A few months ago, many of us were living completely different lives: going to rare disease conferences, heading to work each day, going out for food, seeing family and friends. Even in March, as COVID-19 became more present in the news, I wasn’t quite worried…yet. But now, it is easy to see how COVID-19 changed the world. As of the morning of May 22nd, there are 5.11 million diagnosed cases worldwide, with 1.61 million in the United States.
Every day, scientists and researchers are working to discover more about the virus. One big focus is how the virus spreads, its long-term impact, and how/why it impacts the body in different ways. Now, StatNews’ Sharon Begley describes how coronavirus doesn’t just infect cells; it “orchestrates a hostile takeover…unlike any other known viruses.”
COVID-19: A Brief Overview
By this point, I’m sure that many of you know at least something about COVID-19. But let me give you the basics:
What We Know
- COVID-19 is a novel coronavirus. Basically, it has never been seen or researched before prior to the pandemic. It is caused by SARS-CoV-2. The “19” stands for 2019, not for the 19th strain of the virus.
- There are certain groups more at risk of severe complications. These include older individuals, people with prior underlying health conditions, men, and minority patients.
- Recently, an inflammatory condition – believed to be caused by COVID-19 – has been affecting children. Scientists think it may be similar to Kawasaki disease, which causes arterial inflammation.
- COVID-19 is extremely infectious and can easily spread from person to person. Respiratory droplets from someone who is infected can spread the virus to others. This is why social distancing, and staying over 6 feet apart, is important. Despite prior information, the CDC now claims that the virus does not easily spread from surface contamination.
- There are 100 vaccines in development to treat and prevent COVID-19. However, most of these will not make it to trial, much less to market.
- COVID-19 impacted rare disease research and patient outcomes. A lot of research unrelated to COVID-19 has been halted. Additionally, non-urgent medical procedures or visits are being postponed.
What You Can Do
- There are multiple ways you can get involved in fighting COVID-19. That’s right – you can chip in to the change.
- Many medical practices are looking for blood donations.
- The NIH is running a survey on COVID-19 in the rare disease community.
- Enroll your medical practice, or find resources, in the American Society of Oncology‘s Cancer and COVID-19 registry.
- Make masks for yourself and others.
- Find ways to advocate for rare disease patients.
- If you are a member of the rare disease community, and impacted by COVID-19, you can apply for relief. The NORD COVID-19 Critical Relief Program is offering qualified Americans up to $1000 for necessary non-medical expenses like housing, utilities, and phone service.
COVID-19’s Hostile Takeover
When virologist Benjamin tenOever began studying SARS-CoV-2, he was surprised at what he found. In fact, he states that the way COVID-19 infects cells is:
“something I have never seen in my 20 years of [work].”
COVID-19 “orchestrates a hostile takeover” of someone’s genes, taking control of the gene and changing its DNA expression.
Genes and Immunity
Basically, there are two types of genes that play a role in immune response.
The first type of genes, which tenOever refers to as “call to arms” genes, creates interferons. These proteins are released by infected cells. As a result, interferons tell other cells to slow down, activate certain genes, and stop the virus’ ability to replicate. For up to 10 days, the interferons do their best to regulate viral growth until the second type of genes (“call for reinforcement” genes) kick in.
These genes produce chemokines, which play a role in cell migration, stop tumor growth, and sound the alarm when they find foreign invaders. This brings T-cells (which fight viruses) and B cells (which make antibodies) to fight the source of infection. When these cells are successful, they start killing the virus.
In the original SARS outbreak, as well as the flu, the virus messes with both sets to interrupt immune response. However, COVID-19 reacts differently. Instead of stopping both genes from launching, it only interferes with one set of genes, allowing the other to launch.
In their study in Cell, tenOever and his colleagues show how these cellular defenses are activated and inactivated. The research team studied ferrets, lung cells from patients with COVID-19, and then healthy human lung cells. Within 3 days of viral infection, COVID-19 stopped the “call-to-arms” genes, allowing the virus to more freely replicate. But it still allowed for “call-for-reinforcement” genes to produce cytokines.
So the virus continues to grow and replicate. But then a cytokine storm occurs. This “unique” and “aberrant” consequence can lead to severe reactions and fatalities. In fact, the cytokine storm is cited for some of the more fatal responses to COVID-19 as the uncontrolled immune reaction overwhelms the body.
Another study explored how SARS-CoV-2 was able to control “call to arms” genes while allowing the other genes to release. Researchers discovered that the virus’ ORF3B gene produces transcription factor, a type of protein that prevents cells from acknowledging a virus. As a result, interferons don’t notice the virus and so it isn’t stopped from replicating.
tenOever and his team looked at lung cells from COVID-19 patients to validate this research. These lung cells showed no interferons. As a result, says tenOever:
“There is nothing to stop the virus from replicating and festering in the lungs forever.”
However, cytokines begin accumulating more and more. All of a sudden, the lungs become so inflamed that it prompts additional inflammation. The cycle repeats, with the patient getting sicker and sicker. The virus also damages and kills lung cells, making it more difficult to breathe.
One reason why elderly adults, as well as people with underlying health conditions, may be more severely affected by COVID-19 is their genes. Their “call to arms” genes are already weaker. So, even though COVID-19 dampens this, younger or healthier individuals may still have a better chance of fighting the virus.
Using Interferons to Combat COVID-19
In a preprint, researchers studied the relationship between interferons and human cells. They also saw the SARS-CoV-2 stopped most interferon genes from launching. However, they wanted to see whether treating these cells with interferon IFN-1 would change the outcome.
Before exposing cells to COVID-19, researchers applied INF-1. Next, the cells were exposed to the virus. Within a few days, the viral levels were 1,000-10,000x lower in interferon-treated cells than in non-treated cells. As a result, researchers note that preventative interferon treatment may slow or stop COVID-19 infection.
Of course, there are issues with this proposal. First, interferon drugs can cause nausea, fatigue, depression, anxiety, and other psychiatric issues. Next, the drug would need to be administered to “healthy” (non-infected) individuals. But doing this on a wide scale means it may negatively impact many people. Finally, there are already a lack of medical resources at this time. So interferon accessibility could present a problem.
However, researchers note that it could present a new and more effective way of combating the virus. Clinical trials to determine its usage, tolerability, and efficacy are in the works.