Featured Article November 17, 2020

COVID-19 update: Where we are and where we need to be

During the The Jackson Laboratory’s (JAX) final event in its 2020 JAXtaposition Speaker Series JAXtaposition: During this fire-side chat, researchers will share how their cutting-edge genomic testing is giving physicians access to the most advanced precision cancer care for their patients.JAXtaposition speaker series, JAX President and CEO  Edison Liu, M.D.Conducts research focused on the functional genomics of breast cancer through an exploration of the entire genomic space.Edison T. Liu, M.D., discussed the basic scientific facts of COVID-19, our journey toward a vaccine, potential long-term effects of the virus, and the post-COVID-19 world. 

Liu also shared why he is hopeful for the future and has confidence in the development of an effective vaccine in this virtual conversation, which was moderated by  Madeleine BraunResponsible for developing and coordinating the next horizon of large scale scientific endeavors at JAX. Madeleine Braun, Ph.D., M.B.A., chief of presidential initiatives at the Laboratory.

What do we know now?

Liu, who earned the President's Public Service Medal for leading Singapore's scientific response to the 2003 SARS crisis, opened the conversation by reiterating some basic scientific facts that we have learned about COVID-19 over the past nine months:

SARS-CoV-2, the virus that causes COVID-19, affects individuals in very different ways.

“There is a clear preponderance of infection, especially in terms of morbidity, with males, with individuals who are obese, and in individuals with advancing years,” he said. Liu said that we also know now that approximately 50% of individuals who are infected are completely asymptomatic.

There are individuals who are more likely to spread the virus to others.

“We know now that there are ‘super spreaders,’ individuals that we cannot actually determine, who are more likely to spread the virus to others,” said Liu, citing the example of a choir practice during which one individual infected some 50 others.

We now know that the primary source of infection is through respiratory means.

This includes not only the large respiratory droplets that you may see when people cough, but also the small aerosols that tend to linger on in space. “Originally, we were very concerned about how the virus would land on surfaces, but thus far, we have found that even though you can detect the RNA, the nucleic acid, it's unlikely that a major source of infection is really through surfaces. The primary transmission actually is through the respiratory pathway,” said Liu.

The immune response that your body has against the virus can be a major source of damage.

“In fact, the knowledge of this and the mechanisms of this damage has led us to new therapies coming that are effective,” said Liu.

The quest for a vaccine

“This pandemic will not end until we have an effective vaccine,” said Liu. He said there is tremendous activity in the development of vaccines, citing 44 vaccines in clinical development with approximately 200 in pre-clinical development.

Vaccines mimic a natural infection in which our immune systems generate an antibody against a virus, blocking and potentially clearing it. “It is the mimicking of that first infection that will allow individuals to have neutralizing antibodies and antibodies that will block the infection itself,” he said.

He explained the differences among major vaccines that are in clinical trials right now: 

Vaccines that use proteins

In this case, the virus itself is generated and then killed, leaving the protein shell. The immune system recognizes the proteins as antigens—external substances that need to be neutralized—and generates antibodies against them. Upon subsequent viral infection, the antibodies can then recognize and eliminate live viruses. Liu said these vaccines are cumbersome to produce and to scale, and that inactivating the virus is the key safety factor. Additionally, this type of vaccine can actually be too precise.

“Not every protein in that virus is a good antigen for your immune system, and we can't, in advance, predict which ones would be a lot better than the others,” he explained.

A viral vector

A viral vector is a different virus that is made to mimic the biology and the proteins of coronaviruses. “You take a segment of the SARS-CoV-2 virus, put it into a shell of another virus of which we know the biology, and the artificial virus infects your body, and tricks your immune system into recognizing the SARS-CoV-2,” said Liu.

Raw nucleic acids

“The most contemporary of these types of vaccines is naked DNA or RNA,” said Liu. In this case, RNA is put into a capsule in such a way that it gets into the cells and actually produces the protein itself. “It’s quite fast, it’s modular, but like the viral vectors and the protein sub-units, it can be too precise,” said Liu.

The most advanced version of this is the messenger RNA (mRNA) vaccine approach, which is the type of vaccine that both Moderna and Pfizer are currently working on producing. With the mRNA vaccine, an injection goes into the muscle cells and the muscle becomes a “factory” for producing SARS-CoV-2 proteins, said Liu.

“The reason this is intriguing is that we can generate these mRNAs very quickly and can be responsive to a variety of pathogens, not just SARS-CoV-2. If it works, it will be the first time for mass deployment of a mRNA a vaccine in medical history,” he said. 

In relative terms, Liu said, we are potentially witnessing the fastest vaccine development in the history of mankind. Vaccine development requires recruiting tens of thousands of individuals for clinical trials, vaccinating half of the enrollees, and then waiting for infections to arise in sufficient quantities to determine whether the vaccine is effective or not.

“Normally it takes about two years,” he explained, “and we are looking at anywhere from nine to 12 months from the time of the pandemic to potentially the first deployment, which is almost unheard of.”

The post-COVID-19 world

Liu says that another newly evident aspect of the virus is that upon recovery, a number of individuals have persistent problems, including symptoms like “foggy thinking,” exhaustion, some shortness of breath upon exercise and mobility, and cardiovascular outcomes including myocarditis. “The heart has one of the highest contents of the ACE-2 protein [the receptor to which SARS-CoV-2 binds], and we know for a fact that heart muscles are actually infected by the virus,” explained Liu.

“In culture systems and in clinical studies, we know that heart function is diminished in people with active infections. Most will recover, but we know also some will have much longer recovery time.”

Liu estimates that at the earliest, we will be able to deploy a vaccine in the first quarter of 2021. “We're going to have to have a vaccine before we can let go of the mask and social distancing, and the repetitive testing,” he said. “I don't see an end to our actions until the latter part of 2021, but we're going to come close. I'm optimistic.”

In the meantime, Liu said, social distancing, masks and testing are proven, effective ways to control any pandemic, and especially this one. “These are the key components proven to be effective in controlling the virus,” he said. “We’re very, very hopeful going forward.”