PANDEMIC TO ENDemic

By Zubin Damania, MD

Guest Columnist

Eyes on the future

So, people have been freaking out because the COVID-19 vaccines don’t seem to prevent reinfections, sometimes. And they’re thinking the pandemic’s just going to go on forever, especially when we’re back with masks and some countries have lockdowns. Let’s do some science on this, because it turns out it’s very likely, which is something we’ve been saying from the beginning, that this pandemic of SARS-CoV-2 is ultimately going to turn into an endemic, meaning a virus that lives with us seasonally and is no different than the common cold in the severity of disease it causes. When you look at the endemic cold viruses, everybody’s been infected at some point. Elders are protected from severe disease through multiple reinfections every cold season or so. The only new primary infections are in young kids and babies who innately blow it off, partially because they may have a lower concentration of ACE receptors, or - in the case of infants - antibodies from their mother. The seasonal cold “auto-vaccinates” us, that’s why we don’t have a vaccine against the common cold, honestly. There are four endemic human coronaviruses that cause common cold-type symptoms around the world in a seasonal fashion. These have been with us for hundreds or thousands of years. Then we have three kinds of newschool coronaviruses: SARS-CoV-1, MERS, and SARS-CoV-2 (which causes COVID-19). MERS and SARSCoV-1 never achieved pandemic status because they were infectious only when you were having symptoms, so they were easier to contain; you could just identify, test, and isolate symptomatic people. SARS-CoV-2 is different, because asymptomatic people could infect others, and that’s why control and containment became pretty much impossible after it got out of the bag. When we consider antibody studies in the human population against those original four coronaviruses, we find there are two types of antibodies produced; one is IgM, which mounts an immediate response immediately after you're first infected, and the other is

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IgG, which takes longer to produce and can mount a memory response if you’re reinfected. IgM positivity really only happens in kids. So at some point, nearly every kid up until age 15 gets infected with these endemic coronaviruses and mounts an IgM response that then evolves into an IgG response. After 15, there is almost no IgM response; they generate immunity through the IgG response that persists into adulthood, but that immunity does not prevent reinfection. These studies came up with three aspects of immunity you ought to think about when discussing how a virus goes from pandemic to endemic. are usually still protected from severe disease and death.

One is immune resistance to infection in the first place. How susceptible are you, and how much does your immunity help? When you get naturally infected or vaccinated (they’re really kind of the same thing) against a disease like measles, you get sterilizing immunity. You are no longer susceptible to infection. But infection from coronaviruses (and vaccination against SARS-CoV-2) generates immunity that wanes over time, so that you can get reinfected. The second aspect of immunity is protection against severe disease. While protection against infection by SARS-CoV-2 from vaccination looks like it wanes fast, protection against severe disease does not seem to wane quickly. Natural infection probably does the same thing to some degree. Reducing severe disease is a feature of protection that matters, especially for people who are older or have compromised immune systems because those are the people that fill up our hospitals. Nobody cares about getting a cold; we care about people dying in hospitals on ventilators. Overflowing hospitals mean we can’t do elective procedures and prevent cancer with screenings. It turns out, if you study a vaccinated (or naturally infected) breakthrough case who gets a rip-roaring reinfection with a high viral load, they

The third aspect of immune protection is transmissibility. So how much does your immunity prevent you from transmitting? It’s pretty clear - and the CDC has looked at this - that the vaccines still allow you, if reinfected, to transmit SARS-CoV-2. But how much? The majority of vaccinated and previously infected people may still get infected and even get symptoms, but the duration of their transmissibility is narrowed. They clear the virus faster, which means there’s less transmission overall. It looks like that’s what happens with endemic coronavirus - our common colds - as well. Can you see how these dynamics of susceptibility, severe disease, and transmissibility can modify how you think about a pandemic? Let’s put this together into a picture comparing SARSCoV-2 and MERS Here's the punchline: (Middle Eastern Respiratory Synthe early part of the pandemic is over. drome). Both of them are coronaviruses, but MERS is Stop panicking. It's going to be okay... more fatal, particularly in young people and old people. MERS kills kids. If it became a pandemic, you would lock down early, protect as many people as you can, mask everybody, be very cautious, and aggressively work on a vaccine. At that point, you would vaccinate everybody, including little babies, and it would become a routine childhood vaccination once MERS became endemic. SARS, however, affects an age gradient that gets worse as you get older, or it attacks comorbidities like obesity, diabetes, and other risk factors. Kids generally don’t die from it. If you vaccinate against SARS-CoV-2 - or you get naturally infected - your immunity will likely prevent severe disease, particularly in the most vulnerable people. Reinfection will still occur, particularly in younger groups that then generate a broader disease protection over some period of time, probably years. But this process can be sped up by increased transmission through repeated reinfection or revaccination (boosters).

So, with a disease like SARS-CoV-2, you start out by bending the curve early on when you don’t have a vaccine to protect targeted populations like the elderly and people at risk. There has been a lot of controversy about how to do that when it comes to masking and shutting down businesses. Are we driving our children crazy? Are we creating mental illness? Are we hurting the economy? Are we harming poor people? These are all the things we’ve been talking about over the entire pandemic, and that’s up to debate because people are still at risk. You have to weigh costs and benefits. But when you get a vaccine, you now have a bypass switch where the vaccine’s going to behave like natural infection in terms of preventing severe disease. You start vaccinating as many people as you can, beginning with people at high risk, and get the jump on turning the pandemic to endemic. Classic herd immunity is tough to achieve when you can get reinfected. It may take multiple exposures to turn this virus safe long-term, but we’re creating immunity against severe disease in the process. We have a real-world case example of this with Iceland. They did a great job early in the pandemic. Iceland has a small population with integrated healthcare. They genotyped and tested everybody with a hightech kind of approach to it, and it worked really well without a very aggressive lockdown. They reached an 80% vaccination rate. Now we’re seeing their cases reach the highest rate they’ve ever been in the pandemic. Anti-vaxxers are using Iceland as an example of “look, the vaccines don’t work, right?” So what happened? They opened up, they travelled, the mask requirements were gone, and the very contagious Delta variant of SARS-CoV-2 emerged, which is so contagious that if you haven’t been vaccinated or naturally infected, it’s going to get you. But it’s Delta in the setting of an 80% vaccination rate, meaning cases may be high and

hospitals get busier because some breakthroughs will lead to some disease that requires hospitalization, but Iceland’s severe disease and deaths are very low, and they have a jumpstart on endemicity. Here’s the punchline: the early part of the pandemic is over. Stop panicking. It’s going to be okay, but we have to get through this phase where people are at risk. That means get vaccinated. Kids and young adults may get naturally infected anyway, but you can also vaccinate as many as you can. Boost for people who are at higher risk and anyone else who wants one. Maybe you’re one of those people who has diabetes, hypertension, or kidney disease, and you’re at higher risk for breakthrough infection and severe disease. If you’ve been previously infected, get a jump on that extra immunity against severe disease by getting a vaccine. Now, the thing is, this may take a little ...but we have to get while. It may take multiple re-expothrough this phase where people are at sures, which is why, when mixed with boosters and natural risk. That means get vaccinated. infection, the Delta variant may be a blessing to people who are vaccinated, because it could make this thing endemic for them quicker.

After completing a residency as an internist at Stanford University School of Medicine, Dr. Zubin Damania spent ten years as a hospitalist at the Palo Alto Medical Foundation while he began producing videos under the the pseudonym “ZDoggMD” that have since gone viral among healthcare professionals and general viewers alike. This article was condensed from a transcript of the video Pandemic to Endemic (ZDoggMD, August 17, 2021, YouTube) Used with permission.

watch the video using this link