Daily update Covid - 19

Daily update Covid - 19

As the UK reported its highest number of cases (58k) since early January 2021, researchers in the US find that COVID-19 was the third leading cause of death in November 2021. They also find that in October, COVID-19 was the number 1 cause of death for people age 45-54 and in the top 7 leading causes of death for other age groups, aside from infants. They also estimate that 163,000 COVID-19 deaths could have been prevented by vaccination since June 2021, when safe and effective COVID-19 vaccines were widely available to all adults in the US:

https://www.healthsystemtracker.org/brief/covid19-and-other-leading-causes-of-death-in-the-us/

In S Africa, new confirmed cases have softened recently, maybe due to testing limitations as the positive testing rate continues to increase. Hospitalizations have continued to rise in the Gauteng Province. ICU utilization and patients on ventilators have both been significantly smaller as a share of hospitalizations in the Omicron wave so far relative to the Delta wave. While this likely partly reflects the younger age of patients and the steepness of the wave, it also might indicate a strong vaccine or prior infection effect against severe cases or possibly a lower severity of Omicron. Evidence remains reassuring regarding Omicron symptoms and protection provided by vaccines, and while hospital admissions have begun to rise, length of stay and mortality remain much lower than previous waves.

A worry with Omicron is clearly kids. Young children in South Africa now make up a larger share of COVID cases than they did at the start of Q2, and this has been attributed to Omicron. At the start of Q2, children aged 0-9 made up 2.3% of cases. In the week ending December 4th, young children made up 4.2% of cases:


The number of South African children aged 0-9 that are admitted to the hospital has risen more sharply than it did during the Beta wave earlier in the year. The recent acceleration in cases has also been much sharper than it was earlier in the year, and children in this age group are not vaccinated in any case. The lag between cases and hospital admissions seems to have shortened substantially, however. There could be multiple explanations for this: Omicron infection might lead to severe outcomes more quickly than Beta did. Or perhaps testing behaviour has changed – maybe tests are increasingly conducted at the time of hospital admission:


Consistently however I am hearing that Omicron in kids is mild. And, yesterday the head of health surveillance for South Africa’s National Institute for Communicable Diseases said there has been a “disconnect” between the number of infections and hospital admissions in the current wave. A study in Japan using data from South Africa found that the Omicron variant is 4.2 times more transmissible than the Delta strain, adding to concerns about its contagiousness.

The World Economic Forum said its annual gathering in Davos will go ahead next month as planned and will be “conducted under sensible and strict public health measures”. The share of the population having received a first shot stands at 82% in Canada and Spain, 79% in Italy and Japan, 78% in Australia, 77% in Brazil and France, 75% in the UK, 72% in the US and Germany, 58% in India, and 47% in Russia. The daily pace of new doses administered (7DMA) decreased to 33mn globally, 1.2mn in the US, 2.9mn in the EU, 8mn in China, and 7.8mn in India. The share of the population having received a booster shot stands at 47% in Chile, 44% in Israel, 32% in the UK, 20% in Germany, 17% in Turkey, France, and Italy, 15% in the US, 13% in Spain, 11% in Singapore, 10% in Malaysia and South Korea, 9% in Brazil, 7% in Canada, 6% in Argentina, 5% in Thailand, 4% in Russia, 3% in New Zealand, and 2% in Australia. Over the past week outbreaks have worsened in China, South Africa, France, Norway, South Korea, Switzerland, and the US and improved in New Zealand, Germany, Hungary, the Czech Republic, and Singapore. In developed markets virus spread remained low in Japan, decreased in Germany, increased in the US, Canada, Spain, Italy, and the UK, and surged in France:

Apart from Omicron and as it’s the weekend, main finding for me last week was a chewing gum that could reduce SARS-CoV-2 transmission:

https://penntoday.upenn.edu/news/chewing-gum-could-reduce-sars-cov-2-transmission

Some UK data on 581 Omicron cases found a 70-75% vaccine effectiveness against symptomatic infection in the “early period after a booster dose.” The study was conducted starting two weeks after the booster jab.   This is much lower compared to Delta infection.  The effectiveness was measured for two groups: (1) those who received a Pfizer primary course and Pfizer booster and (2) those who received an AstraZeneca primary course and Pfizer booster.  The report cited five preliminary live virus studies, finding a 20-40X reduction in neutralizing activity for two doses of the Pfizer vaccine. This is bad news for those who lack a booster—and are running out of time to get one. Eventually, it is likely the Centers for Disease Control (CDC) definition of who qualifies as “fully vaccinated” will be challenged.  Without better data, we do not know the extent to which the vaccine protects against severe disease or death from Omicron. However, as the report highlights, protection against severe disease has historically been higher than vaccine efficacy against symptomatic infection for other COVID variants:

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1040076/Technical_Briefing_31.pdf

No suprise with respect to this:

As of Tuesday, anyone aged 12 or above wishing to travel to the U.K. will need to show a negative test (lateral flow or PCR) no more than 48 hours before departure, marking a U-turn for the government under pressure to do more to slow the importation of Omicron.

The U.K. government also added Nigeria to its red list. British and Irish citizens, or those with residence rights, arriving in England are required to book a 10-day stay in a quarantine hotel ahead of time. Don’t even try boarding your flight if you haven’t done this.

France announced last weekend that all travellers arriving from non-European countries, vaccinated or not, will also have to provide a negative test on departure (antigen test within 24 hours or PCR test within 48 hours of travel).

In addition, all unvaccinated travellers from Europe must now demonstrate a negative test of less than 24 hours (antigen or PCR) on departure to enter France, according to the Prime Minister’s office. There’s a chance this could be extended to vaccinated people, if EU countries agree to a standardized approach.

Ireland has announced similar measures: all visitors must show a negative test prior to departure. Both lateral flow and PCR tests can be used for vaccinated or recovered people, while unvaccinated people must get a negative PCR test, the health ministry said a week ago.

Austria has lifted its requirement for visitors from high-risk countries to go into quarantine. At the same time, it has tightened testing for visitors including those who are vaccinated or have recovered from COVID-19. In addition to taking a PCR or rapid antigen test before traveling, a second test is now required between the fourth and seventh day after arrival. Additional social distancing measures, including requiring COVID certificates and mask wearing in a wider range of settings, are aimed at saving the winter ski season.

The European Commission is looking into Portugal’s requirement for all passengers flying into Portugal to show a negative test before boarding, with airlines facing a fine of €20,000 per passenger for failing to check. “It remains crucial to ensure the proportionality of any measures taken and we will continue to monitor the situation closely,” a Commission spokesman said.

Hong Kong is not a recommended destination for anyone who wants to spend Christmas outside of a tiny quarantine hotel room. Since the emergence of Omicron, it is not even possible for anyone apart from residents or citizens to travel from most European countries to the territory. With probably the strictest quarantine requirements in the world, the Hong Kong authorities have promised to prosecute anyone who steps outside their hotel room during their three weeks of incarceration, with penalties of up to six months in prison and a HK$25,000 fine.

In science news, T cell epitopes (the bit T cells recognised on the virus) are reasonably conserved versus Omicron:

Boston Covid wastewater tracker:

In regulatory news, the FDA expanded the emergency use authorization for Pfizer Covid-19 booster shot to cover 16- and 17-year-olds, making it the only booster shot currently available in the United States for teenagers in this age group. Within hours, Rochelle Walensky, director of the Centers for Disease Control and Prevention, signed off on the expanded authorization, clearing the way for 16- and 17-year olds to book booster shot appointments. “Today, CDC is strengthening its booster recommendations and encouraging everyone 16 and older to receive a booster shot,” Walensky said in a statement. “We know that Covid-19 vaccines are safe and effective, and I strongly encourage adolescents ages 16 and 17 to get their booster if they are at least 6 months post their initial Pfizer vaccination series.”

I note virtual care companies think they could speed up the process of getting patients new oral antivirals for Covid-19 in the window when they are most effective. Last week, digital health company Truepill announced it would launch a platform to support telehealth consultations, prescriptions, and next-day delivery of the new drugs, from Merck and Pfizer, when authorized. Carbon Health which has both brick-and-mortar clinics and virtual care, plans to extend its acute Covid care program to include the oral antivirals. And direct-to-consumer company Ro says it has the capability to prescribe and deliver the drugs and expects to make them available through its platform. 

Wealthy countries donating Covid-19 vaccines with a relatively short shelf life has been a “major problem” for the Covax dose sharing programme, a senior official at the WHO has said. Kate O’Brien, the WHO’s vaccine director, said in a briefing the proportion of wasted doses is smaller in countries receiving doses through Covax than in many high-income countries. Her comments come as concerns grow that many African countries in particular are finding they do not have the capacity to get shots in arms before they expire.

In a rebuke of the Biden administration’s Covid-19 vaccine-or-test mandate policy, two Senate Democrats defected and voted with Republicans to roll back the administration’s requirement that businesses with more than 100 employees require their workers to get vaccinated or get tested weekly. Republicans have framed vaccine-or-test mandates as an issue of grocery store employees and nurses being forced to quit their jobs, as opposed to the Biden administration’s argument that the measure is an evidence-based public health tool to prevent deaths due to Covid-19. While the vast majority of U.S. adults have gotten vaccinated — nearly 72% are fully vaccinated — the vote last night showed some Democrats are still concerned about crossing big business.

Interesting view here. Belgium has vaccine passports. Germany has vaccine passports. France has vaccine passports. Ireland has vaccine passports. The UK doesn’t have vaccine passports, but it’s a tax right:


https://mobile.twitter.com/MahyarTousi/status/1467882481273737220

Interestingly, new Covid vaccinations in the U.S. have slowed down among children aged 5 to 11, a new KFF analysis says. As of this week, 17% of these kids got at least one dose and 4% reached full vaccination:


https://www.kff.org/coronavirus-covid-19/issue-brief/an-update-on-vaccine-roll-out-for-5-11-year-olds-in-the-u-s/?

Moderna presented flu data yesterday which I think looked very decent. Interestingly, flu vaccinations are growing slowly in the US, this shows the % of people vaccinated 2014 – 2021:

Flu activity was unusually low throughout the 2020-2021 flu season both in the United States and globally, despite high levels of testing. During September 28, 2020–May 22, 2021 in the United States, 1,675 (0.2%) of 818,939 respiratory specimens tested by U.S. clinical laboratories were positive for an influenza virus. The low level of flu activity during this past season contributed to dramatically fewer flu illnesses, hospitalizations, and deaths compared with previous flu seasons. For comparison, during the last three seasons before the pandemic, the proportion of respiratory specimens testing positive for influenza peaked between 26.2% and 30.3%. In terms of hospitalizations, the cumulative rate of laboratory-confirmed influenza-associated hospitalizations in the 2020-2021 season was the lowest recorded since this type of data collection began in 2005. For pediatric deaths, CDC received one report of a pediatric flu death in a child during the 2020–2021 flu season. Since flu deaths in children became nationally notifiable in 2004, reported flu deaths in children had previously ranged from a low of 37 (during 2011-2012) to a high of 199 (during 2019-2020).

What are possible explanations for the unusually low flu activity? COVID-19 mitigation measures such as wearing face masks, staying home, hand washing, school closures, reduced travel, increased ventilation of indoor spaces, and physical distancing, likely contributed to the decline in 2020-2021 flu incidence, hospitalizations and deaths. Influenza vaccination may also contributed to reduced flu illness during the 2020–2021 season. Flu vaccine effectiveness estimates for 2020-2021 are not available, but a record number of influenza vaccine doses (193.8 million doses) were distributed in the U.S. during 2020-2021.
How many people got vaccinated against flu during the 2020-2021 flu season and how does that compare to previous seasons? While final estimates are pending, early estimates based on survey data suggest flu vaccination uptake for 2020-2021 was similar to the prior season, with small increases among some groups of people and small decreases among other groups of people. Estimates indicate that 50% to 55% of adults got a flu vaccine (compared with the 2019–2020 estimate of 48% by end of May 2020). But influenza vaccines in kids dropped 4.1 percentage points from 62.3% during 2019-2020 to 58.2% during 2020–2021 and estimates for pregnant people and health care personnel indicated slight decreases in influenza vaccine coverage. Racial and ethnic disparities in flu vaccine uptake persisted for children and adults. Because racial and ethnic minority groups might be at higher risk for developing serious illness, resulting from flu that may lead to hospitalization, flu vaccination is especially important for these communities.
Flu viruses are constantly changing so it’s not unusual for new flu viruses to appear each year. During the 2020-2021 flu season, there was very low circulation of seasonal flu viruses. During that same period, public health laboratories reported 61.4% of influenza positive samples were influenza A and 38.6% of positive samples were influenza B. The majority (52.5%) of influenza A viruses were H3N2, and the majority (60%) of influenza B viruses were of Victoria lineage. In terms of novel influenza viruses, CDC reported 5 human infections with an influenza virus that usually spreads in pigs and not people (called a variant influenza virus) in the United States. All five of these infections occurred in people who reported that they had direct exposure to pigs or lived on a property where pigs were present. No person-to-person spread of variant influenza was identified associated with any of these patients. These types of infections occur in people rarely, and usually in the context of exposure to pigs, but are concerning because of their pandemic potential. Since 2005, a total of 489 variant influenza virus infections have been identified:

https://www.cdc.gov/flu/season/faq-flu-season-2020-2021.htm

Having a new variant around rejiggers the pandemic risk landscape, and that landscape is now looking less favourable to us. Pfizer, for instance, now says that, based on early data, a booster might be necessary to maintain a high level of protection against Omicron. Booster uptake’s been somewhat spotty, though, even among people for whom it’s been recommended since September. In the US about one in four fully vaccinated adults says they will either “probably not” or “definitely not” boost, according to a recent KKF poll though Omicron seems a boost to those who are undecided. And >50% of inoculated adults >65, obviously a group at highest risk of severe COVID-19, and one of the earliest groups to be urged to vaccinate again, have not received an additional injection:


No single concern is keeping millions of eligible Americans on the booster fence, and some of these numbers almost certainly reflect a pre-Omicron mindset. Anecdotally, finding a booster appointment in many parts of the country is now nearly impossible. But a few key questions seem to be percolating on repeat. Here’s a rundown of the thinking that helped some of the now-boosted reckon with the choice—and roll up our sleeves again.

Do I really need a booster? Understanding the benefits of boosting now means acknowledging two truths. Our vaccines are still doing an amazing job at staving off really severe disease. And adding an extra dose will probably keep people even safer. When COVID vaccines first started rolling out last winter, they were an absolute knockout on just about every metric by which they were measured, not only preventing serious disease and death, but also limiting infections and transmission to a very high degree. Now, several months out, more vaccinated people are briefly contracting the coronavirus, and maybe getting a little sick as antibody levels naturally tick down over time. But the vaccines are still stellar enough to keep most people from getting really sick. That’s thanks to a legion of immune memory cells that can pump out more when needed, or blow up virus-infected cells. Those hyper-durable defences take some time to kick in, though, and can’t block all mild cases.

Boosters, then, remind the immune system of an old threat, lifting antibody levels or T cell responses and recruiting new immune cells to the front line. People who receive boosters are less likely to be infected versus those who don’t. The shots are clearly conferring benefits, though the jury’s still out on how long they’ll last. The pluses are especially big for people who are older, and they’re essential for t he immunocompromised (who probably needed a three-dose vaccine to begin with).

For everyone else, boosting has looked more like a perk than a must-have: If defences against the most serious forms of COVID-19 were holding, a touch-up wasn’t urgent. But a vaccine’s effectiveness can be chipped away from two ends: a drop in the body’s defences, and a swell in the virus’s offences. And Omicron has clearly raised the stakes. The variant’s genome is laced with dozens of mutations that weren’t present in its predecessors’. Even if my body retained a perfect memory of my vaccines’ contents, these changes might still bamboozle it.

Now we have a mismatch between variant and vaccine, thus, there will be a “significant drop” in our antibodies’ ability to protect us from milder outcomes, a trend that appears to be borne out by early data. An extra dose of vaccine—even one that’s an imperfect pantomime of Omicron—would shore up important defences in advance of a surge. A drop in antibody protection would likely still happen because of Omicron’s genetic quirks, but the fall would be cushioned by sheer quantity—a trend that a press release from Pfizer now appears to confirm. While other studies contradict that.

We’re also still dealing with Delta, a variant that vaccines definitely keep in check, especially as we head into the holidays. So this could be a double whammy. While case rates remain high, reinforcing protections against infection and transmission could cocoon the still-vulnerable, and tamp down outbreaks.

Shouldn’t we be holding out for an Omicron booster? If we could, then, yes, the ideal defence against Omicron would involve inoculating everyone (everyone) with a vaccine that’s a perfect match for the variant. To some, boosting with a vaccine modelled on the now-obsolete coronavirus might feel a bit like upgrading to an iPhone SE three months before an iPhone 13 mega-sale.

And yet, every expert I’ve spoken with has delivered an unequivocal verdict: boosting now is still the right choice—to get ahead of Omicron, to prepare ourselves. A bespoke Omicron recipe isn’t yet available, and won’t be for at least 2 months. The goal is to provide interim protection before the wave of Omicron crests. And we may never need an Omicron-specific booster, making a wait unwise. Omicron’s genetic tweaks make it a touch unfamiliar, but not completely unrecognisable. Additional doses of vaccine have been shown to enhance the quantity and quality of antibodies that can thwart all known variants, maybe.

Even if an Omicron-specific vaccine is on the horizon, we should be able to get both, if they need to. That could be warranted if Omicron’s really, really good at dodging some of our immune defences. In that case, getting an Omicron-keyed booster would almost be like rolling out an entirely new vaccine. It would coax our body into recruiting fresh crops of immune cells to fight, rather than only marshalling old ones back to the fore.

If we’re boosting so often, won’t side effects get worse? This is one of the most common concerns I’ve heard. Some people had such rough experiences with their first set of vaccines that they’ve been so far unwilling to sign up for a repeat. Side effects can mean taking time off work, or sleeping through an entire weekend, and on very rare occasions, even worse outcomes. Second shots, on average, were tougher to take than the first. But that doesn’t mean the third shot will ratchet up the gnarliness. Thus far we have found that boosters’ side-effect profile is actually pretty comparable to that of the initial two doses, or somewhere in between them. The body’s had months to calm down since its last exposure. And for those on Team Moderna, the booster’s just a half dose, less likely to rile cells up.

A few other people are worried that boosting now would mean they’d have to boost again, and again, and again. That won’t necessarily be the case: some experts hope that a third dose will, for at least the mRNA vaccines, take us up to a new and lasting level of protection. In that optimistic scenario, we might not need another dose of vaccine, or another bout of side effects, for a long time—unless, of course, more problem variants show up.

Several people also raised concerns over the very rare, but very serious, side effects that have been linked to the vaccines—the blood clots that have occasionally followed the Johnson & Johnson shot, and the heart inflammation that can appear after mRNA vaccination. These events are so uncommon that even large trials can’t always identify them, and researchers are still trying to figure out how often they occur after boosts. Still, the chances of a severe side effect popping up after a booster dose remain, in absolute terms, extremely low. And the calculus is clear: eventually, all of us will be exposed to the virus. That’s the framework we should be using when deciding to boost: the risk of experiencing a truly negative health outcome is much higher with COVID itself.

What about vaccine equity? Boosters, by lifting up antibody levels, make bodies less hospitable to the virus; that cuts the conduits the pathogen needs to travel. On a population scale, that logically translates into trimmer, tamer outbreaks, but boosters alone can’t be pandemic-enders, especially when so many people remain entirely unvaccinated. Omicron might be shifting the conversation on boosters but getting the unvaccinated vaccinated is more important.

Declining a boost won’t magically inject a vaccine into the arm of someone in Burundi, one of a large number of countries with immunisation rates <1%. But the heavy focus on boosters in wealthy countries risks diverting attention, resources, and human power away from administering first doses, the goal most prioritised by the WHO. It also sends a pretty strong signal about where nations’ priorities lie. At this point, the number of American booster doses that have been doled out exceeds the number of primary injections that have been given in most other countries. Neglecting vaccine equity can also have compounding consequences: the more who remain unprotected, the more variants will arise.

Snippets:

The emergence of the B.1.617.2 (delta) variant and the reduced effectiveness over time of the BNT162b2 vaccine (Pfizer–BioNTech) led to a resurgence of coronavirus disease 2019 (Covid-19) cases in populations that had been vaccinated early. On July 30, 2021, the Israeli Ministry of Health approved the use of a third dose of BNT162b2 (booster) to cope with this resurgence. Evidence regarding the effectiveness of the booster in lowering mortality due to Covid-19 is still needed. A total of 843,208 participants met the eligibility criteria, of whom 758,118 (90%) received the booster during the 54-day study period. Death due to Covid-19 occurred in 65 participants in the booster group (0.16 per 100,000 persons per day) and in 137 participants in the nonbooster group (2.98 per 100,000 persons per day). The adjusted hazard ratio for death due to Covid-19 in the booster group, as compared with the nonbooster group, was 0.10 (95% confidence interval, 0.07 to 0.14; P<0.001). Participants who received a booster at least 5 months after a second dose of BNT162b2 had 90% lower mortality due to Covid-19 than participants who did not receive a booster:


https://www.nejm.org/doi/full/10.1056/NEJMoa2115624

After promising initial results from the administration of a third (booster) dose of the BNT162b2 messenger RNA vaccine (Pfizer–BioNTech) to persons 60 years of age or older, the booster campaign in Israel was gradually expanded to persons in younger age groups who had received a second dose at least 5 months earlier. The rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of approximately 10 (range across five age groups, 9.0 to 17.2) and was lower in the booster group than in the early postbooster group by a factor of 4.9 to 10.8. The adjusted rate difference ranged from 57.0 to 89.5 infections per 100,000 person-days in the primary analysis and from 34.4 to 38.3 in the secondary analysis. The rates of severe illness in the primary and secondary analyses were lower in the booster group by a factor of 17.9 (95% confidence interval [CI], 15.1 to 21.2) and 6.5 (95% CI, 5.1 to 8.2), respectively, among those 60 years of age or older and by a factor of 21.7 (95% CI, 10.6 to 44.2) and 3.7 (95% CI, 1.3 to 10.2) among those 40 to 59 years of age. The adjusted rate difference in the primary and secondary analyses was 5.4 and 1.9 cases of severe illness per 100,000 person-days among those 60 years of age or older and 0.6 and 0.1 among those 40 to 59 years of age. Among those 60 years of age or older, mortality was lower by a factor of 14.7 (95% CI, 10.0 to 21.4) in the primary analysis and 4.9 (95% CI, 3.1 to 7.9) in the secondary analysis. The adjusted rate difference in the primary and secondary analyses was 2.1 and 0.8 deaths per 100,000 person-days. Across the age groups studied, rates of confirmed Covid-19 and severe illness were substantially lower among participants who received a booster dose of the BNT162b2 vaccine than among those who did not:

On the basis of this decline in vaccine effectiveness against infection and the growing number of hospitalizations among vaccinated persons, Israel recommended booster doses of the BNT162b2 vaccine (Pfizer–BioNTech) in July 2021, starting with persons 60 years of age or older and then quickly expanding to all persons 12 years of age or older. At the time, no data regarding the effectiveness of booster doses had been published. However, studies above provide much-needed evidence of the effectiveness of the booster dose.

Booster vaccine effectiveness can be calculated as 1 minus the adjusted rate or hazard ratio among persons who received a booster, as compared with persons who did not receive a booster or with unvaccinated persons. Whereas the absolute effectiveness can be calculated by comparing the risk among persons who received two vaccine doses plus a booster with the risk among unvaccinated persons, the investigators in these two studies evaluated the effect of the booster by comparing the risk among those who received two doses plus a booster with the risk among those who received two doses. Although neither study showed a formal calculation of booster vaccine effectiveness, data from both studies indicated relative effectiveness against severe disease or death of 90 to 95%. This means that if the absolute effectiveness of two vaccine doses is 90%, the absolute effectiveness of two doses plus a booster is 99 to 100%.

In a setting such as Israel, where vaccination coverage is high and vaccine supply is sufficient, the analytic approach taken in these studies is reasonable. The few remaining unvaccinated people are probably different from vaccinated people in terms of characteristics beyond vaccination status that affect the risk of infection — for example, they may have different behaviours — and such differences could lead to bias. Persons who received the booster were different from those who did not receive the booster in terms of age group, which affects the risk of infection. Their secondary analysis, which compared the rates among persons who had received the booster at least 12 days earlier with the rates among persons who had received the booster 3 to 7 days earlier, is useful in supporting their findings, because it decreases some of the bias that arises in comparing the rates with those among two-dose recipients. Data provided by these two studies, along with other data regarding booster effectiveness and safety that are being generated, will provide valuable guidance for decision making in other countries, as the risk–benefit balance of introducing a booster dose is assessed.

As of November 23, 2021, a total of 107 countries are providing additional or booster doses to at least some segment of the population. However, while some countries are offering booster doses, many countries are still struggling to vaccinate their population with the primary series. Population coverage with a full primary series is less than 10% in 45 countries and less than 40% in 105 countries. The low current vaccination rates are largely due to limited vaccine supply in low-income countries, which is forecasted to be resolved by early 2022, although challenges will remain in ensuring that everyone is vaccinated.

Many factors must be considered in a decision to offer a booster. A country might choose to introduce a booster dose in certain segments of the population, depending on the epidemiologic situation, vaccination coverage, population immunity due to infection-induced immunity, and other factors, such as the need to maintain an essential workforce. However, many countries need to determine the best use of their limited vaccine supply in the near future. In most settings, more is still to be gained by focusing on vaccinating the unvaccinated. One U.S. analysis of direct benefits showed that, among those 65 years of age or older, 481 persons needed to be vaccinated with a booster dose to prevent one hospitalization, whereas 50 persons needed to be vaccinated with the primary series to prevent one hospitalization; among those 18 to 29 years of age, 8738 persons needed to be vaccinated with a booster dose to prevent one hospitalization, whereas 396 persons needed to be vaccinated with the primary series. Thus, it is important that vaccination with the primary series, especially in high-risk populations, remain a top priority everywhere, because this will ultimately lead to a greater reduction in severe disease and death:

https://www.nejm.org/doi/full/10.1056/NEJMoa2115926

Using national data (mainly from the CMS Covid-19 Nursing Home Public File database), researchers classified 12,364 nursing homes (81% of all nursing homes in the United States) into quartiles of provider staff Covid-19 vaccination coverage as of June 13, 2021. They determined the number of Covid-19 cases among residents, the number of Covid-19 cases among staff, and the number of Covid-19–related deaths among residents (each per 100 facility beds) between June 13 and August 22, 2021. In counties in the highest quartile of prevalence of Covid-19, the lowest quartile of staff vaccination coverage was associated with 1.56 (95% confidence interval [CI], 1.05 to 2.07) additional Covid-19 cases per 100 beds among residents, 1.50 (95% CI, 1.06 to 1.94) additional cases per 100 beds among staff, and 0.19 (95% CI, 0.08 to 0.30) additional Covid-19–related deaths of residents per 100 beds relative to facilities in the same county that were in the highest quartile of staff vaccination. These values represented outcomes that were 132%, 58%, and 195% higher, respectively, than those of predicted outcomes if all the facilities had had high vaccination coverage. In counties in the lowest quartile of prevalence of Covid-19, higher staff vaccination coverage was associated with small differences in Covid-19 outcomes. Estimates suggest that if all the nursing homes in their sample had been in the highest quartile of staff vaccination coverage (82.7% on average), 4775 cases among residents (29% of the total during the study window), 7501 cases among staff (29% of the total), and 703 Covid-19–related deaths among residents (48% of the total) could possibly have been prevented. In the presence of high community prevalence of Covid-19, nursing homes with low staff vaccination coverage had higher numbers of cases and deaths than those with high staff vaccination coverage. These findings show the extent to which staff vaccination protects nursing home residents, particularly in communities with high Covid-19 transmission:


https://www.nejm.org/doi/full/10.1056/NEJMc2115674

Soon after the first case of infection with the B.1.1.7 (alpha) variant was identified in the United Kingdom in September 2020, researchers determined that the new variant had several genetic alterations: a N501Y mutation, which increased the viral binding affinity with angiotensin-converting–enzyme 2 receptor; a H69del/V70del mutation, which was potentially associated with immune evasion and affected S-gene polymerase-chain-reaction (PCR) assays, resulting in S-gene target failure; and a P681H mutation, which potentially facilitated epithelial-cell entry. Direct estimates of the potential of a variant for expansion and increased transmission are limited but have important implications for the global dissemination of these and future SARS-CoV-2 variants. Their direct population-level analysis confirmed that the SARS-CoV-2 alpha variant was associated with a higher infection rate than other variants that were circulating in the United Kingdom during the study period:


https://www.nejm.org/doi/full/10.1056/NEJMc2103227

In an ongoing phase 2–3, placebo-controlled trial, researchers randomly assigned healthy adolescents (12 to 17 years of age) in a 2:1 ratio to receive two injections of the mRNA-1273 vaccine (100 μg in each) or placebo, administered 28 days apart. A total of 3732 participants were randomly assigned to receive mRNA-1273 (2489 participants) or placebo (1243 participants). In the mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 93.1% and 92.4%, respectively), headache (in 44.6% and 70.2%, respectively), and fatigue (in 47.9% and 67.8%, respectively); in the placebo group, the most common solicited adverse reactions after the first or second injections were injection-site pain (in 34.8% or 30.3%, respectively), headache (in 38.5% and 30.2%, respectively), and fatigue (in 36.6% and 28.9%, respectively). No serious adverse events related to mRNA-1273 or placebo were noted. The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24), and the absolute difference in serologic response was 0.2 percentage points (95% CI, −1.8 to 2.4), which met the noninferiority criterion. No cases of Covid-19 with an onset of 14 days after the second injection were reported in the mRNA-1273 group, and four cases occurred in the placebo group. The mRNA-1273 vaccine had an acceptable safety profile in adolescents. The immune response was similar to that in young adults, and the vaccine was efficacious in preventing Covid-19:


Justin Stebbing
Managing Director

105 Wigmore Street
London W1U 1QY
 

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