The Elephant and the Virus

With respect to the coronavirus pandemic, I am concerned about India. Given their population density and more than 1.3 billion residents, the virus situation there could soon make what’s happening in Italy and Spain look tame.

Earlier this week India was reporting only 129 infections and 2 deaths. Today it’s at 249 cases and 5 deaths. While those numbers may seem ridiculously low relative to India’s population, they appear to be starting out much the same as any other country.

While mathematical illiterates might dismiss these numbers as trivial, fortunately India’s Prime Minister and their National Security Council are paying serious attention to what’s happening elsewhere. Consequently, India has been on lockdown since March 18 and plans to continue through March 31. I think they’ll need significantly longer, but it’s good to see them taking this step.

India’s director of the Center for Disease Dynamics, Economics, and Policy, Dr. Ramanan Laxminarayan, warns that India may have to deal with a tsunami of about 300 million coronavirus cases. He estimates that India has 70K-100K ICU beds in the entire country. Note that the total ICU beds in the USA are also estimated to be in this same range, and the USA is already on a path to overflow these beds in the weeks ahead but with a billion fewer people.

One of my concerns is that India may be severely under-testing. So I’d pay a lot more attention to the death count than to the infections reported and watch what that number does in the weeks ahead. When testing is weak, deaths are more likely to be noticed than infections, especially as more people who are struggling to breathe seek medical care.

If you look at other countries with death totals close to India’s, many are reporting significantly more infections. Austria, Denmark, Norway, Malaysia, and Portugal all report 3-7 coronavirus deaths so far, and their reported infections range from 1020 to 2491. Now there are lots of other countries with similar death totals but with lower infection counts closer to India’s, and by and large these are countries where testing appears to be very limited.

Since the death numbers are so low, they may not be significant right now, but this is something for people in India to watch carefully in the weeks ahead.

Note that just 25 days ago on February 24, Italy was at 229 reported cases and 7 deaths, which is very close to where India is today. Now Italy is at 47,021 cases and 4032 deaths – 5986 of those cases and 627 of those deaths in the last 24 hours – and still rising faster and faster. Also note that India’s population is 22 times the size of Italy’s.

That said, I am seeing solid evidence that India is being a lot more intelligent and cautious about this virus than many other countries. They’re way ahead of the USA, getting to lockdown much sooner. In the U.S. the inevitable lockdown is unfolding on a state by state and even city by city basis. California just went into statewide lockdown last night. Other U.S. states will soon follow. Slow-rolling a countrywide lockdown instead of going there immediately means more people will suffer and die, including more medical staff. This should be coordinated at the federal level like India has done. The leadership void at the top means that state governors have to step up now more than ever to help compensate as best they can.

Many countries are seeing their infections and deaths ramp up tremendously, and this will go considerably higher in the weeks ahead as we go higher up the exponential growth curve. In time this will reveal the price each country pays for underestimating this virus.

While practicing social distancing and going into lockdown are key steps that will save many lives, abundant testing is crucial as well to understand what’s happening and to know if measures are being effective or if more is needed.

One key risk I’m seeing in India is overconfidence. This is an easy trap to fall into when the numbers are still low and especially when you’re already in lockdown and practicing social distancing. While it’s commendable that India has implemented serious measures sooner than most, there’s still a potent risk of falling into the overconfidence trap by assuming that it’s enough.

Moreover, compliance can be a real problem too. In my home state of Nevada, we’re under partial measures for at least 30 days. The hotels and casinos are closed statewide, which hasn’t happened since President Kennedy’s assassination in 1963, and that was only one day of closure back then. As extreme as this may seem, especially for the 206K casino employees who are out of work now, we’re still just stair-stepping our way towards a full lockdown. Meanwhile it’s being reported that non-essential businesses remain open, including some restaurants and retail stores. Some businesses are still telling their employees to come into work, even where people must work in close proximity to each other, and the employees feel they have to show up because they don’t want to lose their jobs. Some will lose their lives because of it. So the existing directives aren’t being complied with yet. In fact, the Vegas police have been getting so many phone calls about these violations of the Governor’s order that they’re telling people to stop calling to report such businesses.

Even with really good government measures in place, the practical reality of this situation is that when we think we’re doing enough, it’s more likely that we’re being overconfident and not being cautious enough.

The challenge this virus presents is that in order to get aligned with its behavior and respond appropriately, we must consistently do more than we think is necessary, which is an uncomfortable place to be. When we think we’ve finally implemented what’s necessary and can settle in at that level because surely it’s enough now, we’ve succumbed to overconfidence, and the virus will make additional gains because of that, including overwhelming hospitals and medical staff.

So in this case, it’s good to feel like you’re overdoing it by being more cautious than you think is necessary. It’s also good to feel like you’re taking more social risk than usual to rein in sociopathic behavior.

The most caring and compassionate people I know are feeling very socially uncomfortable these days; they’re all getting some social blowback because they’re stretching themselves to do what it takes to save lives and reduce suffering. They can see plain as day that it’s the right response under the circumstances though. When they get overwhelmed, they do whatever they need to do to recharge, to accept reality, and to forgive, and they go right back into the fray. Heroes all of them. The people who’s lives they save may never know it, and the work they’re doing is largely thankless, but I want them to know that I personally appreciate and applaud their efforts.

Under current circumstances, the torrent of vitriol that was unleashed upon the Floridiot Governor for permitting spring breakers to crowd the beaches earlier this week was an appropriate response to sociopathic behavior. And it was effective. That Governor quickly caved to the onslaught of social and political pressure and shut those beaches down.

At the national and individual levels, we all need to stretch ourselves further into the zone of discomfort. For the next several weeks at least, we need to bid enoughness adieu and embrace the discomfort of toomuchness.

Perhaps India has achieved enoughness in their response, which may impress some humans but isn’t enough to earn the respect of this virus. This virus eats American enoughness for breakfast, Spanish enoughness for lunch, and Italian enoughness for dinner. And presently it seems to be developing an appetite for British enoughness at tea time. Along with the rest of us, India’s challenge is to push further into toomuchness and stay there for a while. Maybe they can teach this virus a thing or two about fasting.

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Health24.com | Preemies’ impaired immune systems quickly catch up

Premature infants’ immune systems develop at a rate similar to full-term infants, a new study finds.

British researchers tracked immune system development in babies born before 32 weeks, including identifying different immune cell populations and the types of bacteria present in stool samples.

All of the preemies’ immune systems progressed similarly as they got older, regardless of how early they were born.

Babies born after the shortest gestation – earlier than 28 weeks – had a greater degree of immune system progress over a similar time period than those who spent more time in the womb.

Environment after birth

The findings suggest that preterm and full-term infants’ immune system development follows a set pattern after birth, according to the study authors.

“These data highlight that the majority of immune development takes place after birth and, as such, even those babies born very prematurely have the ability to develop a normal immune system,” said study author Deena Gibbons, a lecturer in immunology at King’s College London.

Infection and related complications are significant causes of death among premature babies, but researchers said there is limited understanding of how their immune systems develop and how that can be influenced by the environment after birth.

Researchers also found that some preterm babies who developed infection had reduced CXCL8 (interleukin 8)-producing T-cells at birth. T-cells play a key role in immune response to infection.

Improving outcomes

The finding suggests that infants at risk of infection and complications in the first few months of life could be identified shortly after birth, which may improve their outcomes.

“We are continuing to study the role of the CXCL8-producing T-cell and how it can be activated to help babies fight infection,” Gibbons said in a university news release. “We also want to take a closer look at other immune functions that change during infection to help improve outcomes for this vulnerable group.”

The findings were published in the journal Nature Communications.

Image credit: iStock

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Health24.com | The new coronavirus: The urgent, but long race for a vaccine

The virus which causes Coronavirus Disease 2019 (Covid-19), has been spreading rapidly globally, putting pressure on vaccine and drug developers to invent new products to stop infections and save lives.

The desperate need for a vaccine to curb the respiratory infection is driving research and development, with more than 24 companies estimated to be in the race. Vaccines are entering human clinical trials much faster than ever before. 

Apart from the life-saving impact of an effective Covid-19 virus vaccine, these new technologies and approaches are expected to also inform future scientific research on badly needed vaccines for HIV and tuberculosis. 

First vaccine trial underway

In the first human clinical trial to protect against the Covid-19 virus, four volunteers were injected with a candidate vaccine in Seattle in the United States earlier this week, according to the Kaiser Permanente Washington Health Research Institute. Start-up biotechnology company Moderna Inc. set a drug industry record by identifying their candidate vaccine in only 42 days after the Covid-19 virus was sequenced. 

In total, 45 young, healthy men and women, between 18 and 55 years, enrolled in the US National Institutes of Health-funded clinical trial. The volunteers will get different doses of the vaccine in order to establish the safety of different doses.

The objective of this first trial is only to find out if the potential vaccine called mRNA 1273 is safe and does not have any serious adverse events (side effects). If things go well, further larger trials will be conducted. 

Even if all goes to plan, the vaccine will only be ready for use in 12 to 18 months.

The vaccine is made using a new process that is much faster than older methods. It doesn’t contain any part of the virus itself as is the case in most vaccines. Instead, it includes a short segment of so-called messenger RNA that is made in a lab and is designed to stimulate human cells to produce a viral protein, to which the body would develop a protective antibody response. 

Other contenders 

Another company called Inovio Pharmaceuticals has a DNA vaccine it says can generate protective antibodies to shield people from infection with coronavirus. Human testing of their vaccine called INO_4800 is expected to start later this year. Development from there is likely to follow a similar 12 to 18 month timeline.

Researchers at the Precision Vaccines Programme (PVP) at America’s Boston Children’s Hospital are on the frontline of developing a vaccine which specially targets older populations.

According to the hospital’s website, the current antigen used for vaccine development is the coronavirus spike protein, named because it sits on top of the spike of a coronavirus particle. This is the part of the virus that the immune system “remembers”. Vaccine-induced antibodies, made by the immune system against the spike protein, can prevent infection.

PVP’s strategy, it says, is to combine the coronavirus spike protein with adjuvants: small molecules added to a vaccine to boost the recipient’s immune response. Adjuvants can be crucial for getting a stronger, longer-lasting, broader immune response, especially among those with weakened immunity, like the elderly.

The Gates Foundation, a major medical research funder, is spreading its bets among several cutting-edge vaccine platforms, including those using genetic material and the ones based on synthetic biology that hold promise. 

Relevance for potential HIV and TB vaccines

Professor Willem Hanekom, Director of the African Health Research Institute (AHRI) in KwaZulu-Natal (KZN) said traditional vaccines have taken a long time to be developed. For example, the new M72 vaccine in development to fight TB has taken about 15 years to reach currently planned efficacy trials. The trial of the M72 subunit vaccine developed by GSK, contains a fragment of the bacterium to stimulate an immune response and has been the only new vaccine, so far, showing protection against TB disease in vaccine trials.

Hanekom says the new approaches will “undoubtedly” be used in vaccine development for HIV and TB but there are still some significant “unknowns” which complicate things. “For some viruses like Ebola and Covid-19, it may be easier to predict which proteins need to be included in the vaccine, as immune response to these proteins is likely to be associated with protection.” 

As with the Moderna Inc. coronavirus candidate, he says, “You can make a piece of synthetic RNA which encodes for a protein that elicits an immune response, associated with protection.” The same, he says, could be achieved with the HI virus and the TB bacterium if “we knew which proteins are linked to protection, but we don’t have a full understanding of this at the moment”. So, while these technologies can be used it’s not as simple with HIV and TB.

For Hanekom, the number one research question is what impact the new coronavirus will have on immuno-compromised South Africans. AHRI does research on prevention of HIV and TB transmission and non-communicable diseases in Somkhele, in northern KZN, which has a high HIV prevalence of 38%. Would people with HIV do worse if infected with the novel coronavirus?

He says surveillance needs to be done to find out. In comparison to Italy whose demographics are skewed toward older people, South Africa with a younger population may be at an advantage when it comes to coronavirus morbidity and mortality. The WHO has said that infected elderly people are most at risk of dying as well as those with underlying chronic illnesses.

Regarding TB Hanekom says, people with chronic lung disease are at risk of developing more severe Covid-19. “We don’t yet know if people with lung disease associated with current or previous TB are at greater risk of Covid-19, but it is likely,” he said.

‘South Africa needs a break’

Heroes Director of the Desmond Tutu HIV Centre, Professor Linda-Gail Bekker, says unlike SARS which came and went, the new coronavirus is likely to be endemic and there will be a need for a vaccine in the short and long term. She said HIV is “tricky”, but new technologies are already opening up new possibilities. Johnson and Johnson’s so-called HIV mosaic concept trial is based on a synthetic approach. 

Meanwhile scientists in Australia have reported that medicines (not vaccines) to treat HIV and malaria could be used to tackle coronavirus. Infectious disease experts at the University of Queensland in Brisbane report that Chloroquine, an anti-malarial drug, and an HIV-suppressing combination lopinavir/ritonavir have both shown promising results in human tests and made the virus “disappear” in infected patients.

Bekker said a good research question would be to see if Chloroquine can be used prophylactically and as treatment for people co-infected with HIV and the Covid-19 virus. 

In addition, she said there is also discussion in South Africa on being part of the pharmaceutical company Gilead’s trial of the experimental medicine remdesivir, an intravenous treatment, which has already been used to treat an infected patient in the United States. Gilead is recruiting around 1 000 patients with Covid-19 for large-scale studies in Asia, to find out whether multiple doses of remdesivir can reverse infection.

Bekker praised volunteers in current and future clinical trials for a coronavirus vaccine and treatment as “heroes”. “We are holding our breath that all measures will flatten the infection curve. “South Africa needs a break!”

*Adele Baleta is an independent science writer, media consultant and facilitator

*This article was produced for Spotlight – health journalism in the public interest.

Image credit: iStock

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Virus vs Culture

Some people may be surprised to learn that most viruses don’t have much respect for the following:

  • Optimism, blind or otherwise
  • Fearlessness
  • Mathematical illiteracy
  • Feelings
  • Opinions
  • Conspiracies
  • Spring break
  • Jobs
  • Economics
  • Lying
  • Denial
  • Ignorance
  • Irrationality
  • Insults
  • Politics
  • Excuses
  • Incompetence
  • Toilet paper abundance

Relative to human beings, who may be compassionate and understanding about some of the above, the behavior of viruses could be considered by some to be borderline rude.

For example, the recent coronavirus has shown a most unpleasant disregard for Italian culture and optimism, now claiming 3405 lives in Italy (more than 900 of them in the past 2 days) and infecting more than 41K. It seems particularly obnoxious in its treatment of Italian medical personnel, infecting more than 2600 of them so far. In response the Italians have opted to accelerate the graduation of thousands of medical students, so they can join the fight against the virus months ahead of schedule. So far the virus hasn’t revealed what it thinks about that when asked.

Many Spaniards noted how the virus treated the Italians and assumed it would treat them quite differently. The virus, however, seems to find Spanish bodies at least as hospitable as its Italian hosts, which may be why it proceeded to infect 18K and to claim 831 lives in Spain, promising more to follow.

The virus was nonplussed when Iran’s Deputy Health Minister denied its potential, even while he was coughing quite a bit due to being infected himself. Shortly thereafter, the virus proceeded to claim the lives of dozens of Iranian government officials. Presently it would appear that the virus considers more of the same to be a good use of its time.

Iranians have been sharing videos of bodies piling up and being placed into new mass graves – literally with a twist of lime. Iranian locals have shared that the bodies they’ve counted in certain limited areas exceed the official totals being reported for the entire country (currently 18K+ cases and 1284 deaths). Some estimate that Iran is heading towards millions of deaths, which may be impressive numbers for humans but not particularly so for the virus. It’s been said that in private, the virus considers the number 1,000,000 about as daunting as most humans would find the number 6. So not very.

Presently the virus is finding American culture most receptive to its propagation, having just finished its initial tour of all 50 states. So far it has infected 14K and claimed 214 American lives. It seems to be developing a fondness for American irrationality, although some say that it may be slightly disappointed that its initially pleasant spring break in Florida is being cut short.

Additionally the virus is warming up to the culture of Brazil, noting the welcoming words of Brazil’s President like “hysteria” and “fantasy.” There the virus is still working on its first 1000 infections, which it expects to surpass sometime this weekend.

The virus doesn’t seem to mind all the recent testing, having passed such tests nearly 250K times thus far. It considers the 10K lives it has recently claimed a modest achievement, while noting that reaching 100K from this point should take even less effort.

The virus has been quietly observing increased chatter about social distancing, which it considers a non-issue as long as the humans don’t actually practice it well. While normally possessing a rather reserved demeanor, the virus does appear to elevate its contentment slightly above baseline levels when humans spend more time discussing their economic concerns.

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Maize, not metal, key to native settlements’ history in NY

New Cornell University research is producing a more accurate historical timeline for the occupation of Native American sites in upstate New York, based on radiocarbon dating of organic materials and statistical modeling.

The results from the study of a dozen sites in the Mohawk Valley were recently published in the online journal PLoS ONE by Sturt Manning, professor of classical archaeology; and John Hart, curator in the research and collections division of the New York State Museum in Albany.

The findings, Manning said, are helping to refine our understanding of the social, political and economic history of the Mohawk Valley region at the time of early European intervention.

The work is part of the Dating Iroquoia Project, involving researchers from Cornell, the University of Georgia and the New York State Museum, and supported by the National Science Foundation.

The new paper continues and expands upon research on four Iroquoian (Wendat) sites in southern Ontario, published by the project team in 2018. Using similar radiocarbon dating and statistical analysis methods, the 2018 findings also impacted timelines of Iroquoian history and European contact.

“The Mohawk case was chosen because it is an iconic series of indigenous sites and was subject to one of the first big dating efforts in the 1990s,” said Manning. “We have now examined a southern Iroquois (Haudenosaunee) case as well as a northern Iroquois (Wendat) case, and we again find that the previous dating scheme is flawed and needs revision.”

The Mohawk and Hudson river valleys were key inland routes for Europeans entering the region from the coast in the 16th and early 17th centuries. Colonization of the new world enriched Europe — Manning has described this period as “the beginning of the globalized world” — but brought disease and genocide to indigenous peoples, and their history during this time is often viewed in terms of trade and migration.

The standard timeline created for historical narratives of indigenous settlement, Manning noted, has largely been based on the presence or absence of types of European trade goods — e.g., metal items or glass beads. Belying this Eurocentric colonial lens, trade practices differed from one native community to another, and not all of them accepted contact with, or goods from, European settlers.

To clarify the origins of metal goods found in the upstate New York settlements, the team used portable X-ray fluorescence (pXRF) analysis to determine whether copper artifacts were of native or European origin. They then also re-assessed the dates of the sites using radiocarbon dating coupled with Bayesian statistical analysis.

Bayesian analysis, Manning explained, is “a statistical method that integrates prior knowledge in order to better define the probability parameters around a question or unknown. In this case, archaeological and ethno-historic information was combined with data from a large set of radiocarbon dates in order to estimate occupation dates for a set of Mohawk villages across the 13th to early 17th centuries.”

The focus was on the period from the late 15th to the early 17th century, he said, or “the long 16th century of change in the northeast.”

The results “add to a growing appreciation of the interregional variations in the circulation and adoption patterns of European goods in northeastern North America in the 16th to earlier 17th centuries,” Manning said.

In previous indigenous site studies, where artifacts indicated trade interactions, researchers might assume “that trade goods were equally available, and wanted, all over the region,” and that different indigenous groups shared common trade practices, he said.

Direct radiocarbon dating of organic matter, such as maize kernels, tests those assumptions and removes the colonial lens, allowing an independent timeframe for historical narratives, Manning said.

At several major Iroquois sites lacking close European connections, independent radiocarbon studies indicate substantially different date ranges from the previous estimates based on trade goods.

“The re-dating of a number of Iroquoian sites also raises questions about the social, political and economic history of indigenous communities from the 14th to the 17th centuries,” Manning said. “For example … a shift to larger and fortified communities, and evidence of increased conflict,” was previously thought to have occurred around the mid-15th century.

But the radiocarbon findings from some larger sites in Ontario and their cultivated maize fields ¬- 2,000 acres or more in some instances — date the sites from the mid-16th to the start of the 17th century, he said.

“However, as this New York state study shows, other areas had their own and differing trajectories. Thus with direct dating we start to see real, lived, histories of communities, and not some imposed generic assessment,” Manning said. “The emerging new and independent timeframe for northeast North America will now form the basis of a wider indigenous history,” Manning said, “free from a Eurocentric bias, with several past assumptions open for an overdue rethink.”

Cornell University has dedicated television and audio studios available for media interviews supporting full HD, ISDN and web-based platforms.

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