Could a more severe, but less contagious variant become dominant at this point, or will each new dominant variant be more contagious

So the pattern seems to be each new variant that becomes dominant is more contagious than the last. Which makes sense since the more contagious variant will spread to more people and crowd out the less contagious variant.

However what happens if we have a highly contagious variant that spreads through the population, then burns out as it runs out of new victims. Would that allow a less contagious (but potentially more deadly) variant to then become the dominant strain? Do viruses ever evolve in that direction?

The Covid case is breaking a lot of new ground. For many reasons, that combine in so many variable ways. At this point, world travel is getting back to more normal. But there are wildly varying situations in different countries. What variants are prevalent, what countermeasures are in place, variants of vaccines, travel restriction measures. So many different petri dishes with different levels of isolation and such.
It seems that the vaccines that targeted the spike protein have lessened the severity of infection. Which may have lessened the transmission of those variants a bit. But that protein is a small part of the virus. Variants without that specific protein gained prominence as they sidestepped the vaccine almost completely. Good. A less harmful virus overall.
But what is brewing in more isolated places? Places with different protocols?
Just my opinion. I think that overall we will see the whole thing burn out due to massive mild infection. But there is a chance that some situation somewhere has set it up for a bad, high infection rate variant to come out of there. Unlikely but possible. I wildly guess that a year from now, if it has not happened. It won’t happen.

The answer is “It depends”.

All things being equal, the more infectious variant will become dominant as it spreads more rapidly until the threshold of ‘herd immunity’ is achieved, and the conventional thinking is that this would then forestall further spread, causing the virus to become endemic in the population. However, as has been seem with this pathogen, mutations have offered significant immune escape such that prior infection or vaccination (even with multiple boosters) does not provide protection against infection or even severe disease (though vaccination and boosting does require substantial protection against severe morbidity and mortality for most people).

A variant that is less transmissible but more virulent could take hold if it has substantial immune escape; that is, that prior infection or vaccination against other variants is not an effective shield. This is a real concern because the other human-infecting betacoronaviruses of lineage B and C (SARS-CoV-1 and MERS-CoV) have significantly higher mortality rates (estimated at 9% and >30%) compared to SARS-CoV-2 (~0.3%). A mutation that made the already well-adapted SARS-CoV-2 have a mortality compared to these viruses would obviously be catastrophic given its transmissibility and fast rate of evolution and transmission.

It should be noted that the COVID-19 pandemic is the first time we’ve really been able to observe an aresol-transmitted zoonotic virus evolve to adapt to human hosts in real time with the kind of gene sequencing tools we have today. It took years to even understand the fundamentals of how HIV transmitted and developed in human hosts, and viral pathogens such as Ebola and Marburg are not transmissible enough to have diversified within human hosts and produced multiple highly infectious strains and do not utilize a respiratory route for infection, so normal body substance isolation (BSI) measures are adequate to prevent transmission. Epidemiologists and virologists have long warned about a highly transmissible respiratory virus although prior to the 2003-4 SARS outbreak most were concerned about strains of Influenza A, in particular H1N1 (responsible for the ‘Spanish flu’ pandemic of 1918-1920) and H3N2 (‘Hong Kong flu’) although i recent years H5N1 and H7N9 (both bird transmitted influenzas) have been monitored for zoonotic potential to develop into pandemic agents.

It is often assumed that any widely-distributed virus will eventually become inherently endemic as it evolves to be more benign and becomes one of the “childhood diseases” like measles and chicken pox which are not a major threat as long as people are exposed when they are in childhood with a robust immune system and underdeveloped reproductive organs. However, it should be pointed out that there are many extant pathogens such as smallpox, yellow fever, and various encephalitis viruses that are known to have spread in epidemic outbreaks for thousands of years without ever having evolved to become benign in human hosts, so that evolutionary process can take many thousands of years. There is no reason to believe that SARS-CoV-2 is done mutating or will become less virulent in the foreseeable future, and every reason to be concerned about it evolving a pathogenicity similar to other virulent betacoronaviruses while evading immunogenicity from current infection and vaccines.

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When Omicron appeared and people said it showed the virus was weakening, I saw several articles warning that the next variant could be more severe as well as highly transmissible. Here’s a couple of quotes from one of them, saying:

“Viruses evolve to survive. That can mean greater transmissibility, antibody-evasion or more serious infection. Omicron mutated for the former two. There’s a chance some future Sigma or Upsilon lineage could do all three.”

“Imagine a lineage that’s as transmissible as Omicron but also attacks the lungs like Delta tends to do. Now imagine that this hypothetical lineage is even more adept than Omicron at evading the vaccines.
That would be the nightmare lineage. And it’s entirely conceivable it’s in our future. There are enough vaccine holdouts, such as the roughly 50 million Americans who say they’ll never get jabbed, that the SARS-CoV-2 pathogen should have ample opportunities for mutation.”

“As long as we have unvaccinated people in this country—and across the globe—there is the potential for new and possibly more concerning viral variants to arise,” Aimee Bernard, a University of Colorado immunologist, told The Daily Beast."

Omicron has an advantage in being able to escape the vaccines, so it can affect more people.

There isn’t any evolutionary advantage to a virus in killing its own host. Then those copies of the virus die as well.

Not to argue with you - as this is true and you’re right - but with the number of involuntarily unvaxxed (through no fault of their own) and the anti-vaxxers (through all fault of their own), Covid can afford the inherent inefficiencies of killing a few million here or there while experimenting with more and less lethal versions of itself.

So I believe that at some point we will be hit by something really, really horrible.

Pathogens don’t have any volition and will act as mutations modify their pathogenicity and transmissibility. While it would be detrimental for a pathogen to be so lethal that it expires the host before it has a chance to reproduce and be transmitted to other hosts, there are plenty of viruses that are quite lethal. Variola major (the virus that causes smallpox), for instance, was transmitted in waves back and forth across the Eurasian continent for millennia and still maintained a 20%-30% mortality; when it entered the Americas by being carried by European conquistadors and colonists the mortality rate among Native Americans may have exceeded 90% and is widely considered the major cause of catastrophic depopulation of North America even prior to colonial exploration and expansion into the interior.

SARS-CoV-2 gains a foothold in a host so quickly, has such broad tropism, replicates so efficiently, and becomes transmissible before symptoms of immune response are even evident that a highly virulent strain of the virus could easily take root and burn through the population despite being a couple of orders of magnitude more lethal than the currently circulating variants. Virologists and epidemiologists have been warning for decades about what might happen if a virus capable of aerosol transmission and rapid antigenic shift achieved epidemic proportions and how it might mutate to become even more infectious, and now we are seeing this play out in real time. The virus could very well be just a few modified amino acids in the envelop or open reading frame (ORF) genome sequence away from becoming far more virulent, which argues for maintaining strong genome and contagion surveillance as well as doing everything possible to limit epidemic spread to forestall an adverse mutation from getting a foothold.

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I guess at what point does Covid become endemic, if it hasn’t already?

To answer the question here, seems unlikely that a more severe but less contagious variant could outcompete Omicron.

The question is, why can’t a different, existing coronavirus mutate to become a new terror? Or the flu or the common cold? Or a brand new coronavirus emerges the way Covid did? I think if the answer is “yes this could happen, but at this point it’s no more likely with Covid than with anything else” then we’re endemic now. So some of these speculations, I’m not sure how relevant they are if they can’t be tied to the particulars of Covid, and would equally apply to any other extant virus.

By definition, SARS-CoV-2 will become endemic when we no longer have epidemic outbreaks. Given the relatively low persistence of immunogenicity and high mutation rate of the virus it will probably be several years or possible decades before that happens if a universal vaccine that covers the wide range of genomic combinations is not discovered. We’re already seeing people dying of the BA.2 subvariants despite being fully vaccinated and boosted against the original ‘wild-type’ virus; fortunately not many as the mRNA and adenovirus vaccines seem to provide good protection against severe illness, but those who are succumbing are not always people who have underlying or pre-existing conditions which suggest that this virus has some additional capacity for greater virulence than observed to date. A “more severe but less contagious variant” doesn’t have to “outcompete” the Omicron variants if it achieves substantial immune escape from immunity provided by current vaccines or infection by Omicron or previous variants, and in fact that is exactly what occurred with Omicron which is currently doing devastating damage in Singapore and China where natural immunity is low and the quality and uptake of available vaccines is poor.

I highly recommend following Dr. Michael Osterholm’s CIDRAP podcast in which he has been consistent about noting that the assumptions many people—even qualified experts—are making about the evolutionary path of this virus and the progress of the global pandemic it is causing are based more on wishes and hopeful pleading than on the evidence. We’ve never seen a virus emerge de novo and spread like this before, so how long it will take to essentially exhaust all genetic permutations and become an endemic virus of low pathogenicity like the many ‘common cold’ viruses (which still kill thousands of people every year) or influenza (global deaths in the tens and sometimes hundreds of thousands even in years where it scarcely breaks the P&I epidemic threshold) is anyone’s guess, and guesses they are indeed because no one has validated and reliable models to make accurate predictions.

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