Can bats teach us to develop immunity to COVID-19


Virus loves bats. Flying nocturnal mammals make excellent hosts because – like people – they live in large, dense groups; Their air travel spreads germs among the population; And their longevity enables a virus to persist for years in an individual animal.

The major difference is that the bat’s remarkable immune system tame and tolerate many viruses, including the coronavirus responsible for COVID-19, which causes havoc when it spreads to humans.

“We should look at what bats are doing to control the virus and imitate it in some way,” said Bernard Crespi, a professor of evolutionary biology at Simon Fraser University in Canada, one of a growing group of scientists, Who is searching for clues of epidemic through the bat. Immunology.

Immunology is at the center of scientific and medical investigations of COVID-19. Every effort to explain the exceptionally diverse course of the disease, to treat it with drugs, and to prevent it with vaccines, depends on understanding how the virus affects the human immune system – or vice versa.

In the popular imagination, “immunity” means resistance to a disease, while for scientists it is much more granular and complex. Immunologists think of it more as a question of degree: how fast was a person’s initial response to a pathogen? Did the person’s cells recognize this from the risk of the past and kick into action more quickly? How many antibodies produced, and were they correct?

Coronaviruses have been developing in bats for thousands or millions of years. They have moved into people very recently – perhaps as recently as last year in the case of SARS-CoV-2, the virus responsible for COVID-19.

A large number of dangerous zoonotic diseases are transmitted by bats in humans, often through an intermediate animal host, compared to all other mammals. This roll call of the vicious virus includes Ebola, Marburg and Nipah as well as coronaviruses that include SARS, Mars and now COVID-19.

“The viruses are much more viral when they are spread by bats to humans than other mammals,” Crispy said. “Yet they themselves do very little damage to bats.”

Defendants

The explanation lies in the way these flying mammals control infection. The biggest difference from other animals is in the “innate immune system”, the first line of defense against invading pathogens, said Catherine Belisch, a viral immunologist at Stanford University. In particular, bats produce large amounts of interferons, molecules that play an important role in activating the broader immune response and preventing the virus from re-forming.

Coronavirues such as SARS-COV-2 evolved by interferons to spread and thrive in bats, Crispy said: “The virus is carrying out a covert attack, shutting down the system that the body uses to show that It is infected. ”

Bat-derived viruses are also unaffected by another aspect of the human innate response – developing fever to make the body less guests for germs.

Andrew Cunningham, deputy science director of the Zoological Society, said, “Bat body temperature rises twice a day due to the incredible effort of flying. High zoology of London Institute of Zoology.”

A graphic depicting the innate immune system and interferon.

Recent research suggests that in many critically ill COVID-19 patients, the virus performs their immune response incorrectly and then becomes fearless. The body responds to infection too late, indiscriminate barrage of interferons and exposing other immune signaling molecules called cytokines. This “cytokine storm” activates a highly inflammatory response, flooding the patient with antibodies and blood cells that destroy human tissues without preventing infection.

In the 1970s and 80s, interferon was seen as a possible “surprise drug”. They have not lived up to that billing, although they are an important treatment for multiple sclerosis. But some believe that their role in modulating the immune system may be important in the fight against COVID-19.

On July 20, Synairgen, a spinoff company at Southampton University in the UK, announced that its earthly beta interferon significantly reduced the risk of severe lung disease in COVID-19 patients who were hospitalized.

Stephen Holgate, co-founder of Synehmen and a professor of immunopharmacology in Southampton, said interferons should work over time to prevent patients’ immune systems from going into harmful overdrive. The company is conducting a second diagnostic test to find out if the first inhalation of interferon will prevent hospitalization.

Adaptive response

When innate immunity, the initial defense against infection, is functioning properly – as in most people infected with SARS-CoV-2 who develop mild or no symptoms of the disease – second stage, adaptive immunity, some Kicks after days.

Adaptive immunity is the part of the system that has received the most attention during epidemics. This includes T-cells, B-cells and the antibodies they produce. All have evolved to find and destroy specific antigens – protein molecules on invading pathogens – and remember these in case of future infections.

While the adaptive immune system is at work, messenger cells and chemicals escape to areas of the body where these specialized blood cells are stored and warn them of the arrival of the virus. Some of these cells can already be programmed to attack the virus, and if they are present, they will reproduce rapidly and launch an invasive.

A graphic showing the adaptive immune system, receptors and memory cells.

Danny Altman, a professor of immunology at Imperial College London, said that COVID-19 has generated a high level of public interest in its field of adaptive immunity. The emergence of AIDS only came to a close in the 1980s.

The organs of T- and B-cells that recognize antigens and latch the virus are their receptors.

“We have made an unprecedented genetic investment to be able to produce a large number of different receptors to identify different pathogens,” Altman said.

Scientists are beginning to study an almost miraculous variety of immune cells generated by a process of genetic recombination called V (D) J, in which the body combines three components together to form receptors that can deal with new pathogens.

It can produce billions of different sized receptors. Each person is likely to have between 10 million and 100 million different T- and B-cells, depending on the state of the immune system and how many antigens the person has to go through life.

Felix Breeden, a geneticist at Simon Fraser University in Canada, said, “When you come in contact with a virus, your immune system selects the systems that can best deal with the infection, copying it And can rapidly expand these clones. ”

He is the Scientific Manager of iReceptor, an international consortium funded by the European Union and Canada creating a genetic database of immune cell receptors from COVID-19 patients. It already has 200 million DNA sequences provided by seven research teams in different countries.

Adaptive Biotechnology, a Seattle-based company, has developed a similar open database with Microsoft, called ImmuneCode, that has mapped the response of 1,000 COVID-19 patients to T-cells with specific antigens of SARS-CoV-2. .

“Looking at the response to SARS-Cove-2, you find what we call ‘public’ receptors, with genetic sequences shared by many, and ‘private’ that are often seen,” of Adaptive. Chief Officer Lance Baldo said. Biotechnology.

“We’re starting to see patterns in the data,” Baldo said. “Data sharing will greatly accelerate research in COVID therapy and vaccine. If you are developing a vaccine, you want it to produce immune cells with genetic sequences that appear in as many COVID-19 patients as possible. ”

Within an infected person, “building B- and T-cell division and antibody production takes time,” Altman said. “To achieve a complete immune response to COVID-19, you will need 11 or 12 days after infection.”

Further exposure

After that, the big question is how long the immune response will protect against further exposure to the virus. After several unconfirmed reports of reinforcement with SARS-CoV-2, the first confirmed case was published last month by researchers at the University of Hong Kong.

A 33-year-old man hospitalized in Hong Kong in March with moderate COVID-19 symptoms tested positive again in August, when he was shown at the airport upon his return from a trip to Spain. By taking genetic fingerprints on each occasion, scientists proved that instead of coronoviruses remaining in their bodies, they were reabsorbed. These showed that there were already 24 differences in the second virus – one could have been higher through mutation while hanging within a person.

Immunologists were not surprised by the revision news and expect more cases to be confirmed in the coming months. He was reassured that the man had shown no symptoms of the disease on the second occasion, suggesting that his immune system – which had previously flared up with infection – controlled the virus more successfully when he met again.

It may also not be necessary for the adaptive immune system to withstand SARS-CoV-2 to provide some protection against COVID-19. “The biggest surprise is that there are some memory T-cell responses in people who were not infected with SARS-CoV-2,” said Jennifer Juno, a viral immunologist at the University of Melbourne.

This “cross-reactivity” occurs because the associated coronaviruses, which have been circulating in people for centuries or millennia, and very rarely the disease is worse than the common cold, are similar to identifying SARS-CoV-2. But sufficient evidence is not yet available to limit cross-reactivity in populations worldwide or to protect them against COVID-19.

Genetic change

Vaccines are certainly a more systematic and deliberate way to prevent disease from a virus that has not been encountered before. Many companies and countries are in the running to develop COVID-19 vaccines at a total cost of billions of dollars, and dozens are in various stages of clinical trials, although none are yet sufficient to provide clear evidence of safety and efficacy have not received.

A well-designed vaccine may provide better immunity than a natural infection with the virus, immunologists say, but the first generation of the COVID-19 vaccine may be sufficient rather than simply cure symptoms. , Instead of preventing infection.

Meanwhile, SARS-CoV-2 itself is evolving as it spreads to its new Yejamanas: humans. Coronaviruses mutate more slowly than the flu but are faster than many other viruses.

Scientists are observing some genetic changes, in particular the “spike protein” that SARS-CoV-2 uses to enter human cells, which can make it more contagious as well as immune system. It is easy to identify and deal with. But no one has modified the nature of the virus.

When a virus crosses the species barrier, there is strong Darwinian pressure to adapt to its new environment. Evolutionary theory suggests that viruses do not want to kill their hosts but head of medical science at Oxford University, Gavin Skritton, said they want to spread as efficiently as possible while doing little harm.

“In the long run, they can adapt to the host and become less contagious,” he said. The four coronaviruses that today cause cold-like symptoms may be more toxic pathogens when they first move into humans – two from bats; Give it to rodents.

Professor of Experimental Medicine at Imperial College London, Peter Openshaw said that there is much scientific speculation about whether SARS-CoV-2 would be as vulnerable as the common cold.

Whatever happens, he said, “We have an amazing opportunity to watch in real time as the virus develops after a species jumps.”

Immunologists will learn valuable lessons from COVID-19 for the inevitable next pandemic after a fatal virus leap from a bat (or a rat) in humans.

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