Eyeworld

N EWS 42 | EYEWORLD | MAY 2020 COVID-19 NEWS YOU CAN USE Contact Trattler: wtrattler@gmail.com Wortz: garywortzmd@gmail.com dependent RNA polymerase of other corona- viruses, which is essential for viral replication. 6 Additionally, hydroxychloroquine is a zinc ion- ophore, he said, and since zinc has a hard time getting inside of cells, it can aid in this. "We also know that hydroxychloroquine is an immune modulator; that's why it's prescribed in patients who have lupus and other rheumato- logic conditions, so there's a theory that hy- droxychloroquine is calming down the cytokine storm that happens in patients who are going on to be more critically ill," Dr. Wortz said. Dr. Wortz also advocated looking for anti- viral medications that block viral transcription and reproduction. "Remdesivir is looking like a great candidate," he said, adding that it was developed for Ebola a few years ago. Ebola, like COVID-19, is an RNA virus, seeming to share a lot of characteristics in some transcription factors. "Remdesivir seems to be doing a good job at actively inhibiting the virus," he said. "Additionally, a recent study out of Germa- ny showed that blocking the serine protease TMPRSS2 with the drug camostat mesylate (approved to treat pancreatic inflammation in Japan) effectively prevented SARS-CoV-2 from gaining intracellular entry into lung cells through the ACE2 receptor. 7 This has great promise for both treatment and prevention." Dr. Wortz said it's also important to "target our own immune response to COVID-19." Studies from China have identified tocilizumab, an IL-6 blocker, as helpful. Anakinra blocks IL- 1, which is one of the master control cytokines of the inflammatory system, Dr. Wortz said. Vaccine development is also underway, but until then Dr. Wortz said we may see different phases of the disease, necessitating different strategies. Those who have recovered might have anti- bodies against COVID-19, and evidence shows that plasma transfusions to those with current infection could be effective, Dr. Wortz said. Additionally, Dr. Wortz said that there are some trials being done with BCG, an old tuberculosis vaccine that stimulates the immune system. Dr. Wortz said mortality rates might go down once more data from all of these studies are available to better guide COVID- 19 treatment. Some doctors have already been incorporat- ing hydroxychloroquine in COVID-19 treat- ment regimens, and several have shared their outcome studies, he said. The biggest challenge in an outcome study is it's hard to extrapolate how those treated would compare to untreated patients. Dr. Trattler pointed to lab studies of hy- droxychloroquine and chloroquine that found that these medications can prevent infection of cells and treat already infected cells. Additional- ly, he said that a number of clinics in China be- gan to use hydroxychloroquine for COVID-19. A non-peer-reviewed study of 62 patients (31 patients on hydroxychloroquine and 31 con- trols) found those on the drug had reduced fe- ver and cough and improvement in pneumonia measured by chest CT, Dr. Trattler said. 4 In Europe, Didier Raoult, MD, performed a comparative study with 36 patients (16 on pla- cebo, 20 on hydroxychloroquine). 5 Six patients in the hydroxychloroquine group also received azithromycin. The researcher found this com- bination fared better than hydroxychloroquine alone. He treated an additional 74 patients with this combination (all patients received an EKG before and were monitored due to risks of this combination with arrhythmia). "We know hydroxychloroquine is a generic drug that's cheap to make in mass quantities," Dr. Wortz said. "We're seeing production ramp- ing up across the world." The use of hydroxychloroquine, also a current treatment for rheumatoid arthritis and lupus, is putting pressure on pharmacies to get enough supply for patients with established prescriptions as well as new prescriptions coming in for COVID-19, Dr. Trattler said. Dr. Trattler noted that some experts have opined that there's not enough data to support use of hydroxychloroquine for this indication—com- bined with the fact that you're taking it away from people who need it for other conditions. Though it's important to understand that treat- ment with hydroxychloroquine for patients with COVID-19 is short term, between 12 and 30 pills total for therapy, he said. Dr. Wortz said zinc could be helpful for treating COVID-19, as it's been shown to decrease duration and severity of viral colds. It has been shown to specifically inhibit the RNA continued from page 41 References 1. Simon AK, et al. Evolution of the immune system in humans from infancy to old age. Proc Biol Sci. 2015;282:20143085. 2. Chang WS, et al. Age-related changes in immunological factors and their relevance in allergic disease development during childhood. Allergy Asthma Immu- nol Res. 2016;8:338–345. 3. Berger A. Th1 and Th2 responses: what are they? BMJ. 2000;321:424. 4. Chen Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial. MedRxiv. 2020. Epub ahead of print. 5. Gautret P, et al. Hydroxychlo- roquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020. Epub ahead of print. 6. te Velthuis AJ, et al. Zn(2+) inhibits coronavirus and arteri- virus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog. 2010;6:e1001176. 7. Hoffmann M, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibi- tor. Cell. 2020;181:271–280.

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