Common ocular presentation of COVID-19 similar to that of less potent adenovirus
SARS-CoV-2, or COVID-19, has proven to be a formidable challenge worldwide.
We are still in the first wave of this pandemic. Both globally and in the United States, we are experiencing a first wave surge of both cases and deaths. According to the Worldometer coronavirus tally, as I write this commentary on July 23, we have 15,805,785 reported cases in the world and are adding a record 276,278 cases a day. In the U.S., we are at 4,208,618 cases and adding more than 70,000 new cases a day. The death rate vs. reported cases globally is about 4%. In the U.S., the death rate is slightly lower, but perhaps not meaningfully lower, at 3.5%, but a promising trend is that in the advanced countries, death rates are declining as treatments improve.
This is a virulent virus, so far challenged in impact on the global population and economy only by the 1918 H1N1 influenza epidemic, in which an estimated 500 million were infected and more than 50 million died, with a near 10% mortality among a four times smaller global population. For COVID-19 to challenge the 1918 influenza epidemic case numbers and deaths globally, we would need to reach 2 billion global cases and 200 million deaths, a nearly unthinkable outcome.
The cause of death in both viral pandemics was similar, a severe immune response with an accompanying cytokine storm resulting in a necrotizing pneumonitis and multiple organ failure. So, the 1918 H1N1 influenza epidemic was at least 100 times worse than what we have experienced to date in this COVID-19 pandemic, but we are not done yet. We are learning how to reduce viral spread and how to better treat those morbidly sick, but a strong societal commitment to social distancing, mask wearing, frequent hand washing, screening, cleaning, testing and quarantining of those contacted by infected individuals remains elusive.
We ophthalmologists have been spared from the worst of this disease, but we are nearly all back to work now, and we will need to be vigilant in diagnosing and managing the occasional COVID-19 case that presents as an ocular problem. The most common ocular presentation is follicular conjunctivitis, usually associated with flu-like symptoms and signs including a mild fever, a sore throat, or upper respiratory syndrome and a dry cough. This presentation is not new to us and is similar to the well-known pharyngeal conjunctival fever (PCF) caused by the less virulent adenovirus 3, 8, 9 and 37. PCF cases still present to our offices every year, and today in each patient we will need to consider COVID-19 conjunctivitis in the differential diagnosis.
The findings and presentation of adenovirus PCF and COVID-19 follicular conjunctivitis are similar. The differentiation cannot be made in a reliable fashion with history and examination alone. As a first step, we need to remember that both are highly contagious. A red eye room or, for some doctors, screening patients before they are allowed into the office and immediate referral to an emergency room may well be the best approach. If a patient with possible COVID-19 viral conjunctivitis makes it into your examination lane, use extreme care in examining them. Extensive personal protective equipment is recommended, and do not touch the patient without gloves, mask, a face shield and perhaps even a gown. The ultimate diagnosis will depend upon laboratory testing. There is a CDC official test called the CDC 2019 Novel Coronavirus Real-Time Reverse Transcriptase (RT)-PCR Diagnostic Panel. To get it, refer the patient to an emergency room equipped to diagnose and manage these patients.
The ocular clinical course for COVID-19 follicular conjunctivitis is similar to that of PCF. There is a 6- to 12-day incubation period before symptoms appear. Unfortunately, during the last several days of this asymptomatic period, the patient is infectious and shedding virus. Then there is another 6 to 12 days of active infection with follicular conjunctivitis and flu-like signs and symptoms. During this entire time, the patient continues to shed virus and can easily infect you or others. For those who recover, there is another 6 to 12 days of sign and symptom resolution. For those who go on to severe acute respiratory syndrome, the virus continues to shed until they die or recover.
The patient with PCF or COVID-19 follicular conjunctivitis needs to be quarantined while they are shedding virus. They must be instructed to use careful personal hygiene at home and not interact closely with family or friends, not use the same bath towels and ideally should separate themselves as completely as possible. Treatment is primarily supportive, but we do have some agents that might be useful. Their use is all off label.
Betadine (povidone-iodine, Avrio Health) can kill both adenovirus and coronavirus and is proving useful in decontaminating donor corneas in eye banks with a double immersion technique. Some prior research suggests an ideal concentration for treating viral conjunctivitis is about 1% povidone-iodine. Benzalkonium chloride (BAK) is another potential killer, and several inexpensive over-the-counter topical eye washes and lubricants contain significant BAK. One inexpensive and widely available example is Rite Aid Eye Wash. For myself, if infected, or for my next patient, I will offer a 1% solution of povidone-iodine in Rite Aid Eye Wash placement in the office twice and then a drop every 4 to 6 hours.
Another potentially useful and readily available treatment is 0.01% hypochlorous acid in a spray bottle. My favorite is Avenova (NovaBay), and I use it for mild meibomian gland dysfunction and find it quite soothing. It has both an antimicrobial and anti-inflammatory benefit. Bleach at the proper concentration can also kill virus, and hypochlorous acid is basically a purified dilute form of bleach. These drops and sprays for the patient with active follicular conjunctivitis can be placed in the refrigerator and applied to the eye cold with a soothing effect. A mild decongestant such as Lumify from Bausch + Lomb can also reduce hyperemia and be soothing, cold or at room temperature.
In the patient with severe inflammation, a topical steroid remains an option. Azithromycin has shown some value systemically, and a 1% solution is available commercially as AzaSite (Akorn) and in a compounded formulation as Klarity-A (Imprimis).
It is likely that we will all see a patient with active follicular conjunctivitis sometime this fall or winter. We each need to have a plan as to how to manage them. As suggested above, for many comprehensive ophthalmologists, the prudent approach may well be to screen the patient before entry into the clinic and send them to the emergency room. In that case, we still may be called upon by the emergency room physician and asked for a recommended treatment. An OTC decongestant such as Lumify, 0.01% hypochlorous acid spray every 4 to 6 hours and frequent BAK containing eye wash or artificial tears seems a safe, readily available and low-cost approach. For the more aggressive, a 1% povidone-iodine solution in a BAK-containing artificial tear or eye wash or a prescription for 1% azithromycin drops four times a day is another option.
These patients are likely best managed by telehealth from a distance, as once in the office they can do much damage. I believe the patient can be monitored, and the decision to add more aggressive therapy such as a topical steroid can be made with an iPhone photograph and a web-based telehealth interview. It is important to remember these patients continue to shed virus until resolution of sign and symptoms. And, while exposure to adenovirus can give you or your employees a nasty red eye, a significant exposure to COVID-19 can kill you, them or both.