Report
Ocular Findings and Proportion conjunctival SARS-CoV-2 detection. For the ordinal categorical
with Conjunctival SARS-COV-2
in COVID-19 Patients
See Commentary on page 984.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
responsible for the current pandemic of corona virus disease 2019
(COVID-19), is highly contagious and has posed a tremendous
threat to global public health.1 Recent studies have reported that this
novel coronavirus strain may produce conjunctival findings and can
be detected in tears and conjunctival secretions.2,3 An implication is
that there may be a potential hazard to healthcare workers,
especially the ophthalmologists, who perform examination in
close proximity to COVID-19 patients and may come in contact
with tears or conjunctival secretions. In December 2019, Wuhan,
China, became the epicenter of the COVID-19 pandemic, and we
undertook a cross-sectional study to characterize ocular symptoms,
examine conjunctival swabs for presence of SARS-CoV-2 RNA,
and determine whether a correlation existed between ocular findings
and duration of disease.
From January 17 through February 16, 2020, a total of 121
patients who had been managed in the Renmin Hospital of
Wuhan University were recruited. Based on the standard of the
National Health Commission of China,4 all patients were
confirmed COVID-19 cases with at least 1 positive result for
SARS-CoV-2 from respiratory specimens, such as nasopharyn-
geal swabs or sputum, or other clinical specimens, such as blood
or stool, using real-time reverse-transcriptase polymerase chain
reaction (RT-PCR) or genetic sequencing, or positive results for
specific antibody through the serologic test. Clinical disease was
classified as mild, moderate, severe, or critical based on disease
severity. The study was approved by the ethics committees of
Renmin Hospital of Wuhan University and was conducted with
strict adherence to the tenets of the Declaration of Helsinki.
Written informed consent was obtained from all patients before
the study. Relevant clinical information and any ocular symp-
toms that developed either at onset or during the later course of
the disease were obtained through the review of medical records
and implementation of the external eye examination with a
penlight. We collected the conjunctival and nasopharyngeal
swabs from all patients on the same day. The conjunctival
samples were obtained from one of the affected eyes of patients
with ocular symptoms or randomly from 1 eye of patients
without ocular symptoms. All the sampling operations were
carried out by 2 experienced physicians (Y.Z. and C.D.). The
presence of SARS-CoV-2 RNA was detected by real-time RT-
PCR assay in a clinical diagnostic laboratory with the kits and
protocols recommended by the Chinese Center for Disease
Control and Prevention.5
We used the paired chi-square test (McNemar-Bowker test) to
compare the proportion with positive results for SARS-CoV-2
RNA between nasopharyngeal and conjunctival swab samples.
The Fisher exact test was used to analyze the statistical correlation
between the proportion of patients with ocular symptoms and
982
variable, the Spearman rank correlation analysis was performed to
assess the statistical correlation between the proportion of patients
with ocular findings and the duration of disease. All statistical
analyses were performed using the statistical software package
IBM SPSS Statistics version 26.0 (IBM, Chicago, IL).
Of the 121 patients with confirmed COVID-19, 63 patients
(52.1%) had mild or moderate disease and 58 patients (47.9%)
had severe or critical disease. The median age was 48 years
(range, 22e89 years) and the male-to-female ratio was 0.78
(53:68). The mean
standard deviation of the duration of
disease was 15.0
8.8 days. Eight patients (6.6%) showed
ocular symptoms; only 1 of them showed positive results for
SARS-CoV-2 in the conjunctiva. The ocular symptoms and
abbreviated findings included itching (5 [62.5%]), redness (3
[37.5%]), tearing (3 [37.5%]), discharge (2 [25%]), and foreign
body sensation (2 [25%]). The 1 patient with ocular symptoms
and positive SARS-CoV-2 conjunctival swab results was clas-
sified as a severe or critical case. Two patients without ocular
symptoms showed positive results for conjunctival SARS-CoV-
2, with one of them classified as a severe or critical case and
another classified as a mild or moderate case. Of 8 patients with
ocular symptoms, 7 were severe or critical cases and 1 was a
mild or moderate case. For the correlation analyses of these
ocular findings and the duration of disease, we additionally
found that the proportion of patients with ocular symptoms was
not correlated statistically with the duration of disease (Table 1;
Spearman rank correlation analysis: correlation coefficient,
0.111; P ¼ 0.22) and that the proportion with positive results
for conjunctival SARS-CoV-2 was not correlated statistically
with the duration of disease, either (Table 1; Spearman rank
correlation analysis: correlation coefficient, 0.074; P ¼ 0.42).
The proportion with positive results for conjunctival SARS-CoV-2
detection was 2.5% (3/121), which was significantly different from the
nasopharyngeal SARS-CoV-2 detection rate (Table S1, available at
www.aaojournal.org; positive proportion, 2.5% vs. 70.2%;
McNemar-Bowker test: chi-square value, 85.571; P < 0.001). Of 3
patients who showed positive results for conjunctival SARS-CoV-2, 2
were severe or critical cases and 1 was a mild or moderate case. The
finding of ocular symptoms was not associated significantly with the
results of conjunctival SARS-CoV-2 detection (Table S2, available at
www.aaojournal.org; odds ratios, 2.548 [95% confidence interval,
0.268e24.192]; P ¼ 0.39, Fisher exact test).
Our study has several limitations. First, because of the risk to
healthcare workers and the acuity of the condition of patients, we
were unable to perform biomicroscopic slit-lamp examination.
Second, the conjunctival swabs were collected at only 1 time point.
Recent data obtained from an animal study6 suggest that the presence
of the virus may be transient in conjunctiva after ocular conjunctival
inoculation. Therefore, the single time point for conjunctival
sampling and a wide range of time from diagnosis to sampling
may have reduced recovery rates. This may be compounded by the
possible false-negative rate of real-time RT-PCR assays. Finally,
the study is limited by the small number of patients.

Table 1. Correlation between the Proportion of Patients with Ocular Findings and Duration of Disease
Duration of Disease (days)
No. 1e10
Ocular symptoms, no. (%)
Yes 8 1 (12.5)
No 113 45 (39.8)
Conjunctival SARS-CoV-2
detection, no∙ (%)
þ 3 0 (0.0)

4 1 (25.0)
e 114 45 (39.5)
SARS-CoV-2 ¼ severe acute respiratory syndrome coronavirus 2; þ ¼ positive (cycle threshold values, <37);
¼ suspicious (cycle threshold values,
37e40); e ¼ negative (no cycle threshold value or cycle threshold values ¼ 40).
*Spearman rank correlation analysis.
In conclusion, this study characterizes the ocular symptoms in
COVID-19 patients, reports the proportion of samples with posi-
tive conjunctival and nasopharyngeal RT-PCR results from pa-
tients with COVID-19, and incorporates the duration of disease
into the analysis. A minority of the 121 patients showed ocular
symptoms and findings, which when present were mild. Three of
121 patients showed positive RT-PCR results from conjunctival
swabs. The appearance of symptoms and penlight findings or the
results of positive conjunctival swab analysis were not correlated
significantly with the duration of disease. One patient showed both
symptoms and positive conjunctival swab results and was classified
as a severe or critical case; 2 patients showed no symptoms but
revealed positive swab results, with one classified as a severe or
critical case and another was classified as a mild or moderate case.
The proportion with positive results for SARS-CoV-2 RNA was
significantly different between the conjunctival and nasopharyn-
geal specimens. However, this study is limited by its small number
of patients. The potential for conjunctival transmission of SARS-
CoV-2 is worth further exploration. Recognizing the risk for
viral exposure, all physicians and ophthalmologists should adopt
proper precautions to reduce the risk for disease transmission while
caring for patients.
YUNYUN ZHOU, MD1,*
CHAOYE DUAN, MD1,*
YUYANG ZENG, MB1,*
YONGQING TONG, MD2
YUHONG NIE, MD1
YANG YANG, MD1
ZHEN CHEN, MD, PHD1,*
CHANGZHENG CHEN, MD, PHD1,*
1
Department of Ophthalmology, Renmin Hospital of Wuhan University,
Wuhan, China; 2Department of Laboratory Medicine, Renmin Hospital
of Wuhan University, Wuhan, China
*
Yunyun Zhou, Chaoye Duan, and Yuyang Zeng contributed equally
and should be regarded as first authors.
Financial Disclosure(s): The author(s) have no proprietary or commercial
interest in any materials discussed in this article.
HUMAN SUBJECTS: Human subjects were included in this study. The
human ethics committees at Renmin Hospital of Wuhan University
Report
11e20 21e38 Correlation Coefficient P Value*
0.111 0.22
4 (50.0) 3 (37.5)
35 (31.0) 33 (29.2)
0.074 0.42
2 (66.7) 1 (33.3)
2 (50.0) 1 (25.0)
35 (30.7) 34 (29.8)
approved the study. All research adhered to the tenets of the Declaration
of Helsinki. All participants provided informed consent.
No animal subjects were included in this study.
Author Contributions:
Conception and design: C.Chen, Z.Chen
Analysis and interpretation: Zhou, Duan, Zeng, C.Chen, Z.Chen
Data collection: Zhou, Duan, Zeng, Tong, Nie, Yang
Obtained funding: N/A
Overall responsibility: Zhou, Duan, Zeng, C.Chen, Z.Chen
Keywords:
Eye findings, conjunctivitis, RT-PCR, nasopharyngeal swab.
Correspondence:
Changzheng Chen, MD, PhD, and Zhen Chen, MD, PhD, Department of
Ophthalmology, Renmin Hospital of Wuhan University, 238 Jiefang
Road, Wuhan, 430060, Hubei Province, China. E-mail:
chenchangzheng@whu.edu.cn.
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