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Corneal Physician

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Contending With COVID-19 Conjunctivitis

A look at its prevalence, diagnosis, and management

By: William Binotti, MD, Pedram Hamrah, MD
Corneal Physician November 1, 2021 Vol 25, Issue November 2021 Page(s): 34, 36, 38, 41

The global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), also named the coronavirus disease 2019 (COVID-19), unfortunately remains a global health threat, most recently with the Delta variant of the virus taking center stage. Reports have highlighted conjunctivitis as the main ocular manifestation of SARS-CoV-2-infected patients.1-4 (See “Ocular Transmission: An Overview,” below.)

In fact, some studies have suggested that conjunctivitis can present as the first sign of SARS-CoV-2 prior to the onset of systemic symptoms, such as fever, cough and shortness of breath.5-8 Other studies have demonstrated that conjunctivitis can present as the only manifestation of SARS-CoV-2.7-9 Interestingly, one study revealed 5 cases of acute follicular conjunctivitis as the sole expression of SARS-CoV-2.9

Given these facts, we should be on high alert for COVID-19 conjunctivitis. Here, we discuss its prevalence, diagnosis, and management. (See “Ocular Surface Disorders Associated With Severe COVID-19”.)

OCULAR TRANSMISSION: AN OVERVIEW

It has now been established that the spike protein from SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, which serves as a key factor for cellular susceptibility.26,27

After the viral spike, protein binds to ACE2, a cell-surface-associated protease called transmembrane serine protease 2 (TMPRSS2) that plays an important role in allowing cell entry of SARS-CoV-2.28,29

These cell-surface components are present in nasal epithelial cells, and bronchial secretory cells. Further, the presence of ACE2 and TMPRSS2 have been predominantly found on the superficial epithelial surface of human conjunctival, limbal, and corneal cells.30

Although there is controversy on whether the conjunctiva truly serves as an important route for SARS-CoV-2 infections,2 there is accumulating evidence that the conjunctiva might have a role as an entry point and reservoir for the virus.1,3,31,32 Further, it is possible that other unidentified receptors in the conjunctiva could be involved in SARS-CoV-2 inoculation, although the viral replication rate in the conjunctiva remains unknown.14

Prevalence

While the literature has shown a wide incidence range (0.8% and 31.6%) of COVID-19 conjunctivitis, this can be explained by the heterogeneity of the studies.10 Specifically, some studies relied on questionnaires from infected patients after they were discharged from the hospital. Other studies reported ocular findings on hospitalized or critically ill SARS-CoV-2 patients without slit-lamp examination. Additionally, the ocular manifestations of the virus might be underestimated due to its secondary nature in an acute life-threatening situation. Thus, the true incidence of ocular findings in SARS-CoV-2 infections remains unclear. Nevertheless, the pooled data from a recent meta-analysis showed an incidence of 11.6% (95%CI= 5.5-17.7) for all ocular manifestations in COVID-19.8

There is additional controversy as to whether conjunctivitis is an early manifestation of the systemic SARS-CoV-2 disease, or whether it presents mainly in severe SARS-CoV-2 pneumonia. One meta-analysis study showed ocular symptoms as the first manifestation of SARS-CoV-2 pneumonia in 2.26% of patients (95%CI= 0.03-4.49), followed by systemic symptoms.,8 Others revealed conjunctival congestion 2 weeks after SARS-CoV-2 pneumonia symptom onset.4,11 When grouping non-hospitalized and hospitalized COVID-19 patients, only 6.9% (95%CI= 1.7–15.5) of patients with ocular manifestations presented with severe SARS-CoV-2 pneumonia.8 Patients with severe SARS-CoV-2 pneumonia who presented with conjunctivitis on hospital admission were associated with worse outcomes, likely due to a higher viral load.12

Diagnosis

In patients presenting with conjunctivitis, a thorough history, including exposure to SARS-CoV-2, history of vaccination, and recent fever, cough, or shortness of breath are suspicious for COVID-19 conjunctivitis.

It is important to highlight that patients who have breakthrough infections after receiving their full vaccination dose seem to acquire a milder form of the disease. It is still unknown at the moment how vaccination status impacts the ocular manifestations. Therefore, ophthalmologists should maintain suspicion of COVID-19 conjunctivitis in fully vaccinated patients who have ocular symptoms, and had a recent history of exposure to confirmed patients.

Something else to consider: The most common ocular signs and symptoms have been conjunctival chemosis, ocular pain 31.2% (95%CI= 23.7-38.7), conjunctival redness or congestion 10.8% (95%CI= 3.0-18.7), follicular conjunctivitis 7.0% (95%CI= 2.1-11.8), and itching 6.55% (95%CI= 0.2-12.8).8 The average duration of conjunctival congestion was 5.9 ± 4.5 days.11

To confirm the diagnosis, a conjunctival swab with reverse transcriptase–polymerase chain reaction (RT-PCR) analysis may be helpful in early disease.2 One study, for example, showed a positive yield in 24% of RT-PCR data when tear samples were collected from both eyes with conjunctival swabs.2 Other studies have revealed an overall low yield (0 to 7%) for detection of viral nucleic acid in conjunctival or tear samples.2,13 These findings may suggest a low viral replication in the conjunctiva.14 That said, the inconsistencies in the results from various studies can also be attributed to the differences in the collection methods, the collected volume, and timing of the swabs during the course of the disease.2,7

One hypothesis is that viral replication in the conjunctiva is higher in early disease. Hence, by the time the virus invades the nasopharyngeal and respiratory tract, and pneumonia symptoms are evident, the viral load is low in the conjunctiva with a low positive yield on ocular swabs.1,7 In moderate-to-severe COVID-19 pneumonia, the higher positive yield is likely explained by the greater systemic viral load in these patients, where the clinical outcomes are worse.3 Another hypothesis is that the eye is a conduit for viral spread, where the virus does not gain cell entry directly through the ocular surface, but migrates from the nasolacrimal to the respiratory mucosa to cause infections.15,16

 

Reports have highlighted conjunctivitis as the main ocular manifestation of SARS-CoV-2-infected patients.STOCK.ADOBE.COM / LUUUUSA
Reports have highlighted conjunctivitis as the main ocular manifestation of SARS-CoV-2-infected patients.STOCK.ADOBE.COM / LUUUUSA

Management

COVID-19 conjunctivitis is self-limiting, like other forms of viral conjunctivitis.14

Supportive management is indicated with frequent cold compresses, and preservative-free artificial tears (every 1 to 2 hours) for 7 days. If symptoms do not resolve after 7 to 10 days, complications or other causes should be considered.

Two case reports of acute bilateral follicular conjunctivitis in SARS-CoV-2 positive patients improved within 4 days of topical ribavirin and ganciclovir use, respectively.4,17 However, their use is off-label, as there is no evidence of their benefit for SARS-CoV-2 conjunctivitis. Moreover, the ocular manifestations likely improve secondary to systemic medications when these are indicated for systemic disease.18 Nonetheless, systemic medications are not indicated solely for conjunctivitis treatment.

Topical povidone iodine has been suggested as a possible prophylaxis during accidental ocular exposure to SARS-CoV-2.19 Although it has been found highly effective against coronavirus in vitro,20,21 more evidence is required to establish ocular povidone iodine treatment as a post-exposure prophylaxis. Its role and safety are well-established in ophthalmology for preoperative antisepsis, thus its high anti-coronavirus activity is reassuring in this setting.22


To confirm the diagnosis, a conjunctival swab with reverse transcriptase–polymerase chain reaction (RT-PCR) analysis may be helpful. STOCK.ADOBE.COM / MARIAKRAY
To confirm the diagnosis, a conjunctival swab with reverse transcriptase–polymerase chain reaction (RT-PCR) analysis may be helpful. STOCK.ADOBE.COM / MARIAKRAY

OCULAR DISORDERS ASSOCIATED WITH SEVERE COVID-19

It is known that critically ill patients who require mechanical ventilation or high-flow oxygen are at risk for developing ocular surface disorders from mild exposure keratitis to severe infectious keratitis.33

These patients may present with a decreased blink reflex, increased tear evaporation, carbon dioxide retention, reduced venous return from the eye, renal failure, cardiopulmonary failure, and exposure to multi-resistant pathogens, which predispose the ocular surface to injury.7

Thus, it is important to adopt safety precautions on critically ill SARS-CoV-2 patients to prevent permanent visual loss. Such measures include proper mask fitting, proper eye seal with gel-formulated lubricant drops in sedated patients, daily assessment of the ocular surface integrity, and early intervention when possible.33

Protection is Paramount

COVID-19 has affected over 200 million people and caused closed to 5 million deaths worldwide, as of current press. The common initial symptoms of this airborne pathogen are cough, fever, sore throat, fatigue, and headaches, among others.23-25 Given the susceptibility of the ocular surface to viral infections, and its potential reservoir function for person-to person transmission, safety precautions, including protective eye gear and face shields, and hand hygiene and avoidance of hands to the face and eyes are prudent in preventing SARS-CoV-2 spread, specifically during exposure to infected patients. These recommendations should be encouraged until there is more substantial data confirming otherwise. CP


Safety precautions, including protective eye gear and face shields are prudent in preventing SARS-CoV-2 spread, specifically during exposure to infected patients.STOCK.ADOBE.COM / MILOS
Safety precautions, including protective eye gear and face shields are prudent in preventing SARS-CoV-2 spread, specifically during exposure to infected patients.STOCK.ADOBE.COM / MILOS

References:

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  2. Arora R, Goel R, Kumar S, et al. Evaluation of SARS-CoV-2 in tears of patients with moderate to severe COVID-19. Ophthalmology. 2021;128(4):494-503.
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DR. BINOTTI is an ophthalmology resident at Tufts Medical Center, in Boston. His clinical training in Brazil and research focus at Tufts Medical Center are ophthalmic imaging with a focus on advanced technology for anterior segment diseases and surgery. Disclosures: none.

 

 

DR. HAMRAH is a clinician-scientist and cornea specialist at Tufts Medical Center, and professor of ophthalmology, immunology, neuroscience, and bioengineering at Tufts University School of Medicine. His clinical focus areas are cornea and anterior segment diseases, and surgery, corneal transplantation, corneal imaging, and dry eye disease. Disclosures: no relevant disclosures.

 

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