Princeton pivots toward COVID-19

People walking with masks on

By Catherine Zandonella

Within days of shutting down their laboratories in response to the COVID-19 pandemic in March, Princeton researchers were asking how they could help.

“Many members of the Princeton faculty reached out with requests for opportunities to use their knowledge, ideas and skills to assist in combating the COVID-19 pandemic,” said Dean for Research Pablo Debenedetti, the Class of 1950 Professor in Engineering and Applied Science and a professor of chemical and biological engineering.

In response, the University created a fund of over half a million dollars to support research on COVID-19. The projects, which are still ongoing, range from vaccines and treatments to policy, social and economic topics.

The manual of physical distancing

In the early months of 2020, professors of architecture Paul Lewis and Guy Nordenson realized that the COVID-19 pandemic would make a significant and long-lived impact on cities. New strategies would be needed to rework the design of cities during peak infection and after restrictions are eased.

“The city’s density, historically its greatest asset, is now perceived to be at odds with the realities of the pandemic, and is now a crippling vulnerability,” Lewis said.

Lewis and Nordenson teamed with David Lewis of the Parsons School of Design, Marc Tsurumaki of Columbia University, and a team of architects and designers to create the Manual of Physical Distancing, an online visual tour of how the virus affects the areas where we live, learn, play and work. The manual distills information from universities, institutes and governments into easily understandable graphical explanations.

“We sought to negotiate the incompatibility between the functional density of urban spaces and the protection of health,” Nordenson said.

Domestic violence and the pandemic

As unemployment rose and large numbers of people began working from home, Maria Micaela Sviatschi, assistant professor of economics and public affairs in Princeton’s School of Public and International Affairs, recognized the potential for an increase in domestic violence. Roughly 12 million people in America report experiencing domestic violence annually and 35% of the worldwide population has reported at least one incident.

Sviatschi and collaborators quickly assembled a survey of 8,000 women to assess their attitudes and access to information about domestic partner violence, including interventions such as hotlines and counseling. The research team included economist Sofia Amaral of the ifo Institute at the University of Munich, as well as graduate student Lindsey Buck and Associate Professor of Economics Nishith Prakash of the University of Connecticut.

Although the study is not yet complete, some women reported abusive behaviors such as having their phone constantly checked, being isolated from their friends and family, and being told what they can or cannot wear. A small number of women reported physical abuse, and a high proportion of the women reported self-blaming.

COVID-19’s economic impact

To study the effect of business shutdowns and government stimulus on consumer behavior, assistant professors of economics Natalie Cox and Arlene Wong, with coauthors at the University of Chicago, examined credit card and bank account data from millions of customers. They found that household spending plunged similarly across all income levels in March and April, and that government payments appear to have benefited low-income households, which despite job losses, showed faster rebounds in spending than higher-income households.

The uniform spending cuts across all income levels suggest that the economic shutdown, rather than job losses, were likely the primary driver of spending declines.

“Overall declines in spending were much larger than what could be explained by the rise in unemployment,” the authors wrote in a paper published in the summer 2020 special edition of the Brookings Papers on Economic Activity.

The team also concluded that stimulus programs likely played a sizable role in helping to stabilize spending and savings, especially for low-income households.

Therapeutics and vaccines

To make SARS-CoV-2 safer for handling in the laboratory, Alexander Ploss, associate professor of molecular biology, and his team are developing a less virulent version of the virus. The strain, developed by reverse engineering the virus, lacks components needed to infect cells. Researchers can use this non-infectious version to test new therapies.

To search for treatments for SARS-CoV-2 acute respiratory distress syndrome, the team collaborated with scientists at Boston University to develop new mouse models that contain human lung tissue. The Ploss lab and their collaborators in Boston are working on a vaccine against the virus modeled on a successful vaccine against yellow fever.

“In addition to these lines of experiments, we have been able to establish very productive collaborations with others at Princeton to identify components that are essential for SARS-CoV-2 entry and replication,” Ploss said.

Closing the door on COVID-19

When the virus SARS-CoV-2 attacks the body, the virus’s spike proteins must latch onto the human protein ACE2 on the surface of cells to open the door for the virus to enter. Clifford Brangwynne, the June K. Wu ’92 Professor of Chemical and Biological Engineering, and colleagues are testing small molecules to see if they can block this process.

The researchers’ first step was to develop a way to identify small molecules that thwart the fusion of the virus spike protein with ACE2. The test involves labeling the proteins with colorful fluorescent markers that light up when a molecule successfully stymies spike-ACE2 fusion.

The team is collaborating with colleagues on campus, and around the country, to understand the biophysics of how ACE2 and spike proteins interact, and to study promising small-molecule candidates as treatments for COVID-19. “We are also excited about the potential broader application of this drug-screening approach for other types of common viral infections, particularly those that affect children,” Brangwynne said.





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