Within the next few years, as the SARS-CoV-2 virus becomes endemic in the global population, COVID-19 may behave like other common-cold coronaviruses, affecting mostly young children who have not yet been vaccinated or exposed to the virus, according to new modeling results.
“Yet, our modeling results suggest that the risk of infection will likely shift to younger children as the adult community becomes immune either through vaccination or exposure to the virus.”
Bjornstad explained that such shifts have been observed in other coronaviruses and influenza viruses as they have emerged and then become endemic.
“Historical records of respiratory diseases indicate that age-incidence patterns during virgin epidemics can be very different from endemic circulation,” he said. “For example, ongoing genomic work suggests that the 1889-1890 pandemic, sometimes known as the Asiatic or Russian flu – which killed one million people, primarily adults over age 70 – may have been caused by the emergence of HCoV-OC43 virus, which is now an endemic, mild, repeat-infecting cold virus affecting mostly children ages 7-12 months old.”
Bjornstad cautioned, however, that if immunity to reinfection by SARS-CoV-2 wanes among adults, disease burden could remain high in that group, although previous exposure to the virus would lessen the severity of disease.
“Empirical evidence from seasonal coronaviruses indicates that prior exposure may only confer short-term immunity to reinfection, allowing recurrent outbreaks, this prior exposure may prime the immune system to provide some protection against severe disease,” said Bjornstad.
The U.S.-Norwegian team developed what is known as a “realistic age-structured (RAS) mathematical model” that integrates demography, degree of social mixing, and duration of infection-blocking and disease-reducing immunity to examine potential future scenarios for age-incidence and burden of mortality for COVID-19.
Specifically, the researchers examined disease burden over immediate, medium and long terms – 1, 10 and 20 years, respectively. They also examined disease burden for 11 different countries – including China, Japan, South Korea, Europe, Spain, United Kingdom, France, Germany, Italy, United States, Brazil and South Africa—that differed widely in their demographics. They used data from the United Nations for each of these countries to parameterize the model.
“Regardless of immunity and mixing, the population-level burden of mortality may differ among countries because of varying demographics,” said Ruiyun Li, postdoctoral fellow, University of Oslo.
“Our general model framework allows for robust predictions of age-dependent risk in the face of either short or long-term protective immunity, reduction of severity of disease given previous exposure, and consideration of the range of countries with their different demographics and social mixing patterns.”
According to Li, social distancing is well documented to affect transmissibility, and many countries implemented interventions, such as “shelter in place,” during the build-up of the virgin COVID-19 epidemic. Therefore, the team’s model assumes that the reproduction number (R0) – or the level of transmissibility – on any given day is linked to the amount of mobility on that day.
The model also incorporates a variety of scenarios for immunity, including both independence and dependence of disease severity on prior exposure, as well as short- (either three months or one year) and long-term (either 10 years or permanent) immunity.
The team’s results appear today (August 11) in the journal Science Advances.
“For many infectious respiratory diseases, prevalence in the population surges during a virgin epidemic but then recedes in a diminishing wave pattern as the spread of the infection unfolds over time toward an endemic equilibrium,” said Li. “Depending on immunity and demography, our RAS model supports this observed trajectory; it predicts a strikingly different age-structure at the start of the COVID-19 epidemic compared to the eventual endemic situation.
In a scenario of long-lasting immunity, either permanent or at least 10 years, the young are predicted to have the highest rates of infection as older individuals are protected from new infections by prior infection.”
Jessica Metcalf, associate professor of ecology, evolutionary biology and public affairs, Princeton University, noted that this prediction is likely to hold only if reinfections produce only mild disease. However, she said, the burden of mortality over time may remain unchanged if primary infections do not prevent reinfections or mitigate severe disease among the elderly.
“In this bleakest scenario, excess deaths due to continual severe reinfections that result from waning immunity will continue until more effective pharmaceutical tools are available,” she said.
Interestingly, due to variations in demographics, the model predicts different outcomes for different countries.
“Given the marked increase of the infection-fatality ratio with age, countries with older population structures would be expected to have a larger fraction of deaths than those with relatively younger population structures,” said Nils Chr. Stenseth, professor of ecology and evolution, University of Oslo. “Consistent with this, for example, South Africa – likely due, in part, to its younger population structure – has a lower number of deaths compared to older populations such as Italy.
We found that such ‘death disparities’ are heavily influenced by demographics. However, regardless of demographics, we predict a consistent shift of the risk to the young.”
The researchers said that they designed their model so that health authorities will have a powerful and flexible tool to examine future age-circulation of COVID-19 for use in strengthening preparedness and deployment of interventions.
Bjornstad said, “The mathematical framework we built is flexible and can help in tailoring mitigation strategies for countries worldwide with varying demographics and social mixing patterns, thus providing a critical tool for policy decision making.”
The SARS-CoV-2 coronavirus will not be eradicated but will become endemic, continuing to circulate in pockets of the global population for years to come and causing outbreaks in regions where it had been eliminated, scientists working in the field believe.
But the impact of the virus on the world in terms of deaths, illness, and the need for social isolation will lessen, they say, as more of the population acquires some immunity to it through exposure to the virus or from vaccination.
The predictions come from a survey carried out in January by the journal Nature of more than 100 immunologists, infectious disease researchers, and virologists working on SARS-CoV-2.1 Almost 90% of respondents said that they expected the coronavirus to become endemic, although more than a third thought that it would be possible to eliminate SARS-CoV-2 from some regions of the world.
While there would be a continual risk of covid-19 outbreaks in areas where the virus had been eliminated, these could be stifled quickly by herd immunity if most people had been vaccinated, said Christopher Dye, an epidemiologist at the University of Oxford, UK. He told Nature, “I guess covid will be eliminated from some countries, but with a continuing and maybe seasonal risk of reintroduction from places where vaccine coverage and public health measures have not been good enough.”
Covid-19 is still classed as in a pandemic phase because infections continue to increase worldwide and many people are still susceptible. In an endemic phase the number of infections becomes relatively constant across years, with occasional flare-ups.
Antibodies and reinfection
Over time covid-19 could become a disease first encountered in early childhood, when it would typically cause mild infection or none at all, Jennie Lavine, an infectious disease researcher at Emory University in Atlanta, USA, told Nature. Although that defence would wane quickly and not be sufficient to block reinfection entirely, it could be enough to protect adults experiencing severe symptoms.
Scientists consider this scenario likely because it matches four existing endemic coronaviruses—OC43, 229E, NL63, and HKU1—but it is not certain. A large study has shown that levels of neutralising antibodies start to decline after around six to eight months after infection with SARS-CoV-2.2 If a new infection arises, memory B cells can manufacture antibodies and T cells that can eliminate virus infected cells, but it has yet to be established whether this immune memory can block viral reinfection.
It could take years or even decades to reach a state where enough of the population has sufficient immunity, Lavine added. Allowing the virus to spread unchecked would be the fastest way to get to that point, but it would result in many millions of deaths, so the most palatable path is through vaccination, she said.
If vaccines do block transmission and are effective against newer variants it may be possible to achieve herd immunity in regions where enough people are vaccinated. A model developed by Alexandra Hogan at Imperial College London and her colleagues showed that a vaccine that is 90% effective would need to reach at least 55% coverage to achieve temporary herd immunity with some social distancing measures, such as face masks and many people working from home.3 The same vaccine would need 67% coverage to provide herd immunity if all social distancing measures were lifted—and even higher levels if the vaccine was less than 90% effective at blocking transmission or if transmission increased because of a new variant.
Already, preprint results from laboratory studies suggest that neutralising antibodies in the blood of people who have had covid-19 are less capable of recognising a viral variant first identified in South Africa (called 501Y.V2) than variants that circulated earlier in the pandemic.4
More than 70% of the researchers surveyed by Nature believed that the ability to adapt and evade immune defences would drive continued circulation of SARS-CoV-2. As a result, updated vaccines may need to be developed and administered, possibly every year like the flu vaccine.
The future impact of SARS-CoV-2 will also depend on how well it establishes itself in a wild animal population. Several diseases that have been brought under control, including yellow fever, Ebola, and chikungunya virus, persist because of animal reservoirs. SARS-CoV-2 probably originated in bats and can readily infect many animals, including cats, rabbits, and hamsters, and it is particularly infectious in mink.
reference link : https://www.bmj.com/content/372/bmj.n494
More information: A general model for the demographic signatures of the transition from pandemic emergence to endemicity, Science Advances (2021). DOI: 10.1126/sciadv.abf9040