There seems to be a public perception that the COVID pandemic is over and has turned into just another upper respiratory disease. That’s simply not the case as is evidenced in data such as wastewater, excess mortality, pediatric hospitalizations, and the prevalence of long COVID.
Earlier, I’ve addressed the false notion that the omicron strain is mild. It isn’t, However, it’s fair to ask why hospitalizations are down. There are a number of reasons for this that work synergistically together.
Evolution
First, we haven’t had a major new variant emerge in some time (genetic shift, such as delta and the first round of omicron). What has been occurring are small genetic changes in omicron (genetic drift). However, even drift can create havoc as evidenced by the resurgence in Manaus, Brazil early in the pandemic. Much of the population had been infected with the original strain of the virus only to be reinfected by the gamma variant (P.1), leading to the need for mass graves. This was also an early warning that herd immunity, pushed by both some in the current administration (Dr. Jay Bhattacharya at the NIH and Dr. Vinay Prasad who briefly held a role at the FDA) as well as in the Great Barrington Declaration, wouldn’t work, thus ending the notion of natural herd immunity as a useful approach to the end of the pandemic, in spite of the extensive disease and death that would cause in the process.
While it doesn’t bring the pandemic to an end, the result of that is immune systems among the population that either have some residual immune response either to infection or vaccination. However, it’s important to keep in mind that the robustness of that response fades over time.
The genetic drift has been relatively slow changes to the omicron strain over time since it emerged. When the virus proteins stay relatively stable, that allows whatever residual response in the immune system to more readily identify the virus and react. That could easily change with BA.3.2 (Cicada), which has over 30 mutations to the spike protein alone, but this is still framed as risk, not certainty as an outcome.
Immunity
The immune response reduces susceptibility more than infectiousness, but it provides some of both. If the immune system already has neutralizing antibodies and primed memory B/T cells, the virus faces an immediate immune response. This is why it’s better to get vaccinated as opposed to relying on disease driven immunity. Getting a disease to gain some immune protection from that disease is insanity.
There are a few outcomes from a primed immune response:
- It shortens the period of high viral replication
- It reduces peak viral load
- It reduces the duration of viral shedding
- It reduces the chance of severe inflammatory cascades, such as a cytokine storm
It should also be noted that the waning of immunity varies. For example, mucosal immunity wanes the fastest and T-cell memory lasts the longest. This has implications for both infection and vaccine derived immunity related to how recently either occurred. Immune imprinting could also play a role in response to new variants because it biases the immune system to prefer updating old defenses rather than creating new ones from scratch, which is a risk for those who get COVID vaccines frequently.
Severity
When the immune system is primed, the virus will have less time to replicate before the adaptive immune system fully activates. This reduces the chances of a number of factors that contribute to the severity of disease and need for hospitalization:
- Tissue damage (the virus binds to ACE-2 receptors, which are found in most tissues except most immune cells, red blood cells, bone marrow stem cells, and the lens of the eye).
- Inflammatory response
- Major complications (hypoxia, blood clots, and organ damage/failure)
The take home is that omicron’s intrinsic virulence hasn’t meaningfully changed; what has changed is its effective virulence in a population with widespread immune priming, which makes the same virus appear less severe than it actually is.
An Exponential Illustration
It’s estimated that it takes between 100-1,000 infectious SARS-CoV-2 virions to cause infection to 50% of human hosts. When a viral particle infects a human cell, depending on the type of cell, it creates 1,000-100,000 infectious particles when the cell ruptures. That should clearly illustrate why reducing the number of infected cells early on is so important. Each of those newly produce viruses goes on to infect other cells in the body until the immune system can get it under control. When the immune system has been primed, it has a head start on doing so. That leads to less virus being produced, thereby less tissue damage and less viral load, meaning less spread to others.
For example, I’ll use the midpoint of each range to illustrate the consequences of a few generations of infection within the body without the benefit of an immune response.
- Initial infection: 500 viruses.
- First generation: 500 x 50,000 = 25,000,000
- Second generation: 25 million x 50,000 = 1.25 trillion
Given that the human body has about 30-40 trillion cells, it’s a good thing that we have immune system to stop this kind of exponential growth. It’s also worth mentioning that many of the virions produced in the cell won’t be infectious, but that doesn’t change the mathematical illustration.
Most importantly, SARS-CoV-2 replicates in a period of about 8-12 hours, so that exponential illustration occurs in under one day, thus adding to the importance of preventing infection or vaccination to help mitigate it.
Summary
Hopefully that explains why hospitalizations and infections are down. It’s a combination of repeat infections, vaccinations, and little viral mutation recently. As alluded to earlier, BA.3.2 could change this quickly given its potential for immune escape. That doesn’t bode well for either the vaccinated, the recently infected, or for healthcare capacity. Reduced hospitalizations do not mean reduced risk, they mean the immune system is doing more of the work that hospitals used to do.
We still don’t have enough data to really understand this variant and its impact on humans, but the smartest thing to do is to continue to work upstream from getting infected in the first place by using the various nonpharmaceutical interventions (NPIs), such as respiratory protection, air filtration, and ventilation.
