SARS-CoV-2 is a “predatory virus” that appears to have multiplied the risk of death by a similar amount for most adults in the UK regardless of their underlying health status, according to new research published in PLOS Medicine.
The London School of Hygiene & Tropical Medicine (LSHTM)-led research team estimated excess mortality in the UK during Wave 1 of the COVID pandemic in nearly 10 million adults aged 40 and over. They then estimated and compared relative rates of all-cause mortality in people with and without more than 50 health and socio-demographic characteristics before the pandemic and during Wave 1.
The rate of death during Wave 1 increased on average by a factor of just over 40% (x1.4) for the study population compared to before the pandemic. This relative increase in the rate of death was surprisingly consistent across much of the population, regardless of health conditions and other characteristics.
However, before the pandemic, those with pre-existing health conditions such as heart disease or asthma had a higher mortality rate than those without a further mortality rate increase of 40% had a bigger absolute impact on them.
Exceptions included those with dementia and learning difficulties; both groups had approximately 3x the rate of death compared to people without the condition before the pandemic but approximately 5x the rate of death compared to people without the condition during Wave 1.
Non-white ethnicities were another exception: black people had 20% reduced rate of death compared to white people before the pandemic but a 50% increase in relative rate of death compared to white people during Wave 1. Also, those living in London also had a lower rate of death before the pandemic compared to people living outside of London, but substantially elevated relative rate during Wave 1.
Researcher co-leader, LSHTM’s Dr Helen Strongman, said: “Our work has shown that the threat posed by COVID increases evenly with frailty or ill health caused by ageing and a wide range of respiratory and non-respiratory medical conditions. This compares to flu, which also tends to be more dangerous in the elderly but also affects young children and is more strongly associated with respiratory conditions such as asthma, COPD and smoking.”
Whilst the health and demographic factors studied are known to be associated both with mortality in non-pandemic years and mortality due to COVID during the pandemic, this is the first time the two have been linked – analysing all-cause mortality rather than COVID-specific mortality.
Dr Strongman said: “As we learn to live with COVID, we all need to be aware of and manage our own risk and that of others around us. Our study shows that SARS-CoV-2 is a predatory virus, amplifying mortality rates across the board, and having the biggest impact on those with existing ill health or who are frail. This emphasises how important it is for everyone to protect themselves and the most vulnerable in society through measures such as vaccination and wearing face masks. However, more basic research about why and how the virus exploits any vulnerability is needed.”
Dr Helena Carreira from LSHTM and co-lead author, added: “While we saw increases in the rate of death during the first wave of the pandemic across the population, our study also reinforced how COVID has disproportionately affected some groups, including people with dementia and learning disabilities, possibly through higher levels of exposure due to institutional or home-based care or occupation.”
Further research is needed to clarify whether there were differences across waves in the UK, especially for ethnicity, deprivation and other factors, and independent effects of individual health and demographic risk factors should be investigated.
Limitations include possible misclassification of the date of death for some individuals and the misclassification of health factors through incomplete information. However, the similarity of the results obtained from sensitivity analyses suggest only a minor impact on their findings.
COVID heat map. Photo by Giacomo Carra on Unsplash
South Africa may have gotten off more lightly from Omicron due to widespread immunity from previous infection combined with vaccine coverage, researchers think, which may not bode well for other countries which have not completed their vaccination nor seen the worst COVID surges.
The South African Medical Research Council in collaboration with Discovery Health on Tuesday last week presented data from a large study showing that South Africans infected with Omicron are, on average, less likely to be hospitalised, and recover faster, compared to the other variants.
Their study looked at more than 200 000 COVID cases in South Africa during a Delta-driven surge in September and October, and the start of the Omicron-driven surge in November, as that variant began increasing rapidly. About a quarter of the people in the study already have a chronic illness, putting them at higher risk of severe COVID.
The researchers found a hopeful trend: The risk of hospitalisation for adults dropped 30% during the early days of the Omicron surge from the levels seen there in September and October.
“The hospital admissions during omicron, standing at 58 per 1000 infections, are the lowest of the four COVID waves, and one-third of what we experienced during the delta surge,” said Discovery Health CEO Ryan Noach.
Why was this so? One explanation could be the immunity from COVID recovery present in the population. South Africa had experienced three huge COVID surges with low vaccination rates compared to the US and Europe.
When the Omicron variant appeared, only about a quarter of the population were vaccinated but the vast majority of residents had likely already been infected with previous variants of SARS-CoV-2. This was based on the excess mortality rate observed in the country through the pandemic, and so it is thought that South Africans likely had some immunity granted by infection.
“Thus, Omicron enters a South African population with considerably more immunity than any prior SARS-CoV-2 variant,” concluded Dr Roby Bhattacharyya, an infectious disease specialist, and epidemiologist William Hanage in a recent working paper. This means that most Omicron cases are likely to be reinfections, rather than first infections. Other countries will not have as broad a ‘coverage’ of vaccination and previous infection as South Africa. Around 125 million Americans are unvaccinated, and a recent study estimated that about 20% of Americans had been infected with COVID from the start of the pandemic, up to August, 2021.
The data therefore suggest that a minimum of 20% of Americans who are completely ‘naive’, as scientists term it, when it comes to exposure to SARS-CoV-2.
Convalescent plasma from COVID patients was likely of benefit to patients early on in the pandemic, before the introduction of remdesivir and corticosteroids as treatments, according to results of a landmark study published in JAMA Internal Medicine.
The randomised clinical trial, CONTAIN COVID-19, was established to evaluate the safety and efficacy of convalescent plasma in hospitalised coronavirus patients. Overall, the trial showed that convalescent plasma was safe and well tolerated. It worked best in the early days of the pandemic, when plasma had higher antibody levels, when it was given early in the disease, and particularly for immunosuppressed people.
“This landmark study shows once and for all that convalescent plasma is an important countermeasure early in a pandemic when no other therapies are available. It was an important finding that lays the foundation for the rapid response to future pandemics,” said Luis Ostrosky, MD, professor and director of the Division of Infectious Diseases at McGovern Medical School at UTHealth Houston. “This trial, the largest of its kind, also showed that with proper funding and structure, researchers across the country were able to come together quickly in the middle of a global crisis to explore this therapeutic intervention.”
Trial results also showed a drop in efficacy after the introduction of remdesivir and corticosteroids, and by the end of the 11-month trial, there was no difference in outcome between plasma and placebo in patients at 14 and 28 days. However, patients on corticosteroids, but not remdesivir, appeared to benefit from convalescent plasma at day 14.
Since the patient characteristics, available treatments, and the virus, all changed over time, subgroup analyses were done, which showed a possible benefit for patients in the first quarter of the trial, a period from April to June 2020.
Participants in that first quarter were older, less severely ill, had a longer duration of symptoms, and received high-titer plasma. Shorter symptom duration can indicate a more severe case of the viral infection.
“Convalescent plasma could be an important early treatment tool in places that don’t have access to monoclonal antibodies, corticosteroids, remdesivir, or other therapies,” said the study’s co-investigator, Professor Bela Patel, MD. “It should also be considered for patients who are immunosuppressed and those whose B cell function is compromised.”
The researchers also suggested that, in addition to the introduction of corticosteroids and remdesivir, the decrease in efficacy over time may have been due to using convalescent plasma that originated from New York City before the emergence of other SARS-Co-V-2 variants .
Researchers working with ‘humanised mice’ have found why some mild cases of COVID tip over into more severe and life-threatening disease.
An estimated 80 to 90% of people infected with COVID experience only mild cases while 10 to 20% face more severe or life-threatening symptoms.
Yale University researchers working with mice they have engineered to possess human-like immune systems may have found why this is so. Their findings, published in Nature Biotechnologyrevealed that the causes of severe COVID may lie in our own antiviral inflammatory response to the virus.
The study also showed that two well-known therapies, monoclonal antibodies and the steroid dexamethasone, can help treat COVID infections. But in the case of the antibodies, treatment is only effective if administered early in the course of disease. In the case of steroids, it’s only effective if administered during later stages of the disease.
Standard laboratory animals and humans have different immune responses, which has made it difficult for scientists to pinpoint the tipping point between mild and severe cases of COVID, so mice engineered to have a human-like immune system, were able to offer an answer.
“If you infect a standard laboratory mouse with SARS-CoV-2 they will get infected, but not get seriously ill,” said Flavell, Sterling Professor of Immunobiology at Yale and senior author of the paper. “But our humanised mice get sick and just don’t get better. Their whole immune system is on fire.”
The research team introduced SARS-CoV-2 virus taken from seriously ill human patients into the nasal passages of their humanised mice and then followed the course of the disease.
They found that the infected mice exhibited the same symptoms as severely ill human patients, such as lung damage, weight loss, and a heightened, persistent inflammatory immune response that damages tissues. They then treated the mice with monoclonal antibodies which specifically target the virus, and were found to be effective if given before or very early after infection but did little to stifle symptoms if administered in later stages of infections.
Conversely, during the early stages of infection the immune suppressant dexamethasone was fatal to mice when it suppressed the initial immune response that was crucial to combat the virus. However, during later stages of disease, it helped clear infection by suppressing the inflammatory response that had begun damaging organs.
“Early in the course of disease, a strong immune response is crucial for survival,” said first author Esen Sefik. “Later in the disease, it can be fatal.”
The humanised mice models might also reveal strong clues to the causes and potential treatments of so-called long and severe COVID, the scientists said.
Wastewater monitoringhas shown that COVID infections are falling in Gauteng, indicating that the Omicron wave may have peaked, while the World Health Organization warns that the variant should not be taken lightly despite its mildness.
The findings align with comments by Health Minister Joe Phaahla on Friday that the Omicron-driven wave may be peaking in the province.
Despite Gauteng’s peaking, cases are on the rise in seven of the nine provinces and last week the country saw a new high in cases. Of the infections confirmed on Thursday, Gauteng accounted for 27%, down from 72% of new infections on December 3.
However, the surge of Omicron will likely not be confined to Gauteng. “Early indications are that we might have reached the peak in Gauteng,” Dr Phaahla said in an online media briefing. “But there is a corresponding, rapid increase of cases in the other big provinces.”
He also noted a 70% increase in hospitalisations, though he stressed that this was off of a low base rate. Meanwhile, the WHO has warned that countries should not take the Omicron variant likely in spite of its apparent low severity.
“Countries can – and must – prevent the spread of Omicron with the proven health and social measures. Our focus must continue to be to protect the least protected and those at high risk,” said Dr Poonam Khetrapal Singh, Regional Director of the WHO South-East Asia Region.
Omicron should not be dismissed as mild, she cautioned, adding that even if it does cause less severe disease, the sheer number of cases could once again overwhelm health systems. Hence, health care capacity including ICU beds, oxygen availability, adequate health care staff and surge capacity need to be reviewed and strengthened at all levels.
The overall threat posed by Omicron largely depends on three key questions – its transmissibility; how well the vaccines and prior SARS-CoV-2 infection protect against it, and how virulent the variant is as compared to other variants.
From what we know so far, Omicron appears to spread faster than the Delta variant which has been attributed to the surge in cases across the world in the last several months, Dr Singh said.
She added that emerging data from South Africa suggests increased risk of re-infection with Omicron, and said that there is still limited data on Omicron’s limited severity. Further information is needed to fully understand the clinical picture of those infected with Omicron, and more information is expected in the coming weeks.
Her statements echo those of WHO chief Tedros Adhanom Ghebreyesus, who earlier last week warned that health systems could still be overwhelmed by cases.
While two doses of a COVID vaccine offered less protection against Omicron, a booster shot restored immunity back to high levels, according to real-world data from the UK.
Two doses of Pfizer vaccine provided just under 40% protection against symptomatic infection with the Omicron variant about 25 weeks after the second dose compared with around 60% protection against Delta, according to a technical briefing released by the UK Health Security Agency. [PDF]
“These early estimates suggest that vaccine effectiveness against symptomatic disease with the Omicron variant is significantly lower than compared to the Delta variant,” the agency noted in the report. However, “moderate to high” vaccine effectiveness was observed in the early period after a booster shot, they added.
The agency found that a Pfizer booster increased vaccine effectiveness to 76%. Among people who received the AstraZeneca series for their initial immunisation (which offered almost no protection against Omicron), vaccine effectiveness jumped to 71% after a Pfizer booster.
The reportcompared vaccine effectiveness against Omicron versus Delta, including 581 people who were infected with the new strain and more than 56 000 infected with Delta from the end of November to December 6.
Omicron’s reinfection rate was also much higher than Delta’s. Of 329 individuals infected with Omicron, 7% had a previous infection, compared with 0.4% of the approximately 85 000 people infected with Delta.
After adjustments for age and area, the risk ratio of reinfection for Omicron was 5.2 (95% CI 3.4-7.6).
The report also found a 20- to 40-fold reduction in neutralising antibody activity compared with the viruses used to develop the vaccines. However, a booster dose significantly improved neutralising antibodies, regardless of which vaccine was given in the initial immunisation.
Katelyn Jetelina, PhD, an epidemiologist at the University of Texas Health Science Center at Houston, said that the study data confirm what researchers have already discovered in lab research: vaccines offer significantly less protection against Omicron, and reinfection rates are expected to be high.
Dr Jetelina noted that it was reassuring to see that “we can curb infection still with a booster, which is really quite phenomenal.” However, she said that cases were likely to increase.
“I think all this data is showing us that we’re going to have a lot of infections with Omicron,” Jetelina told MedPage Today. While a high rate of infection does not necessarily translate to severe illness, Dr Jetelina said that she is concerned about population-level outcomes resulting from a flood of new cases.
“That’s where I get a bit more nervous,” she said. She pointed out that “even if the rate of severe disease is low […] those numbers start adding up real quickly.”
The UK Health Security Agency advised interpreting the results with caution, due to the low number of Omicron cases. Additionally, more data are needed before scientists can determine how well vaccines will work against severe illness, hospitalisation, and death from the Omicron strain.
“It will be a few weeks before effectiveness against severe disease with Omicron can be estimated,” the agency stated. “However, based on this experience, this is likely to be substantially higher than the estimates against symptomatic disease.”
A highly anticipated clinical trial in eight sub-Saharan countries is the first to specifically evaluate the efficacy of a COVID vaccine in people living with HIV, including those with poorly controlled infections. It also is the first study to evaluate the efficacy of vaccines – in this case, Moderna mRNA-1273 – against the Omicron variant of SARS-CoV-2.
In addition to examining the efficacy of COVID mRNA vaccines in people living with HIV, the study investigators seek to identify the optimal regimen for this population and how it might vary based on whether an individual has previously had COVID-19 or not.
The trial will be conducted in East and Southern Africa – regions of the world that have been highly impacted by HIV. It is expected to enrol about 14,000 volunteers at 54 clinical research sites in South Africa, Botswana, Zimbabwe, Eswatini, Malawi, Zambia, Uganda and Kenya, where adult HIV prevalence ranges from 4.5% to 27%.
“Sub-Saharan Africa has been hit hard by the COVID pandemic, but access to effective vaccines, especially mRNA technology, has been very limited,” said Dr. Nigel Garrett, co-chair of the study and head of Vaccine and HIV Pathogenesis Research at the Center for the AIDS Program of Research in South Africa (CAPRISA). “The Ubuntu trial will provide safety data to regulators and assess correlates of protection from COVID-19, and it will answer important questions on mRNA vaccine dosage regimens among people living with HIV.”
About 12 600 people living with HIV and about 1400 who are HIV-negative are expected to be enrolled in the study. About 5000 will have previously had COVID, confirmed by an antibody blood test done at initial enrollment. All participants will receive the Moderna vaccine, but dosages and schedules will vary depending on previous SARS-CoV-2 infection. Participants living with HIV will get access to optimal HIV treatment throughout the trial.
“This region faces a huge HIV burden,” said Dr Glenda Gray, Ubuntu study protocol lead adviser and president of the South African Medical Research Council (SAMRC). “Although safe and effective vaccines have been developed for COVID-, HIV and COVID are on a collision course,” she added. “The impact of COVID-19 on people living with HIV is a concern for the continent, particularly in light of the recently-sequenced omicron variant set to drive South Africa’s fourth wave and further infections globally.”
Dr Philip Kotzé, one of the lead study investigators, said the Ubuntu study would not be possible without the crucial participation of rural communities across Southern and East Africa. “These communities have been disproportionately impacted by the twin pandemics of HIV and COVID-19, and they now have an unprecedented opportunity to help advance science and improve our understanding of the immune response to SARS-CoV-2 in the context of HIV.”
Dr Larry Corey, principal investigator of both the HIV Vaccine Trials Network (HVTN) and the COVID-19 Prevention Network (CoVPN), and co-leader of the network’s vaccine testing pipeline, said this study seeks to address the knowledge gap around HIV status and COVID vaccination.
“Vaccination and treatment are critical for those who face the dual threat of HIV and COVID, as they remain at high risk of acquisition and transmission and potentially can be the origin of future variants,” Dr Corey said. “It is imperative that we as scientists and as society double-down on global efforts to find and make available effective vaccines and treatments. This study represents an important step forward in our efforts to reduce the burden of COVID among HIV-infected persons and understand whether current dosage regimens are adequate.”
Rather than a World Trade Organization (WTO) patent waiver, COVID vaccine equity requires improvements to manufacturing and distribution of vaccines in the Global South and compulsory licensing mechanisms, according to a statement by ALLEA, the European Federation of Academies of Sciences and Humanities.
They state that the low level of COVID vaccination in the Global South is ethically unacceptable and risks prolonging the pandemic. At the end of 2021, access to Covid-19 vaccines is still a priority. Only 5.9 % of people in low-income countries have received at least one dose (on 29 November 2021, compared with 0.3% on 14 April), with numbers in Africa remaining very low, save for Morocco. The patent waiver being discussed within the WTO since 2020 will not solve these vaccination bottlenecks in the short-term. For instance, the waiver as proposed by South Africa and India would in practice require unanimity between the 164 WTO Members to be adopted – to achieve this in practice would simply delay the waiver until after the pandemic.
Rather, measures should be undertaken to accelerate local manufacturing and distribution of vaccines in low- and middle-income countries (LMICs), ramp up investment in vaccination campaigns, and facilitate the compulsory licensing of patents and knowledge transfer.
In particular, the statement advocates for (i) practical measures that could accelerate the production, export, distribution, and administration of vaccines worldwide and ii) an international mechanism affording additional scrutiny of the manufacturing bottlenecks combined with new measures in the intellectual property (IP) framework such as flexibility for the compulsory licensing of patents.
According to the experts, the current co-sponsored waiver proposal at the WTO is “not well-tailored to the urgent vaccine problem” and needs additional national legislation to have any practical effect. A WTO waiver would only remove the obligation for WTO Member States to grant IP protection, but would not ensure that stakeholders can effectively benefit from the invention and related know-how.
“A waiver (in the sense of the co-sponsored proposal at the WTO) of IP protection, including of trade secrets, would never make this know how publicly accessible, but only remove the possibility for companies enjoying confidentiality protection to sue for trade secret infringement”, the experts argued.
Other IPR measures need to be considered instead, with the WTO waiver debate raising other IP fixes that are needed in the field of health. The WTO rules on compulsory licensing of health-related patents should be amended. Important adjustments to patents and trade secret protections should also be adopted by the EU, its Member States, and other countries. In particular, improved procedures and institutional design should help to streamline the process for compulsory licensing on pharmaceutical products, including vaccines.
With the COVID test positivity rate climbing above 30%, President Cyril Ramaphosa is widely expected to address the nation in the coming days. Health Minister Dr Joe Phaahla said on Friday that the National Coronavirus Command Council would be meeting on Tuesday or Wednesday to discuss new restrictions in the face of surging infections.
The main concern is centred around the large number of gatherings that will take place over the festive period: under Level 1 lockdown rules, gatherings of up to 750 individuals are permitted indoors. The Bureau for Economic Research issued a report saying that data so far indicates that there are fewer hospitalisations and less severe disease with the Omicron variant, in line with observations made since the start of the variant’s outbreak.
A partial ban on alcohol sales seems likely, according to a source cited by City Press: “He is considering proposing to the NCCC and cabinet a few adjustments, which include banning the sale of alcohol on weekends and public holidays until mid-January. Don’t be surprised when we have a family meeting before Thursday. He is serious about protecting the country.”
He initially had no plans to address the nation, sources said, but was motivated to change his view in light of the increasing rate of transmission.
Meanwhile, the UK appears set to scrap its controversial red list, which had been widely viewed as unfairly targeting South Africa. The red list amounted to a virtual travel ban, with travellers forced to pay £2285 (R48 400) per person for a ten day stay in often substandard quarantine accommodation. However, it will come too late for many people who have cancelled travel plans.
In a windfall for South Africans, the cost of PCR testing has been revised downward to R500 from R850 as of Sunday following a complaint lodged with the Council for Medical Schemes against private pathology laboratories, alleging the pricing for COVID PCR tests was unfairly inflated. Pricing for rapid antigen tests is said to be next on the list for the Competition Commission.
On Sunday, a technical glitch caused the National Health Laboratory Service to delay release of a large portion of test results. The glitch meant that initially 18 035 cases were released initially, which rose to over 37 000 after the correction.
The cause was put down to IT difficulties with various laboratories.
A report in Nature examines why Omicron was such a surprise, and how the possible evolutionary pathways available to SARS-CoV-2 shape future scenarios of the COVID pandemic.
Currently, Delta and its descendants still dominate worldwide, and they were expected to eventually outcompete the last holdouts. But Omicron has undermined those predictions. “A lot of us were expecting the next weird variant to be a child of Delta, and this is a bit of a wild card,” said Aris Katzourakis, a specialist in viral evolution at the University of Oxford, UK.
The Omicron surge in South Africa suggests that the new variant has a fitness advantage over Delta, said Tom Wenseleers, an evolutionary biologist and biostatistician at the Catholic University of Leuven in Belgium. Omicron has some of the mutations associated with Delta’s high infectivity – but if increased infectivity alone explained its rapid growth, it would mean an R0 (reproduction number) in the 30s, said Wenseleers. “That’s very implausible.”
At present, Omicron appears to have an R0 of 1.36, after its initial surge, based on a continually updated estimate by Louis Rossouw, head of research and analytics at Gen Re. Weneseelers and other researchers instead suspect that Omicron’s rise may be due to its re-infection and vaccine evasion ability.
If Omicron is spreading, in part, because of its ability to evade immunity, it fits in with theoretical predictions about how SARS-CoV-2 is likely to evolve, says Sarah Cobey, an evolutionary biologist at the University of Chicago in Illinois.
As SARS-CoV-2’s infectivity gains start to slow, the virus will maintain its fitness by overcoming immune responses, said Cobey. If mutation halved a vaccine’s transmission blocking ability, this could open up a vast number of hosts. It’s hard to imagine any future infectivity gains providing the same boost.
The evolutionary path towards immune evasion and away from infectivity gains, is common among established respiratory viruses such as influenza, said Adam Kucharski, a mathematical epidemiologist at the London School of Hygiene and Tropical Medicine. “The easiest way for the virus to cause new epidemics is to evade immunity over time. That’s similar to what we see with the seasonal coronaviruses.”
Analysis has shown a wealth of Spike protein mutations that weaken the potency of neutralising antibodies resulting from infection and vaccination. Variants like Beta that have such mutations, have degraded – but not destroyed – vaccine effectiveness particularly against severe disease.
Compared with other variants, Omicron contains many more of these mutations, particularly in the region of spike that recognises host cells. Preliminary analysis from evolutionary biologist Jesse Bloom suggests that these mutations might render some portions of Spike unrecognisable to the antibodies raised by vaccines and previous infection with other strains. But lab experiments and epidemiological studies will be needed to fully appreciate the effects of these mutations.
Evolutionary costs and benefits Evolving to evade immune responses such as antibodies could also carry some evolutionary costs. A Spike mutation that dodges antibodies might reduce the virus’s ability to recognise and bind to host cells. The receptor-binding region of Spike, the main target for neutralising antibodies. is relatively small, explained Jason McLellan, a structural biologist at the University of Texas at Austin. Thus, the region might tolerate only small changes if it retains its main function of attaching itself to host cells’ ACE2 receptors.
Repeat exposures to different Spike versions, through infection with different virus strains, vaccine updates or both, eventually might build up a wall of immunity that SARS-CoV-2 will have difficulty overcoming. Mutations that overcome some individuals’ immunity might not work on the whole population, and T-cell-mediated immunity, another arm of the immune response, seems to be more resilient to changes in the viral genome.
SARS-CoV-2’s evasion of immunity might be slowed by these constraints, but they are unlikely to stop it, said Bloom. Evidence shows that some antibody-dodging mutations do not carry large evolutionary costs, said McLellan. “The virus will always be able to mutate parts of the Spike.”
A virus in transition How SARS-CoV-2 evolves in response to immunity has implications for its transition to an endemic virus. There wouldn’t be a steady baseline level of infections, says Kucharski. “A lot of people have a flat horizontal line in their head, which is not what endemic infections do.” Instead, the virus is likely to cause outbreaks and epidemics of varying size, like influenza and most other common respiratory infections do.
To predict what these outbreaks will look like, scientists are investigating how quickly a population becomes newly susceptible to infection, says Kucharski, and whether that happens mostly through viral evolution, waning immune responses, or the birth of new children without immunity to the virus. “My feeling is that small changes that open up a certain fraction of the previously exposed population to reinfection may be the most likely evolutionary trajectory,” said Rambaut.
The best outlook for SARS-CoV-2, but also the least likely, would be for it to follow measles. Lifetime protection results from infection or vaccination and the virus circulates largely on the basis of new births. “Even a virus like measles, which has essentially no ability to evolve to evade immunity, is still around,” said Bloom.
A more likely, but still relatively hopeful, parallel for SARS-CoV-2 is a pathogen called respiratory syncytial virus (RSV). Most people get infected in their first two years of life. RSV is a leading cause of hospitalisation of infants, but most childhood cases are mild. Waning immunity and viral evolution together allow new strains of RSV to sweep across the planet each year, infecting adults in large numbers, but with mild symptoms thanks to childhood exposure. If SARS-CoV-2 follows this path – aided by vaccines that provide strong protection against severe disease – “it becomes essentially a virus of kids,” Rambaut said.
Influenza offers two other scenarios. The influenza A virus, which drives global seasonal influenza epidemics each year, is characterised by the rapid evolution and spread of new variants able to escape the immunity elicited by past strains. The result is seasonal epidemics, propelled largely by spread in adults, who can still develop severe symptoms. Flu jabs reduce disease severity and slow transmission, but influenza A’s fast evolution means the vaccines aren’t always well matched to circulating strains.
But if SARS-CoV-2 evolves to evade immunity more sluggishly, it might come to resemble influenza B. That virus’s slower rate of change, compared with influenza A, means that its transmission is driven largely by infections in children, who have less immunity than adults.
How quickly SARS-CoV-2 evolves in response to immunity will also determine the need for vaccine updates. The current offerings will probably need to be updated at some point, says Bedford. In a preprint5 published in September, his team found signs that SARS-CoV-2 was evolving much faster than seasonal coronaviruses and even outpacing influenza A, whose major circulating form is called H3N2. Bedford expects SARS-CoV-2 to eventually slow down to a steadier state of change. “Whether it’s H3N2-like, where you need to update the vaccine every year or two, or where you need to update the vaccine every five years, or if it’s something worse, I don’t quite know,” he says.
Although other respiratory viruses, including seasonal coronaviruses such as 229E, offer several potential futures for SARS-CoV-2, the virus may go in a different direction entirely, say Rambaut and others. The sky-high circulation of the Delta variant and the rise of Omicron, aided by inequitable vaccine roll-outs to lower-income countries and minimal control measures in certain large developed countries such as the US, offer fertile ground for SARS-CoV-2 to take additional surprising evolutionary leaps.
For instance, a document prepared by a UK government science advisory group in July raised the possibility that SARS-CoV-2 could become more severe or evade current vaccines by recombining with other coronaviruses. Continued circulation in animal reservoirs, such as mink or white-tailed deer, brings more potential for surprising changes, such as immune escape or heightened severity.
It may be that the future of SARS-CoV-2 is still in human hands. Vaccinating as many people as possible, while the jabs are still highly effective, could stop the virus from unlocking changes that drive a new wave. “There may be multiple directions that the virus can go in,” said Rambaut, “and the virus hasn’t committed.”
