COVID-19 – Treatment Updates

I wanted to give some updates on the various treatments that are showing promising outcomes.

With hundreds of ongoing initiatives, it’s near impossible to be aware of them all. The ones I outline below I’ve categorized into anti-viral medicines and antibodies.

Anti-viral: An agent that kills a virus or that suppresses its ability to replicate, hence inhibiting its capability to multiply and reproduce. Some anti-viral medications can be taken in a preventative manner, but doing this too early may prohibit the immune system from creating the antibodies needed to fight the infection once the treatment is complete, thereby allowing the person to catch the virus again in the future.

Hydroxychloroquine: The FDA just emergency approved hydroxychloroquine for off label use in hospitals to treat COVID-19. Many studies are showing remarkable results on using this antimalarial drug to combat the virus. Approved for medical use in the United States in 1955, hydroxychloroquine is on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.

Hydrochloride was rated the most effective treatment in a survey of 6,227 physicians treating COVID-19 in 30 countries worldwide. The survey was conducted March 25-28 of this year.

Two French studies showed incredible results using hydroxychloroquine, especially when combined with azithromycin (antibiotic) and zinc.

Hydroxychloroquine_final_DOI_IJAA-24-1038x553.jpg

Family medicine physician Dr. Zev Zelenko published his results treating 500 patients in New York with the following outpatient regimen:

1.  Hydroxychloroquine 200mg twice a day for 5 days

2.  Azithromycin 500mg once a day for 5 days

3.  Zinc sulfate 220mg once a day for 5 days

This was the treatment protocol in the pre-hospital setting:

1.  Any patient with shortness of breath regardless of age was treated.

2.  Any patient in the high-risk category even with just mild symptoms was treated.

3.  Young, healthy and low risk patients even with symptoms were not treated (unless their circumstances changed and they fell into category 1 or 2).

The paper is worth a read. A few quotes are below:

“I combined the data available from China and South Korea with the recent study published from France. We know that hydroxychloroquine helps Zinc enter the cell. We know that Zinc slows viral replication within the cell. Regarding the use of azithromycin, I postulate it prevents secondary bacterial infections. These three drugs are well known and usually well tolerated, hence the risk to the patient is low.”

Basically…he used common sense.

“The results are staggering: We have had ZERO deaths, ZERO hospitalizations, and ZERO intubations. In addition, I have not heard of any negative side effects other than approximately 10% of patients with temporary nausea and diarrhea.”

Infectious Disease Specialist Dr. Stephen Smith said the data is unequivocal that the hydroxychloroquine protocol is a game changer. Dr. Smith has been treating coronavirus patients at the Smith Center for Infectious Diseases and Urban Health in East Orange, New Jersey.

Dr. Stephen Smith stated that not a single coronavirus patient under his care who was on the hydroxychloroquine regimen needed to be intubated. “No person who has received five days or more of the hydroxychloroquine azithro combination has been intubated. The chance of that occurring by chance … are .000 something. It’s ridiculously low. It’s ridiculously low however you look at it.  We were looking at selection bias in this situation. But I cannot think of a reason why. If all else is equal why people that received 5 days or more or even four days or more of this hydroxychloroquine-azithro regimen wouldn’t get intubated… It’s a game-changer. An absolute game-changer. I think this data goes to really support the French data…I think this is the beginning of the end of the pandemic.”

He has stated he believes it needs to be given to people earlier to prevent hospitalizations and ICU patients in the first place.

If patients do not need to be intubated, that would eliminate the massive need and shortage of respirators.

Dr. Anthony Cardillo, CEO of Mend Urgent Care, believes the key to hydroxychloroquine effectiveness is to take it with zinc. He made the following remarks during an interview with ABC 7 news anchor Jory Rand.

“What we’re finding clinically with our patients is that it really only works in conjunction with zinc. So the hydroxychloroquine opens the zinc channel, zinc goes into the cell, it then blocks the replication of the cellular machinery,” Cardillo said. “So, it has to be used in conjunction with zinc.”

“Every patient I’ve prescribed it to has been very, very ill and within 8-12 hours they were basically symptom free and so, clinically I am seeing a resolution that mirrors what we saw in the French study and some of the other studies worldwide,”

The people that say hydroxychloroquine is not proven to work are looking for a traditional double-blind study. The good news is that such a study coming. The University of Pennsylvania has a new trial to evaluate whether the drug hydroxychloroquine (HCQ) can benefit people infected with COVID-19, as well as whether taking the drug preventatively may help people avoid infection altogether. The study, called Prevention and Treatment of COVID-19 with HCQ (PATCH), is currently enrolling patients in three separate sub-studies (NCT04329923).

So, sometime after this outbreak is over, we should have a study proving if this treatment works.

Chloroquine: The FDA just emergency approved chloroquine for off label use in hospitals to treat COVID-19. Chinese medical officials have approved the drug to treat pneumonia caused by COVID-19.

A common antimalarial drug, chloroquine is also used for rheumatoid arthritis, amebiasis, and lupus erythematosus. Discovered in 1934 by Hans Andersag, it is has seen widespread use since 1945. Like hydroxychloroquine, it is on the World Health Organization’s List of Essential Medicines. It is available as a generic medication. The wholesale cost in the developing world is about US $0.04. In the United States, it costs about US $5.30 per dose (an infuriating price difference that merits a series of blogs at a future time).

Recent guidelines from South Korea and China report that chloroquine is an effective antiviral therapeutic treatment against COVID-19. Use of chloroquine tablets is showing favorable outcomes in humans infected with coronavirus, including faster recovery times and shorter hospital stays. US Centers for Disease Control and Prevention (CDC) research shows that chloroquine also has strong potential as a prophylactic preventative measure against coronavirus in the lab. 

Basically, both antimalarial drugs work in similar ways with similar results.

Favilavir: Regulatory officials in China announced in mid-February that they had approved the antiviral favilavir for use in the treatment of the novel coronavirus COVID-19. The approval by the National Medical Products Administration was based on the drug’s efficacy against the virus in clinical trials started in response to the ongoing outbreak.

The drug was tested in 70 patients with confirmed COVID-19 infection in the city of Shenzhen. Specific results of the clinical trial involving favilavir, formerly known as fapilavir, have not been released at this time (or I was unable to find them). This makes comparing the results of favilavir to hydroxychloroquine or chloroquine difficult, but it does increase the supply of antiviral medicine that is shown to be effective against this outbreak. The drug was originally developed to treat catarrhal, or inflammation of the nose and throat.

Aviptadil (VIP): VIP has been used for 20 years in trials for sarcoidosis, pulmonary fibrosis, and pulmonary hypertension. It was approved for the treatment of acute lung injury, and it’s used to treat erectile dysfunction in Europe.

VIP is supposed to be used to stop acute respiratory distress syndrome (ARDS) that develops in severe COVID-19 cases and kills about 50% of patients. ARDS is a respiratory failure that can follow the severe lung inflammation affecting certain categories of patients, including the elderly and those people suffering from other medical conditions. These patients often need to be intubated and ventilated with a machine, while a secondary ECMO may help oxygenate the blood. Not all patients who are given oxygen therapy and who are placed on ventilators are guaranteed to survive.

Therefore, VIP could be one of the last lines of defenses against the novel coronavirus in those cases where significant complications appear, like sepsis.

“In a previous trial of VIP for ARDS caused by sepsis, seven out of eight patients on mechanical ventilation showed substantial improvement, and six ultimately left the hospital alive,” NeuroRx CEO Prof. Jonathan Javitt said. “Patients on ventilators for COVID-19 (without this drug) have only a 50 percent chance of survival.”

The Food and Drug Administration (FDA) has issued a “study may proceed” letter for NeuroRx, in partnership with Swiss drug development company Relief Therapeutics, to go forward with a Phase 2 trial of the drug. 

Remdesivir: Remdesivir was approved for treatment in China. Intended to treat Ebola virus, remdesivir has reportedly been used to treat one American sickened with COVID-19, and the patient in question fully recovered. But clinical trials for remdesivir have not shown as positive results as the antimalarial drugs.

Ritonavir:  Doctors in South Korea reported that they used the HIV combination drug lopinavir plus ritonavir — marketed as Kaletra — to successfully treat COVID-19 in a 54-year-old patient. Results in the first clinical trial were disappointing.

Overall, the medical community has adapted and found ways to attack the virus and help patients. While not all of the originally touted medicines have turned out to be consistently effective, they definitely have found some that will have a profound impact on COVID-19 care. With supplies of these drugs currently limited, anti-viral medicines are primarily being used to kill the virus in those hit the hardest, often in conjunction with antibiotics (to help fight bacterial comorbidities like pneumonia), to keep people from the ICU. Preventative use may be limited to high risk populations such as healthcare workers. As supplies increase and as testing becomes prevalent and timely, anti-viral medicine may be prescribed at first diagnosis or first sign of respiratory issues to prevent any hospitalization or severe symptoms.

Let’s move to the next section of the treatments, antibodies.

Antibody: Also called immunoglobulin, a protective protein produced by the immune system in response to the presence of a foreign substance, called an antigen. Antibodies recognize and latch onto antigens in order to remove them from the body. A wide range of substances are regarded by the body as antigens, including disease-causing organisms and toxic materials such as insect venom.

There are four main ways for the human body to develop antibodies to COVID-19 (or any antigen).  Contract and recover from the disease, receive the antibody from someone who has caught and recovered from the disease, receive an injection of lab created antibodies directly, or receive a vaccination shot which will start the body producing an antibody that hopefully will work on COVID-19.

Herd Immunity: Catching COVID-19 will be the primary way most people develop the antibodies.  Studies are showing 25% – 75% of people that catch the virus are asymptomatic. Of those symptomatic, the majority of cases are mild (no hospitalization) with a minimum of 80% of symptomatic patients in this category. This is why I believe a test for the antibodies is the most important test in this whole process. Once people discover they have the antibodies, they can resume life and donate blood to help those that have not developed the antibodies.

Convalescent plasma: Convalescent plasma is a century-old technique that involves taking antibodies from the blood of a person who has survived an illness, in this case COVID-19, spinning it to extract the antibodies, and transferring them into an infected person.

Various countries, including China and the United States, have also asked patients who have fully recovered from COVID-19 to donate their blood plasma for possible use as the basis of a new treatment for the virus. Mike Ryan, executive director of the World Health Organization’s Emergencies Program, said the approach, known as hyperimmune globulin therapy, has been used for decades in the treatment of viral diseases. The theory is that those who have recovered from viral infections have antibodies against the disease in their blood, and that those antibodies can be passed on to others who have been infected via transfusion, providing their immune system with a needed “boost,” he explained. However, the key to its effectiveness is timing — transfusions need to be performed early enough in the course of the disease for the antibodies to work. 

My old roommate is recovered from COVID-19 and he and his wife are going back in to be tested for antibodies in a few weeks. They will donate blood if they meet the requirements. According to a close friend working with COVID-19 patients in Illinois, that treatment will be starting soon here. New York is also undergoing a trial.

Engineered Antibody: Dr. Glanville is one of the doctors featured in the Netflix show “Pandemic.” His team in the Bay Area has been working around the clock trying to come up with a drug to treat COVID-19. On Monday, he announced he believes they’ve found one.

“We are happy to announce we have completed the engineering and we have some very potent antibodies that can be effective against the virus,” said Dr. Glanville.

Glanville’s team had developed antibodies to neutralize SARS and their lab adapted them to recognize COVID-19. Dr. Glanville has sent samples to the military.

His full interview was fascinating and very educational.

Vaccine: A preparation of killed microorganisms, living weakened organisms, or living fully virulent organisms that is administered to produce or artificially increase immunity to a particular disease.

When I listen to the media, a vaccine seems to be the only solution they can comprehend at times. Vaccines have an advantage because they can be administered in advance of an outbreak to increase herd immunity if there is no antibody treatment available.

There are also some significant disadvantages.

Even though many vaccines are aggressively in the process of being developed, it will likely be over a year before a vaccine can be developed, tested, approved and produced at scale. This pandemic will be so far along that they likely will not make much of a difference. The SARS and MERS vaccine development stopped or slowed down once the epidemics stopped.

Vaccine Timeframe.GIF

Vaccines must be administered far in advance of catching the disease, so the body has time to fight it and develop antibodies. They do no good, and, in fact, can only cause harm to someone that already has the virus.

Many vaccines try to emulate the virus, but viruses morph over time in order to avoid antibodies.  As we see with the flu vaccine, which the CDC says is effective about 50% of the time. 

Vaccines also, by necessity, contain multiple ingredients that are likely to not be good for the human body. The immune system can also associate these ingredients with the virus and have intense auto-immune reactions in the future.

Vaccines are also a more expensive form of healthcare than some of the other options. Shots like the flu shot are annual. Anything mandatory has a huge market (and huge corresponding cost). The malaria drugs that have been around for 80 years and cost very little will be less profitable for large pharmaceutical companies.

There is no doubt someone will create a COVID-19 vaccine at some point. Links to a few of the ones in process now are below.

https://time.com/5790545/first-covid-19-vaccine/

https://www.nbcnewyork.com/news/health/covid-19-are-we-close-to-a-novel-coronavirus-vaccine/2312199/

Antibodies do not always last in the body. If a person is not exposed to the virus within some period, the antibody will disappear from their system.  In the case of the four respiratory coronaviruses, cases of reinfections are observed after eight to 12 months. This has not been determined for COVID-19 yet.

8 month immunity.GIF

Although a person can catch a virus again (flu, cold) the thought is their body will react faster, and the severity will be lessened. This principle applies to all four antibody therapies above.

Vaccine impact.GIF

Proning: This does not fall into the antiviral or antibody category – but it is an important development in the care of patients. Proning (placing people on their stomachs to get their heart weight off their lungs when incubated or having trouble breathing) is a very effective way to help those having trouble breathing. It increases lung capacity when people are desperately in need of oxygen supply. In my last conversation with staff treating the worst COVID-19 cases in the Chicagoland area, the sentiment was that proning was turning out to be a lifesaver for some people.

I realize I’ve shared a great deal of information, but I’m encouraged by all the amazing progress that has been made in the fight against COVID-19. 

Stay safe, stay strong!