Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China | External Eye Disease | JAMA Ophthalmology | JAMA Network
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Table 1.  Clinical Laboratory Results of Patients With Coronavirus Disease 2019 (COVID-19)
Clinical Laboratory Results of Patients With Coronavirus Disease 2019 (COVID-19)
Table 2.  Characteristics of 12 Patients With Ocular Manifestations
Characteristics of 12 Patients With Ocular Manifestations
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)30251-8PubMedGoogle ScholarCrossref
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.1597PubMedGoogle ScholarCrossref
3.
Peiris  JS, Yuen  KY, Osterhaus  AD, Stöhr  K.  The severe acute respiratory syndrome.   N Engl J Med. 2003;349(25):2431-2441. doi:10.1056/NEJMra032498PubMedGoogle ScholarCrossref
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.2003.035931PubMedGoogle ScholarCrossref
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/NEJMc2001899PubMedGoogle Scholar
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.0010717PubMedGoogle Scholar
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    1 Comment for this article
    EXPAND ALL
    Are Those With Conjunctivitis as A First Symptom Less Likely to Ultimately Require Hospitalization?
    Nathan David Blech | Public
    This study has been cited as supporting the conclusion that conjunctivitis is associated with more serious COVID-19 illness. For instance: "The more severe a patient's COVID-19 is, the more likely it is that he or she will also have pink eye, according to the report published online March 31 in JAMA Ophthalmology." (https://www.webmd.com/lung/news/20200401/pink-eye-often-a-symptom-of-covid-19#1). Might such a reading be missing important nuance? Could, even, the opposite be true when the conjunctivitis appears before respiratory symptoms?

    Take note that this case series was of hospitalized patients. What about COVID-19 patients who do not end up needing hospitalization?

    Additionally, in this
    paper we read: "Of note, we found only 1 patient presenting with conjunctivitis as the first symptom." Might experiencing conjunctivitis as the first symptom be more prevalent in a mildly symptomatic population than in this series of hospitalized patients?

    In the course of my own presumed COVID-19 infection, conjunctivitis appeared as an early symptom before any respiratory symptoms. Aching, especially in the neck, was the first symptom I noticed. Onset of conjunctivitis followed and lasted several days, while an intermittent dry cough appeared last and lingered for a couple of weeks. Fortunately, no serious symptoms developed.

    Onset of conjunctivitis before respiratory symptoms may point to having contracted the virus via the eye. Might that route of infection be (one of the factors) influencing a better prognosis? Might that route allow the patient's body to marshal defenses before the virus enters the very vulnerable respiratory system?

    Might such a hypothesis explain, in part, a puzzling phenomenon? Those who developed very serious and even fatal illness have included, albeit as a minority, some formerly healthy people in the prime of their lives. And those who only developed mild symptoms have included individuals with one or more risk factors. Might the route of infection account for some of those outcomes?

    Might vaccine administration via eye drops prove helpful in COVID-19 and possibly in other respiratory illnesses? If robust data were to clearly confirm the above hypothesis, might we even consider resorting to deliberate inoculation with live virus via an eye drop until a vaccine is developed?
    CONFLICT OF INTEREST: None Reported
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    Brief Report
    March 31, 2020

    Characteristics of Ocular Findings of Patients With Coronavirus Disease 2019 (COVID-19) in Hubei Province, China

    Author Affiliations
    • 1Department of Ophthalmology, The First College of Clinical Medical Science, Yichang Central People’s Hospital, China Three Gorges University, Yichang, China
    • 2Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, Guangzhou, China
    JAMA Ophthalmol. 2020;138(5):575-578. doi:10.1001/jamaophthalmol.2020.1291
    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.

    Abstract

    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.

    Introduction

    Since December 2019, coronavirus disease 2019 (COVID-19) has been reported among patients in China. Currently, the disease is quickly spreading worldwide. The pathogen of COVID-19 is a novel coronavirus (severe acute respiratory 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 respiratory syndrome.1 Compared with SARS-CoV-1, SARS-CoV-2 has a similar binding receptor and similar pathologic features systemically and epidemiological characteristics.1,2 Although there is no direct evidence that SARS-CoV-1 replication results in conjunctivitis and other ocular diseases, reports have emphasized the eye as a potential site for virus transmission.3 Similarly, SARS-CoV-2 transmission through the eye has been suspected.

    Nevertheless, there are no reports in the medical literature at this time, to our knowledge, that identify a direct relationship 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 presence detected in the tears of patients with COVID-19. The objective of this study was to evaluate ocular involvement systematically in patients highly suspected of having or confirmed to have COVID-19.

    Methods

    From February 9 to 15, 2020, patients with COVID-19 hospitalized in Yichang Central People’s Hospital were diagnosed based on the 5th edition of the National Guideline on Prevention 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 conjunctival swabs for SARS-CoV-2 were noted and analyzed. This study was approved by the ethics committee of Yichang Central 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 t test when the data were normally distributed; otherwise, the Mann-Whitney test was used. Proportions for categorical variables were compared using the χ2 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 nasopharyngeal 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 symptoms 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, including conjunctival hyperemia, chemosis, epiphora, and increased 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-NCP4: moderate indicated fever and/or respiratory 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 fraction of oxygen inspiration ratio of 300 or less; and critical indicated 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 experienced 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 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.

    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 patients with COVID-19, 31.6% (95% CI, 17.5-48.7) have ocular abnormalities, with most among patients with more severe 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. Previous reports have shown the shedding of potentially infectious 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.

    Limitations of this study include a relatively small sample size and absence of detailed ocular examinations to exclude intraocular 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 preliminary results are shared in an effort to inform ophthalmologists and others around the world regarding ocular symptoms with COVID-19.

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    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. © 2020 Wu P et al. JAMA Ophthalmology.

    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-sen University, 54 S Xianlie Rd, Guangzhou 510060, China (wukaili@maill.sysu.edu.cn).

    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’s Hospital, 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)30251-8PubMedGoogle ScholarCrossref
    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.1597PubMedGoogle ScholarCrossref
    3.
    Peiris  JS, Yuen  KY, Osterhaus  AD, Stöhr  K.  The severe acute respiratory syndrome.   N Engl J Med. 2003;349(25):2431-2441. doi:10.1056/NEJMra032498PubMedGoogle ScholarCrossref
    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.2003.035931PubMedGoogle ScholarCrossref
    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/NEJMc2001899PubMedGoogle Scholar
    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.0010717PubMedGoogle Scholar
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