoV-OC4339 and SARS-CoV40 have been shown to infect the respiratory tract in mice and to have neuroinvasive behavior.41,42 Interestingly, several viruses, including the neurotropic strains of murine coronavírus (MuCoV) and the mouse hepatitis virus (MHV) reach the CNS through the olfactory nerve.43 However, Brann et al concluded that mouse and human olfactory sensory neurons do not express two key genes needed for SARS-CoV-2 entry, ACE2 and transmembrane serine protease 2 (TMPRSS2). On the other hand, olfactory support epithelial cells and stem cells express these two genes, as well as cells in the nasal respiratory epithelium. These findings suggest possible local mechanisms through which SARS-CoV-2 infection can lead to anosmia or other forms of olfactory dysfunction.44

Coronavirus and the eye

Although COVID-19 is transmitted mainly by respiratory droplets and direct contact, a recent report has raised the question of whether ocular surfaces could be a potential site for SARS-CoV-2 invasion, in part, due also to virus hepatitis murine aerosols.45

As previously mentioned, many studies have described the binding of SARS-CoV-2 to human ACE2-R, resulting in the invasion of host cells.46,47 In the eye, the ACE2-R is expressed mainly in the posterior tissues, namely in the retinal pigment epithelium. Whether ACE2 /ACE2-R expression and activity are present in the ocular surface cells of humans and rabbit models (including cornea and conjunctiva) remains controversial.48

The polymerase chain reaction (PCR) technique in human tears has been widely used by ophthalmologists to diagnose eye infections, especially of the herpesviridae family, such as the herpes simplex virus types 1,49-51 the Epstein-Barr vírus52 or even adenovirus.53 There is also evidence that some coronaviruses can occasionally cause conjunctivitis in humans. In fact, the human coronavírus NL63 (HCoV-NL63) was first identified in a baby with bronchiolitis and conjunctivitis.54 Later, in a study of twenty-eight cases of children with confirmed HCoV-NL63 infection, 17% had conjunctivitis.55

Guan et al reported nine cases of conjunctival congestion in 1099 studied cases of COVID-19 positive patients.56 However, other ocular manifestations of COVID-19 are still unknown and can include as increased conjunctival secretion, epiphora and decreased vision. In a study by Chen et al of 534 patients with COVID-19, twenty-five (4.68%) had conjunctival congestion and in three patients this was the initial symptom.

That same study also found that ocular dryness, foreign body sensation and blurred vision were the three main eye symptoms in these patients (20.9%, 11.8% and 13.9%), which may be due to the fact that these patients spend much time using electronic devices.57

In another study with thirty patients, there was only one patient with conjunctivitis. Viral RNA was isolated in his tear fluid and conjunctival secretion twice. Its clinical signs were similar to a common viral conjunctivitis, with conjunctival congestion and watery discharge. The patient did not have severe fever or respiratory symptoms when his samples were collected. No viral RNA was detected in the tear fluid and conjunctival secretions of critically ill or common patients without conjunctivitis.58 These findings have led to the speculation that the virus present in tears can reach the respiratory system through the nasolacrimal ducts.59

It is known that the virus can trigger other pathological processes in the eye besides conjunctivitis and keratitis. In fact, the herpes simplex virus and the varicella zoster virus have been implicated in acute retinal necrosis60,61 and cytomegalovirus is capable of inducing retinitis in immunosuppressed individuals.62 Degenerative changes in the retina have also been observed in Creutzfeldt-Jakob disease and in subacute sclerosing panencephalitis due to rubella infection.63 Also, it is common for a viral or flu-like illness to precede Multiple evanescente white dot syndrome (MEWDS), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and acute macular neuroretinopathy, which led some to suspect of a viral etiology.64,65 In addition, the MuCoV and the MHV, induce an acute and chronic eye disease in BALB/c mice.66,67 In the early acute phase, 1 to 7 days after inoculation, mild retinal vasculitis is observed and in the second stage, on the 10th day and progressing for several months, retinal degeneration can be observed in the absence of vasculitis or inflammation. It is interesting that the development of the degenerative phase is controlled by a genetic predisposition of the host and it has been associated with the development of anti-retinal and anti-retinal pigment epithelium (RPE) autoantibodies.68

Murine coronavirus infections can be modified or regulated by several factors including virus serotype, route of inoculation, genetic and age or stage of development of the host.69 In fact, the host’s genetic context can influence the type and intensity of the immune response, the presence of cell membrane surface molecules used for viral adsorption and penetration, and the intracelular composition of the cell that allows viral replication. In the retina, the RPE cell is a potent regulatory cell and appears to play a critical immune role, probably presenting foreign proteins, retinal proteins and viral RNA present in the infected cells to helper T cells.70-73 Several studies indicate that MHV can cause acute and persistente infections in the central nervous system, such as acute necrotizing encephalitis followed by chronic CNS demyelinating disease.74-76 In fact, according to Bergmann et al, despite the T cell-mediated control of acute virus infection, host regulatory mechanisms, probably designed to protect the integrity of the CNS, contribute to the failure in eliminating the virus.77

Moreover, hypoxia, ischemia and edema may also be implicated in retinal vasculitis as reported in patients infected with Rift Valley fever vírus78,79 and West Nile virus.78,80-82

If observed, retinal vasculitis in CoV Infected patients may be due to a cytokine storm associated with elevated IL-6, which can lead to edema and increased permeability of vascular walls as proposed in cases of myocarditis.83 In Portugal there are already unpublished reports of retinal vasculitis and a VI cranial nerve palsy in patients that tested positive for SARS-CoV-2.

Standards for protecting and preventing the spread of SARS-CoV-2

Ophthalmologists examine patients at close distances and inadvertent physical contact with patients’ eyes is almost inevitable. This is a potential hazard to healthcare workers given the close contact with the face, including the nose, mouth and the eyes of SARS patients. Therefore, particular care is advisable when examining any patient. There is a potential possibility of transmission to other patients with reusable eye equipment such as the Goldmann applanation tonometer, trial contact lenses, trial frames, and even reusable pinhole devices which come in close contact with the patient’s eyes.84,85

According to Lian et al, no virus particles were detected in the tears and conjunctival secretions in patients without conjunctivitis.86 However, the low abundance of the virus in tear and conjunctival secretions does not eliminate the risk of transmission through conjunctival tissue. For the same reasons, the use of contact lenses should be discontinued until the COVID-19 emergency comes to an end.

Moreover, the most commonly used noncontact tonometer for ophthalmologic examination, the air puff tonometer, forces an air puff during the examination, which produces a large amount of aerosols in the local area.Aerosols may be concentrated in the local air for a long time, and general alcohol wipe disinfection is ineffective, causing widespread concern in the field of ophthalmology.87 The noncontact tonometer, ultrasound biomicroscopy, corneal confocal microscope, and others do not theoretically cause cross-infection.88-91

During an ophthalmological examination the use of adequate protections, including gloves, eye protection devices (eye shields), adequate protective masks (FFP2 and FFP3 or N95 and N99) and protective shields to be mounted on slit lamps is mandatory for community safety and to limit the risk of disease transmission between ophthalmologists and patients. Should the lack or incomplete availability of such devices be verified, ophthalmological practice ought to be suspended.92,93

Conclusion

The eye can be not only the entry point for CoV, but also one of its target organs. Conjunctivitis, uveitis, vasculitis, retinitis, optic neuritis and other neuro-ophthalmological diseases will be probably reported in the future.

Knowing that especially the most serious forms of COVID-19 infection have neurological semiology, we believe that concurrent neuro-ophthalmological findings are likely underdiagnosed and undervalued because this disease is life-threatening. We also believe that, in the future, and particularly in survivors of intensive care, there will be reports of neurodegenerative and demyelinating eye pathologies linked to the previous infection with SARS-CoV-2.

References

1. Taubenberger JK, Kash JC, Morens DM. The 1918 influenza pandemic: 100 years of questions answered and unanswered. Sci Transl Med. 2019;11. [ Links ]

2. Glezen WP. Emerging Infections: Pandemic Influenza. Epidemiol Rev. 1996;18:64-76. [ Links ]

3. Dawood FS, Iuliano AD, Reed C, Meltzer MI, Shay DK, Cheng PY, et al. Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: A modelling study. Lancet Infect Dis. 2012;12:687-95. [ Links ]

4. WHO | World Health Organization. [cited 2020 Apr 10]. Available from: Available from: https://www.who.int/Links ]

5. Eurosurveillance Editorial Team. World Health Organization declares novel coronavirus (2019-nCoV) sixth public health emergency of international concern. Eurosurveillance. 2020;25:200131e. [ Links ]

6. Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavírus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents. 2020;55:105924. [ Links ]

7. Adams N. Cracking the code to the 2019 novel coronavírus (COVID-19): Lessons from the eye.Eye Reports .2020;6. [ Links ]

8. Worldometer. Coronavirus Cases. Worldometer. 2020 [cited 2020 Apr 16]. Available from: Available from: https://www.worldometers.info/coronavirus/coronavirus-cases/#daily-casesLinks ]

9. Hayden FG, Palese P. Influenza Virus. In: Clinical Virology. Washington: ASM Press; 2016. p. 1009-58. [ Links ]

10. Salata C, Calistri A, Parolin C, Palù G. Coronaviruses: A paradigma of new emerging zoonotic diseases. Vol. 77, Pathogens and Disease;. Oxford: Oxford University Press 2020. [ Links ]

11. WHO | Summary table of SARS cases by country, 1 November 2002 - 7 August 2003. [cited 2020 Apr 11]. Available from: Available from: https://www.who.int/csr/sars/country/2003_08_15/en/Links ]

12. Peiris JS, Yuen KY, Osterhaus AD, Stöhr K. The severe acute respiratory syndrome. N Engl J Med. 2003;349:2431-41 [ Links ]

13. Zaki AM, Van Boheemen S, Bestebroer TM, Osterhaus ADME, Fouchier RAM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:1814-20. [ Links ]

14. Killerby ME, Biggs HM, Midgley CM, Gerber SI, Watson JT. Middle east respiratory syndrome coronavirus transmission. Emerg Infect Dis. 2020;26:191-8. [ Links ]

15. Elkholy AA, Grant R, Assiri A, Elhakim M, Malik MR, Van Kerkhove MD. MERS-CoV infection among healthcare workers and risk factors for death: Retrospective analysis of all laboratory-confirmed cases reported to WHO from 2012 to 2 June 2018. J Infect Public Health. 2020;13:418-22. [ Links ]

16. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367:1444-8. [ Links ]

17. Li YC, Bai WZ, Hirano N, Hayashida T, Hashikawa T. Coronavirus infection of rat dorsal root ganglia: Ultrastructural characterization of viral replication, transfer, and the early response of satellite cells. Virus Res. 2012;163:628-35. [ Links ]

18. Ding Y, Wang H, Shen H, Li Z, Geng J, Han H, et al. The clinical pathology of severe acute respiratory syndrome (SARS): A report from China. J Pathol. 2003;200:282-9. [ Links ]

19. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203:631-7. [ Links ]

20. Bernstein HG, Dobrowolny H, Keilhoff G, Steiner J. Dipeptidyl peptidase IV, which probably plays important roles in Alzheimer disease (AD) pathology, is upregulated in AD brain neurons and associates with amyloid plaques. Neurochem Int. 2018;114:55-7. [ Links ]

21. Desforges M, Le Coupanec A, Dubeau P, Bourgouin A, Lajoie L, Dubé M, et al. Human coronaviruses and other respiratory viruses: Underestimated opportunistic pathogens of the central nervous system? Viruses. 2019;12:1-28. [ Links ]

22. Mengeling WL, Boothe AD, Ritchie AE. Characteristics of a coronavirus (strain 67N) of pigs. Am J Vet Res. 1972;33:297-308. [ Links ]

23. Andries K, Pensaert MB. Immunofluorescence studies on the pathogenesis of hemagglutinating encephalomyelitis vírus infection in pigs after oronasal inoculation. Am J Vet Res. 1980;41:1372-8. [ Links ]

24. Matsuda K, Park CH, Sunden Y, Kimura T, Ochiai K, Kida H, et al. The vagus nerve is one route of transneural invasion for intranasally inoculated influenza A virus in mice. Vet Pathol. 2004;41:101-7. [ Links ]

25. Chasey D, Alexander DJ. Morphogenesis of avian infectious bronchitis virus in primary chick kidney cells. Arch Virol. 1976;52:101-11. [ Links ]

26. Winter PM, Dung NM, Loan HT, Kneen R, Wills B, Thu LT, et al. Proinflammatory Cytokines and Chemokines in Humans with Japanese Encephalitis. J Infect Dis. 2004;190:1618-26. [ Links ]

27. Campbell IL, Stalder AK, Chiang CS, Bellinger R, Heyser CJ, Steffensen S, et al. Transgenic models to assess the pathogenic actions of cytokines in the central nervous system. Mol Psychiatry. 1997;2:125-9. [ Links ]

28. Sheng WH, Chiang BL, Chang SC, Ho HN, Wang JT, Chen YC, et al. Clinical manifestations and inflammatory cytokine responses in patients with severe acute respiratory syndrome. J Formos Med Assoc. 2005;104:715-23. [ Links ]

29. Wong CK, Lam CW, Wu AK, Ip WK, Lee NL, Chan IH, et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin Exp Immunol. 2004;136:95-103. [ Links ]

30. Yu D, Zhu H, Liu Y, Cao J, Zhang X. Regulation of Proinflammatory Cytokine Expression in Primary Mouse Astrocytes by Coronavirus Infection. J Virol. 2009;83:12204-14. [ Links ]

31. Singh A, Kulshreshtha R, Mathur A. Secretion of the chemokine interleukin-8 during Japanese encephalitis virus infection. J Med Microbiol. 2000;49:607-12. [ Links ]

32. Arbour N, Day R, Newcombe J, Talbot PJ. Neuroinvasion by Human Respiratory Coronaviruses. J Virol. 2000;74:8913-21. [ Links ]

33. Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of COVID-19. medRxiv. 2020;10.1101/2020.02.22.20026500. [ Links ]

34. Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8:420-2. [ Links ]

35. Wu A, Peng Y, Huang B, Ding X, Wang X, Niu P, et al. Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China. Cell Host Microbe. 2020;27:325-8. [ Links ]

36. Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis. 2020 (in press). doi: 10.1093/cid/ciaa330. [ Links ]

37. Porciatti V, Burr DC, Morrone MC, Fiorentini A. The effects of aging on the pattern electroretinogram and visual evoked potential in humans. Vision Res. 1992;32:1199-209. [ Links ]

38. Berth SH, Leopold PL, Morfini G. Virus-induced neuronal dysfunction and degeneration. Front Biosci. 2009;14:5239-59. [ Links ]

39. Jacomy H, Talbot PJ. Vacuolating encephalitis in mice infected by human coronavirus OC43. Virology. 2003;315:20-33. [ Links ]

40. McCray PB, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L, et al. Lethal Infection of K18-hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus. J Virol. 2007;81:813-21. [ Links ]

41. Butler N, Pewe L, Trandem K, Perlman S. Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated. Virology. 2006;347:410-21. [ Links ]

42. Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe Acute Respiratory Syndrome Coronavirus Infection Causes Neuronal Death in the Absence of Encephalitis in Mice Transgenic for Human ACE2. J Virol. 2008;82:7264-75. [ Links ]

43. Barnett EM, Perlman S. The olfactory nerve and not the trigeminal nerve is the major site of CNS entry for mouse hepatitis virus, strainJHM. Virology. 1993;194:185-91. [ Links ]

44. Brann D, Tsukahara T, Weinreb C, Logan DW, Datta SR. Non-neural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients. bioRxiv. 2020 27; 10.1101/2020.03.25.009084. [ Links ]

45. Lu C wei, Liu X fen, Jia Z fang. 2019-nCoV transmission through the ocular surface must not be ignored. Lancet. 2020;395:e39. doi: 10.1016/S0140-6736(20)30313-5 [ Links ]

46. Zhou P, Yang X Lou, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-3. [ Links ]

47. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol. 2020;94. [ Links ]

48. Sun C, Wang Y, Liu G, Liu Z. Role of the Eye in Transmitting Human Coronavirus: What We Know and What We Do Not Know. Preprints. 2020 [cited 2020 Apr 11]. Available from: Available from: https://www.preprints.org/manuscript/202003.0271/v1Links ]

49. Koizumi N, Nishida K, Adachi W, Tei M, Honma Y, Dota A, et al. Detection of herpes simplex virus DNA in atypical epitelial keratitis using polymerase chain reaction. Br J Ophthalmol. 1999;83:957-60. [ Links ]

50. Robert PY, Traccard I, Adenis JP, Denis F, Ranger-Rogez S. Multiplex detection of herpesviruses in tear fluid using the “stair primers” PCR method: Prospective study of 93 patients. J Med Virol. 2002;66:506-11. [ Links ]

51. Hidalgo F, Melón S, de Oña M, Do Santos V, Martínez A, Cimadevilla R, et al. Diagnosis of herpetic keratoconjunctivitis by nested polymerase chain reaction in human tear film. Eur J Clin Microbiol Infect Dis. 1998;17:120-3. [ Links ]

52. Willoughby CE, Baker K, Kaye SB, Carey P, O’Donnell N, Field A, et al. Epstein-Barr virus (types 1 and 2) in the tear film in Sjogren’s syndrome and HIV infection. J Med Virol. 2002;68:378-83. [ Links ]

53. Loon SC, Teoh SCB, Oon LLE, Se-Thoe SY, Ling AE, Leo YS, et al. The severe acute respiratory syndrome coronavirus in tears. Br J Ophthalmol. 2004;88:861-3. [ Links ]

54. Van Der Hoek L, Pyrc K, Jebbink MF, Vermeulen-Oost W, Berkhout RJM, Wolthers KC, et al. Identification of a new human coronavirus. Nat Med. 2004;10:368-73. [ Links ]

55. Vabret A, Mourez T, Dina J, Van Der Hoek L, Gouarin S, Petitjean J, et al. Human coronavirus NL63, France. Emerg Infect Dis. 2005;11:1225-9. [ Links ]

56. Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020. (in press). doi: 10.1056/NEJMoa2002032. [ Links ]

57. Chen L, Deng C, Chen X, Zhang X, Chen B, Yu H, et al. Ocular manifestations and clinical characteristics of 534 cases of COVID-19 in China: A cross-sectional study. medRxiv. 2020;: 10.1101/2020.03.12.20034678. [ Links ]

58. Xia J, Tong J, Liu M, Shen Y, Guo D. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J Med Virol. 2020:1-6. [ Links ]

59. Qing H, Li Z, Yang Z, Shi M, Huang Z, Song J, et al. The possibility of COVID-19 transmission from eye to nose. Acta Ophthalmol. 2020;65580903. [ Links ]

60. Culbertson WW, Blumenkranz MS, Pepose JS, Stewart JA, Curtin VT. Varicella zoster virus is a cause of the acute retinal necrosis syndrome. Ophthalmology. 1986;93:559-69. [ Links ]

61. Sarkies N, Gregor Z, Forsey T, Darougar S. Antibodies to herpes simplex virus type I in intraocular fluids of patients with acute retinal necrosis. Br J Ophthalmol. 1986;70:81-4. [ Links ]

62. Jabs DA, Green WR, Fox R, Polk BF, Bartlett JG. Ocular Manifestations of Acquired Immune Deficiency Syndrome. Ophthalmology. 1989;96:1092-9. [ Links ]

63. Payne FE, Baublis J V., Itabashi HH. Isolation of measles vírus from cell cultures of brain from a patient with subacute sclerosing panencephalitis. N Engl J Med. 1969;281:585-9. [ Links ]

64. Ryan SJ, Maumenee AE. Acute posterior multifocal placoid pigment epitheliopathy. Am J Ophthalmol. 1972;74:1066-74. [ Links ]

65. Wright BE, Bird AC, Hamilton AM. Placoid pigment epitheliopathy and Harada’s disease. Br J Ophthalmol. 1978;62609-21. [ Links ]

66. Robbins SG, Detrick B, Hooks JJ. Ocular tropisms of murine coronavirus (strain JHM) after inoculation by various routes. Invest Ophthalmol Vis Sci. 1991;32:1883-93. [ Links ]

67. Robbins SG, Hamel CP, Detrick B, Hooks JJ. Murine coronavírus induces an acute and long-lasting disease of the retina. Lab Invest. 1990;62:417-26. [ Links ]

68. Hooks JJ, Percopo C, Wang Y, Detrick B. Retina and retinal pigment epithelial cell autoantibodies are produced during murine coronavirus retinopathy. J Immunol September; 1993;151:3381-9. [ Links ]

69. Roos RP. Genetically controlled resistance to virus infections of the central nervous system. Prog Med Genet. 1985;6:241-76. [ Links ]

70. Percopo CM, Hooks JJ, Shinohara T, Caspi R, Detrick B. Cytokine-mediated activation of a neuronal retinal resident cell provokes antigen presentation. J Immunol. 1990;145:4101-7. [ Links ]

71. Detrick B, Rodrigues M, Chan CC, Tso MO, Hooks JJ. Expression of HLA-DR antigen on retinal pigment epithelial cells in retinitis pigmentosa. Am J Ophthalmol. 1986;101:584-90. [ Links ]

72. Detrick B, Newsome DA, Percopo CM, Hooks JJ. Class II antigen expression and gamma interferon modulation of monocytes and retinal pigment epithelial cells from patients with retinitis pigmentosa. Clin Immunol Immunopathol. 1985;36:201-11. [ Links ]

73. Hooks JJ, Chan CC, Detrick B. Identification of the lymphokines, interferon-gamma and interleukin-2, in inflammatory eye diseases. Invest Ophthalmol Vis Sci. 1988;29:1444-51. [ Links ]

74. Lavi E, Gilden DH, Wroblewska Z, Rorke LB, Weiss SR. Experimental demyelination produced by the a59 strain of mouse hepatitis virus. Neurology. 1984;34:597-603. [ Links ]

75. Stohlman SA, Weiner LP. Chronic central nervous system demyelination in mice after JHM virus infection. Neurology. 1981;31:38-44. [ Links ]

76. Wang Y, Burnier M, Detrick B, Hooks JJ. Genetic predisposition to coronavirus-induced retinal disease. Invest Ophthalmol Vis Sci. 1996;37:250-4. [ Links ]

77. Bergmann CC, Lane TE, Stohlman SA. Coronavirus infection of the central nervous system: Host-virus stand-off. Nat Ver Microbiol. 2006;4:121-32. [ Links ]

78. Siam AL, Meegan JM, Gharbawi KF. Rift Valley fever ocular manifestations: Observations during the 1977 epidemic in Egypt. Br J Ophthalmol. 1980;64:366-74. [ Links ]

79. Al-Hazmi A, Al-Rajhi AA, Abboud EB, Ayoola EA, Al-Hazmi M, Saadi R, et al. Ocular complications of Rift Valley fever outbreak in Saudi Arabia. Ophthalmology. 2005;112:313-8. [ Links ]

80. Kaiser PK, Lee MS, Martin DA. Occlusive vasculitis in a patient with concomitant West Nile virus infection. Am J Ophthalmol. 2003;136:928-30. [ Links ]

81. Chan CK, Limstrom SA, Tarasewicz DG, Lin SG. Ocular Features of West Nile Virus Infection in North America. A Study of 14 Eyes. Ophthalmology. 2006;113:1539-46. [ Links ]

82. Teitelbaum BA, Newman TL, Tresley DJ. Occlusive retinal vasculitis in a patient with West Nile virus. Clin Exp Optom. 2007;90:463-7. [ Links ]

83. Zeng JH, Liu Y-X, Yuan J, Wang F-X, Wu W-B, Li J-X, et al. First Case of COVID-19 Infection with Fulminant Myocarditis Complication: Case Report and Insights. Preprints. 2020;2020030180. [ Links ]

84. Jones L, Walsh K, Willcox M, Morgan P, Nichols J. The COVID-19 pandemic: Important considerations for contact lens practitioners. Contact Lens Anterior Eye. 2020 (in press). doi: 10.1016/j.clae.2020.03.012. [ Links ]

85. Zeri F, Naroo SA. Contact lens practice in the time of COVID-19. Contact Lens and Anterior Eye. Amsterdam: Elsevier B.V.; 2020. [ Links ]

86. Lian KY, Napper G, Stapleton FJ, Kiely PM. Infection control guidelines for optometrists 2016. Clin Exp Optom. 2017;100:341-56. [ Links ]

87. Recomendações de Oftalmologia perante a situação de risco epidemiológico de infecção por COVID-19 - Ordem dos Médicos. [cited 2020 Apr 14]. Available from: Available from: https://ordemdosmedicos.pt/recomendacoes-de-oftalmologia-perante-a-situacao-de-risco-epidemiologico-de-infeccao-por-covid-19/Links ]

88. Osterholm MT, Kelley NS, Sommer A, Belongia EA. Efficacy and effectiveness of influenza vaccines: A systematic review and meta-analysis. Lancet Infect Dis. 2012;12:36-44. [ Links ]

89. Wan KH, Huang SS, Young A, Chiu Lam DS. Precautionary measures needed for ophthalmologists during pandemic of the coronavirus disease 2019 (COVID-19). Acta Ophthalmol. 2020;98:221-2. doi: 10.1111/aos.14438. [ Links ]

90. Lai TH, Tang EW, Chau SK, Fung KS, Li KK. Stepping up infection control measures in ophthalmology during the novel coronavírus outbreak: an experience from Hong Kong. Graefe’s Arch Clin Exp Ophthalmol. 2020;258:1049-55. doi: 10.1007/s00417-020-04641-8. [ Links ]

91. Li JPO, Lam DSC, Chen Y, Ting DSW. Novel Coronavirus disease 2019 (COVID-19): The importance of recognising possible early ocular manifestation and using protective eyewear. Br J Ophthalmol. 2020;104:297-8. doi: 10.1136/bjophthalmol-2020-315994. [ Links ]

92. Aleci C. COVID-19 and Opthalmologists. Neuro Ophthalmol Vis Neurosci. 2020;5:1-1. [ Links ]

93. Lai TH, Tang EW, Chau SK, Fung KS, Li KK. Stepping up infection control measures in ophthalmology during the novel coronavirus outbreak: an experience from Hong Kong. Graefe's Archive for Clinical and Experimental Ophthalmology 2020;258:1049-55. doi: 10.1007/s00417-020-04641-8. [ Links ]

Ethical disclosures

Financing support: This work has not received any contribution, grant or scholarship

Provenance and peer review: Not commissioned; externally peer reviewed

Responsabilidades éticas

Suporte financeiro: O presente trabalho não foi suportado por nenhum subsídio ou bolsa

Proveniência e revisão por pares: Não comissionado; revisão externa por pares

Received: April 29, 2020; Accepted: April 30, 2020; Published: May 22, 2020

Corresponding Author/Autor Correspondente: João Paulo Cunha [joao.cunha@jmellosaude.pt] R. Fernão Lopes 60, 2750-663 Cobre, Cascais, Portugal ORCID iD: 0000-0002-3162-0531

Conflicts of interest:

The authors have no conflicts of interest to declare.

Conflitos de interesse:

Os autores declaram não possuir conflitos de interesse.

Creative Commons License This is an open-access article distributed under the terms of the Creative Commons Attribution License