Virus World

Nations short of vaccine should get first doses to curb the pandemic, researchers say.  Israel has announced plans to begin giving booster shots to older adults next week, in the hope of increasing their protection against COVID-19 — and a number of other wealthy countries are considering the same. But global-health researchers warn that this strategy could set back efforts to end the pandemic. Each booster, they say, represents a vaccine dose that could instead go to low- and middle-income countries, where most citizens have no protection at all, and where dangerous coronavirus variants could emerge as cases surge. Data do not yet show that extra doses are needed to save lives, researchers say, except perhaps for people with compromised immune systems, who might fail to generate much of an antibody response to the initial COVID-19 shots.  An internal analysis from the World Health Organization (WHO) estimates that if the 11 rich countries that are either rolling out boosters or considering it this year were to give the shots to everyone over 50 years old, they would use up roughly 440 million doses of the global supply. If all high-income and upper-middle-income nations were to do the same, the estimate doubles. The WHO maintains that these shots would be more useful for curbing the pandemic if they were sent to low- and lower-middle-income countries, where more than 85% of people — some 3.5 billion — haven’t had a single jab. “The priority now must be to vaccinate those who have received no doses,” said WHO director-general Tedros Adhanom Ghebreyesus at a briefing on 12 July.

All of the COVID-19 vaccines authorized by most high-income countries reduce a person’s risk of hospitalization and death by more than 90%. Scientists don’t yet know how much more a booster — typically an extra jab of an mRNA-based vaccine on top of the standard doses — would protect the average person, although data are beginning to trickle in. The effects of not receiving any vaccine are more certain. On the African continent, where only 2% of people have been vaccinated, COVID-19 rates are escalating, with fatality rates higher than the global average.  Without vaccines, researchers say, the best tools for slowing the spread of infections are interventions such as closing businesses and schools, which can have devastating economic consequences. The International Monetary Fund (IMF) estimates that 95 million people were pushed into extreme poverty during the pandemic last year, and numbers are rising. On 27 July, the organization reported a widening wealth gap between rich countries and the rest of the world. What’s more, evolutionary biologists say that countries with low vaccination coverage are ripe for the emergence of further dangerous variants of the coronavirus SARS-CoV-2. “Right now, our destiny relies on distributing vaccines so that continued transmission doesn’t occur,” says Nahid Bhadelia, director of the Center for Emerging Infectious Diseases Policy and Research at Boston University in Massachusetts. “We don’t want to be chasing our tail in terms of new variants.”

Contemplating boosters

Israel is not alone in considering boosters for older people. Spurred partly by data1 suggesting that antibody levels wane over time, the United Kingdom has drawn up plans — but not given final approval — for a booster programme to begin in September for older people, front-line health workers and others at high risk of COVID-19. In early July, the US government decided against boosters for the time being, but said it was prepared to roll them out when science demonstrated a need. Last week, the United States purchased another 200 million mRNA vaccines made by pharmaceutical firm Pfizer, based in New York City, and biotechnology firm BioNTech, based in Mainz, Germany, that might be used for booster shots if studies show they are necessary.  The United States and other nations are hesitating because current COVID-19 vaccines still protect people, despite uncertainty about how long their effects will last. This week, a not-yet peer-reviewed report from Pfizer2 found that its vaccine’s efficacy rate against symptomatic COVID-19 fell from 96% for the two months after the usual two doses to 84% six months later. But its efficacy against severe disease remained high, at 97%. Decisions on boosters might also be influenced by the rise of the Delta variant in many parts of the world, and the possibility that vaccinated people could transmit it to others if they become infected. In theory, further reducing the risk of infection for vaccinated people diminishes the possibility of Delta's spread.

The variant was first reported in India in late 2020, but remained relatively rare until March, when a surge occurred. Few people in the country had been vaccinated at the time, allowing the virus to spread in India and beyond. A similar scenario might play out again in an area with low vaccination coverage and a lot of COVID-19. A new variant could arise that is more transmissible or deadlier than Delta, or that allows the virus to escape — at least to some extent — immunity gained from vaccination or a previous infection, says Katrina Lythgoe, an evolutionary biologist at the Big Data Institute at the University of Oxford, UK. “Making predictions is really hard,” she adds, but it’s safe to say that in places with more infections, there are more viruses replicating and therefore more opportunities for variants to evolve....

• A new Ipsos-World Economic Forum survey shows a notable increase in COVID-19 vaccination intent since December in all 15 countries studied.
• Eighty-nine percent of people in Brazil say they’re ready to be vaccinated, with confidence also very high in Italy, China and Spain.
• Confidence in the vaccines has risen most in Italy – up 36 percentage points since December.

Forget boosters and more trials. America’s overly prudent vaccination strategy is killing people.  In the race to prevent ever more deaths from Covid-19, the United States faces two major problems: not having enough doses of vaccine on hand and struggling to deliver those that are available. According to data from the Centers for Disease Control and Prevention, as of Jan. 28 about 48.4 million doses had been distributed, but only 26.2 million administered. The Food and Drug Administration has granted emergency-use authorization to two vaccines requiring two doses — with the first shot and the booster to be delivered three weeks apart in the case of the Pfizer-BioNTech vaccine, and four weeks apart for the Moderna vaccine As of Thursday, just 4.2 million people in America had received both doses, according to the C.D.C. Uncertain about vaccine supplies, some inoculation centers have canceled first-time appointments while keeping second appointments on schedule. This is exactly backward. The Biden administration’s Covid-19 response and pandemic preparedness plan aims to provide 100 million doses within 100 days of the president’s inauguration, especially to people over 65, all essential workers (not only those in health care services) and “the highest-risk members of the public, including racial, ethnic and rural populations and those in congregate facilities.” Both the plan’s sense of urgency and its focus on some of the most vulnerable groups are welcome. But the proposal also backs the use of second doses and supports sticking to F.D.A.-recommended timelines for administering them, and that is misguided. We think more lives would be saved by providing as soon as possible (a) just one dose of vaccine (b) to all people who face the highest risk of dying from Covid-19, whatever the reason (advanced age, other medical conditions, severe obesity), and (c) just forgetting about any boosters for a while, maybe even a very long while. Second doses should be deferred for the time it takes to achieve this primary goal.

The two vaccines’ manufacturers and the F.D.A. have been reluctant to endorse any change to the vaccination schedules that were tested in Phase 3 clinical trials, on grounds that other options weren’t tested and so their efficacy is unknown. On the face of it, this position seems sensible; yet under current circumstances, it is dangerously overcautious. The C.D.C. has authorized giving a second dose up to six weeks after the first one if sticking to the recommended interval is “not feasible.” But this is an arbitrary extension — it wasn’t tested any more than any other modification — and we think it’s too short to accomplish much good society-wide. Bear in mind that the clinical trials performed for both the Pfizer-BioNTech and Moderna vaccines weren’t designed to identify the optimal number of doses for inoculation, nor the perfect schedule for administering them. The goal of those trials was only to test whether two doses of vaccine given according to the schedule chosen by the manufacturers did confer sufficient protection against Covid-19. Note, too, that in the case of both those vaccines the intervals tested (three and four weeks) were unusually short. In standard schedules for childhood vaccines in the United States, for example, the gap between the first shot and the booster typically is no less than two months. The fact that the trials did not test whether administering a second dose much later, or not at all, might work just as well than the recommended schedule, or well enough, also means that it could work. And there is good reason to think that it would. With some vaccines, like those for hepatitis A or human papillomavirus (HPV), delaying the second dose by as long as several years has been shown to not decrease the protection conferred by the vaccine. In other cases, such as influenza vaccines, increasing the interval actually improves the response. (This likely is because the cells in the body that develop the immune memory necessary to repeatedly fend of infections can take weeks or months to develop.)

In trials for another Covid-19 vaccine not currently available in the United States — this one developed by Oxford-AstraZeneca — study subjects were supposed to get a booster one month after the first shot but some received it up to 12 weeks later. Results for the latecomers were outside the trials’ formal ambit, but they are available, and they suggest that the subjects who waited to get their booster beyond the recommended delay displayed better immune responses than the subjects who got it on time. In non-pandemic situations, the usual approach is to give a vaccine to the wider public in precisely the same way that it was studied and vetted in Phase 3 trials, as well as to initiate new clinical trials or real-world studies to evaluate alternative ways of administering it. As a result of this practice, recommended doses were reduced for vaccines against, for example, HPV (from three to two) and meningococcal B in infants (from four to three) — with no significant reduction in immune responses. Such precedents may be one reason that some doctors and social scientists are now calling for promptly conducting studies to assess the performance of single doses of Pfizer-BioNTech’s and Moderna’s Covid-19 vaccines in young, healthy subjects, the group least likely to become severely sick with Covid-19. Yet this approach, too, misses the mark. With the pandemic raging as it is — one person is dying of Covid-19 about every 30 seconds in America — there is no time to wait for the results from additional clinical trials, which would take months to complete, before vaccine-rollout plans are modified. And studying the efficacy of single doses only among individuals who face a very low risk of dying from Covid-19 wouldn’t say much anyway about the viability of using single doses with the people most at risk of death.........

The Trump administration moved on Tuesday to accelerate vaccinations of Americans against COVID-19, releasing the rest of the doses it had been keeping in reserve and recommending states immediately open inoculations to those aged 65 and over.  Federal and state health officials have scrambled in recent days to step up vaccination programs that had given shots to only 9.3 million Americans as coronavirus infections remain at record highs in many U.S. states nearly two weeks into the new year. Many U.S. states had strict rules in place giving shots to healthcare workers and nursing home residents first, telling “non-essential workers” they might wait months for their turn. “We’ve already distributed more vaccine than we have healthcare workers and people in nursing homes,” U.S. Health and Human Services Secretary Alex Azar told ABC News. “We’ve got to get to more channels of administration.” Roughly 27.5 million doses have been distributed by the U.S. government to states so far, according to the U.S. Centers for Disease Control and Prevention.Azar said the outgoing administration, which had been keeping doses in reserve to make sure that all those who got a first inoculation receive their second shot on schedule, was now confident enough in the supply chain to release that stockpile. 

Last week, a spokesman for Joe Biden said the president-elect, who takes office on Jan. 20, would release more of the reserved doses. The pace of vaccinations has risen to 700,000 a day nationwide and was expected to hit 1 million a day within 10 days, officials said. “Michigan and states across the country remain ready to get more shots in arms, which is why the Trump Administration’s decision to grant our request and release millions of doses of the vaccine is so crucial,” Michigan Governor Gretchen Whitmer said in a statement. Whitmer, who had backed the lower vaccination age, is seeking permission from the U.S. government to purchase 100,000 vaccine doses directly from manufacturer Pfizer Inc.  The U.S. Food and Drug Administration has authorized the vaccine from Pfizer and partner BioNTech SE and a second vaccine from Moderna Inc for emergency use. As of Monday night, the United States had reported a total of 22.5 million coronavirus infections and 376,188 deaths during the pandemic, the most of any country. Nearly 130,000 Americans were hospitalized with COVID-19 at midnight on Monday.

GRIM SCENES AT CALIFORNIA HOSPITAL

A Reuters tally has shown that the number of COVID-19 patients requiring hospitalization may have leveled off, at least temporarily, although public health officials warn that further spread may still be seen from holiday gatherings. California Health and Human Services Secretary Dr. Mark Ghaly cited several promising trends in COVID metrics statewide in recent days, including a slowing in confirmed daily case numbers and a leveling off in positive tests. The number of new COVID hospitalizations statewide has fallen to about 2,500 admissions a day over the past two days from a daily average of about 3,500 admissions in previous days. Ghaly called that “the biggest signal to me that things are beginning to flatten and potentially improve."  Despite the encouraging statistics, staff at Providence St. Mary Medical Center in Apple Valley, California, said that the situation was grim. “Where in the beginning we were overloaded with a lot of patients - we still have a lot of patients - but now it seems like they’re sicker than they’ve ever been before,” said Mary Mendy, executive director of acute care services at the hospital some 90 miles northeast of Los Angeles.  “And every day there’s Code Blues on the floor and more and more patients are updated to ICU. It’s devastating,” Mendy said. The latest surge has potentially been compounded by a more infectious variant of the virus first seen in the UK and now found in at least 10 U.S. states - California, Florida, New York, Colorado, Georgia, Indiana, Connecticut, Minnesota, Pennsylvania and Texas.

Nearly half of doses administered so far have gone to high-income countries — just 16 percent of the world’s population.  The globe is quickly being split into coronavirus vaccine “haves” and “have-nots,” creating a gap that may define the next phase of the pandemic. Using publicly available figures from Our World in Data, The Washington Post found that nearly half — 48 percent — of all vaccine doses administered so far have gone to just 16 percent of the world’s population in what the World Bank considers high-income countries.  Through the summer and fall of last year, wealthy nations cut deals directly with vaccine-makers, buying up a disproportionate share of early doses — and undermining a World Health Organization-backed effort, called Covax, to equitably distribute shots. So now, in a small number of relatively wealthy nations, including the United States, doses are relatively plentiful and mass immunization campaigns are progressing apace. But much of the world is still struggling to secure enough supply. For many, herd immunity is many months — if not years — away, which could extend the crisis. A team at Duke University’s Global Health Innovation Center found that high-income countries locked up 53 percent of near-term vaccine supply. They estimate that the world’s poorest 92 countries will not be able to reach a vaccination rate of 60 percent of their populations until 2023 or later.

Israel has so far immunized the largest number of people per capita. As of April 19, nearly 60 percent of Israelis had received at least one dose and nearly 58 percent were fully vaccinated, according to Our World in Data. Though Israel was later than some countries to sign vaccine deals, it offered to pay premium prices and give drug companies access to its health-care data. The country reportedly spent $788 million on coronavirus vaccines by March, most notably on a large shipment of Pfizer-BioNTech’s RNA vaccine. While Israel has been criticized for neglecting the Palestinian population in its midst, its vaccination campaign has otherwise been deemed a success and has allowed the return of a more normal way of life, including the lifting of outdoor mask requirements.

Britain is another country leading the way. Between developing, buying and administering vaccines, the country will spend about $16 billion, according to a National Audit Office estimate. To stretch supply as far as possible, Britain opted to space doses by several months, meaning that while nearly 50 percent of the country has had at least one shot, just over 16 percent is fully vaccinated. The campaign was set back this month when concerns about rare blood clots in people receiving the AstraZeneca vaccine led the government to restrict use in adults under 30. Still, early studies in Britain show significant reductions in infections and hospitalizations after a first dose of the AstraZeneca or Pfizer vaccines. And the country has been able to slowly begin lifting its lockdown.

The United States, after experiencing one of the world’s most deadly outbreaks, is now the envy of the world with its abundant vaccine supply and rapidly progressing inoculation campaign. The country spent billions on vaccine development, deals and distribution. About 41 percent of U.S. residents have received at least one dose and more than 26 percent are fully vaccinated. As of this week, all Americans over the age of 18 are eligible to get a shot — a milestone that may renew questions about what the country plans to do with its predicted hundreds of millions of surplus doses. The Biden administration faces growing calls from public health advocates and activists to share, either by donating doses to countries in need, transferring technology to boost manufacturing capacity, or by easing export restrictions that have kept a disproportionate number of shots, as well as critical vaccine materials, in the United States.......

Maccabi health fund releases preliminary results of a study comparing vaccinated and not vaccinated members’ likability to contract the disease and said vaccine 92% effective.  A total of 371 out of 715,425 Israelis who passed at least a week after receiving two doses of the Pfizer coronavirus vaccine have contracted the virus – 0.04%, with 16 being sent to the hospital – according to a Health Ministry report released on Thursday. Immunity to COVID-19 is supposed to kick in a week after receiving the second dose of the Pfizer vaccine. According to the studies conducted by Pfizer, the vaccine had an efficacy of about 95%, which is considered very high. The Israeli data appear to confirm the inoculation’s effectiveness, showing an even more promising result. Later in the day, Maccabi Healthcare Services – one of the country’s four health maintenance organizations – released the first results of the vaccination campaign of its members, with the organization also comparing the data to a control group that did not get inoculated.

Israel is currently leading the global vaccination drive, with around 30 per cent of its citizens having had at least a single dose of a jab so far. 

• Israeli healthcare firm KSM Maccabi Research and Innovation Center on Friday reported on vaccination data 
• It said there had been a 'significant decrease' coronavirus infections among vaccinated over-65s 
• Also found that hospitalisations in the same group had plunged by more than 60 per cent 
• Over 2.5 million of Israeli citizens have had the first vaccine dose, around 30 per cent of population 
• Teenagers aged 16-18 are now being given the first dose of the vaccine, starting on Saturday 

An Israeli healthcare group on Friday said coronavirus infections had plunged among people aged over 60 who had been vaccinated with the Pfizer Biontech vaccine. Israel is currently leading the global vaccination drive, with around 30 per cent of its citizens having had at least a single dose of a jab so far. But concern had risen globally over infection, death and hospitalisation rates in the country, which remained stubbornly high.  Out of 82,930 active cases on Thursday, 1,918 were hospitalized. Last week, the hospitalisation figure was just over 1,000.   Officials had hoped that the vaccine drive - which began on December 19 - would start to show an effect by mid-February But KSM Maccabi Research and Innovation Center claimed on Friday there had been a 'significant decrease' in the number of coronavirus infections among people aged over 60 who were vaccinated between December 19 and 24. After analysing data of more than 50,000 patients aged over 60, they also found that hospitalisations in the same group had plunged by more than 60 per cent.  Israel secured access to large amounts of Pfizer's jab by agreeing to provide data about its citizens for the company to track how well the jab works. The new figures are a sign of hope that nationwide infections, deaths and hospitalisations could soon start to see a sustained fall.  It came amid reports that England's chief medical officer was so infuriated by a newspaper story which claimed that a single dose of the Pfizer vaccine might only be 33 per cent effective that he threatened to report it to a press watchdog.  Chris Whitty told colleagues The Guardian's report was 'total nonsense' which could threaten the uptake of the jab. 

KSM Maccabi Research and Innovation Center's report was based on data 50,777 members of Maccabi who were aged over 60 and were vaccinated 23 days ago.  KSM, which is part of Israeli healthcare provider Maccabi, noted that there was a 'significant decrease within the vaccinated members aged 60+', reaching a decrease of around 60 per cent in new infections.  They added that there was also a 'decrease of slightly more than 60 per cent in the number of new hospitalised patients.'  However, KSM cautioned that 'on this level of efficiency, there should be no exemption from performing Corona tests, isolation, or the enablement of crowded gatherings, until additional convincing data is obtained.  'And of course continue to wear masks and keep social distancing, as recommended'. In their story about the effectiveness of a single dose of the Pfizer jab, The Guardian had quoted 'Israeli experts' as saying only a third of people who have received one injection were protected. No 10's vaccine advisers say the real figure is 89 per cent, starting 14 days after the first jab. It was reported yesterday that a single shot of the Pfizer vaccine had led to a 'major presence' of antibodies in 91 per cent of doctors and nurses who received it in Israel within 21 days. A source told the Mail On Sunday: 'It is not every day that a member of the liberal academic establishment is angered by The Guardian.' On Friday, Israel announced a further 6,159 new cases, an 18 per cent increase on the figure of 5,235 announced seven days ago, but down from Wednesdays and Thursdays totals, of 10,213 and 7,027 respectively. 

Since the rollout of vaccinations one month ago, more than 2.5 million of Israel's nine-million-strong population have been vaccinated already, the health ministry said on Friday. It came as the Israeli health ministry on Thursday announced it was allowing the inoculation of high school students aged 16-18, subject to parental approval.  The health ministry had on Thursday announced it was allowing the inoculation of high school students aged 16-18, subject to parental approval. Expanding the campaign to include teens came days after Israel extended on Tuesday till the end of the month its third national coronavirus lockdown due to a surge in coronavirus infections despite the vaccinations.....  

Health care systems in California, Illinois, Wisconsin, and Kansas expect to still be giving staff their first shots in mid-January. Hospitals across the United States are preparing for a Covid-19 vaccine distribution timeline that’s well behind official government targets as they face ongoing confusion about the process for inoculating frontline employees.  Leaders of Operation Warp Speed have repeatedly said they are on track to vaccinate 20 million people in December, enough for nearly all the health care workers and long-term care residents who are first in line to get a vaccine. But those involved in vaccine planning at four health care systems, in California, Illinois, Wisconsin, and Kansas, told STAT they expect to still be giving staff their first shots in mid-January. These workers would then receive their second vaccine dose three to four weeks later, depending on the vaccine, and would receive the full immunization effects a week after that, in mid-February. With hospitals across the U.S. filling up, as numerous states set daily records for Covid cases, federal officials have pledged a massive distribution push within days of the expected FDA approval this month of the first two vaccines. Moncef Slaoui, head of Operation Warp Speed, said in a briefing last week he was confident “we will be able to distribute … enough vaccine to immunize 20 million people in the U.S. in December.” But on the ground, the reality is murkier. “We’re not going to get 300 doses [immediately] for a hospital that has 300 employees,” said Pat Schou, director of the Illinois Critical Access Hospital Network, which works with 57 critical access rural hospitals. “I think it’s going to take a couple months. By mid-February, I would hope that we would have almost all our health care workers and EMS and be moving into long-term care. I think that’s the best we can hope for.”

Wisconsin’s health department recently released prioritization plans for those within the first tier of vaccination. “If we were able to [vaccinate] all almost immediately, I’m not sure they would have gone to that trouble,” said Tim Size, executive director of Rural Wisconsin Health Cooperative. These delayed expectations reflect the basic questions and concerns that many of the first Covid-19 vaccination sites still have about a process due to start in a matter of weeks. “We don’t know a lot yet,” said Dave Dobosenski, chief executive of St. Croix Regional Medical Center in Wisconsin, a state with one of the highest case rates in the country. “We’re craving to get some information here to understand what we’re doing.” The biggest questions among health care systems include when they will receive their vaccines, and how many. But there are also logistical hurdles, including not wasting unused doses, not leaving patients unattended while staff are vaccinated, and not having workers take sick days all at once when they experience expected side effects of the vaccines, including fatigue and fever. 

Even when health care providers have information, it can frequently change. Houston Methodist Hospital was originally told it was a “pre-position” vaccine site, due to receive the vaccine five to seven days ahead of other providers in the state, said chief executive Roberta Schwartz. But the vaccine will no longer be going to pre-positioned sites first, said Texas health department spokesperson Chris Van Deusen. Schwartz said she was most recently told to expect a delivery on Dec. 12 or 13. “If you asked me that tomorrow, I’ll give you another day,” she added. Sanford Health, with hospitals in North Dakota, South Dakota, Minnesota, and Iowa, has received an estimate of how many vaccines it will first receive from only one of those states, said Jesse Breidenbach, senior executive director of pharmacy support services. That delivery would be sufficient to cover the majority of staff who have volunteered to take the vaccine in that state....