Operation Warp Speed, Don’t Leave Us Behind

During an interview hosted by the American Medical Association, Peter Hoetz, the co-director of the Texas Children’s Hospital Center for Vaccine Development discussed the challenges of maintaining public confidence in the vaccine development process. Since the initiation of Operation Warp Speed by the white house, money and other resources have been poured into vaccine development at a rate like we’ve never seen before. But one thing Operation Warp Speed didn’t have a plan for was how it would communicate progress and setbacks to the public. This is incredibly important as we get closer to having workable vaccines because, as Dr. Hoetz points out, there is an enormous amount of information that needs to be communicated to the public. Just a few of the confusing things people will need to understand are that some vaccines will be better than others, some will require continued use of masks and social distancing (really all of them will), some vaccines will require booster shots, and there may be confusion about whether to get a booster with the same vaccine or a different one. With this much information yet to be communicated to the public and especially because informing the public doesn’t need to wait until a vaccine is ready, Operation Warp Speed is leaving the public behind. 

Dr. Hoetz also touched on the need to remove anti-vaccine websites that promote fake information from the web and from major social media platforms. Hoetz says that he had hoped this would happen last year when measles returned to the U.S. because of clustered groups of people who refused to vaccinate their children. Apparently after holding a few initial hearings on the matter, the Senate Health Committee “dropped the ball” on it. Despite the relative disorder of vaccine information at the moment, we can prepare by learning about the different types of vaccines that are already in stage three clinical trials. Most importantly, we should all be ready to get vaccinated when a proven safe and effective vaccine comes out. 

- Renata

https://www.ama-assn.org/delivering-care/public-health/ama-covid-19-daily-video-update-improving-patient-confidence-vaccine

Coordination of COVID-19 Vaccine Development

At a symposium [1] in October, 2020, a panel of scientists, academicians, journalists and public health experts came together to describe the US government’s COVID-19 vaccine trial program and the ways they are protecting the integrity of the process of design, regulation, safety and efficacy assessment, communications, and recommendations for access, allocation and use of the vaccine.  Accurate, truthful information about both the development and deployment of vaccines is absolutely critical given both the importance of the topic and the amount of misinformation that continues to circulate.

Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, gave an excellent overview of all of the companies and researchers involved and their roles in the vaccine development program, Operation Warp Speed. This program has reached unprecedented levels of cooperation and coordination between academic centers, government agencies and industry. At the time of the talk there were four phase 3 trials underway. As to other players, he reminded the audience that it is the CDC who recommends who is vaccinated as well and when and which vaccine. They are also the organization that defines who has the priority to receive the vaccine when there is not enough vaccine for everyone.  Following Dr. Fauci, Dr. Moncef Slaoui, the Chief Advisor of Operation Warp Speed, working for $1 per year, went on to describe the progress and coordination of this massive effort.

Dr. Francis Collins contributed perhaps the most interesting summary of the afternoon describing the “unprecedented science going on that should give people confidence that we are trying to arrive at solutions.”  He reminded the audience that the title, Operation Warp Speed, in no way suggests that the project will be moving too quickly or too unsafely. Instead, he said, “It is cutting corners with bureaucracy….it is certainly not cutting corners with safety or efficacy.” Perhaps most importantly, the data and safety monitoring board charged with making decisions about moving forward with the vaccines is the only “unblinded group” that will have full access to all results of the studies. The board will have access to all of the groups and companies’ data, all except Pfizer. Having a group that is able to look across the data from all of the different groups is absolutely key to safely and rapidly developing vaccines.  The companies, he said, are fully onboard for not putting anything forward that does not meet the “high expectations” of the board. The FDA has put forward “clear guidelines for safety and efficacy” that must be met before release. At that point, there will also be a public discussion where all interested parties can review the data.  Dr. Collins then reassured the group saying, “It would be pretty darn hard for mischief to derail this process.”

As an optimistic participant in this project, Dr. Collins is hoping for one or more vaccines to be ready by early January. He described that we do have a National Academy panel ready for distribution, but he reminded the group to be sure we are focusing our attention globally.  He went on, “We in the US have been so focused on ourselves for the most part that we haven't paid enough attention to the fact that we're part of a global community, and we have a moral imperative to consider that as part of any plans that we make. That clearly needs to be worked on probably and talked about a bit more than it has so far given the tendency we have to look in the mirror at ourselves.” He concluded his section that we must address the issue of “vaccine hesitancy” through public education and reminding the group with the following words, "Let's not slip into this polarization of everything circumstance that seems to be the only way we talk about any topic these days."

Dr. Ellen Mackenzie, Dean of the Johns Hopkins Bloomberg School of Public Health, concluded the afternoon with the following words, “The importance of scientific integrity, data integrity, and the fundamental principle that while our science does need to impact the body politic it must be free of political interference....The primacy of science must be vigorously defended and upheld by us all. And our science must be conducted in a way that benefits all segments of our society.”  Scientific integrity, thankfully, has not been and will not be compromised in this important race to develop a vaccine for COVID-19.

[1] Preserving the scientific integrity of getting to COVID-19 vaccines. 6 Oct 2020. A Johns Hopkins University + University of Washington Symposium

https://coronavirus.jhu.edu/live/events/covid-19-vaccine-symposium

- Claire Hillier

Preventing Viral Diseases Through Behavior

The COVID-19 pandemic has placed a new focus on behavioral interventions. The idea that viral infections can be prevented through changing human behavior seems so simple. Unfortunately, the reality of implementing these behavioral changes has been difficult. 

The same is true for another form or emerging disease, mosquito borne diseases. Mosquitoes can transmit viruses that cause diseases like Zika, West Nile, St. Louis encephalitis, dengue fever, yellow fever and chikungunya. As mosquitos spread across the United States, these diseases present a greater public health threat. We do not have the luxury of a vaccine for any of these diseases besides Dengue, and even this vaccine is only available to a small part of the population in specific areas. 

Behavioral interventions present an option for prevention of mosquito borne diseases. We can avoid irritating mosquito bites by covering our skin, using insect repellant, and keeping mosquitos outside. Taking a public health approach, vector control teams in the United States use insecticides to keep the mosquito population low to decrease overall risk to communities. 

However, a study in Texas has been testing the effectiveness of commonly used insecticides on local mosquitos. This study found that almost 70% of mosquito populations tested survived exposure to the insecticides. This means that these mosquitoes have developed resistance to the commonly used insecticides. In the short term, this study provided feedback to areas that needed to change the type of insecticide they were using. Next, the researchers hope to identify how the mosquitos are developing resistance and how widespread this phenomenon is. However, as with many public health challenges, a long term approach is going to be required to identify a solution that does not just postpone the problem.

-Olivia

https://today.ttu.edu/posts/2020/10/Stories/researchers-widely-used-mosquito-control-insecticides-becoming-less-effective

https://www.cdc.gov/dengue/prevention/dengue-vaccine.html

https://www.cdc.gov/ncezid/dvbd/media/stopmosquitoes.html

Coronavirus Vaccine Trials: How Fast is Too Fast?

      The race to a vaccine has seen unprecedented speed globally; however, if we look back at why vaccine development usually takes a while, pushing out the vaccine for political reasons may be ill-advised. And might only make this disaster worse... SARS-COV2 already does not seem to elicit long lasting immunity in humans, which makes the development of this vaccine and the stringent monitoring for long term effects all the more critical. Several trials including the mRNA vaccine from Moderna, the non-replicating adenovirus type 5 vector vaccine from CanSino, Inovio's DNA vaccine, and AstraZeneca are all deep into their trials.

    We need to be smart and look comprehensively at our history of vaccine failures along with successes to see why racing to put out a vaccine may not solve the problem in the way we hope. For example, in several different trials an increase in viral activity in a term called 'vaccine-associated disease enhancement' has been shown. Many of these trials caused disease exacerbation through immune systems, through antibodies or Th2 cells or often both. For example, Dengue Fdc cells can bind to FcR-bearing cells and actually cause antibody-dependent enhancement upon second exposure to Dengue which can result in a cytokine storm and higher viral loads, thus causing even more disease. The tragic failure of the RSV vaccine is also pertinent, as this vaccine caused an enhanced respiratory disease during subsequent infections. All trials were immediately suspended after hospitalizations and deaths occurred. It's also prudent to look at SARS COV, which bears similarity in structure and tropism as SARS-COV2, particularly in the key ACE receptor to enter cells. SARS vaccines showed that they could induce excess eosinophils and TH2 cell skewed immune responses, similar to the overactive immune responses shown in RSV vaccine trials. ADE was also observed in some SARS trials.  

    Governments should be extremely cautious and allow scientists to track the safety of vaccines before they push them out to their countries, and to millions of people globally. The SARS-COV2 vaccine should elicit a balanced T cell response, be rigorously evaluated in animals and humans, and be tracked over time before passed out to humans. Certainly there is a race against the clock to end this pandemic, but cheating time and the wisdom that comes from time may not be the intelligent move in the long run. Time may actually be on our side with this one. 

-Sammy 

https://www.nature.com/articles/s41579-020-00462-y 

    

To What End? Debates on Bioethics of Proposed Vaccine Trials

A SARS-CoV-2 vaccine trial has been proposed in the UK. It’s unique because it proposes deliberately infecting test subjects to see if they get sick. This type of trial is known as a “challenge trial” and it has been used to test vaccines for things like malaria and typhoid. The big difference between those vaccine trials and the proposed SARS-CoV-2 vaccine trial is that if the vaccine failed and subjects did become ill, incredibly effective drugs could be used to treat malaria and typhoid. Proponents of the challenge trial methodology for COVID argue that it will help bring an effective vaccine to market more rapidly. But there are some critical flaws to their logic. The first is simply that several other vaccine trials are already approaching the phase III clinical trial stage. So there isn’t much of a need for this challenge trial. But a more important question is whether or not challenge trials would even be effective in bringing a vaccine to market. The problem here is that vaccines need to be tested against many different demographics before they can be safely released for public administration. Ethically, challenge trials can only expose young, healthy people to the virus after vaccination. The risk of exposing at-risk populations is just too great because they could easily die as a result. The elderly, people with diabetes, and other vulnerable populations are the ones who are most in need of a vaccine, so developing a vaccine that has only been tested on young, healthy people is in the best case only beneficial to a small group of people who can get it, and in the worst case can be harmful to populations that the vaccine was not properly tested on before approval. 

- Renata

https://www.nature.com/articles/d41586-020-02821-4

What’s All This About The Great Barrington Declaration?

The White House continues to push for a herd immunity approach to dealing with COVID-19 - an effort that would cost tens of millions of lives and is not likely to be successful based on a lack of historical evidence of any virus burning itself out in a population. The dramatically titled Great Barrington Declaration authored in early October and now being touted by Scott Atlas calls for young people to return to their normal lives, become infected, and allow society to develop herd immunity over time while protecting vulnerable populations. The declaration was authored by professors from three prestigious universities including Harvard, Stanford, and Oxford, but as academics, they are a minority amongst their colleagues. Most medical experts agree that trying to achieve herd immunity is comparable to mass murder. 

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What’s more, their plan is a catfish. It’s a catfish for two reasons: One, it argues that we can do something that we cannot - protect vulnerable populations while the virus spreads amongst the rest of us. Two, the enticingly “normal” reality they offer a return to is not what we would actually see if we follow their plan. 

The authors of the Great Barrington Declaration argue that if we protect vulnerable populations, the rest of society can go back to normal. Protecting vulnerable populations would require isolation until the rest of society becomes immune which would probably take years if it were even likely to happen. As it stands, younger generations need to take care of their elderly parents and grandparents, and doctors need to see and treat immunocompromised patients. The degree to which these people would need to be protected while the virus spreads freely amongst society is greater than we are capable of. The best way we can protect them is by stopping the spread of the virus. When we protect ourselves, we protect those who can die from this disease. 

One of the most enticing things about a proposed return to “normalcy” is that we can all get back to our lives as they were. But stop and think for a moment. Would you really be living life as you were pre-COVID or would you still worry about getting sick and giving it to your parents? Would you see all your friends without a second thought or would concerns about the emerging long term effects of COVID give you pause? The reality that we’d “go back to” is not the reality we are expecting. The Great Barrington Declaration proposes a dangerous plan and should be considered critically for what it has to offer and for where it may be misleading. 

- Renata

Wall Street Journal - Scientists Push Back on Herd Immunity Approach

The Great Barrington Declaration

The flu is coming!

This summer, many questions arose with the approach of influenza season. What would influenza mean during the COVID-19 pandemic? Would having one make a person more susceptible to the other? Would identification and isolation of COVID-19 positive patients become more difficult with the addition of influenza cases? Or would the introduction of physical distancing and mask wearing decrease the rates of influenza? 

Well we are starting to get some answers. The World Health Organization’s surveillance influenza rates are coming back lower than in previous years worldwide. The southern hemisphere’s seasonal influenza levels stayed low. The northern hemisphere’s inter-seasonal levels also stayed low. Only in South East Asia was an increase in influenza cases reported. 

These numbers should be taken in context, understanding that the realities of COVID-19 have affected surveillance activities. Influenza cases are likely being missed as people are seeking medical care less often during the pandemic. The constraints of the pandemic have also limited influenza surveillance testing abilities and testing priority. 

Given these factors, the WHO still acknowledged that the lower levels of influenza are likely due to hygiene and distancing measures meant to decrease COVID-19 transmission. We will have to wait and see if COVID-19 and influenza will overlap in any further ways.

-Olivia

https://www.who.int/influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en/

He was right all along - How an Immune System Imbalance May be Exacerbating COVID19

As we’ve grown more familiar with our coronavirus foe, the data is starting to tell us that there’s more to the picture than first meets the eye. Beth Daley, an immunologist at Emory University, described findings of an immune system imbalance in patients with severe COVID-19. In the article that she and her colleagues published, they found that patients who went on to develop severe COVID-19 had a rapid onset of extrafollicular B cell activation. Extrafollicular B cell activation is one means by which the body initiates an immune response during the interim between infection and the production of highly specific B cells. B cells activated in this manner bypass many of the checks the immune system has in place to make sure they don’t target the body’s own tissues. In a normal immune reaction, this response is short lived, so risk of targeting one’s own tissue is mitigated, and is later replaced by a more targeted immune response.

Some autoimmune diseases, such as Lupus, are caused by chronic activation of this extrafollicular response. Some COVID-19 patients experience a rapid onset of this autoimmune-like B cell activation. Potentially due in part to non-specific antibodies that target their own cells, these patients experience high incidences of organ failure and death during the course of infection. This research could provide physicians important clues into how they can more effectively treat COVID-19 using targeted immunosuppression. 

Patients who have long-term continued symptoms after supposedly recovering from COVID-19 are referred to as COVID long-haulers, and recently they have been gaining public attention and concern. Daley hypothesizes that ongoing autoreactive response may be the cause of these persistent symptoms. 

- Renata

The Conversation - Autoimmune-Like Antibody Response
Nature Immunology - Extrafollicular B Cell Response in COVID19 Morbidity 

Public Push for Research on COVID-19 Long Haulers

There is certainly no shortage of things to be worried about when it comes to the current COVID-19 pandemic. But one concern seems to be gathering increased attention from medical professionals -- so called “long COVID”. After 10 months of enforced proximity to the virus, the number of recovered patients is growing and so are reports of continued difficulty breathing, muscle aches, fatigue, and persistent changes in vision and hearing. In cases of COVID longhaulers, these symptoms persist despite repeated negative testing. Researchers and patient groups are advocating for increased attention and funding be paid to long COVID. On this topic, Nisreen Alwan, a public health researcher from the University of Southampton, UK, wrote in an article that “measuring recovery from COVID-19 should be more sophisticated than checking for hospital discharge or testing negative for active infection”. The WHO and other public health authorities have responded to the advocacy for research into long COVID saying that they have “heard loud and clear that long COVID needs recognition”. 

- Renata

Nature Magazine - Long COVID

Nature Magazine - Nisreen Alwan on COVID-19 Recovery

Bloomberg - COVID Everlasting