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Keratoconjunctivitis as the initial 60
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medical presentation of the novel 62
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10 coronavirus disease 2019 64

(COVID-19): X A case report

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12 Q1 66
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15 Q2 1X XMarvi
XD Cheema, D2X XMD,*,a D3X XHelya Aghazadeh, D4X XMD,*,a D5X XSamir Nazarali, D6X XMD,*,a D7X XAndrew Ting, D8X XMD, FRCSC,* 69
16 D9X XJennifer Hodges, D10X XMD, FRCSC,* D1X XAlexandra McFarlane, D12X XMD, FRCP(C),y,z 70
17 D13X XJamil N. Kanji, D14X XMD, DTM&H, FRCP(C),y,x D15X XNathan Zelyas, D16X XMD, MSc, D(ABMM), FRCP(C),x,║ 71
18 D17X XKarim F. Damji, D18X XMD, FRCSC,*,b D19X XCarlos Solarte, D20X XMD, MPH*,b 72
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20 Q3 We present a case of coronavirus X Xdisease 2019 (COVID-19) with an initial medical presentation of keratoconjuncti- 74
21 vitis, the first such reported case in North America. This patient presented initially to ophthalmology with kerato- 75
22 Q4 conjunctivitis and X Xmild respiratory symptoms, without fever, and developed worsening symptoms over the course 76
23 of the next several days. This case emphasizes the importance of ensuring that first-line health care providers, 77
24 including ophthalmologists, optometrists, emergency physicians, and family physicians, consider COVID-19 on 78
25 the differential for any patient with recent travel who presents with acute conjunctivitis. Having a high index of sus- 79
26 picion with this presentation would allow for appropriate precautions to be taken to prevent further spread of 80
27 COVID-19. 81
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31 CASE 3, she had worsening eye-related symptoms of photophobia, 85
32 a sore and swollen eyelid, and mucous discharge of the right 86
A 29-year-old, otherwise healthy woman presented to the
33 eye. On examination, she had 20/20 visual acuity OU. 87
emergency eye clinic with a 1-day history of right eye con-
34 Anterior segment examination of the affected eye was 88
junctivitis, photophobia, and clear watery discharge from
35 remarkable for 12+ conjunctival injection, 3+ follicles, 1 89
the right eye. She returned from a 1-month vacation in the
36 small pseudodendrite in the inferior temporal cornea, and 8 90
Philippines 3 days before presentation; she spent 1 day in
37 small (0.2 mm) subepithelial infiltrates with overlying epi- 91
San Francisco en route to her return to Canada. During her
38 thelial defects at the superior temporal limbus. Fundus 92
time in the Philippines, she swam in the ocean and hotel
39 examinations were unremarkable without any evidence of 93
swimming pools. She was feeling well on her date of return
40 inflammation (Table 1 and Fig. 2). The patient was started 94
on February 29. In Canada, she visited a public swimming
41 on oral valacyclovir 500 mg PO TID and moxifloxacin 1 95
pool the day after return. On March 1, 18 hours after return
42 drop QID to the right eye based on a presumed diagnosis of 96
from her trip, she developed rhinorrhea, cough, nasal con-
43 herpetic keratoconjunctivitis. 97
gestion, and right eye conjunctivitis; she denied any fever
44 The following day, the patient’s family physician coordi- 98
Q5 though took over-the-counter antipyretic medication .X X Her
45 nated a throat swab to screen for acute pharyngitis, which 99
travel partner developed a cough and rhinorrhea soon after
46 was negative for group A Streptococcus. Blood work was 100
she did (although he has tested negative for coronavirus dis-
47 done, including a complete blood count and electrolytes, 101
ease 2019 [COVID-19]).
48 which were all within normal limits. 102
The patient was initially seen by her family doctor on the
49 The patient returned to the eye clinic on March 5 owing 103
day of symptom onset and referred to ophthalmology
50 to worsening redness, pain, and irritation. A tender right 104
(Fig. 1). Upon the first presentation to our service on March
51 pre-auricular node was noted. Visual acuity was measured to 105
52 be 20/20 OU. On slit-lamp examination, 2+ conjunctival 106
53
Q6 a
Denotes co-authors .X X injection was noted along with a change in the appearance 107
54 b
Denotes senior co-authors. of cornea, showing the development of numerous 108

https://doi.org/10.1016/j.jcjo.2020.03.003
ISSN 0008-4182
© 2020 Canadian Ophthalmological Society.
Published by Elsevier Inc. All rights reserved.
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Fig. 1—External photograph of the right eye after instillation of fluorescein taken under cobalt blue light demonstrating areas of fluo- 182
rescein uptake consistent with the epithelial changes. Photograph was taken by the patient at her family doctor’s office (March 2nd)
127 before her first visit to the eye clinic; photograph provided by the patient (used with permission). 183
128 184
129 subepithelial infiltrates with overlying epithelial defects. 185
130 Table 1—Summary of clinical findings over progressive visits Right after initial fluorescein, there was only pin-point 186
131 to ophthalmology staining with associated overlying epithelial defects on the 187
132 Ophthalmology Visit March 3 March 5 March 6 temporal cornea (Table 1 and Fig. 3). The patient was con- 188
133 Vision tinued on oral valacyclovir and moxifloxacin drops, but a 189
OD 20/20 20/20 20/40 ! pinhole to
134 presumed diagnosis of epidemic keratoconjunctivitis was 190
20/30
135 OS 20/20 20/20 20/20 given and contact precautions were suggested X X. Q8 191
136 Intraocular pressure (measured by tonopen), mm Hg 192
Fig. 4.
137 OD 16 21 22 The patient was seen by ophthalmology the next day on 193
OS 13 18 18
138 March 6th owing to persistently worsening symptoms and 194
Pupils
139 vision decline. At this visit, vision in the right eye was 20/ 195
Q7 No RAPD No RAPD No RAPD X X
140 Left eye examination 30 with pinhole to 20/30. A tender right preauricular lymph 196
141 node was again noted, as well as cervical lymphadenopathy. 197
Within normal Within normal Within normal
142 limits limits limits Slit-lamp examination of the eye revealed follicular con- 198
143 junctivitis with 2+ conjunctival injection and over 50 199
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162 Fig. 2—Schematic representation of the slit-lamp examination findings over progressive clinic visits; note the increase in the cornea 218
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lesions over time. 219
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Keratoconjunctivitis as the initial medical presentation of the novel coronavirus

221 discrete areas of subepithelial infiltrates with overlying epi- the American Academy of Ophthalmology discussed con- 277
222 thelial defects spread diffusely through the entire cornea junctivitis as a presenting symptom of COVID-19 in 278
223 (Table 1; Fig. 2). The patient was continued on valacyclo- affected patients.4 This was based on increasing awareness 279
224 vir, counselled regarding this being very contagious given and information provided by the U.S. Centers for Disease 280
225 the presumed viral etiology. Conjunctival swabs to test for Control and Prevention and the WHO. 281
226 chlamydia, gonorrhea, and bacterial culture were sent and Initial reports of COVID-19 did not report ocular transmis- 282
227 were negative. sion as a possibility. Xia and colleagues at the First Affiliated 283
228 At the time of the visits to our clinic (March 3rd and Hospital of Zhejiang University evaluated the conjunctival 284
229 5th), the patient did not meet provincial health authority secretions of 30 confirmed cases of COVID-19.5 In one of 285
230 recommendations for testing of coronavirus infectious dis- these patients, both tear and conjunctival secretions tested 286
231 ease 2019 (COVID-19) based on country of travel. By positive for the virus by rRT-PCR.5 Additionally, data 287
232 March 6, however, testing recommendations in terms of from 1099 patients were published in the New England 288
233 geographic locations visited had expanded to any person Journal of Medicine, in which “conjunctival congestion” 289
234 with symptoms who had travelled outside of Canada. Thus, was found in 0.8% of the patients.6 Despite these uncom- 290
235 the Medical Officer of Health and institutional Infection monly reported statistics, there are numerous anecdotal 291
236 Prevention and Control were contacted and facilitated test- reports of a red eye being the initial symptom before the 292
237 ing. A nasopharyngeal (NP) swab collected on March 8th onset of pneumonia, including that of Guangfa Wang, a 293
238 was positive for detection of the SARS-CoV-2 virus (the national expert on the panel for pneumonia during the 294
239 causative agent of COVID-19) by an in-house real-time early investigations in Wuhan, China.7 Mr. Wang wore an 295
240 reverse transcriptase polymerase chain reaction (rRT-PCR), N95 mask during his initial investigations of patients in 296
241 Q9 using the E X X and the RNA-dependent RNA polymerase Wuhan but did not have any protective eye equipment. 297
242 (RdRp) genes as targets, respectively. Several days before his respiratory symptoms, he reported 298
243 Retrospective testing of the eye swab originally submitted having a red eye, suggesting possible ocular transmission.8 299
244 for gonorrhea/chlamydia PCR on March 6th was found to Given this, eye care professionals, most notably ophthal- 300
245 be weakly positive for the SARS-CoV-2 virus (COVID-19) mologists, may be the first point of contact in the health 301
246 as well. Although the viral loads were not directly quanti- care field for patients with possible COVID-19, before the 302
247 fied, cycle thresholds of rRT-PCR assays from the NP swab onset of characteristic respiratory symptoms. 303
248 produced stronger signal than those from the eye swab In this case report, it can be seen that the clinical presen- 304
249 (2325 cycles in NP vs 37 in eye; negative considered tation can vary and fluctuate. The patient did not present 305
250 undetectable or >40 cycles). with conjunctivitis as previously reported for COVID-19 306
251 Workplace Health and Safety, Public Health, and Infec- cases, but as keratoconjunctivitis. It was also apparent from 307
252 tion Prevention and Control collaborated on follow-up of the clinical examinations that the epithelial defects varied 308
253 health care workers and clinic patients who may have been from one examination to the next and appeared as a pseudo- 309
254 in contact with the case patient. dendrite perhaps from a healing epithelial defect or possibly 310
255 as a progressing subepithelial infiltrate. 311
256 Therefore, front-line health care and eye care providers, 312
257 including family physicians, emergency physicians, ophthal- 313
DISCUSSION
258 mologists, and optometrists, seeing patients presenting with 314
259 To the best of our knowledge, this is the first reported case a red eye should ensure that a thorough review of infectious 315
260 of COVID-19 (caused by the SARS-CoV-2 virus) present- contacts and travel history is undertaken. Patients who 316
261 ing with keratoconjunctivitis as the main symptom. have red eye; respiratory symptoms such as X X cough and short- Q10 317
262 On January 5, 2020, the World Health Organization ness of breath; and recently travelled to areas with known 318
263 (WHO) published a report on a pneumonia of unknown outbreaks are at higher risk of having COVID-19. Clinical 319
264 cause detected in Wuhan City, Hubei Province of China.1 interactions with any patients presenting with similar upper 320
265 Analysis of lower respiratory tract samples isolated from respiratory tract symptoms should be done with mouth and 321
266 affected cases implicated a novel coronavirus as the causa- eye protection routinely, if exposure to the patient’s secre- 322
267 tive agent in this illness. As of March 11, 2020, COVID-19 tions is possible. This would be expected during the proxim- 323
268 has been confirmed in 118 326 individuals worldwide, with ity of an eye examination.9 Our case highlights the 324
269 4292 associated deaths.2 This illness is being compared with necessity of using these additional precautions as the 325
270 other global coronavirus-related outbreaks such as severe patient’s conjunctival swab was positive for SARS-CoV-2, 326
271 acute respiratory syndrome (SARS) and Middle East respira- indicating the presence of potentially infectious virus. 327
272 tory syndrome, which affected approximately 8000 and There was a delay in testing our patient for COVID-19 328
273 2400 people worldwide, respectively. Signs and symptoms because the initial guidelines from the Government of Can- 329
274 of COVID-19 have thus far been described as fever, cough, ada (February 25, 2020) suggested testing for COVID-19 in 330
275 myalgia, fatigue, sputum production, headache, hemoptysis, any patient who presented with fever and/or new onset of 331
276 and diarrhea.3 Interestingly, a recent update provided by (or exacerbation of chronic) cough and had travelled to an 332

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Fig. 3—External photograph of the right eye taken by the patient before the second visit (March 5th) to the eye clinic demonstrating
353 marked conjunctival injection and watery discharge. Photograph provided by the patient (used with permission). 409
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369 Q11 Fig. 4—Timeline depicting the patient’s clinical course. X X 425
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371 affected area within the past 14 days. Affected areas at that treating patients with suspected and/or confirmed COVID- 427
372 time included mainland China, Hong Kong, Iran, Italy, 19 infection use contact and droplet precautions.1214 This 428
373 Japan, Singapore, and South Korea. Other exposure criteria includes wearing a gown, gloves, face mask covering the 429
374 included close contact with a confirmed or probable case of mouth and nose, and eye shield/goggles. Regardless of travel 430
375 COVID-19 or laboratory exposure to biological material history or known or suspected infectious pathogen, every 431
376 known to contain COVID-19.10,11 Our patient did not patient interaction should include an assessment of the risk 432
377 meet the initial testing guidelines and was only tested once of exposure to bodily fluids (including respiratory or eye 433
378 the guidelines were updated to include all travel outside of secretions) to the health care worker and the appropriate 434
379 Canada, emphasizing the importance of adapting quickly to PPE should be selected.9,15 The WHO also notes that a 435
380 rapidly evolving epidemiology in the context of an evolving number of aerosol-generating medical procedures, including 436
381 pandemic. Unfortunately, this case resulted in 5 physicians and tracheal intubation and manual ventilation, have been asso- 437
382 3 health care workers being placed in 14 days of self-isolation. ciated with an increased risk of coronavirus trans- 438
383 As we learn more about the virus and its pathogenesis, we mission.1214 As a result, health care workers engaging in 439
384 recommend that all practitioners caring for patients sus- such aerosol-generating medical procedures should addition- 440
385 pected of COVID-19 wear appropriate personal protective ally use a certified N95 mask.1214 As always, for patients 441
386 equipment (PPE) to mitigate mouth, eyes, and nose expo- suspected of having infectious red eye, it is imperative to fol- 442
387 Q12 sure.
10,11
Because COVID-19 is a respiratory illness, X X the low disinfection practices that have already been outlined to 443
388 WHO recommends that health care workers examining and prevent the spread of viral infection before and after each 444

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445 patient visit. Given that COVID-19 is owing to an envel- 6. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavi- 501
446 oped virus, it is susceptible to the alcohol and bleach disinfec- rus disease 2019 in China [E-pub ahead of print]. N Engl J Med.X X Q14 502
447 tants that are typically used in current ophthalmic practice.16 7. Lu CW, Liu XF, Jia ZF. 2019-nCoV transmission through the 503
448 A formalized protocol for all hospital-based and private ocular surface must not be ignored. Lancet 2020;395:e39. 504
449 eye clinics should be developed to minimize the risk of 8. Li JP, Lam DS, Chen Y, Ting DS. Novel Coronavirus disease 505
2019 (COVID-19): the importance of recognising possible
450 exposure for patients and health care providers. A report 506
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451 from the Hong Kong experience suggests that protocols 507
Ophthalmol 2020;104:297–8.
452 should include prescreening at the administrative level to 9. Government of Canada. Infection prevention and control for 508
453 call and reschedule nonurgent patients with symptoms or coronavirus disease (COVID-19): interim guidance for acute 509
454 travel history in the last 14 days, avoiding micro-aerosol healthcare settings. www.canada.ca/en/public-health/services/ 510
455 generating procedures such as noncontact tonometry, envi- diseases/2019-novel-coronavirus-infection/health-professio- 511
456 ronment, and infection control protocols to reduce droplet nals/interim-guidance-acute-healthcare-settings.html. 512
457 transmission and availability of proper PPE.17 Patients can Accessed March 14, 2020. 513
458 also be screened or managed through tele-ophthalmology if 10. Government of Canada. COVID-19 affected areas list. www. 514
459 patients are able to send photographs of their eye to their canada.ca/en/public-health/services/diseases/2019-novel-coro- 515
460 eye care professional. Importantly, it should be noted that navirus-infection/health-professionals/covid-19-affected- 516
areas-list.html. Accessed March 10, 2020.
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CONCLUSIONS
465 12. World Health Organization. Infection prevention and control 521
466 We present a case of COVID-19 that presented initially to during health care when novel coronavirus (nCoV) infection 522
467 ophthalmology with keratoconjunctivitis and respiratory is suspected - Interim guidance. www.who.int/publications- 523
468 symptoms, without fever. The case emphasizes the impor- detail/infection-prevention-and-control-during-health-care- 524
469 tance for eye care professionals to remain vigilant and con- when-novel-coronavirus-(ncov)-infection-is-suspected- 525
470 sider SARS-CoV-2 as the causative agent in patients 20200125. Accessed March 10, 2020. 526
471 presenting with viral conjunctivitis, particularly in high-risk 13. World Health Organization. Advice on the use of masks in the 527
patients with travel to areas of active transmission of the community, during home care and in health care settings in
472 528
the context of the novel coronavirus (2019-nCoV) outbreak -
473 virus. These cases could represent an early presentation of 529
Interim guidance. www.who.int/publications-detail/advice-on-
474 COVID-19. Protocols should be put in place to minimize 530
the-use-of-masks-in-the-community-during-home-care-and-in-
475 exposure risk to other patients and health care providers. healthcare-settings-in-the-context-of-the-novel-coronavirus- 531
476 (2019-ncov)-outbreak. Accessed March 10, 2020. 532
477 14. World Health Organization. Rational use of personal protec- 533
Supplementary Material
478 tive equipment for coronavirus disease 2019 (COVID-19). 534
479 Supplementary material associated with this article can be apps.who.int/iris/bitstream/handle/10665/331215/WHO-2019- 535
480 found in the online version at doi:10.1016/j.jcjo.2020.03.003. nCov-IPCPPE_use-2020.1-eng.pdf. Accessed March 10, 2020. 536
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500 556

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557 The authors would like to acknowledge Dr. Yi (Fay) Zhai Control, Alberta Health Services, Edmonton, Alta.; 613
x
558 Q16 for X Xrelaying the experiences of ophthalmologists in China in Provincial Laboratory for Public Health (Microbiology), 614
559 response to the COVID-19 outbreak, and Dr. Errol Prasad Alberta Health Services, Edmonton, Alta.; ║Department of 615
560 at DynaLife Medical Labs (Edmonton, Alberta, Canada) for Laboratory Medicine and Pathology, University of Alberta, 616
561 coordinating the viral testing of the conjunctival swab. Edmonton, Alta. 617
562 618
From the *Department of Ophthalmology and Visual Scien- Correspondence to Carlos Solarte MD, Department of Oph-
563 619
ces, University of Alberta, Edmonton, Alta.; yDivision of thalmology and Visual Sciences, University of Alberta,
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Infectious Diseases, Department of Medicine, University of Edmonton, Alta. T6W0N9. [email protected]
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Alberta, Edmonton, Alta.; zInfection Prevention and
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