[Snorlax94]

https://www.statnews.com/2020/09/08/astr...n-the-u-k/

AstraZeneca's phase 3 trial on hold for a severe adverse reaction. Not great. But not necessarily unusual. Good reminder that a successful vaccine is no sure thing.

How bad is this? How common is this? Will we get details soon and any context of what this could be and how long the hold could be? How likely is it that this could affect other vaccines as well?

[Snorlax94]

https://www.statnews.com/2020/09/08/astr...n-the-u-k/

AstraZeneca's phase 3 trial on hold for a severe adverse reaction. Not great. But not necessarily unusual. Good reminder that a successful vaccine is no sure thing.

How bad is this? How common is this? Will we get details soon and any context of what this could be and how long the hold could be? How likely is it that this could affect other vaccines as well?

[BostonCard]

Some quick drug-safety terms:

"Serious" in this context has specific meaning.  The patient had to meet one of the following:

• They were hospitalized
  
• If already hospitalized, their hospitalization was prolonged
  
• The event was considered life-threatening
  
• The event was fatal (not in this case, since the patient is expected to recover)
  
• The event caused long term disability
  
• There was a fetal malformation or led to the loss of the fetus
  
• Urgent medical action was required to prevent one of the above
  

An "adverse drug reaction" in the above context means that the investigator (or whoever assessed the AE) tied it to the vaccine.  This is challenging, of course, because it is hard to know if someone who developed a migraine a day after the vaccine would have had it anyways.  It is in the judgment of the investigator who (hopefully) knows the details about the nature of the event (like whether it is a typical vaccine reaction, how often it happens in the underlying population), the timing of the event (whether it occurred in the first couple days after the vaccine was given versus weeks later), etc.  There is a nice study (in oncology populations) that something like 15% of more severe reactions attributed to the study drug, actually occurred in people in the placebo arm, so it is by no means certain.

The temporary hold by AZ makes sense for the reasons they say "out of an abundance of caution" to figure out the details and because it is very  difficult to come to definitive conclusions from n = 1 events.  There is a pretty good chance that they will resume dosing again, and it is certainly possible that they won't see an event like this again in the trial, but I agree with dabigv... with a half dozen vaccines in advanced trials, it was probably inevitable that an event like this would happen in one or more of the vaccines.

Regardless, this is why multiple shots on goal is important.  If this winds up being fatal for the development program (I hope not and I think it won't be), at least we have a bunch of other vaccines in the pipeline.

BC

[BostonCard]

Some quick drug-safety terms:

"Serious" in this context has specific meaning.  The patient had to meet one of the following:

• They were hospitalized
  
• If already hospitalized, their hospitalization was prolonged
  
• The event was considered life-threatening
  
• The event was fatal (not in this case, since the patient is expected to recover)
  
• The event caused long term disability
  
• There was a fetal malformation or led to the loss of the fetus
  
• Urgent medical action was required to prevent one of the above
  

An "adverse drug reaction" in the above context means that the investigator (or whoever assessed the AE) tied it to the vaccine.  This is challenging, of course, because it is hard to know if someone who developed a migraine a day after the vaccine would have had it anyways.  It is in the judgment of the investigator who (hopefully) knows the details about the nature of the event (like whether it is a typical vaccine reaction, how often it happens in the underlying population), the timing of the event (whether it occurred in the first couple days after the vaccine was given versus weeks later), etc.  There is a nice study (in oncology populations) that something like 15% of more severe reactions attributed to the study drug, actually occurred in people in the placebo arm, so it is by no means certain.

The temporary hold by AZ makes sense for the reasons they say "out of an abundance of caution" to figure out the details and because it is very  difficult to come to definitive conclusions from n = 1 events.  There is a pretty good chance that they will resume dosing again, and it is certainly possible that they won't see an event like this again in the trial, but I agree with dabigv... with a half dozen vaccines in advanced trials, it was probably inevitable that an event like this would happen in one or more of the vaccines.

Regardless, this is why multiple shots on goal is important.  If this winds up being fatal for the development program (I hope not and I think it won't be), at least we have a bunch of other vaccines in the pipeline.

BC

[Snorlax94]

Some details from the NYTimes:

“A person familiar with the situation, and who spoke on the condition of anonymity, said that the participant had been enrolled in a Phase 2/3 trial based in the United Kingdom. The individual also said that a volunteer in the U.K. trial had been found to have transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections. However, the timing of this diagnosis, and whether it was directly linked to AstraZeneca’s vaccine, is unclear.”

What does this mean? What are the implications?

[Snorlax94]

Some details from the NYTimes:

“A person familiar with the situation, and who spoke on the condition of anonymity, said that the participant had been enrolled in a Phase 2/3 trial based in the United Kingdom. The individual also said that a volunteer in the U.K. trial had been found to have transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections. However, the timing of this diagnosis, and whether it was directly linked to AstraZeneca’s vaccine, is unclear.”

What does this mean? What are the implications?

[dabigv13]

A great post BC.

One thing that concerns me about the major early vaccine candidates is they are all new approaches (and of course they are the early ones partly because more traditional approaches historically have taken longer). No mRNA vaccines have ever been through large human trials. Adenovirus vaccines have been around longer and tested in some trials, but none have passed FDA or European approval (the Chinese have approved some) AFAIK. I'm certainly no specialist in vaccines, but just that on it's face gives me a higher level of skepticism about both safety and efficacy.

Some articles that I've found infromative-

https://cen.acs.org/pharmaceuticals/vacc...-19/98/i19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/

[dabigv13]

A great post BC.

One thing that concerns me about the major early vaccine candidates is they are all new approaches (and of course they are the early ones partly because more traditional approaches historically have taken longer). No mRNA vaccines have ever been through large human trials. Adenovirus vaccines have been around longer and tested in some trials, but none have passed FDA or European approval (the Chinese have approved some) AFAIK. I'm certainly no specialist in vaccines, but just that on it's face gives me a higher level of skepticism about both safety and efficacy.

Some articles that I've found infromative-

https://cen.acs.org/pharmaceuticals/vacc...-19/98/i19

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/

[lex24]

What is considered acceptable, risk wise?  I’m talking in general for a vaccine?  And does that change in a pandemic?  In other words, is the acceptable risk increased a bit?

[lex24]

What is considered acceptable, risk wise?  I’m talking in general for a vaccine?  And does that change in a pandemic?  In other words, is the acceptable risk increased a bit?

[BostonCard]

What is considered acceptable, risk wise?  I’m talking in general for a vaccine?  And does that change in a pandemic?  In other words, is the acceptable risk increased a bit?

In general, because a vaccine is going into people that start out healthy, the tolerance for risk is going to be low, and the safety bar is going to be high.  That will probably change in the context of a pandemic, but there is still a fundamental problem which is that the people who harmed by a vaccine are easily identifiable (and some may even ascribe coincidental but unrelated ailments to the vaccine, as was the case with the MMR vaccine and autism), while the people who benefit are unidentifiable.  If you get vaccinated and don't get symptomatic coronavirus infection, you have no way of knowing whether that was because you got vaccinated or whether you would have been one of the many people who don't get symptomatic disease.

I do think that in the context of a pandemic, the safety bar ought to be relaxed a bit (within reason), as the number of people whose lives can be saved by a vaccine will number in the hundreds of thousands in the US alone, and the number harmed will be a lot lower even with a somewhat relaxed safety bar.  On the flip side, that has to be balanced against a small but vocal minority of people who are very distrustful of vaccines and could amplify their anti-vaccination message.  A vaccine that is ultimately deemed to be unsafe in the court of public opinion would be a disaster.  I wish it weren't so.

You can get an idea of what the safety bar has been historically from vaccines that have been withdrawn or restricted from the market for safety reasons:

For rotavirus:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462159/

The first rotavirus vaccine (RotaShield (Rotavirus, Live, Oral, Tetravalent – Wyeth)was licensed and recommended for routine use in the US by the Advisory Committee on Immunization Practices (ACIP) in 1998.5 This vaccine, was evaluated in 18,000 infants. A summary of the pre-licensing trials reported five cases of intussusception among 10,054 infants receiving vaccine and one case in 4,633 placebo patients (0.05% vs. 0.02%, P > .45). The FDA approved the vaccine on August 31, 1998, and the ACIP recommended routine use the following October for infants at age 2, 4, and six months. On July 16, 1999, the Vaccine Adverse Event Reporting Systems (VAERS) reported 15 cases of intussusception among recipients.6 The CDC placed a temporary suspension on routine administration until a case control investigation could evaluate these cases.7 This investigation demonstrated a strong relationship between RotaShield and intussusception, prompting the ACIP to withdraw its recommendation for routine use in October, 1999.8 The manufacturer voluntarily withdrew this product from the market shortly thereafter.

For dengue:
https://www.virology.ws/2017/12/07/a-pro...s-vaccine/

The numbers are small but significant. For example, during year 5 after the third dose of vaccine, 295 of 20,439 children (1.44%) were hospitalized with dengue virus infection. Severe dengue was also observed during years 2-4 after the third dose. Considering that millions of children will eventually receive this vaccine, serious disease occurring at a rate of 1.44% is not acceptable.

For H1N1 influenza:
https://jamanetwork.com/journals/jama/fu...le/1216476

Results Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8-week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64-5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years.

BC

---

A great post BC.



One thing that concerns me about the major early vaccine candidates is they are all new approaches (and of course they are the early ones partly because more traditional approaches historically have taken longer). No mRNA vaccines have ever been through large human trials. Adenovirus vaccines have been around longer and tested in some trials, but none have passed FDA or European approval (the Chinese have approved some) AFAIK. I'm certainly no specialist in vaccines, but just that on it's face gives me a higher level of skepticism about both safety and efficacy.



Some articles that I've found infromative-



https://cen.acs.org/pharmaceuticals/vacc...-19/98/i19



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/

That's a fair concern.  I think the most mature technology (among the frontrunners) is probably the one from Novavax, and they have a partnership with CEPI, which should be reassuring.  This COVID-19 vaccine tracker from the NY Times is very good.

https://www.nytimes.com/interactive/2020...acker.html

Maryland-based Novavax makes vaccines by sticking proteins onto microscopic particles. They’ve taken on a number of different diseases this way; their flu vaccine finished Phase 3 trials in March. The company launched trials for a Covid-19 vaccine in May, and the Coalition for Epidemic Preparedness Innovations has invested $384 million in the vaccine. In July the U.S. government awarded $1.6 billion to support the vaccine’s clinical trials and manufacturing.

BC

[BostonCard]

What is considered acceptable, risk wise?  I’m talking in general for a vaccine?  And does that change in a pandemic?  In other words, is the acceptable risk increased a bit?

In general, because a vaccine is going into people that start out healthy, the tolerance for risk is going to be low, and the safety bar is going to be high.  That will probably change in the context of a pandemic, but there is still a fundamental problem which is that the people who harmed by a vaccine are easily identifiable (and some may even ascribe coincidental but unrelated ailments to the vaccine, as was the case with the MMR vaccine and autism), while the people who benefit are unidentifiable.  If you get vaccinated and don't get symptomatic coronavirus infection, you have no way of knowing whether that was because you got vaccinated or whether you would have been one of the many people who don't get symptomatic disease.

I do think that in the context of a pandemic, the safety bar ought to be relaxed a bit (within reason), as the number of people whose lives can be saved by a vaccine will number in the hundreds of thousands in the US alone, and the number harmed will be a lot lower even with a somewhat relaxed safety bar.  On the flip side, that has to be balanced against a small but vocal minority of people who are very distrustful of vaccines and could amplify their anti-vaccination message.  A vaccine that is ultimately deemed to be unsafe in the court of public opinion would be a disaster.  I wish it weren't so.

You can get an idea of what the safety bar has been historically from vaccines that have been withdrawn or restricted from the market for safety reasons:

For rotavirus:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462159/

The first rotavirus vaccine (RotaShield (Rotavirus, Live, Oral, Tetravalent – Wyeth)was licensed and recommended for routine use in the US by the Advisory Committee on Immunization Practices (ACIP) in 1998.5 This vaccine, was evaluated in 18,000 infants. A summary of the pre-licensing trials reported five cases of intussusception among 10,054 infants receiving vaccine and one case in 4,633 placebo patients (0.05% vs. 0.02%, P > .45). The FDA approved the vaccine on August 31, 1998, and the ACIP recommended routine use the following October for infants at age 2, 4, and six months. On July 16, 1999, the Vaccine Adverse Event Reporting Systems (VAERS) reported 15 cases of intussusception among recipients.6 The CDC placed a temporary suspension on routine administration until a case control investigation could evaluate these cases.7 This investigation demonstrated a strong relationship between RotaShield and intussusception, prompting the ACIP to withdraw its recommendation for routine use in October, 1999.8 The manufacturer voluntarily withdrew this product from the market shortly thereafter.

For dengue:
https://www.virology.ws/2017/12/07/a-pro...s-vaccine/

The numbers are small but significant. For example, during year 5 after the third dose of vaccine, 295 of 20,439 children (1.44%) were hospitalized with dengue virus infection. Severe dengue was also observed during years 2-4 after the third dose. Considering that millions of children will eventually receive this vaccine, serious disease occurring at a rate of 1.44% is not acceptable.

For H1N1 influenza:
https://jamanetwork.com/journals/jama/fu...le/1216476

Results Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8-week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64-5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years.

BC

---

A great post BC.



One thing that concerns me about the major early vaccine candidates is they are all new approaches (and of course they are the early ones partly because more traditional approaches historically have taken longer). No mRNA vaccines have ever been through large human trials. Adenovirus vaccines have been around longer and tested in some trials, but none have passed FDA or European approval (the Chinese have approved some) AFAIK. I'm certainly no specialist in vaccines, but just that on it's face gives me a higher level of skepticism about both safety and efficacy.



Some articles that I've found infromative-



https://cen.acs.org/pharmaceuticals/vacc...-19/98/i19



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/

That's a fair concern.  I think the most mature technology (among the frontrunners) is probably the one from Novavax, and they have a partnership with CEPI, which should be reassuring.  This COVID-19 vaccine tracker from the NY Times is very good.

https://www.nytimes.com/interactive/2020...acker.html

Maryland-based Novavax makes vaccines by sticking proteins onto microscopic particles. They’ve taken on a number of different diseases this way; their flu vaccine finished Phase 3 trials in March. The company launched trials for a Covid-19 vaccine in May, and the Coalition for Epidemic Preparedness Innovations has invested $384 million in the vaccine. In July the U.S. government awarded $1.6 billion to support the vaccine’s clinical trials and manufacturing.

BC

[dabigv13]

Some details from the NYTimes:

“A person familiar with the situation, and who spoke on the condition of anonymity, said that the participant had been enrolled in a Phase 2/3 trial based in the United Kingdom. The individual also said that a volunteer in the U.K. trial had been found to have transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections. However, the timing of this diagnosis, and whether it was directly linked to AstraZeneca’s vaccine, is unclear.”

What does this mean? What are the implications?

If they think the vaccine caused someone to get transverse myelitis, that would be bad news. Neurological complications like Guillain-Barre and transverse myelitis are rare events generally, and may be associated with vaccinations. If they can't find any other reason for it.....hard to say. N of 1. But worth pausing. If one in 30,000 gets transverse myelitis, that vaccine is definitely getting pulled. If one in 300,000 does, probably the same.
- EDIT -
Just realized I got my math wrong here. Should have said 15,000, since half the trial is getting placebo.
- EDIT -
During a pandemic, safety should be paramount. You're ideally injecting most of your populace in a short period of time. If a small fraction end up paralyzed or dead or in constant pain or ....., that could be a lot of people. Especially for a virus that kills less than a half percent of the people that get it, and a significantly lower percentage than that for younger and healthier people who will still need to be vaccinated.

[dabigv13]

Some details from the NYTimes:

“A person familiar with the situation, and who spoke on the condition of anonymity, said that the participant had been enrolled in a Phase 2/3 trial based in the United Kingdom. The individual also said that a volunteer in the U.K. trial had been found to have transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections. However, the timing of this diagnosis, and whether it was directly linked to AstraZeneca’s vaccine, is unclear.”

What does this mean? What are the implications?

If they think the vaccine caused someone to get transverse myelitis, that would be bad news. Neurological complications like Guillain-Barre and transverse myelitis are rare events generally, and may be associated with vaccinations. If they can't find any other reason for it.....hard to say. N of 1. But worth pausing. If one in 30,000 gets transverse myelitis, that vaccine is definitely getting pulled. If one in 300,000 does, probably the same.
- EDIT -
Just realized I got my math wrong here. Should have said 15,000, since half the trial is getting placebo.
- EDIT -
During a pandemic, safety should be paramount. You're ideally injecting most of your populace in a short period of time. If a small fraction end up paralyzed or dead or in constant pain or ....., that could be a lot of people. Especially for a virus that kills less than a half percent of the people that get it, and a significantly lower percentage than that for younger and healthier people who will still need to be vaccinated.

[dabigv13]

Some more thoughts about this- I doubt these phase III trials will have many/any pregnant women or children. Our knowledge of potential risks in those subgroups may only become apparent after widespread adoption.

More on the Oxford AstraZeneca vaccine's background from the article on adenovirus vector vaccines I linked above-

Some labs have sought to avoid the problem of preexisting immunity altogether by using adenoviruses that don’t normally infect humans but do infect our closest relatives. In the early 2000s, Wilson’s lab at Penn began hunting for chimpanzee adenoviruses, which the researchers isolated from the animal’s feces. Soon after, Ertl’s lab at Wistar began collaborating with Wilson to use the chimpanzee adenoviruses as a novel vaccine vector.

Other groups adopted the idea too. “Chimpanzees are very protected, but stools can be easily collected,” says Stefano Colloca, who worked on adenoviral vectors at Merck Research Laboratories’ center in Rome in the early 2000s. He later helped form a company, Okairos, that was spun out of that work when Merck discontinued its Ad5 programs in 2007.

MilliporeSigma worked with scientists at the University of Oxford to improve the process of manufacturing its chimpanzee adenoviral vector vaccine for COVID-19.
Okairos focused on developing chimpanzee adenoviral vectors that closely resembled human Ad5, and it soon formed a collaboration with a newly founded vaccine center at the University of Oxford called the Jenner Institute. The Oxford team used one of the Okairos chimpanzee-derived vectors to develop a malaria vaccine, which became the first chimpanzee-derived vector to be tested in humans.

In 2012, the Oxford group developed its own chimpanzee-derived vector, dubbed ChAdOx1, based on an adenovirus discovered in chimpanzee feces. The Oxford team went on to create the spin-off company Vaccitech in 2016 and has developed experimental vaccines for a number of diseases, including AIDS, malaria, tuberculosis, and Middle East respiratory syndrome, which is caused by the MERS coronavirus.

A small safety study of that MERS vaccine was conducted in 2018. The results, published this April, showed that most of the 24 people in the trial still had T cells that targeted the MERS virus 12 months after a single injection of the vaccine. They also still had elevated levels of antibodies a year later. But only about half the people who got the highest dose of the vaccine had antibodies that neutralized the MERS virus in lab experiments.

That MERS work allowed the Oxford team to move fast on a COVID-19 vaccine, which essentially swaps in the genetic instructions for the SARS-CoV-2 spike protein. To improve the manufacturing process for its vaccine, Oxford enlisted the help of MilliporeSigma, which will supply equipment to multiple contract manufacturers that could collectively develop tens of millions of doses of the vaccine.

In July, Okairos, which has since morphed into a company now called ReiThera, plans to start a clinical trial of its own COVID-19 vaccine, which is based on an adenovirus discovered in gorilla feces. The biggest drawback to the great-ape adenoviral vector vaccines may be their lack of prior testing in humans. Before the coronavirus pandemic, Oxford’s ChAdOx1 vector had been given to only about 320 people, and ReiThera’s new gorilla-derived vector has never been tested in humans. Although preexisting immunity could limit the effectiveness of the Ad5- and Ad26-based vaccines, at least their developers have a better idea of their vectors’ safety.

I don't mean to be alarmist. There is very sound science behind all these vaccines I'm sure. But we should be cognizant that they are novel.

[dabigv13]

Some more thoughts about this- I doubt these phase III trials will have many/any pregnant women or children. Our knowledge of potential risks in those subgroups may only become apparent after widespread adoption.

More on the Oxford AstraZeneca vaccine's background from the article on adenovirus vector vaccines I linked above-

Some labs have sought to avoid the problem of preexisting immunity altogether by using adenoviruses that don’t normally infect humans but do infect our closest relatives. In the early 2000s, Wilson’s lab at Penn began hunting for chimpanzee adenoviruses, which the researchers isolated from the animal’s feces. Soon after, Ertl’s lab at Wistar began collaborating with Wilson to use the chimpanzee adenoviruses as a novel vaccine vector.

Other groups adopted the idea too. “Chimpanzees are very protected, but stools can be easily collected,” says Stefano Colloca, who worked on adenoviral vectors at Merck Research Laboratories’ center in Rome in the early 2000s. He later helped form a company, Okairos, that was spun out of that work when Merck discontinued its Ad5 programs in 2007.

MilliporeSigma worked with scientists at the University of Oxford to improve the process of manufacturing its chimpanzee adenoviral vector vaccine for COVID-19.
Okairos focused on developing chimpanzee adenoviral vectors that closely resembled human Ad5, and it soon formed a collaboration with a newly founded vaccine center at the University of Oxford called the Jenner Institute. The Oxford team used one of the Okairos chimpanzee-derived vectors to develop a malaria vaccine, which became the first chimpanzee-derived vector to be tested in humans.

In 2012, the Oxford group developed its own chimpanzee-derived vector, dubbed ChAdOx1, based on an adenovirus discovered in chimpanzee feces. The Oxford team went on to create the spin-off company Vaccitech in 2016 and has developed experimental vaccines for a number of diseases, including AIDS, malaria, tuberculosis, and Middle East respiratory syndrome, which is caused by the MERS coronavirus.

A small safety study of that MERS vaccine was conducted in 2018. The results, published this April, showed that most of the 24 people in the trial still had T cells that targeted the MERS virus 12 months after a single injection of the vaccine. They also still had elevated levels of antibodies a year later. But only about half the people who got the highest dose of the vaccine had antibodies that neutralized the MERS virus in lab experiments.

That MERS work allowed the Oxford team to move fast on a COVID-19 vaccine, which essentially swaps in the genetic instructions for the SARS-CoV-2 spike protein. To improve the manufacturing process for its vaccine, Oxford enlisted the help of MilliporeSigma, which will supply equipment to multiple contract manufacturers that could collectively develop tens of millions of doses of the vaccine.

In July, Okairos, which has since morphed into a company now called ReiThera, plans to start a clinical trial of its own COVID-19 vaccine, which is based on an adenovirus discovered in gorilla feces. The biggest drawback to the great-ape adenoviral vector vaccines may be their lack of prior testing in humans. Before the coronavirus pandemic, Oxford’s ChAdOx1 vector had been given to only about 320 people, and ReiThera’s new gorilla-derived vector has never been tested in humans. Although preexisting immunity could limit the effectiveness of the Ad5- and Ad26-based vaccines, at least their developers have a better idea of their vectors’ safety.

I don't mean to be alarmist. There is very sound science behind all these vaccines I'm sure. But we should be cognizant that they are novel.

[Hurlburt88]

Personal anecdote:  
My brother had Devic's Syndrome back in 1989 after receiving a flu vaccine as a senior in college.  Transverse myelitis and optical neuritis specifically.  Almost killed him--at one point paralyzed from neck down and blind.   Everything came back except his legs.   He went on to become a physician and while he does not get a flu vaccine personally he recommends it and other vaccines for his family and all the rest of us.

[Hurlburt88]

Personal anecdote:  
My brother had Devic's Syndrome back in 1989 after receiving a flu vaccine as a senior in college.  Transverse myelitis and optical neuritis specifically.  Almost killed him--at one point paralyzed from neck down and blind.   Everything came back except his legs.   He went on to become a physician and while he does not get a flu vaccine personally he recommends it and other vaccines for his family and all the rest of us.

[Goose]

[If they think the vaccine caused someone to get transverse myelitis, that would be bad news. Neurological complications like Guillain-Barre and transverse myelitis are rare events generally, and may be associated with vaccinations. If they can't find any other reason for it.....hard to say. N of 1. But worth pausing. If one in 30,000 gets transverse myelitis, that vaccine is definitely getting pulled. If one in 300,000 does, probably the same.

During a pandemic, safety should be paramount. You're ideally injecting most of your populace in a short period of time. If a small fraction end up paralyzed or dead or in constant pain or ....., that could be a lot of people. Especially for a virus that kills less than a half percent of the people that get it, and a significantly lower percentage than that for younger and healthier people who will still need to be vaccinated.

I agree with what you are saying here. This virus, while causing major numbers of deaths, is still not a "big problem" to most people who get it. The vaccine has to be significantly "safer" than the alternative of just getting the virus.

One very large problem that is still in play is the nature and duration of immunity. If a vaccine conveys only a short-lived immunity people will have to take it multiple times to avoid getting COVID-19. If it is similar to the flu, you would need it once a year. The repeated administration requirement and a cumulative risk would require a vaccine that is even "safer" than something you take once in your life. Unfortunately, we don't know much about the immunity duration for COVID-19 since the disease has not yet been in existence for a full year.

We will know even less experimentally about the immunity conferred by a vaccine, although there would be reasons to assume it was similar to getting the disease. This situation will make the decision process even more difficult for individuals at "low" risk from COVID-19. They just won't know what their immunity duration will be. If you are "probably going to get it anyway", why bother?

[Goose]

[If they think the vaccine caused someone to get transverse myelitis, that would be bad news. Neurological complications like Guillain-Barre and transverse myelitis are rare events generally, and may be associated with vaccinations. If they can't find any other reason for it.....hard to say. N of 1. But worth pausing. If one in 30,000 gets transverse myelitis, that vaccine is definitely getting pulled. If one in 300,000 does, probably the same.

During a pandemic, safety should be paramount. You're ideally injecting most of your populace in a short period of time. If a small fraction end up paralyzed or dead or in constant pain or ....., that could be a lot of people. Especially for a virus that kills less than a half percent of the people that get it, and a significantly lower percentage than that for younger and healthier people who will still need to be vaccinated.

I agree with what you are saying here. This virus, while causing major numbers of deaths, is still not a "big problem" to most people who get it. The vaccine has to be significantly "safer" than the alternative of just getting the virus.

One very large problem that is still in play is the nature and duration of immunity. If a vaccine conveys only a short-lived immunity people will have to take it multiple times to avoid getting COVID-19. If it is similar to the flu, you would need it once a year. The repeated administration requirement and a cumulative risk would require a vaccine that is even "safer" than something you take once in your life. Unfortunately, we don't know much about the immunity duration for COVID-19 since the disease has not yet been in existence for a full year.

We will know even less experimentally about the immunity conferred by a vaccine, although there would be reasons to assume it was similar to getting the disease. This situation will make the decision process even more difficult for individuals at "low" risk from COVID-19. They just won't know what their immunity duration will be. If you are "probably going to get it anyway", why bother?

[lex24]

What is considered acceptable, risk wise?  I’m talking in general for a vaccine?  And does that change in a pandemic?  In other words, is the acceptable risk increased a bit?

In general, because a vaccine is going into people that start out healthy, the tolerance for risk is going to be low, and the safety bar is going to be high.  That will probably change in the context of a pandemic, but there is still a fundamental problem which is that the people who harmed by a vaccine are easily identifiable (and some may even ascribe coincidental but unrelated ailments to the vaccine, as was the case with the MMR vaccine and autism), while the people who benefit are unidentifiable.  If you get vaccinated and don't get symptomatic coronavirus infection, you have no way of knowing whether that was because you got vaccinated or whether you would have been one of the many people who don't get symptomatic disease.

I do think that in the context of a pandemic, the safety bar ought to be relaxed a bit (within reason), as the number of people whose lives can be saved by a vaccine will number in the hundreds of thousands in the US alone, and the number harmed will be a lot lower even with a somewhat relaxed safety bar.  On the flip side, that has to be balanced against a small but vocal minority of people who are very distrustful of vaccines and could amplify their anti-vaccination message.  A vaccine that is ultimately deemed to be unsafe in the court of public opinion would be a disaster.  I wish it weren't so.

You can get an idea of what the safety bar has been historically from vaccines that have been withdrawn or restricted from the market for safety reasons:

For rotavirus:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462159/

The first rotavirus vaccine (RotaShield (Rotavirus, Live, Oral, Tetravalent – Wyeth)was licensed and recommended for routine use in the US by the Advisory Committee on Immunization Practices (ACIP) in 1998.5 This vaccine, was evaluated in 18,000 infants. A summary of the pre-licensing trials reported five cases of intussusception among 10,054 infants receiving vaccine and one case in 4,633 placebo patients (0.05% vs. 0.02%, P > .45). The FDA approved the vaccine on August 31, 1998, and the ACIP recommended routine use the following October for infants at age 2, 4, and six months. On July 16, 1999, the Vaccine Adverse Event Reporting Systems (VAERS) reported 15 cases of intussusception among recipients.6 The CDC placed a temporary suspension on routine administration until a case control investigation could evaluate these cases.7 This investigation demonstrated a strong relationship between RotaShield and intussusception, prompting the ACIP to withdraw its recommendation for routine use in October, 1999.8 The manufacturer voluntarily withdrew this product from the market shortly thereafter.

For dengue:
https://www.virology.ws/2017/12/07/a-pro...s-vaccine/

The numbers are small but significant. For example, during year 5 after the third dose of vaccine, 295 of 20,439 children (1.44%) were hospitalized with dengue virus infection. Severe dengue was also observed during years 2-4 after the third dose. Considering that millions of children will eventually receive this vaccine, serious disease occurring at a rate of 1.44% is not acceptable.

For H1N1 influenza:
https://jamanetwork.com/journals/jama/fu...le/1216476

Results Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8-week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64-5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years.

BC

---

A great post BC.



One thing that concerns me about the major early vaccine candidates is they are all new approaches (and of course they are the early ones partly because more traditional approaches historically have taken longer). No mRNA vaccines have ever been through large human trials. Adenovirus vaccines have been around longer and tested in some trials, but none have passed FDA or European approval (the Chinese have approved some) AFAIK. I'm certainly no specialist in vaccines, but just that on it's face gives me a higher level of skepticism about both safety and efficacy.



Some articles that I've found infromative-



https://cen.acs.org/pharmaceuticals/vacc...-19/98/i19



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/

That's a fair concern.  I think the most mature technology (among the frontrunners) is probably the one from Novavax, and they have a partnership with CEPI, which should be reassuring.  This COVID-19 vaccine tracker from the NY Times is very good.

https://www.nytimes.com/interactive/2020...acker.html

Maryland-based Novavax makes vaccines by sticking proteins onto microscopic particles. They’ve taken on a number of different diseases this way; their flu vaccine finished Phase 3 trials in March. The company launched trials for a Covid-19 vaccine in May, and the Coalition for Epidemic Preparedness Innovations has invested $384 million in the vaccine. In July the U.S. government awarded $1.6 billion to support the vaccine’s clinical trials and manufacturing.

BC

Thanks, BC. That is helpful. One other aspect - who are having the adverse reactions?  If it’s kids - my guess is a whole lot of people won’t vacinate their kids - no matter how low the risk.

[lex24]

What is considered acceptable, risk wise?  I’m talking in general for a vaccine?  And does that change in a pandemic?  In other words, is the acceptable risk increased a bit?

In general, because a vaccine is going into people that start out healthy, the tolerance for risk is going to be low, and the safety bar is going to be high.  That will probably change in the context of a pandemic, but there is still a fundamental problem which is that the people who harmed by a vaccine are easily identifiable (and some may even ascribe coincidental but unrelated ailments to the vaccine, as was the case with the MMR vaccine and autism), while the people who benefit are unidentifiable.  If you get vaccinated and don't get symptomatic coronavirus infection, you have no way of knowing whether that was because you got vaccinated or whether you would have been one of the many people who don't get symptomatic disease.

I do think that in the context of a pandemic, the safety bar ought to be relaxed a bit (within reason), as the number of people whose lives can be saved by a vaccine will number in the hundreds of thousands in the US alone, and the number harmed will be a lot lower even with a somewhat relaxed safety bar.  On the flip side, that has to be balanced against a small but vocal minority of people who are very distrustful of vaccines and could amplify their anti-vaccination message.  A vaccine that is ultimately deemed to be unsafe in the court of public opinion would be a disaster.  I wish it weren't so.

You can get an idea of what the safety bar has been historically from vaccines that have been withdrawn or restricted from the market for safety reasons:

For rotavirus:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462159/

The first rotavirus vaccine (RotaShield (Rotavirus, Live, Oral, Tetravalent – Wyeth)was licensed and recommended for routine use in the US by the Advisory Committee on Immunization Practices (ACIP) in 1998.5 This vaccine, was evaluated in 18,000 infants. A summary of the pre-licensing trials reported five cases of intussusception among 10,054 infants receiving vaccine and one case in 4,633 placebo patients (0.05% vs. 0.02%, P > .45). The FDA approved the vaccine on August 31, 1998, and the ACIP recommended routine use the following October for infants at age 2, 4, and six months. On July 16, 1999, the Vaccine Adverse Event Reporting Systems (VAERS) reported 15 cases of intussusception among recipients.6 The CDC placed a temporary suspension on routine administration until a case control investigation could evaluate these cases.7 This investigation demonstrated a strong relationship between RotaShield and intussusception, prompting the ACIP to withdraw its recommendation for routine use in October, 1999.8 The manufacturer voluntarily withdrew this product from the market shortly thereafter.

For dengue:
https://www.virology.ws/2017/12/07/a-pro...s-vaccine/

The numbers are small but significant. For example, during year 5 after the third dose of vaccine, 295 of 20,439 children (1.44%) were hospitalized with dengue virus infection. Severe dengue was also observed during years 2-4 after the third dose. Considering that millions of children will eventually receive this vaccine, serious disease occurring at a rate of 1.44% is not acceptable.

For H1N1 influenza:
https://jamanetwork.com/journals/jama/fu...le/1216476

Results Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8-week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64-5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years.

BC

---

A great post BC.



One thing that concerns me about the major early vaccine candidates is they are all new approaches (and of course they are the early ones partly because more traditional approaches historically have taken longer). No mRNA vaccines have ever been through large human trials. Adenovirus vaccines have been around longer and tested in some trials, but none have passed FDA or European approval (the Chinese have approved some) AFAIK. I'm certainly no specialist in vaccines, but just that on it's face gives me a higher level of skepticism about both safety and efficacy.



Some articles that I've found infromative-



https://cen.acs.org/pharmaceuticals/vacc...-19/98/i19



https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5906799/

That's a fair concern.  I think the most mature technology (among the frontrunners) is probably the one from Novavax, and they have a partnership with CEPI, which should be reassuring.  This COVID-19 vaccine tracker from the NY Times is very good.

https://www.nytimes.com/interactive/2020...acker.html

Maryland-based Novavax makes vaccines by sticking proteins onto microscopic particles. They’ve taken on a number of different diseases this way; their flu vaccine finished Phase 3 trials in March. The company launched trials for a Covid-19 vaccine in May, and the Coalition for Epidemic Preparedness Innovations has invested $384 million in the vaccine. In July the U.S. government awarded $1.6 billion to support the vaccine’s clinical trials and manufacturing.

BC

Thanks, BC. That is helpful. One other aspect - who are having the adverse reactions?  If it’s kids - my guess is a whole lot of people won’t vacinate their kids - no matter how low the risk.

[fullmetal]

I agree with what you are saying here. This virus, while causing major numbers of deaths, is still not a "big problem" to most people who get it. The vaccine has to be significantly "safer" than the alternative of just getting the virus.

Agreed.  We can't agree to a vaccine that is exactly what some have feared as a "cure" worse than the disease.  Having said that, the incidence of psot-covid symptom sufferers (including long-haulers) is probably greater than any rate of adverse vaccine reaction...

[fullmetal]

I agree with what you are saying here. This virus, while causing major numbers of deaths, is still not a "big problem" to most people who get it. The vaccine has to be significantly "safer" than the alternative of just getting the virus.

Agreed.  We can't agree to a vaccine that is exactly what some have feared as a "cure" worse than the disease.  Having said that, the incidence of psot-covid symptom sufferers (including long-haulers) is probably greater than any rate of adverse vaccine reaction...

[Snorlax94]

I agree with what you are saying here. This virus, while causing major numbers of deaths, is still not a "big problem" to most people who get it. The vaccine has to be significantly "safer" than the alternative of just getting the virus.

Having said that, the incidence of psot-covid symptom sufferers (including long-haulers) is probably greater than any rate of adverse vaccine reaction...

This makes it sound like the only options are to catch Covid, or to take a vaccine that has not been proven safe and effective.

There is the natural and obvious third option, to not congregate in large groups, to not congregate indoors without a mask, and to wear a mask until a safe, effective vaccine is available.  This is unfortunately not completely possible for absolutely everyone (someone in a LTC facility may be unable to wear a mask and may be stuck indoors), but this option is readily available for many people. Even for essential workers, again, none of the workers in the Starbucks super spreader event in Korea caught Covid, because they were wearing masks.

[Snorlax94]

I agree with what you are saying here. This virus, while causing major numbers of deaths, is still not a "big problem" to most people who get it. The vaccine has to be significantly "safer" than the alternative of just getting the virus.

Having said that, the incidence of psot-covid symptom sufferers (including long-haulers) is probably greater than any rate of adverse vaccine reaction...

This makes it sound like the only options are to catch Covid, or to take a vaccine that has not been proven safe and effective.

There is the natural and obvious third option, to not congregate in large groups, to not congregate indoors without a mask, and to wear a mask until a safe, effective vaccine is available.  This is unfortunately not completely possible for absolutely everyone (someone in a LTC facility may be unable to wear a mask and may be stuck indoors), but this option is readily available for many people. Even for essential workers, again, none of the workers in the Starbucks super spreader event in Korea caught Covid, because they were wearing masks.

[82lsju]

Thanks, BC. That is helpful. One other aspect - who are having the adverse reactions?  If it’s kids - my guess is a whole lot of people won’t vaccinate their kids - no matter how low the risk.

not BC, but from what I have seen in requirements to be in the trials you have to be 18 or older so to me it does not appear that the reaction of kids will be specifically tested by the trials

[82lsju]

Thanks, BC. That is helpful. One other aspect - who are having the adverse reactions?  If it’s kids - my guess is a whole lot of people won’t vaccinate their kids - no matter how low the risk.

not BC, but from what I have seen in requirements to be in the trials you have to be 18 or older so to me it does not appear that the reaction of kids will be specifically tested by the trials

[lex24]

Thanks, BC. That is helpful. One other aspect - who are having the adverse reactions?  If it’s kids - my guess is a whole lot of people won’t vaccinate their kids - no matter how low the risk.

not BC, but from what I have seen in requirements to be in the trials you have to be 18 or older so to me it does not appear that the reaction of kids will be specifically tested by the trials

That makes sense.

[lex24]

Thanks, BC. That is helpful. One other aspect - who are having the adverse reactions?  If it’s kids - my guess is a whole lot of people won’t vaccinate their kids - no matter how low the risk.

not BC, but from what I have seen in requirements to be in the trials you have to be 18 or older so to me it does not appear that the reaction of kids will be specifically tested by the trials

That makes sense.

[BostonCard]

At around the time any drug enters phase 3 trials, the Sponsor will need to present a pediatric plan or request a waiver (this is a requirement) which would probably mean a separate pediatric study shortly after efficacy in adults is established. Particularly for COVID-19, where the risk of the disease in kids is very low, you will want to have shown benefit before you expose a pediatric population to risk.

Here’s the relevant excerpt from the FDA’s COVID vaccine guidance.

It is important for developers of COVID-19 vaccines to plan for pediatric assessments of safety and effectiveness, given the nature of the COVID-19 public health emergency, and to help ensure compliance with the Pediatric Research Equity Act (PREA) (section 505B of the FD&C Act (21 U.S.C. 355c)) (Ref. 18). The epidemiology and pathogenesis of COVID-19, and the safety and effectiveness of COVID-19 vaccines, may be different in children compared with adults. In order to ensure compliance with 21 CFR Part 50 Subpart D (Additional safeguards for children in clinical investigations), considerations on the prospect of direct benefit and acceptable risk to support initiation of pediatric studies, and the appropriate design and endpoints for pediatric studies, should be discussed in the context of specific vaccine development programs

BC

[BostonCard]

At around the time any drug enters phase 3 trials, the Sponsor will need to present a pediatric plan or request a waiver (this is a requirement) which would probably mean a separate pediatric study shortly after efficacy in adults is established. Particularly for COVID-19, where the risk of the disease in kids is very low, you will want to have shown benefit before you expose a pediatric population to risk.

Here’s the relevant excerpt from the FDA’s COVID vaccine guidance.

It is important for developers of COVID-19 vaccines to plan for pediatric assessments of safety and effectiveness, given the nature of the COVID-19 public health emergency, and to help ensure compliance with the Pediatric Research Equity Act (PREA) (section 505B of the FD&C Act (21 U.S.C. 355c)) (Ref. 18). The epidemiology and pathogenesis of COVID-19, and the safety and effectiveness of COVID-19 vaccines, may be different in children compared with adults. In order to ensure compliance with 21 CFR Part 50 Subpart D (Additional safeguards for children in clinical investigations), considerations on the prospect of direct benefit and acceptable risk to support initiation of pediatric studies, and the appropriate design and endpoints for pediatric studies, should be discussed in the context of specific vaccine development programs

BC

[OutsiderFan]

I get that there is going to be public interest in SARS-CoV-2 vaccine development. However, it seems to me we would be far better off treating it as a Manhattan Project, keeping the progress and testing top secret until there is an actual vaccine.  This is for two reasons.

1. If we operate like there is no vaccine in sight, we'll have to really on other measures to contain, mitigate, and stop virus spread.

2. This play-by-play of vaccine development is going to make an incredibly uninformed public that doesn't know what people like BC do about it, become more skeptical of the process.

It seems it might be best to report researchers are working on vaccines and then only do any reporting when something is actually approved.

[OutsiderFan]

I get that there is going to be public interest in SARS-CoV-2 vaccine development. However, it seems to me we would be far better off treating it as a Manhattan Project, keeping the progress and testing top secret until there is an actual vaccine.  This is for two reasons.

1. If we operate like there is no vaccine in sight, we'll have to really on other measures to contain, mitigate, and stop virus spread.

2. This play-by-play of vaccine development is going to make an incredibly uninformed public that doesn't know what people like BC do about it, become more skeptical of the process.

It seems it might be best to report researchers are working on vaccines and then only do any reporting when something is actually approved.

[fullmetal]

You know what those conspiracy theorists will do though...

"They're lying to us!  There's no vaccine coming!  The government is going to use this pandemic to permanently steal our rights!  We need to act now!"

...or some form of hysteria along those lines.

TERRELL: Maybe it's something we can transplant.
CHEKOV: You know what she'll say.

[fullmetal]

You know what those conspiracy theorists will do though...

"They're lying to us!  There's no vaccine coming!  The government is going to use this pandemic to permanently steal our rights!  We need to act now!"

...or some form of hysteria along those lines.

TERRELL: Maybe it's something we can transplant.
CHEKOV: You know what she'll say.

[Goose]

I agree with what you are saying here. This virus, while causing major numbers of deaths, is still not a "big problem" to most people who get it. The vaccine has to be significantly "safer" than the alternative of just getting the virus.

Having said that, the incidence of psot-covid symptom sufferers (including long-haulers) is probably greater than any rate of adverse vaccine reaction...

This makes it sound like the only options are to catch Covid, or to take a vaccine that has not been proven safe and effective.

There is the natural and obvious third option, to not congregate in large groups, to not congregate indoors without a mask, and to wear a mask until a safe, effective vaccine is available.

I think that is what a lot of people are going to do, myself included. However, that also means I am not going to be dining indoors in a restaurant or drinking in a bar. I also won't be attending a Stanford football game with even our naturally socially distanced fan base. One might say there are different levels of caution, but for "most people" who want to live their life as they did before COVID-19, the only two options are a vaccine or risk getting COVID-19. Note that risking getting COVID-19 isn't the same as getting COVID-19. Most people who take some risks will get away with it and not get sick. They know that, and they aren't going to wait for a vaccine "forever".  In fact, many of them aren't waiting now. That is one big reason why our society is seeing lots of people die who didn't have to do so.

[Goose]

I agree with what you are saying here. This virus, while causing major numbers of deaths, is still not a "big problem" to most people who get it. The vaccine has to be significantly "safer" than the alternative of just getting the virus.

Having said that, the incidence of psot-covid symptom sufferers (including long-haulers) is probably greater than any rate of adverse vaccine reaction...

This makes it sound like the only options are to catch Covid, or to take a vaccine that has not been proven safe and effective.

There is the natural and obvious third option, to not congregate in large groups, to not congregate indoors without a mask, and to wear a mask until a safe, effective vaccine is available.

I think that is what a lot of people are going to do, myself included. However, that also means I am not going to be dining indoors in a restaurant or drinking in a bar. I also won't be attending a Stanford football game with even our naturally socially distanced fan base. One might say there are different levels of caution, but for "most people" who want to live their life as they did before COVID-19, the only two options are a vaccine or risk getting COVID-19. Note that risking getting COVID-19 isn't the same as getting COVID-19. Most people who take some risks will get away with it and not get sick. They know that, and they aren't going to wait for a vaccine "forever".  In fact, many of them aren't waiting now. That is one big reason why our society is seeing lots of people die who didn't have to do so.

[BostonCard]

I will probably need to vaccinated in order to go back to work.

For me, I will likely get the vaccine once it is available to me (which will not be in the initial wave based on age and occupation), but I will of course look at the data.

BC

[BostonCard]

I will probably need to vaccinated in order to go back to work.

For me, I will likely get the vaccine once it is available to me (which will not be in the initial wave based on age and occupation), but I will of course look at the data.

BC