Covid-19 +

Nice Covid-19 info state by state. And more.

The increasing use of hydroxychloroquine (sometimes given in combination with azithromycin) is because it is an FDA-approved drug. In theory, Remdesivir as a treatment option makes more sense though.

I wish experimental treatment options could be made available prior to onset of ARDS, especially for immunocompromised and/or elderly populations. Same goes for the vaccines undergoing clinical trials. I know some elderly folks with underlying health conditions willing to roll the dice on untested vaccines.

So far, one issue I see with outcomes of "compassionate use" of Remdesivir is it is often given so late in the progression of the disease. With seasonal influenza, for example, Tamiflu should be administered within 48 hours of symptoms onset in order to be effective.

A small trial finds that hydroxychloroquine is not effective for treating coronavirus
20, 8:40 AM EDT

Like the Marseille study, the Molina trial was also a small pilot study. Molina and colleagues used the same dosing regimen as Gautret. In contrast, however, to the Gautret study, eight of the 11 patients had underlying health conditions, and 10 of 11 had fevers and were quite ill at the time the dosing began.

These Paris researchers found that after five to six days of treatment with hydroxychloroquine (600 mg per day for 10 days) and azithromycin (500 mg on day 1 and 250 mg on days 2 to 5), eight of the 10 patients still tested positive for COVID-19. Of these 10 patients, one patient died, two were transferred to the ICU and another had to be removed from the treatment due to serious complications.

Study of a total of eleven patients.
Eight of which had underlying health conditions.
Ten of the eleven had fevers and we're quite ill at the time the dosing began.

Fact: Zinc has been shown to help with other coronaviruses.

Fact: Hydroxychloroquine is a zinc ionophore.

Definition of ionophore (Source: Google):
"a substance which is able to transport particular ions across a lipid membrane in a cell."

However, I read today that hydroxychloroquine may be contraindicated for diabetic patients taking Metformin.

I am also concerned about the cardiotoxicity of hydroxychloroquine, especially in cardiac patients in advanced stages of COVID-19.

Early intervention for high-risk patients is crucial.

Knowing the risks is also important.

COVID-19 is no laughing matter.

Hydroxychloroquine is not 'snake oil'.

Multiple treatment modalities should be pursued simultaneously.

High-risk patients deserve access to experimental treatments in consultation with medical professionals.

As pointed out earlier, hydroxychloroquine may be contraindicated for diabetics and patients with cardiac issues.

National Institutes of HealthU.S. National Library of MedicineNCBI

Advanced
Case Reports
The Antiinflammatory and Antiviral Effects of Hydroxychloroquine in Two Patients With Acquired Immunodeficiency Syndrome and Active Inflammatory Arthritis
M H Ornstein et al. Arthritis Rheum. Jan 1996
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Abstract
Objective: To report the antiinflammatory and antiviral effects of hydroxychloroquine (HCQ) treatment in 2 patients with AIDS and inflammatory arthritis.

Methods: Two patients with AIDS and inflammatory arthritis were treated with HCQ, which was given in a loading dose of 600 mg/day. The maintenance dosage was calculated to remain below 6.5 mg/kg/day. Both patients had initial T cell subset studies; 1 patient, had serum and plasma collected before and after 1 year of HCQ treatment. Assays were performed for T cell subsets, recoverable human immunodeficiency virus type 1 (HIV-1) RNA, mitogen- and antigen-specific proliferation, and interleukin-6 (IL-6) levels. New studies on the use of HCQ as an anti-HIV-1 agent are reviewed.

Results: Both patients had a dramatic decrease in their arthritis activity. Neither patient required immunosuppressive therapy or developed an opportunistic infection. In the patient who was studied after 1 year of therapy, there was a 1-log decrease in recoverable HIV-1 RNA, improved mitogen- and antigen-specific immune responses, and a large decrease in the IL-6 level while taking HCQ. Recent in vitro and in vivo assays in patients with HIV infection have shown similar antiviral and antiinflammatory effects from HCQ.

Conclusion: HCQ may exert simultaneous anti-inflammatory and antiviral effects in patients with HIV infection and inflammatory arthritis. If larger studies confirm this observation, it may be the drug of choice in this population of patients.

There have been many studies throughout the years, on the antiviral effects of hydroxychlorquine.

That's why it was even considered.

National Institutes of HealthU.S. National Library of MedicineNCBI

Effect of Chloroquine on Human Immunodeficiency Virus (HIV) Vertical Transmission
Michael Neely et al. Afr Health Sci. Aug 2003
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Abstract
Introduction: Over 2 million children globally are HIV positive. More than 90% are infected in utero from their mothers. Current pharmacological methods to reduce the rate of vertical transmission are too expensive for the developing world. Chloroquine, a cheap, widely available drug, has anti-HIV properties. We conducted a pilot study to determine if chloroquine can reduce HIV vertical transmission.

Methods: 287 samples of stored, frozen cord blood from a cohort of Ugandan infants born to HIV positive mothers were analyzed for concentrations of chloroquine and its two major metabolites, monodesethylchloroquine and didesethylchloroquine. The HIV status of each infant was determined by ELISA with Western Blot confirmation at 15 and 18 months of age.

Results: 49% of samples had measurable chloroquine or metabolite. Of those with measurable drug, the higher concentrations of chloroquine and its metabolites were more frequently associated with HIV negative infants. However, only the median concentration of didesethylochloroquine was significantly higher in HIV negative infants vs. HIV positive infants (1.6 ng/ml vs. 0.9 ng/ml, p=0.05).

Conclusions: Nearly half of all infants in a Ugandan cohort are exposed to chloroquine in the last trimester of pregnancy. Such random maternal chloroquine use may be associated with a decreased rate of HIV vertical transmission. The issue of maternal chloroquine use requires controlled study before any clinical conclusions may be drawn.

National Institutes of HealthU.S. National Library of MedicineNCBI

Targeting Endosomal Acidification by Chloroquine Analogs as a Promising Strategy for the Treatment of Emerging Viral Diseases
Md Abdul Alim Al-Bari. Pharmacol Res Perspect. 2017
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Abstract
Emerging viruses such as HIV, dengue, influenza A, SARS coronavirus, Ebola, and other viruses pose a significant threat to human health. Majority of these viruses are responsible for the outbreaks of pathogenic lethal infections. To date, there are no effective therapeutic strategies available for the prophylaxis and treatment of these infections. Chloroquine analogs have been used for decades as the primary and most successful drugs against malaria. Concomitant with the emergence of chloroquine-resistant Plasmodium strains and a subsequent decrease in the use as antimalarial drugs, other applications of the analogs have been investigated. Since the analogs have interesting biochemical properties, these drugs are found to be effective against a wide variety of viral infections. As antiviral action, the analogs have been shown to inhibit acidification of endosome during the events of replication and infection. Moreover, immunomodulatory effects of analogs have been beneficial to patients with severe inflammatory complications of several viral diseases. Interestingly, one of the successful targeting strategies is the inhibition of HIV replication by the analogs in vitro which are being tested in several clinical trials. This review focuses on the potentialities of chloroquine analogs for the treatment of endosomal low pH dependent emerging viral diseases.

Keywords: Chloroquine analogs; antiviral actions; endosomal pH and viral replication.

National Institutes of HealthU.S. National Library of MedicineNCBI

Review
Effects of Chloroquine on Viral Infections: An Old Drug Against Today's Diseases?
Andrea Savarino et al. Lancet Infect Dis. Nov 2003
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Abstract
Chloroquine is a 9-aminoquinoline known since 1934. Apart from its well-known antimalarial effects, the drug has interesting biochemical properties that might be applied against some viral infections. Chloroquine exerts direct antiviral effects, inhibiting pH-dependent steps of the replication of several viruses including members of the flaviviruses, retroviruses, and coronaviruses. Its best-studied effects are those against HIV replication, which are being tested in clinical trials. Moreover, chloroquine has immunomodulatory effects, suppressing the production/release of tumour necrosis factor alpha and interleukin 6, which mediate the inflammatory complications of several viral diseases. We review the available information on the effects of chloroquine on viral infections, raising the question of whether this old drug may experience a revival in the clinical management of viral diseases such as AIDS and severe acute respiratory syndrome, which afflict mankind in the era of globalisation.

Please note that these are all old articles.

National Institutes of HealthU.S. National Library of MedicineNCBI

Chloroquine Analogues in Drug Discovery: New Directions of Uses, Mechanisms of Actions and Toxic Manifestations From Malaria to Multifarious Diseases
Md Abdul Alim Al-Bari. J Antimicrob Chemother. 2015
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Abstract
Antimalarial drugs (e.g. chloroquine and its close structural analogues) were developed primarily to treat malaria; however, they are beneficial for many dermatological, immunological, rheumatological and severe infectious diseases, for which they are used mostly today. Chloroquine and hydroxychloroquine, two of the most fascinating drugs developed in the last 50 years, are increasingly recognized for their effectiveness in myriad non-malarial diseases. In advanced research, chloroquine and hydroxychloroquine have been shown to have various immunomodulatory and immunosuppressive effects, and currently have established roles in the management of rheumatic diseases, lupus erythematosus (different forms) and skin diseases, and in the treatment of different forms of cancer. Recently, chloroquine analogues have also been found to have metabolic, cardiovascular, antithrombotic and antineoplastic effects. This review is concerned with the lysosomotropic, anti-inflammatory and immunomodulatory mechanisms of chloroquine, hydroxychloroquine, quinacrine and related analogues, and the current evidence for both their beneficial effects and potential adverse manifestations in various diseases.

All medications, have contraindications.

Technology
Gilead Generates Street Skepticism Ahead of Covid-19 Results

By Cristin Flanagan
April 7, 2020, 7:34 AM EDT
Updated on April 7, 2020, 10:03 AM EDT

Remdesivir China data expected this month, U.S. results in May

Barclays sees 20% chance that Chinese studies will succeed

Bottles of Remdesivir at a hospital in Wuhan, China, in Feb.
Bottles of Remdesivir at a hospital in Wuhan, China

Results from a study of Gilead Sciences Inc.’s experimental Covid-19 medicine are top-of-mind for Wall Street as cases surpass 1.35 million and deaths approach 76,000.

With a potential vaccine more than a year away, Gilead’s antiviral remdesivir offers one of the nearest-term hopes for a treatment in the pandemic that’s sweeping across the globe and putting many countries, including most of the U.S., on lockdown.

Results from late-stage studies out of China are expected this month with results from U.S. trials following in May.

After the company’s valuation surged more than $20 billion from late January to early March, some Wall Street analysts are cautioning there may not be much more room for shares to gain. The stock has traded sideways since hitting a two-year high on March 6.

“We see a highly negatively skewed risk/reward,” Barclays analysts led by Carter Gould warned ahead of the April data.

They rate Gilead underweight.

Gilead reached a 23-month high in March on remdesivir optimism

Barclays is assigning a 20% chance that the two studies out of China --- one in patients with mild to moderate symptoms and another in the severely ill -- will succeed.

Even if the pair hit the mark, Gilead’s gains could lead to a sell-off on “the commercial realities facing remdesivir,” the analysts said. That could include a complex manufacturing process and the difficulties pricing and selling a drug for a global pandemic.

Shares of Gilead fell as much as 5.4% on Tuesday, the biggest intraday drop in almost two weeks as the broader market rallied.

Covid-19 patients in the placebo-controlled studies are likely getting treated after the virus has already reached the height of its powers in the body, instead of before when a treatment could potentially be more effective, Barclays said.

If the two studies fail, Gilead shares could fall back to the low-$60 range where they traded before the crisis.

Wall Street investors have been scrambling to position themselves ahead of the data. Gilead appeared not only as a top long pick for investors in 2020 but also among the top short picks in a JPMorgan Chase & Co. buy-side survey. Options data suggest the stock could swing 17% in either direction by May 1.

Bearish bets against Gilead peaked at $1.97 billion on March 19, according to data from financial analytics firm S3 Partners. The stock was ripe for a short squeeze two weeks ago but that’s no longer the case, S3’s Ihor Dusaniwsky said Monday. Gilead is still one of the top three largest short stories in the biotech sector with $1.77 billion, or 1.8% of its float, shorted as of Monday, he said.

Even the bulls have doubts about the upcoming data.

Evercore ISI analyst Umer Raffat, who has an outperform rating on the stock, said he expects the study in severely ill patients “may underwhelm,”

though he said remdesivir could help those who received the drug early enough in their course of treatment.

Optimism that Gilead has started ramping up production because it knows the medicine works is also unfounded, he said, noting management confirmed they haven’t seen results from the Chinese trials.

For antivirals, “it is NOT about the overall trial result,” Raffat said. “All that matters is being able to identify the time point post-infection until which you can initiate an antiviral and expect efficacy.”

als

I don't mean to cause any offense.

I'm so happy that you survived your ordeal.

And lived to dance another day.
And to enjoy eggnog whenever it suits you.

As always I hope you and your family stay safe.

Complications
Inflammation caused by lupus can affect many areas of your body, including your:

Kidneys. Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus.
Brain and central nervous system. If your brain is affected by lupus, you may experience headaches, dizziness, behavior changes, vision problems, and even strokes or seizures. Many people with lupus experience memory problems and may have difficulty expressing their thoughts.
Blood and blood vessels. Lupus may lead to blood problems, including anemia and increased risk of bleeding or blood clotting. It can also cause inflammation of the blood vessels (vasculitis).
Lungs. Having lupus increases your chances of developing an inflammation of the chest cavity lining (pleurisy), which can make breathing painful. Bleeding into lungs and pneumonia also are possible.
Heart. Lupus can cause inflammation of your heart muscle, your arteries or heart membrane (pericarditis). The risk of cardiovascular disease and heart attacks increases greatly as well.
Other types of complications
Having lupus also increases your risk of:

Infection. People with lupus are more vulnerable to infection because both the disease and its treatments can weaken the immune system.
Cancer. Having lupus appears to increase your risk of cancer; however the risk is small.
Bone tissue death (avascular necrosis). This occurs when the blood supply to a bone diminishes, often leading to tiny breaks in the bone and eventually to the bone's collapse.
Pregnancy complications. Women with lupus have an increased risk of miscarriage. Lupus increases the risk of high blood pressure during pregnancy (preeclampsia) and preterm birth. To reduce the risk of these complications, doctors often recommend delaying pregnancy until your disease has been under control for at least six months.

As you can see lupus can be extremely serious.
Not all patients experience all these complications.
It can range from mild to life threatening.

So, I ask, if hundreds of thousands of lupus patients can take hydroxychloroquine, without serious adverse effects, why will it be so detrimental to the general public?

Most COVID-19 Patients Placed on Ventilators Died, New York Study Shows
https://www.usnews.com/news/health-news/articles/2020-04-22/most-covid-19-patients-placed-on-ventilators-died-new-york-study-shows

Excerpts;

[i]"Among the 2,634 patients for whom outcomes were known, the overall death rate was 21%, but it rose to 88% for those who received mechanical ventilation..."

"Recognizing that complications from ventilator use can occur, some intensive care units (ICUs) have started to delay putting a COVID-19 patient on a ventilator until the last possible moment, when it is truly a life-or-death decision..."

"Ventilators do have side effects. Because a machine is breathing for them, patients often experience a weakening of their diaphragm and all the other muscles involved with drawing breath..."

"These patients also are at risk of ventilator-associated acute lung injury, a condition caused by overinflating the lungs during mechanical ventilation..."

"Ventilated patients also are at increased risk of infection, and many are at risk of psychological complications... A quarter develop post-traumatic stress disorder, and as many as half might suffer subsequent depression."

"The study, published online April 22 in the Journal of the American Medical Association, was conducted by the Northwell Health COVID-19 Research Consortium..."[/i]

For those who have lost loved ones to this disease, I feel your pain. It seems to go through nursing homes rapidly.

Dang, looks like both HQC and remdesivir may be ineffective. Exploring other meds, hope something works...