I suggest you skip this one. Instead, ask AI whether coronaviruses or influenza are more likely to cause the next pandemic. That’s a better answer than asking me in 2020 to tell you it will become another cause of the common cold.
Influenza & Pandemics
We can learn a lot about pandemics by studying influenza. While Covid-19 and influenza are different, comparing and especially contrasting these two respiratory viruses will help us better understand the ongoing Covid-19 pandemic.
Influenza is GOAT, first-in-class for causing seasonal and pandemic outbreaks. We worry about influenza every respiratory season. Any time people get sick during this period—from a runny nose to an upset stomach—folks often say they have the flu. There are many different types of respiratory viruses; however, most people mistakenly think influenza is the cause of the flu. I like to say: If you feel like you got hit by a truck, then it might be influenza.
We monitor the progress of seasonal influenza, which typically begins in the warmer southern states. Then, like a wave, we see cases gradually increase from the south to the north. Positive tests rise quickly until epidemiologists declare: Influenza is here. At that point, most mild to severe respiratory illnesses seen in emergency rooms are assumed to be influenza. There’s usually a spike in cases as people gather for the holidays and spend more time indoors together. Later, cases decline as spring arrives.
These annual influenza waves, however, are only remnants of past pandemic influenza viruses. The 1918 influenza virus, for example, circulated as seasonal influenza for several decades before disappearing and being replaced by other strains. It reemerged as the H1N1 swine flu epidemic in 2009 and has caused seasonal outbreaks ever since. We have been vaccinating against this H1N1 strain annually since 2009. [I think this was true in 2020.]
Influenza is very adaptable and can better evade the immune system than other respiratory viruses. Each year, it experiences small changes called antigenic drift, where tiny mutations modify immune recognition. We update vaccines to match circulating strains, sometimes successfully, sometimes not. Seasonal vaccines typically offer 20-50% protection.
With SARS-CoV-2, don’t expect the equivalent of antigenic drift to happen. Even though all RNA viruses are susceptible to accumulating mutations, there are scant examples that suggest coronaviruses mutate and escape the immune system. The difficulty lies in the need to change the spike protein so that the immune system no longer recognizes it. At the same time, the virus maintains the ability to attach to cellular receptors to enter the cell. It is possible that SARS-CoV-2 could have a mutation that escapes immune detection yet still binds the cells in the respiratory tract. Still, this type of antigenic drift is not a common feature of coronaviruses. We will likely see different strains of SARS-CoV-2, but less likely that these will entirely evade the immune system. At the very minimum, there should be some cross-reactivity or partial immunity to any drifted strain. [2025 update: I did not change this paragraph a bit from the book text. Prove me wrong. By the way, AI says I am wrong on this subject of drift in Coronaviruses.}
Instead of drifting to evade the immune system, the issue with coronavirus is that immunity to it doesn’t last long. Within 6-24 months, even after an effective initial immune response, you might catch the same virus again as your immunity fades. Therefore, drifting isn’t the main reason for relapsing COVID-19 infections, but rather the loss of immunity.
Immunity to influenza, on the other hand, can last for a very long time. In fact, when H1N1 re-emerged in 2009, many people who had it during its previous circulation in the 1960s still had immunity. As a result, the elderly—despite having weaker immune systems from normal aging—were relatively protected from H1N1. Unlike coronavirus, influenza can induce long-lasting immunity after infection.
While antigenic drift causes seasonal influenza as the virus gradually mutates, antigenic shift leads to influenza pandemics. Antigenic shift is a major genetic change often involving the reassortment of influenza viruses from different species. Non-human animals like pigs and birds commonly carry influenza. What if human and bird influenza strains infect a pig at the same time and the virus recombines? The pig could begin producing humanized bird influenza strains. These recombinant strains might then be transmitted back to humans, and if effective human-to-human transmission occurs, a new influenza pandemic could start.
The H and N labels for influenza relate to antigenic shifts. For example, H1 and H3 are current human strains, while H5 and H7 are bird strains. The N type can also vary, such as N1 or N9. H and N are key functional proteins that help identify different influenza viruses. If influenza replaces its human H1 with a bird version, it could create a virus that the population has no immunity against. If the virus can still spread efficiently among people, many might become infected with this new strain simultaneously. Pandemic.
Fortunately, most cases of recombined humanized-bird influenza do not effectively spread from human to human. If a new strain jumps into a human, we see a few cases in people exposed to animals, but they don’t pass it on. These viruses fail somewhere in the chain: either in cell-to-cell movement, making copies in the cell, or in human-to-human transmission. [2025 comment: see egg prices]
Humans are often exposed to animal coronaviruses. However, pandemics are rare because these viruses usually don’t bind well to human receptors or spread easily among people. SARS and MERS, which we will learn about, are non-human coronaviruses that adapted to infect humans after passing through intermediary species. SARS-CoV-2 also originated from a bat coronavirus that likely passed through an intermediary animal before infecting humans. Importantly, SARS-CoV-2 can spread efficiently between people.
Multiple classes of medications will likely be developed for coronaviruses. The question is not only how effective they are but also how toxic they might be, especially when Covid-19 becomes the common cold.
When considering how to treat influenza, we also need to understand what exactly a pandemic is—essentially, a collection of regional epidemics. This simple definition often confuses the media and politicians, leading to poor reporting and misguided policy decisions. You cannot view the world as a whole, nor can you see an entire country the same way, because an epidemic impacts different regions in different ways. In fact, in the United States, it’s often inaccurate to consider a state as a whole. Large states like California and New York have vastly different geographies, population densities, healthcare resources, and socioeconomic factors that influence the spread and severity of an epidemic like COVID-19. Although there have been calls for national- or state-specific policies to handle COVID-19, such measures are unlikely to succeed. The pandemic is not your community’s pandemic—it’s your epidemic, which combines across communities to form a pandemic. Only within your community can you take effective action.
While a pandemic involves multiple simultaneous outbreaks worldwide, focusing on your regional epidemic is crucial. How well can your local healthcare and public health systems meet your community’s specific needs? What steps can we take now to make a difference? Although we all share resources like PPE or testing supplies, and infectious diseases do not respect borders, interventions succeed or fail depending on the time and place. It may be that your local ICU is full or has capacity, and your local public health department is overwhelmed or able to respond. The saying “think global, act local” applies not only to the environment but also to pandemics.
Influenza has caused many pandemics throughout human history, serving as a key reference for pandemic planners. COVID-19 disrupted these plans. Compared to influenza pandemics, coronavirus pandemics are less understood. However, there are significant differences between these viruses, and an influenza plan cannot be directly applied to a COVID-19 pandemic. Now, let’s focus specifically on human coronaviruses. SARS and MERS are examples of coronavirus pandemics that faded out, and studying them provides valuable insights.