Content uploaded by Fariba Tohidinezhad
Author content
All content in this area was uploaded by Fariba Tohidinezhad on Jun 26, 2020
Content may be subject to copyright.
Full Terms & Conditions of access and use can be found at
https://www.tandfonline.com/action/journalInformation?journalCode=ioii20
Ocular Immunology and Inflammation
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ioii20
Ocular Manifestations of Hospitalized Patients
with COVID-19 in Northeast of Iran
Mojtaba Abrishami , Fariba Tohidinezhad , Ramin Daneshvar , Arash
Omidtabrizi , Mahnaz Amini , Alireza Sedaghat , Shahram Amini , Hamidreza
Reihani , Abolghasem Allahyari , Mohsen Seddigh-Shamsi , Mohammad
Tayyebi , Hamidreza Naderi , Amin Bojdy , Rozita Khodashahi & Saeid Eslami
To cite this article: Mojtaba Abrishami , Fariba Tohidinezhad , Ramin Daneshvar , Arash
Omidtabrizi , Mahnaz Amini , Alireza Sedaghat , Shahram Amini , Hamidreza Reihani ,
Abolghasem Allahyari , Mohsen Seddigh-Shamsi , Mohammad Tayyebi , Hamidreza Naderi ,
Amin Bojdy , Rozita Khodashahi & Saeid Eslami (2020): Ocular Manifestations of Hospitalized
Patients with COVID-19 in Northeast of Iran, Ocular Immunology and Inflammation, DOI:
10.1080/09273948.2020.1773868
To link to this article: https://doi.org/10.1080/09273948.2020.1773868
Published online: 22 Jun 2020.
Submit your article to this journal
Article views: 191
View related articles
View Crossmark data
ORIGINAL ARTICLE
Ocular Manifestations of Hospitalized Patients with COVID-19 in Northeast of Iran
Mojtaba Abrishami, MD, MSc
a
, Fariba Tohidinezhad, MSc
b
, Ramin Daneshvar, MD
a
, Arash Omidtabrizi, MD
a
,
Mahnaz Amini, MD
c,d
, Alireza Sedaghat, MD
c
, Shahram Amini
d
, Hamidreza Reihani, MD
e
, Abolghasem Allahyari, MD
f
,
Mohsen Seddigh-Shamsi, MD
f
, Mohammad Tayyebi, MD
g
, Hamidreza Naderi, MD
h
, Amin Bojdy, MD
h
,
Rozita Khodashahi, MD
h
, and Saeid Eslami, PharmD, PhD
b,i,j
a
Eye Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;
b
Department of Medical Informatics, Mashhad University of Medical
Sciences, Mashhad, Iran;
c
Lung Diseases Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;
d
Division of Sleep Medicine,
Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran;
e
Department of Emergency Medicine,
Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;
f
Department of Hematology Oncology, Faculty of Medicine, Mashhad
University of Medical Sciences, Mashhad, Iran;
g
Department of Cardiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;
h
Department of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;
i
Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;
j
Department of Medical Informatics,
Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
ABSTRACT
Purpose: To evaluate ocular findings in patients with Coronavirus Disease 2019 (COVID-19) in the
Northeast of Iran.
Methods: In a cross-sectional, observational study all consecutive patients with confirmed COVID-19
diagnosis at the central referral center of these patients in northeast of Iran were included. Ocular
examinations (external and slit) were randomly performed for the patients who were admitted to the
Intensive Care Unit (ICU) and six COVID wards of the hospital. Moreover, Chart records and serum
chemistry results were collected.
Results: A total of 142 patients with the mean age of 62.6 ± 15 years (range: 23–96 years) and almost
equal gender distribution (male: N = 77, 54.2%) were included in the study. During the initial external
examination by the ophthalmologist, 44 (31%) patients were found to have conjunctival hyperemia and
22 (15.5%) patients had chemosis. Consecutive slit examination showed 41 (28.9%) conjunctival hyper-
emia, 22 (15.5%) chemosis, 11 (7.7%) cataract, and 9 (6.3%) diabetic retinopathy. The patients with at
least one ocular manifestation had significantly higher blood urea levels at the time of admission
compared to those with no obvious ocular involvement (median: 41.5, IQR: 28–66.3 vs. median: 33,
IQR: 23.8–51.8, P = .023). Moreover, a significant difference was observed in the total white blood cell
count, lymphocyte percent, neutrophil count, Erythrocyte Sedimentation Rate (ESR), and blood urea
level between patients with positive and negative Polymerase Chain Reaction (PCR) for SARS-CoV-2
virus. None of the patients reported ocular symptoms prior to systemic involvement. The proportion of
patients with at least one ocular manifestation was significantly higher in those admitted in the ICU
compared to the non-ICU wards. wards. While conjunctival hyperemia was the most prevalent ocular
finding in all patients, chemosis was the most common ocular manifestation in ICU admitted patients.
Conclusion: Ocular manifestation was observed in more than half of our COVID-19 patients. Hence, it
seems important to involve ophthalmologist in the diagnosis and management of these patients.
ARTICLE HISTORY
Received 26 April 2020
Revised 18 May 2020
Accepted 21 May 2020
KEYWORDS
SARS-CoV-2; Coronavirus
disease 2019; COVID-19;
conjunctival hyperemia;
chemosis
Coronaviruses are a family of viruses that can cause a wide
range of diseases, from common colds to severe acute respira-
tory syndrome (SARS). Seven coronaviruses have shown to
infect humans up to know. Of these, four viruses, named as
229E, NL63, OC43 and HKU1, cause mild disease. Three
other types can cause more severe and life-threatening dis-
eases and include the virus causing SARS in 2003 (SARS-
CoV),, the one cause Middle East Respiratory Syndrome
(MERS) in 2012 (MERS-CoV) and most recently, the corona-
virus that causes the recent SARS pandemic (SARS-CoV-2).
1
The latest virus infection was first detected and reported in
December 2019 in Wuhan, Hubei province in the People’s
Republic of China, and quickly spread from mainland China
to other parts of the country and the world.
2
Following China,
epidemics of Coronavirus Disease 2019 (COVID-19) have
also began rapidly in Iran, threatening the health of the gen-
eral population and medical staff and, leading to incremental
mortality.
3
Coronaviruses have been shown to cause ocular infection
in mammals and considering the similarity between different
types of coronaviruses, one would expect that COVID-19
patients have ocular manifestations.
4
Although no significant
eye involvement, including conjunctivitis, was reported in
those infected by SARS-CoV and MERS-CoV,
5
ocular mani-
festations including conjunctival injection, chemosis, epi-
phora, and conjunctivitis, were detected since first reports of
COVID-19; furthermore, it was noticed that the ocular find-
ings can be the presenting picture of the disease.
6
There are
CONTACT Arash Omidtabrizi arash_omid2001@yahoo.com Eye Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad,
Iran
OCULAR IMMUNOLOGY AND INFLAMMATION
https://doi.org/10.1080/09273948.2020.1773868
© 2020 Taylor & Francis Group, LLC
also controversial reports on the presence of the SARS-CoV-2
virus in the patients’ tears, which can be decisive in the
possibility of transmitting the virus through eye secretions.
Ping Wu and colleagues detected the virus in the conjunctival
sample of two of the 28 patients whose nasopharyngeal sam-
ples were also positive.
5
In another study on 17 patients with
COVID-19, the results of several virus cultures and
Polymerase Chain Reactions (PCRs) in tear samples were
negative during the disease course.
7
A study in Thailand at the time of the report (March 6, 2020)
reported a total of 48 patients with COVID-19. All of these 48
cases had a complete eye examination, including direct ophthal-
moscopy and further scraping of the cornea in suspected cases,
and none of them had a manifest ocular finding. However, the
authors concluded that it is possible that eye demonstrations of
the disease are often overlooked by Thai physicians.
8
Regarding the widespread dissemination of this virus in
Iran and the lack of comprehensive data on the ocular signs
and symptoms of this disease, we conducted a cross sectional
study to evaluate the ophthalmologic findings of these
patients in a referral center in Mashhad, Iran.
Methods
Study Population
This was a cross-sectional study conducted in Imam Reza
General Hospital; this is a tertiary, university based hospital,
dedicated as a referral center for COVID-19 patients in
Northeast Iran following the onset of the pandemic. The study
sample included all eligible patients admitted to this hospital
with a confirmed diagnosis of COVID-19. The diagnostic cri-
teria were a positive result of reverse transcription-PCR (RT-
PCR) test of nasopharyngeal swab sample for SARS-CoV-2, or
high clinical suspicion based on a typical chest CT scan view
along with typical clinical symptomsand high C reactive protein
(CRP) in the blood sample and/or lymphopenia < 1100/mm
3
.
Complete medical history on systemic symptoms was
obtained and recorded. The examiner specifically and proac-
tively asked about fever, cough, headache, sore throat, chest
pain, myalgia, dyspnea, vomiting, diarrhea, anosmia; however,
any other symptom expressed by the patient and detailed past
medical history were also recorded. To pinpoint any ocular
finding, all conscious and cooperative subjects were specifi-
cally interviewed about ocular symptoms such as red-eye,
burning, itching, foreign body sensation, eye pain, photopho-
bia, and any other visual complaints. The interviewer also
recorded the chronological data of any symptoms. In non-
conscious patients the clinician tried to obtain a history from
other household members and relatives. Clinical examination,
including slit-lamp examination, and indirect ophthalmo-
scopy (if possible with pupillary dilation), were performed at
the same hospital setting. In unconscious patients and those
unable to sit at the slit lamp, a hand-held portable slit lamp
and direct ophthalmoscope were utilized for examination. If
either eye of a subject had a specific sign or symptom, we
consider that patient positive for that sign or symptom (e.g.
Chemosis), and the laterality was not considered.
Figure 1. (a and b) Conjunctival chemosis and hyperemia in a patient admitted in ICU non-intubated. (c) Mild chemosis in another patient in ICU, intubated. (d)
Moderate chemosis in a patient under oxygen therapy with mask, recently admitted in the ward.
2M. ABRISHAMI ET AL.
Statistical Analysis
The normal distribution of numerical variables was evaluated
using the Shapiro-Wilk test and normality and Q-Q plots.
Central tendency parameters and frequency tables were used
to summarize data. The independent-samples t-test (or
Mann-Whitney U test when appropriate), Fisher’s exact, and
Chi-square tests were used to test the statistical significance of
differences between various subgroups. Statistical significance
was set at a level <0.05. All statistical analyzes were done using
the R studio (version 3.5.3, R Foundation for Statistical
Computing, Vienna, Austria).
Ethical Considerations
The study was in accordance with Declaration of Helsinki
1964 and its successive amendments. Moreover, the study
protocol was approved by the Regional Ethical Committee at
Mashhad University of Medical Sciences, Mashhad, Iran (IR.
MUMS.REC.1399.104).
Results
A total of 142 patients with the mean age of 62.6 ± 15 years
(range: 23–96) and almost equal gender distribution (male:
N = 77, 54.2%) were included in the study. Four patients were
not Iranian (one from Iraq and three from Afghanistan).
A total of 28 (19.7%) patients were receiving intensive cares
and 14 (50%) of them were intubated. The most prevalent
non-ocular findings at the time of examination were: cough
(N = 79, 55.6%), dyspnea (N = 68, 47.9%), myalgia (N = 64,
45.1%), fever (N = 55, 38.7%), nausea (N = 39, 27.5%), chest
pain (N = 33, 23.2%), headache (N = 25, 17.6%), sore throat
(N = 20, 14.1%), smell disorder (N = 19, 13.4%), and taste
disorder (N = 7, 4.9%).
Patients admitted in the ICU had conjunctival hyperemia
(50% vs. 26.3%, p = .022) and chemosis (60.7% vs. 4.4%,
p < .001) with higher frequencies compared to those receiving
care in other wards (Figure 1 and Table 1). It should be noted
that patients with at least one ocular manifestation had sig-
nificantly higher baseline serum urea levels compared to those
with no ocular involvement [41.5 (28.0–66.3) vs. 33.0 (23.8–-
51.8), p = .023] (Table 2).
A total of 77 (54.2%) patients had positive RT-PCRs
(Table 3). The patients with negative RT-PCR had
significantly higher White Blood Cell (WBC) counts (8900
(6600–11800)/µL vs. 7300 (5400–10000) µL, p = .041),
lower lymphocyte percentages (12.8% (9.5%-18.4%) vs.
16.5% (10.7%-22%), p = .049), higher neutrophil count
(726 (462–1001)/µL vs. 569 (373–818)/µL, p = .024), lower
Erythrocyte Sedimentation Rate (ESR) (50.0 (26.5–71.0)
mm/1 hr vs. 58 (45–83.5) mm/1 hr, p = .029), and higher
serum urea level (42.0 (32.5–65.5) mg/dL vs. 34.0
(23.5–53.0) mg/dL, p = .021). Moreover, in terms of ocular
manifestations, there was no significant difference between
the patients with positive and negative PCR. About 30.5%
of the patient with high serum urea level had conjunctival
hyperemia.
A total of 33 (23.2%) patients reported that they had
tearing, 23 (16.2%) had red eyes, 19 (13.4%) had eye irritation,
12 (8.5%) had eye itching, 4 (2.8%) had foreign body sensa-
tion, 5 (3.5%) had periorbital pain, 1 (0.7%) had photophobia,
and 1 (0.7%) had blurred vision. With external examination
by the ophthalmologist, 44 (31%) patients were found to have
Table 1. Demographic, Ocular, and Laboratory Characteristics of the Study Sample.
Variable Total (N = 142) Non-Intensive Care (N = 114) Intensive Care (N = 28) P-value
a
Age (year) 62.6 ± 15 62.7 ± 15 62.6 ± 15 0.990
Male Gender 77 (54.2%) 61 (53.5%) 16 (57.1%) 0.833
Days Since Hospitalization (day) 5 (3–9) 4 (3–8) 8 (3–12) 0.083
Diabetes Mellitus 67 (47.2%) 59 (51.8%) 8 (28.6%) 0.035
External Eye Examination (per subject)
Conjunctival Hyperemia 44 (31%) 30 (26.3%) 14 (50%) 0.022
Chemosis 22 (15.5%) 5 (4.4%) 17 (60.7%) <0.001
Keratitis 3 (2.1%) 1 (0.9%) 2 (7.1%) 0.099
Slit Examination (per subject)
Conjunctival Hyperemia 41 (28.9%) 31 (27.2%) 10 (35.7%) 0.364
Chemosis 22 (15.5%) 7 (6.1%) 15 (53.6%) <0.001
Cataract 11 (7.7%) 9 (7.9%) 2 (7.1%) 0.998
Diabetic Retinopathy 9 (6.3%) 8 (7%) 1 (3.6%) 0.689
Laboratory Measures
WBC (10^3/µl) 7.9 (6–11.1) 7.3 (5.4–10.3) 9.7 (7.6–12.8) 0.003
Lymphocyte (N) 113 (82.8–142.4) 111 (81–139) 123 (101–150) 0.091
Lymphocyte (%) 14.6 (9.9–20) 15.6 (10.1–20.4) 13.1 (8.8–19.5) 0.209
Neutrophil (N) 638 (424.2–894.2) 595 (373.8–849.6) 816 (606–1042) 0.003
Neutrophil (%) 79.9 (73.4–85) 78.9 (72.2–85) 81.7 (75.7–85.8) 0.211
Neutrophil/Lymphocyte 5.3 (3.7–8.6) 5.2 (3.6–8.3) 6.1 (3.9–9.8) 0.188
ESR (mm/hr) 58 (34–81) 58 (34.8–82.4) 58 (23.3–77) 0.513
CRP (mg/dL) 83 (34.3–140.4) 83 (36.6–140.4) 81.5 (25.1–148.7) 0.998
LDH (U/L) 584 (412–714) 588 (415–701.5) 561 (364–788.5) 0.854
Urea (mg/dL) 37 (25–58) 36 (24.8–57.3) 44 (25.5–70) 0.353
Creatinine (mg/dL) 0.9 (0.8–1.2) 0.9 (0.8–1.2) 1 (0.8–1.7) 0.396
BS (mg/dL) 121 (99–150) 127 (101–150.3) 112 (95.5–146.3) 0.376
a
Analyses by independent-samples T test, Mann-Whitney U test, Fisher’s exact test (2-Sided), or Chi-Square test.
Values represented as median (IQR), mean ± SD, or N (%).
Abbreviations: WBC, White Blood Cell; ESR, Erythrocyte Sedimentation Rate; CRP, C-Reactive Protein; LDH, Lactic Acid Dehydrogenase; BS, Blood Sugar.
OCULAR IMMUNOLOGY AND INFLAMMATION 3
red eyes and 22 (15.5%) patients had conjunctival swelling.
Slit-lamp examination and ophthalmoscopy revealed that 41
(28.9%) patients had conjunctival hyperemia, 22 (15.5%)
patients had chemosis, 11 (7.7%) patients had cataract, and
9 (6.3%) patients had diabetic retinopathy. None of the
patients had noticed ocular symptoms before developing
Table 2. Comparison of Study Variables between COVID-19 Patients with and without Ocular Manifestations.
Variable No Ocular Manifestation (N = 50) Ocular Manifestation (N = 92) P-value
a
Age (year) 61.5 ± 15.7 63.3 ± 14.7 0.500
Male Gender 25 (50%) 52 (56.5%) 0.485
Diabetes Mellitus 18 (36%) 49 (53.3%) 0.055
Intubated 48 (96%) 80 (87%) 0.138
Non-Ocular Symptoms
Cough 32 (64%) 47 (51.1%) 0.160
Dyspnea 31 (62%) 37 (40.2%) 0.015
Myalgia 24 (48%) 40 (43.5%) 0.724
Fever 18 (36%) 37 (40.2%) 0.719
Nausea 17 (34%) 22 (23.9%) 0.239
Chest Pain 14 (28%) 19 (20.7%) 0.406
Headache 10 (20%) 15 (16.3%) 0.647
Sore Throat 8 (16%) 12 (13%) 0.623
Smell Disorder 8 (16%) 11 (12%) 0.607
Taste Disorder 2 (4%) 5 (5.4%) 0.998
Laboratory Measures
WBC (10^3/µl) 7.9 (5–11.3) 7.9 (6.4–10.9) 0.382
Lymphocyte (N) 105 (80.3–156) 114 (85.6–138) 0.605
Lymphocyte (%) 15 (10.8–20.1) 14.5 (9.1–20.1) 0.604
Neutrophil (N) 619 (356–851) 649 (458–929) 0.244
Neutrophil (%) 78.2 (72–85) 81.1 (74.2–85.8) 0.145
Neutrophil/Lymphocyte 5.2 (3.5–8.1) 5.5 (3.7–9.3) 0.541
ESR (mm/hr) 58 (41.5–79.5) 58 (32.5–82.5) 0.732
CRP (mg/dL) 69.6 (23.9–111.8) 95.5 (48–152) 0.079
LDH (U/L) 576.5 (402–667.5) 595 (415–788.5) 0.306
Urea (mg/dL) 33 (23.8–51.8) 41.5 (28–66.3) 0.023
Creatinine (mg/dL) 0.9 (0.8–1.1) 1 (0.8–1.5) 0.122
BS (mg/dL) 110 (99.8–146.8) 130 (98.3–150) 0.296
a
Analyses by independent-samples T test, Mann-Whitney U test, Fisher’s exact test (2-Sided), or Chi-Square test.
Values represented as median (IQR), mean ± SD, or N (%).
Abbreviations: WBC, White Blood Cell; ESR, Erythrocyte Sedimentation Rate; CRP, C-Reactive Protein; LDH, Lactic Acid Dehydrogenase;
BS, Blood Sugar.
Table 3. Comparison of Study Variables between Patients with Positive and Negative Polymerase Chain Reaction.
Variable Negative PCR (N = 65) Positive PCR (N = 77) P-value
a
Age (year) 64.5 ± 15.8 61.1 ± 14.3 0.172
Male Gender 34 (52.3%) 43 (55.8%) 0.736
Days Since Hospitalization (day) 4 (2–8) 6 (3–10) 0.019
Diabetes Mellitus 29 (44.6%) 38 (49.4%) 0.615
External Eye Examination
Conjunctival Hyperemia 18 (27.7%) 26 (33.8%) 0.471
Chemosis 8 (12.3%) 14 (18.2%) 0.363
Keratitis 1 (1.5%) 2 (2.6%) 0.998
Slit Examination
Conjunctival Hyperemia 21 (32.3%) 20 (26%) 0.459
Chemosis 9 (13.8%) 13 (16.9%) 0.650
Cataract 8 (12.3%) 3 (3.9%) 0.112
Diabetic Retinopathy 3 (4.6%) 6 (7.8%) 0.508
Laboratory Measures
WBC (10^3/µl) 8.9 (6.6–11.8) 7.3 (5.4–10) 0.041
Lymphocyte (N) 108 (86–133.5) 118 (82–148) 0.657
Lymphocyte (%) 12.8 (9.5–18.4) 16.5 (10.7–22) 0.049
Neutrophil (N) 726 (462–1001) 569 (373–818) 0.024
Neutrophil (%) 81.3 (75–86.2) 79 (72–84.8) 0.125
Neutrophil/Lymphocyte 6.5 (4.3–9.1) 4.9 (3.3–7.9) 0.052
ESR (mm/hr) 50 (26.5–71) 58 (45–83.5) 0.029
CRP (mg/dL) 77.3 (22.4–122.5) 86.3 (43.8–146.8) 0.213
LDH (U/L) 513 (369–732) 594 (436.5–713) 0.211
Urea (mg/dL) 42 (32.5–65.5) 34 (23.5–53) 0.021
Creatinine (mg/dL) 1 (0.8–1.2) 0.9 (0.8–1.3) 0.746
BS (mg/dL) 119 (99.5–177) 123 (98–143) 0.554
a
Analyses by independent-samples T test, Mann-Whitney U test, Fisher’s exact test (2-Sided), or Chi-Square test.
Values represented as median (IQR), mean ± SD, or N (%).
Abbreviations: PCR, Polymerase Chain Reaction; WBC, White Blood Cell; ESR, Erythrocyte Sedimentation Rate; CRP, C-Reactive Protein; LDH,
Lactic Acid Dehydrogenase; BS, Blood Sugar.
4M. ABRISHAMI ET AL.
systemic manifestations and the clinicians failed to detect any
COVID-19 patients based on ocular manifestation as
a presenting complaint.
Discussion
In this study, we reviewed the signs and symptoms of hospi-
talized COVID-19 patients with special focus on ocular man-
ifestations. There are few published studies on eye
involvement in COVID-19 and almost all of them have been
reported from East Asia. To the best of our knowledge, this is
the first report of COVID-19 ocular findings in a Middle
Eastern country.
Our results demonstrated that 64.8% of patients with
COVID-19 had at least one ocular finding and the frequency
was proportional to the severity of disease; notably, 82.1% of
patients admitted in ICU and 60.5% of patients admitted at
other wards had ocular manifestations. Contradictory reports
of the frequency of ocular findings in patients with COVID-
19 have been published. This discrepancy could be due to the
different study populations, disease severity and diagnostic
criteria in these studies. For instance, outpatients with mild
general symptoms may be less likely to have eye manifesta-
tions than patients with severe symptoms. Chen et al, in
a study with a large study size (534 patients) in a primary
referral hospital and a mobile hospital, reported dry eye as the
most common (about 21%) ocular finding in COVID-19
patients.
9
Zhang et al looked for SARS-COV-2 in 102 patients
suspected to COVID-19.
10
Seventy-two patients had a positive
RT-PCR for the virus in the pharyngeal sample. Of these, only
two patients had symptoms of conjunctivitis and one of them
had viral RNA fragments in the conjunctival specimens. In
another study by Ping Wu, thirty-eight patients with sus-
pected COVID-19 were examined and 12 of them (31.6%)
had ocular symptoms.
5
Of these 12 patients, 11 had a positive
PCR of the pharynx, and two had a positive PCR of the
pharynx and throat at the same time. In their study, the
presence of ocular symptoms was associated with higher levels
of procalcitonin, CRP, lactate dehydrogenase (LDH), and
a higher count of neutrophils in the peripheral blood. In our
study, the most common ocular finding was conjunctival
hyperemia (28.9%), which is consistent with Ping Wu’s
study. Chemosis (15.5%), tearing (23.2%), and eye irritation
(13.4%) were the next prevalent symptoms, respectively. The
reason for the higher prevalence of ocular symptoms in this
study compared to some similar studies maybe the severity of
the disease: more than half of our patients had severe disease
and one-fifth of them were admitted at ICU.
We found a higher frequency of conjunctival hyperemia
and chemosis in patients admitted to the ICU compared to
those in other wards. The patients admitted to the intensive
care unit were associated with increased risk of developing
chemosis (OR: 0.057, 95% CI: 0.02–0.165). However, odds of
developing hyperemia (OR: 0.672, 95% CI: 0.28–1.16) was not
significantly higher for the patients in ICU.
In our study, external and slit examinations showed that
26.3% and 27.2% of the patients had conjunctival hyperemia,
respectively. Chen et al. reported that only 4.68% of the
patients had conjunctival hyperemia which is much lower
than the result of this study (27.2%). The difference might
be mainly due to different examination protocols as well as
disparate study samples. Chen and coworkers did not men-
tion the proportion of ICU admitted patients in their series.
Moreover, it is not clear if all of their patients in the mobile
hospital were hospitalized or a part of them were managed as
outpatients.
An interesting finding in our patients was higher serum
urea level in patients with at least one ocular symptom. About
30.5% of the patient with high serum urea level had conjunc-
tival hyperemia. Perhaps the release of inflammatory cyto-
kines causes a relative dysfunction of the kidneys as well as
tissue hyperemia. Moreover, many other hypotheses may pre-
sent, like common receptors/antigen expression in kidney and
conjunctiva, higher blood pressure/hypertension in those with
nephropathy and hypertensive vasculopathy in the conjunc-
tiva, drier eye in these subjects.
The study was limited by the inherent limitations of any
cross-sectional study. Most prominently, we are not aware of
the longitudinal course of the manifestations and could not
infer on the chronological sequence of ocular findings during
the disease course. Also, one should consider that all of our
patients were hospitalized COVID-19 patients; however, the
majorities of infected subjects have mild disease and even, are
asymptomatic careers. As the frequency of ocular manifesta-
tions could depend on disease severity, the results of the
current study are not generalizable to the public COVID-19
cases.
In conclusion, we found a high frequency of ocular man-
ifestations in at lease hospitalized COVID-19 patients.
Moreover, the ocular involvement could be the presenting
finding of disease. Hence, we believe that ophthalmologist
should be a member of the therapeutic team for comprehen-
sive management of these patients.
Acknowledgments
We would like to thank Minoo Armand, Soosan Helmi, Mahdi Azhdari,
Alireza Rajayi Manesh, Zahra Haghipanah, Afsaneh Sanee, and Eisa
Karazma, personnel of nursing office of Imam Reza Hospital for their
kind assistance with this research project. Authors also would like to
thank Mr. Amir Reza Samad Zadeh, for his support with PPE for
examinations. It is a pleasure for us to appreciate kindn supports of
Capt. Reza Kashani.
Authors’ contributions
All authors contributed to conception and study design. All authors
agreed to be accountable for all aspects of the work. All authors made
critical revision and final approval on the manuscript.
Availability of data and material
The datasets used and analyzed during the current study are available
from the corresponding author on reasonable request.
Disclosure statement
None of the authors has a conflicting financial or propriety interest to
disclose.
OCULAR IMMUNOLOGY AND INFLAMMATION 5
Ethics approval
The study was approved by the Regional Ethic Committee at Mashhad
University of Medical Sciences (IR.MUMS.REC.1399.104).
Funding
The authors would like to acknowledge the financial support of Vice-
Chancellor of Research, Mashhad University of Medical Sciences for this
research project (code: 990069).
References
1. Fu L, Wang B, Yuan T, et al. Clinical characteristics of corona-
virus disease 2019 (COVID-19) in China: a systematic review and
meta-analysis. J Mil Med. 2020;22(1):1–11. doi:10.30491/
JMM.22.1.1.
2. Farnoosh G, Alishiri G, Hosseini Zijoud SR, Dorostkar R, Jalali
Farahani A. Understanding the severe acute respiratory syndrome
Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease (COVID-19)
based on available evidence - a narrative review. J Mil Med. 2020;22:1.
3. Seah I, Agrawal R. Can the Coronavirus Disease 2019
(COVID-19) affect the eyes? A review of coronaviruses and ocular
implications in humans and animals. Ocul Immunol Inflamm.
2020;28(3):391–395. doi:10.1080/09273948.2020.1738501.
4. Yuen KS, Chan W-M, Fan DS, et al. Ocular screening in severe
acute respiratory syndrome. Am J Ophthalmol. 2004;137
(4):773–774. doi:10.1016/S0002-9394(03)01148-6.
5. Wu P, Duan F, Luo C, et al. Characteristics of ocular findings of
patients with Coronavirus Disease 2019 (COVID-19) in Hubei
Province, China. JAMA Ophthalmol. 2020;138(5):575–578.
doi:10.1001/jamaophthalmol.2020.1291.
6. Seah IYJ, Anderson DE, Kang AEZ, et al. Assessing viral shedding
and infectivity of tears in Coronavirus Disease 2019 (COVID-19)
Patients [published online ahead of print, 2020 Mar 24].
Ophthalmology. 2020;S0161-6420(20)30311–0.
7. Li JO, 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(3):297–298. doi:10.1136/bjophthalmol-
2020-315994.
8. Mungmungpuntipantip R, Wiwanitkit V. Ocular manifestation,
eye protection, and COVID-19. Graefes Arch Clin Exp
Ophthalmol. 2020;258:1339. doi:10.1007/s00417-020-04662-3.
9. Chen L, Deng C, Chen X, et al. Ocular manifestations and clinical
characteristics of 534 cases of COVID-19 in China: a cross-sectional
study. medRxiv. 2020. doi:10.1101/2020.03.12.20034678.
10. Zhang X, Chen X, Chen L, et al. The evidence of SARS-CoV-2
infection on ocular surface [published online ahead of print, 2020
Apr 11]. Ocul Surf. 2020;S1542-0124(20)30065–3.
6M. ABRISHAMI ET AL.
