1 hour ago, nocl said:

The one place where I would disagree would be along the lines of one of the trials Lilly is doing.  It is a very specific preventative trial in a nursing home environment, where there is a COVID outbreak actively occurring.  That kind of limited scope application as a preventative could very easily be both medically and economically reasonable.  When one compares the cost of a number of patients having to be transferred to a hospital for treatment including potentially several days in intensive care and the use of ventilators the numbers would tilt pretty quickly to use the MAB. if the trial shows it to be effective in such settings.  But even there you would be talking fairly small number of doses  for a limited period to stop an active outbreak. Even there it would be expensive, but not in comparison to a couple of people spending a few days in intensive care.

 

I have seen MAB cost of product per dose in the  $1000 to $2000 range. They will sell for much more but mostly due to the price for MAB treatments are driven by two factors 1. limited market size  2. Economic benefit compared to other treatments.

A MAB that cures an illness at $100,000 is cheap compared to the cost of controlling a chronic condition for years.

 

Also the prices reported tend to be annual costs, not single dose costs.  A drug whose annual costs are $100,000 might have an dose cost of less than $10k

 

The biggest issue is that many MABs are small market, with small production runs.  There is an interesting paper from 2009 that discusses the potential for dramatic cost reductions with newer technology and larger size runs.

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759494/

Hi,

I agree with all your comments. 

However, the present cost is unknown and I'm only repeating 

what I read (it's expensive). Even if it's $1000 or $10,000 it's

still an expensive procedure that many people/countries may not

be able to afford.

The mAb are difficult and expensive to produce. Even Lilly said

in August that it would take till the end of the year to make 100,000 doses.

How long would it take to make 100's of million doses?

They also mention that the cost would be affordable but did not

give any dollar figure.

Also they are "usually" given intravenously which is an  expensive

delivery (several hundred dollars even for a saline iv drip).

You need an experienced nurse. 

To decrease cost they are looking for more potent mAb that would lower

the dose needed. Also, by modifying the mAb they can increase

it's half life and be more effective for a longer period.

3 hours ago, BP99 said:

Hi,

I think that the monoclonal antibody therapy is a great approach to treating

patients with covid. However (IMO), all FDA approved monoclonals for

other diseases (eg. cancer) are outrageously expensive. They are expensive

to produce and deliver. To be used as a preventative would be costly

(unlike most vaccines).

 

To further add numbers:

There have been 7,500,000 infected with covid in the USA (total).

Usually 1 in 5 requires hospitalization (1,500,000).

The "average" cost for "other" monoclonal treatment ~ $100,000

(but usually ~ $250,000 for annual cancer treatment).

To treat all early covid hospital cases (which is recommend with

the monoclonals) would cost $150,000,000,000. YES, I think

this cost is worth paying to save 100's of thousands of lives!

The companies who make these monoclonals may decrease

the cost for this pandemic but I haven't seen anything on this.

All the numbers I obtained are guestamations and may not

be correct. My examples are at the "high" end. Hopefully

the cost will be reasonable so that no further deaths happen

during treatment of patients.

2 hours ago, Doris&Nereus said:

What do you think about this article on an antibody therapy that could be of tremendous help? I know that I posted about this before, but I just don't see why we can't

expand our efforts to include more therapies. We should not put all our eggs in one basket, INMHO.

 

https://www.washingtonexaminer.com/opinion/op-eds/an-antibody-therapy-could-get-us-to-the-new-normal

Hi,

I think that the monoclonal antibody therapy is a great approach to treating

patients with covid. However (IMO), all FDA approved monoclonals for

other diseases (eg. cancer) are outrageously expensive. They are expensive

to produce and deliver. To be used as a preventative would be costly

(unlike most vaccines).

21 hours ago, markeb said:

 

Can't find it this morning, but saw either a press release or actual story on this last night. Had to do some looking this morning.

 

Inovio is working on a DNA vaccine. This concept has been around for probably 20 years, but I'm unaware of any being licensed. Naked DNA doesn't get into cells, so historically (and sounds like what Inovio is doing, but their PR is somewhat vague) the DNA that codes for the immunogenic protein was embedded in tiny gold beads, and administered via an electrostatic device that essentially produces an electrostatic charge that momentarily opens up the cells in the deeper layers of the skin to accept the beads and the DNA, which then gets incorporated into protein synthesis in the cell, and bingo, you have SPIKE (in this case). The superficial skin layers are dead cells, so you've got to get it into the living, deeper layers.

 

It looks like the device is in question. I'll confess when I was working vaccine requirements in a previous life, I was never a fan, because there's so much that can go wrong, and you need the device everywhere you're going to administer the vaccine. They seemed to work really well in pre-clinical trials, but the logistics of using them always seemed a bridge too far. Most of the lead candidates in the US now are using novel technologies, which means they're great if all goes well, but they all have potential Achilles heels. The subunit vaccine from Novovax is probably the safest candidate from a regulatory standpoint, but we are just now entering the danger zone on delivering a safe and effective vaccine...

Hi,

The pause for Inovio "may" be the device BUT they also have had lots of bad

press lately about lawsuits due to manufacturing (a change) and information

to shareholders. Do a google with "Inovio and lawsuits".

9 hours ago, markeb said:

 

#1 I'm not going to minimize the risk of reinfection, but I haven't seen anything that proves it. Early reports were of recovery of viral RNA via PCR, which is not an indication of viability. Probably need to hit the search engines again, but I've not seen anything (yet) that makes it more than an academic concern, and also not common if it does occur. That could change with more data. Certainly there was early data suggesting a lesser immune response to a less serious infection, so asymptomatic or minimally symptomatic individuals might have a lesser immune response and viral recovery from subsequent exposure might be more likely in them.

 

#2 Early reports on the vaccine candidates showed good T-Cell responses. Antibodies can decline fairly rapidly, but if there's a good population of T-Cells, you still can get a good anamnestic response from exposure, and a rapid increase in antibodies when actually needed. The various clinical trials should get a better feel for that through whatever booster studies they do. For their biological license application, the various sponsors will almost certainly report antibody titers over time, as they're easy to review. They may also have limited meaning. So I think we should all take a deep breath on antibodies. The challenge for licensure and vaccination schedules could be if there's immunity, but antibody titers prove to not be a great correlate of immunity. The natural exposure studies in Phase III should smooth out that data.

 

We're hitting that point that demonstrates why most vaccine development takes a long time and a lot of money...

Hi,

There was an interesting article on CNN by Dr. William Haseltine about herd

immunity and reinfection. He is an OUTSTANDING scientist! He gives

some info on another coronavirus  NL63 (HCoV-NL63) that was well

studied and is quite interesting about reinfection. I also totally agree

with your comments that immune cellular memory is important.

3 hours ago, cangelmd said:

Not sure who,I’m responding to because I’ve been MIA the last week, and now we’re having a hurricane - 2020 just keeps getting better!

 

 I never pictured monoclonal as anything but a therapy for very ill hospitalized patients - think of it as a concentrated version of convalescent plasma, but instead of giving a person a cocktail of whatever antibodies another individual produced in response to the virus, you are giving the sick person a very specific antibody that will have an effect on the virus OR on the immune response.

You can’t exactly compare monoclonal Abs used in different diseases or extrapolate, because while they each bind to a specific protein, what happens after that step varies depending on type protein is bound and what the mechanism of disease is. I think that would also affect the duration of the effect that the antibody (drug in this case) is trying to produce.

 

 

Hi,

Normally mAb's when given to people last in high enough levels for 1-4 weeks.

However by altering them (FC region, glycosylation, combing them with

carriers etc) can increase their half life. AstraZeneca reported that they are

planing a Phase 1 study with their mAb that  their modified antibody

that "should be" protective for 6 months (see below). Also a review of mAbs.

https://www.contagionlive.com

August 25, 2020

AstraZeneca Begins Phase 1 Trial for Monoclonal Antibody Combination for COVID-19

AstraZeneca announced this morning it has started its phase 1 clinical trial for AZD7442, its investigational therapy which is in development for the prevention and treatment of coronavirus 2019 (COVID-19).

This therapeutic could afford at least 6 months of protection from COVID-19, according to a statement released by the company.

June 15, 2020

Monoclonal Antibodies for Prevention and Treatment of COVID-19

Mary Marovich, MD¹; John R. Mascola, MD¹; Myron S. Cohen, MD²

Author Affiliations Article Information

JAMA. 2020;324(2):131-132. doi:10.1001/jama.2020.10245

25 minutes ago, markeb said:

 

You can at least theoretically use mAbs a couple of ways. Using them in high risk settings prior to infection is essentially the same as the old days of using Gamma Globulin as protection against hepatitis A. As long as it's on board and can bind the virus, it will provide some protection. They'll have a limited lifespan in the body, and unlike an active immunization, you won't make more. It's hard to say where that would be most useful; maybe an outbreak in a high risk population, or preprocedure? It's hard to imagine more widespread use.

 

For treatment, the big challenge with most respiratory viruses is by the time you know what you've got, they've done most of their damage, and you're now fighting the body's own immune response. That's why most folks advocate for early use of mAb or convalescent serum, which sounds counterintuitive, and why the concerns that using mAbs later in the disease won't stop the current disease (they'll bind the virus, but the inflammatory response to dead and infected cells is causing the pathology). And I think that's what BP99 is saying.

 

In theory, if there's enough virus (or SPIKE in this case), someone infected with the virus and treated, either before or after infection, with a mAb should mount their own immune response, which would last a lot longer.

 

As with most things with this virus (and immunology!), it's complicated.

 

 

Yes, you are correct with what I was trying to explain earlier. I was actually 

typing my response when your reply was posted. Sorry for the repeat info.

There are MANY FDA approve mAbs but mostly for cancer treatments.

There are a few against other diseases. To make enough mAbs for

a "preventable" world wide pandemic would be excessively expensive. 

36 minutes ago, Doris&Nereus said:

BP99, you say that the mAb will not kill the current infection.  So they just drop off , and the same infection just comes back after the 4 months or so. I thought that the person who got the treatment could get another infection, but not the same one would get back into the cells. That is why I was hoping for mAbs to work on sick people and those at very high risk until we can get the vaccine to work. Also, there are some people who have poor immune response to vaccines, and they could benefit.

The mAb WILL remove and kill the virus in infected people. This is a "treatment".

If given in high enough doses (and long enough) it should theoretically cure most

infected people. Although this has to be tested. This also greatly depends

on how much damage the virus has already caused prior to using the mAbs.

There are treatments for other infections using mAb that are approved. 

However, if given to people that are NOT infected it will only prevent getting the

virus for a short term. This is a "preventative" treatment. A vaccine is

also a  "preventative" method that is usually better/cheaper/longer lasting method

 without giving the virus a chance to cause damage.

1 hour ago, TeeRick said:

Yes this is my main concern too with mAb's .  If they work as a therapeutic that would be great but like Remdesivir would be used in a setting with hospitalized COVID patients (presumably with health insurance).  I cannot see any scenario where mAb's would be used longer term for preventing viral infection in healthy people.  They do not take the place of a decent vaccine.

Yes, I agree that they (the companies) are pushing the term "preventative" treatment

since the mAb have a limited half life (weeks/months) depending on the dose and

NO potential memory (T&B cells). They also mention using mAb's that don't

have FC receptors to increase their half life but you are still left with clearing

the virus once the mAb's bind to the virus. They are used effectively to treat

certain disease but are EXPENSIVE to make/use.

3 hours ago, Arizona Wildcat said:

Rick - my statement does have a typo.  Sorry.  Should have said or instead of "of".  There are viruses that are almost 100% controlled such as smallpox.  rDNA viruses like flu easily mutate and for whatever reason - I am not a doctor - the multiple strains are not all in the vaccine.   Viruses are not all like flu.

Huh? I am not a virologist but for some friendly clarification:

Flu viruses (Influenza) are RNA viruses. I'm not sure what you mean by a rDNA

virus?? rDNA usually means "recombinant DNA".

The flu virus uses an enzyme (RNA dependant RNA polymerase) to replicate

that does not have proofreading and thus makes errors and causes mutations.

Flu viruses have a segmented genome and can swap genes with other flu

viruses.

1 hour ago, Travelexpert35 said:

Last year on Sept 5, my husband & I were flying to Vancouver to catch our first Transpacific cruise -15 nt Bering Sea & Japan on Sept 6 on the Millennium. What a trip we had. We both loved those sea days, just relaxing. There was lots to do on-board, seminars, painting classes and even learning Japanese phrases. I really got to know the ship on those sea days as I walked for 2 hrs every day getting in my steps.

Oh, I wish we were going again. 

We did the same cruise. Loved it!

Beats flying anytime!! No jet lag when you arrive!

8 minutes ago, BP99 said:

Hi,

It seems like the "new news" is also not that accurate.

Some report that the Moderna vaccine is stable  

at -20C (sorry I'm from Canada) which is very close to a

home freezer. It could be shipped on dry ice.

The Pfizer vaccine is the one that needs the "ultra" -70C storage.

These -70C freezers are more rare but mostly found in hospitals

and research labs. From personal experience these -70C freezers

breakdown often and have huge ice build ups if opened and closed

often. You also need thermal glows to handle the material inside.

However, both vaccines are still probably doable. 

 

Forgot to add the source:

https://www.fiercepharma.com/manufacturing/pfizer-moderna-s-covid-19-shot-rollouts-could-be-ice-as-analysts-question-cold

Also typo: gloves not glows

7 minutes ago, TeeRick said:

Yes I do remember your post from a couple of weeks ago and that this issue has been in the news but mostly glossed over.  

Hi,

It seems like the "new news" is also not that accurate.

Some report that the Moderna vaccine is stable  

at -20C (sorry I'm from Canada) which is very close to a

home freezer. It could be shipped on dry ice.

The Pfizer vaccine is the one that needs the "ultra" -70C storage.

These -70C freezers are more rare but mostly found in hospitals

and research labs. From personal experience these -70C freezers

breakdown often and have huge ice build ups if opened and closed

often. You also need thermal glows to handle the material inside.

However, both vaccines are still probably doable. 

5 hours ago, TeeRick said:

So some disappointing news about the mRNA type vaccines (Moderna, Pfizer).  They require temperatures for storage that will not be met in most traditional pharmacies or doctor's offices for that matter.  Not sure about the adenovector vaccines (AZ/Oxford).  

https://www.marketwatch.com/story/moderna-and-pfizers-covid-19-vaccine-candidates-require-ultra-low-temperatures-raising-questions-about-storage-distribution-2020-08-27

 

But there is an ongoing effort to overcome this too.

https://www.dw.com/en/coronavirus-covid-19-vaccine-ups-astrazeneca-oxford/a-54691039

 

Presumably the traditional protein subunit vaccine (Novavax) would just require refrigeration.

Hi,

This information (low temperature for storage and distribution) was discussed 

3-4 months ago in the news and also mentioned by me 2 weeks ago in a CC

blurb. Since Moderna is getting HUGE positive news weekly some are

now interested in whether the can actually distribute and injected it into

the masses effectively. There are some reports that others have

been able to store mRNA vaccines at higher temperatures. This may be a bit

of a stumbling block but if it is as great as they report it still may be doable.

6 hours ago, markeb said:

 

Probably. Let's see what the clinical trials say. Co-administration is one of those controversial things in vaccines that's become more of a question (issue?) over the last 15-20 years. If they don't interfere, or cause undesirable effects, then probably OK. 

 

Honestly, a lot of the co-administration discussion came out of the military where multiple vaccines at the same time was common. That's been something of a controversy since the first Gulf War. It's also a big question in veterinary medicine, where a lot of veterinarians really don't like administering multiple vaccines; a lot of clients hate coming back for the next shot.

 

How about a "we'll see what the data shows" answer? I don't know of any reason why it won't work, but there's no data...

Hi,

I agree, co-adminstration of different "types" of vaccines may be problematic.

mRNA vaccines are reported to be more "fragile" and require strict refrigeration.

The DTP childhood vaccines are a mixture (3 different bacterial vaccines)

and are usually given 5 times and are very effect even when co-adminstered.

There are also other vaccine mixtures (Hep A & B). 

It also depends on if the vaccine contains an adjuvant (immune stimulant)

and IF it is compatible with the other antigen components.

Complicated, and must be tested and approved.

37 minutes ago, UnorigionalName said:

 

Think of it this way: Diseases our immune system CAN clear by themselves -> easy to make a vaccine.  Diseases our immune system CAN'T clear by themselves -> more challenging to impossible to make a vaccine.  So HIV is a bad analogy for COVID.

 

 

I feel like one thing these predictions fail to take into account is the mechanism of action of these novel vaccines.  I would agree if it was a normal conjugated vaccine, that these predictions are probably accurate.

 

For me the question is if the RNA transfected/infected cells eventually die or get cleared.  If they don't, potentially the immunity could be very long lasting.

 

In any event, I think it's pretty clear at least some vaccine in some form that will decrease morbidity and mortality will come out and be effective.  Everyone hoping vaccine fails are going to be disappointed.  

Hi,

TOTALLY agree with your comments!

In addition to infected individuals that immunologically clear the infection

it was shown that convalecent serum from these individuals can be

successfully used to treat those who have severe symptoms.

This would clearly indicate that a vaccine should work! Also, very early

work showed that covid vaccines can prevent severe illness in monkeys.

However it turns out that monkeys do not die from covid infections and

not a perfect model to show effectiveness. As for RNA vaccines, I've

never read anything on cell mediated killing of these RNA infected cells.

Most likely they should present antigen like virally infected cells and be

cleared by cytotoxic T cells (CTL).

monkeys were a poor model since the

Forgot to add:

All antibodies decrease in the blood with time. They have a half life.

Early immune antibodies (IgM) have a half life of 5-6 days while latter 

antibodies (IgG) have a half life of 21 days.

This is required because:

These are HUGE multi chain glycoproteins. Eg. IgG is 4 chains 10nm

and the heavy chain has 450 amino acids.

If we had high levels of antibodies to every pathogen/vaccine we

encountered in life our blood would be like honey/molasses/engine oil.

Not great for blood flow (clogging arteries)!

1 hour ago, SunsetPoint said:

Unfortunately, an effective vaccine may NEVER be available.  There is still no vaccine for AIDS after all these years or the human coronavirus known as the common cold, and they're now finding that the antibodies that develop when someone gets Covid-19 only last for approximately two to three months and then the person is susceptible to becoming reinfected with Covid-19 again. Two to three months of  immunity does not seem like it bodes well for a long-term vaccine. 

Hi,

Although I agree with "some" of your comments I would like to add some

friendly comments:

1) Although the antibodies decrease with time (common with many vaccines)

we get memory T and B cells that last many years (decades for a few vaccines).

Upon exposure (reinfection) these cells kick in more rapidly making new 

antibodies and cellular immunity. So you do not come down with full blown 

symptoms. Most elderly people get FEWER colds and not as many severe

effects because of these memory cells AND cross reactivity with other 

types of cold/flu viruses. However this virus is different. However, there is

crossreactivity to 3 other cold viruses which MAY explain why some are 

immune/asymptomatic?. Young kids get MANY colds because they haven't

been exposed to to 100's of cold virus strains (4 major types).

2) Even if the vaccine is not GREAT it may be good enough to prevent

death. This dying part is what concerns MOST people. Having a runny

nose/cough is usually okay with most. I mentioned this on a CC post several

months ago and MANY scientists also recently mentioned that a not so

great vaccine MAY prevent death and be good enough.

3) Since nearly all cold viruses did NOT kill many people in the past it

was uneconomical for vaccine companies to spend hundreds of millions

(for research/approval) of a common cold vaccine. Also multiply the cost

a hundred times (for the hundred strains). 

4) The AIDS virus is a different virus having different biological effects.

It is now well treated with drugs and there are still vaccines that are

being developed. It is not air bourn. 

5) Some individuals immune system goes into hyper overdrive. Called

a cytokine storm (hormones of the immune system) which causes

MAJOR effects and death

Bottom line: Don't rule out Covid vaccines yet!

On 6/23/2020 at 10:03 PM, cruise kitty said:

I'm still missing about $500 from my refund 😞

Hi,

Have you gotten your missing $500?

I'm still waiting.

Hi,

We usually spend a 2-3 week land trip before or after a cruise.

We really had a GREAT time in:

1) Southern France (Stayed in Montpellier-CHEAP $70/night EXCELLENT,

rented a car and drove to Nimes (Pont du Guar), Avignon, Orange, Marseille,

Aix-en-Province, Carcassone and many other AWESOME small towns. 

2) Rhine valley towns in Germany (use trains)

3) All of Spain (use trains)

4) All of Scotland, Wales, England (use trains)

5) All of Italy (use trains)

6) Loire Valley- EXCELLENT! Did without a cruise

7) Austria- Did without a cruise. Vienna is my favourate European city!!

From Vienna take a day trip by train to Salzburg (a MUST see) 

Budapest, or Prague.

8 hours ago, cruise kitty said:

I'm still missing about $500 from my refund 😞

Hi,

Many of us are still missing $500. Two weeks for me.

Any idea why $500? or when to expect it? Do you 

need to complain to get it?

35 minutes ago, Wannacruise81 said:

Wow more than 50% off!

Hi,

Is this from 2017 news? Or is this something recent? Please give source.

Thanks.

4 hours ago, hcat said:

We are not that happy with X right now over the way it handled refunds, requiring final payments knowing cruises would be cancelled  and other  Covid related issues.. but seems many cruise lines  had similar  issues. We have one booking left with X and will see how that goes.  It will be on the now unrefurbished Connie.but hoping for the best. M Class is a nice size ship for relaxing.

 

Our last 2 cruises were on EDGE  and both were excellent .as were our past experiences on other X ship over the years. We did find Reflection more crowded and did not like some aspects of the layout compared to other S Class ships.

 

We have been averse to HAL since  we stayed pre cruise at a motel in FLL awhile ago which had many HAL cruisers.  Although we qualify as  seniors ourselves, many of these folks could be described as super seniors... Just did not seem like a good demographic  fit for us...Maybe things have changed????

 

We enjoy good healthy dining, live music, shows, indoor pool/ solarium, spa and gym....and a relaxing atmosophere during the day but more lively in the evenings,,,

Hi,

Yes, I agree with your comments but didn't initially want to dwell on the ages

of Holland America cruisers because we are also seniors and aging rapidly.

However, on a recent Holland America cruise (2 week Alaska cruise) I haven't 

seen as many scouters (been run down a few times), walkers, canes, oxygen

lines etc in all my cruises. I commend them for going on a cruise!! Hopefully

when I reach their age, I'll will still want to enjoy a cruise. Yes, after 9/10 pm

(as mentioned by others) you can have the whole ship to yourselves!

We had a GREAT cruise and I STRONGLY recommend a Holland America

Alaska cruise. The killer whales swimming next to the ship, the salmon runs,

the baby bear, and the ports of call were awesome and I'll always remember

this one.

by others) 

you can can the whole ship to yourse

I

Hi,

Am I the ONLY one who has NOT got a 100% refund (not FCC)

after this LONG wait?

It's day 77 since I applied. Not close to the 30 days they said 

(or 45 days for the latest cancellations).

I tried getting an an answer from my TA and Celebrity and they have

no idea.

Thanks

On 6/7/2020 at 8:39 AM, bouhunter said:

This is from a new NCL announcement on things to come:

 

Temperature Screenings
Touchless temperature checks will occur:

• Prior to embarkation
• Upon returning to the ship from a port of call
• Prior to all meals in dining venues
• Prior to all activities in public venues
• Prior to disembarkation

 

If they don't have a way to QUICKLY test for Covid, one has to wonder how many guests with normal colds and flu's will get caught up in this, and what they'll do with all of them..

 

Sounds like there will be temperature check lines all over the ships all the time...….

Hi,

Dogs can be trained to detect people that are infected.

The sniff armpits!

Interestingly some detected people that were negative with the normal

screening test. They re-screened these people and they were

found to be positive! Looks like the dogs are more accurate!!