[COLOR=#1a42eb]Do the SARS-CoV-2 vaccines protect against infection and prevent transmission of the virus, or do they simply reduce symptoms of COVID-19?[/COLOR]
This is a key question that is being widely discussed, and rightfully so as it determines what benefits would be provided by the current population-level vaccination efforts ongoing around the world.
While reduction of symptoms would provide a clear direct benefit for any vaccinated individuals and reduce population hospitalizations and deaths, the indirect benefit of vaccines on the population is potentially much greater, protecting not just the vaccinated but all those with whom they come in contact. Reducing the proportion of the population susceptible to infection strongly reduces the rate of community transmission, preventing many infections, and helping get the pandemic under control and return society more quickly to its pre-pandemic activity levels. If great enough, this could lead to herd immunity, whereby there are not enough susceptible individuals in the population for epidemic spread of the virus to be possible, effectively ending the pandemic and converting SARS-CoV-2 to an endemic, manageable virus. But this indirect benefit is only realized if the vaccines protect people against infection and transmission.
So, are the SARS-CoV-2 vaccines protecting against infection and preventing transmission? The short answer to this question is "we don't know for sure" because of limitations in the phase 3 study designs that prevent us from being able to definitively prove efficacy against asymptomatic infections or for reduction of transmission.
This is the reason for the disclaimers we see by the vaccine companies and scientific leaders that "we do not know whether the vaccines reduce infection or transmission," including the World Health Organization. But I am afraid this disclaimer is causing confusion in many about what the vaccine does or how it is designed to work.
I see numerous people boldly state "the companies admit the vaccines don't prevent infection, they only reduce symptoms" and even claim that the vaccines are "not really vaccines, they are biological treatments." As we statisticians and other scientists well know, the statements "we do not know whether the vaccines reduce infection or transmission" and "we know the vaccines do not reduce infection or transmission" are two very different things, but those who boldly claim that the vaccines are not preventing infections but only reducing symptoms are clearly confusing the two.
While it is true that limitations in the phase 3 study designs keep us from having definitive evidence that the vaccines are preventing infections or transmission, in this blog post I will explain why I think it is all but certain that the SARS-CoV-2 vaccines must be protecting against infection, and exceptionally likely that they are reducing transmission, at least to some degree.
While they may not be providing full sterilizing immunity that prevents all viral replication and provides 100% protection against infection or transmission, they are CERTAINLY doing more than "just reducing symptoms," and are likely to be protecting against infection and transmission enough to yield the intended effect once near population-wide vaccination is accomplished. I support this assertion based on a basic explanation of how the vaccines are designed, how our immune system works, and interpretation of the existing data from the phase 3 trials.
How are the vaccines designed to work?
So far, the USA has approved two vaccines for emergency use, the Moderna and Pfizer/BioNTech mRNA vaccines, and on February 18 will consider a third one, Johnson & Johnson/Janssen, which is a "viral vector" vaccine. The key component of all of these vaccines is the genetic code for making SARS-CoV-2's spike protein, the key protein of the virus that is necessary for its entry into cells and replication. The key difference between the mRNA vaccines and viral vector vaccines is the vehicle of delivery. While the Johnson & Johnson vaccine splices the spike protein genetic code into a deactivated human adenovirus, a common cold, and delivers it into the cells like a Trojan horse, the mRNA vaccines do not use a viral vector but instead encase the mRNA in lipid nanoparticles for protection and entry into the cell. In both cases, the spike protein mRNA in the cytoplasm generates spike proteins in the cell that stimulate the individual to produce an immune response against it.
There are claims circulating around social media suggesting the "SARS-CoV-2 vaccines are not really vaccines" because they are not made from deactivated or weakened versions of the target virus or because "they only reduce symptoms, don't stop infection". While it is true that the oldest vaccines were constructed from deactivated or weakened versions of the target virus, there are many other modern strategies for vaccination, including the viral vector technique underlying the Johnson & Johnson vaccine and the mRNA technique underlying Moderna and Pfizer's. Although only containing a part of the genetic code for the target virus, these are designed to do the same thing that all vaccines are designed to do: stimulating immune response for protection against future exposure to the virus. By design, they are not meant to simply be "treatments" that "only reduce symptoms", but are meant to train the body's immune system to protect against future infection and transmission.
They work differently than monoclonal antibodies or convalescent plasma that can be injected into an infected COVID-19 patient to boost their immune system and help treat the disease. These introduce externally produced antibodies into a person to supplement their own immune system in fighting off a current infection, so are designed to be treatments meant to reduce symptoms in an already-infected patient. This is in contrast to the vaccines, that are designed to expose a non-infected person's immune system to a part of the virus to stimulate their body to produce its own immune response, with hope of building immune memory to help the immune system respond promptly if exposed to the virus sometime in the future.
All of these SARS-CoV-2 vaccines are designed to work in a similar fashion -- to expose the immune system to a part of the SARS-CoV-2 virus to generate a vigorous immune response against it, in order to build immune memory, such that when later exposed to the SARS-CoV-2 virus, the immune system is able to react quickly and neutralize the virus.
How does our immune system fight the virus and what does "infection" really mean?
Once exposed to an invading virus, a race between the virus and immune system commences that will determine the eventual fate of the infected person.
Our immune systems are designed to recognize an invading virus and begin constructing an immune response consisting of T-cells and antibodies to neutralize it. Unfortunately, this takes time, especially for a novel virus to which the system has not been previously exposed, and in the time the immune system is trying to construct the immune response the virus is rapidly replicating and spreading to other cells, which can be measured by increased viral load.
Viral load influences symptoms and transmissibility. For SARS-CoV-2, higher viral loads have been shown to increase transmissibility of the virus, leading to the exhalation of sufficient viral particles such that others nearby might be exposed to enough virus to infect them. Higher viral levels also tend to worsen symptoms and increased viral replication can lead to more severe disease. If the SARS-CoV-2 virus replicates sufficiently so that it spreads down the respiratory tract into the lungs, it finds fertile ground for enhanced replication, and that is when it tends to produce the most severe and life-threatening conditions that make the virus so dangerous. In those situations, the spread gets out of control like a forest fire and the immune system struggles to keep up. In those cases, the virus wins the race.
If the immune system works quickly enough, the virus can be neutralized before it can get to that point. Using the analogy of a forest fire, the hope is that the immune system recognizes and extinguishes the localized brush fire before it can become an inferno that burns the forest down. If the virus is neutralized before it replicates sufficiently to produce a positive viral test, then you could argue the person was never effectively infected even if technically the virus replicated to some degree, since their infection would be completely undetectable. And even if it produces a positive test, if it is neutralized before it can produce any sickness, symptoms, or transmit to others, then it still provides equivalent direct and indirect protection to society even if not strictly preventing replication or detection of the virus. In that case, the person's virus is as indolent as if they had not been infected at all. Thus, in practice the concept of preventing infection is not as straightforward as one might think.
By design, an effective vaccine will produce immune memory so that when the vaccinated individual is later exposed to the virus, their immune system has a head start in the race and can produce a rapid immune response against it. If sufficiently rapid, it can prevent sickness, symptoms and transmission, and possibly even prevent a positive viral test. This is the goal of vaccination, since if the exposed individual is protected against sickness the vaccine has produced a direct benefit for them, and if they cannot effectively transmit to others then it is providing the intended indirect effect for the rest of the population.
Some vaccines, such as measles and smallpox, provide what is called sterilizing immunity, which means the immune system responds so quickly that the virus cannot replicate at all, which would prevent all sickness, symptoms, and transmission, as well as positive viral tests. In this sense, it provides 100% protection against symptoms, infection and transmission. Others, including vaccines against Hepatitis B and C, pertussis (whooping cough), inactivated polio vaccine (IPV), and inactivated flu vaccines, do not provide full sterilizing immunity, but still provide variable levels of protection against sickness, symptoms, and transmission. Some prevent sickness and suppress symptoms, but do not remove the virus from the individual's system, as it can still be detected by a viral test. In that case, if the viral levels are high enough, transmission may still be possible, although if the viral levels are sufficiently suppressed such non-sterilizing immunity might still significantly reduce transmission. One example is rotavirus vaccines that do not provide sterilizing immunity but have been shown to significantly reduce viral loads and reduce transmission.
In spite of how it is sometimes portrayed in the media (e.g. see this
BBC article), the protection afforded by vaccines is not an either-or proposition of full sterilizing immunity or simple suppression of symptoms. There is a continuum of protection based on how rapidly it can produce an immune response, and what proportion of those vaccinated realize that rapid response.
