Scientists fear “catastrophic” combination of COVID with MERS virus

The SARS-CoV-2 virus is highly contagious, but the current dominant strains are not particularly lethal. Its much rarer cousin in the betacoronavirus family of pathogens, MERS-CoV, is highly lethal but not highly contagious. Imagine a mixture of the two – a respiratory virus with the most dangerous properties of both. Contagious and deadly.

There is a real risk, according to a new study from China. And there is a strong argument for a new, more effective vaccine.

Different viruses from the closely related families can combine through a process called “recombination” and produce hybrids called “recombinants.”[ads1]; This recombination requires that the viruses share an infectious mechanism. For the first time, a team of researchers in China has identified the mechanism by which SARS and MERS can combine – by entering human cells via colocated receptors. Basically, cells are entry points for external molecules.

If a single person ever catches SARS and MERS at the same time through neighboring receptors and the two viruses combine, we could have a whole new pandemic – one that could be far worse than the current COVID-19 pandemic.

The risk of recombination is a driver of a global effort to develop new vaccines that can prevent, or reduce the severity of, infection with a variety of SARS viruses, MERS and any hybrid of them. A universal vaccine for an entire family of viruses.

Good news: Universal vaccines are under development. Bad news: They’re still a long way from large-scale human trials—and an even longer way from regulatory approval and widespread availability. Years, maybe.

A team led by Qiao Wang, a virologist at the Shanghai Institute of Infectious Disease and Biosecurity, part of Fudan University in Shanghai, highlighted the SARS-MERS recombination risk in a peer-reviewed study that first appeared in the journal Signal transduction and targeted therapy on 15 March.

SARS-CoV-2 tends to favor a receptor called ACE2, while MERS-CoV tends to favor the DPP4 receptor, Wang and their co-authors explained. Our cells tend to have one or the other, not both. In the very unlikely chance that someone catches both SARS and MERS at the same time, the viruses should stay safe in their separate cells.

But Wang and company identified a few cell types, in the lungs and intestines, that have both ACE2 and DPP4 receptors, thus “providing an opportunity for co-infection by both SARS-CoV-2 and MERS-CoV.” Wang and a teammate did not respond to a request for comment.

This hypothetical co-infection – SARS-CoV-2 and MERS-CoV mixing and mutating in the same cells – “could result in the emergence of recombined [betacoronavirus]”, wrote Wang and their co-authors. Call it “SARS-CoV-3” or “MERS-CoV-2.”

Regardless, this new virus “could carry high SARS-CoV-2-like transmissibility along with a high MERS-CoV-like death rate, which would have catastrophic consequences,” Wang and their teammates wrote.

How bad can it be? The most infectious forms of SARS-CoV-2, the XBB subvariants – also called “The Kraken” – are by far the most transmissible respiratory virus anyone has ever observed. It is not without reason that XBB subvariants quickly out-competed rival subvariants to become globally dominant in just a few weeks early this year.

But Kraken is less severe — that is, less likely to kill — than earlier forms of SARS-CoV-2. Vaccines and natural immunity help a lot, but there are also signs that the new coronavirus is slowly evolving towards higher transmissibility but lower severity. At its worst in 2021, COVID killed almost 5 percent of infected people in the worst affected countries such as Peru and Mexico. Today, the global death rate is around 0.9 percent.

MERS, on the other hand, spreads much more slowly. It mostly affects camels. When it infects humans, it is usually when these humans are in close contact with the animals. Human-to-human transmission is extremely rare. “Only a few such transmissions have been found among family members living in the same household,” noted the World Health Organization.

In 27 small outbreaks since 2012, fewer than 900 people have died from MERS. Compare that to the 6.9 million people who have died from SARS-CoV-2 since the end of 2019. The problem with MERS is that the 900 or so deaths represent a third of the infections. That is, MERS is at least six times more deadly, on a case-by-case basis, than SARS was at its worst.

So if a SARS-MERS recombinant inherited the former’s transmissibility and the latter’s lethality, it could quickly kill millions. That’s why Wang and their co-authors, in their own words, “urge the development of pan-CoV vaccine.”

Do not panic. Epidemiologists not involved in Wang and company’s study did not necessarily agree with the Chinese authors’ sense of possible impending doom. “The life cycle of a virus is delicate and recombination between different viruses is usually uncommon,” Lihong Liu, a COVID researcher at Columbia University, told The Daily Beast. “We have not seen any recombination between SARS-CoV-2 and MERS during the COVID-19 pandemic, despite millions of SARS-CoV-2 infections worldwide. Therefore, such an event is expected to be unlikely to occur in the future .”

Michael Letko, a virologist at Washington State University, told The Daily Beast that Wang’s team is actually half right. Yes, there is a big risk from a possible recombinant. But not necessarily a SARS-MERS recombinant. It is more likely that the new coronavirus will recombine with a Russian bat virus called Khosta-2, Letko said.

Khosta-2 is even more closely related to SARS-CoV-2 than MERS is, Letko pointed out. Not only does Khosta-2 love the same ACE2 receptor that the new coronavirus prefers, the two viruses also replicate in roughly the same way. “The machinery the viruses use to copy their genetic material can become confused, leading to mixing and matching of the genomes,” Letko said of SARS-CoV-2 and Khosta-2. It increases the risk of recombination.

Prevention plan

But exactly which cousin virus might combine with SARS-CoV-2 is beside the point. Barton Haynes, an immunologist at Duke’s Human Vaccine Institute, told The Daily Beast. There are dozens of betacoronaviruses. We should develop a vaccine that works against all of them. “If a vaccine could do all that, one would probably also be able to protect against any … recombinant virus as well,” Haynes said. SARS-MERS. SARS-Khosta-2. MERS-Khosta-2. Whatever.

There are about two dozen pan-coronavirus vaccine projects underway worldwide. Haynes and his colleagues at Duke have been working on one since 2020 — and it could be among the first to produce a deployable vaccine. Animal experiments and small-scale experiments on humans are already underway. But if history is any guide, it could be years before the Duke vaccine or any other pan-CoV jab is ready for widespread distribution.

The wait is worth it, Haynes said. “The current goal of pan-coronavirus vaccines currently being tested in monkeys and humans is to create vaccines that will both prevent infection by any new COVID variant that may arise, to create vaccines that will prevent any new CoV-2-like CoV -outbreaks that may arise from bats or other animals also to protect against any MERS-like virus that may arise.”

That should cover all the bases, at least when it comes to betacoronaviruses including SARS-CoV-2, MERS-CoV and Khosta-2. If luck holds and we avoid a dangerous SARS recombinant for a few more years, we might have a universal vaccine—Duke’s or some other—that could prevent mass death should the hybrid finally emerge.

Of course, the “universal” vaccine would not be really universal. It would not save us from RSV, monkeypox, polio or – perhaps most worryingly – bird flu. For these viruses, we need a completely different approach.