Three Graduate Students Post Newest Developments in SARS-CoV-2 Research

Written by
Department of Molecular Biology, Princeton University, Molecular Biology Staff
April 20, 2020

A big talking point this week was progress towards “re-opening society”, which means loosening social distancing protocols and allowing businesses to re-open. While some states are on track to re-open within a few short weeks, others are still struggling with the worst of the outbreak. Yet others risk re-opening too soon, before the peak is past, potentially making the surge worse. There are lessons here from history, with different American cities experiencing drastically different ‘second waves’ while re-opening during the 1918 Spanish Flu (spoiler alert: more stringent measures meant fewer deaths). This week’s post focuses on the spread of the disease — through our bodies and communities — and the strategies that science and society are developing to slow the spread, and to facilitate the return to normalcy.

1. Effects of infection beyond the lungs.

While it is well known that SARS-CoV-2 wreaks havoc on the respiratory tract, the effects on other systems remain mysterious. Patient data have shown that SARS-CoV-2 can impact the liver, kidneys, intestines, brain, eyes, nose, and blood vessels.

An analysis of symptoms reported by the COVID Symptom Tracker App developed by Harvard, Stanford, and Massachusetts General Hospital revealed that anosmia (loss of smell), fatigue, and a cough are the most commonly reported symptoms of COVID-19. Some patients have also been exhibiting other neurological conditions such as stroke, hallucinations, agitation and confusion, brain damage, and seizures. In a study of 214 COVID-19 positive patients in Wuhan, China, more than a third presented with neurological symptoms. There has also been reports of myocardial injury, putting patients with preexisting heart conditions at greater risk for adverse outcomes. This appears to be quite a far-reaching coronavirus, with the long-term effects remaining unknown.

As for the neurological consequences of SARS-CoV-2, there is some idea for how it induces sensory dysfunction: while the mature olfactory sensory neurons involved in smell and taste do not express the receptors needed for SARS-CoV-2 infection, the support and stem cells of the olfactory system do. This could cause COVID-19 positive individuals to report a loss of smell and taste when those cells become infected by SARS-CoV-2.

2. Tracking community spread is tough.

Recent studies in Boston and California found many more positive cases than anticipated in affected communities, findings which worried local authorities. They both relied on detecting antibodies against the virus, but it is worth asking the question: what exactly does it mean to have the antibodies for SARS-CoV-2? On Friday, April 17, the WHO announced that serological tests for antibodies do not indicate that a person is immune to COVID-19, just that an infection has taken place. This means that although someone has previously come into contact with SARS-CoV-2, that does not make them immune to COVID-19 in the future. The length of immunity — if obtained — is still unknown.

Still, antibody tests serve as a valuable tool to understand how COVID-19 spreads through communities, aiding policy decisions from controlling the contagion to reopening its economy. Germany is the first large Western democracy to begin broad antibody testing to understand how many people, symptomatic or not, have already had the virus. Today, New York Governor Andrew Cuomo announced that the state will begin widespread and aggressive antibody testing over the next week. However, antibody tests are not without their problems. The tests are not always completely specific to this SARS-CoV-2 coronavirus, so someone with the cold or the flu might test positive. Also, the people who choose to get tested likely have a reason to think it worthwhile in the first place. Despite their difficulties, these so-called serosurveys are crucial for tracking how COVID-19 is moving through our communities, information we need to help drive it out.

Multiple new therapies with different strategies have been proposed to treat patients infected with SARS-CoV-2 — at last count, more than 160 potential therapies are being investigated. The pharmaceutical company Eli Lilly announced that it will begin testing baricitinib, approved to treat moderate to severe rheumatoid arthritis in adults, as a potential treatment for hospitalized patients with COVID-19. The drug is anti-inflammatory and is thought to act on the inflammatory cascade that results from SARS-CoV-2 infection.

Eagle Pharmaceuticals submitted an application to the FDA to begin Phase II clinical trials on its drug, Ryanodex. Originally approved to treat malignant hyperthermia (rapidly increased body temperatures and muscle contractions), Ryanodex regulates intracellular calcium levels and was shown in vitro studies to inhibit SARS-CoV-2 infection and had low cytotoxicity to in healthy cells.

As of this week, more than 70 vaccines are under development with three in clinical trials. Of the three, the candidate developed by CanSino Biologics and the Beijing Institute of Biotechnology is the farthest along — in Phase II trials. CanSino Biologicals and the Beijing Institute of Biotechnology are known for their work on an Ebola vaccine in 2017 which was taken from a concept to approval in a three year time span. On April 16th, The United States-based company Moderna was awarded $483 million by the Biomedical Advanced Research and Development Authority (BARDA) to help facilitate their mRNA vaccine candidate during the clinical trail process. BARDA is part of the U.S. Department of Health and Human Services and was established in 2006 to secure the nation from chemical, biological, radiological, and nuclear as well as infectious disease threats by funding the development of medical countermeasures. Previously, BARDA partnered with Johnson & Johnson to commit $1 billion to the development of a vaccine candidate.

Innovative vaccine strategies are also being developed. The company Ligandal recently unveiled AI-designed peptides that can not only bolster the immune system, but also act as an antidote and vaccine for SARS-CoV-2. Other research groups have designed vaccine-linked delivery platforms that consist of viral proteins on microneedle arrays that can be administered like a band-aid.

Recently, countries that have BCG vaccinations for tuberculosis (TB) were observed to have lower rates of COVID-19 cases, prompting reports that the BCG vaccine (consisting of a weakened TB bacteria) may be protective against SARS-CoV-2. The BCG vaccine has been known to reduce auto-inflammation , offering a protective effect against type I diabetes, as well as increasing cellular sugar uptake, regulating blood sugar levels. While the WHO issued a report recommending people against using the BCG as a vaccine, several research groups are beginning to launch trials to evaluate its efficacy against SARS-CoV-2.

4. Curves flattening, end lockdown?

Data from the Johns Hopkins Coronavirus Resource Center indicate that overall, the curve of new cases is flattening in countries around the world.

While these data appear promising, we know that coronaviruses can have a seasonal pattern. Scientists are predicting that SARS-CoV-2 outbreaks may occur after this current pandemic in seasonal waves. They also state that social distancing measures — to varying degrees — may be needed until 2022. One strategy to help economies re-open sooner proposes repeated cycles of regular work and lockdown, to contain the virus spread while allowing for economic activity to restart. We can hope that this and other rational strategies make their way into ongoing policy discussions on how to ease out of lockdowns.

Science continues to supply guidance and insight despite the virus-imposed slow-down, and serves as a source of hope during otherwise uncertain days. While keeping up can seem overwhelming, Princeton GMOP is here to help bring you important updates on our understanding of the virus. What was your favorite highlight from this week? Did we miss anything that caught your attention? Comment on this article, and let us know at [email protected].