The loss of smell and taste with a COVID infection during the delta wave was a prevalent symptom and wasn’t prevented by vaccination, suggests a new study is published in the journal Med.
The small Ohio State University study also found that some people with the earliest COVID infections were continuing to experience loss of these senses months later without realising it.
In participants with active infections during the delta surge, a majority (22 of 25) had been vaccinated. Objective screenings found that 100% were experiencing a diminished or lost sense of smell – but only 54.5% self-reported any problem with odour detection.
“We’re getting this quick communication out as an early warning. We need to continue to take a closer look at COVID infection’s impact on smell and taste,” said Dr Kai Zhao, associate professor of otolaryngology in Ohio State’s College of Medicine and senior author of the study. “Even if COVID doesn’t cause death or hospitalisation, it can have long-lasting effects on some of our sensory functions.
“A lot of people are potentially suffering, which is probably not appreciated by society.”
Data for this study emerged from an earlier project the researchers started to test the use of hard candy as a screening tool for the loss of taste and smell in populations at risk for exposure to the SARS-CoV-2 virus.
As part of that work, the team used an existing objective screening tool to collect sensory function data from 123 never-infected control participants and 65 people who had previous or active COVID infections. During the delta surge, the researchers became alarmed by what they found.
“At that time, there were a lot of speculations about whether smell loss is associated with the delta variant and whether the vaccine could protect against these symptoms. So we decided to do this interim data analysis,” Dr Zhao said.
In addition, about three-fourths of participants whose mostly mild COVID infections had occurred before delta’s dominance reported no ongoing smell and taste losses – however, over half of those participants were found by the objective screening, conducted between 102 and 785 days after their infection diagnosis, to have a loss of smell.
“Many people who had COVID in the past, probably with the original variants of the virus, underwent some degree of smell loss, even if they didn’t think they did,” said co-author Susan Travers, professor of biosciences in Ohio State’s College of Dentistry. “This suggests the long-term impact on sensory function isn’t captured by self-reporting.”
Beyond these silent smell and taste losses, there were also people who reported that they hadn’t regained taste or smell function for longer than six months, said first author Kym Man, a graduate student in food science and technology.
“We’re still collecting data on these long haulers, some of whom have been experiencing smell and taste loss for over a year,” she said.
Effects on the senses include diminished or complete loss of smell and/or taste, disordered smell and/or taste and, least common, smelling odors that are not present at all.
The sensory function screenings were conducted with a National Institutes of Health tool consisting of a 9-item scratch-and-sniff odour identifier and an intensity rating of bitterness in a sip of quinine. The odour-detection results were adjusted for age – in general, smell sensitivity declines with age, Dr Zhao said.
Beyond affecting the quality of life, the loss of smell and taste has health ramifications that include negative effects on nutrition intake and a reduced ability to detect danger – such as a fire or spoiled food.
“The disease’s impact on smell and taste is underreported. This is a public health concern that there may potentially be some broader impacts of COVID that we don’t realise are there,” Dr Zhao said.
South Africa is now on the cusp of a fifth wave, experts warn, as indicators rise and new variants begin to circulate. Social media monitoring indicates a level of public apathy.
After a period of reduced cases, cases rose for three consecutive days, prompting concern. Health Department deputy director-general, Nicholas Crisp, noted possible explanations.
“It may be associated with one of the sub-variants of Omicron, certainly that is what’s dominant at the moment but it also might be just because we are all a bit lax at the moment, we don’t wear our masks so diligently,” he said.
Crisp said that they would be watching the data closely, before pronouncing on whether this was indeed the start of the fifth wave.
“We are not sure if this is the variant that’s going to do whatever is going to happen in the fifth wave, what we are seeing at the moment is what we call a flare-up,” Crisp said.
Wastewater monitoring has seen an uptick in coronavirus levels, according to the NICD’s weekly brief [PDF]. The BA.4 and BA.5 Omicron variants have been observed but it is not clear what impact they will have on the fifth wave. The Delta variant has been sequenced in wastewater, but the significance of this is still unclear.
Gauteng has reported the highest weekly incidence at 27.4 per 100 000 people, followed by Western Cape (23.4 per 100 000), and KwaZulu-Natal (13.4 per 100 000). However, testing rates are down in a number of provinces. The highest incidence is among young teenagers.
As of 25 April, 1954 new cases with a 19.3% positivity rate were recorded by the NICD.
The Health Department’s Vaccine Social Listening progamme has seen a significant drop in engagement across social media, down by 50% on Twitter, 60% on Facebook. Engagements with digital news articles are down 70%. Fears over a fifth wave have been dismissed on social media as “fear mongering” and there is a belief that “covid-19 is over”.
Business Leadership South Africa chief executive Busi Mavuso said the fifth wave will test the government’s new COVID regulations.
Writing in her weekly open letter, Mavuso noted South Africa is currently in the 30 day transition period from the end of the state of disaster on 5 April and the new National Health Act regulations.
She noted some risk, with mistakes from earlier regulations being built upon. However, increased background immunity levels was credited with the reduced impact of the Omicron wave in hospitalisation and deaths. Based on the assumption that the new wave will be less impactful, economically damaging measures can be avoided.
Mavuso added that the previous waves have proven that the country can find the best balance in managing the pandemic and the economy if there is full consultation so that the consequences of regulations can be understood and planned for. “I look forward to engaging our public sector counterparts to find that balance.”
Wits University’s Professor Shabir Madhi said that with a clear increase in cases, the country was on the cusp of a resurgence. The country will however be much better positioned with higher immunity levels and a demonstrated decoupling of infections and disease severity.
Further lockdowns would likely be unnecessary, given how past lockdowns have repeatedly failed.
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.”
In a recent study published in Scientific Reports, researchers found that older people previously infected with COVID, when vaccinated, had higher antibody levels than previously infected individuals. These antibodies were also effective against the Delta variant, which wasn’t present in Canada when the samples were taken in 2020.
Joelle Pelletier and Jean-François Masson, both professors in Université de Montréal’s Department of Chemistry, wanted to find out whether natural infection or vaccination led to more protective antibodies being generated. The focussed on an understudied group: people who have been infected but not hospitalised by SARS-CoV-2.
Consequently, 32 non-hospitalised COVID positive adults were recruited 14 to 21 days after being diagnosed through PCR testing. This was in 2020, before the Beta, Delta and Gamma variants emerged.
“Everyone who had been infected produced antibodies, but older people produced more than adults under 50 years of age,” said Prof Masson. “In addition, antibodies were still present in their bloodstream 16 weeks after their diagnosis.”
Antibodies produced after an infection by the original, “native” strain of the virus also reacted to SARS-CoV-2 variants that emerged in subsequent waves, namely Beta (South Africa), Delta (India) and Gamma (Brazil), but to a lesser extent: a reduction of 30 to 50%.
“But the result that surprised us the most was that antibodies produced by naturally infected individuals 50 and older provided a greater degree of protection than adults below 50, ” said Prof Pelletier.
“This was determined by measuring the antibodies’ capacity to inhibit the interaction of the Delta variant’s spike protein with the ACE-2 receptor in human cells, which is how we become infected,” he added. “We didn’t observe the same phenomenon with the other variants.”
When someone who has had a mild case of COVID is vaccinated, the antibody level in their blood doubles compared to an unvaccinated person who has been infected by the virus. Their antibodies are also better able to prevent spike-ACE-2 interaction.
“But what’s even more interesting,” said Prof Masson, “is that we have samples from an individual younger than 49 whose infection didn’t produce antibodies inhibiting spike-ACE-2 interaction, unlike vaccination. This suggests that vaccination increases protection against the Delta variant among people previously infected by the native strain.”
Both scientists believe more research should be conducted to determine the best combination for maintaining the most effective level of antibodies reactive to all variants of the virus.
In a study of more than 40 000 COVID cases, those infected with the delta variant have about twice the hospitalisation risk as those infected with the alpha variant. The findings were published in The Lancet Infectious Diseases.
The risk of hospitalisation or emergency hospital care within 14 days of infection with the delta variant was 1.45 times greater than the alpha variant. This is the first study reporting hospitalisation risk for the delta versus alpha variants based on cases confirmed by whole-genome sequencing.
Dr Gavin Dabrera, one of the study’s lead authors and a Consultant Epidemiologist at the National Infection Service, Public Health England, said: “This study confirms previous findings that people infected with Delta are significantly more likely to require hospitalisation than those with Alpha, although most cases included in the analysis were unvaccinated.”
The delta variant emerged in India in December 2020 and early studies found it to be up to 50% more transmissible than the alpha variant, which first appeared in the UK. A preliminary study from Scotland previously reported a doubling of hospitalisation risk with the delta variant over the alpha variant and it is suspected that delta is associated with more severe disease. The previous study used patients’ initial PCR test results and determined which variant they had by testing for a specific gene that is more common in the delta variant.
The researchers analysed healthcare data from 43 338 COVID-positive cases in England between 29 March and 23 May 2021. During the study period, there were 34 656 cases of the alpha variant (80%) and 8682 cases of the delta variant (20%). While the proportion of delta cases in the study period overall was 20%, it eventually encompassed two thirds of new COVID cases in the week starting 17 May 2021 (65%), effectively becoming the dominant strain in England.
Around one in 50 patients were admitted to hospital within 14 days of their first positive COVID test (2.2% alpha cases; 2.3% delta cases. After accounting for factors that are known to affect susceptibility to severe illness from COVID, including age, ethnicity, and vaccination status, the researchers found the risk of being admitted to hospital was more than doubled with the delta variant compared with the alpha variant (2.26-fold increase in risk).
It has been shown in multiple studies that full vaccination prevents both symptomatic infection and hospitalisation, for both alpha and delta variants. Indeed, in this study, only 1.8% of COVID cases (with either variant) had received both doses of the vaccine; 74% of cases were unvaccinated, and 24% were partially vaccinated. With the small number of vaccinated people being hospitalised, it is not possible to statistically compare hospitalisation risk between alpha and delta in such cases, so the results of the study apply to unvaccinated or partially vaccinated cases.
One of the study’s lead authors, Dr Anne Presanis, Senior Statistician at the MRC Biostatistics Unit, University of Cambridge, said: “Our analysis highlights that in the absence of vaccination, any Delta outbreaks will impose a greater burden on healthcare than an Alpha epidemic. Getting fully vaccinated is crucial for reducing an individual’s risk of symptomatic infection with Delta in the first place, and, importantly, of reducing a Delta patient’s risk of severe illness and hospital admission.”
Limitations to the study included some demographic groups possibly being more likely to seek hospital care, which could have biased the results, and there may have been changes in hospital admission policy during the period of the study, although adjustment for demographics and calendar time should have minimised such bias. The authors also did not have access to information about patients’ pre-existing health conditions, which are known to affect the risk of severe illness from COVID. By using age, gender, ethnicity, and estimated level of socioeconomic deprivation, they were able to account for this.
If infected with the Delta variant, virus levels in fully vaccinated adults are as high as unvaccinated people, according to a UK analysis. This adds to evidence indicating that achieving herd immunity is unlikely.
While COVID vaccination has been shown to protect against hospitalisation and death, recent data shows that fully vaccinated people, when infected, carry the same levels of virus as those unvaccinated.
How this affects transmission remains unclear, the researchers have cautioned. “We don’t yet know how much transmission can happen from people who get COVID after being vaccinated – for example, they may have high levels of virus for shorter periods of time,” said Sarah Walker, a professor of medical statistics and epidemiology at the University of Oxford.
“But the fact that they can have high levels of virus suggests that people who aren’t yet vaccinated may not be as protected from the Delta variant as we hoped.”
Recently in the UK, positive tests, hospitalisations and deaths linked to COVID have been rising slowly. In South Africa, the third wave has still not yet abated, with a slight uptick in test positivity rates as noted by Ridhwaan Suliman at the CSIR.
The study, awaiting peer review, found vaccine effectiveness fell against Delta compared to Alpha.
The analysis did not directly investigate whether the lower level of vaccine protection against Delta affected jabs’ ability to prevent severe disease, but low rates of hospitalisation shows it is conferring protection.
The study compared the results of swabs taken from more than 384,500 adults between December 2020 and mid-May 2021, against those from 358,983 adults between mid-May and 1 August 2021 (when Delta became dominant).
The UK findings on peak virus levels after Delta infections in vaccinated people echoed data from a small study cited by the US Centers for Disease Control and Prevention (CDC) last month which prompted the agency to recommend continued mask wearing.
These datasets highlight that vaccinated individuals could still transmit COVID, and testing and self-isolation are still important to cut transmission, said Dr Koen Pouwels, a senior Oxford University researcher. This potential for transmission makes achieving herd immunity even more challenging, he suggested.
It had been hoped the vaccinated would protect the unvaccinated, added Prof Walker. “I suspect that, partly, the higher levels of virus that we’re seeing in these [Delta] infections in vaccinated people are consistent with the fact that unvaccinated people are just going to be at higher risk.”
Compared with AstraZeneca, two doses of the Pfizer vaccine has about 15% greater initial effectiveness against new infections, but its protection declines faster compared with two doses of AstraZeneca. Four to five months after being fully vaccinated, the vaccines’ effectiveness is the same, said Prof Walker.
“Even with these slight declines in protection against all infections and infections with high viral burden, it’s important to note that overall effectiveness is still very high because we were starting at such a high level of protection,” added Dr Pouwels.
MedPage Today investigates whether, according to some reports, there is in fact a difference in Delta symptoms compared to earlier variants.
Though hard data are lacking, ZOE study leader Tim Spector, MB, MSc, MD, of King’s College London, said his app’s data suggests the disease is “acting different now. It’s more like a bad cold in this younger population.”
Headache, followed by sore throat, runny nose, and fever were now the most common reported symptoms.
“All those are not the old classic symptoms,” Dr Spector said, adding that cough dropped to fifth place, and “we don’t even see loss of smell coming into the top 10 anymore. This variant seems to be working slightly differently.”
Dr Spector’s data however is only preliminary and comes from self-reports, and has not even been peer reviewed or published. However, other experts also have noticed a change in reported COVID symptoms.
One of those who has heard reports but is cautious about their interpretation is David Kimberlin, MD, a paediatric infectious diseases expert at the University of Alabama at Birmingham.
“I don’t think with what we know right now that we can conclude [Delta] is much different in terms of symptoms,” Dr Kimberlin told MedPage Today. “There have been some reports that it causes more cold-like illness, but so did the original COVID. I think we’ll know more over the next couple of months as we have the opportunity to realise the data.”
Purvi Parikh, MD, of NYU Langone in New York City and a spokesperson for the American College of Allergy, Asthma & Immunology, has also heard of COVID being mistaken for allergies, but allergies do not come with high fever, nausea, vomiting, or diarrhoea.
Other symptoms unlikely in allergy include myalgia and chills, said Alan Goldsobel, MD, of Allergy & Asthma Associates of Northern California, who is also a professor at Stanford University. Allergy indicators include the time of year (for those with seasonal allergy), as well as itching, he added.
Distinguishing COVID from common cold symptoms could be harder, Drs Parikh and Goldsobel noted.
“If you aren’t sure, I do recommend COVID testing,” Dr Parikh said.
In an article published in the South African Medical Journal, Shabir Madhi, Professor of Vaccinology at Wits, argues that COVID variants have made the initial goal of attaining herd immunity no longer feasible, even for well-resourced countries. However, vaccine protection against severe COVID seems a more realistic path to normalcy.
In low and middle income countries (LMICs), the official COVID case estimates are likely grossly underestimated, Prof Madhi writes, due to a lack of testing coverage. Even in South Africa, the true number of COVID cases is likely in the region of 10 times the 2.39 million recorded through testing. The true number of COVID-related deaths in India is also estimated as 3.4–3.9 million, again 10 times the official count, and in South Africa it is likely three times the official figure of 70 388 in July 2021.
While New Zealand researchers have suggested that COVID eradication is feasible, it is likely a very long term goal if at all attainable. The herd immunity goal can be considered with the equation (p1 = 1 – 1/R0), where p1 is the proportion of immune individuals who will also no longer transmit the virus, and R0 is the reproduction rate, ie the number of susceptible individuals a single infected person can further infect. However, this ignores key aspects of the virus.
The problem is that the proportion of people that would need to be immunised to achieve herd immunity was initially calculated at 67%, based on an assumed R0 of 3, derived from the Wuhan strain’s R0 of 2.5 to 4. However, the Delta variant has an R0 of 6, meaning that to reach herd immunity, 84% of the population would need to be vaccinated. In South Africa, this would be 100% of the population aged over 12.
The emergence of SARS-CoV-2 variants, especially the Beta variant with the E484K mutation, showed that existing vaccine protection, including the Pfizer variant, can be degraded to an extent.
Studies have strongly suggested that neutralising and antibody titers are associated with mild to moderate COVID protection, while protection from severe COVID may be mediated by T-cell immunity.
Real world data showed that in Israel, with a world best immunisation of 61.6% using the Pfizer vaccine which produces the greatest antibody response, herd immunity appeared to be successful until an outbreak of the more transmissible Delta variant combined with waning vaccine effectiveness.
However, in the UK, excess death data showed that, even with a resurgence of cases caused by the Delta variant, there was a significant decoupling of deaths from cases. This points to the effectiveness of vaccines in preventing severe illness, as opposed to reaching herd immunity.
Vaccine rollouts have therefore not interrupted COVID transmission. Prof Madhi concludes that, based on an estimated R0 of 6 for the Delta variant, “it is unlikely that any country could have a sustainable strategy for durable high level of protection against infection by the delta variant. Mutations of the SARS-CoV-2 genome are likely to continue resulting in enhanced transmissibility, infectiousness and resistance to neutralising activity.”
He observes that the “UK approach seemingly concedes that the goal of herd immunity, even in a highly resourced setting, is unattainable.”
He adds that aspiring to reach herd immunity by wealthy countries comes at the cost of exacerbating vaccine inequality, which he says “is immoral.” Antibody dynamics modelling suggests that a booster would be required every 2–3 years to protect against severe COVID, and every 6–9 months to protect against moderate disease. This is a challenging goal, and likely unattainable for most LMICs, especially given the slow rate of vaccination in those settings.
An 11-month-old girl in Houston, Texas, had to be airlifted to a hospital in a different city because no paediatric hospitals in Houston would accept her as a transfer patient.
“She needed to be intubated immediately because she was having seizures,” said Patricia Darnauer, the administrator for LBJ Hospital. “We looked at all five major paediatric hospital groups and none [had beds] available.”
The little girl will be receiving treatment at Baylor Scott & White McLane Children’s Medical Center some 220 kilometres away.
The situation is sad but not surprising for Dr Christina Propst, who is one of the most outspoken pediatricians in Houston. Ever since the pandemic began in the US, Dr Propst has encouraged masking, social distancing, and being cautious to anyone who would listen.
“The emergency rooms at the major children’s hospitals here in Houston, the largest medical center in the world, are extremely crowded,” said Dr Propst. “They are filling, if not full, as are the hospitals and intensive care units.”
Delta variant infecting more children Dr Propst and other clinicians ascribed the scarcity of paediatric beds, to the delta variant of COVID noticeably affecting more children, as well as being more transmissible. Texas Children’s Hospital has 30 children and adolescents hospitalised with COVID, compared to their January peak of 40.
However, the problem is worsened by widespread cases of Respiratory Syncytial Virus (RSV) in children. This is all taking place during the summer break for US schools, where doctors are used to injuries from playing outdoors.
Darnauer spoke of high numbers of patients at her hospital. “We are back beyond our pre-pandemic volumes at LBJ.”
Dr Propst advises mask wearing for those children not old enough for the vaccine, and she would also like to see Texas once again allow public schools to mandate masks. Unlike many other countries, COVID health regulations are largely up to individual states.
“If children are not masking in schools, it will be a major problem,” said Dr Propst.
She added that, even in normal times, the start of the school year generally causes a lot of germs to spread.
“It is typical that two weeks after school we see a great surge of strep and other sources of infection. We are bracing ourselves, not a question of when, it will be bad,” she said.
Researchers found that the L452R mutation of the SARS-CoV-2 spike protein, common to two mutant strains, the Epsilon and Delta, can evade cellular immunity through the human leukocyte (HLA) A24 and can increase viral infectivity.
The study, by researchers at the Kumamoto University and Weizmann Institute of Science, was published in the journal Cell Host & Microbe. It showed emerging mutations L452R and Y453F in the SARS-CoV-2 spike receptor-binding motif evade (HLA) A24-restricted cellular immunity. The L452R mutation also enhances spike stability, viral fusogenicity, and viral infectivity. Hence, the findings suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes.
Emerging variants of concern (VOC) may escape immune responses induced by vaccination or natural infection, threatening global vaccination efforts.
The first reported and well-studied mutant contains a D614G substitution in the spike (S) protein. The D614G mutation has recently been shown to enhance the binding affinity of SARS-CoV-2 to the ACE2 receptor. It is also more infectious and easily transmissible. However, there is no evidence suggesting that the D614G variant is tied to increased lethality.
At the end of 2020, the emergence of new variants was reported – the B.1.1.7 (Alpha), the B.1.351 (Beta), and the P.1 (Gamma) in the United Kingdom, South Africa, and Brazil, respectively. At the end of 2020, another lineage, the B.1.427 also called the CAL.20C, occurred in California, United States.
The Delta variant is becoming dominant globally, and has been linked to increased infectivity, transmissibility, severe illness, and even death.
Interestingly, mutated viruses are mainly due to error-prone viral replication, and the spread of new variants is linked to their escape from immune responses. SARS-CoV-2 mutants may resist neutralising mediated antibodies from COVID patients and vaccinated individuals.
Further, the new emerging variants may escape the cellular immunity conferred by cytotoxic T lymphocytes (CTLs), which recognise non-self epitopes present on virus-infected cells through the HLA class I molecules. This is called CTL-mediated antiviral immunity.
Human CTLs were recently shown to be able to recognise HLA-restricted SARS-CoV-2-derived epitopes. Also, the functionality of virus-specific cellular immunity correlates inversely with COVID-19 severity. Thus, CTLs play pivotal roles in controlling SARS-CoV-2 infection.
The team explored the potential emergence of SARS-CoV-2 mutants that can evade HLA-restricted cellular immunity in the current study.
The team used immunological experiments to show that an antigen to the SARS-CoV-2 spike protein is strongly recognised by the HLA-A24-restricted cellular immunity, which is often seen in Japanese people.
The team also conducted a large-scale sequence analysis of SARS-CoV-2 strains and demonstrated that HLA-A24 could recognize mutations in the spike protein region.
The team found that at least two naturally occurring substitutions in the receptor-binding motif of the SARS-CoV-2 spike protein, the L452R and Y453F identified in the B.1.427 and B1.1.298, can be resistant to the HLA-A24 cellular immunity.
The mutants also increase ACE2 binding affinity. Pseudovirus experiments show that L452R also enhances viral infectivity. The L452R mutation does so by stabilising the S protein, enhancing viral replication.
“These data suggest that HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes and that a further threat of the SARS-CoV-2 pandemic is its ability to escape cellular immunity,” the team concluded in the study.
Investigating the L452R mutation further should be a priority since it is borne by the highly infectious Delta variant.
