Among the 100 million people around the world who struggle with coronavirus infections, scientists refer to the case of a 45-year-old COVID-19 patient in Boston to understand how the virus can outwit humans.
During his 154-day illness – one of the longest recorded – the patient’s body became a crucible of riotous viral mutation. He presents the world with one of the first observations of a major mutation in the ear protein of the virus that gave rise to alarm bells when it was later found in strains in the United Kingdom, South Africa and Brazil.
In the British tribe, it is suspected that the genetic change, known as N501Y, could improve the viability of the virus by about 50%. In the South African strain, it may reduce the effectiveness of COVID-19 vaccines and treatments. Tests of its effect on the Brazilian variant are still ongoing.
The Boston patient is now considered an important forerunner of the coronavirus’ ability to ward off new and more dangerous versions of itself. Although he died during the summer, the medical file he left behind helps experts anticipate the emergence of new strains by focusing on the role of a growing population of patients with an affected immune system fighting the virus for months.
Among the sickest COVID-19 patients, it appears that this population of “long-rangers” plays a key role in incubating new variants of coronavirus, some of which may alter the trajectory of the pandemic.
The mutations that result from this single patient are a microcosm of the viral evolution that we see worldwide, ‘says Dr. Jonathan Z. Li, an infectious disease specialist at Brigham and Women’s Hospital in Boston who treated him. ‘He showed us what can happen’ when a germ with the ability to reverse genetic deformity ends up under conditions that reward it.
Situations where patients are unable to clear a viral infection are ‘the worst case scenario for the development of mutations’, said Dr. Bruce Walker, an immunologist and founding director of the Ragon Institute in Boston, said.
As weeks of illness turn into months, a virus copies itself millions of times. Each copy is an opportunity to make random mistakes. When it shuts down new mutations, the virus can occur in medications that help resist drugs, evade the immune system and come back stronger.
SARS-CoV-2, the coronavirus that causes COVID-19, was an unpredictable adversary. The chance to witness its transformation in near real time and see where and how it mutates in a single host could lead to the design of vaccines and drugs that do not lose their effectiveness over time, Walker said.
COVID-19 patients only began filling the beds of Brigham and Women’s Hospital in the spring of 2020, when the Boston patient was first admitted. He had fever, nausea and a CT of his lungs which had the characteristic ‘ground glass’ appearance of the new disease, says Li, who was part of a team covering the case of the man in the New England Journal of Medicine set out.
But COVID-19 was just one of its challenges. For 22 years he suffered from a rare disorder called antiphospholipid syndrome, which caused his immune system to attack his own organs and cause dangerous blood clots in his body.
To prevent his rogue immune system from killing him, the patient needed an arsenal of immunosuppressive drugs. But in its fight against the coronavirus, the drug tied the patient’s punch arm behind its back.
The Boston patient was tested four times over 22 weeks four times separately for SARS-CoV2 infections. He was admitted to the hospital six times, including intensive care. Doctors treated him with three doses of antiviral drug remdesivir, and once with Regeneron’s experimental cocktail of monoclonal antibodies.
A patient who fought COVID-19 for 154 days was admitted to Brigham and Women’s Hospital in Boston four times during his illness.
(Brigham and Women’s Hospital)
Swabs taken from his nose and throat during his second hospital stay gave the first indication of the staggering pace of genetic transformation: compared to a sample taken during his first hospitalization, 11 letters in the coronavirus’ series of 30,000 letters were flipped, and nine such nucleotides were dropped.
His next trip to the hospital landed him in the ICU. Tests showed that another ten letters in the virus’ genetic code had changed and another was removed in a period of just five weeks. Three weeks later, after he looked, he tested positive again and was put on a mechanical ventilator to help him breathe. This time, researchers found another 11 letter edits and another 24 deletions in the genome of the virus.
Scientists could not say whether the Boston patient could not kick the virus and whether it had changed so completely that his immune system could not recognize it.
One thing was clear: more than half of the changes occurred in a genetic code that determines the structure of the virus’ ear protein, the protrusion that adheres to human cells, and causes an infection. The ‘receptor-binding domain’ of the virus – essentially the key to one’s cell – makes up only 2% of the virus’ genetic code. But 38% of the mutations that were turned off during the long-term illness of the Boston patient were concentrated only in that spot.
At the end of December, British scientists speculated that just such a scenario with an immunocompromised patient could have caused the mutations that distinguish the British tribe somewhere in England.
Walker said he fears there are many more such patients out there, including people with untreated HIV infections. Immunocompromised by HIV, sick with COVID-19, and given drugs that reward SARS-CoV-2 for the design of ‘escape’ mutations, such people can become crucibles of viral mutation.
Scientists in South Africa share the anxiety.
‘In South Africa, the country with the largest HIV epidemic in the world, prolonged viral replication and intra-host evolution in the context of HIV infection is a concern,’ write the authors of a preliminary study covering the world warned about the new variant. in early December.
COVID-19 patients are treated with oxygen at Tshwane District Hospital in Pretoria, South Africa.
(Jerome Delay / Associated Press)
To date, there is no evidence that patients with HIV are more likely to develop long-term cases of COVID-19. And even if it were, a long chain of immunocompromised patients would probably have been needed to generate the numerous mutations that distinguish the South African tribe, its discoverers said.
Scientists are still trying to understand how certain mutations such as N501Y originated in so many places simultaneously. Did the mold of the pandemic give the virus too many opportunities to change itself? Or do these mutations arise in a small number of people, like the Boston patient, and then somehow ride around the world?
Both factors are likely to be at work, and the longer and hotter the pandemic rages, the greater the chance the virus has of devising random mutations.
The Boston patient shows why it can be so dangerous. In his case, the pieces of genetic code that were most likely to change are affected structures that COVID-19 vaccines and drugs have designed to recognize. Now there are hints that the changes could undermine the value of those drugs.
Tulio de Oliveira, a researcher in infectious diseases at the University of KwaZulu-Natal, sees a pattern in which uncontrolled spread and long-range infections work together to stimulate coronavirus mutations.
Many of the places where new variants have been identified, including South Africa, Britain and California, have experienced two waves of outbreaks, divided by just a few months. De Oliveira suspects that this is not merely coincidental.
In the first wave, he said, the spread of infections gives the virus ample opportunity to make genetic changes that can survive in the bodies of patients with weakened immune systems. By the time a second wave begins, new varieties that breed in these long-rangers are also starting to circulate. When they encounter a large number of new hosts, the result is a fertile environment for tribes to establish themselves – if their genetic modifications have an advantage.
The best way to prevent the emergence of more mutations is to expand both vaccinations and do more to protect people with an affected immune system, De Oliveira said.
“If we keep the virus for a long time, we will have more opportunities to be smart,” he said.