Eyeworld

N MAY 2020 | EYEWORLD | 41 by Ellen Stodola Editorial Co-Director reproduction. This and other pro-inflammatory cytokines are what actually make us feel sick. So the virus replicates unchecked for a period of time, and it's not until we reach a tipping point where the immune system wakes up. At that point, we are fighting a losing battle. In response, the Th1 mounts a blitzkrieg attack of pro-inflammatory cytokines. Rather than being helpful, in many cases this overexuberant cyto- kine response ends up causing more harm. This is called a cytokine storm, and it may be one of the most important and under-recognized aspects of the disease process. Since adults don't have a well-developed Th2 system to calm the storm, it is important to be looking for this in patients who are declining. Elevated serum ferritin is the classic marker for cytokine storm. Given that the immune systems of older adults may be set up for failure, it is important that we aggressively pursue treatment and prevention options." Treatment options There is a push from hospitals and doctors trying to understand how effective hydroxychlo- roquine is in different scenarios, with various studies being conducted, said William Trattler, MD. The University of Minnesota's random- ized, double-blinded study for post-exposure prophylaxis began enrolling a 3,000-subject study in late March. The Duke University study, which began in April, is a double-blind, pla- cebo-controlled study with 15,000 healthcare workers at risk for COVID-19 exposure. Prophylaxis with hydroxychloroquine, a drug commonly used to prevent and treat malaria, is a potential option that could address the issue before patients even start to feel sick or show signs. "With any study, it's going to depend on the entry criteria, who they're enrolling, what the regimen is going to be," Dr. Trattler said. "As we get more data points, it will help us with our treatment regimen for patients, both those exposed to COVID-19 as well as those with confirmed COVID-19." P otential treatments for COVID-19 are being researched worldwide. One pro- posed option is hydroxychloroquine. EyeWorld reached out to ophthalmol- ogists who discussed this and other treatment options being explored. Gary Wortz, MD, said that before physicians can decide on treatment, it's import- ant to understand how this virus is affecting people, both young and old. One of the most interesting things about COVID-19 is the way it affects older patients. "That struck me as a reason to look at differences in the immune system responses between children and adults. If we can identify the differences and formu- late a strategy for immune modulation, maybe there's an opportunity to prevent morbidity and mortality in older patients." Dr. Wortz specifically looked at some of the differences between younger and older patients' immune systems and recognized that there's generally a difference in the balance between Th1 and Th2 immune responses. 1 An ideal immune system has a balance between the two. However, children tend to be more Th2 shifted (resulting in more atopy and allergies), and adults tend to be more Th1 shifted (more prone to autoimmune diseases). 2 Th1, the pro-inflammatory side of the adaptive immune system, is moderated by cytokines, like inter- feron gamma, as well as TNF alpha, IL-1, IL-6, and IL-18, among others. The Th2 system, he said, tends to be anti-inflammatory and produc- es cytokines IL-4, IL-5, IL-10, and IL-13. 3 "For reasons that are not clear yet, chil- dren infected with COVID-19 mount a quicker immune response and resolve the infection effi- ciently. They tend not to get the cytokine storm as their Th2 system is more dominant. In adults, it seems the virus is replicating silently before the patient feels sick, allowing for asymptomatic spread of the disease," Dr. Wortz said. "To fight a virus, we have to rely on our Th1 adaptive immune responses," he continued. "COVID-19 doesn't seem to be allowing inter- feron gamma to be stimulated, and interferon gamma is perhaps the most important of all of our cytokines in terms of blocking viral Exploring treatment options for COVID-19 continued on page 42 About the doctors William Trattler, MD Center for Excellence in Eye Care Miami, Florida Gary Wortz, MD Commonwealth Eye Surgery Lexington, Kentucky Relevant disclosures Trattler: None Wortz: None

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