Why The Oxford Chadox1-Ncov-19 Vaccine Is So Promising by Dr. Nana Dadzie Ghansah

Chadox1-Ncov-19 Vaccine Is So Promising

And The Concept

Written by Dr. Nana Dadzie Ghansah

The Oxford ChAdOx1- nCoV19 vaccine holds a lot of promise, not only as a way to deal with COVID-19 but also with future viral outbreaks.The method of using a viral vector as a way of presenting antigens into the human body allows for a very novel and fast way of getting new vaccines.

Let’s say Virus X has caused an outbreak of a disease and you need to make a vaccine to fight it.

Classically, to get a vaccine against it, you have to introduce a piece or all of virus X into the human body. You could also use another virus (a piece of it or the whole virus) from the same family that Virus X comes from. Now if you use the whole virus, you need to either kill it, inactivate or weaken it so it does cause disease.

Once the virus or a piece of it gets into the human body, the immune system recognizes it as something foreign and builds antibodies against it. These antibodies last a long time so the next time you get an infection caused by Virus X, the antibodies attack the virus and inactivate it before it makes you sick. Thus, you can use it to prevent disease in those who haven’t fallen sick yet.

The Oxford team used another method. Instead of using the SARSCoV-2 virus or even a piece of it, they use a vector to get a part of SARS-CoV-2 into the body. The vector they use is another virus. This virus is called an Adenovirus and they use the type found in chimpanzees.

Once they have that adenovirus, they modify it to the point where it is unable to replicate anymore or make any mammal sick. It becomes basically a shell. Once they have that adenovirus shell, they get the RNA from the SARSCoV-2 virus and get out the part of the RNA that makes the Spike Protein that SARS-CoV-2 needs to get into the cells of the lungs. Once that piece of RNA gets into the adenovirus shell, it causes the building of the Spike on the outside of the shell. (Remember, RNA and DNA code for the building of proteins. If you get them into the right environment, and they have the right materials, they’ll build the proteins they are coded for.).

So now the team has a modified, inactivated adenovirus with the Spike Protein of SARS-CoV-2. When they inject that into the human body, the immune system sees the Spike Protein and recognizes it as something foreign. The adenovirus shell does not cause any immune reaction, only the spike. Antibodies are then made against the Spike Protein.

Now since this is the Spike Protein from SARS-CoV-2, if the virus should attack, there are already antibodies against that. Since that is what SARS-CoV-2 needs to enter the cell, once the antibodies attack and destroy it, it will be unable to enter the cell and thus unable to cause COVID-19.

Using using the spike protein is genius because in all the variants of the virus found in the bat RaTG13, in pangolins, in SARS or MERS, the Spike Protein has stayed largely constant.

The piece or part of the virus used has to stay unchanged over time to ensure the vaccine works for a long time. There is always a risk that the virus can change that part through mutation.

The question now is whether the modified adenovirus + spike protein contraption will get the human body to mount a powerful enough immune reaction in humans. It did in monkeys.

Also, since they are using the whole virus, there is no need to find out what works best - killing it off or weakening it. Since the team already had the adenovirus shell, all they needed was the genetic info from SARS-CoV- 2 and they could get the RNA sequence for the Spike Protein and plug it in.

This also means they could do this for other diseases. They can even do this for any viral disease that may break out in the future, as long as they can isolate the virus from bats, birds or pigs and sequence the genomes.

That is why the Oxford ChAdOx1nCoV-19 vaccine is so promising and the concept so exciting. 1

Corona Conundrum

Written by Dr. Nelson Nicolasora

This piece was written in response to Coronavirus and the Fallacy of the False Dilemma | American Council on Science and Health https://www.acsh.org/ news/2020/04/22/coronavirus-and-fallacy-false-dilemma-14736

The conundrum we are experiencing is by all means due to the drastic deviation from our norm, and the challenging, adaptive measures that we initiate to continue functioning as individuals, and as a society. The very opinionated will, understandably, react in a more dramatic and diverse fashion, oftentimes expressing concerns about the extent by which our individual liberties, motivations, and goals are affected.

As we continuously navigate through this crisis, the protracted and strenuous measures that people endure will generate significant stress upon certain segments of the population, especially those who find their personal interests--including one’s economic status, in jeopardy. Not surprisingly, after months of lockdown, we observe an outpouring of various opinions. Moreover, the release of ques- tionable data, whether in favor of or against the lockdown, has created a further divide within our society, comprised of different special interest groups.

Patience and acceptance of discomfort/inconvenience represent quite a challenge to those who typically function best under more optimal conditions, subject to minimal annoyances and struggles. The novelty of every pandemic will always test a society’s capacity to adapt, and how it responds is not necessarily culture-specific. This is further magnified by preexisting, polarizing beliefs amid a collective distrust towards those in positions of power and authority, along with individual and group perceptions about the available facts, news, opinion, or scientific data. Unfortunately, the existence of misinformation, or lack of good information, often influences our politi- cal views and proclivities, and how that corresponds to personal experiences and socioeconomic status.

Being an adult immigrant who came to live in this great country, I think I offer a slightly different perspective from what the author conveys, certain aspects of which I have already outlined. One has to take into account that digital technology now plays a significant role, greatly intertwined in the lives of at least a billion or so, among the world’s 7+ billion population. This phenomenon appears to be more pronounced in the United States given its socioeconomic status, in particular, allowing for relatively easier access to electronic platforms, often for the purpose of expressing ourselves. Incidentally, it seems that the author partly undermined the very same platform used to propagate his message.

ART BY MARKO BELLO

serious topics of discussion, like the controversy surrounding this lockdown, we may feel empowered and/or influenced by available information, which we can then use to formulate our own personal opinions, allowing us to even cast votes as to whether we believe this policy is doing more harm than good, whether it was actually necessary in the first place, and whether it remains necessary moving forward.

How did Americans actually respond to these lockdown initiatives? Have we been more compliant or belligerent? Have we noticed a decline in public transport or movement, public gatherings, and/ or hospital visitations? Have we freed up the supply of masks by not masking when initially told not to do so or have we started masking, in compliance with the supporting wave of data and opinion?

that would have encouraged viewpoints similar to what he proposes, an important feature of a good op-editorial. What good are observations that analyze society as a whole if they only seek to elevate the author or the audience that endorses the opinion presented?

It is not unusual in this day and age of information explosion that social media becomes the driving force for disseminating various points of view, and making these easily accessible. We can surmise that the opinion of just one individual, catering or even pandering to the personal feelings and beliefs of a particular group or groups, can easily go viral on Twitter, FB, YouTube, and other online media environments, thereby triggering strong, emotional reactions that can translate into accompanying behaviors.

I have never seen a “virus” with a R nought higher than what I have observed as it pertains to the spread of certain ideas on social media, and how that can affect human response actions. The transmissibility of opinion can now be accomplished with just a short, written message and the click of a button. On

Now, I think we should tolerate certain contrarian views as a way of conforming to our democratic ideals, although extreme recommendations or suggestions should be construed as outliers that are, sometimes, seen as inevitable. Situations that call for draconian policies in the interest of the public good could border on violating individual civil liberties no matter how well intentioned they are. These also have the power to cause dire consequences to the economic, social, and personal well-being of those who are already marginalized. We are operating within tight or limited windows of opportunity, related to this unique environment.

Personally, I think the best we can do is to support measures that, hopefully, will lessen this widening social divide that has existed even before the outbreak of this pandemic.

Attaching disparaging labels to members of our society certainly does not help. The author who, with all due respect, may be a hundred times more eloquent than many of us should have expounded more on his “3rd option,” however, he falls short of doing so. His interest in what the 3rd option has to offer was also not evident as he failed to solicit other ideas or pose a rhetorical question

What we should work on during this pandemic is to call for more transparency and more concise messaging from our leaders and public health officials. We should demand facts and work on the logistics and accurate scientific process to gather the much needed data (e.g. well-conducted immunoprevalence/ immunoprotection data followed by longitudinal surveys to see how robust the post-infection antibody response is). We should harness creative forces to help protect the vulnerable segments of our population (e.g. HCW, the elderly, those with comorbid conditions, and those affected severely by the economic downturn).

We should implement measures that would allow different parts of the economy to resume their functions. We should support and utilize technology, alongside government, as well as non-governmental measures that will help keep the economy afloat, assist our young population in becoming properly educated, the vulnerable population protected, and the able-bodied citizens, employed and generating income. We should also be gearing up to prepare for the next wave of infections, whenever it may be and in whatever magnitude it may present itself.

A crisis can always bring the best and, unfortunately, the worst in us. I fervently hope and pray, that we can agree that in the process of achieving our goals, most of us need to be part of the solution. 1

The Hydroxychloroquine Quandary

Written by Dr. Mark Lopatin

As a rheumatologist, I write many prescriptions for hydroxychloroquine (HCQ) for my rheumatoid arthritis (RA) and lupus patients. HCQ used to be a quiet drug minding its own business, avoiding the limelight. Until now.

With the onset of COVID-19, HCQ has suddenly taken center stage, with many opinions on using it to treat COVID. Our president has declared it a “game changer,” and he has recently admitted to the world that he is taking the medication himself as prophylaxis after having been exposed. There are no well done studies looking at efficacy, but many observations have been reported.

The Marseilles study,1 the most frequently cited study promoting HCQ,

“From Fox News, a Big Dose of Dumb on Hydroxychloroquine”

Anyone Who Questioned The Drug’s Efficacy Was “In Total Denial”

“Why Are Media Pundits Trying To Discredit Hydroxychloroquine?”

”They ( The Press) Opposed Finding A Cure For Corona Virus Because They Feared It Might Give The President Some Political Advantage” was a small study assessing the presence of virus on nasal swabs at six days. 26 patients received HCQ, but data was excluded in six patients. Clinical status was not assessed. Six patients also received Azithromycin (AZ). Eight of the 14 patients who received HCQ alone had negative viral swabs at six days. All six who received both drugs cleared the virus. This study was contradicted by another French study 2 which showed no change in viral presence in 8/10 patients treated with both drugs.

Dr. Vladimir Zelenko has reported great success 3 in treating several hundred patients with a regimen of HCQ, AZ and zinc. His report has been criticized 4 for lacking adequate diagnostic information and for not being of long enough duration, but it does represent a larger sample size than other studies and shows excellent results. It is unclear whether his observations constitute adequate evidence of efficacy.

A Chinese study5 assessed 62 patients with COVID. 31 received traditional therapy and 31 received an additional five day course of HCQ. The study6 cited improvement in time to clinical recovery, changes in body temperature and cough in the HCQ group. 81% of the patients in the HCQ group demonstrated improvement in pneumonia compared with 58% of the control group. Furthermore all 4 patients who developed severe illness were in the control group.

Another French study7 of 1061 patients treated with HCQ and AZ found that only 4.3% had poor clinical outcomes with only 8 deaths. The study was retrospective with no control group. The poor outcome patients were considerably sicker at baseline and had a mean age of 69, compared with a mean age of 42 in the patients who did well. The study suggests benefit for HCQ/ AZ, but has significant flaws as noted.

Other support for using HCQ 8 comes from the Indian Council of Medical Research, which recommends a prophylactic regimen9 for health care workers caring for COVID patients. It is unclear what data was used to make this recommendation.

A subsequent trial was done in China looking at prophylaxis.10 205 patients with a known exposure to COVID were treated with HCQ 400 mg/ day for 14 days and were quarantined. None were + for virus at 14 days. There were no significant adverse events although 32 patients reported minor side effects. The study supports prophylaxis with HCQ in people with known exposure.

Alternatively, The Centre for Evidence-Based Medicine at the University of Oxford noted 142 ongoing trials11 evaluating HCQ and chloroquine in the treatment of COVID. They reviewed the five studies with published results and concluded that:

“Current data do not support the use of hydroxychloroquine for prophylaxis or treatment of COVID – 19. There are no published trials of prophylaxis. Two trials of hydroxychloroquine treatment that are in the public domain, one non peer reviewed, are premature analyses of trials whose conduct in both cases diverged from the published skeleton protocols registered on clinical trial sites. Neither they, nor three other negative trials that have since appeared, support the view that hydroxychloroquine is effective in the management of even mild COVID-19 disease.”

A VA study12 retrospectively analyzed 368 patients who received either HCQ, HCQ + AZ or no HCQ (32% of these patients received AZ) and reported a higher incidence of death and mechanical ventilation in the HCQ and HCQ + AZ groups. The study is seriously flawed however as there were significant differences between the 3 groups in terms of blood pressure, lab tests (creat, ALT, Hct, CRP) and baseline respiratory status. Hydroxychloroquine, with or without azithromycin, was more likely to be prescribed to patients with more severe disease.

The next question is whether HCQ is “safe”. My patients typically take HCQ for a number of years. I do not get screening EKG’s and do not routinely discuss cardiac risks as they are felt to be minimal. My rheumatology colleagues concur in this regard. I have had only one patient who had to stop HCQ due to a prolonged QT interval. Eye toxicity, although unlikely, remains the major concern with prolonged use. I feel the drug is safe enough to use empirically in some patients in whom I suspect RA or lupus even without proof.

There are potential downsides however in using HCQ to treat COVID.

Our president has stated “what do you have to lose?” First is that although the drug is relatively safe, the risk of adverse effects is not zero. I have had patients experience gastrointestinal (GI) side effects and severe rash.

One study examined 84 COVID patients13 treated with the combination of HCQ and AZ, looking at the incidence of QT prolongation. It is unclear how to interpret the results. 11% of these patients had an increase in QT interval to greater than 500 ms, placing them at high risk for arrhythmias, yet none of these patients actually developed arrhythmia. One cannot draw any conclusions from this study regarding risks of HCQ alone.

Another report concluded the following:14

“Worryingly, significant risks are identified for combination users of HCQ+AZ even in the short-term as proposed for COVID19 management, with a 1520% increased risk of angina/chest pain and heart failure, and a two-fold risk of cardiovascular mortality in the first month of treatment.” This study was retrospective with 62 authors looking at over a million patients. The sheer volume makes the conclusions suspect in terms of consistency.

A trial in Brazil15 compared the risk of toxicity of Chloroquine using high and low doses. The study found that those in the high dose group had a significantly increased incidence of death and the study was stopped prematurely on that basis. This has been used as an argument against the use of chloroquine and by proxy HCQ, but the question remains as to whether we should not be using these drugs at all based on toxicities noted with very high doses, or whether we should simply not use those high doses.

Finally, a study done at Beth Israel16 looked at the incidence of QT prolongation in 90 patients receiving HCQ or HCQ + AZ. They found that 21/ 90 patients developed either prolonged QT intervals greater than 60 ms, or QT intervals greater than 500 ms placing them at greater risk for arrhythmias. One of these patients developed Torsade’s, which the authors state has not been noted elsewhere in the literature.

In view of these and other studies, the American Heart Association, American College of Cardiology and the American Heart Rhythm Association have concluded that we should avoid using both HCQ and AZ in patients with baseline congenital long QT syndrome or QT > 500 ms and that patients using both should have monitoring of their cardiac rhythm and QT interval.

A second downside separate from possible adverse drug reactions is that promoting HCQ as a potential cure sets patients and their families up for disappointment if reality fails to meet expectations.

Finally, the most significant downside is the inability of some lupus and RA patients to obtain HCQ. Additionally, prior authorizations, now required when prescribing HCQ, can result in further delays for patients even if the drug is available.

The main question here is whether there is “enough” evidence of efficacy of HCQ in treating COVID to warrant the potential downsides. That depends on one’s definition of the word “enough”.

What is especially troubling is that how one defines “enough” seems to depend on their political leanings. Those on the right tend to be staunch supporters of HCQ while those on the left emphasize the downsides. Both the efficacy and toxicity of this drug have been amplified in order to serve individual political narratives.

I oppose this “politicization” of medical treatments.

Despite strong opinions on both sides, we do not yet know how well HCQ works in treating COVID, and if so, exactly when and how to use it. That does not preclude its use. There are numerous circumstances where physicians treat patients empirically. Not knowing if a drug works is different than knowing that it doesn’t. Ideally, we should wait for a properly designed study, but in a crisis situation, can we afford the delay? Again, it depends on how one defines “enough.”

Medications should not be used for political capital. HCQ should not be promoted as a “game-changer” based on a “good feeling”. Politicians and media should not be cherry-picking the data to suit their underlying agendas. Treatment decisions should be made by physician and their patients without interference. Public policies forbidding the use of HCQ and threatening physicians are not appropriate.

Ultimately we will have answers to the HCQ quandary, but for now, physicians must care for our patients as best we can with the information available to us. Physicians are the ones who must do risk/ benefit analysis and inform our patients. That is what we are trained to do. That is what we do every day. COVID-19 should not change that. 1

Note: since the writing of this article, there have been new studies reported on HCQ, which are not reflected in this article.

Chadox1-Ncov-19 Vaccine Is So Promising