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The tide of the COVID pandemic is going out – but that doesn’t mean big waves still can’t catch us

Omicron variants BA.4 and BA.5 are behind an increasing wave of infections in the UK. So what happens now?

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1 year ago

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In February, Prime Minister Boris Johnson said the public would have to get used to “living with COVID”, and announced the phasing out of all COVID-related restrictions over the following months. For many people, life since then has begun to return to something resembling normal.

Of course, there are some notable differences to pre-pandemic times, with a huge increase in working from home, and worryingly, many people still suffering from long COVID. But in most respects, you could be forgiven for thinking the pandemic was over.

Yet, over the past few weeks, there have been indications that a new wave of COVID is coming. The latest data from the Office for National Statistics’ (ONS) infection survey suggests that around 1.7 million people in the UK had COVID in the week ending June 18 – an increase of over 80% in the previous three weeks. Given the infection survey data is published with a delay of at least one week, these figures almost certainly underestimate the number of cases today.

COVID cases across the UK are rising

Line chart showing the estimated proportion of the population who would test positive for COVID by UK nation, showing a rise in recent weeks

One significant change in the last few months has been the end of free mass testing, which stopped in April. While this was inevitable at some stage because of the significant costs involved, it has taken away one of the UK’s key early warning systems.

In the past, an increase in positive tests in the community has been among the first signs that a new wave was coming. Without this, we may not realise the seriousness of a new variant until it’s already well established and people start turning up in hospitals in increasing numbers.

BA.4 and BA.5

Two new omicron variants, BA.4 and BA.5, are making up most of the infections in the current wave. Both of them are more transmissible than BA.2, the previously dominant variant. The evidence is still unclear on whether these variants are more or less severe than earlier forms of omicron, but the UK Health Security Agency (UKHSA) has classified them as “variants of concern”.

The latest hospital data shows that the number of new COVID patients (a combination of new admissions and people who catch COVID in hospital) in England is rising. In the most vulnerable age groups (65 and over) these figures are at almost two-thirds of the January peak seen during the initial omicron wave.

Rate of new COVID hospital admissions in England by age

A line chart showing the rate of new COVID admissions in England by age, indicating the recent rise across all age groups.

The situation is most acute in the north-west of England, where there are currently around 200 new COVID admissions every day. The north-west was also one of the worst affected parts of the country in terms of hospital admissions during the BA.1 and BA.2 waves.

The key question at this stage is how long this increase will carry on for. Without the early warning system of mass testing, it’s hard to know. Ultimately, this wave will start to subside when the growth advantage of the new variants comes up against the wall of immunity put up by vaccinations and previous infections.

Although we’ve done an excellent job of getting initial doses of COVID vaccines in arms in this country, a combination of immunity waning over time and the fact that newer variants are generally better at overcoming this immunity means that this wall is not as strong as it once was.

There are, however, a few reasons to be cautiously optimistic. South Africa, which has often been a bellwether for new variants, and where BA.4 and BA.5 were first identified, saw a much smaller wave as a result of these variants, with relatively few hospitalisations and deaths compared with previous waves. Portugal was one of the first European countries to see a BA.4/5 wave and, while it did see a significant increase in hospital admissions, case numbers now appear to have begun to fall without reaching the same severity as previous waves.

Some cause for concern

Even if the BA.4/5 wave isn’t as big as earlier waves, there are two major concerns. The first is the pressure already placed on the NHS, which has been stretched to the limit by the events of the last two years. Ambulance waiting times are at record levels, as are A&E waiting times, with over one-quarter of patients waiting more than four hours to be seen. This comes alongside a huge backlog of operations and other types of medical care that were delayed during the pandemic. Even a modest BA.4/5 wave is only going to add to these pressures.

The second issue is the growing number of people with long COVID. As many as 1.4 million people in the UK report symptoms that affect their day-to-day lives. And these figures are from May, before infections started rising again.

Read more: Long COVID: female sex, older age and existing health problems increase risk – new research

So what can we do? If you were taking precautions earlier in the year that you’ve since dropped, it would be wise to think about picking these up again. These include things like wearing a mask in crowded places, not meeting people if you have any symptoms, and testing if possible if you’re feeling unwell or are going to spend time with someone who is vulnerable. The UKHSA also suggest meeting other people outdoors or in well-ventilated places.

To help reinforce our protection against these new (and future) variants, there might be merit to bringing the autumn booster campaign, which will offer a fourth dose to people over 65 and other more vulnerable groups, forward. It may also be worthwhile to consider offering fourth doses to younger age groups soon, and additional boosters to the most vulnerable groups.

The tide of the pandemic is going out. But as with any receding tide, there will always be the odd bigger wave that can catch you out if you’re not careful. The end of mass testing and threats to the future of the invaluable ONS COVID infection survey make it more likely that these waves will catch us unprepared. The parlous state of the NHS and the threat of long COVID mean we shouldn’t be complacent to the potential threat of this, or subsequent waves, even as the tide continues to go out.

Colin Angus does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Rational design of mRNA nanovaccine for cancer immunotherapy

Messenger RNA (mRNA) vaccines are revolutionizing the therapy of cancer. It can be flexibly developed in a short period of time, allowing transient expression…

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20 mins ago

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October 16, 2023

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Messenger RNA (mRNA) vaccines are revolutionizing the therapy of cancer. It can be flexibly developed in a short period of time, allowing transient expression of multiple antigens for safe and efficient immunization. A diversity of mRNA vaccines is being explored in clinic to benefit patients with cancer. However, the translation of mRNA vaccines is still hampered by multistage delivery barriers before initiating strong immunity, including rapid clearance, poor targeting to lymphoid organs and dendritic cells, catalytic hydrolysis and weak capability to pass through phospholipid bilayers. Besides, vaccination with mRNA alone can barely induce strong immune responses in the absence of adjuvants. It remains challenging to improve cytosolic delivery of mRNA and promote its in vivo vaccination efficacy in combination with adjuvants.

Credit: ©Science China Press

Messenger RNA (mRNA) vaccines are revolutionizing the therapy of cancer. It can be flexibly developed in a short period of time, allowing transient expression of multiple antigens for safe and efficient immunization. A diversity of mRNA vaccines is being explored in clinic to benefit patients with cancer. However, the translation of mRNA vaccines is still hampered by multistage delivery barriers before initiating strong immunity, including rapid clearance, poor targeting to lymphoid organs and dendritic cells, catalytic hydrolysis and weak capability to pass through phospholipid bilayers. Besides, vaccination with mRNA alone can barely induce strong immune responses in the absence of adjuvants. It remains challenging to improve cytosolic delivery of mRNA and promote its in vivo vaccination efficacy in combination with adjuvants.

In past decades, a huge number of nanocarriers have been reported to promote transfection efficacy of nucleic acid drugs or deliver drugs to lymph nodes. These studies provide valuable features including size, surface charge, modification, responsiveness, components and cytotoxicity to achieve the goal for lymph nodes drainage or cytosolic access. Machine learning techniques provide powerful tools for exploring the physicochemical characteristics and biological features of these nanoparticles, and facilitate the design of nanocarriers with high efficiency. Commonly, machine learning models were trained, selected and optimized with high quality and massive datasets from computations and high-throughput experimental data, and in turn guide the rational design, screening and optimization of nanocarriers. By leveraging existing nanocarriers’ databases, machine learning may provide insights into rational design of nanovaccines with high efficiency.

In a new research article published in the Beijing-based National Science Review, scientists from the Chinese Academy of Sciences and Shanghai Jiao Tong University used machine learning to guide the rationalized design of mRNA nanovaccines. This study identified the key parameters of nanovaccines for efficient delivery of mRNA and cGAMP based on a machine learning model from the Nanocarrier Database (2010-2021, web of science). The mRNA/cGAMP nanocomplexes based on phenylboronic acid grafted polyethyleneimine were prepared and further encapsulated with anionic lipids to obtain the nanovaccine. (1) The negative surface charge of the nanovaccine reduces the interaction with negatively charged glycosaminoglycans in matrix and improves accumulation in the lymph nodes. (2) The nanovaccine, after being internalized by the antigen-presenting cells (APCs) in the lymph nodes, promotes the release of mRNA and cGAMP from the endosomes to the cytoplasm, which activates the STING pathway and induces the presentation of tumor antigens. (3) The activation of STING pathway promotes the release of IFN-I, which activates T cell immune response to kill tumor cells and inhibit tumor growth and metastasis. Compared with the mRNA alone, the therapeutic strategy based on this nanovaccine demonstrated stronger anti-tumor effects in melanoma and colorectal cancer models.

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See the article:

STING agonist-boosted mRNA immunization via intelligent design of nanovaccines for enhancing cancer immunotherapy

https://doi.org/10.1093/nsr/nwad214

Journal

National Science Review

DOI

10.1093/nsr/nwad214

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Can ChatGPT diagnose your condition? Not yet

A research group led by Tokyo Medical and Dental University (TMDU) finds that when common orthopedic symptoms are given, ChatGPT’s diagnosis and recommendations…

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20 mins ago

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October 16, 2023

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A research group led by Tokyo Medical and Dental University (TMDU) finds that when common orthopedic symptoms are given, ChatGPT’s diagnosis and recommendations are inconsistent

Credit: Division of Medical Design Innovations, TMDU

A research group led by Tokyo Medical and Dental University (TMDU) finds that when common orthopedic symptoms are given, ChatGPT’s diagnosis and recommendations are inconsistent

Tokyo, Japan – ChatGPT, a sophisticated chatbot driven by artificial intelligence (AI) technology, has been increasingly used in health care contexts, one of which is assisting patients in self-diagnosing before seeking medical help. Although it seems very useful at first glance, AI may cause more harm than good to the patient if it is not accurate in its diagnosis and recommendations. A research team from Japan and the United States recently found that the precision of ChatGPT’s diagnoses and the degree to which it recommends medical consultation require further development.

In a study published in September, the multi-institutional research team led by Tokyo Medical and Dental University (TMDU) evaluated the accuracy (percentage of correct responses) and precision of ChatGPT’s response to five common orthopedic diseases (including carpal tunnel syndrome, cervical myelopathy, and hip osteoarthritis) because orthopedic complaints are very common in clinical practice and comprise up to 26% of the reasons why patients seek care. Over a 5-day course, each of the study researchers submitted the same questions to ChatGPT. The reproducibility between days and researchers was also calculated, and the strength of the recommendation that the patient seek medical attention was evaluated.

“We found that accuracy and reproducibility of ChatGPT’s diagnosis are not consistent over the five conditions. ChatGPT’s diagnosis was 100% accurate for carpal tunnel syndrome, but only 4% for cervical myelopathy,” says lead author Tomoyuki Kuroiwa. Additionally, reproducibility between days and researchers varied from “poor” to “almost perfect” among the five conditions even though researchers entered the same questions every time.

ChatGPT was also inconsistent in recommending medical consultation. Although almost 80% of ChatGPT’s answers recommended medical consultation, only 12.8% included a strong recommendation as set by the study standards. “Without direct language, it is possible that the patient is left confused after self-diagnosis, or worse, experience harm from a misdiagnosis,” says Kuroiwa.

This is the first study to evaluate the reproducibility and degree of the medical consultation recommendation of ChatGPT’s ability to self-diagnose. “In its current form, ChatGPT is inconsistent in both accuracy and precision to help patients diagnose their disease,” explains senior author Koji Fujita. “Given the risk of error and potential harm from misdiagnosis, it is important for any diagnostic tool to include clear language alerting patients to seek expert medical opinions for confirmation of a disease.”

The researchers also note some limitations of the study including the use of questions simulated by the research team and not patient-derived questions; focusing on only five orthopedic diseases; and using only ChatGPT. While it is still too early to use AI intelligence for self-diagnosis, the training of ChatGPT on diseases of interest could change this. Future studies can help shed light on the role of AI as a diagnostic tool.

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The article, “The potential of ChatGPT as a self-diagnostic tool in common orthopedic diseases: exploratory study,” was published in Journal of Medical Internet Research at DOI: 10.2196/47621

Journal

Journal of Medical Internet Research

DOI

10.2196/47621

Article Title

The Potential of ChatGPT as a Self-Diagnostic Tool in Common Orthopedic Diseases: Exploratory Study

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Ancient Egypt had far more venomous snakes than the country today, according to our new study of a scroll

Ancient texts are still teaching us new things about the prevalence of wildlife.

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50 mins ago

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October 16, 2023

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How much can the written records of ancient civilisations tell us about the animals they lived alongside? Our latest research, based on the venomous snakes described in an ancient Egyptian papyrus, suggests more than you might think. A much more diverse range of snakes than we’d imagined lived in the land of the pharaohs – which also explains why these Egyptian authors were so preoccupied with treating snakebites!

Like cave paintings, texts from early in recorded history often describe wild animals the writers knew. They can provide some remarkable details, but identifying the species involved can still be hard. For instance, the ancient Egyptian document called the Brooklyn Papyrus, dating back to around 660-330BC but likely a copy of a much older document, lists different kinds of snake known at the time, the effects of their bites, and their treatment.

As well as the symptoms of the bite, the papyrus also describes the deity associated with the snake, or whose intervention might save the patient. The bite of the “great snake of Apophis” (a god who took the form of a snake), for example, was described as causing rapid death. Readers were also warned that this snake had not the usual two fangs but four, still a rare feature for a snake today.

The venomous snakes described in the Brooklyn Papyrus are diverse: 37 species are listed, of which the descriptions for 13 have been lost. Today, the area of ancient Egypt is home to far fewer species. This has led to much speculation among researchers as to which species are being described.

The four-fanged snake

For the great snake of Apophis, no reasonable contender currently lives within ancient Egypt’s borders. Like most of the venomous snakes that cause the majority of the world’s snakebite deaths, the vipers and cobras now found in Egypt have just two fangs, one in each upper jaw bone. In snakes, the jaw bones on the two sides are separated and move independently, unlike in mammals.

The nearest modern snake that often has four fangs is the boomslang (Disopholidus typus) from the sub-Saharan African savannas, now only found more than 400 miles (650km) south of present-day Egypt. Its venom can make the victim bleed from every orifice and cause a lethal brain haemorrhage. Could the snake of Apophis be an early, detailed description of a boomslang? And if so, how did the ancient Egyptians encounter a snake that now lives so far south of their borders?

Representation of Apep (Apophis) in Ancient Egyptian wall painting. Note resemblance to boomslang (above).

To find out, our masters student Elysha McBride used a statistical model called climate niche modelling to explore how the ranges of various African and Levantine (eastern Mediterranean) snakes have changed through time.

Niche modelling reconstructs the conditions in which a species lives, and identifies parts of the planet that offer similar conditions. Once the model has been taught to recognise places that are suitable today, we can add in maps of past climate conditions. It then produces a map showing all the places where that species might have been able to live in the past.

On the trail of ancient snakes

Our study shows the much more humid climates of early ancient Egypt would have supported many snakes that don’t live there today. We focused on ten species from the African tropics, the Maghreb region of north Africa and the Middle East that might match the papyrus’s descriptions. These include some of Africa’s most notorious venomous snakes such as the black mamba, puff adder and boomslang.

We found that nine of our ten species could probably once have lived in ancient Egypt. Many could have occupied the southern and southeastern parts of the country as it then was - modern northern Sudan and the Red Sea coast. Others might have lived in the fertile, vegetated Nile valley or along the northern coast. For instance, boomslangs might have lived along the Red Sea coast in places that 4,000 years ago would have been part of Egypt.

Similarly, one entry of the Brooklyn Papyrus describes a snake “patterned like a quail” that “hisses like a goldsmith’s bellows”. The puff adder (Bitis arietans) would fit this description, but currently lives only south of Khartoum in Sudan and in northern Eritrea. Again, our models suggest that this species’ range would once have extended much further north.

Read more: Wildlife wonders of Britain and Ireland before the industrial revolution – my research reveals all the biodiversity we've lost

Since the period we modelled, a lot has changed. Drying of the climate and desertification had set in about 4,200 years ago, but perhaps not uniformly. In the Nile valley and along the coast, for instance, farming and irrigation might have slowed the drying and allowed many species to persist into historical times. This implies that many more venomous snakes we only know from elsewhere might have been in Egypt at the time of the pharaohs.

Our study shows how enlightening it can be when we combine ancient texts with modern technology. Even a fanciful or imprecise ancient description can be highly informative. Modelling modern species’ ancient ranges can teach us a lot about how our ancestors’ ecosystems changed as a result of environmental change. We can use this information to understand the impact of their interactions with the wildlife around them.

Wolfgang Wüster receives funding from the Leverhulme Trust.

Isabelle Catherine Winder does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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