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Sunday, April 4, 2021

Concerns about SARS-CoV-2 evolution should not hold back vaccination expansion

 Sarah Cobey , Daniel B. Larremore, Yonatan H. Grad and Marc Lipsitch

Abstract  

When vaccines are in limited supply, expanding the number of people who receive some vaccine, such as by halving doses or increasing the interval between doses, can reduce disease and mortality compared with concentrating available vaccine doses in a subset of the population. A corollary of such dose-sparing strategies is that the vaccinated individuals may have less protective immunity. Concerns have been raised that expanding the fraction of the population with partial immunity to SARS-CoV-2 could increase selection for vaccine-escape variants, ultimately undermining vaccine effectiveness. We argue that, although this is possible, preliminary evidence instead suggests such strategies should slow the rate of viral escape from vaccine or naturally induced immunity. As long as vaccination provides some protection against escape variants, the corresponding reduction in prevalence and incidence should reduce the rate at which new variants are generated and the speed of adaptation. Because there is little evidence of efficient immune selection of SARS-CoV-2 during typical infections, these population-level effects are likely to dominate vaccine-induced evolution.

https://www.nature.com/articles/s41577-021-00544-9.pdf

J&J Takes Over Contractor's Covid-19 Vaccine Manufacturing Plant

 Johnson & Johnson is taking over manufacturing of its Covid-19 vaccine at a contract manufacturer's plant that makes the main ingredient, after a production problem ruined a batch.

In order to give J&J full control, production of AstraZeneca PLC's vaccine at the Emergent BioSolutions Inc. plant in Baltimore will move elsewhere, according to a person familiar with the matter.

The moves, which the person said were facilitated by the Biden administration and which were confirmed by the companies, mark a rapid response to the recent discovery of the contaminated batch.

The Emergent plant hadn't yet been cleared by regulators when J&J discovered the quality problem during a routine inspection, and none of the batch had been shipped for use to make vaccines.

Yet J&J and U.S. health authorities have looked forward to the plant coming online and producing the key ingredient to bolster the overall supply of vaccine doses.

Under the changes, J&J is assuming full responsibility for operations and manufacturing of its vaccine's key ingredient at the Emergent plant, including installing a new leadership team and boosting the number of technical, quality and other workers.

J&J continues to work through manufacturing issues with the U.S. Food and Drug Administration, and no product will come out of the Baltimore facility without authorization by FDA, the person said.

J&J said it is working with the FDA to secure authorization of the plant, which would clear the way for doses containing the ingredient made at the plant to be distributed.

The federal government worked with AstraZeneca to move production of its vaccine out of the plant so it could focus exclusively on making J&J's vaccine, the person familiar with the matter said.

AstraZeneca said it is working with the U.S. government to find another plant to make the main ingredient for the company's vaccine.

Emergent is committed to supporting production of the Covid-19 vaccines, and it will still control the facility and work with J&J to add its personnel to the plant's staff, an Emergent spokesman said.

The Emergent plant was supposed to play an important role in Covid-19 vaccine production, making the main ingredients for the J&J and AstraZeneca shots.

AstraZeneca's vaccine hasn't been authorized for U.S. use, though the company said it is preparing a submission.

The FDA has been investigating what caused the quality lapse at the Baltimore plant.

J&J has said the failed batch of the vaccine's main ingredient at the Emergent plant never advanced to the vial-filling stage, and no doses were distributed from the batch.

J&J has said the problem didn't affect doses distributed since the vaccine was authorized for U.S. use in late February.

For doses already distributed, J&J has made the main ingredient at its own plant in the Netherlands. J&J also said it expects to distribute to the U.S. government, as planned, 100 million doses of its vaccine by the end of May.

https://www.marketscreener.com/quote/stock/JOHNSON-JOHNSON-4832/news/J-J-Takes-Over-Contractor-s-Covid-19-Vaccine-Manufacturing-Plant-32883848/

Nations Begin to Shape Post-Covid Global Economy Amid Diverging Fortunes

 The world's top economic officials plan to confront at a virtual meeting this week the prospect of new Covid-19 variants and shutdowns undermining the global rebound and weigh measures to prevent lasting damage to the poorest and most vulnerable populations.

The international economy is recovering faster than many economists projected just weeks ago, powered by growth in the U.S. and China and by the accelerating pace of Covid-19 vaccinations in many rich countries. Yet a new wave of lockdowns -- from Europe to Canada -- is threatening that growth, as many low- and middle-income nations with limited financial resources lag behind.

"The window of opportunity is closing fast," said Kristalina Georgieva, managing director of the International Monetary Fund, co-host with the World Bank of the gathering, in previewing the issues facing central bankers and finance ministers. "The longer it takes to speed up vaccine production and rollout, the harder it will be to achieve these gains," she said.

In a report to be released on Tuesday, the IMF plans to raise its forecast for global growth for this year, from the 5.5% expansion projected in January, Ms. Georgieva said in her presentation Wednesday. That would follow an estimated 3.5% contraction in 2020, the worst peacetime outcome since the Great Depression.

The annual spring meeting of the IMF and the World Bank will be held virtually between April 5 and 11, bringing together policy makers from the Group of 20 nations and others. The pandemic response, including vaccine distribution and aid to struggling nations, is expected to dominate the conversations this year. Officials will also discuss ways to rebuild the global economy, with a particular focus on strengthening the resilience against climate change.

The recovery under way is in large part a result of the roughly $16 trillion in fiscal stimulus and liquidity injections from governments and central banks, primarily in wealthy nations, the IMF said. The U.S. government alone has pledged roughly $5 trillion in stimulus spending since the pandemic began.

The IMF in January projected 5.1% growth this year in the U.S., but private forecasters have since boosted their forecasts to 7% or more, following the March enactment of a new $1.9 trillion stimulus package. China, which more quickly brought the pandemic under control to resume production and exports, was forecast to grow 8.1%.

At the same time, one mounting risk to the economic outlook is the emergence of virus variants. Three identified first in the U.K., South Africa and Brazil have since spread around the globe. All share worrisome features that threaten to undo progress in beating back the pandemic, if the virus is left unchecked.

Researchers say there is convincing evidence these variants and their descendants are more transmissible than older versions of the pathogen. Already they are sparking new outbreaks and growth-sapping public-health responses. The U.K. is only now beginning to ease its way out of a lockdown in place since January. French President Emmanuel Macron announced a new national lockdown this past week, citing surges in cases attributed to these more infectious variants.

In Canada, Ottawa saw a record number of cases on Saturday, and Ontario maintains restrictions that have closed restaurants, gyms and personal-care services for weeks. Brazil and India have seen sharp increases in cases.

In the U.S., states are easing restrictions, as the vaccine rollout has accelerated. But with the number of new cases on the rise due in part to variants, officials have cautioned about a possible surge.

Some lab studies have suggested that the current crop of vaccines might lose some of their potency when faced with the South Africa and Brazil variants especially. The worry is that the virus will chance upon new mutations that can help it evade our vaccine-acquired immunity and seed new outbreaks that prompt governments to once again shut down chunks of their economies.

Scientists are broadly optimistic because the vaccine technologies being deployed against the virus -- and our own immune systems -- are capable of adapting too. Still, the emergence of these variants, scientists say, reinforces the need to snuff out chains of transmission and vaccinate as widely as possible to give the virus fewer chances to replicate, acquire advantageous new mutations and come roaring back.

"This will be like a real-world evolution experiment: Can the variants beat the vaccines?" said Alex Sigal, who leads a team of researchers who have been probing coronavirus variants at the Africa Health Research Institute in South Africa.

Even before the new worries about the variants, global policy makers have worried about growing disparities in the world economy this year. In emerging and developing countries, the Covid-19 crisis has reduced per-capita gross domestic product by one-fifth -- nearly twice the loss among advanced economies, the IMF estimates. Last year, more than 100 million people, mostly in South Asia, fell into extreme poverty, defined as living on less than $1.90 a day. Globally, six million children could drop out of school this year, clouding their future prospects, the IMF says.

"Economic fortunes are diverging," said Ms. Georgieva. "Vaccines are not yet available to everyone and everywhere. Too many people continue to face job losses and rising poverty. Too many countries are falling behind."

Money to aid poor nations has been limited, as major economies focused on fighting the pandemic and repairing their own economies. The Group of 20 major economies has provided $5 billion in debt-service relief for more than 40 low-income nations, but private-sector lenders haven't joined the effort. The external debts of low-income countries more than doubled between 2010 and 2019, to more than $750 billion, according to the Institute of International Finance.

"Rich governments have been able to approve trillions of dollars in stimulus packages for businesses, for cash transfers for people, vaccines, and for education, but what about lower- and middle-income countries?" asked Nadia Daar, head of the Washington office of Oxfam International. "The financial response the world has provided has just not been sufficient."

To tackle the problem without adding to that burden, the IMF has proposed issuing $650 billion in SDRs, which could be exchanged for dollars or other hard currencies to cover obligations. Critics say that is an inefficient way to help poor nations because most of the SDRs will be given to rich countries that are the largest IMF shareholders. Republican lawmakers in the U.S. also say the issuance could aid repressive regimes and state-sponsored terrorism.

In response to those objections, the U.S. Treasury Department said Thursday that advanced economies are pursuing ways to lend some of their SDRs to low-income countries. The Treasury also said the U.S. can refuse to swap dollars for SDRs of countries whose policies diverge from U.S. interests.

Concerns are also emerging over the possible negative effects of the massive stimulus spending by the U.S. and other wealthy nations on the developing world. Stimulus could stoke inflation, prompting central banks to raise interest rates, thereby boosting the debt burden for countries.

"One big question, which is common to all economies, is how quick should the withdrawal of the stimulus be, and what happens when they are withdrawn and whether you'll see an increase in bankruptcies," said Odile Renaud-Basso, president of the European Bank for Reconstruction and Development, in an interview. She added that so far, the global economy has shown enormous resilience.

Federal Reserve Chairman Jerome Powell has repeatedly said he doesn't anticipate changing the central bank's easy monetary policy soon. Even so, the yield on the benchmark 10-year Treasury note was 1.72% late last week, up from 0.91% at the end of last year, on signs of an accelerating economic rebound but remains low by historical standards.

Rising U.S. yields have drawn capital away from emerging markets, putting downward pressure on their currencies while fueling both inflation and future inflation fears. Last month, Turkish President Recep Tayyip Erdogan ousted the country's central bank governor, who had raised interest rates repeatedly in an effort to tame inflation.

https://www.marketscreener.com/news/latest/Nations-Begin-to-Shape-Post-Covid-Global-Economy-Amid-Diverging-Fortunes-2nd-Update--32883938/


1 in 4 parents won't vaccinate their kids against COVID-19: poll

 More than one-quarter of U.S. parents don't plan to vaccinate their kids for COVID-19, and roughly as many oppose school-required coronavirus shots, a new study finds.

This opposition was more common among moms than dads, and was especially common among white mothers who identified as Republican/Republican-leaning, the researchers said.

"Women tend to serve as family  managers within the family so they are generally more likely than men to follow expert medical recommendations for avoiding ," said study co-author Jessica Calarco. She is a professor of sociology at Indiana University Bloomington.

"However, with the onslaught of misinformation around the , the pressure women face to control risks may be leading them to disproportionately oppose some new efforts to promote public health," Calarco said in a university news release.

The study looked at a survey of nearly 2,000 U.S. parents and interviews from Calarco's Pandemic Parenting Study. It included 64 mothers of diverse political, economic and racial backgrounds.

Preliminary findings were posted on the preprint server SocArXiv and have not been peer-reviewed.

In all, 34% of the mothers said they do not plan to vaccinate their kids against COVID-19. That number was higher for white mothers who identified as Republican or Republican-leaning (47%).

Only 17% of fathers, however, said they do not plan to vaccinate their children, the findings showed.

The survey also found that, overall, 33% of the mothers oppose school-required coronavirus vaccinations, including 54% of white Republican and Republican-leaning mothers. That compared to one in five dads.

Calarco said that she was surprised by the  because women usually take medical experts' advice.

"In the U.S., we expect people to take responsibility for their health by avoiding health risks. Mothers, in particular, face strong pressure to control risks to their families' health," she said.

"With rampant misinformation, many mothers perceive themselves as able to control the risks of COVID-19 (including through the use of masks) but not the risks of the vaccines. So, they are planning to limit their children's exposure to the virus rather than depend on the vaccine," Calarco added.

The researchers also found that parents without a college degree were significantly more likely than others to oppose school-required immunizations. Black parents are more likely than white parents, overall, to oppose school-mandated shots.

In addition, the survey found that parents who have had COVID-19 were significantly more likely than others to oppose school-required shots and mask mandates.

While moms were more apt than dads to oppose school-required shots, they were less likely to oppose school mask mandates. Roughly 70% of  said their youngest school-aged child wears a mask the entire time they are out in public and 47% said the same for their youngest preschooler.

These findings have important implications for the success of stopping the virus, including school-based  initiatives, Calarco said.

"One way we can help turn this around is by changing the current culture that pressures and blames  to a culture that includes community care," Calarco said. "Treating children's health and well-being as a collective responsibility—not an individual one—is what vaccines are all about."

https://medicalxpress.com/news/2021-04-parents-wont-vaccinate-kids-covid-.html

Genome sequencing shows coronavirus variation drives pandemic surges

 Genome sequencing of thousands of SARS-CoV-2 samples shows that surges of COVID-19 cases are driven by the appearance of new coronavirus variants, according to new research from the School of Veterinary Medicine at the University of California, Davis published April 1 in Scientific Reports.

"As variants emerge, you're going to get new outbreaks," said Bart Weimer, professor of population health and reproduction at the UC Davis School of Veterinary Medicine. The merger of classical epidemiology with genomics provides a tool public health authorities could use to predict the course of pandemics, whether of , influenza or some new pathogen.

Although it has just 15 genes, SARS-CoV-2 is constantly mutating. Most of these changes make very little difference but sometimes the virus becomes more or less transmissible.

Weimer and graduate student DJ Darwin R. Bandoy initially analyzed the genomes of 150 SARS-CoV-2 strains, mostly from outbreaks in Asia prior to March 1, 2020, as well as epidemiology and transmission information for those outbreaks. They classified outbreaks by stage: index (no ), takeoff, exponential growth and decline. The ease of transmission of a virus is set by the value R, or reproductive number, where R is the average number of new infections caused by each infected person.

They combined all this information into a metric called GENI, for pathogen genome identity. Comparing GENI scores with the phase of an epidemic showed that an increase in  immediately preceded exponential growth in cases, for example in South Korea in late February. In Singapore, however, bursts of variation were associated with smaller outbreaks that public health authorities were able to quickly bring under control.

20,000 virus samples

Weimer and Bandoy then looked at 20,000 sequences of SARS-CoV-2 viruses collected and from February to April 2020 in the United Kingdom and compared them with data on cases.

They found that the GENI variation score rose steadily with the number of cases. When the British government imposed a national lockdown in late March, the number of new cases stabilized but the GENI score continued to rise. This shows that measures such as banning gatherings, mask mandates and social distancing are effective in controlling spread of disease in the face of rapid virus evolution.

It could also help explain "superspreader" events when large numbers of people get infected in a single incident where precautions are relaxed.

Weimer said he hopes that public health authorities will take up the approach of measuring  variation and linking it to the local transmission rate, R.

"In this way you can get a very early warning of when a new outbreak is coming," he said. "Here's a recipe for how to go about it."

More information: Scientific Reports (2021). DOI: 10.1038/s41598-021-86265-4

https://medicalxpress.com/news/2021-04-genome-sequencing-coronavirus-variation-pandemic.html

Goldman, JPM Expect Econ Activity In April, May To Top 'Anything We'll See In Our Careers'

 Last week, ahead of both the March payrolls and a burst of closely watched economic data in the coming weeks, we warned readers that we are about to experience the craziest base effect since the great depression, as the US economy laps the 1-year anniversary of the Covid shutdowns which ground the US economy to a halt virtually overnight last March, and which now mean that when looked at on a year-over-year basis, March (and onward) data will looks like this.

But while it's true that the base effect will lead to some impressive if mostly meaningless Y/Y charts, the reality is that the US economy is about to ramp even higher not just on the simple accounting of calendar effects, but because of the continued flood of fiscal stimulus that is about to send the US economy overheating to never before seen levels.

First consider the latest observation from JPMorgan economist Jesse Edgerton, who looks at the latest credit card/high frequency data contained in JPM's Quant Econ Dashboard and notes that a meaningful portion of the US never fully shutdown or had minimal restrictions. So as we approach April 19, the date when Biden says that 90% of all US adults will have vaccine access within 5 miles of their home, JPMorgan urges its clients to consider the magnitude of what could happen: the combined population of California, Illinois, Massachusetts, and New York is ~78.5mm people.

These are states that had some of the more stringent lockdowns and are poised to reopen. In the chart below you can see the differential in perhaps the most popular reopening activity, dining out, in some of those states relative to Florida and Texas. Florida and Texas did not have the same magnitude of restrictions as the states mentioned.

In short, in just two weeks, the US could experience a spending spree the likes of which have never been seen before.

But wait, there's more... and for that we go to Goldman head of hedge fund sales Tony Pasquariello who - as we noted earlier - is becoming concerned about "fat tail" outcomes after the subsurface turmoil of the first quarter, although as he expounded, the risk/reward "will be on the right tail" as the US quickly moves towards herd immunity. Specifically, he says to consider the following three data points:

  • i. $4.44tr currently sits in US money market funds ($1.5tr is held by retail, $2.94tr is held by institutions). since February of 2020, that $4.44tr pile has grown by … $830bn.
  • ii. US households have accumulated about $1.5tn in 'excess' or 'forced' savings, and Goldman expects that to rise to about $2.4tn, or 11% of GDP, by the time that normal economic life is restored around mid-year
  • iii. attendant to the largest jump in US consumer confidence in 18 years: a record share of respondents said they plan to purchase a home in the coming months. a measure of consumers' plans to buy cars and major appliances also rose. A separate report Tuesday showed U.S. home prices surged to the highest since February 2006.

His conclusion: after the change observed in the markets in Q1, which presents a different setup for Q2, Pasquariello notes that "if April and May are THE peak growth months for US economic activity - perhaps as robust as anything we'll see in the remainder of our careers - there's still a lot to play for, and I still believe a reflationary framework is the right place to anchor your risk-taking."

Which, however, is not necessarily good news: judging by the ramp higher in yields after the blockbuster, goldilocks payrolls report on Friday which has nonetheless triggered a new round of the reflationary dynamic, the Goldman strategist warns that "the path higher from here is apt to be choppier and risk/reward is not what it was four or five months ago" and "in practical terms, this argues for a more tactical trading stance where illiquid positions - and recency bias - are the enemy."

Young Pakistanis rush to purchase Russian vaccine as private sales open

 Thousands of Pakistanis rushed to get inoculated in the first round of commercial sales of COVID-19 vaccines that began over the weekend, with vaccination sites in the southern city of Karachi saying on Sunday they had already sold out.

\Pakistan is currently offering free vaccines to frontline healthcare workers and people over the age of 50, but the drive has thus far been slow, and last month the country allowed commercial imports by the private sector for the general public.

The first round saw the commercial sale of the two-shot Russian Sputnik V to the general public for about 12,000 Pakistani rupees ($80) for a pack of two doses.

Despite the cost, a number of centres offering the shot reported long queues, with some in Karachi waiting in line for close to three hours. Most in the queue were young Pakistanis still not eligible for government’s free vaccination.

“I am very happy to get it, since now it is required for travelling,” Saad Ahmed, 34, told Reuters on Sunday after he got his shot at an upscale private sector hospital in Karachi.

While the private sale of vaccines has begun, the government and importers are still locked in a pricing dispute.

Pakistan initially agreed to exempt imported vaccines from price caps, but later rescinded the exemption and said it would set maximum prices.

One pharmaceutical company, which had already imported 50,000 doses of Sputnik V, took the government to court, where it won an interim order allowing it to sell it until pricing is decided.

As soon as vaccination was opened for walk-in customers, there were long lines of people, Dr Nashwa Ahmed, who runs vaccination at Karachi’s South City Hospital, told Reuters.

Pictures of queues outside the hospital late into the night were shared on social media.

The hospital procured 5,000 doses of Sputnik V and in just over two days all its stock had been administered or pre-booked, said a hospital official who asked not to be identified.

Companies, including one of Pakistan’s largest banks, have also purchased large quantities to have staff inoculated, the official said.

The private sales start as the country deals with a fresh wave of COVID-19 infections and healthcare facilities are fast filling to capacity.

The number of patients now in critical care has reached 3,568, the highest since the pandemic started, a cabinet minister, Asad Umar, said on Twitter. Pakistan has thus far reported 687,908 infections and 14,778 deaths.

https://www.reuters.com/article/us-health-coronavirus-pakistan-vaccine/young-pakistanis-rush-to-purchase-russian-vaccine-as-private-sales-open-idUSKBN2BR0LH