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A million deaths from coronavirus and so many unanswered questions: seven experts on their burning question

A million deaths from coronavirus and so many unanswered questions: seven experts on their burning question

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The pandemic has reached a grim milestone: one million people have now died of COVID-19, according to Worldometers.

On January 13, we published “Mystery China pneumonia outbreak likely caused by new human coronavirus” by Connor Bamford, a virologist at Queen’s University Belfast. Since then, we have published more than 3,500 articles on the now not-so-novel coronavirus, officially named Sars-CoV-2. Despite this huge output from the world’s leading experts, we have merely skimmed the surface of all there is to know about this perplexing pathogen. So much remains a mystery.

At this important juncture, we asked several experts from different fields what their burning question about the coronavirus is. Here is what they said:

Connor Bamford, Research Fellow, Virology, Queen’s University Belfast

How did Sars-CoV-2 enter the human population?

We must understand how Sars-CoV-2-like viruses jump into humans if we are to stop the next pandemic, as we do for influenza. Although originally thought to have emerged in the Huanan Seafood Wholesale Market in December 2019, the earliest patient had no link to the market suggesting the virus had emerged before then. How did this happen?


Read more: Mystery China pneumonia outbreak likely caused by new human coronavirus


Since the original investigations into the beginnings of Sars coronaviruses in 2002, horseshoe bats in south-east Asia have been implicated as the reservoir hosts, and a virus (RmYN02) that is extremely similar to Sars-CoV-2 has already been found in bats. However, similar viruses have also been found in pangolins, raising the possibility that Sars-CoV-2 may not have jumped directly from a bat.

Also, Sars-CoV-2 has already spread to cats, dogs, tigers and mink, and for Sars-CoV-1 (the virus that caused the 2002-04 Sars epidemic), farmed civet cats and raccoon dogs acted as intermediate hosts, bringing a bat virus into proximity to humans. It is possible that Sars-CoV-2 is a generalist virus, capable of spreading through a wide range of species.

With the increase in contact between humans and wildlife, zoonoses are becoming an ever-growing threat. We must be vigilant. An important step now is to figure out the events that led Sars-CoV-2 to go from bat to human.

A pangolin in a cage.
Similar viruses have been found in pangolins. Arief Budi Kusuma/Shutterstock

Sarah Caddy, Clinical Research Fellow, Viral Immunology, University of Cambridge

How can we tell if someone is protected from Sars-CoV-2?

The immune response to Sars-CoV-2 infection aims to eliminate the virus from the body. Many studies have carefully described the various stages of the immune response after initial infection, but we do not know which aspects of immunity are essential for preventing repeat infections. What are the relative roles of different types of antibodies, or the importance of different T cell subsets?

An important goal of Sars-CoV-2 immunological research is, therefore, to identify which immune component (or components) can show a person is protected from future infection. Such a marker would be termed a “correlate of protection”.

The ability to measure an accurate correlate of protection would be valuable for two reasons. First, it could tell us whether someone who has recovered from COVID-19 is likely to get re-infected. Second, identifying an easily measurable correlate of protection would be helpful for vaccine trials – it could speed up the evaluation of vaccine efficacy.

However, identifying good correlates of protection for other coronaviruses has proven notoriously difficult. Useful results have previously only been generated when volunteers were experimentally infected with viruses. The first human Sars-Cov-2 challenge studies are now due to begin early next year, so it is hoped that this will enable correlates of protection to be found more rapidly.


Read more: Coronavirus: why I support the world's first COVID vaccine challenge trial


Derek Gatherer, Lecturer and Fellow of the Institute for Social Futures, Lancaster University

How can we explain the extreme geographical variation in COVID-19 mortality rates?

Cumulative deaths from COVID-19 per million of population (dpm), are very unevenly distributed across Europe (see map below) ranging from 7dpm in Slovakia to 856dpm in Belgium. A wedge of relatively lightly affected countries extends from Finland southwards to the northern Balkans.

There are similar pockets of low COVID-19 mortality on other continents, notably south-east Asian countries. Could the populations of low mortality countries have some cross-immunity to Sars-CoV-2 generated by recent exposure to another coronavirus – the obvious candidates being the milder “common cold” coronaviruses: 229E, NL63, OC43 or HKU1?

A hint that this may be the case is provided by the observation that antibodies from the original 2003 Sars patients have some binding to coronaviruses 229E, NL63 and particularly OC43. But so little attention has been paid to seasonal coronaviruses, indeed, to seasonal non-flu respiratory infections, in general, that relevant clinical field data is extremely sparse and often old (for instance, one-third of residents of Hamburg had antibodies to coronavirus OC43 in 1975 or 58% of Hungarians sampled five years later).

We urgently need more lab studies to understand how much cross-immunity coronaviruses confer on each other, while population studies are needed to determine the prevalence of coronavirus antibodies, not just to Sars-CoV-2 but also its milder yet potentially significant cousins.

Serology – the study of antibody prevalence – has long been the Cinderella of virology compared with the more glamorous world of genome sequencing, but its significance and the consequences of its neglect are now becoming apparent.

Map of deaths per million in Europe, North Africa and the Middle East.
Deaths per million (dpm) of population in Europe and surrounding countries, as of mid-September 2020. Red: >200dpm; Blue: 100-200dpm; Black <100dpm. By San Jose - own map, based on the Generic Mapping Tools and ETOPO2 (annotated by DG). Data from WHO Epidemiological Update., CC BY-SA

Anne Moore, Senior Lecturer in Biochemistry and Cell Biology, University College Cork

For a vaccine, what does success look like in the short versus long term?

The endgame to the COVID-19 pandemic requires the identification and manufacture of a safe and effective vaccine and a subsequent global immunisation campaign.

Candidate Sars-CoV-2 vaccines were rapidly developed based on years of vaccine development efforts. The unprecedented and significant input of global funding into this pandemic vaccine effort can only buy so much time for trials to succeed or fail. A successful trial needs the virus to be circulating in the community so we can determine how many vaccinated people (versus those receiving a placebo) become infected.

Short-term success will show that a safe vaccine will provide at least 50% protection. And if we see short-term success, what does long-term success look like?

The biggest question is, what is the duration of protection? If it is short-lived, then how do we boost immunity back to protective levels? How do we figure this out without relying on a traditional empirical approach? If there isn’t short-term success, then how do we ensure that global commitment is maintained to prevent Sars-CoV-2 vaccines from ending up in the same situation as terminated vaccine efforts for Sars? There will be another pandemic; we need a long-term vision and commitment to have short-term future success.

Susan Michie and Robert West, Professors of Health Psychology, UCL

How can COVID-safe behaviour become embedded in people’s lives?

It looks as though COVID-19 will be with us for the foreseeable future. We will all have to adopt a range of behaviours to keep ourselves from getting infected or infecting others. We know what these are: the question is how they can become embedded in our lives?

The behaviours include keeping a greater physical distance from others; carrying a COVID kit (face mask, hand sanitiser and tissues) whenever we are outside the home; wearing a face mask properly in indoor public areas and storing or disposing of it safely; disinfecting hands and surfaces after possible contamination; catching coughs and sneezes in tissues; never touching our eyes, nose or mouth unless we know our hands are clean; avoiding or leaving unsafe situations, such as poorly ventilated indoor areas where there are lots of people; getting vaccinated; and staying at home and getting tested if we have symptoms.

A man and a woman sit apart on a park bench wearing face masks.
How can we get people to embed good behaviours in their lives. Kzenon/Shutterstock

The challenge is how to get these adopted at scale and maintained over time, in other words, embedded in people’s lives as routines and habits. This requires an understanding of what maintains and changes human behaviour. We need to equip people with the skills to develop routines that can become habits over time, provide the time and social and environmental support to achieve this and motivate them to use these opportunities.

David Hunter, Richard Doll Professor of Epidemiology and Medicine, University of Oxford

What is the full spectrum of health consequences of COVID-19 infection?

We now have good data on deaths from COVID-19 infection, showing an astonishing increase in risk of death with increasing age. This contrasts with the 2009 H1N1 flu epidemic, in which the aged were relatively less affected, and reminds us that we have a great deal more to learn about this virus.

While most of the focus has been on deaths, small studies of COVID-19 survivors discharged from hospital suggest that many do not return to their baseline health status. We know little about “long COVID” among those who did not require hospital admission, despite many individual reports of recurrent bouts of fever, fatigue, and a wide range of other symptoms.

Follow-up of COVID-19 patients suggest evidence of damage to the heart, lungs and other organs that may cause problems in the future, and there is some evidence that this may be true even among those with mild symptoms. Many viral infections can cause undiagnosed pathology, but severe long-term effects are relatively uncommon. If these effects are more common for COVID-19, however, then an exclusive focus on deaths means that we will not be considering the full costs of failing to control the epidemic, nor the full benefits of doing so.

Studies have started among patients after discharge from hospital. We urgently need well-controlled studies among the majority of those infected who did not need hospitalisation in case we are only seeing the tip of the COVID iceberg.

Anne Moore has received funding from HRB and Enterprise Ireland for vaccine research and from small and medium scale vaccine development companies in the EU and the USA.

Connor Bamford receives funding from Wellcome Trust and UKRI.

Derek Gatherer receives funding from the UK Economic & Social Research Council and the Ministry of Health of the Kingdom of Saudi Arabia.

Robert West is a participant in the behavioural subgroup of England's Scientific Advisory Group on Emergencies and the Independent Scientific Advisory Group on Emergencies. He is an unpaid director of a not-for-profit company that aims to support behaviour change for the public good.

Susan Michie receives grant funding from various research funding organisations

David Hunter and Sarah L Caddy do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.

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Analyst reviews Apple stock price target amid challenges

Here’s what could happen to Apple shares next.

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They said it was bound to happen.

It was Jan. 11, 2024 when software giant Microsoft  (MSFT)  briefly passed Apple  (AAPL)  as the most valuable company in the world.

Microsoft's stock closed 0.5% higher, giving it a market valuation of $2.859 trillion. 

It rose as much as 2% during the session and the company was briefly worth $2.903 trillion. Apple closed 0.3% lower, giving the company a market capitalization of $2.886 trillion. 

"It was inevitable that Microsoft would overtake Apple since Microsoft is growing faster and has more to benefit from the generative AI revolution," D.A. Davidson analyst Gil Luria said at the time, according to Reuters.

The two tech titans have jostled for top spot over the years and Microsoft was ahead at last check, with a market cap of $3.085 trillion, compared with Apple's value of $2.684 trillion.

Analysts noted that Apple had been dealing with weakening demand, including for the iPhone, the company’s main source of revenue. 

Demand in China, a major market, has slumped as the country's economy makes a slow recovery from the pandemic and competition from Huawei.

Sales in China of Apple's iPhone fell by 24% in the first six weeks of 2024 compared with a year earlier, according to research firm Counterpoint, as the company contended with stiff competition from a resurgent Huawei "while getting squeezed in the middle on aggressive pricing from the likes of OPPO, vivo and Xiaomi," said senior Analyst Mengmeng Zhang.

“Although the iPhone 15 is a great device, it has no significant upgrades from the previous version, so consumers feel fine holding on to the older-generation iPhones for now," he said.

A man scrolling through Netflix on an Apple iPad Pro. Photo by Phil Barker/Future Publishing via Getty Images.

Future Publishing&sol;Getty Images

Big plans for China

Counterpoint said that the first six weeks of 2023 saw abnormally high numbers with significant unit sales being deferred from December 2022 due to production issues.

Apple is planning to open its eighth store in Shanghai – and its 47th across China – on March 21.

Related: Tech News Now: OpenAI says Musk contract 'never existed', Xiaomi's EV, and more

The company also plans to expand its research centre in Shanghai to support all of its product lines and open a new lab in southern tech hub Shenzhen later this year, according to the South China Morning Post.

Meanwhile, over in Europe, Apple announced changes to comply with the European Union's Digital Markets Act (DMA), which went into effect last week, Reuters reported on March 12.

Beginning this spring, software developers operating in Europe will be able to distribute apps to EU customers directly from their own websites instead of through the App Store.

"To reflect the DMA’s changes, users in the EU can install apps from alternative app marketplaces in iOS 17.4 and later," Apple said on its website, referring to the software platform that runs iPhones and iPads. 

"Users will be able to download an alternative marketplace app from the marketplace developer’s website," the company said.

Apple has also said it will appeal a $2 billion EU antitrust fine for thwarting competition from Spotify  (SPOT)  and other music streaming rivals via restrictions on the App Store.

The company's shares have suffered amid all this upheaval, but some analysts still see good things in Apple's future.

Bank of America Securities confirmed its positive stance on Apple, maintaining a buy rating with a steady price target of $225, according to Investing.com

The firm's analysis highlighted Apple's pricing strategy evolution since the introduction of the first iPhone in 2007, with initial prices set at $499 for the 4GB model and $599 for the 8GB model.

BofA said that Apple has consistently launched new iPhone models, including the Pro/Pro Max versions, to target the premium market. 

Analyst says Apple selloff 'overdone'

Concurrently, prices for previous models are typically reduced by about $100 with each new release. 

This strategy, coupled with installment plans from Apple and carriers, has contributed to the iPhone's installed base reaching a record 1.2 billion in 2023, the firm said.

More Tech Stocks:

Apple has effectively shifted its sales mix toward higher-value units despite experiencing slower unit sales, BofA said.

This trend is expected to persist and could help mitigate potential unit sales weaknesses, particularly in China. 

BofA also noted Apple's dominance in the high-end market, maintaining a market share of over 90% in the $1,000 and above price band for the past three years.

The firm also cited the anticipation of a multi-year iPhone cycle propelled by next-generation AI technology, robust services growth, and the potential for margin expansion.

On Monday, Evercore ISI analysts said they believed that the sell-off in the iPhone maker’s shares may be “overdone.”

The firm said that investors' growing preference for AI-focused stocks like Nvidia  (NVDA)  has led to a reallocation of funds away from Apple. 

In addition, Evercore said concerns over weakening demand in China, where Apple may be losing market share in the smartphone segment, have affected investor sentiment.

And then ongoing regulatory issues continue to have an impact on investor confidence in the world's second-biggest company.

“We think the sell-off is rather overdone, while we suspect there is strong valuation support at current levels to down 10%, there are three distinct drivers that could unlock upside on the stock from here – a) Cap allocation, b) AI inferencing, and c) Risk-off/defensive shift," the firm said in a research note.

Related: Veteran fund manager picks favorite stocks for 2024

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Major typhoid fever surveillance study in sub-Saharan Africa indicates need for the introduction of typhoid conjugate vaccines in endemic countries

There is a high burden of typhoid fever in sub-Saharan African countries, according to a new study published today in The Lancet Global Health. This high…

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There is a high burden of typhoid fever in sub-Saharan African countries, according to a new study published today in The Lancet Global Health. This high burden combined with the threat of typhoid strains resistant to antibiotic treatment calls for stronger prevention strategies, including the use and implementation of typhoid conjugate vaccines (TCVs) in endemic settings along with improvements in access to safe water, sanitation, and hygiene.

Credit: IVI

There is a high burden of typhoid fever in sub-Saharan African countries, according to a new study published today in The Lancet Global Health. This high burden combined with the threat of typhoid strains resistant to antibiotic treatment calls for stronger prevention strategies, including the use and implementation of typhoid conjugate vaccines (TCVs) in endemic settings along with improvements in access to safe water, sanitation, and hygiene.

 

The findings from this 4-year study, the Severe Typhoid in Africa (SETA) program, offers new typhoid fever burden estimates from six countries: Burkina Faso, Democratic Republic of the Congo (DRC), Ethiopia, Ghana, Madagascar, and Nigeria, with four countries recording more than 100 cases for every 100,000 person-years of observation, which is considered a high burden. The highest incidence of typhoid was found in DRC with 315 cases per 100,000 people while children between 2-14 years of age were shown to be at highest risk across all 25 study sites.

 

There are an estimated 12.5 to 16.3 million cases of typhoid every year with 140,000 deaths. However, with generic symptoms such as fever, fatigue, and abdominal pain, and the need for blood culture sampling to make a definitive diagnosis, it is difficult for governments to capture the true burden of typhoid in their countries.

 

“Our goal through SETA was to address these gaps in typhoid disease burden data,” said lead author Dr. Florian Marks, Deputy Director General of the International Vaccine Institute (IVI). “Our estimates indicate that introduction of TCV in endemic settings would go to lengths in protecting communities, especially school-aged children, against this potentially deadly—but preventable—disease.”

 

In addition to disease incidence, this study also showed that the emergence of antimicrobial resistance (AMR) in Salmonella Typhi, the bacteria that causes typhoid fever, has led to more reliance beyond the traditional first line of antibiotic treatment. If left untreated, severe cases of the disease can lead to intestinal perforation and even death. This suggests that prevention through vaccination may play a critical role in not only protecting against typhoid fever but reducing the spread of drug-resistant strains of the bacteria.

 

There are two TCVs prequalified by the World Health Organization (WHO) and available through Gavi, the Vaccine Alliance. In February 2024, IVI and SK bioscience announced that a third TCV, SKYTyphoid™, also achieved WHO PQ, paving the way for public procurement and increasing the global supply.

 

Alongside the SETA disease burden study, IVI has been working with colleagues in three African countries to show the real-world impact of TCV vaccination. These studies include a cluster-randomized trial in Agogo, Ghana and two effectiveness studies following mass vaccination in Kisantu, DRC and Imerintsiatosika, Madagascar.

 

Dr. Birkneh Tilahun Tadesse, Associate Director General at IVI and Head of the Real-World Evidence Department, explains, “Through these vaccine effectiveness studies, we aim to show the full public health value of TCV in settings that are directly impacted by a high burden of typhoid fever.” He adds, “Our final objective of course is to eliminate typhoid or to at least reduce the burden to low incidence levels, and that’s what we are attempting in Fiji with an island-wide vaccination campaign.”

 

As more countries in typhoid endemic countries, namely in sub-Saharan Africa and South Asia, consider TCV in national immunization programs, these data will help inform evidence-based policy decisions around typhoid prevention and control.

 

###

 

About the International Vaccine Institute (IVI)
The International Vaccine Institute (IVI) is a non-profit international organization established in 1997 at the initiative of the United Nations Development Programme with a mission to discover, develop, and deliver safe, effective, and affordable vaccines for global health.

IVI’s current portfolio includes vaccines at all stages of pre-clinical and clinical development for infectious diseases that disproportionately affect low- and middle-income countries, such as cholera, typhoid, chikungunya, shigella, salmonella, schistosomiasis, hepatitis E, HPV, COVID-19, and more. IVI developed the world’s first low-cost oral cholera vaccine, pre-qualified by the World Health Organization (WHO) and developed a new-generation typhoid conjugate vaccine that is recently pre-qualified by WHO.

IVI is headquartered in Seoul, Republic of Korea with a Europe Regional Office in Sweden, a Country Office in Austria, and Collaborating Centers in Ghana, Ethiopia, and Madagascar. 39 countries and the WHO are members of IVI, and the governments of the Republic of Korea, Sweden, India, Finland, and Thailand provide state funding. For more information, please visit https://www.ivi.int.

 

CONTACT

Aerie Em, Global Communications & Advocacy Manager
+82 2 881 1386 | aerie.em@ivi.int


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US Spent More Than Double What It Collected In February, As 2024 Deficit Is Second Highest Ever… And Debt Explodes

US Spent More Than Double What It Collected In February, As 2024 Deficit Is Second Highest Ever… And Debt Explodes

Earlier today, CNBC’s…

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US Spent More Than Double What It Collected In February, As 2024 Deficit Is Second Highest Ever... And Debt Explodes

Earlier today, CNBC's Brian Sullivan took a horse dose of Red Pills when, about six months after our readers, he learned that the US is issuing $1 trillion in debt every 100 days, which prompted him to rage tweet, (or rageX, not sure what the proper term is here) the following:

We’ve added 60% to national debt since 2018. Germany - a country with major economic woes - added ‘just’ 32%.   

Maybe it will never matter.   Maybe MMT is real.   Maybe we just cancel or inflate it out. Maybe career real estate borrowers or career politicians aren’t the answer.

I have no idea.  Only time will tell.   But it’s going to be fascinating to watch it play out.

He is right: it will be fascinating, and the latest budget deficit data simply confirmed that the day of reckoning will come very soon, certainly sooner than the two years that One River's Eric Peters predicted this weekend for the coming "US debt sustainability crisis."

According to the US Treasury, in February, the US collected $271 billion in various tax receipts, and spent $567 billion, more than double what it collected.

The two charts below show the divergence in US tax receipts which have flatlined (on a trailing 6M basis) since the covid pandemic in 2020 (with occasional stimmy-driven surges)...

... and spending which is about 50% higher compared to where it was in 2020.

The end result is that in February, the budget deficit rose to $296.3 billion, up 12.9% from a year prior, and the second highest February deficit on record.

And the punchline: on a cumulative basis, the budget deficit in fiscal 2024 which began on October 1, 2023 is now $828 billion, the second largest cumulative deficit through February on record, surpassed only by the peak covid year of 2021.

But wait there's more: because in a world where the US is spending more than twice what it is collecting, the endgame is clear: debt collapse, and while it won't be tomorrow, or the week after, it is coming... and it's also why the US is now selling $1 trillion in debt every 100 days just to keep operating (and absorbing all those millions of illegal immigrants who will keep voting democrat to preserve the socialist system of the US, so beloved by the Soros clan).

And it gets even worse, because we are now in the ponzi finance stage of the Minsky cycle, with total interest on the debt annualizing well above $1 trillion, and rising every day

... having already surpassed total US defense spending and soon to surpass total health spending and, finally all social security spending, the largest spending category of all, which means that US debt will now rise exponentially higher until the inevitable moment when the US dollar loses its reserve status and it all comes crashing down.

We conclude with another observation by CNBC's Brian Sullivan, who quotes an email by a DC strategist...

.. which lays out the proposed Biden budget as follows:

The budget deficit will growth another $16 TRILLION over next 10 years. Thats *with* the proposed massive tax hikes.

Without them the deficit will grow $19 trillion.

That's why you will hear the "deficit is being reduced by $3 trillion" over the decade.

No family budget or business could exist with this kind of math.

Of course, in the long run, neither can the US... and since neither party will ever cut the spending which everyone by now is so addicted to, the best anyone can do is start planning for the endgame.

Tyler Durden Tue, 03/12/2024 - 18:40

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