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Bats, viruses, immunity and Covid-19

Three things in particular I have found striking, amongst the avalanche of information circulating about Covid-19 – the “novel coronavirus” now infesting humanity.

One: whenever any group does random testing of groups of people, a surprising proportion proves to be infected with the virus but has no symptoms whatever.

Two: the worst of the illness caused by the virus is actually wrought by the immune system of the host victim.

Three: bats are apparently the reservoir for large numbers of viruses – and are said to be the source of this one – but tend not to be made sick by them.

Carriers and spreaders with no symptoms

The first point I have seen reinforced in many articles. One example: the village of Vo, in northern Italy. Vo was the site of Italy’s first coronavirus-related death on February 23 and was one of 11 villages quickly locked down by authorities. Researchers from Padua University tested all the village’s 3300 residents, whether they showed any symptoms of infection or not, and were surprised to find that about 3 per cent – 89 people – were infected. Those people were rapidly isolated and the village’s infection rate dropped immediately. Significantly, many of those infected showed absolutely no symptoms. They were, to all appearances, completely well.

Another example was seen more recently when more than 350 residents of a shelter for homeless people in Boston, USA, were tested. More than 140 were found to be infected but none of them had any symptoms at all. Similar results were found in other shelters in Boston.

And still another example, courtesy of the US Navy.

That’s a major issue with this virus. Although it kills a small minority of the people it infects, there is an unknown percentage of infected people who show no symptoms at all. It isn’t clear whether this symptomless state would last indefinitely, or whether at some point the virus might make its presence felt in some way. But what does seem fairly clear is that these people with no symptoms are able to spread the virus to others. In the absence of testing it is obviously impossible to identify these carriers and potential spreaders of the virus.

Another implication of this is that, if the percentage of infected people who show no symptoms actually proves to be quite large, then this will drag down the mortality rate of the infection. Not that this is any consolation to those who are badly affected, and not that this is an argument for relaxing social distancing practices. Even if the mortality rate is lower than initial data suggested, the fact that the virus is new to humans means the numbers badly affected will be very high if the infection is allowed to run rampant.

Over-reacting immune systems

The second point, that the real damage is done to victims by their own immune systems, probably doesn’t surprise people with medical backgrounds, but it was news to me. Apparently some people’s immune systems (especially older people, it seems), tend to jump into overdrive when they are challenged by Covid-19. This can lead to what is known as a “cytokine storm” leading in turn to hyper-inflammation of the lungs and other organs.

According to an article by Ruth Williams, recently published in The Scientist, a recent study (Science Advances, April 15, 2020) “glucose metabolism is a driving force underlying the development of the often deadly inflammatory response known as a cytokine storm”. “During an infection, the body’s immune system ramps up the release of molecules called cytokines, which circulate in the blood stream like messengers calling upon immune cells to come and join the fight. In some patients, for largely inexplicable reasons, this battle cry continues even after the invading pathogen begins to retreat,” Williams wrote.

To begin with the response is aimed at repelling the viral invader, but if it continues out of control it damages the host victim’s own tissues, especially in the lungs. Such cytokine storms are effectively the cause of death in a number of diseases including influenza, Ebola and Covid-19.

Scientists have protected lab mice against cytokine storms produced by influenza by editing their genetic makeup – deleting a factor responsible for cytokine production. “The inflammatory response to influenza infections is also known to drive up glucose metabolism, in part so that immune cells have the necessary energy to mount a strong response, and also because the virus needs the sugar to replicate”, Williams wrote. Now researchers at Wuhan University in China have shown that a well-known metabolic process (it’s called the hexasomine biosynthesis pathway, if you want to know) seems to be a key factor in helping create cytokine storms.

This might lead to a treatment for Covid-19. Not a vaccine, but a possible therapy that would halt the development of cytokine storms and also slow down viral reproduction. In some ways, perhaps, a successful treatment of this kind might be preferable to a vaccine which may be only partly successful and perhaps only confer temporary immunity anyway.

Why do bats carry viruses but not get sick?

The third point that I find fascinating about the Covid-19 story so far is the presumed role of bats in bringing the novel virus to humans. I’m not proposing to delve into the troubled topic of whether or not the virus leapt “naturally” from an animal host to humans or whether it somehow came into the world via a laboratory somewhere. But bats are clearly a major focus of research into viruses.

An article published in the scientific journal PLoS ONE this year (Detection of novel coronaviruses in bats in Myanmar) noted that new infectious diseases have been emerging at a growing rate since the 1940s, apparently as humans open up areas of wilderness to development and bring themselves into close contact with animals that carry previously unknown infections. These infections can cross into humans, or into animals farmed by humans in intensive commercial operations.

I don’t understand why bats seem to carry such a lot of potentially dangerous viruses, but historically they have certainly been seen to do so. It has been suggested that their affinity with viruses might be due to the facts that they travel long distances and live in dense colonies. Notably, it appears established that Covid-19 shares “96 per cent identity with a bat-borne coronavirus”. The authors of the study went to Myanmar to examine bats there for potentially new viruses. They captured and tested 464 bats of at least 11 species and found six previously unknown coronaviruses, as well as viruses previously described. They concluded that bats need to be allowed to thrive, since they are critically important links in the ecological chain. But they also concluded that in places where people are crowding in on bat populations, a close watch has to be kept in case more bat-borne viruses make the jump to humans.

Still on the topic of bats, it has been reported that a scientist at Wuhan’s Institute of Virology, Dr Peng Zhu, has been trying to discover why bats carry the various viruses they are known to host and yet don’t appear to become sick themselves. In a paper Dr Peng and others published in the journal Cell Host and Microbe on February 22, 2018, it was reported that “in bats, an antiviral immune pathway called the STING-interferon pathway is dampened, and bats can maintain just enough defence against illness without triggering a heightened immune reaction”. “The authors hypothesize that this defense strategy evolved as part of three interconnected features of bat biology: they are flying mammals, have a long lifespan, and host a large viral reservoir,” a press release attributed to Dr Peng stated. He hinted that this discovery might point the way to helping humans deal with viruses while avoiding the horrors of auto-immune cytokine storms.

I confess that I am relying on the accuracy of the translation of the press release attributed to Dr Peng found on the website ZeroHedge. I stumbled on this site by chance and do not in any way endorse any of its commentary or the particular thrust of the article referencing Dr Peng. I just happened to be interested in the research, as reported, into why bats carry coronaviruses but don’t get sick. It strikes me that this might prove to be an extremely valuable field of research for those who want to protect humans from viruses like Covid-19.

Here are some more interesting perspectives on bats and viruses.

And an alternative point of view here.

Thanks to Kim O’Toole for sharing the articles from The Scientist and PLoS ONE.

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