In this study, we evaluated the ocular signs and symptoms, as well as the presence of SARS-CoV-2 in conjunctival swab samples among patients with COVID-19 in one tertiary referral center during March and April of 2020. Outcomes were compared to a control group of patients negative for COVID-19, admitted during a similar period to a different ward. The results show that active conjunctival injection was present in 19% of cases and was associated with loss of smell and taste as part of the clinical presentation. Patients with COVID-19 were also more likely to complain of foreign body sensation and redness of the eye compared to patients negative for COVID-19. Conjunctival swabs for viral RNA were negative in patients with and without ocular involvement.
To date, little is known regarding the presence of SARS-CoV-2 on the ocular surface. Currently there are limited studies that report on the subject, all from East Asia [5, 7, 14, 15]. Reported positive conjunctival swab rates were between 0 and 5%. Furthermore, a recent meta-analysis reported that the pooled sensitivity of ocular tissue and fluid in detecting SARS-CoV-2 was only 0.6% in comparison with nasopharyngeal and sputum swabs . It is interesting to note the recent publication by Seah et al. who examined 64 samples from 17 patients using a Schirmer test strip. They reported all examinations negative for viral RNA . Our sampling technique was different. While Shea et al. focused on the existence of viral load in the tears, the method we employed benefits from direct scraping of conjunctival cells. The similarity in results however is consistent with the presumption of a low viral load in this tissue.
In our study none of the conjunctival swab samples were positive for SARS-CoV-2. This result could have been influenced by the limited sensitivity of the test, which was not designed or validated for conjunctival sampling, but rather for oropharyngeal testing. Another interesting possibility however relates to the limited viral load present in the conjunctiva. This possibility could have implications on the infectious capacity of this tissue. Some evidence suggests that droplets expelled from the mouth or nose of a patient can come in contact with an examiner’s eyes, forming an avenue of infection . However the authors could find no evidence of infection originating from conjunctival tissue of an infected patient. Which appears in agreement with our results here. This could be an encouraging fact for ophthalmologists, who should nevertheless be highly protected due to the close proximity to patients during examination.
Active conjunctival involvement was associated with loss of smell and taste as part of the clinical presentation and a trend existed for a more severe disease course. Loss of smell or taste was a relatively late symptom to be revealed as associated with the disease. Little is currently known on the pathophysiologic mechanism by which it develops [18, 19]. We theorize that ocular involvement was associated with increased viral load in the nasal cavity and could perhaps have led to this association.
Previous studies have also suggested that ocular involvement is associated with a more severe disease presentation . Several clinical measures related to disease severity were more pronounced among patients with ocular involvement in our study group. However, these did not reach statistical significance. The inability to reach statistical significance might be related to our exclusion of highly severe cases on account of their inability to provide consent to participate in the study. In addition, the relatively young patient age seen in our patient group (59 ± 24 years), might also have inadvertently excluded more severe cases. Patient’s mean age might have been influenced by the lesser ability of older patients to provide consent given the more severe manifestations of the disease at older ages. More data is needed, however conjunctival involvement should prompt the treating physicians to carefully monitor and evaluate the patient for other markers of disease severity.
It is interesting to note that ocular involvement was seen as a late presentation in patient #1, with ocular symptoms appearing at 9 days (after the onset of respiratory symptoms and 2 days into her admission), while in patients #2 and #3 ocular symptoms preceded respiratory ones. In patient #2 they occurred 1 day prior to respiratory symptoms onset (which coincided with loss of smell and taste) and in patient #3, 4 days prior to respiratory symptoms onset (sore throat and loss of smell and of taste). It should also be noted that when COVID-19 patients were questioned on redness or discharge in the 30 days prior to admission, five (Patients #2, #3 and three additional patients) responded positively (compared to none in the control group, p = 0.001, Table 3). A review of their charts reveals that the three additional patients had respiratory symptoms well before admission to our medical facility. This might suggest that these three patients with COVID-19 could have had ocular involvement at early stages as well. However due to the fact that these resolved, and could not be verified in clinical examination, they were excluded from the primary analysis.
In April of 2020 Neri and Pichi  suggested that an animal model where murine coronavirus induced an acute and long-lasting disease of the retina might serve as a model to examine COVID-19 associated inflammatory reaction. This model termed experimental coronavirus retinopathy (ECOR), suggests that SARS-COV-2 could have tropism for ocular tissues and induce a primary infection triggering the immune system, followed by a second autoimmune stage in which postviral inflammation can develop. Although in the ECOR model, using murine coronavirus, specific retinotropism was seen, humans affected by SARS-COV-2 might react differently, in ways also affecting the ocular surface. It would be interesting to follow the long-term retinal involvement of patients affected by COVID-19-associated conjunctivitis.
This study has several limitations. First, to reduce the risk of cross contamination of equipment, the use of a slit-lamp was avoided, as was indirect ophthalmoscopy. We therefore cannot comment on the rates of anterior or posterior uveitis as well as retinal pathologies. Second, patients with a highly severe course of disease were inherently excluded as they were unable to provide consent. Third, ocular sampling for SARS-CoV-2 among patients with active conjunctival injection were available in only one patient. Finally, this study included a relatively small sample size. The strengths of this study include the combination of clinical and molecular analysis and the use of an independent control group, as well as the assessment of a patient population outside of East Asia.
To conclude, among patients admitted to a tertiary referral center with confirmed COVID-19, active conjunctival injection was present in 19% of cases and was associated with loss of smell and taste as part of the clinical presentation. Patients with COVID-19 were also more likely to complain of foreign body sensation and redness of the eye compared to those negative for COVID-19. Conjunctival swabs for viral RNA were negative in patients with and without ocular involvement. These results could have implications on screening and triage of patients affected by COVID-19 as well as on implementation of appropriate protective measures for ophthalmology staff treating affected patients.