Coronavirus - how much infected?

Since maybe early April when the number of new cases in the U.S. began rapidly rising, I have wondered: Doesn't it matter to what extent a person is infected by the coronavirus? Mildly infected likely means no or mild symptoms. Severely infected likely means severe symptoms, maybe hospitalization or worse. Of course, the strength of the person's immune system can constrain the severity of symptoms.

I finally saw an article that has some answers to my question.

40% of people with coronavirus have no symptoms. Might they be the key to ending the pandemic?

The article taught me another word, inoculum, the amount of virus someone is exposed to. It also says that wearing a mask might constrain the degree of infection.

A different article includes the following.

“When we looked in the setting of Covid disease, we found that people who had prior vaccinations with a variety of vaccines — for pneumococcus, influenza, hepatitis and others — appeared to have a lower risk of getting Covid disease,” Dr. Andrew Badley, an infectious disease specialist at Mayo Clinic told CNN’s Anderson Cooper on Monday night.

It’s what immunologists call immune training: how your immune system creates an effective response to fight off infections, Badley says.

This article has more about the immune response.

This article has more about potential immunity to the coronavirus.

Website about Wokeness

Three days ago I became aware of the website New Discourses. I have read only two articles from it but found them interesting. 

1. The Complex Relationship between Marxism and Wokeness.

2. No, the Woke Won’t Debate You. Here’s Why.

The first title is self-explanatory. The second isn't. Much of the article is about the philosophical mindset of a typical "Woke" person. It includes the Woke view of racism, oppression, and truth.

The author of both articles is James Lindsay, co-author of the soon-to-be-released book Cynical Theories. 

Coronavirus – clinical trials #4

If an experiment or clinical trial were to show that a drug treatment could cure Covid-19 or block it from making the patient sicker, then Mill’s Method of Difference only identifies that the drug treatment works. A more complete causal explanation would include explaining why the drug treatment works. I have not seen any such explanation why regarding hydroxychloroquine (HCQ) or HCQ + zinc. Maybe somebody can explain why, but I can't. The only drug treatment I have read about that plausibly explains why it works is RLF-100, i.e. aviptadil (Coronavirus - drug news).

News

Yesterday Yahoo News reported that the FDA granted Investigational New Drug (IND) permission to test the use of RLF-100, i.e. aviptadil, for patients with moderate and severe Covid-19 in order to prevent progression to respiratory failure (Yahoo News). 

Also yesterday President Trump signed an executive order requiring U.S. government agencies to purchase “all essential medicines” from American sources (NBC News). The patent for RLF-100 is owned by a Swiss company. On the other hand, it is partnering with NeuroRx, a USA-Israel company, to produce and sell the drug in the USA. I won't try to predict how the executive order will affect RLF-100's future. 

Coronavirus – clinical trials #3

Yesterday’s post was about a clinical trial for a coronavirus vaccine and Mill’s Method of Difference. In this post I consider a clinical trial for a Covid-19 cure and Mill’s Method of Difference.

A clinical trial for a cure for Covid-19 would enroll patients who already have Covid-19. There is no contingency analogous to becoming infected like there is for a coronavirus vaccine clinical trial. On the other hand, there are a lot more variables – a variety of patients’ ages, each patient’s health status, degree of infection, and so forth. Dosage amounts may also differ, for which the logic is also Mill’s Method of Concomitant Variation.

Dr. Anthony Fauci often invokes the “gold standard” for clinical trials (randomized double blind placebo control studies) when he comments on any drug doctors might prescribe to treat patients. This standard is mainly for new drugs, but may also be used for already FDA approved medications for treating medical conditions outside the scope of prior approval, e.g. remdesivir for Covid-19. These are often called “off label” uses. It is also called repurposing. The FDA has relaxed its standards for drugs to treat Covid-19 patients. The FDA has made emergency use authorizations (EUA). The FDA may grant Investigational New Drug (IND) permission to test a drug. To my knowledge no drugs – even Remdesivir, which Fauci personally approves -- have passed the “gold standard” for treating Covid-19.

The following are the NIH guidelines for the treatment of Covid-19 with four different drug therapies.  Remdesivir.  Chloroquine and Hydroxychloroquine.  Hydroxychloroquine Plus Azithromycin.  Dexamethasone.

Conspicuously non-existent are web-pages for (1) Hydroxychloroquine (HCQ) Plus Zinc and (2) HCQ Plus Zinc Plus Azithromycin, especially with outpatients. Several doctors who recommend using HCQ for Covid-19, mainly with outpatients, have said zinc is a necessary enabler and without zinc the HCQ is minimally effective. Note that the NIH's web-page for HCQ + Azithromycin page concerns only trials with inpatients (hospitalized).

Dr. Anthony Fauci still approves using remdesivir. Regardless, it falls far short of a cure for Covid-19. Like the above web-page shows, some clinical trials have shown at best that remdesivir reduced  recovery time compared to a placebo. Other trials have shown no observed improvement or the data is insufficient. I would not call that passing the “gold standard.”

Dr. Fauci and the NIH recommend dexamethasone for some patients. The web-page above says clinical trials have shown significant mortality reduction in patients requiring supplemental oxygen, with or without a ventilator. On the other hand, no benefit of dexamethasone was observed in patients who did not require supplemental oxygen. Does this mean that dexamethasone passed the “gold standard”? Arguably 'yes' in some cases, but a cure? Many who got the drug still died during the trial.

Despite the many unknowns about the coronavirus and Covid-19 and the long time frame of clinical trials, Dr. Fauci often appeals to the “gold standard” as an argument against anything that doesn’t meet his or the FDA’s approval. In effect, he has little regard for individual judgments of practicing physicians to prescribe drugs absent his or the FDA’s approval, despite the lack of “gold standard” drugs for curing Covid-19 or halting its progress.

Dr. Fauci also consequently has shown little regard for giving placebos to patients who are seriously ill with Covid-19. Assume such patients participate in a clinical trial hoping to be cured and they later learn – if they survive – they were given a placebo and other patients in the trial who got the drug benefited. I suspect they would not be content.

Coronavirus – clinical trials #2

My previous post posited that the logical basis of clinical trials is Mill’s Method of Difference. The following is a simple example of a clinical trial based on Mill’s Method of Difference. Suppose there are N patients with disease D and the clinical trial is to treat some, e.g. two-thirds, of the N patients with medicine M and give the other one-third a placebo. Assume the later result is that the patients who are given M are cured of D, but the patients who are given the placebo are no better off than at the start. Then one could conclude that M is a cure for D. Call this the SDMT (for simple disease medicine trial).

A real world clinical trial is probably rarely as clear-cut as SDMT. It also seems to me that a clinical trial for a vaccine against the coronavirus would be far less clear-cut, for at least the following reasons.

1. The SDMT has a huge advantage over the coronavirus vaccine trial at the start. The participants at the start of the vaccine trial presumably have all tested negative for the coronavirus.* Some get the vaccine and the rest get a placebo. Then they wait to see if they do become infected by the virus to some degree. If they do become infected, and the vaccine protects against Covid-19, whereas those given the placebo get Covid-19, then the vaccine justifiably worked. However, many of the participants may not become infected any by the virus. They provide no basis for any conclusion about the efficacy of the vaccine. Presumably, such a vaccine trial must have many, many more participants than a SDMT kind of trial to make up for the probability of not becoming infected.

2. Those given the placebo might get infected, but their natural immune system might protect them from testing positive for the coronavirus or getting very ill from Covid-19 anyway.

3. Some participants may become only mildly infected and others far more so. This might come about due to the extent of precautions they take while in the trial, such as wearing a mask, keeping a safe distance from others, and washing hands. 

4. Some given the vaccine may be infected and the vaccine works. Others given the vaccine may be infected and the vaccine doesn't work or works poorly.

For all these reasons, and more not stated, a clinical trial for a coronavirus vaccine falls far short of all factors being the same except for one key difference for ideally applying Mill’s Method of Difference. It makes me quite skeptical about achieving a “gold standard” vaccine clinical trial per the wishful Dr. Anthony Fauci.

*The trial might also include groups of people who tested positive and are (a) asymptomatic or (b) have mild symptoms. They should be considered as separate trials.

Coronavirus – clinical trials #1

The coronavirus pandemic has pushed the concept and use of clinical trials into the mainstream media. Searching the Internet for {coronavirus clinical trials news} or {coronavirus clinical trials method} or {clinical trials logic} yields many results about clinical trials underway, but very little about the logic behind such trials. For example, this web-page is about clinical trials for a Covid-19 vaccine. The title says “here’s what you need to know”, but none of it is about the logic behind such trials.

When I became aware of clinical trials, I supposed that such trials are an application of John Stuart Mill’s Method of Difference. Researching it very recently, I found this web-page which supports the supposition. Despite that, it doesn’t link the logic of clinical trials directly to the influence of John Stuart Mill himself. Another web-page addresses the direct influence of Mill, but such influence is sketchy.

Coronavirus - drug news

A Reuters article says: "Critically ill COVID-19 patients recovered rapidly from respiratory failure after three days of treatment with RLF-100, a therapy granted fast-track designation in the United States, two drug companies said on Sunday."

The drug plausibly blocks replication of the SARS-CoV-2 virus in human lung cells and monocytes (white blood cells).

  

The article also appeared in the New York Post and Jerusalem Post.

A Science Alert article says: "A paper came out in Nature on July 22 that further underscores earlier studies that show that neither the malaria drug hydroxychloroquine nor chloroquine prevents SARS-CoV-2 – the virus that causes COVID-19 – from replicating in lung cells."

Zinc was used with hydroxychloroquine in some cases, but the article doesn't mention zinc.

RLF-100 was used to treat critically ill patients, whereas earlier alleged successes with hydroxychloroquine were mainly with early-stage mildly infected patients or as prevention. The blocking versus not blocking replication of the virus is a big difference, too. 

Update August 4 

This page shows a transcript of Dr. Anthony Fauci testifying about hydroxychloroquine. He is acutely asked about using zinc with hydroxychloroquine, and he evades the question. (He refers to corticosteroids, which contain no zinc.) He clings to the "gold standard" despite its very long time frame and requiring giving very ill patients a placebo, and the urgency of finding a cure.