The New York Times, in an article on October 5th, laid out a great framework for understanding both how infection and the body’s immune response progress – and are intertwined to determine the severity of disease and outcomes that are experienced. With clear, explanatory charts, they map out how:
are triggered and kick-in after infection to produce either mild or severe disease outcomes. The article then covers different types of treatment, including “anti-virus treatments” are used to combat COVID-19.
The NYT on Antibodies
With kudos and thanks, we will discuss in a bit more detail here exactly the role that antibodies can play in this process – and why they can be so powerfully applied to:
- prevent infection in the first place, if given prior to exposure; and/or
- prevent severe symptoms and disease if given immediately after exposure.
Here’s what they had to say:
One way for doctors to fight the coronavirus is through experimental treatments that may reduce the amount of virus in the body.
On Friday, the president received an experimental antibody cocktail developed by drug maker Regeneron. The next day he began a course of the antiviral remdesivir. Experts say such treatments might be best administered early in infection, to rein in the virus before it runs amok.
Regeneron’s product contains two types of monoclonal antibodies — synthetic, mass-manufactured mimics of natural antibodies that, in the lab, sequester and neutralize the coronavirus. Monoclonal antibodies have not yet been given an emergency green light from the Food and Drug Administration to treat people infected by the coronavirus. But preliminary results suggest they might be able to reduce viral loads and speed recovery.New York Times, October 5, 2020, Charting a Covid-19 Immune Response
How Antibodies Work
The Times missed two key points and attributes of how antibody-based treatments work, and can be applied to protect people that are vulnerable through prevention of infection in the first place, or stop a new infection rapidly and prevent severe symptoms and disease in the second. The mechanism is the same in both cases: antibody-based treatments simulate the body’s adaptive immune response – which is far more specific and effective at stopping viral replication than the innate immune response. Why? Because these antibodies have seen the virus before! They can immediately attack, bind and block the ability of the virus to enter the host’s cells and replicate.
So that Adaptive Immune Response, instead of starting a week later and rising over time, starts from a baseline. That’s an enormous difference when you are facing something that has exponential growth. If you think of the virus like a fire, this represents the opportunity to put it out when the match is lit, rather than waiting for it to grow – sometimes beyond control.
Prior to Exposure
If given prior to exposure, If the antibodies are effective and properly dosed, in most cases this baseline will be sufficient to stop the viral replication in its tracks. Just like stopping a fire, being able to respond immediately when the match is lit is a game changer.
Immediately After Exposure
If given immediately or very rapidly after exposure, then we have the diagram as the Times drew it. But of course, it is easy to see that the sooner after exposure it is given, the lower the curve of uninterrupted viral replication and load, and the more effective it is likely to be. This is why doctor’s rushed to treat President Trump recently with Regeneron’s REGN-COV2 antibody cocktail – to prevent the progression of the disease. In his case, based on the symptoms that have been reported, he may well have been 5 days or more into his infection. Thus, other antivirals were also added to the treatment regime. If he could have received REGN-COV2 within a few days after exposure, he might well have avoided severe symptoms. Just like putting out a fire, the speed of response makes all the difference.
What Are the Caveats?
Of course, there are no guarantees in life or in science. We are still awaiting peer review of the comprehensive data set on the Phase 3 trials, as well as additional ongoing studies, of the different monoclonal and polyclonal antibody cocktails, and Immunoglobulin and Hyper-Immune Globulin drugs in development. However, all of the early data have indicated very positive results – such as Regeneron’s Phase 3 Trial data showing a 70% plus decrease in hospitalizations and similar results from Eli Lilly. These are very statistically significant clinical result, which are in line with both laboratory and animal model studies which demonstrate their effectiveness at dramatically and rapidly reducing viral loads.
These results are also in line with what we are seeing from vaccine trials, and most importantly the long history of immunoglobulin and monoclonal antibodies all predict that such results are to be expected. Both of these therapeutics have now received Emergency Use Authorizations, received billions of dollars in funding for production and are in distribution across the United States, have been highlighted by the NIH for physicians for outpatients at high risk of disease progression, and have a playbook from HHS/Operation Warp Speed for public health departments to put them into action to save lives. While it is still very important to continue to gather data to study and validate both efficacy safety, we also must not err too much on the side of caution. These are not normal times.
Given the severity of the epidemic, the paucity of alternatives for treatment – in contrast to the huge sums being poured into vaccine production – this is why we are advocating for resources and focus be put immediately into scaling the production of antibody-based drugs. Every week that goes by costs us more in lives and treasure. The risks of inaction far outweigh risks of action.
- Association of SARS-CoV-2 Genomic Load with COVID-19 Patient Outcomes (ATS Journal)
- High SARS-CoV-2 viral load is associated with a worse clinical outcome of COVID-19 disease (BMJ, Yale, CSH on MedRXiv)
- SARS-CoV-2 viral load is associated with increased disease severity and mortality (Nature)
- SARS-CoV-2 viral load predicts COVID-19 mortality (The Lancet)
- In vivo antiviral host response to SARS-CoV-2 by viral load, sex, and age (Cold Spring Harbor Labs in BioRXiv)