Covid-19 Research Roundup

Published in Wilmer - Summer 2020

As the COVID-19 pandemic transformed the world in spring 2020, Wilmer researchers — both basic scientists and clinician-scientists — sprang into action to learn more about a myriad of topics relevant to patients. Running the gamut from drug development to public health to ophthalmic care-seeking behaviors, the subjects researchers are focusing on right now offer a snapshot of the many ways COVID-19 has changed our lives.

A Promising Drug to Fight the ‘Cytokine Storm’

In June, a promising therapeutic for COVID-19 received approval for phase II testing by the U.S. Food and Drug Administration (FDA).

Known as OP-101, the drug was developed by Kannan Rangaramanujam, Ph.D., Wilmer’s Arnall Patz Distinguished Professor, and his research collaborator and wife Sujatha Kannan, M.B.B.S., an anesthesiologist at the Johns Hopkins University School of Medicine. The two researchers created a company that then licensed the compound to expedite its journey to market

Initially, the drug’s target was neuro-inflammation. As COVID-19 was flaring in the U.S., Rangaramanujam, co-director of Wilmer’s Center for Nanomedicine, realized that COVID-19 landed people in the hospital because of a viral attack on the lungs as well as a systemic “cytokine storm” — both of which lead to inflammation. “Our compound targets the very cells that play a significant role in both of these,” he says.

“If you look at the drugs that are being created and used for COVID-19, you will find that a lot of them are potent but target a single mechanism and can have side effects,” says Rangaramanujam. “We expect that our safety profile is likely to be much better in treating inflammation broadly, compared to other drugs.” This is because the compound targets only cells implicated in inflammation and is quickly cleared from the rest of the body.

If the drug gains FDA approval for treatment of COVID-19, he believes it could also be used to treat other conditions caused by inflammation — including diseases such as age-related macular degeneration and central nervous system disorders. “Since it treats inflammation, it treats many different conditions, including ocular disorders,” he says. “It is actually a pretty exciting compound.”

Keeping Kids Connected to Health Care

On March 13, the world changed for millions of children in the United States —and all of the children in Baltimore City Public Schools — when schools closed.

Megan Collins, M.D., M.P.H., a pediatric ophthalmologist at Wilmer, leads the Vision for Baltimore program, which aims to screen the vision of all children in Baltimore City Public Schools and provide glasses to those who need them.

Because of her close working relationship with the public school system, she knows well the concerns raised as the physical school buildings closed down: concerns around continuity of learning, food security, supervision, safety and housing, and health services.

Collins is focused on the latter. In April, she received a Johns Hopkins University Alliance for a Healthier World COVID-19 Launchpad Grant to examine how children who were receiving health services in the school are currently interacting with providers.

The grant is funding a research project that will focus on conducting interviews with key stakeholders from schools to understand what steps they are taking to connect children with health care needs and health care providers.

Flattening the Curve of Inaccessibility

Approximately 61 million Americans have a disability, equating to one out of four adults, and disability is most common among older adults, occurring in more than 40% of Americans 65 and older. How people with disabilities access both health care and public health messages is always important, but because COVID-19 disproportionately affects older people, it has become paramount.

Wilmer’s Bonnielin Swenor, Ph.D., M.P.H., associate professor of ophthalmology, is the director of the Johns Hopkins University Disability Health Research Center. Since the beginning of the pandemic, Swenor has been involved in research examining the degree to which people with disabilities can access health care for and health information about COVID-19.

One project already yielding results is Flattening the Inaccessibility Curve, which involved a survey broadcast via different channels such as the National Federation of the Blind and the American Foundation for the Blind. “This survey assessed the impact of COVID-19 on people who are blind or have low vision, and results are being published for the public rapidly on the website flatteninaccessibility.com,” says Swenor. “It was deployed quickly and tells us information about gaps and needs in the response and the ways that people with vision loss are uniquely experiencing COVID.”

Conjunctivitis and SARS-CoV-2

In March 2020, Wilmer ophthalmologist Sezen Karakus, M.D., and her colleagues noticed an uptick in patients presenting with conjunctivitis. She and her colleagues had begun reading clinical reports from other countries that indicated conjunctivitis was a symptom, albeit a rare one, of COVID-19, but none indicated conjunctivitis alone as a presenting symptom or an isolated eye infection.

“We hypothesized that this new coronavirus, SARS-CoV-2, might be responsible for some of these conjunctivitis cases like other respiratory viruses,” says Karakus. To determine the prevalence of conjunctivitis caused by SARS-CoV-2, Karakus and her collaborators designed a study, for which they will enroll everyone who presents to Wilmer with a red eye condition that ophthalmologists think could be viral conjunctivitis. For these patients, the doctors will collect conjunctival, nasal and nasopharyngeal swabs, and then Wilmer researcher James Foster, Ph.D., will perform polymerase chain reaction tests on these samples to see if SARS-CoV-2 is present.

If a significant number of patients do appear to have conjunctivitis caused by SARSCoV-2, this could end up changing several facets of the public health response to COVID-19. For example, guidelines about the correct personal protective equipment could change or an additional screening question about eye redness could be added when asking patients and employees about symptoms that could indicate COVID-19.

Exploring Possible Delays in Care

Researchers at Wilmer Eye Institute have joined forces with those at 16 other eye hospitals across the country to explore whether patients experiencing retinal emergencies during the COVID-19 pandemic may have delayed vital care.

James Handa, M.D., Wilmer’s Robert Bond Welch, M.D., Professor of Ophthalmology, and J. Fernando Arevalo, M.D., Ph.D., Wilmer’s Edmund F. and Virginia Ball Professor of Ophthalmology, are among those gathering data on the number of patients seeking treatment for urgent and emergent retinal problems, including retinal detachments, eye trauma and eye infections, from January 2019 to May 2020. Handa, the chief of the Retina Division at Wilmer, and Arevalo, chief of Wilmer at Johns Hopkins Bayview Medical Center, were recently joined by new Wilmer faculty member Mark Breazzano, M.D., an assistant professor of ophthalmology, on this project.

If the number of patients seeking care for these conditions decreased, the next step will be to determine why. “Our concern is that during the pandemic, patients may be afraid to come to the hospital or clinic,” says Arevalo. But there may also be another explanation. For example, says Arevalo, if patients are staying home and being more sedentary, there’s less pulling on the retina by the gel inside the eye, which typically causes retinal detachment.

Knowing what is happening and why may indicate the need for more in-depth screening when patients call with these kinds of concerns. The information gleaned from the study may also help inform practices in other specialties. “If this is happening in ophthalmology, it’s likely happening in other specialties as well,” says Arevalo.

Changes in Diagnoses Offer Clues for Resource Allocation

Meghan Berkenstock, M.D., an ophthalmologist at Wilmer, has continued to see patients throughout the COVID-19 pandemic. About six weeks after clinics closed to all but urgent and emergent conditions, she noticed a change in diagnoses in her patients.

Berkenstock acquired the diagnosis codes for patient visits six weeks before the day clinics closed to everything but emergency care and six weeks afterward and began a deep analysis. She and her collaborators made the following observations from this analysis:

  • The amount of telemedicine visits increased sixtyfold in the six weeks after in-person clinics closed to everything but emergency care.
  • The low vision, pediatric ophthalmology, general ophthalmology and cornea divisions had the largest decrease of in-person visits.
  • Ocular trauma visits occurred in equal numbers during both study periods.
  • Ocular inflammatory disease follow-up and high-risk medication monitoring significantly increased during COVID-19.
  • Even in the subspecialty clinics where a significant decrease of visits was noted, diagnostic codes were still used for patients with acute changes in vision, indicating that even when closed to all but emergency care, ophthalmology departments should staff all subspecialty clinics.
Knowing the changes specific to each subspecialty clinic is vital to correctly redistributing available resources, says Berkenstock. It provides generalizable evidence for ophthalmology departments to allocate human resources and materials during a pandemic.