The COVID-19 public health emergency of international concern (PHEIC) has been ended by the World Health Organization1, which was interpreted by many as signalling the end of the pandemic. Declaring the PHEIC over, WHO Director General, Dr Tedros said, “This virus is here to stay. It is still killing, and it’s still changing. The risk remains of new variants emerging that cause new surges in cases and deaths. The worst thing any country could do now is to use this news as a reason to let down its guard, to dismantle the systems it has built, or to send the message to its people that COVID-19 is nothing to worry about.”

The reality is the pandemic had already been declared "over”, as a political matter, in many countries around the globe, and the impression that it is now something in the past has successfully been instilled in the mind of the public. But is this really so, and are we even thinking about the situation properly?

A key part of being able to successfully declare the pandemic “over” is to also define it as the initial period of establishment of SARS-CoV-2 in the human population. Anything that happens beyond that point is thus not part of “the pandemic”, and can be disregarded, as part of “normal” life (the new “normal”, that is).

However, that is not at all the correct way to view the situation.

Variants and serotypes

In order to clear up the confusion, we need to first understand the distinction between “variants” and “serotypes”.

The word “variant” has been used a lot during the pandemic to describe the various lineages into which SARS-CoV-2 diversified during its uncontrolled transmission around the world. It usually refers to minor variation relative to the ancestral lineage.

“Serotypes” are the next level of divergence, at which substantial antigenic differences are observed between lineages, to the point where the immune system, after having encountered one of the two strains, recognizes another poorly or not at all. One can think of the difference between serotypes as that between a domestic cat and a lion, and that between variants as analogous to a persian cat and siamese cat.

But we have never seriously talked about “serotypes” during the pandemic. That is not because the term was not needed, quite the opposite. The appearance of Omicron in late 20212 very much represented a new serotype, but beyond some limited discussion in the literature3, calling it one never gained any traction and the much more benign and reassuring term “variant” continued to be used.

The conclusion that the original BA.1 Omicron strain represents a separate serotype follows directly from the very large number of mutations in Omicron relative to the original SARS-CoV-2 isolate, numbering more than 50 overall, including more than 30 mutations in the spike (S) protein and around 15 mutations in the receptor-binding domain. These mutations confer strong escape from neutralizing antibodies targeting previous SARS-CoV-2 versions4, allowing Omicron to readily reinfect previously infected individuals, as well as dramatic changes in cell entry mechanisms and tissue tropism5. Furthermore, even more divergent Omicron variants – first BA.4 and BA.56, and then a veritable zoo of second-generation saltation variants and recombinants – have appeared since then. Divergence has reached the point where the currently circulating strains are as distinct from the original 2019 SARS-CoV-2 as the latter is from the 2003 SARS-CoV-1 virus7.

Despite that fact, and that there is no cross-protection between SARS-CoV-2 and SARS-CoV-18, we continue to refer even to the more recent lineages, such as XBB.1.16, as “Omicron” and “variants”.

Refusal to acknowledge the nature of Omicron (in all its forms) severely hampers our ability to properly understand and conceptualize the events of the last three years, and handicaps our response to what likely awaits us in the future.

Multiple SARS pandemics

As the first novel serotype to diverge, a question that Omicron naturally presents is whether it will be the last. The accumulated knowledge about other coronaviruses suggests that there is no reason to think so. Within the sarbecoviruses, viruses are known with vastly greater sequence and antigenic divergence than that between Omicron and non-Omicron SARS-CoV-2 that nevertheless still efficiently utilize ACE2 as their receptor. In other words, the virus still has plenty of options to change markedly.

Commonly cited neutralization titre reductions of SARS-CoV-2 sera include ∼50× for SARS-CoV-1, ≥100× for WIV-1, and ∼300× for SHC0148, and as mentioned above, Omicron has already diversified to be as different antigenically from the original SARS-CoV-2 as SARS-CoV-1 is. Nobody expected ∼10% of the receptor binding domain to mutate in the span of just three short years, and yet that is what happened. Thus, the antigenic space for future evolution is vast, and it is likely to be explored under conditions of widespread viral transmission and selection regimes dominated by the pressure to evade existing antibodies.

We have one real-life example of what the future might look like with another coronavirus – that is the history of the Infectious Bronchitis Virus (IBV), a coronavirus that often causes severe disease in poultry and is not too dissimilar from COVID (a serious respiratory infection but also combined with broader tissue tropism in other organs). After first being documented in the 1930s, IBV has widely spread around the world, and in the process has diversified into dozens of new variants and serotypes9. Cross-protection between them is limited, and they can be radically different from each other in spike protein sequence (the S1 subunit of the S protein can differ by more than 20-25% between different serotypes, i.e. a lot more than the difference between even the most divergent Omicron sublineages and non-Omicron SARS-CoV-2), in mutations outside the spike, and in their tissue tropism (and thus the precise symptoms of the disease they cause).

Most importantly, they can also differ drastically in their pathogenicity – some lineages rarely cause mortality, while others are highly lethal, at the level of the most dangerous viruses that infect humans such as Ebola and Nipah9-25.

It is therefore wise to conceptualize Omicron as the first of many new serotypes that can be expected to appear over the coming decades, the properties of which may well be dramatically variable.

A reconceptualization of the events of 2019-2023 and “the COVID-19 pandemic” is necessary. So far it has been often treated as analogous to an influenza pandemic. A wide variety of constantly changing influenza strains circulate continuously, with seasonal peaks, but occasionally more pathogenic strains appear and cause notable named pandemics. The most notorious of these is the 1918-1920 pandemic, caused by a particularly deadly H1N1 strain; since then, several additional (though much less deadly) pandemics followed, in 1957-58 (H2N2), 1968-69 (H3N2), 1977 (a different H1N1 iteration), and 2009 (H1N1/09).

The apparently immense evolutionary potential of coronaviruses means we should expect the evolution of many further SARSCoV-2 serotypes in the future, as well as the possibility of further jumps from non-human animals to our species (there have already been two of these in less than two decades). It is therefore most accurate to think of “SARS” as a category of pathogen and disease of a similar rank as “influenza virus” and “influenza”. The family Coronaviridae, to which SARS viruses belong, is analogous to the Orthomyxoviridae family, which contains influenzaviruses. The Sarbecovirus subgenus (as well as the IBV Igacovirus subgenus) is best thought of as analogous to the Influenza A and Influenza B Alphainfluenzavirus and Betainfluenzavirus genera. Under this framework there have so far been two indisputable SARS pandemics – the 2019-2021 SARS-2 one, driven by the original Wuhan strain and its antigenically close derivatives, and a second, Omicron pandemic, in 2021-2023. There was also the abortive SARS-1 pandemic in 2003, which was contained, and fortunately did not spread widely.


Additional SARS pandemics are therefore expected, like those associated with influenza. Influenza viruses are at present vastly more diverse than SARS-CoV-2, but over decades we are likely to see significant diversification of SARS lineages, if IBV’s history is to guide us. The frequency of these future pandemics is unpredictable, as is their severity. Establishing the “SARS” category as proposed here is necessary for proper preparation for such future events.

Influenza pandemics have all been self-limiting, and early in the first COVID-19 pandemic it was regularly interpreted in a similar manner, i.e. as something that will naturally dissipate. More recently that has shifted towards an acceptance of “endemicity”, where “endemicity” is sold as a state of constant circulation that is not overtly disruptive to normal societal functioning rather than the actual scientific definition, which is constant circulation of the pathogen, and which tells us nothing about its impacts on humans.

If we are to instead view the first COVID-19 pandemic as the initial, and so far appearing to be permanent introduction of an entirely new type of pathogen (SARS) in the human population, and to accept the possibility of many novel SARS serotypes and strains appearing in the future, a rather different picture emerges. So far Omicron exhibits the lowest mortality rate of all sarbecoviruses known to have infected humans, but SARS-1 was much more severe than SARS-2, and the evolution of the first SARS2 serotype was towards more severe disease27 and current data suggests a similar trajectory within many Omicron lineages28.

Therefore it cannot be assumed that all future pandemic serotypes/strains will be “inconsequential”, or even tolerable (where “tolerable” has now been established to mean anything that does not break healthcare systems to the point where refrigeration trucks need to be called in to store the dead bodies), as subsequent iterations of viral evolution that gain a strong fitness advantage due to major antigenic innovations could revert to substantially more pathogenic states, as commentators have previously warned4,25. An understanding of the course of SARS-CoV-2 evolution so far as having already spawned two separate pandemics is needed to raise awareness of and prepare for these possibilities.