Virus World

Rapid Antigen Tests (RAT) have become an invaluable tool for combating the COVID-19 pandemic. However, concerns have been raised regarding the ability of existing RATs to effectively detect emerging SARS-CoV-2 variants. We compared the performance of eight commercially available, emergency use authorized RATs against the Delta and Omicron SARS-CoV-2 variants using individual patient and serially diluted pooled clinical samples. The RATs exhibited lower sensitivity for Omicron samples when using PCR Cycle threshold (CT) value (a proxy for RNA concentration) as the comparator. Interestingly, however, they exhibited similar sensitivity for Omicron and Delta samples when using quantitative antigen concentration as the comparator. We further found that the Omicron samples had lower ratios of antigen to RNA, which offers a potential explanation for the apparent lower sensitivity of RATs for that variant when using CT value as a reference. Our findings underscore the complexity in assessing RAT performance against emerging variants and highlight the need for ongoing evaluation in the face of changing population immunity and virus evolution.

Preprint available in medRxiv (Feb. 10, 2023):

https://doi.org/10.1101/2023.02.09.23285583 

Evidence from sewage reveals resilience of last year’s coronavirus killer, indicating a possible outbreak of Delta or another variant this summer.  Just when we thought we were out of the Covid woods, researchers at Ben-Gurion University of the Negev are sounding the alarm. Omicron, the variant that evolved to be somewhat less deadly than previous Covid flavors, may burn itself out in the next couple of months. Omicron and its sub-variants (BA.2, BA.3, BA.4, BA.5 and presumably more on the way) have been so contagious that the previous big bad – Delta – was thought to be wiped out. 

We identified the co-infection of the SARS-CoV-2 Omicron and Delta variants in two epidemiologically unrelated patients with chronic kidney disease requiring haemodialysis. Both SARS-CoV-2 variants were co-circulating locally at the time of detection. Amplicon- and probe-based sequencing using short- and long-read technologies identified and quantified Omicron and Delta subpopulations in respiratory samples from the two patients. These findings highlight the importance of genomic surveillance in vulnerable populations.

Preprint available in medRxiv (Feb. 15, 2022):

https://doi.org/10.1101/2022.02.13.22270755

Several Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) neutralising monoclonal antibodies (mAbs) have received emergency use authorisation by regulatory agencies for treatment and prevention of Coronavirus Disease 2019 (COVID-19), including in patients at risk for progression to severe disease. Here we report the persistence of viable SARS-CoV-2 in patients treated with sotrovimab and the rapid development of spike gene mutations that have been shown to confer high level resistance to sotrovimab in vitro. We highlight the need for SARS-CoV-2 genomic surveillance in at risk individuals to inform stewardship of mAbs use and prevent potential treatment failures.

Preprint available in medRxiv (Dec. 21, 2021):

https://doi.org/10.1101/2021.12.18.21267628 

The delta variant, first detected in India a little less than a year ago, now represents 99% of sequenced Covid-19 cases globally.

• Almost all of the up to 900,000 Covid cases sequenced worldwide over the last 60 days originated from the delta strain, Maria Van Kerkhove, the WHO’s technical lead on Covid, said.
• Europe accounted for roughly 60% of the more than 3.3 million new cases in the world last week, Van Kerkhove said.
• Covid cases worldwide have been increasing over the last four consecutive weeks, she added. 

The delta variant, first detected in India a little less than a year ago, now represents 99% of sequenced Covid-19 cases globally, making it more prevalent than any other strain, officials from the World Health Organization said Tuesday. Almost all of the up to 900,000 Covid cases sequenced worldwide over the last 60 days originated from the delta strain, Maria Van Kerkhove, the WHO’s technical lead on Covid, said during a Q&A streamed on the organization’s social media channels. Van Kerkhove’s comments come amid an international increase in Covid infections driven by surging cases in Europe. The Continent accounted for roughly 60% of the more than 3.3 million new cases in the world last week, Van Kerkhove said. “Delta is really the dominant one,” Van Kerkhove said. “And there are two variants of interest – mu and lambda – that we’ve been tracking as well, but again, where delta is present, delta takes over.”   

Van Kerkhove said Europe represented more than half of the just under 50,000 global Covid deaths in the last week, a 5% increase in fatalities across the Continent. Covid cases worldwide have been increasing over the last four consecutive weeks, she added. “The pandemic is heading in the wrong direction at the moment,” Van Kerkhove said. The decreased use of masks and social distancing are to blame for Europe’s surge, Van Kerkhove said at a briefing last week. She cautioned Tuesday that societies reopening across the Northern Hemisphere this winter could lead to a rise in respiratory illnesses over the months ahead, including influenza and other pathogens. Select European countries are bearing the brunt of the surge. Germany set a record seven-day average of nearly 39,300 new cases on Monday, up almost 40% from the week before, according to a CNBC analysis of data from Johns Hopkins University. The U.K. tallied a weekly average of more than 38,500 new cases Monday, an increase of 13% from the previous week. Seven-day averages in France and Italy were both up by nearly 40% as well. Russia also saw a pandemic high seven-day average of roughly 1,199 deaths on Monday, Johns Hopkins reported. But its seven-day average case count, over 38,000 infections, decreased by more than 2%.

A new study adds to growing evidence suggesting that the Delta coronavirus variant is not only highly transmissible, but also more dangerous.  Covid-19 patients infected with the Delta variant had about double the risk of hospitalization compared to those infected with the Alpha variant, according to the study published Friday in the journal Lancet Infectious Diseases. "The results suggest that patients with the Delta variant had more than two times the risk of hospital admission compared with patients with the Alpha variant," researchers from Public Health England and the University of Cambridge wrote in their new study. "Emergency care attendance combined with hospital admission was also higher for patients with the Delta variant, showing increased use of emergency care services as well as inpatient hospitalization," the researchers wrote.

Less than a month into a COVID-19 vaccine booster drive, Israel is seeing signs of an impact on the country's high infection and severe illness rates fuelled by the fast-spreading Delta variant, officials and scientists say. Delta hit Israel in June, just as the country began to reap the benefits of one of the world's fastest vaccine roll-outs. With an open economy and most curbs scrapped, Israel went from single-digit daily infections and zero deaths to around 7,500 daily cases last week, 600 people hospitalized in serious condition and more than 150 people dying in that week alone. On July 30, it began administering a third dose of the Pfizer (PFE.N)/BioNtech (22UAy.DE) vaccine to people over 60, the first country to do so. On Thursday it expanded eligibility to 30-year-olds and up whose second dose was given at least 5 months prior, saying the age may drop further.  In the past 10 days, the pandemic is abating among the first age group, more than a million of whom have received a third vaccine dose, according to Israeli health ministry data and scientists interviewed by Reuters. The rate of disease spread among vaccinated people age 60 and over - known as the reproduction rate - began falling steadily around Aug. 13 and has dipped below 1, indicating that each infected person is transmitting the virus to fewer than one other person. A reproduction rate of less than 1 means an outbreak is subsiding. https://tmsnrt.rs/3grj7kv Scientists said booster shots are having an impact on infections, but other factors are likely contributing to the decline as well.  "The numbers are still very high but what has changed is that the very high increase in the rate of infections and severe cases has diminished, as has the pace at which the pandemic is spreading," said Eran Segal, data scientist at the Weizmann Institute of Science and an adviser to the government. "This is likely due to the third booster shots, an uptake in people taking the first dose and the high number of people infected per week, possibly up to 100,000, who now have natural immunity," Segal said. 

BOOSTER VS LOCKDOWN

After reaching one of the highest per-capita infection rates in the world this month, the question now is whether Israel can battle its way out of a fourth outbreak without imposing another lockdown that would damage its economy.  Evidence has emerged showing that while the vaccine is still highly effective in preventing serious illness, its protection diminishes with time. But there is no consensus among scientists and agencies that a third dose is necessary, and the World Health Organization has said more of the world should be vaccinated with a first dose before people receive a third dose. read more The United States has announced plans to offer booster doses to all Americans, eight months after their second vaccine dose, citing data showing diminishing protection. Canada, France and Germany have also planned booster campaigns. About a million of Israel's 9.3 million population have so far chosen not to vaccinate at all and children under 12 are still not eligible for the shots. On Thursday, health officials said they have identified waning immunity among people under 40, although relatively few have fallen seriously ill. read more 

According to Doron Gazit, a member of the Hebrew University's COVID-19 expert team which advises government, the rise in cases of severely ill vaccinated people in the 60 and older group has been steadily slowing to a halt in the last 10 days. "We attribute this to the booster shots and to more cautious behaviour recently," Gazit said.  More than half of those over 60 have received a third jab, according to the Health ministry. The rate of new severe cases among unvaccinated patients 70 and older is now seven times that of vaccinated patients, and the gap will continue to grow as long as infections rise, according to Gazit. Among those over 50, that gap is four-fold. "We are optimistic, but very cautious," Israeli Health Minister Nitzan Horowitz told public broadcaster Kan on Sunday. "It gives us more time, slows the spread and we're moving away from lockdown." But even if the boosters are slowing the pandemic's pace, it is unlikely to fend Delta off entirely. Dvir Aran, biomedical data scientist at Technion - Israel's Institute of Technology, said that while cases are retreating, other measures are needed alongside boosters to stop the pandemic. "It will take a long time until enough people get a third dose and until then thousands more people will getting seriously ill." Since Delta's surge, Israel has reimposed indoor mask wearing, limitations on gatherings and ramped up rapid testing. Its "living with COVID" policy will be tested come September, when schools reopen after summer break and when the Jewish holiday season starts, with families traditionally gathering to celebrate.

Concerns over waning immunity and SARS-CoV-2 variants have convinced some countries to deploy extra vaccine doses — but it’s not clear to scientists whether most people need them.  To boost or not to boost? That is the question facing countries fortunate enough to have vaccinated much of their adult population. In the face of soaring infection numbers caused by the highly contagious Delta variant of SARS-CoV-2, and hints that immunity triggered by COVID-19 vaccines might fade over time, some countries are considering whether to give further doses to those who have been fully vaccinated. Germany and Israel have announced plans for booster-shot programmes, and a growing list of countries including the United Arab Emirates, China and Russia have already started administering extra doses. But scientists say that the case for COVID-19 vaccine boosters at this point is weak. They might not be necessary for most people, and could divert much-needed doses away from others. On 4 August, the World Health Organization called for a moratorium on boosters until at least the end of September. “Wasting resources on boosters for those who are already protected against severe disease does not really make too much sense,” says Laith Jamal Abu-Raddad, an infectious-disease epidemiologist at Weill Cornell Medicine—Qatar in Doha. “Down the line, probably, we would need to think of it. But really, we don’t have strong arguments for it right now.”  The data on whether and when boosters might be needed are trickling in. But it’s likely that key gaps will remain for some time. As a result, people might start getting boosters that have no real benefit. Meanwhile, not enough is known about groups that might really need extra doses, such as older people and those with compromised immune systems. And, as the Delta variant surges in many countries, health authorities might not have the luxury of waiting around for definitive answers. “It’s a difficult call and it will almost certainly have to be made on incomplete evidence,” says Robert Aldridge, an infectious-disease epidemiologist at University College London. Here, Nature looks at what scientists know — and what they wish they knew — about COVID-19 vaccine boosters.

Do boosters actually work?

Vaccination produces an initial surge in the number of immune cells churning out antibodies and other molecules, which then slowly drops. This leaves behind a small pool of long-lasting ‘memory’ B and T cells that patrol the body for future infections by that pathogen.  A booster does several things to these cells, says Ali Ellebedy, a B-cell immunologist at Washington University in St. Louis, Missouri. It causes antibody-making B cells to multiply, elevating the levels of antibodies against the pathogen once more. In time, their numbers will dwindle again, but the pool of memory B cells left behind will be larger than before, leading to a faster, stronger response to subsequent exposures. Boosters also promote a process called affinity maturation, in which ‘engaged’ B cells — those that have been triggered by the vaccine — travel to the lymph nodes. Here, they gain mutations, making the antibodies they produce bind to pathogens more strongly, potentially enhancing their potency. Numbers of memory B cells and antibody levels will eventually plateau with repeated boosting (or reinfection), but it is unlikely that such levels have been reached in people who have had the recommended regimen of COVID-19 vaccine or a previous infection, says Ellebedy. A booster shot should elicit stronger immune responses, says Rafi Ahmed, an immunologist at Emory University in Atlanta, Georgia. “It will boost.” The few trials to have tested extra doses support this. Third doses of vaccines developed by Moderna, Pfizer–BioNTech, Oxford–AstraZeneca and Sinovac prompted a spike in levels of infection-blocking ‘neutralizing’ antibodies, when administered several months after the second dose. An ongoing UK trial will test various combinations of boosters, including using a different vaccine from the original inoculations. Preliminary studies of these ‘mix and match’ strategies suggest that they could lead to more robust immune responses, characterized by high levels of both antibodies and T cells, which kill infected cells and support other antiviral responses1,2,3. These trials also suggest that common vaccine-related side effects, such as headache and fever, aren’t very different from those seen with earlier immunizations. “I would take a third dose at some point,” Ahmed says. “I don’t see a downside.”

Is immunity from vaccines waning?

Scientists typically look at antibody levels, or titres, as a proxy for how well a vaccine has worked. These usually spike along with the surge in short-lived B cells and then fall as the cells dwindle. Memory B cells and bone-marrow plasma cells continue to churn out antibodies, but at reduced levels, for decades. That’s expected. “There isn’t a vaccine where you don’t see a drop over time in antibody titres and T-cell titres,” says Ahmed. “There is always a drop.” Early indications suggest that antibody levels triggered by most COVID-19 vaccines are falling, too4. What scientists don’t know is whether these drops reflect a decline in protection against the virus. Teams around the world are racing to determine what level of neutralizing antibodies or another immune marker is most closely associated with a vaccine’s effectiveness. They’re seeking what’s known as a correlate of protection. “What that magic number is, is something that we have a hint of — but not a firm handle on,” says Kanta Subbarao, a virologist at the Peter Doherty Institute for Infection and Immunity in Melbourne, Australia. Knowing this threshold would allow researchers to determine more precisely whether and when a booster becomes necessary — such as in response to waning immunity or to the emergence of new variants that evade antibody recognition. “Without having that properly defined correlate, it’s hard to say if we really need a booster,” says Ellebedy.

Are vaccinations given months ago still preventing infections?

In the absence of a reliable correlate of protection, researchers are looking for signs of waning immunity in real-world data from countries that have advanced vaccination programmes. Are people who were vaccinated early on getting infected at higher rates than those who were vaccinated more recently? Drawing clear conclusions from such data is fraught, says Dvir Aran, a biomedical data scientist at Technion — Israel Institute of Technology in Haifa. Last month, the Ministry of Health in Israel, a country that has one of the world’s highest vaccination rates, released raw data on vaccinations and infections from December 2020 to July 2021. The ministry estimated that vaccine protection against both infection and disease had dropped from above 90% in the early months of its programme to around 40% by late June — a decline that could be due to the effects of the Delta variant. To look more closely for evidence of waning protection, scientists at Kahn Sagol Maccabi in Tel Aviv — the research arm of Israeli health-maintenance organization Maccabi Healthcare Services — analysed health records from more than 1.3 million people who were vaccinated between January and April 2021. Those vaccinated in January and February were 53% more likely to test positive for SARS-CoV-2 during those four months, compared with people vaccinated in March and April. The differences were even starker among the earliest and latest vaccinated5.  But reduced protection isn’t the only explanation for this observation, says Aran. Data were stratified by age groups, and younger individuals who were vaccinated early on tended to be health-care workers, who are at a higher risk of infection than the younger people vaccinated later. Early-vaccinated individuals also tended to be wealthier than people who got vaccinated later in Israel, and might have taken COVID-19 tests at a higher rate because of worries over the virus or an eagerness to travel internationally. That could introduce biases into the data, says Aran. Another way to weigh the evidence in support of boosters is efficacy trials — the double-blinded, placebo-controlled, randomized studies used to earn vaccine authorization by health authorities. On 28 July, researchers at Pfizer–BioNTech, who have pushed strongly for third doses, published data on the preprint server medRxiv showing that the vaccine’s efficacy against symptomatic disease had slipped from 96% to 84% after 6 months6. Before that, an April press release from Moderna put its vaccine’s efficacy at “greater than 90%” after half a year, compared to its original efficacy figure of 94%. These trials are meant to minimize confounding variables that dog real-world studies. But once vaccines became publicly available, Pfizer and other vaccine-makers unblinded the studies, allowing participants to learn whether they had received a vaccine or a placebo. “All the participants heard the news about the 95% protection and those that received the vaccine would clearly feel more safe and will take more risks,” says Aran, who thinks this behaviour change — and not waning protection — could explain the apparent drop in the efficacy of the Pfizer–BioNTech vaccine. Representatives from Pfizer had no comment on this hypothesis....

Published in Nature (August 5, 2021):

https://doi.org/10.1038/d41586-021-02158-6

Background

The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT162b2 and ChAdOx1 nCoV-19 vaccines against this variant has been unclear.

Methods

We used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Variants were identified with the use of sequencing and on the basis of the spike (S) gene status. Data on all symptomatic sequenced cases of Covid-19 in England were used to estimate the proportion of cases with either variant according to the patients’ vaccination status.

Results

Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant.

Conclusions

Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations. (Funded by Public Health England.)

Published in NEJM (July 21, 2021):

https://doi.org/10.1056/NEJMoa2108891 

What is the delta plus variant of SARS-CoV-2? Learn how it differs from the delta variant, why it is a variant of concern, and whether vaccines work against it. A novel SARS-CoV-2 variant, the delta plus variant, has been identified in over 10 countries. Health authorities are raising concerns that the variant may have an increased ability to transmit, but they also note that this variant’s transmissibility is likely similar to that of the preexisting delta variant.  As ever more SARS-CoV-2 variants emerge, governments and public health experts continue to consider the best strategies to contain their spread. There are currently 11 variants of the SARS-CoV-2 virus that the World Health Organization (WHO)Trusted Source is monitoring. One of these variants, the delta variant — also known as the B.1.617.2 lineage — was first identified in India in December 2020 and quickly became the most common variant in the country. It has demonstrated 40–60% increased transmission, in comparison with the previously dominant alpha variant, and is currently the dominant SARS-CoV-2 variant in the United Kingdom.

Meanwhile, researchers recently identified another variant — the delta plus variant, also known as B.1.617.2.1 or AY.1. The U.K. governmental agency Public Health England first declared it a “variant of concern” in a June 11 briefing, and on June 22, Indian authorities followed suit. Since then, 11 countries have reported a collective 197 cases of COVID-19 caused by the delta plus variant of SARS-COV-2. The delta plus variant is a sublineage of the delta variant, with the only known difference being an additional mutation, K417N, in the virus’ spike protein, the protein that allows it to infect healthy cells. This mutation is also found in the beta and gamma variants, which researchers first identified in South Africa and Brazil, respectively.

The WHO shared with Reuters that “For the moment, this variant does not seem to be common, currently accounting for only a small fraction of the delta sequences.” Yet, “Delta and other circulating variants of concern remain a higher public health risk, as they have demonstrated increases in transmission,” the WHO added. Furthermore, since India has labeled this variant a “variant of concern,” the country’s SARS-CoV-2 Consortium on Genomics (INSACOG), which is made up of 28 laboratories dedicated to whole genome sequencing of the SARS-CoV-2 virus and its evolving variants, continues to follow the evolution of delta plus. INSACOG lists the following concerns regarding the delta plus variant:

• increased transmissibility
• stronger binding to receptors of lung cells
• potential reduction in monoclonal antibody response

The spike protein is responsible for binding to a cell’s surface receptors, allowing the virus to enter. A mutation in the protein may strengthen this interaction, which could increase transmissibility, as per these first two points.

This mutation, however, is present in other variants, as well, so it is likely not a new source of concern. Additionally, virologist Dr. Jeremy Kamil, from the Louisiana State University Health Sciences Center, suggested to the BBC that “Delta plus might have a slight advantage at infecting and spreading between people who were previously infected earlier during the pandemic or who have weak or incomplete vaccine immunity.” But he also noted that this is not much different from the delta variant. Other experts have also raised the third point, about the variant’s potential to reduce the effectiveness of monoclonal antibody treatments. These include therapies such as the bamlanivimab and etesevimab and REGN-COV2 combination therapies, which researchers have shown to be beneficial in treating mild to moderate COVID-19 when given early during the course of the disease. However, this reduced effectiveness “is not a major difference, as the therapy itself is investigational and few are eligible for this treatment,” said epidemiologist and vaccine expert Dr. Chandrakant Lahariya in a CNBC interview.

With concerns surrounding the Delta coronavirus variant rising globally, how effective are the current vaccines in the U.S. at protecting against the new version of the virus? According to medical experts, the three vaccines currently available each offer protection. Here’s a breakdown of each vaccine and what you should know: How effective are the COVID vaccines overall? In clinical trials, Moderna’s  In clinical trials, Moderna's vaccine reported 94.1% effectiveness at preventing COVID-19 in people who received both doses. The Pfizer-BioNTech vaccine was said to be 95% effective. A new CDC study reported that a single dose of Pfizer's or Moderna's COVID vaccine was 80% effective in preventing infections. That number jumped to 90% two weeks after the second dose, the study on vaccinated health care workers showed.  "These findings indicate that authorized mRNA COVID-19 vaccines are effective for preventing SARS-CoV-2 infection, regardless of symptom status, among working-age adults in real-world conditions," the U.S. agency wrote in the study. "COVID-19 vaccination is recommended for all eligible persons." Pfizer's vaccine, the only one currently authorized for use in children as young as 12, also showed heightened effectiveness among adolescents.  Pfizer in late March released preliminary results from a vaccine study of 2,260 U.S. volunteers ages 12 to 15, showing there were no cases of COVID-19 among fully vaccinated adolescents compared with 18 among those given dummy shots. More intriguing, researchers found the kids developed higher levels of virus-fighting antibodies than earlier studies measured in young adults. The FDA said J&J’s vaccine offers strong protection against what matters most: serious illness, hospitalizations and death. One dose was 85% protective against the most severe COVID-19 illness, in a massive study that spanned three continents — protection that remained strong even in countries such as South Africa, where the variants of most concern were spreading at the time.  The CDC reports J&J/Janssen vaccine was 66.3% effective in clinical trials at preventing COVID-19 illness in people who had no evidence of prior infection 2 weeks after receiving the vaccine. "The vaccine had high efficacy at preventing hospitalization and death in people who did get sick," the CDC notes. "No one who got COVID-19 at least four weeks after receiving the J&J/Janssen vaccine had to be hospitalized." It is not known if any of the three vaccines prevent the spread of the virus by people who are asymptomatic, though the CDC noted that "early evidence suggests that the J&J/Janssen vaccine might provide protection against asymptomatic infection." 

How effective are the vaccines against the new Delta variant?

Data surrounding vaccine effectiveness with the Delta variant is so far limited. While studies have shown that the available vaccines work against variants, including the Delta variant, all two-dose vaccines offer significantly more protection following their second dose. Researchers in England studied how effective the two-dose AstraZeneca and Pfizer-BioNTech vaccines were against it, compared with the Alpha variant that was first detected in the U.K. The vaccines were protective for those who got both doses but were less so among those who got one dose. One recent study showed the Pfizer vaccine was 84% effective against the variant after two doses, but only 34% effective after the first dose.  Moderna also announced Tuesday that a new study showed its vaccine also produced promising protection in a lab setting against the Delta variant and others currently circulating. “As we seek to defeat the pandemic, it is imperative that we are proactive as the virus evolves. We remain committed to studying emerging variants, generating data and sharing it as it becomes available. These new data are encouraging and reinforce our belief that the Moderna COVID-19 Vaccine should remain protective against newly detected variants,” Stéphane Bancel, chief executive officer of Moderna, said in a statement. Currently, little data has been released showing just how effective the Johnson & Johnson is at protecting against the Delta variant, though it is believed that the single-shot vaccine does offer protection against the variant. Dr. Scott Gottlieb, former Food and Drug Administration commissioner, reportedly said the Johnson & Johnson vaccine appears to be about 60% effective against the Delta variant. Still, medical experts say any of the three vaccines currently being used in the U.S. continue to show good results as far as protection. ”This will protect them against getting very sick and being hospitalized and even dying from the Delta variant,” Dr. Katherine Gergen-Barnett of Boston Medical Center recently told NBC10 Boston.

Will a booster shot be needed?

So far, there has been no recommendation from the Centers for Disease Control and Prevention surrounding booster shots with the Delta variant. Still, health experts have repeatedly cautioned that COVID-19 booster shots could be needed for fully vaccinated people, particularly as new variants spread. White House chief advisor Dr. Anthony Fauci said during an interview with MSNBC's Medhi Hasan in April that people may need to get booster shots in a year.  Pfizer CEO Albert Bourla also previously said people will "likely" need a third dose within 12 months of getting fully vaccinated.  So far, studies suggest that the vaccines currently in use can recognize the emerging variants — but they may not provide quite as much protection against the new strains. Boosters and new versions of vaccines that target the variants are already being explored. Pfizer-BioNTech was previously testing a third booster shot of its vaccine on fully vaccinated people.   "The flexibility of our proprietary mRNA vaccine platform allows us to technically develop booster vaccines within weeks, if needed," Sahin said in a release in February. Moderna was also testing a potential third dose of its current vaccine, and a possible booster shot specifically targeting the South Africa variant. Citing early data, the company recently said the booster vaccine generated a promising immune response against the B.1.351 and P.1 variants first identified in South Africa and Brazil, respectively. Meanwhile, Johnson & Johnson CEO Alex Gorsky said during an interview with CNBC's "Squawk Box" in March that the company is well-positioned to adapt its vaccine for variants, and is working on developing software that will "help address some of these new and emerging variants."

And what that tells us about the pandemic. Like any virus, SARS-CoV-2 has been mutating constantly since the beginning of the pandemic. Until November 2020, though, that didn’t seem to matter. That’s when scientists in the United Kingdom noticed an alarming change: The virus had mutated in a way that made it more transmissible. Within a month, similar reports were emerging from places around the world. Suddenly, it seemed the virus was changing at an alarming rate. SARS-CoV-2 hasn’t actually been mutating faster, though. Instead, by letting it spread around the world, we’ve just given it more and more opportunities to mutate as it replicates. The result is that after countless random mutations, there are signs that the virus is beginning to adapt to our natural defenses. And because it’s completely normal for a virus to change over time, we shouldn’t expect it to stop. The only real way to stop those changes is to stop giving the virus so many opportunities.

Click on this direct link to watch the video:

https://youtu.be/Ha6yUxze1vk 

Last year, people 65 and older died from Covid at lower rates than in previous waves. But with Omicron and waning immunity, death rates rose again.  This winter’s wave of deaths in older people belied the Omicron variant’s relative mildness. Almost as many Americans 65 and older died in four months of the Omicron surge as did in six months of the Delta wave, even though the Delta variant, for any one person, tended to cause more severe illness. While overall per capita Covid death rates have fallen, older people still account for an overwhelming share of them. “This is not simply a pandemic of the unvaccinated,” said Andrew Stokes, an assistant professor in global health at Boston University who studies age patterns of Covid deaths. “There’s still exceptionally high risk among older adults, even those with primary vaccine series.”  Covid deaths, though always concentrated in older people, have in 2022 skewed toward older people more than they did at any point since vaccines became widely available. That swing in the pandemic has intensified pressure on the Biden administration to protect older Americans, with health officials in recent weeks encouraging everyone 50 and older to get a second booster and introducing new models of distributing antiviral pills. In much of the country, though, the booster campaign remains listless and disorganized, older people and their doctors said.

Patients, many of whom struggle to drive or get online, have to maneuver through an often labyrinthine health care system to receive potentially lifesaving antivirals. Nationwide Covid deaths in recent weeks have been near the lowest levels of the pandemic, below an average of 400 a day. But the mortality gap between older and younger people has grown: Middle-aged Americans, who suffered a large share of pandemic deaths last summer and fall, are now benefiting from new stores of immune protection in the population as Covid deaths once again cluster around older people. And the new wave of Omicron subvariants may create additional threats: While hospitalizations in younger age groups have remained relatively low, admission rates among people 70 and older in the Northeast have climbed to one-third of the winter Omicron wave’s towering peak. “I think we are going to see the death rates rising,” said Dr. Sharon Inouye, a geriatrician and a professor of medicine at Harvard Medical School. “It is going to become more and more risky for older adults as their immunity wanes.”

In comparing breakthrough infections from the SARS-CoV-2 Delta and Omicron variants, the latter, though milder than Delta infections, were associated with lower antibody titers and limited cross-neutralizing immunity, suggesting reduced protection against re-infection or infection from a future variant.

Summary

Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity against Delta and Omicron SARS-CoV-2 variants in 259 samples from 128 vaccinated individuals. Following Delta breakthrough infection, titers against WT rose 57-fold and 3.1-fold compared to uninfected boosted and unboosted individuals, respectively, versus only a 5.8-fold increase and 3.1-fold decrease for Omicron breakthrough infection. Among immunocompetent, unboosted patients, Delta breakthrough infections induced 10.8-fold higher titers against WT compared to Omicron (p=0.037). Decreased antibody responses in Omicron breakthrough infections relative to Delta were potentially related to a higher proportion of asymptomatic or mild breakthrough infections (55.0% versus 28.6%, respectively), which exhibited 12.3-fold lower titers against WT compared to moderate-severe infections (p=0.020). Following either Delta or Omicron breakthrough infection, limited variant-specific cross-neutralizing immunity was observed. These results suggest that Omicron breakthrough infections are less immunogenic than Delta, thus providing reduced protection against reinfection or infection from future variants.

Highlights

1. In breakthrough infections, variant-specific cross-neutralizing immunity is limited.

2. Higher antibody titers are observed in severe versus mild breakthrough infections.

3. Delta breakthroughs exhibited 10.8X higher antibody titers compared to Omicron.

4. The rise in antibody titers from Omicron breakthroughs was 1/3 of that from boosting.

Published in Cell (March 17, 2022):

https://doi.org/10.1016/j.cell.2022.03.019

Following the emergence of SARS-CoV-2 in China in late 2019 a number of variants have emerged, with two of these – Alpha and Delta – subsequently growing to global prevalence. One characteristic of these variants are changes within the Spike protein, in particular the receptor binding domain (RBD). From a public health perspective these changes have important implications for increased transmissibility and immune escape; however, their presence could also modify the intrinsic host-range of the virus. Using viral pseudotyping we examined whether the variants of concern (VOCs) Alpha, Beta, Gamma and Delta have differing host ACE2 receptor usage patterns, focusing on a range of relevant mammalian ACE2 proteins. All four VOCs were able to overcome a previous restriction for mouse ACE2, with demonstrable differences also seen for individual VOCs with rat, ferret or civet ACE2 receptors, changes which we subsequently attribute to N501Y and E484K substitutions within the Spike RBD.

Preprint Available in bioRxiv (Nov. 24, 2021):

https://doi.org/10.1101/2021.11.23.469663

Arkansas health officials reported COVID-19 case data during IDWeek that demonstrate the severe toll the delta variant has had on the state’s children.During a July peak, although the number of pediatric COVID-19 cases was lower than the last peak in January, hospitalizations and other indications of severe disease increased significantly, according to Michael Cima, PhD, MPH,state epidemiologist for the Arkansas Department of Health, and colleagues.  Cima conducted the research with Infectious Diseases in Children Editorial Board Member José R. Romero, MD, the state’s secretary of health, and Donald E. Warden, MPH, another epidemiologist in the department. During a presentation, Cima noted that the delta variant became the dominant circulating SARS-CoV-2 virus in Arkansas in June and early July.  “Growing evidence suggests that the delta variant is not only far more infectious than the next most infectious variant of concern, but it's also potentially more virulent, so naturally the question has been asked, How does the delta variant impact the pediatric population? Is a more severe disease being observed?” Cima said.

The researchers examined pediatric records for the 3 months they called “key inflection points” for the COVID-19 pandemic in Arkansas: July 2020, January 2021 and July 2021. They reviewed rates of hospitalization and ICU use, use of mechanical ventilation and, “to a lesser extent,” multisystem inflammatory syndrome in children (MIS-C), Cima said. Data showed that pediatric COVID-19 cases numbered 3,268 in July 2020, 11,735 in January 2021 and 8,031 in July 2021. Despite nearly 32% fewer cases occurring in July 2021 compared with January, there were around 42% more hospitalizations (105 vs. 74), 69% more ICU admissions (18 vs. 11) and a 300% increase in the use of mechanical ventilation, Cima and colleagues reported. Cima said PICU bed availability reached single digits in the entire state. He also noted that the state observed fewer MIS-C cases over the summer but that it was possible that cases would increase because there is usually a delay between infection and the appearance of MIS-C symptoms.

COVID-19 vaccine effectiveness declined to 66% among a cohort of health care workers after delta became the predominant SARS-CoV-2 variant, according to a report in MMWR. However, a second report in the journal showed that unvaccinated people in Los Angeles County were around five times more likely to be infected and approximately 29 times more likely to be hospitalized with COVID-19 than vaccinated people.  “Vaccines are not bug zappers, and the efficacy that really matters is not against any infection but against severe infection,” Amesh A. Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, told Healio. “By that standard,” Adalja said, “the vaccines are performing extremely well, even in the face of the delta variant. Chasing mild and/or clinically insignificant cases that occur after vaccination is of marginal value.” In the first study, Ashley Fowlkes, ScD, an epidemiologist on the CDC COVID-19 Response Team, and colleagues tested health care personnel, first responders and other essential workers from eight locations in six U.S. states weekly for COVID-19 from Dec. 14, through April 21.  Of a total of 4,217 participants, 3,483 (83%) were fully vaccinated. Of those who were vaccinated, 2,278 (65%) received the Pfizer-BioNTech vaccine, 1,138 (33%) received the Moderna vaccine and 67 (2%) received the Johnson & Johnson shot.

According to Fowlkes and colleagues, the adjusted vaccine effectiveness against COVID-19 dropped to from 91% (95% CI, 81%-96%) during the months before the delta variant predominated to 66% (95% CI, 26%-84%) during the period of delta predominance. “This trend should be interpreted with caution because [vaccine effectiveness] might also be declining as time since vaccination increases and because of poor precision in estimates due to limited number of weeks of observation and few infections among participants,” the authors wrote. In the second study, Jennifer B. Griffin, PhD, supervising epidemiologist at the Los Angeles County Department of Public Health, and colleagues assessed rates of infection and hospitalization among people aged 16 years or older from May 1 through July 25 and found that, during the study period, COVID-19 cases caused by the delta variant increased from 8.6% to 91.2% in fully vaccinated individuals, from 0% to 88.1% in partially vaccinated people, and from 8.2% to 87.1% in those who were not vaccinated. Among 43,127 cases of SARS-CoV-2 infection, 10,895 (25.3%) occurred in fully vaccinated people, 1,431 (3.3%) in partially vaccinated people and 30,801 (71.4%) in unvaccinated participants.

“On July 25, the SARS-CoV-2 infection rate among unvaccinated persons was 4.9 times and the hospitalization rate was 29.2 times the rates among fully vaccinated persons,” they reported. Among those who were fully vaccinated, 3.2% were hospitalized, 0.5% were admitted to the ICU and 0.2% required mechanical ventilation, according to the researchers. Among those who were partially vaccinated, 6.2% were hospitalized, 1% were admitted to the ICU, and 0.3% needed ventilation. Among unvaccinated individuals, 7.6% required hospitalization, 1.5% were admitted to the ICU, and 0.5% required ventilation. “The findings in this report are similar to those from recent studies indicating that COVID-19 vaccination protects against severe COVID-19 in areas with increasing prevalence of the SARS-CoV-2 delta variant,” Griffin and colleagues wrote. “Efforts to increase COVID-19 vaccination coverage, in coordination with other prevention strategies, are critical to preventing COVID-19-related hospitalizations and deaths.”

Study Cited Published in MMWR (Aug. 27, 2021):

 http://dx.doi.org/10.15585/mmwr.mm7034e4 

A key amino-acid change might underlie the coronavirus variant’s ferocious infectivity.  As the world grapples with the hyper-infectious Delta coronavirus variant, scientists are racing to understand the biological basis for its behaviour. A slew of studies has highlighted an amino-acid change present in Delta that might contribute to its swift spread. Delta is at least 40% more transmissible than is the Alpha variant identified in the United Kingdom in late 2020, epidemiological studies suggest. “The key hallmark of Delta is that transmissibility seems to be ramping up to the next notch,” says Pei-Yong Shi, a virologist at the University of Texas Medical Branch in Galveston. “We thought Alpha was pretty bad, very good at spreading. This one seems to be even more.”  Shi’s team and other groups have zeroed in on a mutation that alters a single amino acid in the SARS-CoV-2 spike protein — the viral molecule responsible for recognizing and invading cells. The change, which is called P681R and transforms a proline residue into an arginine, falls within an intensely studied region of the spike protein called the furin cleavage site. The presence of this short string of amino acids set off alarm bells when SARS-CoV-2 was first identified in China, because it is associated with heightened infectivity in other viruses such as influenza, but had not previously been found in other sarbecoviruses, the family of coronaviruses to which SARS-CoV-2 belongs. “This little insert sticks out and hits you in the face,” says Gary Whittaker, a virologist at Cornell University in Ithaca, New York.

Pre-activated virus

To penetrate cells, the SARS-CoV-2 spike protein must be cut twice by host proteins. In the SARS-CoV-1 virus that causes severe acute respiratory syndrome (SARS), both incisions occur after the virus has locked on to a cell. But with SARS-CoV-2, the presence of the furin cleavage site means that host enzymes (including one called furin) can make the first cut as newly formed viral particles emerge from an infected cell. These pre-activated viral particles can then go on to infect cells more efficiently than do particles requiring two cuts, says Whittaker. Delta wasn’t the first SARS-CoV-2 variant to gain a mutation that alters the furin cleavage site. The Alpha variant has a different amino-acid change at the same location as Delta. But the available evidence suggests that the mutation’s effect has been especially profound in Delta. In a study reported as a preprint on 13 August1, Shi’s team found that the spike protein is cut much more efficiently in Delta-variant particles than in Alpha particles, echoing results reported in May by virologist Wendy Barclay at Imperial College London and her team, who compared Delta with an earlier strain2. Follow-up experiments by both groups showed that the P681R change was largely responsible for spike being clipped so much more efficiently. “This really nailed it, in terms of the mechanism,” says Shi.  Researchers are also beginning to join the dots between P681R and Delta’s ferocious infectivity. Shi’s team found that, in cultured human-airway epithelial cells infected with equal numbers of Delta and Alpha viral particles, Delta rapidly outcompeted the Alpha variant, mimicking epidemiological patterns that have played out globally. But Delta’s advantage disappeared when the researchers eliminated the P681R change. The mutation might also speed up the spread of SARS-CoV-2 from cell to cell. A team led by Kei Sato, a virologist at the University of Tokyo, found that spike proteins bearing the P681R change fuse with the plasma membranes of uninfected cells — a key step in infection — almost three times faster than do spike proteins lacking the change3. “I think the virus is succeeding on volume and speed,” says Whittaker. “It’s become a much more efficient virus. It’s going through people and going through cells a lot quicker.”

More than one mutation

Although evidence is building that the P681R change is a crucial feature of Delta, researchers emphasize that it is unlikely to be the only mutation responsible for the variant’s fast spread. Delta carries numerous other mutations to the spike protein, as well as to other less well-studied proteins, that might be important. “It’s very simplistic to say it’s just this 681 change. I think it’s a sum of everything,” says Teresa Aydillo-Gomez, a virologist at Icahn School of Medicine at Mount Sinai in New York City. Context, both epidemiological and genetic, is also likely to have had a role in Delta’s rise, say scientists. One of Delta’s siblings, a variant called Kappa that, like Delta, was first identified in India, carries many of the same mutations, including P681R, but its effects haven't been as devastating as Delta’s. In a preprint posted on 17 August, a team led by structural biologist Bing Chen at Harvard Medical School in Boston, Massachusetts, reports that Kappa’s spike protein is cleaved less frequently and fuses to cell membranes much less efficiently than does Delta’s4. The researchers say this finding raises questions over the role of P681R.  Researchers in Uganda identified the P681R change in a variant that spread widely in the country in early 2021, but that never took off as Delta did, even though it displays many of the same properties in cell-based lab studies. Whittaker’s team inserted the P681R change into a spike protein from the coronavirus that was circulating in Wuhan, China, at the beginning of the pandemic, and found no increase in its infectivity5. “It takes more than one mutation to make a difference,” he adds. Regardless of its role in Delta’s dominance, Whittaker and other scientists say, the mutation has underscored the importance of understanding changes in the coronavirus’s furin cleavage site. Whittaker doesn't expect P681R to be the last furin cleavage site mutation to cause concern. “I’m waiting to see what happens next.”

Published in Nature (August 20, 2021):

https://doi.org/10.1038/d41586-021-02275-2

Increased vaccination and a return to wearing masks could avert worst-case scenarios for the Delta-driven surge. The United States is standing at a dire inflection point, with pandemic coronavirus cases surging and only 50% of the population fully vaccinated. Driving the latest wave is the highly contagious Delta variant, which according to the Centers for Disease Control and Prevention (CDC) caused between 80% and 87% of all U.S. COVID-19 cases in the last 2 weeks of July—up from 8% to 14% in early June. The variant’s exceptional infectiousness has driven cases from a 7-day average of 13,500 daily cases in early June to 92,000 on 3 August. At the same time, an internal CDC document that leaked last week says the variant may make people sicker, citing published reports from Singapore and Scotland and a preprint from Canada.  The good news is that severe disease and death are highly unlikely among the vaccinated—and U.S. vaccination rates are beginning to increase once again, if modestly. How bad will the U.S. surge become, and how long will it take to recede? “Anyone saying they know exactly what is happening is overconfident,” says Natalie Dean, a biostatistician at Emory University. “There is a lot of uncertainty about what will happen in the future, even on a relatively short time scale.” With that proviso, here is what Dean and other scientists closely following the pandemic told Science they foresee....

July 23 (Reuters) - Indonesia is suffering a devastating wave of coronavirus infections, driven by the Delta variant, but the government is already talking about relaxing social curbs enacted earlier this month - a move analysts say is largely led by economic considerations. The impact of the outbreak has been brutal in Indonesia, with stories of people desperately trying to find hospital beds, oxygen and medicine for loved ones. The country's COVID-19 death toll has broken records four times this week, the latest on Friday with 1,566 deaths. Nonetheless, and just over a week after Indonesia recorded its highest number of daily infections, President Joko Widodo flagged that current restrictions could be eased from as early as next week if cases start to drop.  Easing of restrictions is likely premature and potentially dangerous, say some public health experts. While cases have dipped – from more than 56,000 in mid-July to 49,000 on July 23 – epidemiologists say testing rates also dropped in the same period, making it difficult to determine whether there has been a true decline. Even if cases are flattening, relaxing curbs is inadvisable given hospital occupancy and death rates remain high, they say. Indonesia’s death rate is currently three times higher than the global average, according to Our World in Data, while nearly 2,500 people have died in isolation or outside hospitals since June, said independent data initiative, Lapor COVID-19.

Social restrictions in place since July 3 such as working from home and closed shopping malls are currently limited to the islands of Java and Bali and other designated 'red zones' across the country. Senior Minister Luhut Pandjaitan has said these could be eased as early as Monday if cases continue to fall and other indicators improve. He also said the "sociological condition of the people" would be factored into the decision. Concern about the livelihoods of the poor, and a series of small protests in the past week, have raised fears about the risk of social unrest, analysts and government sources say. With 60% of the workforce in the informal sector, experts say protests are a manifestation of frustration, not necessarily against restrictions but over how hard it has become to survive. 

WILL VACCINATIONS PROVIDE A PATH OUT OF THE CRISIS?

The government is counting on vaccinations, largely provided by China's Sinovac, to help reduce the impact of the pandemic. While Indonesia worked hard to kick off an early vaccination programme, logistical hurdles, limited supplies and vaccine hesitancy have held back targets – so far only 6% of the population is fully vaccinated. Pledges to reach 400,000 tests per day and boost contact tracing have also fallen short, while the positivity rate averaged 28.7% in the past week.

WHAT ARE THE POTENTIAL RISKS IF INDONESIA RELAXES CURBS?

The government faces a tricky balancing act in making policy to protect both the economy and the health of 270 million people in the sprawling, developing nation. But as cases have surged and graveyards have filled, the government has faced growing criticism that it has prioritised the economy over people's health. Conversely, a failure to reopen also carries economic risks. Employer groups have warned of mass layoffs unless curbs are relaxed next week, while credit rating agencies say restrictions could challenge the government's goal to reduce a fiscal deficit and undermine ratings. The big question may come down to timing. Public health experts advise that dialling back restrictions too soon could mean that additional support recently provided to health facilities could quickly be undermined, while also allowing the Delta variant to spread to far-flung regions even more ill-equipped to handle a health crisis.

In parts of the country with low vaccination rates, the variant may be responsible for up to 90% of sequenced cases, officials said. The rapidly spreading Delta variant now accounts for 83% of sequenced Covid-19 cases in the United States, the nation’s public health leaders said Tuesday, and in parts of the country with low vaccination rates, it may be responsible for up to 90%.  Rochelle Walensky, the director of the Centers for Disease Control and Prevention, told a congressional hearing the new 83% estimate represents “a dramatic increase” from 50% of sequenced cases that were tallied the week of July 3. In some parts of the country that percentage is even higher, particularly in areas with low vaccination rates, said Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases. As the variant has spread, Covid-19 deaths in the U.S. have risen, climbing by nearly 48% over the past week and now averaging 239 per day, she said.  “We know the majority of deaths could be prevented by vaccination,” Walensky said. Vaccination has been uneven, with levels below half of eligible people in two-thirds of the country, Walensky said. She cited a five-month CDC study that found 99.5% of Covid-19 deaths are among people who are unvaccinated. 

“The best way to prevent the spread of Covid-19 variants is to prevent the spread of disease. And vaccination is the most powerful tool we have,” she said. “We must continue to expand vaccine coverage by building trust and confidence in Covid-19 vaccines. And this is particularly important in communities of color, rural communities, and other population groups at risk.” Pressed to explain why the U.S. has not pursued booster shots as Israel has done with third Pfizer doses, Walensky and Fauci both pushed back. Walensky said the CDC is sharing data with Israel and the U.K. “where they’re several weeks ahead of us in the variant,” while watching more than 20 cohorts of vaccine recipients for any signs that their protection against Covid-19 might be waning. So far protection from recognizable disease continues to hit percentages in the low 90s, Fauci said. “If you see it fall below that into the 80s or even, unfortunately, I hope it never happens, into the 70s, then, you know, you reach the point where the durability needs a boost,” he said. “Those studies are ongoing right now.” Fauci blamed the variant’s high transmissibility for the surge in cases among unvaccinated people. First identified in India, Delta has swept through 90 countries around the world. But the three vaccines approved in the U.S. — mRNA vaccines from Moderna and Pfizer and the adenovirus-delivered vaccine from Johnson & Johnson — continue to be highly effective against Delta and other variants. “We have the tools to end this epidemic,” Fauci told the Senate Committee on Health, Education, Labor and Pensions. “It’s up to us to use those tools to the maximum.”

When the first cases of the SARS-CoV-2 Delta variant were detected in the United Kingdom in mid-April, the nation was getting ready to open up. COVID-19 case numbers, hospitalizations and deaths were plummeting, thanks to months of lockdown and one of the world’s fastest vaccination programmes. Two months later, the variant, which was first detected in India, has catalysed a third UK wave and forced the government to delay the full reopening of society it had originally slated for 21 June. After observing the startlingly swift rise of the Delta variant in the United Kingdom, other countries are bracing for the variant’s impact — if they aren’t feeling it already. Nations with ample access to vaccines, such as those in Europe and North America, are hopeful that the shots can dampen the inevitable rise of Delta. But in countries without large vaccine stocks, particularly in Africa, some scientists worry that the variant could be devastating. “In my mind, it will be really hard to keep out this variant,” says Tom Wenseleers, an evolutionary biologist and biostatistician at the Catholic University of Leuven (KU Leuven) in Belgium. “It’s very likely it will take over altogether on a worldwide basis.”  Delta, also known as B.1.617.2, belongs to a viral lineage first identified in India during a ferocious wave of infections there in April and May. The lineage grew rapidly in some parts of the country, and showed signs of partial resistance to vaccines. But it was difficult for researchers to disentangle these intrinsic properties of the variant from other factors driving India’s confirmed cases past 400,000 per day, such as mass gatherings.

Delta data

The Delta variant has been linked to a resurgence of COVID-19 in Nepal, southeast Asia and elsewhere, but its UK spread has given scientists a clear picture of the threat it poses. Delta seems to be around 60% more transmissible than the already highly infectious Alpha variant (also called B.1.1.7) identified in the United Kingdom in late 2020. Delta is moderately resistant to vaccines, particularly in people who have received just a single dose. A Public Health England study published on 22 May found that a single dose of either AstraZeneca's or Pfizer's vaccine reduced a person’s risk of developing COVID-19 symptoms caused by the Delta variant by 33%, compared to 50% for the Alpha variant. A second dose of the AstraZeneca vaccine boosted protection against Delta to 60% (compared to 66% against Alpha), while two doses of Pfizer’s jab were 88% effective (compared to 93% against Alpha). Preliminary evidence from England and Scotland suggests that people infected with Delta are about twice as likely to end up in hospital, compared with those infected with Alpha. “The data coming out of the UK is so good, that we have a really good idea about how the Delta variant is behaving,” says Mads Albertsen, a bioinformatician at Aalborg University in Denmark. “That’s been an eye-opener.” Denmark, which, like the United Kingdom, is a world leader in genomic surveillance, has also seen a steady rise in cases caused by the Delta variant — although far fewer than most other European countries. It is only a matter of time before the variant becomes dominant in Denmark, says Albertsen, but the hope is that its expansion can be slowed through vaccination, surveillance and enhanced contact tracing. “It’s going to take over,” he says, but “hopefully in a few months and not too soon.” Meanwhile, the Danish government is easing restrictions, not re-imposing them: restaurants and bars have been open for months to individuals who have been vaccinated or received a recent negative test, and, as of 14 June, masks are no longer required in most indoor settings. “It is looking good now in Denmark, and we are keeping a close eye on the Delta variant,” says Albertsen. “It can change quite fast, as it has done in the UK.” Cases of the Delta variant in the United Kingdom are doubling roughly every 11 days. But countries with ample vaccine stocks should be reassured by the slower uptick in hospital admissions, says Wenseleers. A recent Public Health England study1 found that people who have had one vaccine dose are 75% less likely to be hospitalized, compared with unvaccinated individuals, and those who are fully protected are 94% less likely to be hospitalized. 

US spread

Delta is also on the rise in the United States, particularly in the Midwest and southeast. The US Centers for Disease Control and Prevention declared it a variant of concern on 15 June. But patchy surveillance means the picture there is less clear. According to nationwide sampling conducted by the genomics company Helix in San Mateo, California, Delta is rising fast. Using a rapid genotyping test, the company has found that the proportion of cases caused by Alpha fell from more than 70% in late April to around 42% as of mid-June, with the rise of Delta driving much of the shift2. Jeremy Kamil, a virologist at Louisiana State University Health in Shreveport, expects Delta to eventually become dominant in the United States, “but to be somewhat blunted by vaccination”. However, vast disparities in vaccination rates could lead to regional and local variation in cases and hospitalizations caused by Delta, says Jennifer Surtees, a biochemist at the University at Buffalo, New York, who is conducting regional surveillance. She notes that 70% of eligible New Yorkers have received at least one dose of vaccine — a milestone that triggered the lifting of most COVID-19 restrictions last week — but that figure is below 40% in some parts of the state. Communities with high proportions of African American and Hispanic individuals, where vaccination rates tend to be low, could be especially hard hit by Delta. “These are populations that are really at risk of a localized outbreak from Delta, so I think it’s really important to still keep tracking and watch this as much as possible,” Surtees says. Data from Helix2 on nearly 20,000 samples sequenced since April suggest that the Delta variant is spreading faster in US counties where less than 30% of residents have been fully vaccinated, compared to the counties with vaccination rates above that threshold.

Africa at risk

Delta poses the biggest risk, scientists say, to countries that have limited access to vaccines, particularly those in Africa, where most nations have vaccinated less than 5% of their populations. “The vaccines will never come in time,” says Wenseleers. “If these kinds of new variant arrive, it can be very devastating.” Surveillance in African countries is extremely limited, but there are hints that the variant is already causing cases there to surge. Several sequences of the variant have been reported in the Democratic Republic of the Congo, where an outbreak in the capital city of Kinshasa has filled hospitals. The variant has also been detected in Malawi, Uganda and South Africa. Countries that have close economic links to India, such as those in East Africa, are probably at the greatest risk of seeing a surge in cases caused by Delta, says Tulio de Oliveira, a bioinformatician and director of the KwaZulu-Natal Research and Innovation Sequencing Platform in Durban, South Africa. In his country, all of the Delta cases have been detected in shipping crews at commercial ports, with no signs yet of spread in the general community. De Oliveira expects it to stay this way. South Africa is in the middle of a third wave of infections caused by the Beta variant (also known as B.1.351) identified there last year. This, combined with a lack travel from countries affected by Delta, should make it harder for a new variant to take hold. Similar factors could be keeping Delta at bay in Brazil, which is battling another immune-evading variant called P.1, or Gamma, says Gonzalo Bello, a virologist at the Oswaldo Cruz Institute in Rio de Janeiro, who is part of a team conducting national surveillance. So far, Brazil has sequenced just four cases of the Delta variant in the country. While countries gird themselves against the Delta variant — or hope that it passes them by — researchers say we need to watch for even greater threats. “What most people are concerned about are the next variants — if we start to see variants that can really challenge the vaccines,” says Albertsen.

Published in Nature (June 22, 2021):

https://doi.org/10.1038/d41586-021-01696-3