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COVID-19 associated conjunctivitis is an ocular manifestation of a new disease entity called Corona Virus Disease-19 (COVID-19).
COVID-19 pandemic started in December 2019 in Wuhan city of China and within no time evolved into the deadliest pandemic of the present times. Earlier diseases related to Coronavirus were severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS). No cases of conjunctivitis or any other ocular sign or symptoms were reported with either MERS-CoV or SARS-CoV.   However, there are reports of conjunctivitis associated with COVID-19.
The current wild spread is due to human-to-human transmission through droplets and direct contact with the mucous membranes including eyes, nose, or mouth.
The causative organism is a beta coronavirus, which belongs to Coronaviridae family. It is an enveloped single-stranded RNA virus, which is closely related to the severe acute respiratory syndrome coronavirus. It has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Phylogenetic analysis showed that there are more than 100 strains of SARS-CoV-2 with two different types; type L and type S. The receptor-binding region of SARS-CoV-2 is also similar to SARS-CoV. For entry into the cell, the virus uses angiotensin-converting enzyme 2 receptor (ACE2).ACE2 receptors were found in conjunctiva and cornea, although the receptor density in ocular tissues was lower.
Old age, living in a congested area, chronic lung diseases, comorbidities including immuno-compromised states, diabetes, obesity, chronic renal, and liver diseases are the risk factors for severe systemic disease. In addition to this, health care workers are at increased risk of acquiring the infection. The risk factor for COVID-19 associated conjunctivitis is direct contact with a person having COVID. Li Wenliang, the whistleblower of the disease, contracted this virus from an asymptomatic glaucoma patient. This suggested that transmission of the virus may occur through the eyes.
The incubation period of COVID-19 is within 14 days with maximum numbers occurring within 4 to 5 days of exposure. Virus spread may occur through droplets, contact with infected surfaces, mucous membranes of infected persons, and also via the oro-fecal route. The median time of virus shedding is 20 days with a maximum recorded time period of 37 days. According to another study, the mean incubation period for SARS-CoV-2 was 5 to 7 days, and patients were typically infectious for several days prior to symptom onset. Approximately 97% of patients develop symptoms within 11.5 days of exposure. This supported the 14-day quarantine recommendations.
Recently, viral RNA was detected in the samples collected from the rooms of COVID-19 patients admitted in the hospital, which further confirmed spread through direct contact with the surfaces contaminated with virus particles.Conjunctival infection can be due to direct inoculation of the ocular tissues from droplets of an infected patient, from nasopharynx by nasolacrimal duct or from the lacrimal glands. [reference needed]
The pathophysiology of SARS-CoV-2 associated conjunctivitis is not completely understood. However, if we consider the SARS-CoV model, the disease occurs in three stages; viral replication followed by immune hyperactivity and then tissue destruction. Similar to lung tissue, cells in conjunctiva die either by viral-mediated lysis or by immune reactions. Cell death results in the release of the virus into tears.
Preventive measures, which must be adopted by practicing ophthalmologists, to avoid the spread of infection include;
- Pre-appointment screening of the patient. Patients with respiratory symptoms, patients with a history of travel, or contact with a traveler should not be given an appointment unless it is an emergency.
- Wearing masks all the time by the patients, attendants, and the health care personnel.
- Regular hand wash and use of sanitizer.
- Disinfection of instruments and surfaces having potential patient contact, before and after the examination. For surface disinfection, 0.1% of sodium hypochlorite or 70% ethanol for 1 minute is recommended.
- Avoiding air puff tonometer as it poses a danger of aerosol spread. It is preferable to use disposable devices. Tonometers should be sterilized using a 10% diluted sodium hypochlorite solution.
- Minimum examination protocol that can help in diagnosis and management and avoiding additional clinical tests and investigations unless necessary.
- Use of proper slit lamp shields and their regular disinfection after every patient.
- Use of PPE with eye protection when it is necessary to examine a patient with respiratory symptoms
- Implementation of telemedicine wherever possible.
Any patient coming to the clinic with red-eye should be suspected of COVID-19 associated conjunctivitis until proven otherwise. Definitive diagnosis can be done through RT-PCR testing of a conjunctival swab taken from the affected eye. However, conjunctivitis may be an inflammatory response to the systemic disease in a form of conjunctival injection and tearing.
Patients with red-eye must be inquired about recent traveling, cough, flu-like symptoms, fever, and history of similar symptoms in close contacts or recent contact with COVID-19 suspected or diagnosed cases.
Positive clinical findings on physical examination of the patients with COVID-19 include; fever, cough, shortness of breath, myalgias, sore throat, headache, rhinorrhea, new-onset loss of taste or smell, and chest pain. Gastrointestinal symptoms including diarrhea, nausea, and vomiting have also been reported. Although fever is a common symptom there are reports of afebrile COVID patients as well.
Conjunctivitis and keratitis are the only reported ocular signs of COVID-19 to date. No case of uveitis is yet reported. Lack of retinal findings may be attributed to failure to perform the retinal examination in the COVID-19 patients. However, very mild retinal microvascular abnormality involving the ganglion cell and inner plexiform layers of the retina is described by Marinho et al.
COVID-19 conjunctivitis starts as unilateral redness of eye with follicular reaction (inferior palpebral) like any other viral conjunctivitis.It may resolve by itself or progress to involve coarse epithelial keratitis, pseudomembranous conjunctivitis and bilateral hemorrhagic, pseudomembranous conjunctivitis or pseudodendritic keratitis. It may also be associated with tender lymphadenopathy. Animal studies have shown anterior uveitis, retinitis, vasculitis, and optic neuritis, as well.
Patients with COVID-19 can have symptoms of watering, foreign body sensation, and red-eye, or they may be asymptomatic. There are reports in which conjunctivitis was the only sign of COVID-19. Other reports showed that the patients of COVID-19 developed conjunctivitis later in their course of disease after hospitalization.
Clinical diagnosis is through a high level of suspicion
The tear sample collection varies from the use of Schirmer strips to conjunctival swabs. False-negative results are common because of the timing of sampling. Use of topical anesthesia may also alter the results.
For systemic investigations, nasopharyngeal, throat, upper respiratory, and saliva swabs are taken for RT-PCR. Imaging of COVID patients shows pneumonia, multiple mottling, and ground-glass lung opacity and pneumothorax.
Serology and RT-PCR are the most common laboratory tests being performed. Reverse-transcription polymerase chain reaction (RT-PCR) is a specific but less sensitive test in the diagnosis of COVID conjunctivitis. Different RNA gene targets are employed by different manufacturers. It is recommended that two consecutive negative RT-PCR tests results are required before a patient can be considered safe.
Early after acquiring infection, antibodies to SARS-CoV-2 are detected in serum. If a patient is IgM positive and IgG negative, the patient is actively infected. If IgM and IgG are both positive, infection is recent and may or may not be active. If IgM is negative and IgG positive, the infection is old. However, a positive IgG test alone does not mean the patient is no longer contagious or is immune.
Lymphopenia, elevated aminotransaminase levels, elevated lactate dehydrogenase levels and elevated inflammatory markers (eg, ferritin, C-reactive protein, and erythrocyte sedimentation rate) have been reported in hospitalized patients with COVID-19.
Differential diagnosis of COVID conjunctivitis includes all causes of red-eye as there are cases of COVID conjunctivitis, which were otherwise systemically asymptomatic. However, important causes from a never-ending list of red-eye include; Adenoviral, Bacterial, Allergic conjunctivitis, Herpes simplex virus keratitis, Anterior uveitis, Foreign body, Corneal abrasion, Dry eye syndrome, Exposure keratopathy, and Chemosis.
Currently, data to propose or oppose a therapy is insufficient. There was initial data regarding the use of hydroxychloroquine, which later proved ineffective for COVID. Remedisivir is currently approved by the FDA for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. Another recent study showed that patients with COVID-19 who were treated with a combination of lopinavir, ritonavir, ribavirin, and interferon-beta-1b became PCR negative more quickly than those treated with lopinavir and ritonavir (control group). Both these studies suggest the positive role of antiviral therapy if given early in infection. Plasma from recovered patients is also in the trial. Anticoagulant use to prevent thromboembolism caused by COVID is also suggested. Several vaccines are in progress as well.
COVID conjunctivitis like any other viral conjunctivitis is self-limiting and can be managed with lubricants and cold compresses unless cornea is involved. Topical antibiotics can be given to prevent secondary bacterial infection.
Medical follow up
Once the diagnosis is made, the patient should be quarantined and closely followed for the development of complications.
There is no role of surgical management in COVID conjunctivitis.
Surgical follow up
COVID conjunctivitis is self-limiting and so far no ocular complications have been reported. However, the following complications may occur; punctate keratitis with subepithelial infiltrates, bacterial superinfection, conjunctival scarring and symblepharon, severe dry eye, irregular astigmatism, corneal ulceration, and corneal scarring.
Systemic complications include; acute respiratory distress syndrome, pneumonia, stroke, acute cardiac injury, cardiomyopathy, renal failure, and encephalopathy. In children, SARS-CoV-2 infection resulted in a severe multi-system inflammatory syndrome similar to Kawasaki disease and toxic shock syndrome.
COVID conjunctivitis resolves by itself without any morbidity if systemic complications do not occur.
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