COVID Get Vaccinated Against the Covid Delta Variant

[atyy]

https://www.msn.com/en-us/health/medical/a-florida-teacher-who-couldnt-get-vaccinated-because-of-her-cancer-treatment-died-of-covid-19-her-union-says-she-caught-it-from-her-classroom-which-had-no-mask-mandate/ar-AANJ8WH

"Kelly Peterson was not vaccinated against the Coronavirus because she had leukemia and her doctor advised against getting the shot in her already weakened state, her sister, Christin, told KTVU."

While the statement may be technically true, it may lead some to think they shouldn't get vaccinated because of their weakened state. In fact, vaccination is urgent and important for such people. The reason one may receive advice to delay vaccination is that certain medications suppress the effectiveness of vaccination. So it may be advantageous to wait for a point between medication doses to try to maximize the effect of vaccination.

Here are examples of recommendations for people with leukemia to get vaccinated. In the USA, they may be among groups for whom a third dose (considered part of the primary series for these patients, so technically not a booster) is recommended.

https://lls.org/who-we-are/covid-19-vaccines-faq-patients-and-caregivers "Get Vaccinated, Act Unvaccinated"
https://bloodcancer.org.uk/support-for-you/coronavirus-covid-19/covid-vaccine-blood-cancer/
https://www.immunology.org/news/bsi...r-patients-immunocompromised-immunosuppressed
https://www.leukaemia.org.au/covid-19-vaccinations/

 

[atyy]

Michael Baym points out that this US airline still calls it the B.1.617.2 variant.

https://news.delta.com/ed-bastian-memo-covid-19-update
"While we are grateful for the progress we’ve made, the most recent virus variants make it clear that more work remains ahead. The COVID-19 pandemic is a global health crisis, and one of the most dangerous challenges our world has faced in this lifetime. Over the past few weeks, the fight has changed with the rise of the B.1.617.2 variant – a very aggressive form of the virus. Our Chief Health Officer, Dr. Henry Ting, describes the variant as a “heat-seeking missile” that transmits predominantly through the unvaccinated community."

 

[Astronuc]

The United States now has more than 100,000 people hospitalized with Coronavirus across the country for the first time since January, according to a new report.

On Thursday, The Washington Post noted that hospitalization rates are highest in the southeastern United States, including Florida, where 17,000 people are hospitalized, and Texas, where another 14,000 are receiving care.

Citing its own Coronavirus database, the Post reported 2,100 children have been hospitalized nationally this month, topping 2,000 for the first time since August 2020.

https://thehill.com/policy/healthca...-100k-covid-19-hospitalizations-threshold-for

 

[artis]

https://www.worldometers.info/coronavirus/

Looking at the upper general statistical graphs of both daily new cases and daily deaths it seems that the third wave that is happening now is less severe in terms of deaths and also somewhat smaller compared to daily new cases, it also seems that we might be at the very peak of the wave as of now, also if you compare to the previous waves you can see with a naked eye that the climb up until this point as of this day was less steep than the previous climbs.

Unless this God damn virus takes another successful mutation I might speculate that we should be getting better from here on.

 

[jim mcnamara]

@artis https://www.worldometers.info/coronavirus/country/us/ shows the US getting worse in terms of both deaths and new cases. Try looking at the 7 day running average for deaths on Jul 1 2021 == 242 deaths vs today Aug 8 2021 == 921 deaths.

Death peaks generally lag behind new case peaks by 14-30 days because really sick people go to the ICU (if there is a bed available). This helps a majority of them recover.

But the world as a whole is showing a downward trend in new cases.

 

[Astronuc]

The Hill reports that "New study finds 1 in 3 Americans were infected with Coronavirus by the end of 2020"
https://thehill.com/changing-americ...ne-in-three-americans-had-covid-19-by-the-end

"Researchers estimate that nearly one-third of the U.S. population, or 103 million Americans, got COVID-19 last year."
"Nearly half the residents of Chicago, Los Angeles, Miami and New York City were likely infected in 2020, according to a new analysis."

While official numbers report nearly 20 million confirmed cases of COVID-19 last year, according to The COVID Tracking Project, researchers estimate that nearly one-third of the U.S. population, 31 percent or 103 million Americans, had COVID-19 at some point last year.

Columbia University Mailman School of Public Health researchers determined that fewer than one-quarter, 22 percent, confirmed their positive diagnosis for public health reports through testing, according to a news release by the American Association for the Advancement of Science (AAAS).

In the upper Midwest and Mississippi valley, including the Dakotas, Minnesota, Wisconsin and Iowa, nearly two-thirds, 60 percent, of the population was estimated to have had COVID-19 in 2020. Meanwhile, nearly half the residents of Chicago, Los Angeles, Miami and New York City (48 percent, 52 percent, 42 percent and 44 percent, respectively) were likely infected in 2020, according to the study published in the journal Nature.

I'm guessing that the virus was mostly the Alpha variant last year. I wonder how many who had it then now got the Delta variant.

I'm somewhat skeptical about the estimates given that a lot of testing has been done. In New York, as of yesterday, there were 64,592,996 tests (more than 3x state population of 19.45 million est.) for SARS-Cov-2 of which 2,236,634 were positive. Some people have apparently been tested multiple times.

But then, Delta is just about everywhere - https://www.nytimes.com/interactive/2021/07/29/us/delta-variant-risk-map.html

Down in Florida, Lisa Steadman spent more than a week inside Winter Haven Hospital battling COVID-19. https://www.yahoo.com/news/she-had-covid-florida-hospital-174931437.html

She survived.

But when Ms Steadman returned home after eight days in the hospital, on Aug. 18, she found her husband Ron dead in their bedroom. According to WFLA, the couple’s dogs were near starved of food and water. Ron’s doctor told her that her husband had died from COVID-related complications, Fox 13 reported.

"Ron Steadman, 55, had tested positive for the novel Coronavirus before his wife got her own result. He was treated at a walk-in clinic and sent home with meds because “he wasn’t in distress or anything. It was just like he had a bad cold,” Steadman told WFLA NewsChannel 8."

So nobody checked on this guy for a week?! While his wife was in hospital?!

 

[Astronuc]

Newsweek reports, "Central Florida Hospitals Forced to Order Mobile Morgues to Deal With COVID Death Overflow" - https://www.msn.com/en-us/health/medical/central-florida-hospitals-forced-to-order-mobile-morgues-to-deal-with-covid-death-overflow/ar-AANPcaG

For the first time during the Coronavirus pandemic, Advent Health has had to order 14 portable morgues to help make room for an additional 168 bodies.
. . . .
On Thursday, Florida reported its largest single-day increase in the death total, 901, since the pandemic began. On average, the state is reporting 227 COVID-19 deaths a day.

Across the state, more than 3,600 people with COVID-19 are occupying beds in intensive care units—the second-highest total in the country.

The Delta variant of the virus, which has fueled the increase in hospitalizations and deaths, has also caused a shift in infected populations.

Doctors across the U.S. have reported they are seeing higher numbers of young people in their hospitals, and the number of pediatric cases is the highest in Florida.

Daily News reports, "Contracting and beating COVID provides better protection against delta variant than Pfizer shot, new research shows"
https://www.msn.com/en-us/health/medical/contracting-and-beating-covid-provides-better-protection-against-delta-variant-than-pfizer-shot-new-research-shows/ar-AANOSsi

Catching and beating COVID-19 during one of the initial waves of the global health pandemic appears to provide more protection against the highly-contagious delta variant than both doses of the vaccine developed by Pfizer and BioNTech.

The largest real-world analysis comparing natural immunity and the protection provided by Coronavirus vaccines revealed those who have received both jabs of Pfizer’s two-stick shot were almost six-fold more likely to contract a delta infection and seven-fold more likely to show symptoms and become hospitalized than those who have already recovered from COVID.

The paper, by researchers in Israel, also stands in contrast to past reports suggesting those who have been vaccinated are just as protected from the virus as those who have been infected with it.

 

[atyy]

Daily News reports, "Contracting and beating COVID provides better protection against delta variant than Pfizer shot, new research shows"
https://www.msn.com/en-us/health/medical/contracting-and-beating-covid-provides-better-protection-against-delta-variant-than-pfizer-shot-new-research-shows/ar-AANOSsi

https://www.ndm.ox.ac.uk/files/coro...ction-survey/finalfinalcombinedve20210816.pdf
Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections
in the UK
Koen B. Pouwels, Emma Pritchard, Philippa C. Matthews, Nicole Stoesser, David W. Eyre, Karina-Doris Vihta, Thomas House, Jodie Hay, John I Bell, John N Newton, Jeremy Farrar, Derrick Crook, Duncan Cook, Emma Rourke, Ruth Studley, Tim Peto, Ian Diamond, A. Sarah Walker and the COVID-19 Infection Survey Team
"In the Delta-dominant period ... There was no evidence that the effectiveness of two ChAdOx1 vaccinations 14 days previously in preventing new PCR-positives differed from the protection afforded by previous natural infection without vaccination (heterogeneity p=0.33), whereas two BNT162b2 vaccinations afforded greater protection (p=0.04)."

 

[artis]

Well truth be told just as with all science only time will settle down some of the rather high unknown probabilities as of now.
My own opinion is that a mild to medium infection of Covid should provide a slightly better protection than vaccination, at least for many other viruses those who survive an infection in most cases develop immunity for life. Tick encephalitis is one such case, where a vaccine provides you on average for some 6-8 years and then needs a re-vaccination. Covid being a different virus performs differently although given it's now just under 2 years since this began and about a year for the mainstream stuff I'd say it's too early to see how long on average the immunity in those who were infected will last.

As for the infected undercount it might be true I think, at least here in my country I personally know a dozen of folks who were either asymptomatic or had a very easy case and they never got tested, some of them later on saw antibodies in blood, some of whom never even knew they were infected.
Here the drive to not get tested for those that have a light case is that they mostly want to avoid all the paperwork and regulation that comes with self quarantine.
So if the world situation is anything like the local one I'd say the true Covid infected numbers might be as twice as high as the one on the graphs. Maybe even more.

Truth be told from my own small little statistic that I have gathered from those that I know and myself including I could say that Covid unlike the yearly flu is a strange virus, it has a wildly varying severity across even the same age groups. I mean some get severe pneumonia from it while most get just a small cough or runny nose or nothing but small temp. Quite a few don't feel anything at all. I have yet to meet a person who would have been infected with the yearly flu and not feel or experience anything...

@jim mcnamara I was thinking the world as a whole not just US, I think to get the overall picture one cannot look at a specific country because different countries have different trends , the US for example has a lot of obesity and a large percentage of folks with health problems which is a influential factor most likely if not in overall infections then surely in deaths.

 

[Astronuc]

An unvaccinated primary-school teacher in Marin County, California, spread COVID-19 to 26 other people, including 50% of their classroom, after spending two days sick with the Coronavirus at school while not always masking, according to a new Centers for Disease Control and Prevention report.

https://www.businessinsider.com/cdc-unvaccinated-teacher-spread-covid-to-50-of-classroom-2021-8

On a completely different matter,

A Georgia police officer who frequently posted anti-vaxx messages on Facebook and took an anti-parasitic drug instead of a vaccine has died of COVID-19.

https://www.businessinsider.com/georgia-anti-vaxx-cop-took-ivermectin-dies-of-covid-19-2021-8

Ivermectin is used as a deworming medicine in livestock, and is not approved for use in humans.

Manning also wrote on Facebook that he had taken ivermectin himself, and criticized Facebook for disciplining him for spreading misinformation, The Independent reported.

The Centers for Disease Control and Prevention have said the drug does not help prevent or treat coronavirus, and this week issued a health advisory detailing an increase in severe illness caused by taking ivermectin.

Calls to US poison control centers about ivermectin exposures increased five-fold from the pre-pandemic baseline, with an especially sharp rise in July 2021, a CDC report said.

CDC Warning/Advisory - Rapid Increase in Ivermectin Prescriptions and Reports of Severe Illness Associated with Use of Products Containing Ivermectin to Prevent or Treat COVID-19
https://emergency.cdc.gov/han/2021/pdf/CDC_HAN_449.pdf

Do not take unapproved medications recommended by crackpots on social media. Consult one's doctor or a doctor. On the other hand, there are quack doctors who do advise patients/people to take the medication.

 

[Astronuc]

Memorial Hermann announced Monday that due to the continued COVID-19 surge and the strain on the hospital system’s operations, it was closing three of its 24-hour emergency rooms at 5 p.m. Monday evening until further notice.

The three ERs affected at the Memorial Hermann Convenient Care Centers in Kingwood, Spring and Sienna.

“Patients who are currently receiving care inside any of these Emergency Rooms will be safely discharged or transferred to another Memorial Hermann facility. Members of our community who require emergent care should proceed to another nearby Emergency Center for assistance,” the brief statement from the Memorial Hermann Media Relations team said.

http://katytimes.com/stories/memorial-hermann-closes-3-stand-alone-ers-in-greater-houston,4650

As the delta variant continues to prompt increasing hospitalizations, hospitals throughout Greater Houston, including those in the Katy area have stated that staff are exhausted and capacity at hospitals is short or nonexistent.

 

[Astronuc]

In three towns in rural Rogue Valley, Oregon, all three ICU's are 100% full of COVID-19 patients, according to staff.
https://www.npr.org/sections/health...-through-rural-southern-oregon-like-a-buzzsaw

In contrast to earlier phases of the pandemic, the Asante hospitals are now treating COVID-19 patients in their 20s, 30s, 40s and 50s, according to Blumhardt.

"I've been an ICU nurse for ten years. I've never seen anything like this," McCoy says. "It's really terrible seeing these patients who can't breathe. That is a very difficult thing to watch. It's really terrifying for them and it's really difficult for us to see day in and day out."

"We admit nine unvaccinated to every one vaccinated individual. So clearly the vaccine is protecting against hospital admission," he [ICU Medical Director Dr. Michael Blumhardt] says.

Jackson County is recording record numbers of COVID infections. Within weeks, many of those people may worsen and need hospital care. Unfortunately, a new forecast from Oregon Health and Science University predicts that by Labor Day, the state will face a shortfall of 400 to 500 staffed hospital beds.

Blumhardt says smaller hospitals in Oregon have been trying to transfer their sickest patients to Asante, but so far they've had to turn away around 200 people because they don't have the beds, or the staff.

 

[Jarvis323]

Ivermectin is used as a deworming medicine in livestock, and is not approved for use in humans.

That's not exactly true. Ivermectin has been FDA approved as an anti-parasitic drug for humans since the late 80's. It was found to have in vitro antiviral properties against SARS-CoV-2, but clinical trials show wildly different results with some suggesting incredible efficacy and others showing little or no effect. Those arguing in favor of Ivermectin will say that results vary so wildly because of the importance of early treatment and various other factors like combination with other drugs or protocols. The CDCs assessment is that

currently insufficient data to recommend ivermectin for treatment of COVID-19

https://emergency.cdc.gov/han/2021/pdf/CDC_HAN_449.pdf

Still, in several countries besides the US, it has been embraced as a treatment for Covid-19, especially in countries with less access to health care and expensive treatments, and where Ivermectin is a commonly used and very cheap drug already. For example, in India the government sent out Covid-19 treatment kits to people's homes in advance, which include Ivermectin.

https://en.wikipedia.org/wiki/Ivermectin#Pharmacokinetics

Even if ivermectin had some efficacy, it would not seem to be a big deal that a man who took ivermectin died of Covid. Remdesivir, for example, is widely used and appears to have no effect on mortality at all.

 

[Astronuc]

That's not exactly true. Ivermectin has been FDA approved as an anti-parasitic drug for humans since the late 80's.

I should have qualified my comment. It is not approved for the treatment of SARS-Cov-2 (COVID-19), and certainly not at the doses one typically finds in applications to livestock. The FDA has certainly not approved using Ivermectin from the local "Feed and Seed" distributor or the local veterinarian like some are apparently doing.

Ivermectin tablets are approved at very specific doses for some parasitic worms in humans, as well as topical treatments for head lice and skin conditions like rosacea.
https://ldh.la.gov/index.cfm/newsroom/detail/6291

Ivermectin is a medication that is approved by FDA in oral formulations to treat onchocerciasis (river blindness) and intestinal strongyloidiasis. Topical formulations are used to treat head lice and rosacea. Ivermectin is also used in veterinary applications to prevent or treat internal and external parasitic infections in animals. When used in appropriate doses for approved indications, ivermectin is generally well tolerated.

https://emergency.cdc.gov/han/2021/han00449.asp

 

[artis]

https://www.cnbc.com/2021/07/30/cdc...7-YS93bNIeArHrn6rMyRDfPNq0AXXtowfXR3mLV9HZMQ4I guess if we are to make he vaccines a regular thing (seasonal) then we should probably tweak them , the question is how hard it is to do so.
Basically as of now it seems that for those that have been vaccinated and still got the delta the main and only use of the vaccine was to introduce their bodies to "what is about to come" and in such a way "train" the immune system to develop immunity which then helps to "ride out" the disease easier.

can somebody give a more detailed cause for what is the main difficulty in developing a newer vaccine that can match the current strain better? I mean we do know the mutation we have it in our labs as we speak.

 

[Ygggdrasil]

I should be very easy to design new vaccines to target the new variants (e.g. the first mRNA vaccine prototypes were designed days after the SARS-CoV-2 genetic sequence was made public). Indeed, both Pfizer and Moderna started trials to measure the effectiveness of a booster against the Beta variant (which shows some difficulty with developing boosters to the variants -- the circulating variants can change before clinical trials finish). Recently, Pfizer has begun trials for a booster against the Delta variant.

However, there may be some scientific and social issues related to developing new boosters against the variants:

To counteract the impact of viral variants, one suggestion is to develop new vaccines that more closely reflect the circulating viruses. For example, Moderna has developed a novel vaccine targeting the B.1.1.7 VOC, which has been tested in preclinical trials57 and is now in clinical trials (NCT04785144). However, it is not clear how beneficial such vaccines designed specifically to target new variants will be. The main consideration will be how far the circulating viruses in autumn 2021 (when booster vaccination has been proposed in some countries) will have drifted antigenically from the original reference sequence of the SARS-CoV-2 S protein used for the first-generation vaccines. Although studies relating to the VOCs have shown reduced neutralization in vitro, there has been no significant reported impact on vaccine effectiveness, which suggests that the viral mutations predominantly increase transmissibility, but not necessarily immune escape. As the current vaccines still offer good protection against severe disease, there may be limited return on a new variant booster. Indeed, there may actually be negative unintended consequences. The first is that producing a new booster vaccine for the countries with sufficient income to afford substantial coverage with the first-generation vaccines may reduce manufacturing capacity for doses for lower-income countries. Second, boosting with a similar antigen may boost the antibody response to the original strain rather than prime for antibodies specific to the new strain58. This idea of ‘original antigenic sin’ refers to the boosting of responses to previously seen epitopes to the detriment of responses to new epitopes, particularly when they are closely related. Such a phenomenon has been observed for influenza, with individuals who were recently immunized with seasonal influenza vaccine producing lower antibody responses to 2009 pandemic influenza than previously unimmunized individuals59. Furthermore, the variants may be drifting apart, and so priming with a variant might narrow rather than broaden protection. It is our opinion that engineering novel booster vaccines should not be a priority at this time.

Whereas engineering new variant vaccines may not be beneficial, an alternative strategy is to boost immunity with a third dose of vaccine targeting the initial reference strain

https://www.nature.com/articles/s41577-021-00592-1

 

[nsaspook]

"alternative strategy is to boost immunity with a third dose of vaccine targeting the initial reference strain"
This seems be what Israel has decided to do.

In Israel, Being Fully Vaccinated Now Means Three Shots

Holders of Israel’s vaccine passports must get a third dose of the Pfizer -BioNTech vaccine within six months of their second dose, or lose the so-called green pass that allows them more freedom.

“We are updating what it means to be vaccinated,” said Israel’s Coronavirus czar, Salman Zarka, at a press conference Sunday unveiling the new policy.

A study released by the Israeli health ministry on Sunday found that within 12 days, recipients of a third shot were 10 times less likely to become severely ill and 11 times less likely to become infected than people who had received their second dose five months earlier.

Israeli health officials say they don’t know whether additional boosters, beyond the third dose, will be needed. But they are moving aggressively to get as many people as possible vaccinated with a third shot, as the more contagious Delta variant of the virus spreads. All Israelis over the age of 12 are now eligible to receive a booster if five months have passed since their second shot.

 

[atyy]

Here's a Twitter thread from the Milo Lab with a link to the preprint "BNT162b2 vaccine booster dose protection: A nationwide study from Israel" mentioned by @nsaspook. "TL;DR: the booster dose improves protection against confirmed infection and severe disease by a factor of ≈10"

 

[Sagittarius A-Star]

However, there may be some scientific and social issues related to developing new boosters against the variants:

https://www.nature.com/articles/s41577-021-00592-1

They provide no evidence for:

Furthermore, the variants may be drifting apart, and so priming with a variant might narrow rather than broaden protection.
...
Whereas engineering new variant vaccines may not be beneficial, an alternative strategy is to boost immunity with a third dose of vaccine targeting the initial reference strain.

 

[artis]

Seems like there are new studies with regards to mixing of vaccines.

https://www.nature.com/articles/d41586-021-01359-3
https://www.nytimes.com/2021/06/24/world/europe/covid-vaccine-mix-and-match-pfizer-moderna.html

here is an article on boosters
https://www.nature.com/articles/d41586-021-02158-6

I do wonder myself , what could be potential adverse effects if indeed it is decided that at least for some age groups or professions they need to continually use a booster every 6 months or year.
Could it be that for more frequent use of the same vaccine the chances of additional side effects increase in frequency?

 

[Ygggdrasil]

They provide no evidence for:

Furthermore, the variants may be drifting apart, and so priming with a variant might narrow rather than broaden protection.

The idea that priming with a variant might narrow rather than broaden protection is based on the concept of "original antigenic sin" (OAS). The idea is that when boosting with a variant the immune system will preferentially activate memory B cells (which produce antibodies against the original antigen) rather than activate a set of new B cells (which could produce a set of new, more effective antibodies that better target the variant). The authors cite another published article discussing OAS in the context of COVID-19 boosters further:

“Original antigenic sin”: A potential threat beyond the development of booster vaccination against novel SARS-CoV-2 variants
https://www.cambridge.org/core/jour...ov2-variants/C8F4B9BE9E77EB566C71E98553579506

We have also discusses OAS in the context of COVID-19 in a previous thread: https://www.physicsforums.com/threa...o-endemic-coronaviruses.1005206/#post-6523013

The authors also point an example of OAS with previous influenza vaccines:

Reduced Antibody Responses to the Pandemic (H1N1) 2009 Vaccine after Recent Seasonal Influenza Vaccination
https://journals.asm.org/doi/10.1128/CVI.05053-11

[edit: here's a nice popular press article on OAS: https://www.statnews.com/2021/04/16...etter-some-experts-worry-they-could-be-worse/]

Whereas engineering new variant vaccines may not be beneficial, an alternative strategy is to boost immunity with a third dose of vaccine targeting the initial reference strain.

While the authors don't cite any data for this point, there are data to support this idea. See, for example, the pre-print from the study in Israel cited by @atyy https://www.physicsforums.com/threads/covid-delta-variant.1004265/post-6535265

Pfizer and Moderna have also submitted data on booster doses for the FDA to review, which should be publicly available soon.

 

[Ygggdrasil]

Seems like there are new studies with regards to mixing of vaccines.

https://www.nature.com/articles/d41586-021-01359-3
https://www.nytimes.com/2021/06/24/world/europe/covid-vaccine-mix-and-match-pfizer-moderna.html

It's been known for a while that using two different types of vaccines that target the same antigen (a heterologous prime-boost strategy) is often better than two doses of the same type of vaccine (e.g. see this article from 2009 on the topic), so I'm glad people are exploring the strategy with the COVID-19 vaccines.

I do wonder myself , what could be potential adverse effects if indeed it is decided that at least for some age groups or professions they need to continually use a booster every 6 months or year.
Could it be that for more frequent use of the same vaccine the chances of additional side effects increase in frequency?

Would this be much different than an annual flu vaccine? Can you cite any evidence or data to support the idea that frequent use of the same vaccine could lead to additional side effects? Remember, than the FDA requires clinical trials of the booster shots and reviews the data to look for evidence of problems like these. As stated above, the FDA will meet to review data on the Pfizer and Moderna boosters this month, so these safety and efficacy data will be made available to the public then. Furthermore, the CDC also closely monitors adverse effects from vaccines even after they have been authorized or approved in order to catch any unexpected adverse events (which is how they have observed rare one in 100,000 or one in one million adverse events linked to some of the vaccines, such as VITT).

 

[Sagittarius A-Star]

While the authors don't cite any data for this point, there are data to support this idea. See, for example, the pre-print from the study in Israel cited by @atyy https://www.physicsforums.com/threads/covid-delta-variant.1004265/post-6535265

Pfizer and Moderna have also submitted data on booster doses for the FDA to review, which should be publicly available soon.

Maybe we will see this year from clinical studies, which kind of antibodies (old or new) will be created, if 2 doses of Pfizer/BioNTech vaccine are followed by the updated version containing Delta mRNA.

While Pfizer and BioNTech believe a third dose of BNT162b2 has the potential to preserve the highest levels of protective efficacy against all currently tested variants including Delta, the companies are remaining vigilant and are developing an updated version of the Pfizer-BioNTech COVID-19 vaccine that targets the full spike protein of the Delta variant. The first batch of the mRNA for the trial has already been manufactured at BioNTech’s facility in Mainz, Germany. The Companies anticipate the clinical studies to begin in August, subject to regulatory approvals.

Source:
https://investors.biontech.de/news-...h-provide-update-booster-program-light-delta/

 

[Ygggdrasil]

Maybe we will see this year from clinical studies, which kind of antibodies (old or new) will be created, if 2 doses of Pfizer/BioNTech vaccine are followed by the updated version containing Delta mRNA.

Source:
https://investors.biontech.de/news-...h-provide-update-booster-program-light-delta/

We might not have to wait that long. Back in March, Moderna and the NIH initiated a clinical trial to test variant-specific boosters (using a booster targeted against the Beta variant):

Approximately 60 volunteers who previously received mRNA-1273 as a participant in NIAID’s Phase 1 trial of mRNA-1273 (which began in March 2020) will enroll in the new variant Phase 1 trial. Approximately one year ago, these volunteers received two vaccinations of mRNA-1273 28 days apart at varying doses: 50 mcg, 100 mcg or 250 mcg. As part of the variant vaccine trial, these volunteers will be randomized to receive either a single booster vaccination of 50 mcg of mRNA-1273.351 (group 1A) or a single vaccination containing one 25-mcg dose of mRNA-1273 and one 25-mcg dose of mRNA-1273.351 (group 1B). The remaining participants from the March 2020 trial will be offered a booster shot of mRNA-1273 as part of a separate clinical trial protocol (for more information see clincialtrials.gov: NCT04283461).

https://www.nih.gov/news-events/new...ating-moderna-covid-19-variant-vaccine-begins

That clinical trial might have data relevant to whether OAS occurs with the COVID vaccines. Unfortunately, according to the ClinicalTrials.gov site, the trial does not have any results posted yet: https://clinicaltrials.gov/ct2/show/study/NCT04785144

 

[Astronuc]

Children's Hospitals Are Pleading For Federal Help As They Run Out Of Beds​

https://www.npr.org/sections/corona...itals-coronavirus-covid-capacity-federal-help

A group of more than 220 children's hospitals is imploring the Biden administration for help, as a surge of young COVID-19 patients puts an "unprecedented strain" on their facilities and staff across the country.

Pediatric hospitals are "at or near capacity" and they expect to see more child patients as the school year resumes, according to the Children's Hospital Association.

"[T]here may not be sufficient bed capacity or expert staff to care for children and families in need," wrote association CEO Mark Wietecha in a letter to President Biden on Aug. 26.

I am baffled by persons who find it acceptable to exposure children and the general public to a virulent and potentially fatal respiratory virus.

 

[Laroxe]

Well, we know that high levels of antibodies provide good protection against infection against all variants, the two issues to consider is actually achieving the high levels and then maintaining them. The antibody response is highly variable, but we can at least identify some people that are least likely to mount a good response and we now know that the 3 week gap between the 1 & 2nd dose isn't optimal, a longer gap gives a better response. We can also potentially mix vaccines, which provide a wider range of epitomes for the immune system to target, trials in the UK giving the AZ vaccine followed by the Pfizer, suggested it provided better and more enduring protection.

Regardless of these tweaks the fact is that protection from antibodies is a partial and temporary answer, as things stand variant specific vaccines seem to offer little advantage, we would be committed to continually developing and then administering boosters. Each of these carrying their own, albeit small risk, while offering significant enhanced protection for around 7 months of the year. It makes sense, as things stand in the management of the disease, to offer a 3rd vaccination to people at risk, while hoping for more effective treatments, even the WHO support that, despite the global supply problems.
However, the data coming out of Israel and the UK, and remember the UK has dropped all the mitigation requirements, we see a marked increase in infections, which is now at levels seen in the previous peaks, hospitalisations are also increasing, but are at a level less than a third of what it was with this number of infections and with the unvaccinated being disproportionally effected and deaths remaining low.

There have been some recent indications from the UK government, that while people who are considered highly vulnerable will be offered a further booster, the current level of protection in the population is probably as good as it gets. The view appears to be that this disease will be with us for some time and everyone will be exposed, probably repeatedly. The vaccine does offer considerable protection against severe disease and death but not against infection. This implies that vaccine refusal might represent less of a risk to the wider population, it is in fact this group that are already suffering disproportionally. It will be interesting as economies try to recover, to see if the funding to promote vaccination will continue to be made available.
So long as the level of deaths remain low, repeated exposure to the virus, will provide the periodic boosters, perhaps until newer interventions become available.

 

[Sagittarius A-Star]

That clinical trial might have data relevant to whether OAS occurs with the COVID vaccines. Unfortunately, according to the ClinicalTrials.gov site, the trial does not have any results posted yet: https://clinicaltrials.gov/ct2/show/study/NCT04785144

AstraZeneca has developed a new version of their vaccine containing minor genetic alterations to the spike protein based on the Beta (B.1.351, South African) variant. They claim, that they found no evidence for OAS in animal studies.

27 June 2021 13:00 BST
...
The first participants in a Phase II/III trial for the new COVID-19 variant vaccine AZD2816 were vaccinated today to assess its safety and immunogenicity in both previously vaccinated and unvaccinated adults.
The trial will recruit approximately 2,250 participants across UK, South Africa, Brazil and Poland.
...
AZD2816 has been built using the same adenoviral vector platform as with Vaxzevria, with minor genetic alterations to the spike protein based on the Beta (B.1.351, South African) variant. The Beta variant vaccine contains ten changes across the spike protein, many of which are also seen in other variants of concern ...

Source:
https://www.astrazeneca.com/media-c...ase-ii-iii-trial-participants-vaccinated.html

We demonstrate AZD2816 is immunogenic after a single dose and when used as a booster dose in animals primed with original vaccine AZD1222, we see no evidence of original antigenic sin but high titre antibodies against a number of variant spike proteins. In addition, neutralisation titres against B.1.351 (Beta), B.1.617.1 (Kappa) and B.1.617.2 (Delta), are induced in these boost regimens. These data support the ongoing clinical development and testing of this new variant vaccine.
...
AZD2816 as a third dose can further enhance antibody responses induced by two doses of AZD1222
...
Overall the data shows that a booster dose with a new ChAdOx1 against the new variant B.1.351 (AZD2816), can further enhance antibody responses against SARS-CoV-2 B.1.351 and provide cross-reactivity against other variant proteins.

Source:
https://www.biorxiv.org/content/10.1101/2021.06.08.447308v1

In table 1, they compare AZD1222 + AZD1222 + AZD2816 to AZD1222 + AZD1222, but unfortunately not to AZD1222 + AZD1222 + AZD1222 (boost with original vaccine). That might have given evidence for or against OAS.

 

[Rive]

However, there may be some scientific and social issues related to developing new boosters against the variants:

Furthermore, the variants may be drifting apart, and so priming with a variant might narrow rather than broaden protection. It is our opinion that engineering novel booster vaccines should not be a priority at this time.

Whereas engineering new variant vaccines may not be beneficial, an alternative strategy is to boost immunity with a third dose of vaccine targeting the initial reference strain

As long as there is sufficient cross-immunity between variants, it's indeed not a big problem in these transitive times. On long term, however a likely outcome is that there will be several competing main strains established, with very limited cross-immunity between them. That time not just 'variant' but likely multivalent boosters will be needed.

 

[Sagittarius A-Star]

AstraZeneca has developed a new version of their vaccine containing minor genetic alterations to the spike protein based on the Beta (B.1.351, South African) variant.

They will also test boosting an mRNA vaccination with AZD1222 vs. AZD2816. That may give evidence for or against OAS.

mRNA booster: one dose of AZD1222
Previously vaccinated with an mRNA vaccine, dosing on day 1

mRNA booster: one dose of AZD2816
Previously vaccinated with an mRNA vaccine, dosing on day 1

Source:
https://clinicaltrials.gov/ct2/show/NCT04973449

 

[bhobba]

https://www.worldometers.info/coronavirus/

Looking at the upper general statistical graphs of both daily new cases and daily deaths it seems that the third wave that is happening now is less severe in terms of deaths and also somewhat smaller compared to daily new cases,

Oh yes. While vaccine efficacy is interesting and important, the most important statistic is hospitalisation and death prevention. While efficacy is waning with both AZ and Pfizer, protection against hospitalisation and death remains very high.

Interestingly a recent study in Bahrain showed, as far as preventing death is concerned, there was some evidence of all the vaccines they tried the much-maligned in Australia, AZ vaccine, was the most effective:
https://economynext.com/vaccines-wo...-got-sinopharm-vs-pfizer-bahrain-study-85458/

I dearly would like to see the journal preprint, but it just goes to show this pandemic is constantly throwing up surprises.

Thanks
Bill

 

[Astronuc]

The rate of children and teens hospitalized because of the Coronavirus increased nearly five times in mid-August—and 10 times, for children under four—the Centers for Disease Control and Prevention (CDC) reported in two key studies released Friday, which also showed the worst rates of children struggling with the disease happening in the states with lower vaccination rates.

https://www.forbes.com/sites/kimber...y-almost-5-times-cdc-reports/?sh=125ddc501b30

The rate of children with Coronavirus who end up hospitalized is 49.7 per 100,000 children as of August 14, with the highest rate of hospitalizations among kids under the age of 4 (69%) followed by teens between the ages of 12-17 (64%).

Hospitalizations began to climb due to the spread of the delta variant in mid-August, when many students returned to school, and children and teen hospitalizations increased nearly five times mid-August compared to the end of July, while hospitalizations for children under the age of 4 increased 10 times during the same period.

The new studies follow a record-breaking month for U.S. children hospitalizations, with 330 children admitted daily between August 20 and August 26, according to the CDC. The rise in hospitalizations coincide with the return to school for many students along with the rising spread of the delta variant in all states throughout the U.S.

 

[atyy]

Interestingly a recent study in Bahrain showed, as far as preventing death is concerned, there was some evidence of all the vaccines they tried the much-maligned in Australia, AZ vaccine, was the most effective:
https://economynext.com/vaccines-wo...-got-sinopharm-vs-pfizer-bahrain-study-85458/

I dearly would like to see the journal preprint, but it just goes to show this pandemic is constantly throwing up surprises.

https://www.researchsquare.com/article/rs-828021/v1
Morbidity and mortality from COVID-19 post-vaccination breakthrough infections in association with vaccines and the emergence of variants in Bahrain
Manaf AlQahtani, Sujoy Bhattacharyya, Abdulla Alawadi, Hamad Al Mahmeed, Jaleela Al Sayed, Jessica Justman, Wafaa M. El-Sadr, Jack Hidary, Siddhartha Mukherjee

Their data are not purely Delta, but contain a lot of Delta. In terms of naive numbers, AZ turned out the best in their comparison, but I would guess it's not statistically different from Pfizer. While they have data on Sinopharm, Pfizer, Sputnik and AZ, they only did statistical tests comparing Sinopharm and Pfizer.

They report odds ratios for various comparisons, rather than vaccine efficacy. But it's interesting to have a vaccine efficacy number for our rough comparison. In Table 4 (p11), they report that the death rates among people above 50 who are unvaccinated (37.17 per 100,000), Sinopharm vaccinated (5.45) and Pfizer vaccinated (0.96), which corresponds roughly to Sinopharm VE ~ 85%, Pfizer ~97%.

 

[bhobba]

Oh yes. In Aus, when they talk about vaccination rates, several think tanks say the rates needed to start opening up include children under 12. No vaccine has been approved for that, but they think that is what is needed with Delta.

To me, it looks like we are going to need vaccination rates about the same as diseases such as Whooping Cough, which in Aus is about 94%. But people are slack about getting boosters when over 20 - under 20 No-Jab, No Pay applies. I had my last booster about 30 years ago. My sister got it nearly 30 years ago while pregnant - the worst time of all to get it. They were apprehensive about the effect on the baby.

Thanks
Bill

 

[bhobba]

In terms of naive numbers, AZ turned out the best in their comparison, but I would guess it's not statistically different from Pfizer.

That would be my guess as well. From UK data, both are very effective against hospitalisation and death, even against Delta.

Thanks
Bill

 

[.Scott]

If you have already had your 2 mRNA vaccinations, would a Delta infection be a good booster against other Covid-19 variants?

I would claim that the objective is to have a world population that is as exposed to COVID-19 as it is to (other) seasonal flu viruses - so that a COVID-19 infection is no longer an uncommonly lethal threat or one that challenges health care resources any more than the seasonal flu.

Here is my reasoning:
Given that objective, I would rather my first encounter with the actual COVID-19 be sooner rather than later for two reasons:
1) Sooner means my vaccination is still strong - and my reaction to the the virus should not be exceptionally challenging.
2) Sooner means the Delta variant, and the mRNA vaccines provide protection against that variant.

If I get Delta soon, then when something like lambda comes along, my immune system will have seen many lambda components - even though that prominent spike protein won't be one of them.

On the other had, if I dodge Delta, something like lambda could completely blind-side my immune system.

 

[atyy]

If you have already had your 2 mRNA vaccinations, would a Delta infection be a good booster against other Covid-19 variants?

On the other had, if I dodge Delta, something like lambda could completely blind-side my immune system.

Here is a similar discussion: https://www.bbc.com/news/health-58270098. However, it is important to note that it is in the context of the UK, where vaccination and seropositivity rates are much higher than the US, whereas in the certain parts of the US, hospital systems are still under pressure, and it remains important to reduce transmission. Also, there are still deaths of fully vaccinated people who are at higher risk, so such people should continue to take the necessary precautions and a booster if their local health authority makes it available to them. In general, for an endemic virus, the idea is not to get infected deliberately, but rather to take precautions against infection (wash hands, people should not go to work when sick etc), but not to get too worried if one gets sick. Also, lambda and recent new variants are not expected to escape vaccine protection against severe disease, even if the vaccine induced neutralizing antibodies protect less against infection; this is because there are other components of the immune response that are relatively resistant to variants.

 

[bhobba]

If I get Delta soon, then when something like lambda comes along, my immune system will have seen many lambda components - even though that prominent spike protein won't be one of them.

If you got Delta when double vaccinated, it has been shown your immunity to Covid infection is strengthened. But deliberately doing it is a risky strategy because you may, for example, have diabetes and not know it. In such a case, your chance of dying, while still much lower than not being vaccinated, has risen significantly. I have been saying throughout the pandemic that everyone should get a thorough physical, including checking vitamin D levels. That will give you a good idea of your risk, some of which you can do something about - e.g. bring vitamin D levels to what is these days considered normal. Normal has been raised a bit over recent years, but that is another story (previously 30 was considered OK - but is now mildly deficient):
https://www.racgp.org.au/afpbackissues/2008/200812/200812stroud.pdf

Thanks
Bill

 

[artis]

@.Scott I'd say that going out licking door knobs and randomly kissing strangers just to "unlock" next level immunity is probably a bad idea as besides Covid there are the "regular" viruses out there that everyone now seems to have forgotten about.
I think with full vaccination or previous infection (in case one has good level of antibodies) one should simply go out and live a normal life and then if one gets the virus again it's simply destiny.
I had a previous infection I am still being cautious but not to the point where I'm paranoid, stress is actually a health hazard.

 

[Ivan Seeking]

One interesting side note I've learned in all of this: The average body temperature in the US is dropping.
https://med.stanford.edu/news/all-n...mperature-has-decreased-in-united-states.html

 

[atyy]

One interesting side note I've learned in all of this: The average body temperature in the US is dropping.
https://med.stanford.edu/news/all-n...mperature-has-decreased-in-united-states.html

Yeah, I learned that when we had semi-lockdown last year. My employer instructed us to take our temperature every day. And my measurements dropped each day - so I wondered if lockdown causes temperatures to drop, and googled and found that article you linked. But when I finally started having temperatures below 35C, I thought it must be the digital thermometer. So I got a new "mercury" thermometer (no mercury, it's some other non-toxic substance), and my temperature went back up to 36.4C. The digital thermometer stopped functioning shortly after.

 

[Ivan Seeking]

Yeah, I learned that when we had semi-lockdown last year. My employer instructed us to take our temperature every day. And my measurements dropped each day - so I wondered if lockdown causes temperatures to drop, and googled and found that article you linked. But when I finally started having temperatures below 35C, I thought it must be the digital thermometer. So I got a new "mercury" thermometer (no mercury, it's some other non-toxic substance), and my temperature went back up to 36.4C. The digital thermometer stopped functioning shortly after.

It first came to my attention using a liquid thermometer at home for Covid. When I was a kid I was always at 98.6 unless I was sick. But now I never seem to get much above 97. At first I assumed it was the medication I'm taking. But when visiting customer sites where they take everyone's temp, I became aware of the fact that other people's temps were low too. I started asking the people taking the temps and soon it became clear that almost everyone was low! One women didn't even know that the average temp is supposed to be 98.6 because [in her words] nobody is that high.

 

[artis]

So you guys are saying we are cooling in the midst of global warming? I guess nature likes balance.
It's funny @Ivan Seeking but the difference between 98.6 and 97 F is about the same the global average temp has risen since industrial revolution...

 

[Ivan Seeking]

So you guys are saying we are cooling in the midst of global warming? I guess nature likes balance.
It's funny @Ivan Seeking but the difference between 98.6 and 97 F is about the same the global average temp has risen since industrial revolution...

Haha, and here I thought global warming was due to pirates. All this time the problem has been us!

Stop climate change: Go Endothermic!

They say this in the linked reference

The researchers determined that the body temperature of men born in the early to mid-1990s is on average 1.06 F lower than that of men born in the early 1800s. Similarly, they determined that the body temperature of women born in the early to mid-1990s is on average 0.58 F lower than that of women born in the 1890s. These calculations correspond to a decrease in body temperature of 0.05 F every decade.

Of course this is getting way off topic now. But I noticed it because of Covid. A quick search revealed it's true!

 

[.Scott]

@.Scott I'd say that going out licking door knobs and randomly kissing strangers just to "unlock" next level immunity is probably a bad idea as besides Covid there are the "regular" viruses out there that everyone now seems to have forgotten about.

Covid-19 is known to spread by respiration but is only presumed to spread by fomites. So licking door knobs would be unreliable at best. It's not even clear whether kissing would work. But asking them to sing for you ..
What keeps Covid from being a "regular virus" is that it is very unlike what our immune system have been trained for. The point behind catching Delta would be to relegate it to the status of a "regular virus".

I think with full vaccination or previous infection (in case one has good level of antibodies) one should simply go out and live a normal life and then if one gets the virus again it's simply destiny.
I had a previous infection I am still being cautious but not to the point where I'm paranoid, stress is actually a health hazard.

"If you don't do the choosing, life will choose for you, and it may not be the choice you want". - Robert N. Anthony

 

[.Scott]

If you got Delta when double vaccinated, it has been shown your immunity to Covid infection is strengthened. But deliberately doing it is a risky strategy because you may, for example, have diabetes and not know it. In such a case, your chance of dying, while still much lower than not being vaccinated, has risen significantly.

I believe your Math is incomplete. You are comparing a 100% chance of getting Delta while recently vaccinated against an unspecified chance of getting any variant at any time.

I was actually going to try to list off the decision-making Math here - but it gets pretty complicated pretty fast. For examples: You would need to model your vaccination effectiveness, cross-variant immunity effectiveness, and risk of infection as functions of time. And there is value in delaying the inevitable.

You say I might have a risk factor and not know it. But if I don't know it, how much incentive will I have over the next several years to avoid COVID-19 - or any other infection I may be vulnerable to. Given that situation, it might still be better to get it now. If the lethality now versus later is 0.4 vs. 0.9, better to get it now. If it's 0.94 vs. 0.99, better to delay as long as possible. Of course, that doesn't factor in one's personal value of time. If you only want to make it to the end of this year to complete your bucket list, then avoid COVID.

A major factor is the likelihood of avoiding COVID completely. If you know you are at very high risk even when vaccinated, then this is the option for you.

And until recently, is was the strategy for Australians as well. Delta has made that strategy very difficult.

Besides, my HbA1c is 4.9.

 

[.Scott]

Here is a similar discussion: https://www.bbc.com/news/health-58270098. However, it is important to note that it is in the context of the UK, where vaccination and seropositivity rates are much higher than the US, whereas in the certain parts of the US, hospital systems are still under pressure, and it remains important to reduce transmission.

In New England, the vaccination rate is roughly 70% and hospitals are not overly strained by COVID.
This is in great contrast to south-eastern US.

Also, there are still deaths of fully vaccinated people who are at higher risk, so such people should continue to take the necessary precautions and a booster if their local health authority makes it available to them.

People at very high risk need to take exceptional measures to avoid Delta. If society decides to assist them at the "endemic" level (not just their personal quarantine level), then we would need to talk about how to very reliably eliminate Delta ASAP - for example by rapidly spreading the infection while the vulnerable are isolated. I would not recommend that.

In general, for an endemic virus, the idea is not to get infected deliberately, but rather to take precautions against infection (wash hands, people should not go to work when sick etc), but not to get too worried if one gets sick.

But this is not the general case. We have a situation where most of the population has a very low "breadth" (to use the term from the article you cited) of immunization - limited to just one protein.

Also, lambda and recent new variants are not expected to escape vaccine protection against severe disease, even if the vaccine induced neutralizing antibodies protect less against infection; this is because there are other components of the immune response that are relatively resistant to variants.

They won't escape once the "breadth" issue has been addressed - through infection or through a different vaccine.

Yes, there are two or three immune system mechanisms that respond to the vaccination - antibodies, T-Cells, and perhaps other lymphocytes. But with the mRNA vaccinations only, all of them are unvaccinated for any future variant with an unrecognized spike protein.

 

[atyy]

But this is not the general case. We have a situation where most of the population has a very low "breadth" (to use the term from the article you cited) of immunization - limited to just one protein.

It is true that immunization with more antigens could be beneficial in the longer term, but even the one protein used for immunization (in the current Pfizer vaccine) corresponds to many epitopes, and memory B and T cells have the ability to recognize variants. This is likely why protection against severe disease caused by variants has remained either unchanged or fallen much less compared to the decreased protection against infection.

 

[bhobba]

A major factor is the likelihood of avoiding COVID completely. If you know you are at very high risk even when vaccinated, then this is the option for you. And until recently, is was the strategy for Australians as well. Delta has made that strategy very difficult.

Glug glug for Aussies - and don't I know it. It's fine right now in Brisbane, where I live, but it will not last - it is just a matter of time.

The strategy now in NSW and Victoria, where it is out of control with an R of about 1.3 (the highest of just about any other country), is to get vaccinated, vaccinate and vaccinate some more. They have achieved over 70% first doses in NSW and soon will be 80% and hopefully higher. It is expected over 80% two doses by November. That must bring R down - with 70% and just 1 dose at 30% efficiency, my calculation shows it will be below 1 and getting better as more get second doses, and first doses rise above 80%. I am hopeful it soon will be under control here in Aus. But people need to wake up. Queensland only has 53% first doses, and my sister is only getting vaccinated reluctantly. I try to explain the importance, but she says, what do you know.

Immunologists are divided on if we can eradicate it. My calculations indicate 95% vaccination and a third dose could do it - but that is a tough target. Most believe we will have to live with it but take precautions. I wish we would look more at Taiwan, which already has R below 1 and starting from virtually zero is immunising fast - so fast it approved its own homegrown vaccine (Medigen - 600,000 doses administered in a week alone) before stage 3 trials were completed:
https://thediplomat.com/2021/07/why-taiwan-is-beating-covid-19-again/

10 million first doses already - waiting for first doses to be completed before concentrating on second doses. Australia could learn a thing or two from that.

Thanks
Bill

 

[atyy]

Immunologists are divided on if we can eradicate it. My calculations indicate 95% vaccination and a third dose could do it - but that is a tough target. Most believe we will have to live with it but take precautions.

For eradication, one also has to take into account that protection from infection declines over time due to falling antibody levels and viral mutations. It seems that protection from severe disease is quite steady despite that, so I'm in the live with it camp. I think that if the vaccination rate approaches 100% in vulnerable groups, that the precautions we take might not have to be much more than for flu.

Rather amazingly, Portugal is reporting that 99% of people aged above 65 have been fully vaccinated (both doses)!
https://covid19.min-saude.pt/wp-content/uploads/2021/09/Relato%CC%81rio-de-Vacinac%CC%A7a%CC%83o-n.o-29.pdf

 

[artis]

a rather reasonable assessment of the latest situation