California, US, June 2020
Prof. Dr. Michael Stern is Chief Scientific Officer at ImmunEyez, LLC, Orange County, California. Formerly, he was principal scientist and vice president of the Inflammation Research Program at Allergan, where he worked for more than 26 years. Dr. Stern’s focus has been on identifying novel mechanisms and drug targets for immune-based inflammatory diseases that affect the ocular surface.
In this first edition of the IT-DED³ Newsletter, we did not want to miss the opportunity to consult Dr. Stern – Head of the IT-DED³ Advisory Board – on his views about the impact of the COVID-19 pandemic on Dry Eye patients and ongoing research. Dr Stern kindly shared his opinions and thoughts, based on his extensive and well-recognized expertise as an ocular surface immunologist, completed by discussions with experts in complementary fields. We thank Dr. Stern for sharing his thoughts with us and for his continuous contributions to our project.
1. Could the confinement – due to COVID-19 lockdown have an impact on Dry Eye patients and how?
It has been clearly demonstrated in both animal models and human patients that the ambient environment plays a role in both initiating and maintaining the immune-based inflammation associated with Dry Eye. The pandemic, to the best of our knowledge, started in China in the late fall and winter and spread initially across the Northern hemisphere. People who have Dry Eye Disease (DED) or were prone to its initiation were impacted by having to stay in a hot dry environment (indoors) due to the heating systems in their homes and buildings. In the Southern hemisphere which was experiencing summer, many people had a similar ocular surface onslaught due to rapid air movement from fans and air conditioning. These environments have been known to exacerbate disease/symptoms in patients.
Additionally, borderline individuals (peri/post menopausal women, men on anti-androgen therapy for benign prostatic hyperplasia, etc.) could even suffer the initiating event in establishing chronic disease as demonstrated in models.
Access to healthcare during “lockdown” is also seen as an issue. There has been a short paper published recently by Andrea Leonardi et al. on the impact on patients with ocular allergy, in which they discuss whether the patients still had access to ophthalmology clinics during lockdown, to change their treatment regimens etc.
2. Could Dry Eye Disease patients (DED) or contact lens wearers infected with COVID-19 have a worsening of their symptoms?
While DED patients may have seen increases in symptoms due to the reasons given in question #1, there is not a lot of evidence that the ocular surface was directly affected by being infected. There were a few reports of red eyes but no causality has been identified to date. There are, however, several laboratories looking to identify biomarkers of COVID-19 infection in the tears. It is possible that these could be secreted with lacrimal aqueous and not actually be pathogenic to the ocular surface epithelium.
Contact lens wearers could have seen a decrease in the ability to keep their lenses in for extended periods.
This question has been of interest to me in that the virus is known to infect the mucosa of the bronchial tree. In fact, many physicians have surmised that the seriousness of the disease symptoms may be correlated with how deep in the bronchial tree and lungs the infection occurs. It is suspected that the reason so many attending physicians were infected (personal communication) was that they were the ones intubating the patients and that forceful deep breaths at that time helped to aerosolize the virus. This would be a behavioral difference with the mucosa of the ocular surface but may explain why some viral proteins are found in the tear lake.
It is thought that the virus enters epithelial cells using the angiotensin converting enzyme 2 receptor. To this end, there are some studies about to start to investigate ACE-2 receptors on mucosal epithelial cells, comparing lung with eye.
3. Do you think that Dry Eye Disease patients are more vulnerable or have a lower immune response to COVID-19? Or vice-versa, might COVID-19 lead to Dry Eye Disease due to the immune changes?
I addressed some of this in the seminar I gave during the IT-DED³ meeting in Valladolid. All DED is autoimmune, but most patients do not have systemic autoimmune disease. A crucial role of our immune system is the ability to differentiate “self” from “non-self”. In a large percentage of Dry Eye patients, only a local autoimmune process occurs. However, people with systemic autoimmune diseases such as Sjogrens Syndrome, Lupus or Rheumatoid Arthritis are also prone to Dry Eye and usually develop an even more severe form.
There is no evidence that patients in the former group (local autoimmunity) are immunosuppressed and therefore should not be any more vulnerable to infections. Patients with systemic autoimmune diseases may be somewhat suppressed and exhibit an increased risk of infections and may need to be more cautious. Additionally, some of these patients may be on drugs such as the newer biologics, which render them susceptible to infection.
4. In a few studies, the RNA of SARS-COV-2 was detected in tears. In some patients, ocular symptoms emerged before the respiratory symptoms. What would this imply: is there evidence of an impact of SARS-COV-2 on the ocular surface?
Although my career has been in the field of ocular surface immunology, I certainly have no illusions that I am a virologist. However, in the literature that I have read on this topic very few patients with SARS-COV-2 exhibited any sort of conjunctivitis. In a paper by Roberto Lauande and Jayter Silva Paula on Oftalmologia, they cite two studies which showed 1) 1 patient out of 30 tested and 2) 2 patients out of 72 tested who had any type of conjunctivitis. Additionally another study by Chen et al. showed that of 524 patients with COVID-19 tested – only 25 had any sort of conjunctival congestion.
It is of interest that both of these are COVID viruses (single stranded RNA viruses) and seem to affect the two mucosas (ocular and oropharynx) differently. Adenovirus (a double stranded DNA virus), however is extremely virulent on the ocular surface, which causes “pink eye” and is known to spread rapidly though close approximation of populations.
The way DNA and RNA viruses replicate within host cells is different. DNA viruses must access the host nucleus, perform both transcription and translation of viral particles and coat proteins, whereas RNA viruses can stay in the cytoplasm. Whether this has anything to do with the differences in infectivity in this case is best left to others.
5. Which information do we have about immunity to COVID-19 and the duration of protection against reinfection? Does a positive result in a serological test for antibodies imply immunity?
6. Do you think that the global world population can reach herd immunity in a short to medium timeframe? Would herd immunity be a permissible choice?
Answering Questions 5 and 6 together:
Much has been made in the lay press about the role of antibodies resulting from infection with COVID-19. Not a lot of definitive information is available yet, but I have looked at some literature and spoken with people familiar with viruses. Here are the main points:
- Patients who have recovered from a COVID-19 infection have significant levels of serum antibodies.
- In fact, companies developing vaccines against COVID-19 infection use these antibody levels as an initial indication that they are getting the desired immune response to the injected antigens.
- There have been several anecdotal reports in which serum antibodies from a recovered patient have been transferred to a patient with life threatening disease (passive transfer) and actually saved the patient.
- Historically (typically) the presence of post-infective antibodies has been protective. The question becomes “for how long”?
- There is now some discussion that a portion of the population is actually already immune to COVID-19. Could this be an indication of cross protection in those previously exposed to SARS? This has yet to be elucidated. If in fact the typical immunological principles hold here, then herd immunity could occur and be protective for the population as a whole. Should this be used as a strategy by intention? Hell no! There have been some, despicable, politicians in my country who have posited that we should just open everything up to protect the economy and that, while developing herd immunity, the deaths of some elderly and school kids would be acceptable. While this is an interesting question to discuss in a philosophy class, as medical scientists and clinicians we should hold every life sacred.
7. In your view, will private and public research funding focus more on COVID-19 from now on at the expense of other research fields, such as Dry Eye Disease?
In short – I really have no idea how funding will be allocated. Putting a lot of funding on COVID-19 at this point is like closing the barn door after the horse has already left. Many companies are already testing vaccines and therapeutics for COVID-19. If they are successful, they will definitely reap the economic benefits.
Here is what I believe should happen: pandemics are now and will be in the future a fact of life on this planet. As we have just seen, viruses do not respect national borders and can affect the global population with great speed. In my opinion, there should be an international pandemics institute (perhaps under the WHO) which is well funded through an international agreement. This institute would be tasked with developing strategies for research and corporate support in the rapid development of therapeutics and vaccinations. As every pandemics expert I have seen interviewed has said – “response to a pandemic is a race, if it can be identified and isolated quickly it is far less damaging.”
So, to answer the question, this type of effort should really not affect research into other diseases.