Courtesy of Eddie Green

Over the past few months, COVID-19 has skewed the global landscape in unprecedented ways. In response to the aggravating circumstances, there has been an effort by Yale scientists to better understand and address SARS-CoV-2 — the novel coronavirus responsible for what now amounts to over 4 million infections and more than 300 thousand deaths as of May 14.

By performing scientific research that could improve diagnostics, therapy and inpatient support, several Yale experts have shifted their focus from what they were working on before the pandemic to contribute towards a constantly evolving body of scientific knowledge on COVID-19. 

Researchers at the Yale Center for Genome Analysis (YCGA), including YCGA and Keck Biotechnology Resource Laboratory Director Shrikant Mane and Associate Director of Microarray Research Guilin Wang, have been using samples extracted from hospital patients to examine the genes of those who have been infected, as well as sequence the genome enclosed within SARS-CoV-2. The principal objectives are to understand what makes some people more prone to develop grave symptoms and to consolidate knowledge that could inform new courses of treatment for the disease. 

Similarly, Ruth Montgomery, associate dean for scientific affairs at the Yale School of Medicine and director of the Yale Cytometry Time-of-Flight facility, which hosts highly advanced mass spectrometry technology, is also studying patients’ genomes to figure out how the bodies of those who present a healthier response to the virus manage to do so. The intent is to apply this understanding to the development of treatment for those who fall more gravely ill.

Experts generally agree that increased testing could enable better control of COVID-19’s spread, which makes the worldwide sparsity of test kits one of the greatest concerns at present. To address this issue, a team of virologists at Yale New Haven Hospital, led by professor of laboratory medicine Marie-Louise Landry, successfully replicated the COVID-19 test in the beginning of March, allowing more individuals in New Haven County to have access to a prompt diagnosis.

Starting on March 17, multiple drive-through specimen collection sites were established  throughout the state, where outpatients, inpatients and health care workers could come to have their samples collected. Following an initial period of training, Landry’s lab was able to screen between 250 and 300 samples per day, but delayed delivery of materials limited the hospital’s testing capacity, decreasing the screening rate to roughly 100 to 200 samples per day.

Due to these issues on the testing front, professionals at YNHH are also exploring alternative ways to test patients for COVID-19. Associate research scientist in epidemiology Anne Wyllie has been studying the use of saliva samples for testing –– an alternative option that would save time and likely decrease the health risk to which healthcare workers are exposed in the current testing setup, which includes introducing swabs up the patient’s nose and towards the cavity that connects to the upper part of their throat.

The preprint of her study — released on April 22 — found that detection of the virus in saliva samples was more sensitive, meaning that there are fewer false negatives, and generally produced more consistent results than those obtained through tests using nasopharyngeal swabs.

Moreover, researchers at YNHH and the Yale School of Medicine, led by department chair and professor of epidemiology and medicine Albert Ko, are investigating what antibodies for SARS-CoV-2 can tell us regarding immunity against COVID-19. This is crucial information that will most likely ground decisions surrounding the reopening of cities and the development of vaccines. One of the principal questions is the significance of having antibodies. Could they represent total immunity? Could they pose a risk to the host’s immune system? If there are immunizing effects, how long do they last for?

Researchers at YNHH are also seeking ways to enhance immunity to COVID-19 by extracting SARS-CoV-2 antibodies from the blood plasma of patients who have recovered to develop a serum that can be injected into those with a more severe form of the disease. This idea comes from the general consensus that those who have overcome COVID-19 have a high concentration of antibodies circulating within them.

With regards to treatment, YNHH, along with the Yale Center for Clinical Investigation, has adhered to clinical drug trials intended to assess the effectiveness of antiviral drugs in fighting off the infection, as well as its most aggressive symptoms. As of April 6, according to YNHH’s chief medical officer Thomas Balcezak, the hospital was working on over 25 clinical trials.

It is a well known fact that those who present with more severe forms of COVID-19 often need ventilators. However, as ventilator shortages pose a heavy burden on health care systems around the world, the splitting of ventilators between patients has been on the rise.

Ventilators are not normally shared because lung conditions vary from person to person. Conditions such as pressure levels can be perfect for a specific individual but can often prove harmful for someone else. Moreover, if a person who is hooked up to a ventilator takes a breath unassisted, they may take air away from the other patients who are using the same device. 

To tackle this problem, a Yale group led by Laura Niklason, professor of anesthesia and biomedical engineering, has developed a new system that allows for the safe splitting of a single ventilator among several patients. The system, labeled PReVentS, or Pressure Regulated Ventilator Splitting, includes a closed circuit, a three vent design that enables pressure to be controlled, clinical management to be delivered and interventions to be performed for each individual patient.

The reason why many who contract COVID-19 end up needing a ventilator in the first place is often related to acute respiratory distress syndrome — a common symptom that involves the collection of fluid inside the lungs, resulting in breathing difficulties. At the Yale Chemical and Biophysical Instrumentation Center, or CBIC, researchers are investigating a treatment for the condition. Because the CBIC possesses advanced analytical instruments that many research groups across Yale lack, they have allied with New England Discovery Partners — an organization that specializes in drug discovery — to develop an anti-inflammatory agent that could be used to address the syndrome.

As of May 14, over 253,000 infected Americans have recovered from the coronavirus.

Marisa Peryer

Maria Fernanda Pacheco |maria.pacheco@yale.edu