The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has escalated rapidly since December 2019. Understanding the ophthalmic manifestations in patients and animal models of the novel coronavirus may have implications for disease surveillance. Recognition of the potential for viral transmission through tear film has ramifications for patients, physicians, and the public.
Methods:
Information from relevant published journal articles was surveyed using a computerized PubMed search and public health websites. We summarize knowledge of ophthalmic manifestations of SARS-CoV-2 infection in patients and animal models, risk-mitigation measures for patients and providers, and implications for retina specialists.
Results:
SARS-CoV-2 is efficiently transmitted among humans, and although the clinical course is mild in most infected patients, severe complications including pneumonia, acute respiratory distress syndrome, and death can ensue, most often in elderly patients and individuals with comorbidities. Conjunctivitis occurs in a minority of patients with COVID-19, and SARS-CoV-2 RNA has been identified primarily with conjunctivitis. Uveitis has been observed in animal models of coronavirus infection, and cotton-wool spots have been reported recently.
Conclusions:
SARS-CoV-2 and other coronaviruses have been rarely associated with conjunctivitis. Identification of SARS-CoV and SARS-CoV-2 RNA in the tear film of patients and its highly efficient transmission via respiratory aerosols supports eye protection, mask, and gloves as part of infection prevention and control recommendations for retina specialists. Disease surveillance during the COVID-19 pandemic may also include ongoing evaluation for uveitis and retinal disease given prior findings from animal models and a recent report of retinal manifestations.
ZhuNZhangDWangW, et al.China Novel Coronavirus Investigating and Research Team. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med.2020;382(8):727–733. doi:10.1056/NEJMoa2001017
3.
GorbalenyaAEBakerSCBarisRS, et al.The species Severe Acute Respiratory Syndrome-Related Coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nat Microbiol.2020;5:536–544. doi:10.1038/s41564-020-0695-z
4.
ZiółkowskaNPaździor-CzapulaKLewczukB, et al.Feline infectious peritonitis: Immunohistochemical features of ocular inflammation and the distribution of viral antigens in structures of the eye. Vet Pathol. 2017;54(6):933–944. doi:10.1177/0300985817728557
5.
MwaseMShimadaKMumbaC. Positive immunolabelling for feline infectious peritonitis in an African lion (Panthera leo) with bilateral panuveitis. J Comp Pathol. 2015;152(2-3):265–268. doi:10.1016/j.jcpa.2014.12.006
6.
HooksJJPercopoCWangYDetrickB. Retina and retinal pigment epithelial cell autoantibodies are produced during murine coronavirus retinopathy. J Immunol. 1993;151(6):3381–3389.
7.
KomurasakiYNagineniCNWangY. Virus RNA persists within the retina in coronavirus-induced retinopathy. Virology. 1996;222(2):446–450. doi:10.1006/viro.1996.0442
8.
RobbinsSGWiggertBKuttyGChaderGJDetrickBHooksJJ. Redistribution and reduction of interphotoreceptor retinoid-binding protein during ocular coronavirus infection. Invest Ophthalmol Vis Sci. 1992; 33(1):60–67.
9.
RobbinsSGHamelCPDetrickBHooksJJ. Murine coronavirus induces an acute and long-lasting disease of the retina. Lab Invest. 1990;62(4):417–426.
10.
VabretAMourezTDinaJ, et al.Human coronavirus NL63, France. Emerg Infect Dis. 2005;11(8):1225–1229. doi:10.3201/eid1108.050110
11.
AlmeidaJDBerryDMCunninghamCH, et al.Virology: Coronaviruses. Nature. 1968;220:650. doi:10.1038/220650b0
12.
LeeHJShiehCKGorbalenyaAE, et al.The complete sequence (22 kilobases) of murine coronavirus gene 1 encoding the putative proteases and RNA polymerase. Virology. 1991;180(2):567–582. doi:10.1016/0042-6822(91)90071-i
13.
SongZXuYBaoL, et al.From SARS to MERS, thrusting coronaviruses into the spotlight. Viruses. 2019;11(1):59. doi:10.3390/v11010059
14.
ChenYGuoYPanYZhaoZJ. Structure analysis of the receptor binding of 2019-nCoV. Biochem Biophys Res Commun. 2020;525(1):135–140. doi:10.1016/j.bbrc.2020.02.071
15.
WrappDWangNCorbettKS, et al.Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260–1263. doi:10.1126/science.abb2507
16.
SungnakWHuangNBécavinC, et al.HCA Lung Biological Network. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nat Med.2020;26(5):681–687. doi:10.1038/s41591-020-0868-6
17.
SunKGuLMaLDuanY. Atlas of ACE2 gene expression in mammals reveals novel insights in transmission of SARS-CoV-2. bioRxiv2020.03.015655. doi:10.1101/2020.03.30.015644
18.
Human coronavirus types. Centers for Disease Control and Prevention. Published 2020. Last reviewed February 15, 2020. Accessed July 6, 2020. www.cdc.gov/coronavirus/types.html
19.
HamreDProcknowJJ. A new virus isolated from the human respiratory tract. Proc Soc Exp Bio Med. 1966;121(1):190–193. doi:10.3181/00379727-121-30734
20.
McIntoshKDeesJHBeckerWBKapikianAZChanockRM. Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease. Proc Natl Acad Sci USA. 1967;57(4):933–940. doi:10.1073/pnas.57.4.933
21.
Abdul-RasoolSFieldingBC. Understanding human coronavirus HCoV-NL63. Open Virol J. 2010;4:76–84. doi:10.2174/1874357901004010076
22.
YinYWunderinkRG. MERS, SARS and other coronaviruses as causes of pneumonia. Respirology. 2018;23(2):130–137. doi:10.1111/resp.13196
23.
DrostenCGüntherSPreiserW, et al.Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003;348(20):1967–1976. doi:10.1056/NEJMoa030747
24.
LuPRZhaoXLiJ, et al.Genomic characterisation and epidemiology for 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet. 2020;395(10224):565–574. doi:10.1016/S0140-6736(20)30251-8
25.
ZhouPYangXLWangXG, et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273. doi:10.1038/s41586-020-2012-7
26.
LiuPChenWuChenJP. Viral metagenomics revealed Sendai virus and coronavirus infection of Malayan pangolins (Manis javanica). Viruses. 2019;11(11):979. doi:10.3390/v11110979
27.
XiaoKZhaiJFengY, et al.Isolation and characterization of 2019-nCoV-like coronavirus from Malayan pangolins. bioRxiv2020.02.17.951335. doi:10.1101/2020.02.17.951335
28.
GrahamRLBaricRS. Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission. J Virol. 2010;84(7):3134–3146. doi:10.1128/JVI.01394-09
29.
ZakiAMvan BoheemenSBestebroerTMOsterhausADMEFouchierRAM. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367(19):1814–1820. doi:10.1056/NEJMoa1211721
30.
Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. Based on data as of the 31 December2003. World Health Organization. Published 2003. Accessed July 6, 2020. http://www.who.int/csr/sars/country/table2004_04_21/en/
31.
HeJFPengGWZhengHZ, et al.An epidemiological study on the index cases of severe acute respiratory syndrome [which] occurred in different cities among Guangdong province [in Chinese]. Zhonghua Liu Xing Bing Xue Za Zhi. 2003;24(5):347–349.
32.
Severe Acute Respiratory Syndrome (SARS) Epidemiology Working Group. Consensus document on the epidemiology of severe acute respiratory syndrome (SARS). World Health Organization, 2003. Accessed June 25, 2020. www.who.int/csr/sars/en/WHOconsensus.pdf
33.
ZhaoJFangSSHeYQ, et al.Detection of SARS-coronavirus in both humans and animals by RT-PCR [in Chinese]. Wei Sheng Yan Jiu. 2005;34(4):412–415.
34.
BanerjeeAKulscarKMisraVFriemanMMossmanK. Bats and coronaviruses. Viruses. 2019;11(1):41. doi:10.3390/v11010041
35.
Middle East respiratory syndrome coronavirus (MERS-CoV). MERS monthly summary, November 2019. World Health Organization. Accessed June 25, 2020. www.who.int/emergencies/mers-cov/en/
KimKHTandiTEChoiJWMoonJMKimMS. Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics, and public health implications. J Hosp Infect. 2017;95(2):207–213. doi:10.1016/j.jhin.2016.10.008
38.
HaagmansBLAl DhahirySHReuskenCB, et al.Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect Dis. 2014;14(2):140–145. doi:10.1016/S1473-3099(13)70690-X
39.
AzharEIEl-KafrawySAFarrajSA, et al.Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med. 2014;370(26):2499–2505. doi:10.1056/NEJMoa1401505
40.
GuanWJNiZYLiangWH, et al.for the China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–1720. doi:10.1056/NEJMoa2002032
41.
HuangCWangYLiX, et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi:10.1016/S0140-6736(20)30183-5
42.
ShiHHanXJiangN, et al.Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study.Lancet Infect Dis. 2020;20(4):425–434. doi:10.1016/S1473-3099(20)30086-4
43.
ChenNZhouMDongX, et al.Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–513. doi:10.1016/S0140-6736(20)30211-7
44.
PhanLTNguyenTVLuongQC, et al.Importation and human-to-human transmission of a novel coronavirus in Vietnam. N Engl J Med. 2020;382(9):872–874. doi:10.1056/NEJMc2001272
45.
HolshueMLHDeBoltCLindquistS; Washington State 2019-nCoV Case Investigation Team. First case of 2019 novel coronavirus in the United States. N Engl J Med. 2020;382(10):929–936. doi:10.1056/NEJMoa2001191
46.
LiQGuanXWuP, et al.Early transmission dynamics in Wuhan, China of novel coronavirus-infected pneumonia. N Engl J Med.2020;382(13):1199–1207. doi:10.1056/NEJMoa2001316
47.
MunsterVJKoopmansMvan DoremalenNvan RielDde WitE. A novel coronavirus emerging in China—key questions for impact assessment. N Engl J Med. 2020;382(8):692–694. doi:10.1056/NEJMp2000929
48.
ArentzNYimEKlaffL, et al.Characteristics and outcomes of 21 critically ill patients with COVID-19 in Washington State. JAMA. 2020;323(16):1612–1614. doi:10.1001/jama.2020.4326
49.
BhatrajuPKGhassemiehBJNicholsM, et al.Covid-19 in critically ill patients in the Seattle region—case series. N Engl J Med. 2020;382(21):2012–2022. doi:10.1056/NEJMoa2004500
50.
XiaJTongJLiuMShenYGuoD. Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection. J Med Virol. 2020;92(6):589–594. doi:10.1002/jmv.25725
51.
StoecklinSBRollandPSilueY, et al.Investigation Team. First case of coronavirus disease 2019 (COVID-19) in France: surveillance, investigations and control measures, January 2020. Euro Surveill.2020;25(6):2000094. doi:10.2807/1560-7917.ES.2020.25.6.2000094
52.
ZhangXChenXChenL, et al.The evidence of SARS-COV-2 infection on ocular surface. Ocul Surf. 2020;18(3):360–362. doi:10.1016/j.jtos.2020.03.010
53.
JunISYAndersonDEKangAEZ, et al.Assessing viral shedding and infectivity of tears in coronavirus disease 2019 (COVID-2019) patients. Ophthalmology. 2020;127(7):977–979. doi:10.1016/j.ophtha.2020.03.026
54.
ColavitaFLapaDCarlettiF, et al.SARS-CoV-2 isolation from ocular secretions of a patient with COVID-19 in Italy with prolonged viral RNA detection. Ann Int Med. 2020;M20–1176. doi:10.7326/M20-1176
55.
LiuWZhangQChenJ, et al.Detection of Covid-19 in children in early January 2020 in Wuhan, China. N Engl J Med. 2020;382(14):1370–1371. doi:10.1056/NEJMc2003717
56.
MarinhoPMMarcosAAARomanoACNascimentoHBelfortRJr. Retinal findings in patients with COVID-19. Lancet. 2020;395(10237):1610. doi:10.1016/S0140-6736(20)31014-X
57.
Case definitions for surveillance of severe acute respiratory syndrome (SARS). World Health Organization. Revised May 1, 2003. Accessed June 25, 2020. https://www.who.int/csr/sars/casedefinition/en/
58.
ChanWMYuenKSCFanDSPLamDSCChanPKSSungJJY. Tears and conjunctival scrapings for coronavirus in patients with SARS. Br J Ophthalmol. 2004;88(7):968–969. doi:10.1136/bjo.2003.039461
BauerBSKerrMESandmeyerLSGrahnBH. Positive immunostaining for feline infectious peritonitis (FIP) in a sphinx cat with cutaneous lesions and bilateral panuveitis. Vet Ophthalmol. 2013;16(suppl 1):160–163. doi:10.1111/vop.12044
61.
WangYBurnierMDetrickBHooksJJ. Genetic predisposition to coronavirus-induced retinal disease. Invest Ophthalmol Vis Sci. 1996;37(1):250–254.
62.
LoonSCTeohSCBOonLLE, et al.The severe acute respiratory syndrome coronavirus in tears. Br J Ophthalmol. 2004;88(7):861–863. doi:10.1136/bjo.2003.035931
63.
CooperTKSwordJJohnsonJC, et al.New insights into Marburg virus disease pathogenesis in the Rhesus macaque model. J Infect Dis. 2018;218(suppl 5):S423–S433. doi:10.1093/infdis/jiy367
64.
LarsenTStevensELDavisKJ, et al.Pathologic findings associated with delayed death in nonhuman primates experimentally infected with Zaire Ebola virus. J Infect Dis. 2007;196(suppl 2):S323–S328. doi:10.1086/520589
