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How the Covid pandemic ends: scientists look to the past to see the future – STAT


WWe are approaching the mark of a year and a half of the world’s collective experience with the SARS-CoV-2 virus and the Covid-19 pandemic it caused. Right now, it’s fair to assume that people around the world are asking themselves the same two questions: How will this end? And when?

There may be a fleeting opportunity for humans to stop the spread of SARS-2 and return it to nature, as happened with its cousin, SARS-1. But that door closed tightly a long time ago. It also seems that another option – vaccinating to get out of the pandemic – is a toll highway to which few countries will be able to access in the short term.

It probably sounds gloomy, but don’t despair. The truth is that pandemics always end. And to date vaccines have never played a significant role in ending them. (This does not mean that vaccines do not play a critical role on this occasion. Many fewer people will die from Covid-19 because of them).

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But there were no flu vaccines in 1918, when the world still did not know that the big flu was caused by a virus, H1N1. In 1957, when the H2N2 pandemic devastated the world, the flu vaccine was primarily a military tool. In the 1968 pandemic, which brought us H3N2, the United States produced nearly 22 million doses of vaccine, but by the time it was ready the worst of the pandemic had already happened and demand was declining. That “too little and too late” phenomenon re-emerged in 2009, when the world finally had the capacity to manufacture hundreds of millions of doses of H1N1 vaccine; some countries canceled much of their orders because they ended up not needing them.

How did those pandemics end? The viruses have not disappeared; a descendant of the Spanish flu virus, modern H1N1, circulates to this day, as does H3N2. Humans have not developed immunity to them either. That is a phenomenon whereby a pathogen stops spreading because there are a lot of people protected against it because it is already infected or vaccinated.

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On the contrary, the viruses that caused these pandemics have undergone a transition. Or more to the point, I did. Our immune systems have learned enough about them to prevent the deadliest manifestations of infection, at least most of the time. Humans and viruses have reached an immunological distension. Instead of causing tsunamis of devastating diseases, over time viruses have come to cause small waves of milder disease. Pandemic flu has become seasonal flu.

Viruses have become endemic.

If the pattern is maintained and SARS-2 is expected to bind at some point to a handful of human coronaviruses that cause colds, mostly in the winter, when conditions favor its transmission.

When will that happen? That’s the big unanswered question. “I thought we would already be out of this acute phase,” admitted Maria Van Kerkhove, the World Health Organization’s lead coronavirus expert. However, Van Kerkhove’s thinking is influenced by his firm view that the world could stop the pandemic if countries only took the steps that countries like New Zealand, Vietnam and others have taken, and control transmission.

“There’s nothing, there’s nothing, including virus variants, that suggests we couldn’t be out of the acute phase,” STAT said in a recent interview. “Because this is controllable.”

The experience of the last four pandemics, the ones mentioned above, would suggest that viruses transform into pandemic pathogens to endemic sources of disease within a year and a half or two of emergency. But all those pandemics were flu pandemics. A different pathogen may mean we will see a different pattern.

There may have been previous coronavirus pandemics; there is a school of thought that a pandemic in 1889, known in medical histories as “Russian flu,” could be caused by one of the human coronaviruses, OC43. The four human coronaviruses are thought to have jumped on people of an animal species; OC43 is believed to come from cattle, potentially in the late 1800s. But this happens on the ground, it is not a conclusive fact, as it occurred before the era of modern virology.

There is no historical record of how many diseases and how many serious diseases these other coronaviruses caused when they began to infect humans or how long it took them to settle into an endemic state. Therefore, flu pandemics are most similar to road maps. “In recent history, everything has been the flu and the timeline has been in a couple of years,” said Jennie Lavine, a biology researcher at Emory University who was the first author of a model article published in Science that imagined what the pandemic might look like. fin.

Lavine and his co-authors predicted that as older adults, more susceptible to hospitalization and death with Covid, gain experience in managing the virus, it will no longer induce serious illness, at least not in most of those people. (Nothing is absolute; the flu, for example, occasionally kills previously healthy people).

That training of the immune system will likely turn future Covid-19 infections into the equivalent of a cold, the authors concluded. Over time, as the degree of protection becomes more standard in adults, the people who will most often catch Covid will be young children, in whom infections are still rarely severe. That is the pattern of human coronavirus infections.

“I think the scenario … is still the most likely,” said Marc Lipsitch, an infectious disease epidemiologist at Harvard’s TH Chan School of Public Health. “That essentially, almost everyone has some form of immunity to natural infection and / or vaccination and / or one after the other, and that it will persist long enough that they don’t really get sick when they get it again. And then we move on. to endemicity “.

Lavine is not surprised by the idea that SARS-2 could still be with us when the pandemic ends.

“It’s not a death sentence in any way, form or form to say we’re not going to have immunity at the helm,” he said. “It just means it’s going to be endemic and then the question is, will it be mild and endemic, or will it be severe and endemic? And I’d say my chances are mild and endemic at some point. I think that seems very, very likely.”

Lavine isn’t just thinking that we’re not going to control the spread of SARS-2 through herd immunity. Earlier this spring, Jonathan Yewdell, principal investigator in cell biology and viral immunology at the National Institute of Allergy and Infectious Diseases, published an opinion piece in the journal PLOS Pathogens arguing that coronaviruses do not trigger the type of long-term immune protection. we would need the immunity of the herd to be fixed.

Endemic SARS-2 would have a seasonal pattern, extending into the winter months when children are in school and when we spend more time indoors near others. Florian Krammer, a vaccinologist at Icahn School of Medicine on Mount Sinai in New York, said that at the beginning of some of these seasons it may be more severe than others, but not severe.

“If this thing becomes seasonal and you have countries where the vaccination rate is low and the history of immunity is low, those seasons at the beginning may be a little stronger. In countries where vaccination rates are high, they can be very low. “, said Krammer.

He and others told STAT that this transition will take place at different times in the world. “I think we’ll see a huge difference between the West and everyone else who hasn’t received enough vaccines,” Krammer said. “While there could be countries like Iran, where infection rates have been incredibly high, and I think they already have so much background immunity that they are knocking it down now, it’s unlikely to be a wave again.”

Lavine believes the change could happen very soon in countries like the United States that have had high levels of infections and a large number of people vaccinated.

“In the United States, I would say it’s not far off,” he said. “I’m not saying it’s just going to go away, but the idea that it would no longer be this kind of pathogenic scourge, I think maybe we’re not too far from that.”

There are some experts who are more cautious about chronology. Historian John Barry, who wrote the definitive account of the Spanish flu, “The Great Flu,” noted that there are significant differences between Covid infection and transmission and influenza infection and transmission. The incubation period – the time elapsed since exposure to the disease – is longer with Covid. People are sick for longer; they are also infectious for longer.

“This is like the flu moving very slowly,” Barry said. Influenza pandemics have abrupt endings in their waves, with transmission dying anywhere given in a matter of weeks. That was not the case with Covid. On the contrary, human behavior (social closures and reopenings) seems to be a driving pattern.

Lipsitch worries that recent explosive waves in Brazil and India are a reason to be wary of forecasts that a transition is imminent. Both experienced substantial transmission at the onset of the pandemic, but were struck by second waves caused by mutant viruses, the so-called variants of concern.

“I think we have to have some account of how it’s been going all this year with multiple waves and there’s still no real evidence that it ends on its own in any country. And I think a slower natural history is probably a piece,” he said. “He fucked me.”

Cécile Viboud, an infectious disease modeler who has studied influenza pandemics extensively, also believes the pandemic ends with SARS-2 as endemic. But she’s not sure when.

“I’m trying to be cautious, because I’ve always been optimistic and during Covid-19 I proved myself wrong,” said Viboud, who is based at the Fogarty International Center of National Institutes of Health.

He suggested that it is possible that the four seasonal coronaviruses, the ones that cause colds, were always milder than Covid. Or that SARS-2 will continue to throw us variants, especially when pressed to evolve when large numbers of people are vaccinated. “So I think we have to be prudent. We only have 15 months of data or something, right?”

Mike Ryan, head of the WHO Health Emergencies Program, agreed.

“We don’t know where we are, because this is the first pandemic of a SARS coronavirus,” he said. “From my perspective, crystallizing it … we’re not even close to the end.”

Ryan picks up on Van Kerkhove’s chorus, arguing that countries shouldn’t be waiting for vaccines or for the virus to pass into an endemic mode. They should use the other tools demonstrated to stop transmission, he said. “I think we can get to very high levels of disease control, so much so that this is no longer a pandemic in the sense that it is no longer … causing disease and death and filling our hospitals. So in that sense it is no longer a public health crisis “.



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