In May 2015, a South Korean businessman returned from a business trip to the Persian Gulf. Without knowing it, this citizen carried in his body an unknown respiratory virus in South Korea. It was MERS-CoV, a camel-like coronavirus detected in humans for the first time three years earlier. Its lethality was and is much higher than that of the current SARS-CoV-2, thus killing 32% of those infected. Fortunately, in that outbreak, the virus only affected about two hundred people, almost all of them health workers. Now, a study compares that pathogen with the different strains present in these animals. They have found that a few changes in the viral genome protect humans from most variants by now.
MERS-CoV emerged in 2012 when Saudi health authorities detected several cases of a disease that they ended up calling Middle East Respiratory Syndrome (MERS). Later studies confirmed two things: on the one hand, that this new pathogen had a high prevalence among dromedaries and, on the other, that before them it came from another animal. The definitive proof has not been found, but the genetics point to some species of bat to be identified. In that first outbreak, almost 40% of those affected died. But the majority were people who had been in close contact with camelids and there were few episodes of community transmission. Leaving the explosive Korean outbreak, since then, there have been 2,000 people affected, more than 90% in Saudi Arabia and the small Gulf countries. That concentration and the few cases of contagion between people have almost forgotten what is one of the main threats to humanity, according to the World Health Organization (WHO).
Hong Kong University virologist Malik Peiris is one of those who refuses to forget about MERS. He has been investigating it almost since his leap from dromedaries to humans was detected. He acknowledges that part of the neglect is due to the relative low efficacy of the virus: “Most emerging infectious disease threats come from animals. Many of them spread from animal to human with minimal human-to-human transmission, in the case of the H5N1 avian flu. Others are transmitted to humans and also efficiently between humans, for example, the H1N1 pandemic of 2009, SARS of 2003, which spread around the world but was controlled, and covid. Then there are others that fall in the middle, this is the case of the MERS-CoV ”, he says.
Although MERS emerged in Saudi Arabia in 2012, the largest outbreak occurred three years later in South Korea following the return of a businessman from a trip to the Gulf countries.
Indeed, every year there are dozens of jumps from animals to humans, but only on a few occasions is there community transmission. “It has the ability to be transmitted between humans, but it has not fully adapted for sustained human transmission,” says Peiris. “But we know that in its early stages with SARS in 2003, a similar situation occurred before the virus adapted to acquire the capacity for this sustained transmission. That is why MERS-CoV continues to be a virus of pandemic concern, even in the midst of covid, ”he warns.
The latest work by Peiris and his colleagues, published this week in the scientific journal PNAS inquire into one of the unsolved mysteries of this coronavirus, a mystery that hides a great threat. Previous work has shown that between 70% and 80% of dromedaries have antibodies against MERS-CoV, that is, they have had the disease or had it at the time of analysis. In addition, up to 70% of those infected do not live in the Arabian peninsula, but in Africa, where sanitary conditions and overcrowding add risks. However, there have hardly been (or at least detected) cases in humans here. To investigate it, Peiris has collected more than a dozen African variants of the virus, from Morocco to Egypt, through Nigeria or Kenya and has compared them with the human variant that caused the outbreak in South Korea and the dominant one. in Saudi Arabia.
“From a genetic point of view, MERS-CoVs from Africa are grouped separately (referred to as clade C) and are distinct from current clade B viruses circulating in the Middle East. Although phylogenetically distinct, these two groups share 99.18–99.58% similarity at the nucleotide level, ”explains Peiris. By testing the different viruses in human lung cells and genetically modified mice, they found that both the human and arabic variants infected and replicated easily. However, African women were up to 100 times less capable of efficient replication.
Two changes in the protein S of African coronaviruses lower the virus’s ability to replicate
The difference between the variants of the two continents seems to focus on protein S, the famous spike with which coronaviruses latch onto cells. In most African MERS-CoVs there are two changes in amino acids of this protein that could explain its lower pathogenicity, although they do not rule out the existence of other variations that also influence. The definitive proof was when, through reverse genetics, they modified the African coronaviruses to carry the Arabian spicule. They found that it increased its ability to sneak into human bronchial cell cultures.
For the virologist of the National Center for Biotechnology of the CSIC Luis Enjuanes, one of the main conclusions of this work is that “viruses of the type that are disseminated in Africa replicate with a lower titer (giving less virus as a result) than those who have isolated themselves in Saudi Arabia ”. And by reproducing worse, “it is logical that less is transmitted from camels to people.”
However, Peiris himself published three months ago an investigation with people who work with dromedaries. In this case, they were workers from a slaughterhouse in Kano, a city in Nigeria. None were positive for MERS, but 30% had antibodies to MERS-CoV. In other words, MERS has already reached Africa, although not with the virulence of the outbreaks in Saudi Araba or South Korea.
“MERS-CoV continues to be a virus of pandemic concern, even in the midst of covid”
Malik Peiris, Virologist at the University of Hong Kong
Quim Segalés is a researcher at the Institute for Agrifood Research and Technology (IRTA) and has worked on the development of a vaccine against MERS-CoV for camelids. “In addition to dromedaries and camels, alpacas, llamas or vicuñas are also susceptible to the virus,” he recalls. The Catalan scientist highlights a fact that increases the risk: “In dromedaries it is a subclinical infection, the most they have is a very mild cold. As it does nothing to them, there is no interest in vaccinating them. What company is going to spend the necessary money in its manufacture if they are not going to buy it? “
But Segalés, also a professor at the Faculty of Veterinary Medicine at the Autonomous University of Barcelona, recalls that the WHO has already included MERS “among the seven most dangerous emerging diseases.” It would only take the Arabian variant to cross the Suez Strait to become the dominant one among African dromedaries, making the jump to humans easier and more serious. In Peiris’s research, a detail of the weak protection that Africa has is mentioned: the dromedary trade, although relevant, is one-way, Saudi Arabia and the other Gulf countries buy the camelids that African countries sell. The risk is summed up by Peiris: “This has been able to protect us so far. But we should make sure that reverse trade is avoided. “