Authors:Ye Ya1, Song Yanping1, Yan Ming1, Hu Cheng1, Chen Xiao1, Yu Juan1, Ren Xingfeng2
1Department of Ophthalmology, Ophthalmology Center of PLA, Central Theater General Hospital of PLA, Wuhan 430070, China; 2Department of Nephrology, Central Theater General Hospital of PLA, Wuhan 430070, China
Corresponding authors: Song Yanping, Email:email@example.com; Ren Xingfeng, Email:firstname.lastname@example.org
[Abstract] Since January 2020, as ophthalmologists working at the center of the novel coronavirus pneumonia (COVID-19) outbreak in Wuhan, China, we found 3 cases in 30 COVID-19 patients with binocular conjunctivitis. Of them, one case visited for conjunctivitis as a first symptom and then diagnosed as COVID-19 three days later, and two cases visited for binocular conjunctivitis during the COVID-19 onset. In 3 patients, conjunctivitis was manifested as signs of viral conjunctivitis from mild to moderate. Their symptoms of two patients disappeared after treatment with antiviral eyedrops for 7 to 10 days and another patient died of COVID-19. Interestingly, although we detected positive viral nucleic acid in the conjunctiva sacs of 2 of other 27 COVID-19 patients by using swabs and RT-PCR technology, no conjunctivitis occurred in these two patients.
[Key words] Coronavirus; Infection; Novel coronavirus pneumonia; Conjunctivitis
Since the outbreak of Coronavirus disease 2019 (COVID-19) in Wuhan, China in late 2019, as an ophthalmologist at the front line of COVID-19 diagnosis and treatment, we have treated 30 confirmed COVID-19 patients from January 10 to the present in the Wuhan General Hospital of Guangzhou Military Region. Patients, a total of 3 cases of COVID-19 with conjunctivitis and 2 cases of conjunctival sac samples with positive viral nucleic acid detection but no conjunctivitis were reported. The diagnosis and treatment of COVID-19 with conjunctivitis is reported below.
Case 1 A 67-year-old woman living in Wuhan visited the Ophthalmology Department of the General Hospital of Guangzhou Military Region on January 15, 2020 with no obvious incentive to develop hyperemia and itching for 2 days. She had a history of mild dry cough and fatigue 4 d and stable hypertension 10 years with long-term oral antihypertensive drugs (unknown). The patient was diagnosed with binocular uveitis in our hospital 5 years ago. After treatment, his condition was stable and the lesions did not recur. Ophthalmic examination results: Visual acuity: right 0.5,left 0.4; intraocular pressure (IOP): right 13 mmHg，left 15 mmHg（1 mmHg=0.133 kPa）.Slit lamp microscope was used to examine the conjunctival congestion in both eyes. Thin, mucous secretions were seen in the conjunctival sac, the cornea was transparent, KP (-), aqueous humor, the lens was slightly cloudy, and the vitreous was turbid. Fundus examination revealed clear optic disc boundaries, normal color, normal retinal blood vessels, and no bleeding, exudation, or edema in the macular area. Primary diagnosis: binocular viral conjunctivitis. Ganciclovir eye drops for both eyes, 4 times/day; Levofloxacin eye drops, 6 times/day; Ganciclovir was applied to the eyes with gel once per night, and the patient was recommended to go to the fever clinic for further diagnosis. The patient was diagnosed as COVID-19 by clinical examination and chest CT examination and received relevant treatment. The patient’s condition was tracked on February 16, and the patient’s family informed the patient that he died on February 13 due to COVID-19.
Case 2 A 32-year-old man living in Wuhan visited the Ophthalmology Department of the General Hospital of Guangzhou Military Region on January 20, 2020 with no obvious incentive of hyperemia, itching, and blurred vision 1 d. The patient denied any other medical history and no significant physical discomfort. Ophthalmic examination results: Visual acuity: right 0.8,left 0.8; intraocular pressure (IOP):right 17 mmHg，left 18 mmHg. Hyperemia in both eyes, mild chemosis, mucous white secretions can be seen in the conjunctival sac, the cornea is transparent, KP (-), and the lens is transparent. Fundus examination showed that the optic discs of both eyes were normal in color, the border was clear, retinal blood vessels were normal, and the macular foci were visible. Primary diagnosis: binocular viral conjunctivitis. The treatment of conjunctivitis is the same as case 1. Three days later, the patient informed us by phone that he had been diagnosed with NCP in Wuhan Central Hospital after clinical examination and chest CT examination due to fever, cough, and fatigue, and was admitted to the hospital for isolation and treatment. Meanwhile his red eye condition is better than before, and we asked him to continue the eye treatment with the previous method. The patient was clinically discharged after follow-up on the phone, and both eyes were uncomfortable.
Case 3 A 16-year-old man living in Wuhan was diagnosed with COVID-19 after clinical examination and chest CT examination at the General Hospital of Guangzhou Military Region on January 30, 2020, and was admitted to the isolation ward for treatment. The patient presented with hyperemia, itching, and foreign body sensation symptoms on February 2, 2020. There was more secretion in the conjunctival sac and there was no decrease in vision. Ophthalmic examination results: conjunctival congestion in both eyes, thin watery secretions in the conjunctival sac, transparent cornea, other ophthalmic examinations could not be completed due to the patient’s special condition. Primary diagnosis: binocular viral conjunctivitis. The treatment is the same as case 1. After 3 days, the symptoms of both eyes improved significantly, and the medication continued. After 1 week, the eye discomfort completely disappeared. Of the 27 other patients with mild to moderate COVID-19 diagnosed in our isolation ward, two patients had positive conjunctival sac swab virus nucleic acid test results, but no conjunctivitis occurred.
COVID-19 belongs to the beta coronavirus genus, an enveloped RNA virus, and the severe acute respiratory syndrome (SARS) -like coronavirus (bat-SL-CoVZC45), which was prevalent in 2003. Genomic homology up to 85%. Literature reports that COVID-19 is excreted through respiratory secretions, and respiratory droplets and contact transmission are the main routes of transmission. There are currently reports in the literature that live viruses are isolated from blood, saliva, and feces, and that there is a possibility of aerosol transmission when exposed to high concentrations of aerosol for a long time in a relatively closed environment. The main clinical manifestations of COVID-19 are respiratory infections, including fever, cough, fatigue, and a few patients with symptoms such as diarrhea. Severe patients often have dyspnea and / or hypoxemia after 1 week of onset; extremely severe patients quickly progress to acute respiratory distress syndrome, septic shock, difficult to correct metabolic acidosis, and coagulopathy.
Recent reports suggest that COVID-19 may cause conjunctivitis. The ocular surface is not only the tissue in direct contact with the outside world, but also through the nasolacrimal duct, nasal cavity, and then communicates with the respiratory. Literature reports that RT-PCR can detect SARS-CoV nucleic acid positive in the tears of individual SARS patients, suggesting that coronavirus may be present in tears[7,8]. Recently, there have been reports showing positive viral nucleic acid test results in conjunctival sac swab samples from a small number of confirmed COVID-19 patients with conjunctivitis providing objective evidence for 2019-nCoV ocular surface infection. Case 2 in this article reported no symptoms throughout the body when conjunctivitis occurred. Conjunctivitis was the first symptom of COVID-19. Cases 1 and 3 showed conjunctivitis during COVID-19 infection, which is an accompanying symptom of COVID-19. In addition, we chose one of the two NCP isolation wards we were responsible for. We performed a double eye conjunctival sac swab virus nucleic acid test on 27 patients with mild to moderate NCP who had been diagnosed. We found 2 positive but not Conjunctivitis occurred. The patient is still in the process of COVID-19 treatment. Eye performance needs to be further observed. Another 13 patients with severe COVID-19 were treated with intubation and ventilator by a specialist. Due to the serious condition, no history of conjunctivitis and conjunctival sac virus nucleic acid test. Therefore, as far as our clinical observation is concerned, the relationship between ocular surface infection and COVID-19 in COVID-19 patients and whether the disease can be transmitted through the ocular surface needs further research.
The three patients reported in this article have similar Clinical symptoms that is, hyperemia, eye pain, foreign body sensation, stickiness or increased watery exudation, etc., which can be improved in about 1 week after treatment. Studies have shown that ACE2 is a receptor that can adsorb and allow COVID-19 to invade tissues. In addition to high expression in human type Ⅱ alveolar epithelial cells, ACE2 is also expressed[9,10]. Preliminary results from Professor XieLixin’s team showed that the expression of ACE2 in human conjunctival epithelium is higher than that of corneal epithelium, suggesting that ocular surface tissue may also be a potential target tissue for new type of coronavirus eye infection.
It is reported in the literature that ocular infection with coronavirus during the SARS-CoV epidemic is relatively rare, howerer the clinical and epidemiological characteristics of COVID-19 eye infections are still unclear. there are no effective antiviral drugs for COVID-19, so we lack evidence-based evidence for the treatment of conjunctivitis during COVID-19. One of the three patients reported in this article was lost to follow-up due to death, and the other two patients’ symptoms of conjunctival inflammation disappeared after local anti-inflammatory and antiviral treatment, but whether the disappearance of the symptoms was due to the self-limitation of the disease or the drug. The role is not fully understood. In accordance with the Helsinki Declaration Regulations, we respect the patient’s personal wishes and have not obtained patient imaging data. This is the limitation of this report. In addition, because the patients reported in this article were early in the COVID-19 outbreak in Wuhan, no conjunctival sac virus nucleic acid test was performed.
The current COVID-19 eye infection rate is not clear, but through recent research reports and our clinical observations, we have found a small number of COVID-19 patients with ocular surface infection. The patients in cases 1 and 2 reported in this article first went to the ophthalmology clinic. The 3 ophthalmologists and 1 nurse all took protective measures such as wearing a mask, 75% ethanol spray, and hand washing. None of the 3 doctors has any Discomfort. The nurse’s blood tests found that the lymphocyte count and proportion had decreased. After isolation and symptomatic treatment combined with traditional Chinese medicine (medicine unknown), she is now back to normal. Therefore, ophthalmic medical workers must not only do a good job of personal protection in medical work, but also summarize the early manifestations and clinical characteristics of COVID-19 eye infections, research and determine rapid detection methods, and focus on screening the first patients with conjunctivitis. To explore the COVID-19 eye infection rate and the possibility of infection and preventive measures.
Conflict of interest statement: The author of this article is responsible for the authenticity of the reported materials, and there is no conflict of interest.
Conflicts of Interest: None declared
 Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019[J]. N Engl J Med, 2020, 382(8):727-733. DOI:10. 1056/NEJMoa2001017.
 Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia[J/OL]. N Engl J Med, 2020 [2020-02-20]. https://www.nejm.org/doi/full/10.1056/NEJMoa2001316.DOI:10.1056/NEJMoa2001316.
 Holshue ML, De Bolt C, Lindquist S, et al. First case of 2019 novel coronavirus in the United States[J/OL]. N Engl J Med, 2020[2020-02-20]. https://www.nejm.org/doi/ full/10.1056/NEJMoa2001017. DOI: 10.1056/NEJMoa 2001191.
国家卫生健康委员会. 新型冠状病毒肺炎诊疗方案（试行第六版）[S/OL]. 2020-02-19[2020-02-20]. http://www.gov.cn/zhengce/2020-02/19/content_5480958. htm.
 Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J]. Lancet, 2020, 395(10223):497-506. DOI: 10.1016/S0140-6736(20)30183-5.
 Loon SC, Teoh SC, Oon LL, et al. The severe acute respiratory syndrome coronavirus in tears[J]. Br J Ophthalmol, 2004, 88(7): 861-863.
 Zhou Y, Zeng Y, Tong Y, et al. Ophthalmologic evidence against the interpersonal transmission of 2019 novel coronavirus through conjunctiva [J/OL]. New York: medRxiv,2020-02-12[2020-02-20].https://doi.org/10.1101/2020.02.11.20021956.
李雪杰, 汪明, 陈长征, 等.伴发或首发病毒性结膜炎的新型冠状病毒感染下眼科医师的防控策略[J]. 中华实验眼科杂志, 2020, 38(3):276-280. DOI:10. 3760/ cma. j.issn.2095-0160.2020.0002.
Li XJ, Wang M, Chen CZ, et al.Ophthalmologists’ strategy for the prevention and control of coronavirus pneumonia with conjunctivitis or with conjunctivitis as the first symptom[J]. Chin J Exp Ophthalmol,2020, 38(3):276-280. DOI:10. 3760/ cma. j.issn.2095-0160.2020.0002.
 Zhao Y, Zhao Z, Wang Y, et al. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCoV [J/OL]. New York: bioRxiv, 2020-01-26 [2020-02- 20]. https://www.biorxiv.org/content/10.1101/2020.01.26.919985v1.
Zou X, Chen K, Zou JW, et al. The single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to Wuhan 2019-nCoV infection[J/OL]. Front Med, 2020-02-08 [2020- 02-20]. https://Front Med,2020,14. DOI:10.1007/s11684-020-0754-0.
 谢立信, 周庆军, 高华, 等. 加强新型冠状病毒眼部感染的基础和临床研究[J/OL]. 中华眼科杂志, 2020, 56(00): E003-E003[2020-02-20]. http://rs.yiigle. com/yufabiao/1182287.htm.DOI: 10.3760/cma.j.cn112142-20200219-00087.