COVID-19 on the Mind 

In early March 2020, Casey Keuthan, Ph.D., joined the lab of Don Zack, M.D., Ph.D., Wilmer’s Guerrieri Professor of Genetic Engineering and Molecular Ophthalmology, to study stem cell-based therapies for preserving and regenerating the optic nerve. Two weeks later, the lab shut down because of COVID-19. During the pause in his lab’s research, Zack asked his researchers if they would be interested in helping out with any COVID-19 projects that had recently started in other labs. Keuthan said yes.

She went to work in the lab of C. Korin Bullen, Ph.D., who was spearheading a multidisciplinary project “to see if the SARS-CoV-2 virus could potentially infect neurons,” says Keuthan. Their work involved infecting 3D organoid cultures — referred to as “mini brains” — with the virus, collecting the cultures after a certain amount of time and testing the cells for the presence (and if present, the amount) of the virus.

“We did find that the mini-brains could be infected with the virus. This was some of the first evidence that neurons could potentially be directly affected by the virus itself,” says Keuthan. They also demonstrated that “not only can it get in, but it can also proliferate and continue to make more copies of itself.” The research team published the results of the experiment in the October 2020 issue of the peer-reviewed journal ALTEX — Alternatives to Animal Experimentation. Keuthan points out that COVID-19 is so new that any information about how it works in the body is helpful. “There have been many reports about neurological symptoms that are associated with patients who have COVID-19,” says Keuthan.

“We don't know the long-term effects of the virus in the neurons. And in terms of developing drugs that will treat the virus, this might be important to know because a lot of drugs might not be able to cross the blood-brain barrier or the blood-retina barrier as easily as others could,” says Keuthan.

“If you're trying to design therapies for these patients, it would be useful to know that the virus could be [in the brain]. We may want to think of some options that we could use to treat it in those [brain] cells as well.”

Filling the Gap for People with Disabilities

Bonnielin Swenor, Ph.D., M.P.H., an associate professor of ophthalmology at Wilmer, created — and now serves as the director of — the Johns Hopkins University Disability Health Research Center to maximize the health, equity and participation of people with disabilities.

When COVID-19 arrived, she observed how public health efforts targeting the general population seemed to miss people with disabilities. 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 percent of Americans 65 and older — a high-risk group for COVID-19.

To gain a fuller picture of the experience of people with disabilities during the pandemic, her team launched a research project.

“Our qualitative study examines the impact of COVID on people with vision impairment as well as other types of disabilities,” says Swenor. “This [involves] doing focus group interviews with individuals from across the country and aims to understand how COVID-19 has impacted their lives across multiple dimensions, including health care utilization, transportation, if they feel that any of their local or national policies have differentially impacted them.

“The strength of this type of study — a qualitative study — is that it gets the individual's perspective and takes a person-centered approach to research,” says Swenor. “A qualitative study is intended to create hypotheses.” She will launch “deeper quantitative work based on the results of this initial study.

“The goal of this work is to fill what is a really gaping hole in natural disaster and emergency response policies, which often ignore this group of individuals. And so at the end, our hope is to not only publish a paper but also to create a policy brief to help spark more immediate change to fill that gap,” says Swenor.

Surface Deep: SARS-CoV-2 and the Ey

When reports about COVID-19 began surfacing, Elia Duh, M.D., and Lingli Zhou, M.D., began to notice anecdotal accounts from doctors in China who had become infected despite wearing a mask. They wondered if the infections could have occurred through the eyes.

To answer this question, they needed to determine “whether the ocular surface cells possess the critical elements that would allow viral infection by SARS-CoV-2,” says Duh.

Those critical elements include receptors. “In order for the virus to infect the ocular surface, then it needs a gateway,” says Zhou. “A receptor is like a gateway for the virus to enter our body.”

From existing research, Duh and Zhou knew the receptor that SARS-CoV-2 needs in order to access the body: the protein ACE2. After the virus binds to ACE2, a cellular protein called TMPRSS2 facilitates virus entry into the cell. The researchers set out to discover whether these two proteins exist on the ocular surface.

Duh and Zhou acquired specimens from Wilmer colleagues Charles Eberhart, M.D., Ph.D., and Uri Soiberman, M.D. “That was very valuable for us,” says Duh. “They also gave us important feedback and ideas as we were developing the research.” Eberhart also provided critical expertise in the analyses. “My expertise lay in interpreting the immunostains in the various kinds of cells,” says Eberhart. Immunostaining, he explains, is a “tool that lets us recognize and, to some degree, quantify where proteins exist in these cells on the ocular surface.”

“We found those two proteins exist in the ocular surface, and that means the virus could enter the ocular surface through those two proteins,” says Zhou. This experiment is the first step. Just because the virus can enter using these proteins does not mean that it does. The next step is to see if the virus does enter the ocular surface and infect those tissues.

Still, the rapidity of answering the first question surprised all of the researchers. “Within two weeks, we did the bulk of the work. In the third week, we cleaned it up and wrote the paper. The whole thing was a month beginning to end,” says Eberhart. The paper was published in the peer-reviewed journal The Ocular Surface in October 2020.

Duh credits the speed to the enthusiasm of colleagues in contributing to the project. “One of the big strengths here at Wilmer is that we have a collection of expertise and a strong spirit of collaboration,” says Duh.

Equitable School Reopenings

Megan Collins, M.D., M.P.H., a Wilmer pediatric ophthalmologist, spent the majority of the last year focused on a topic that had been on no one’s mind at the beginning of 2020: school reopenings.

Collins is the co-principal investigator of Vision for Baltimore, a public-private research partnership designed to provide all Baltimore City Public Schools’ students with vision care, including glasses if needed, and to evaluate the impact of eyeglasses on academic performance. Prior to the COVID-19 pandemic, Collins also co-founded, and now co directs, the Johns Hopkins Consortium for School-Based Health Solutions. A collaboration between Johns Hopkins’ schools of medicine, education, public health and nursing, the consortium develops and improves the delivery of school-based health care programs.

Both Vision for Baltimore and the consortium have built health care delivery services around physical school buildings, so when the pandemic caused schools to close, Collins and her colleagues had to think quickly about how to continue to provide services that children needed.

The consortium is putting together policies and guidance that schools and school systems can follow to plan how to open safely.

“The consortium is squarely in the middle of how you develop pathways forward, both from developing the testing and contact tracing infrastructure as well as the communication and engagement,” says Collins.

In the wake of school closures last spring, Collins and her consortium partners were well situated to begin conversations with stakeholders about a corollary to school closures and reopenings: equity.

The consortium discusses “this is how you test, this is how you trace,” says Collins. “How you implement that is entirely dependent on what resources and infrastructure you have within a community.” To address this challenge, members of the consortium teamed up with additional faculty members from the schools of public health, education and medicine, and the Johns Hopkins Berman Institute of Bioethics to create the eSchool+ Initiative. “We recognized that all children are negatively impacted by school closures, but kids from low-income and disadvantaged backgrounds are going to suffer disproportionately,” says Collins.

“eSchool+ is working on guidance about how do you think about these different populations, how do you think about supporting English-language learners, children with special education needs, children of color, children from low-income families?” says Collins.