Media reports about COVID-19 coronavirus would lead you to believe that after 6 months, we know nothing about it and are doomed. But that’s not the case. We know quite a bit about this virus, how it behaves and how to treat it, and we learn more every day.
Have you ever heard of A*STAR? Unless you’re a bio-nerd (like me,) probably not. But you may want to check them out. The Agency for Science, Technology and Research in Singapore is on the COVID-19 case, and that’s a very good thing.
When SARS was raging in 2002-2003, A*STAR came up with an accurate testing kit that changed the approach to beating that virus. Their deep familiarity with SARS and other RNA viruses gives them a special insight into SARS-CoV-2, the virus behind COVID-19.
One team has been hard at work combing through the scientific literature and published studies done on SARS-CoV-2 and COVID-19. They’re trying to find the gaps in what we already know. They were convinced this would allow them to focus on specific avenues of research into treatment and prevention and help the scientific community find a better “road map” to the solutions we all need.
Here’s a look at what they believe they know about this pandemic-causing pathogen and how it interacts with the human immune system.
As you undoubtedly know by now, SARS-CoV-2 is a coronavirus. There may be hundreds of strains, the vast majority of which never get out of the various animals in which they arise. Chickens, cows, pigs, rats and as you no doubt know from the news, bats are all potential carriers of coronaviruses. They derive their name from the “crown” of protein studs on the surface of the virus.
There are seven known strains of coronaviruses that can infect humans. Four are considered non-lethal and usually only effect the upper respiratory tract, with minor symptoms. Many “common colds” are actually caused by Human Coronavirus strains. The four that cause these infections are HKU1, NL63, 229E and OC43.
But you’ve probably never heard of them. None of them has ever had their own pandemic. The other three Human Coronaviruses, however, are a different story. Each has created serious problems for humanity. SARS, MERS (Middle East Respiratory Syndrome) and now SARS-CoV-2 are more deadly than the other four and therefore must be taken more seriously.
SARS-CoV-2 is the “next generation” of the SARS virus. While it’s still being investigated, it’s believed by numerous intelligence agencies from around the world that the virus was enhanced in the Wuhan Institute of Virology labs. That “gain-of-function” research was performed, at least in part, under funding from a $3.7 million grant directed to it by Dr. Anthony Fauci.
You know him as the head of the US National Institute of Allergies and Infectious Disease and the man behind stay-at-home orders, the race for a vaccine and our current economic malaise. (You may be interested in Fauci Funneled Millions Of US Dollars To Wuhan Lab For Coronavirus Research) It’s plausible, therefore, that we paid (at least in part) for the virus that caused all this trouble. More on that in the future.
The genomes of SARS-CoV (SARS) and SARS-CoV-2 share a 79 percent similarity. SARS-CoV-2 shares a 98 percent similarity with a bat coronavirus called RaTG13. One of the key researchers in the Wuhan facility is also where China’s famous “Bat Lady,” Dr. Zhi Zhengli, is based. While most of China and much of the US media is screaming that China’s claim that the virus didn’t come from the Wuhan lab is true, that seems unlikely, even at a casual glance.
In terms of transmission, SARS-CoV-2 is similar to both SARS and MERS. Touching contaminated surfaces, then touching your mouth, nose or eyes or inhaling respiratory droplets are the primary means of transmission.
The symptom incubation period for SARS-CoV-2 was identified early on. (Read Symptom Incubation Period For COVID-19 Coronavirus Identified) For the majority of infected patients, symptoms will begin somewhere between 5 and 14 days after infection. The most common of these symptoms seems to be a slowly increasing fever, a dry cough and some mild respiratory distress.
More uncommon symptoms include dizziness, coughing up blood, diarrhea, nausea and muscle or joint pain. The vast majority of people will avoid severe or critical symptoms, like ARDS (acute respiratory distress syndrome.) The elderly and those with comorbidities – diabetes, immuno-compromising syndromes, obesity and cancer, to name a few – have a much higher risk of severe or critical symptoms and death. (Read Death Risk Factors Identified for COVID-19 Coronavirus)
Patients with critical symptoms, especially ARDS, are far more likely to need assistance breathing from a ventilator. Without that mechanical assistance, blood oxygen levels can fall to dangerously low levels. Those same low blood oxygen levels put them at greater risk of developing a secondary bacterial or fungal infection. Of course, use of a ventilator creates risks as well, including damage to the trachea and even potential brain damage.
There is also the risk of a cytokine storm, a situation in which the overproduction of immune regulators called cytokines causes uncontrolled inflammation. It can happen as a result of the response to the SARS-CoV-2 or a secondary infection. The damage caused can result in organ failure and death.
A similar pattern of a hyperactive immune system and resulting lung damage was observed with SARS-CoV. This would suggest that not only the virus, but how the body responds to it, determines the severity of the disease and its symptoms.
Immune response or salf-sabotage
When the SARS-CoV-2 virus gets into the body, it attacks the lungs first. It gets into lung tissue by identifying two key proteins: angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2.) The virus’s spike proteins recognize the ACE2 using a specified body on the spike. The TMPRSS2 facilitates the viral entry into lung cells via the protein spike. Once inside the cell, the virus hijacks the cell’s machinery and begins to make many copies of itself. Eventually the cell dies, releases the virus and the process begins in a new lung cell.
The death of the cell host, as well as the presence of the virus, release molecules that sound the alarm for an immune response. Macrophages show up first. These secrete cytokines, which recruit other cells like monocytes and T cells. In a normal, healthy immune response, these defenders successfully contain and clear the virus without damaging the surrounding tissue. They then go on to produce protective antibodies that can neutralize the virus.
In the case of SARS-CoV-2, however, this process sometimes gets out of control and researchers still don’t fully understand why. The cytokine storm, or the over-production of pro-inflammatory cytokines, can cause serious lung damage and ARDS. If things get really bad, the cytokine storm can spread to other organs. Multi-organ or systemic failure can occur, most often leading to death.
What’s next: treatments and vaccines
The threat posed by SARS-CoV-2 is being mitigated as much by a massive and ever-growing body of research as by social distancing, hand-washing and masks. Knowing the virus’s preference for ACE2 and TMPRSS2, there is promise in an approach that blocks or interferes with these two proteins, and we can do it with existing drugs.
Studies and trials in this area are already underway. In a machine-learning study, it was predicted that baricitinib, which is a rheumatoid arthritis drug, would inhibit ACE2. In a clinical trial involving APEIRON, which is a recombinant form of ACE2, patients will be infused with high levels of soluble ACE2. The belief is this will block the virus from binding to the cells. It’s also known that drugs like camostat mesylate and nafamostat mesylate can inhibit TMPRSS2. These could, theoretically, be repurposed to treat COVID-19.
In an attack plan focused in the other direction, scientists are also trying to block the spike protein on the virus using therapeutic monoclonal antibodies, either based on those found in sera from recovered patients or antibodies previously identified against SARS-CoV. There are also several vaccines which, it’s hoped, can produce antibodies that will neutralize the virus. Other vaccines are built around the idea of provoking a long-lasting memory CD8+ t cell response.
Researchers are also looking at ways to suppress the effect of cytokine storms, since the over-active immune response seems responsible for so many of the severe to critical cases encountered. Several trials are underway for drugs that are able to block the effect of IL-6, a key cytokine.
Other studies are looking at drugs that block granulocyte-macrophage colony-stimulating factor (GM-CSF.) GM-CSF is thought to be a key cause of lung inflammation in COVID-19 patients. One fascinating approach is to filter patients’ blood through specialized columns to trap excess pro-inflammatory cytokines, reducing their impact on organs.
Early on in this pandemic, I advised my readers not to panic. Specifically, I reminded them that the smartest minds in the world were on this. A*STAR is just one group putting their considerable brain power to work helping to create pathways to breakthroughs. Since it’s likely we’ll only need one or two breakthroughs to get ahead of this virus, chances are good we’re going to be just fine, sooner rather than later.
Keep the faith and keep after it!