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Characteristics of Ocular Findings of Patients With Coronavirus Disease
2019 (COVID-19) in Hubei Province, China
Ping Wu, MD; Fang Duan, MD; Chunhua Luo,MD; Qiang Liu, MD; Xingguang Qu, MD;
Liang Liang, MD; Kaili Wu, MD
IMPORTANCE While the outbreak of coronavirus disease 2019 (COVID-19) has resulted in
more than 100 000 infected individuals in China and worldwide, there are few reports on the
association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with ocular
abnormalities. Understanding ocular manifestations of patients with COVID-19 by
ophthalmologists and others may facilitate the diagnosis and prevention of transmission of
the disease.
OBJECTIVE To investigate ocular manifestations and viral prevalence in the conjunctiva of
patients with COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In this case series, patients with COVID-19 treated from
February 9 to 15, 2020, at a hospital center in Hubei province, China, were retrospectively
reviewed for ocular manifestations. During the period of treatment, the ocular signs and
symptoms as well as results of blood tests and reverse transcriptase–polymerase chain
reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for SARS-CoV-2 were noted
and analyzed.
MAIN OUTCOMES AND MEASURES Ocular signs and symptoms as well as results of blood tests
and RT-PCR for SARS-CoV-2.
RESULTS Of the 38 included patients with clinically confirmed COVID-19, 25 (65.8%) were
male, and the mean (SD) age was 65.8 (16.6) years. Among them, 28 patients (73.7%) had
positive findings for COVID-19 on RT-PCR from nasopharyngeal swabs, and of these, 2
patients (5.2%) yielded positive findings for SARS-CoV-2 in their conjunctival as well as
nasopharyngeal specimens. A total of 12 of 38 patients (31.6%; 95% CI, 17.5-48.7) had ocular
manifestations consistent with conjunctivitis, including conjunctival hyperemia, chemosis,
epiphora, or increased secretions. By univariate analysis, patients with ocular symptoms were
more likely to have higher white blood cell and neutrophil counts and higher levels of
procalcitonin, C-reactive protein, and lactate dehydrogenase than patients without ocular
symptoms. In addition, 11 of 12 patients with ocular abnormalities (91.7%; 95% CI, 61.5-99.8)
had positive results for SARS-CoV-2 on RT-PCR from nasopharyngeal swabs. Of these, 2
(16.7%) had positive results for SARS-CoV-2 on RT-PCR from both conjunctival and
nasopharyngeal swabs.
CONCLUSIONS AND RELEVANCE In this study, one-third of patients with COVID-19 had ocular
abnormalities, which frequently occurred in patients with more severe COVID-19. Although
there is a low prevalence of SARS-CoV-2 in tears, it is possible to transmit via the eyes.
JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2020.1291
Published online March 31, 2020.
Invited Commentary
Author Affiliations: Department of
Ophthalmology, The FirstCollege of
Clinical Medical Science, Yichang
Central People’s Hospital, China
Three Gorges University,Yichang,
China (P. Wu, Luo, Liu, Qu, Liang);
Zhongshan Ophthalmic Center, State
Key Laboratory of Ophthalmology,
Sun Yat-Sen University, Guangzhou,
China (Duan, K. Wu).
Corresponding Author: Liang Liang,
MD, Department of Ophthalmology,
The First College of Clinical Medical
Science, Yichang Central People’s
Hospital, China Three Gorges
University,183 Yiling St, Yichang
443003, China (liangliang419519@
163.com); Kaili Wu, MD,Zhongshan
Ophthalmic Center, State Key
Laboratory of Ophthalmology, Sun
Yat-senUniversity, 54 S Xianlie Rd,
Guangzhou 510060, China (wukaili@
maill.sysu.edu.cn).
Research
JAMA Ophthalmology | Brief Report
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Since December 2019, coronavirus disease 2019 (COVID-
19) has been reported among patients in China. Cur-
rently, the disease is quickly spreading worldwide. The
pathogen of COVID-19 is a novelcoronavir us (severe acute re-
spiratory syndrome coronavirus 2 [SARS-CoV-2]), identified as
a member of the Coronaviridae family. Another coronavirus,
named SARS-CoV-1, was responsible for severe acute respira-
tory syndrome.
1
Compared with SARS-CoV-1, SARS-CoV-2 has
a similar binding receptor and similar pathologic features sys-
temically and epidemiological characteristics.
1,2
Although there
is no direct evidence that SARS-CoV-1 replic ationresults in con-
junctivitis and other ocular diseases, reports have empha-
sized the eye as a potential site for virus transmission.
3
Simi-
larly, SARS-CoV-2 transmission through the eye has been
suspected.
Nevertheless, there are no reports in the medical litera-
ture at this time, to our knowledge, that identify a direct re-
lationship between SARS-CoV-2 and the eye. Researchers have
not reported ocular abnormalities nor have they stated in the
medical literature if there was conjunctivitis or viral pres-
ence detected in the tears of patients with COVID-19. The ob-
jective of this study was to evaluate ocular involvement sys-
tematically in patients highly suspected of having or confirmed
to have COVID-19.
Methods
From February 9 to 15, 2020, patients with COVID-19 hospi-
talized in Yichang Central People’s Hospital were diagnosed
based on the 5th edition of the National Guideline on Pre-
vention and Control of the Novel Coronavirus Pneumonia
(PC-NCP) published by the National Health Commission of
China on February 8, 2020.
4
The patient symptoms, ocular
manifestations, chest computed tomographic scans, and
results of blood tests and reverse transcriptase–polymerase
chain reaction (RT-PCR) from nasopharyngeal and conjuncti-
val swabs for SARS-CoV-2 were noted and analyzed. This
study was approved by the ethics committee of Yichang Cen-
tral People’s Hospital, and all patients gave written informed
consent. All statistical analyses were performed using SPSS
version 13.0 (SPSS Inc). Means for continuous variables were
compared using independent-group ttest when the data
were normally distributed; otherwise, the Mann-Whitney
test was used. Proportions for categorical variables were
compared using the χ
2
and Fisher exact test as appropriate.
For unadjusted comparisons, a 2-sided α of less than .05 was
considered statistically significant.
Results
Of the 38 consecutive patients with COVID-19 who were
recruited, 25 (65.8%) were male, and the mean (SD) age was
65.8 (16.6) years (Table 1). Among them, 28 patients (73.7%)
had positive findings for COVID-19 on RT-PCR from naso-
pharyngeal swabs, and of these, 2 patients (5.2%) yielded
positive findings for SARS-CoV-2 in their conjunctival as well
as nasopharyngeal specimens. The other 10 patients who
were hospitalized were judged to have COVID-19 by the
guideline of PC-NCP,
4
with fever and/or respiratory symp-
toms and lung computed tomography imaging features of
COVID-19 pneumonia.
A total of 12 of 38 patients (31.6%; 95% CI, 17.5-48.7) had
ocular manifestations consistent with conjunctivitis, includ-
ing conjunctival hyperemia, chemosis, epiphora, and in-
creased secretions (Table 2). Among these 12 patients, there
were 4 cases judged as moderate, 2 cases judged as severe, and
6 cases judged as critical, which was graded according to the
guideline of PC-NCP
4
: moderate indicated fever and/or respi-
ratory symptoms and lung computed tomography imaging
findings; severe indicated dyspnea (respiratory frequency of
30 cycles per minute or greater), blood oxygen saturation of
93% or less, and an arterial partial pressure of oxygen to frac-
tion of oxygen inspiration ratio of 300 or less; and critical in-
dicated respiratory failure or shock or multiple organ
dysfunction/failure.
4
In these patients, 1 patient experienced
epiphora as the first symptom of COVID-19. None of them ex-
perienced blurred vision. By univariate analysis, patients with
ocular symptoms were more likely to have higher white blood
cell and neutrophil counts and higher levels of procalcitonin,
C-reactive protein, and lactate dehydrogenase than patients
without ocular symptoms (Table 1). In addition, 11 of 12 pa-
tients with ocular abnormalities (91.7%; 95% CI, 61.5-99.8)
had positive results for SARS-CoV-2 on RT-PCR from naso-
pharyngeal swabs. Of these, 2 (16.7%) had positive results for
SARS-CoV-2 on RT-PCR from both conjunctival and naso-
pharyngeal swabs.
Discussion
Few previous investigations have evaluated ocular signs and
symptoms in patients infected with SARS-CoV-1 and SARS-
CoV-2. A few reports have evaluated for the presence of SARS-
CoV-2 in tear fluid.
3,5
Our investigation suggests that among
Key Points
Question What are the ocular manifestations and conjunctival
viral prevalence in patients from Hubei province, China, with
coronavirus disease 2019 (COVID-19)?
Findings In this case series including 38 patients with COVID-19,
12 patients had ocular manifestations, such as epiphora,
conjunctival congestion, or chemosis, and these commonly
occurred in patients with more severe systemic manifestations.
Reverse transcriptase–polymerase chain reaction results were
positive for severe acute respiratory syndrome coronavirus 2 in 28
nasopharyngeal swabs and 2 conjunctival swabs, and more
significant changes in blood test values appeared in patients with
ocular abnormalities.
Meaning These data may assist ophthalmologists and others to
understand the ocular manifestations of COVID-19, thus enhancing
the diagnosis and prevention of the transmission of the disease.
Research Brief Report Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19)in Hubei Province, China
E2 JAMA Ophthalmology Published online March 31, 2020 (Reprinted) jamaophthalmology.com
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patients with COVID-19, 31.6% (95% CI, 17.5-48.7) have ocu-
lar abnormalities, with most among patients with more se-
vere systemic manifestations or abnormal findings on blood
tests. These results suggest that ocular symptoms commonly
appear in patients with severe pneumonia.
Our results show a low prevalence (5.2%; 95% CI, 0.6-
17.8) of SARS-CoV-2 nucleotides in conjunctival specimens of
patients with COVID-19, consistent with previous studies on
severe acute respiratory syndrome.
3
Of note, we found only 1
patient presenting with conjunctivitis as the first symptom. Pre-
vious reports have shown the shedding of potentially infec-
tious virus can occur in people who have no fever and minor
or absent signs of infection.
6
Because unprotected eyes were
associated with an increased risk of transmission of
SARS-CoV-1,
7
in support of our current results, our results might
suggest that SARS-CoV-2 might be transmitted through the eye.
Table 1. Clinical Laboratory Resultsof Patients With Coronavirus Disease 2019 (COVID-19)
Measure
Mean (SD)
Difference (95% CI)
P
valueTotal (N = 38)
Ocular symptoms
Yes (n = 12) No (n = 26)
Age, median (IQR), y 68 (53 to 76) 67 (52 to 76) 70 (62 to 79) −3.39 (−8.47 to 15.25) .28
Male, No. (%) 25 (65.8) 7 (58.3) 18 (69.2) −0.11 (−0.44 to 0.22) .51
Severe type, No. (%)
a
15 (39.4) 8 (66.7) 7 (26.9) 0.40 (0.08 to 0.71) .33
White blood cell count, /μL 7360 (4480) 10 900 (5580) 5730 (2690) 5160 (2460 to 7860) .009
Lymphocyte count, /μL 890 (500) 710 (480) 980 (490) −270 (−610 to 70) .12
White blood cell count to
lymphocyte count ratio
14.96 (20.23) 26.20 (25.36) 9.77 (15. 30) 16.43 (3.02 to 29.85) .06
Neutrophil count, /μL 5920 (4640) 9510 (5820) 4260 (2820) 5250 (2430 to 8070) .01
Monocyte count, /μL 500 (210) 620 (280) 440 (150) 170 (30 to 3100) .06
Platelet count, ×10
3
/μL 184.39
(77.28)
184.58
(89.70)
184.31
(72.80)
0.28 (−55.18 to 55.73) .99
PCT ≥0.05 ng/mL, No. (%) 15 (40.5) 8 (66.7) 7 (28.0)
b
0.39 (0.06 to 0.71) .03
CRP, mg/dL 5.17 (6.30) 8.55 (8.87) 3.61 (4.02) 4.95 (0.7 to 9.15) .04
D-dimer, μg/mL 1.76 (2.42) 2.96 (3.93)
c
1.35 (1.53)
d
1.62 (−0.35 to 3.59) .15
Creatine kinase, U/L 101.82
(85.81)
91.08 (58.35) 106.77
(96.53)
−15.69 (−77.03 to
45.66)
.61
Creatine kinase–MB, ng/mL 11.87 (5.67) 12.42 (4.94) 11.62 (6.05) 0.80 (−3.26 to 4.86) .35
LDH, U/L 281.11
(154.47)
381.7
(196.52)
234.65
(105.89)
147.10 (48.04 to
246.15)
.03
Alanine aminotransferase, U/L 31.08 (27.46) 39.83 (45.25) 27.04 (12.69) 12.79 (−6.43 to 32.02) .36
Aspartate aminotransferase,
U/L
35.58 (26.58) 45.33 (41.73) 31.08 (14.58) 14.26 (−4.20 to 32.71) .27
Urea nitrogen, mg/dL 41.24
(128.83)
20.21 (15.37) 50.94
(155.41)
−30.72 (−122.58 to
61.14)
.50
Creatinine, mg/dL 1.61 (2.84) 1.94 (3.81) 1.46 (2.34) 0.48 (−1.55 to 2.52) .63
Abbreviations: CRP, C-reactive
protein; IQR, interquartile range;
LDH, lactate dehydrogenase;
PCT,procalcitonin.
SI conversion factors: Toconvert
white blood cell count to ×10
9
per
liter, multiply by 0.001; lymphocyte
count to ×10
9
per liter, multiply by
0.001;neutrophil count to ×10
9
per
liter, multiply by 0.001; monocyte
count to ×10
9
per liter, multiply by
0.001;platelet count to ×10
9
per liter,
multiply by 1; CRP to milligrams per
liter, multiply by 10; D-dimer to
nanomoles per liter, multiply by
5.476; creatine kinase to microkatals
per liter, multiply by 0.0167; creatine
kinase–MB to micrograms per liter,
multiply by 1; LDH to microkatals per
liter, multiply by 0.0167; alanine
aminotransferase to microkatals per
liter, multiply by 0.0167; aspartate
aminotransferase to microkatals per
liter, multiply by 0.0167; urea
nitrogen to millimoles per liter,
multiply by 0.357;and creatinine to
micromoles per liter, multiply by
88.4.
a
Includes severe and critical cases of
COVID-19.
b
Data from 1 patient missing.
c
Data from 4 patients missing.
d
Data from 3 patients missing.
Table 2. Characteristics of 12 PatientsWith Ocular Manifestations
Patient
No./Sex/Age, y
Temperature
at ocular
examination, °C Respiratory symptoms Clinical type
a
Ocular manifestations
SARS-CoV-2 RNA test result
Nasopharyngeal
swab
Conjunctival
swab
1/F/80s 38.0 Dyspnea Severe Chemosis, epiphora Positive Negative
2/M/70s 38.0 Cough, expectorate Critical Secretion Positive Negative
3/M/50s 39.9 Cough, expectorate Critical Conjunctival hyperemia, secretion Positive Positive
4/F/80s 39.0 Dyspnea Severe Conjunctival hyperemia, chemosis,
epiphora, secretion
Positive Negative
5/F/60s 36.8 Cough Critical Chemosis, epiphora Positive Positive
6/M/60s 38.7 Cough, expectorate Critical Chemosis, epiphora, secretion Positive Negative
7/F/80s 36.5 None Moderate Chemosis, epiphora, secretion Positive Negative
8/F/70s 38.0 Cough Critical Chemosis, epiphora, secretion Positive Negative
9/M/60s 38.1 None Critical Chemosis, secretion Positive Negative
10/M/30s 39.6 Chest tightness Moderate Chemosis Positive Negative
11/M/40s 37.1 Cough Moderate Conjunctival hyperemia Negative Negative
12/M/70s 36.9 None Moderate Epiphora Positive Negative
Abbreviations: F,female; M, male; SARS-CoV-2, severe acute respiratory
syndrome coronavirus 2.
a
Graded by the National Guideline on Prevention and Control of the Novel
Coronavirus Pneumonia.
4
Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19)in Hubei Province, China Brief Report Research
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Limitations of this study include a relatively small sample
size and absence of detailed ocular examinations to exclude in-
traocular disease owing to the logistical challenges of managing
these patients at this time. In addition, we only sampled once
from the eye of each patient, which can decrease the prevalence
owing to false-negatives. Regardless,these preliminar y results
are shared in an effort to inform ophthalmologists and others
around the world regarding ocular symptoms with COVID-19.
ARTICLE INFORMATION
Accepted for Publication: March 17, 2020.
Published Online: March 31, 2020.
doi:10.1001/jamaophthalmol.2020.1291
Open Access: This is an open access article
distributed under the terms of the CC-BY License.
©2020WuPetal.JAMA Ophthalmology.
Author Contributions: Drs Liang and K. Wu had full
access to all of the data in the study and take
responsibility for the integrity of the data and the
accuracy of the data analysis. Drs P. Wu and Duan
contributed equally to this study.Drs Luo, Liu, and
Qu contributed equally as senior authors.
Study concept and design: Liang, K. Wu.
Acquisition, analysis, or interpretation of data:
P. Wu, Duan, Luo, Liu, Qu, Liang.
Drafting of the manuscript: P. Wu, Duan, Liang.
Critical revision of the manuscript for important
intellectual content: P. Wu, Luo, Liu, Qu, Liang,
K. Wu.
Statistical analysis:P.Wu.
Obtained funding: Liang, K. Wu.
Administrative, technical, or material support: Duan,
Luo, Liu, Qu, Liang.
Study supervision: Liu, Liang, K. Wu.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by
grants 81770896 (Dr K. Wu) and 81770920
(Dr Liang) from the National Natural Science
Foundation of China.
Role of the Funder/Sponsor:The funder had no
role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Additional Contributions: We thank Haijiang
Zhang, MD, Minxing Wu, MD,and Min Liu, MD
(Yichang Central People’sHospital, Yichang, China),
for collecting the data and preparing the Table.
None of these individuals received compensation
for their contributions.
REFERENCES
1. Lu R, Zhao X, Li J, et al. Genomic characterisation
and epidemiology of 2019 novel coronavirus:
implications for virus origins and receptor binding.
Lancet. 2020;395(10224):565-574. doi:10.1016/
S0140-6736(20)30251-8
2. To KF,Lo AW. Exploring the pathogenesis of
severe acute respiratory syndrome (SARS): the
tissue distribution of the coronavirus (SARS-CoV)
and its putative receptor, angiotensin-converting
enzyme 2 (ACE2). J Pathol. 2004;203(3):740-743.
doi:10.1002/path.1597
3. Peiris JS, Yuen KY,O sterhausAD, Stöhr K. The
severe acute respiratory syndrome. N Engl J Med.
2003;349(25):2431-2441. doi:10.1056/
NEJMra032498
4. National Health Commission of the People’s
Republic of China. The guideline on diagnosis and
treatment of the novel coronavirus pneumonia
(NCP): revised version of the 5th edition. Accessed
February 8, 2020.http://www.nhc.gov.cn/xcs/
zhengcwj/202002/
d4b895337e19445f8d728fcaf1e3e13a.shtml
5. Loon SC, Teoh SC, Oon LL, et al. The severe acute
respiratory syndrome coronavirus in tears. Br J
Ophthalmol. 2004;88(7):861-863. doi:10.1136/bjo.
2003.035931
6. Hoehl S, Berger A, Kortenbusch M, et al.
Evidence of SARS-CoV-2 infection in returning
travelers from Wuhan, China. N Engl J Med. Published
online February 18, 2020.doi:10.1056/
NEJMc2001899
7. Raboud J, Shigayeva A, McGeer A, et al. Risk
factors for SARS transmission from patients
requiring intubation: a multicentre investigation in
Toronto,Canada. PLoS One. 2010;5(5):e10717.
doi:10.1371/journal.pone.0010717
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