Coronavirus Treatment : Can an Hydroxychloriquine plus Zinc Work?

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Nelson Vergel

Nelson Vergel

Founder, ExcelMale.com
Old Drug: Chloroquine is a medication used to prevent and to treat malaria in areas where malaria is known to be sensitive to its effects.[1] Certain types of malaria, resistant strains, and complicated cases typically require different or additional medication.[1] It is also occasionally used for amebiasis that is occurring outside the intestines, rheumatoid arthritis, and lupus erythematosus.[1] It is taken by mouth.[1]

Common side effects include muscle problems, loss of appetite, diarrhea, and skin rash.[1] Serious side effects include problems with vision, muscle damage, seizures, and low blood cell levels.[1] It appears to be safe for use during pregnancy.[1][2] Chloroquine is a member of the drug class 4-aminoquinoline.[1] It works against the asexual form of malaria inside the red blood cell.[1]

It is almost impossible to find chloroquine but this version can be found easily: Hydroxychloroquine (Plaquenil®) is a 4-amino-quinoline antimalarial medication that is widely used to treat systemic lupus erythematosus (SLE), rheumatoid arthritis, and related inflammatory and dermatological conditions. It is a hydroxylated version of chloroquine, with a similar mechanism of action.

hydroxychloriquine dose for Coronavirus COVID 19.jpg

From:
In Vitro Antiviral Activity and Projection of Optimized Dosing ...
academic.oup.com › advance-article-pdf › doi › cid › ciaa237 › ciaa237


Zinc doses of 100 to 150 mg/day have been administered for certain patient groups for months with few adverse effects.2,10,35,36 Therefore, a zinc dose of some 80 mg/day for 1–2 weeks starting at the early symptoms of the common cold is unlikely to cause long-term adverse effects. Nevertheless, even though there is strong evidence that properly formulated zinc lozenges can shorten the duration of colds, the majority of zinc lozenges in the market seem to have either too low doses of zinc or they contain substances such as citric acid that bind zinc.8 Therefore, the findings of this study are not directly applicable to the wide variety of formulations of zinc lozenges on the market.

These are tablets of 50 mg: Zinc Supplement on Amazon

Zinc lozenges and the common cold: a meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage

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Can Zinc Help Fight Coronavirus (COVID-19)? - SelfHacked

Zinc supports immune health, but can it help with the new coronavirus? Get the latest science scoop here & find out if you should stock up.
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I highly recommend watching this great video made by pulmonologist Dr. Seheult of https://www.medcram.com where he reviews current data on chloroquine plus zinc.



 
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Nelson Vergel

Nelson Vergel

Founder, ExcelMale.com
drugs for coronavirus.jpg

picture for Science News


Looking to drugs for HIV and flu

One of the drugs already under study is the combination of two HIV medications: lopinavir and ritonavir (Kaletra). Kaletra stops viruses by interfering with the enzymes they need to infect cells, called proteases.

One study being done at the Guangzhou Eighth People’s Hospital in China is testing Kaletra against Arbidol, an antiviral drug approved in China and Russia to treat the flu. Two groups of patients will take the medications along with standard care. A third group in the study will receive only standard care, typically supportive therapy with oxygen and IV fluids that are meant to support the body so the immune system can fight off a virus on its own.

An Ebola drug gets a second look

One repurposed drug generating a lot of buzz is an experimental infusion called remdesivir (Xembify). It was originally tested against the Ebola virus. While it didn’t work for that infection, it has been shown to shut down the new coronavirus, at least in test tubes. It’s been given to a small number of COVID-19 patients already, including one in Washington state.

In order to have better evidence of how well it may work in people, two studies in Beijing are comparing remdesivir to a dummy pill to see if the drug can help patients with both mild and severe symptoms recover from their illnesses. Viruses work by infecting cells, taking over their machinery, and getting them to crank out more copies of the virus, which then goes on to infect more cells. Remdesivir is a mimic that fools a virus into replacing one of its four building blocks with a chemical fake. Once in the virus’s blueprints, the imposter acts like a stop sign that keeps the virus from copying itself.

Other kinds of drugs in the same class – called nucleotide analogs – are used to attack cancer and other infectious viruses like hepatitis.

Last week, Chinese scientists published study showing remdesivir was effective against the new coronavirus, 2019-nCoV. Out of seven drugs tested, only remdesivir and an older drug called chloroquine (Aralen), which is used to treat malaria, worked, at least in test tubes. “It functions like a knife that just cuts off the RNA strand,” says Mark Denison, MD, a pediatric infectious disease specialist at Vanderbilt University in Nashville. “They can’t replicate any more. It stops them from doing that.” Dr. Denison is part of a team of researchers in Tennessee and North Carolina that discovered remdesivir could stop coronaviruses, like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), in test tubes and animals. He has studied coronaviruses in his lab for 30 years. He knew they would pose a threat again. “We’re shocked, but not surprised, that this has happened again,” he says of the China-based outbreak of 2019-nCoV.

After the SARS outbreak, which infected more than 8,000 people in 26 countries during 2002-2003, and MERS, which has infected nearly 2,500 people in 27 countries since 2012, researchers knew they had to start looking for treatments that would work against coronaviruses. Dr. Denison reached out to Gilead Sciences, a company best known for its antiviral medications that treat HIV and hepatitis C, and asked it to send drug candidates for him to test on coronaviruses. “The idea was that we didn’t want a drug that would just work against SARS or MERS,” he says. “We wanted drugs that worked against every coronavirus.”

Many of the agents he tried didn’t work until Dr. Denison and his team knocked out the virus’s pesky proofreader. Remdesivir seems to be able to defeat the proofreader, though Dr. Denison admits that he does not know how the drug gets around a virus’s defenses. He has a grant from the National Institutes of Health to study that. Gilead has been giving remdesivir to “a small number” of coronavirus patients in the United States and Europe on a compassionate basis.

One of those patients was a 35-year-old man in Everett, Wash., who had gotten pneumonia after being infected with the new coronavirus during a trip to see family in Wuhan, China, the epicenter of the outbreak. His doctors started IV remdesivir on the evening of his 7th day in the hospital. On the 8th day, he improved. He was well enough to stop using oxygen. Signs of pneumonia were gone. He got his appetite back. His case was recently published in the New England Journal of Medicine, igniting a firestorm of interest in the therapy.

Unfortunately, though, even Dr. Denison says a single person’s case isn’t enough proof that the medication can treat the new coronavirus. The patient, who has not been identified, was getting expert care. He may have improved on his own, despite getting the drug. He said the challenge in people will be to find out two things: whether the medication can block the spread of virus in the body and whether it can reverse the disease. “You can remove the source of injury, but you still have the injury,” he said. Other important questions include how soon the drug may need to be given after infection for it work and whether it may cause significant side effects.

A promising pill

Another drug, a nucleoside analog, that appears to be able to defeat the coronavirus proofreader, EIDD-2801, was developed by Emory University in Atlanta. It was originally intended to treat the flu but has shown some effectiveness against coronaviruses like SARS and MERS.

The FDA recently reached out to Emory asking if it had any drug candidates that might work against the new coronavirus. “It’s a good shot on goal here,” says George Painter, PhD, CEO of Drug Innovation Ventures at Emory. EIDD-2801 can be taken as a pill, which makes it easier to use outside of a hospital setting.

“The capsules for the trial are being made at the end of this month. So we’re close,” Painter says. “We’re right on the edge.”

Source
 
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Nelson Vergel

Nelson Vergel

Founder, ExcelMale.com
University of California, San Francisco BioHub Panel on COVID-19
March 10, 2020

· Panelists

o Joe DeRisi: UCSF’s top infectious disease researcher. Co-president of ChanZuckerberg BioHub (a JV involving UCSF / Berkeley / Stanford). Co-inventor of the chip used in SARS epidemic.

o Emily Crawford: COVID task force director. Focused on diagnostics

o Cristina Tato: Rapid Response Director. Immunologist.

o Patrick Ayescue: Leading outbreak response and surveillance. Epidemiologist.

o Chaz Langelier: UCSF Infectious Disease doc


What’s below are essentially direct quotes from the panelists. I bracketed the few things that are not quotes.
· Top takeaways

o At this point, we are past containment. Containment is basically futile. Our containment efforts won’t reduce the number who get infected in the US.

o Now we’re just trying to slow the spread, to help healthcare providers deal with the demand peak. In other words, the goal of containment is to "flatten the curve", to lower the peak of the surge of demand that will hit healthcare providers. And to buy time, in hopes a drug can be developed.

o How many in the community already have the virus? No one knows.

o We are moving from containment to care.

o We in the US are currently where Italy was a week ago. We see nothing to say we will be substantially different.

o 40-70% of the US population will be infected over the next 12-18 months. After that level you can start to get herd immunity. Unlike flu this is entirely novel to humans, so there is no latent immunity in the global population.

o [We used their numbers to work out a guesstimate of deaths— indicating about 1.5 million Americans may die. The panelists did not disagree with our estimate. This compares to seasonal flu’s average of 50K Americans per year. Assume 50% of US population, that’s 160M people infected. With 1% mortality rate that's 1.6M Americans die over the next 12-18 months.]

§ The fatality rate is in the range of 10X flu.

§ This assumes no drug is found effective and made available.

o The death rate varies hugely by age. Over age 80 the mortality rate could be 10-15%. [See chart by age Signe found online, attached at bottom.]

o Don’t know whether COVID-19 is seasonal but if is and subsides over the summer, it is likely to roar back in fall as the 1918 flu did

o I can only tell you two things definitively. Definitively it’s going to get worse before it gets better. And we'll be dealing with this for the next year at least. Our lives are going to look different for the next year.


· What should we do now? What are you doing for your family?

o Appears one can be infectious before being symptomatic. We don’t know how infectious before symptomatic, but know that highest level of virus prevalence coincides with symptoms. We currently think folks are infectious 2 days before through 14 days after onset of symptoms (T-2 to T+14 onset).

o How long does the virus last?

§ On surfaces, best guess is 4-20 hours depending on surface type (maybe a few days) but still no consensus on this

§ The virus is very susceptible to common anti-bacterial cleaning agents: bleach, hydrogen peroxide, alcohol-based.

o Avoid concerts, movies, crowded places.

o We have cancelled business travel.

o Do the basic hygiene, eg hand washing and avoiding touching face.

o Stockpile your critical prescription medications. Many pharma supply chains run through China. Pharma companies usually hold 2-3 months of raw materials, so may run out given the disruption in China’s manufacturing.

o Pneumonia shot might be helpful. Not preventative of COVID-19, but reduces your chance of being weakened, which makes COVID-19 more dangerous.

o Get a flu shot next fall. Not preventative of COVID-19, but reduces your chance of being weakened, which makes COVID-19 more dangerous.

o We would say “Anyone over 60 stay at home unless it’s critical”. CDC toyed with idea of saying anyone over 60 not travel on commercial airlines.

o We at UCSF are moving our “at-risk” parents back from nursing homes, etc. to their own homes. Then are not letting them out of the house. The other members of the family are washing hands the moment they come in.

o Three routes of infection

§ Hand to mouth / face

§ Aerosol transmission

§ Fecal oral route



· What if someone is sick?

o If someone gets sick, have them stay home and socially isolate. There is very little you can do at a hospital that you couldn’t do at home. Most cases are mild. But if they are old or have lung or cardio-vascular problems, read on.

o If someone gets quite sick who is old (70+) or with lung or cardio-vascular problems, take them to the ER.

o There is no accepted treatment for COVID-19. The hospital will give supportive care (eg IV fluids, oxygen) to help you stay alive while your body fights the disease. ie to prevent sepsis.

o If someone gets sick who is high risk (eg is both old and has lung/cardio-vascular problems), you can try to get them enrolled for “compassionate use" of Remdesivir, a drug that is in clinical trial at San Francisco General and UCSF, and in China. Need to find a doc there in order to ask to enroll. Remdesivir is an anti-viral from Gilead that showed effectiveness against MERS in primates and is being tried against COVID-19. If the trials succeed it might be available for next winter as production scales up far faster for drugs than for vaccines. [More I found online.]

o Why is the fatality rate much higher for older adults?

§ Your immune system declines past age 50

§ Fatality rate tracks closely with “co-morbidity”, ie the presence of other conditions that compromise the patient’s hearth, especially respiratory or cardio-vascular illness. These conditions are higher in older adults.

§ Risk of pneumonia is higher in older adults.


· What about testing to know if someone has COVID-19?

o Bottom line, there is not enough testing capacity to be broadly useful. Here’s why.

o Currently, there is no way to determine what a person has other than a PCR test. No other test can yet distinguish "COVID-19 from flu or from the other dozen respiratory bugs that are circulating”.

o A Polymerase Chain Reaction (PCR) test can detect COVID-19’s RNA. However they still don’t have confidence in the test’s specificity, ie they don’t know the rate of false negatives.

o The PCR test requires kits with reagents and requires clinical labs to process the kits.

o While the kits are becoming available, the lab capacity is not growing.

o The leading clinical lab firms, Quest and Labcore have capacity to process 1000 kits per day. For the nation.

o Expanding processing capacity takes “time, space, and equipment.” And certification. ie it won’t happen soon.

o UCSF and UCBerkeley have donated their research labs to process kits. But each has capacity to process only 20-40 kits per day. And are not clinically certified.

o Novel test methods are on the horizon, but not here now and won’t be at any scale to be useful for the present danger.


· How well is society preparing for the impact?

o Local hospitals are adding capacity as we speak. UCSF’s Parnassus campus has erected “triage tents” in a parking lot. They have converted a ward to “negative pressure” which is needed to contain the virus. They are considering re-opening the shuttered Mt Zion facility.

o If COVID-19 affected children then we would be seeing mass departures of families from cities. But thankfully now we know that kids are not affected.

o School closures are one the biggest societal impacts. We need to be thoughtful before we close schools, especially elementary schools because of the knock-on effects. If elementary kids are not in school then some hospital staff can’t come to work, which decreases hospital capacity at a time of surging demand for hospital services.

o Public Health systems are prepared to deal with short-term outbreaks that last for weeks, like an outbreak of meningitis. They do not have the capacity to sustain for outbreaks that last for months. Other solutions will have to be found.

o What will we do to handle behavior changes that can last for months?

§ Many employees will need to make accommodations for elderly parents and those with underlying conditions and immune-suppressed.

§ Kids home due to school closures

o [Dr. DeRisi had to leave the meeting for a call with the governor’s office. When he returned we asked what the call covered.] The epidemiological models the state is using to track and trigger action. The state is planning at what point they will take certain actions. ie what will trigger an order to cease any gatherings of over 1000 people.


· Where do you find reliable news?

o The John Hopkins Center for Health Security site. Which posts daily updates. The site says you can sign up to receive a daily newsletter on COVID-19 by email. [I tried and the page times out due to high demand. After three more tries I was successful in registering for the newsletter.]

o The New York Times is good on scientific accuracy.



· Observations on China

o Unlike during SARS, China’s scientists are publishing openly and accurately on COVID-19.

o While China’s early reports on incidence were clearly low, that seems to trace to their data management systems being overwhelmed, not to any bad intent.

o Wuhan has 4.3 beds per thousand while US has 2.8 beds per thousand. Wuhan built 2 additional hospitals in 2 weeks. Even so, most patients were sent to gymnasiums to sleep on cots.

o Early on no one had info on COVID-19. So China reacted in a way unique modern history, except in wartime.


· Every few years there seems another: SARS, Ebola, MERS, H1N1, COVID-19. Growing strains of antibiotic resistant bacteria. Are we in the twilight of a century of medicine’s great triumph over infectious disease?

o "We’ve been in a back and forth battle against viruses for a million years."

o But it would sure help if every country would shut down their wet markets.

o As with many things, the worst impact of COVID-19 will likely be in the countries with the least resources, eg Africa. See article on Wired magazine on sequencing of virus from Cambodia.
 
Nelson Vergel

Nelson Vergel

Founder, ExcelMale.com
"
Many pharmacists across the world are working hard to keep up with therapeutic options for coronavirus / SARS-CoV-2 / COVID-19. This webpage was created to provide insights and resources for pharmacists helping to manage this pandemic. Take note that updates to the page will be made periodically as permitted and the content here may not be completely up-to-date as the situation is evolving quickly. Also beware that much of the data identified below is of relatively poor quality in terms of utility for determining what should be done in clinical practice.

Additionally, there are many potential COVID-19 therapies, I list several at the bottom, but do not discuss them in depth. Some of these can potentially lessen the cytokine storm associated with COVID-19 and help with managing acute respiratory distress syndrome (ARDS).

MOST IMPORTANTLY: Thus far no antiviral drug has been proven to work against COVID-19 in humans, although many randomized controlled trials are ongoing. Inclusion in this webpage is not an endorsement for use of any of these drugs for COVID-19."

www.idstewardship.com

Coronavirus (COVID-19) Resources For Pharmacists

This webpage is dedicated towards providing coronavirus (COVID-19) resources for pharmacists. Maintained By: Timothy P. Gauthier, Pharm.D., BCPS Supported By: Bassam Ghanem, Pharm.D., MS, BCPS Created: 14 March 2020 Last updated: 31 May 2021, update #268 – We are no longer updating this webpage...
www.idstewardship.com www.idstewardship.com
 
Nelson Vergel

Nelson Vergel

Founder, ExcelMale.com
From Harvard School of Medicine

BASIC VIROLOGY, IMMUNOLOGY, AND PATHOGENESIS:

  • SARS-CoV-2 is a new virus belonging to the Coronavirus family, which includes less pathogenic strains responsible for the common cold, as well as the viruses responsible for SARS and MERS. It is genetically related to the coronavirus responsible for the SARS outbreak in 2003; the closest identified relative was isolated from bats.

  • SARS-CoV-2 is spread primarily via droplet, though it can be aerosolized and can persist on plastic and stainless steel surfaces for up to 72 hours. Disinfectants with commercial concentrations of EtOH or H2O2 are effective.

  • Microscopically, the virus is a ssRNA+ enveloped virus with a helical capsid, coated with S protein ‘studs,’ which facilitate receptor binding and membrane fusion. S protein binds to the ACE2 receptor of type 2 pneumocytes.

  • People with severe COVID-19 have a cytokine storm and increased neutrophil migration to the lungs. Protection against reinfection is unclear; CD4+ Th1 and CD8+ cells both are part of the immune response to the virus.

  • Lymphopenia is seen in COVID-19, presumably due to bone marrow suppression by the antiviral response.

CLINICAL PRESENTATION OF COVID-19

  • Common symptoms: cough, fever, and fatigue; however, sputum, shortness of breath, myalgias, sore throat, headache, nasal congestion, and nausea/vomiting/diarrhea have also been reported.

  • The elderly and those with comorbid conditions (most clearly cardiovascular disease, respiratory conditions, and cancer) are at higher risk for a more severe disease course and death.

  • RT-PCR on respiratory samples is the current gold standard. Serologic antibody tests are undergoing FDA approval.

  • Common lab findings: ↓lymphocytes, ↓platelets, ↑CRP. Higher inflammatory markers seen in more severe disease.

  • Common chest CT findings: bilateral ground glass opacities, consolidations, and “crazy paving” patterns.

TREATMENT OF COVID-19

  • Clinical outcomes include mild disease, pneumonia, severe pneumonia, ARDS, and septic shock.

  • Case fatality rate estimated to be ~2%, but many cases likely remain undiagnosed.

  • Triage: Mild symptoms - ~14-day home quarantine. Only admit if there is significant risk of decompensation. Moderate to severe symptoms - admit to the hospital in an airborne isolation room. ICU level care necessary for advanced ventilatory support or support for 2+ organ systems.

  • Standard supportive measures: isolation, conservative fluid management; Possible supportive measures if comorbid conditions: empiric antibiotics, oseltamivir, bronchodilators; Advanced supportive measures: ventilatory support.

INVESTIGATIONAL THERAPIES AND VACCINE DEVELOPMENT

  • There are currently no FDA-approved treatments directed against COVID-19 at this time (3/18/20). A variety of therapies are under investigation, however. These include repurposing of antivirals (remdesivir, lopinavir/ritonavir), antimalarials (chloroquine/hydroxychloroquine), and immunosuppressive medications (tocilizumab), or transfusing antibodies against SARS-CoV-2 analogs/SARS-CoV.

  • It is expected that COVID-19 vaccine development will take a minimum of one year.
 
Nelson Vergel

Nelson Vergel

Founder, ExcelMale.com
A Consumer Guide to Coronavirus COVID-19 Data: Zoom Meeting Tomorrow

MONDAY, Mar 23, 2020 03:00 PM Central Time (US and Canada)

Long time HIV treatment activist and educator Nelson Vergel attempts to make sense of the deluge of information about COVID-19 in lay man's terms.

Join this Zoom Meeting from your phone or computer. No software needed.

https://zoom.us/j/766853275

This data review will be recorded and posted on this YouTube channel right after the meeting.
 
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