Coronavirus 2019, Covid19, SARS CoV2-19.
H. Robert Silverstein, MD, FACC for the Preventive Medicine Center
First principles. Simplicity.
This 2019 corona virus CoV2-19 is an RNA virus (as opposed to a DNA virus) with 30 proteins that is brand new. The word “virus” means “poison.” A human cell has 20,000 different proteins. Being an RNA virus, it is similar to hepatitis C; it is not a DNA virus like hepatitis B. There are 200 viruses that can cause the common cold and several of these are corona viruses. “Corona” is Latin for “crown” which is how the virus looks in the microscope as if it has an encircling crown. The specific CoV2-19 genetic RNA fact and its “spike” projections will affect anti-viral treatment design and decisions. CoV2-19 was detected by it having a new genetic sequence as recognized by GenBank—it may have been around for a thousand years, but it is just now discovered. The Chinese symbol for it is pronounced “wayGee” and means both “crisis” and “opportunity”: two sides of the same coin. The first known novel and important coronavirus was called SARS = Severe Acute Respiratory syndrome. There are only 2 known previous serious corona virus outbreaks: SARS and Middle East respiratory syndrome = MERS, the latter epidemic was smaller, but with a 1/3 (33%!) death rate!
This Covid19/CoV2-19 corona virus was originally named for its site of ORIGIN (Wuhan, China) as was the Ebola (a river in Zaire) virus, German measles, Rocky Mount spotted fever, Norovirus (Norwalk, Connecticut), and Spanish flu, etc. Corona virus 19/CoV2-19 was first documented mid-November, 2019, in China. Although the Chinese government is currently stating that the virus originated in the United States, almost certainly it originated in either what is called a live or “wet” market where wild animals are sold for food in Wuhan, China, or the virus escaped the research Wuhan National Biosafety Laboratory close to Wuhan, China: the latter is less likely. See the comment of world-famous virologist David Ho below. China notified the World Health Organization of this infection 12/31/19 saying “the (corona virus 19) disease is preventable and controllable” incorrectly at that time. 7 million people had been in and then left Wuhan to go else(every)where outside of China beginning December, 2019. Flights were completely stopped from Wuhan to the rest of China, but not elsewhere, during that period of time. China stated in January, 2020, that this corona virus could not be transmitted from person to person: that, too, was wrong. The first overseas CoV2-19 case was documented 1/15/20. The first USA case was found 1/21/20. The city of Wuhan, China, (not the whole country) lockdown began 1/31/20. The shutdown of immigration to the USA for non-Americans began 1/31/20. The virus is now in 185 countries of a total 195 countries in the world.
In 1348, the BLACK PLAGUE killed 1/3 to 1/2 (50%!) of the WORLD’s population. That was due to the bacteria Pasteurella or Yersinia pestis carried by the rat flea. The quite recent MERS = Middle Eastern Severe Respiratory disease was 33% lethal! For a more recent perspective, the 2009-2010 SWINE FLU H1N1 virus originated in Mexico when there was an open Southern USA border. The Swine Flu virus was in the United States 7 months before the government called it a national emergency and that was several months after it was named a pandemic by the World Health Organization/WHO. Learning from the past, the current national emergency was so named 2 months after the virus was first here 1/21/20 and several days after the WHO called it a pandemic. 61 million Americans contracted the 2009-2010 Swine Flu and 12,000 Americans died-currently the CoV2-19 number of deaths is 19,000 deaths. 34 million Americans have been affected by the 2019-2020 INFLUENZA virus (17 times plus more than the current corona virus). 400,000 with influenza have been hospitalized (10 times more than the current corona virus) and 35,000 have died (2 times more than the current corona virus). As further perspective, in 2015, Ian Goldin, an Oxford University professor, in his book The Butterfly Defect, warned of the risks of a “global pandemic in a modern, interdependent world”: no one in the USA federal/state/local governments and other governments, listened or prepared for the future thus affecting our ability to respond appropriately now. These are historical facts.
The FLU vs CoV2-19: the latter is more serious. See this comparison link.
There is no prior experience with this current CoV2-19 virus; it spreads relatively easily. That spread has slowed significantly in China. 95+% of the Chinese population did not contract the virus. In China, infectivity has decreased from 2 to 3 other people per infected case to 1.5 per case. In the beginning, the infection rate doubles every five days as documented with increased testing. New information from The USA Los Alamos Laboratory states that 5 people are infected per case. Social distancing is said to continue until at least 5/1/19. Multiple tests MAY be necessary to prove if a patient is infected. On 3/30/20 there was a report from Wuhan, China, of CoV2-19 corona virus re-infection. The information in the last two sentences is not yet fully confirmed.
As reported by Anthony Fauci, MD, Chief of the National Institutes of Health (NIH) Infectious Disease section, the current influenza virus is 0.1% lethal and this CoV2-19 virus is 3.4% lethal, although in Germany it was found to be 0.37% lethal. ONLY 5% will need the ICU. The true death rate is unknown because the actual number of infected is based on those tested and MANY more who have this infection but are not yet identified as they have not been tested and found. In 80% of the infected it will be a mild cold or flu. 25% may be asymptomatic carriers. The IMHE (Institute for Health Metrics and Evaluation) model that advises the Federal government on the coronavirus has been remarkably incorrect. This model predicted that over 121,000 Americans would be hospitalized by 4/1/20: the actual number is 31,142. The scariest predictions of lethality have NOT come to pass.
See also the more optimistic 3/25/20 Wall Street Journal article by Bendavid and Bhattacharya.
ENTRANCE of the virus is gained to the human body via a protrusion on the virus’s outside called a “SPIKE” that attaches to an enzyme called ACE2 in the human body. Interestingly that is an enzyme that is blocked by certain medications used in the treatment of high blood pressure; it has been reported that patients who are on a related blocker called an “ARB”, such as losartan, are resistant to the CoV2-19 virus infection by replenishing low levels of ACE2 IN CoV2-19. But there is debate about the safety of the use of ACE inhibitors and ARBs being either protective or harmful for CoV2-19 infection. https://www.thepmc.org/lib/corona-virus-4-10-20-and-forward/
SYMPTOMS initially are fever (50% in the beginning and later 90%), dry cough, mild shortness of breath, malaise, headache, reddish eyes (conjunctivitis), 30% will have loss of the sense of SMELL and TASTE, but much less of runny nose, diarrhea, or vomiting. X-Ray/thin slice CT SCAN findings show “ground glass” bilaterally in both lungs, no pneumothorax, lymphadenopathy, or effusions. 80% of non-severe cases have normal chest X-rays or CT scans. Chest ULTRAOUND can also visualize and follow the course of the CoV2-19 pneumonia. Incubation is 2 to 11 days, for an average of five days; that is, symptoms develop on average 5 days after exposure. Reports of NEUROMUSCULAR complications are an axonal peripheral neuropathy or a myopathy with elevated creatinine kinase muscle enzyme in the blood. Pathology showed widespread VASCULITIS in many organs, including striated muscle. These clinical features might be part of the corona virus infection more than just nonspecific complications of any severe illness. There was a report of a patient with olfactory neuropathy (disorder of smell).
Five of 206 patients in Singapore developed large-vessel strokes. Four of these patients had their strokes in the setting of critical illness and 3 were associated with hypotension/low blood pressure.
- Onset to recovery is 12-32 days. Patients at high RISK are over age 65, have high blood pressure, a d-dimer blood test greater than 1 mg/L, and have an adverse SOFA sepsis score. One is SAFE 3 days after having no fever + resolved respiratory symptoms + improved chest CT scan + 2 negative PCR tests for the virus separated by 1 day. Viral shedding can occur for up to 37 days after onset of symptoms. Viral RNA can persist in the blood for up to 29 days and does not correlate with symptoms. It is (medically) believed that that an ALKALINE cellular chemistry impedes the virus: that is thought to be a mechanism for how HYDROXYCHLORQUINE & AZITHROMYCIN work: increasing alkalinity inside the cell. Zinc sulphate is a part of that treatment regimen. There is far too much concern and publicity about the very infrequent although important irregular heartbeat potential (risk vs benefit) that should be observed for as opposed to the very high frequency disastrous effects of not treating corona virus infections with what has proven to be this very safe combination of medications. Here are the current Heart Rhythm Society recommendations:
- Electrocardiographic/QT interval monitoring:
- Hydroxychloroquine and azithromycin should be withheld in patients with baseline QT prolongation or with known congenital long QT syndrome. HRS states that QT prolongation is a very uncommon condition (“rare”) and unless known, in view of the seriousness of the need to treat a quite ill corona virus infected patient, this is very unlikely to be checked and is an unreasonable request at this point in time.
- Cardiac rhythm and QT interval should be monitored; however, this may be difficult in critically ill patients as frequent contact may need to be minimized. HRS says this is absolutely correct and is as just stated above.
- If QTc exceeds a present threshold of 500 msec, the drugs should be discontinued. HRS again states this is unlikely to be as important as the need to treat a quite ill corona virus infected patient and unnecessarily exposes the EKG technician who will be required to do the EKG.
- Correcting hypokalemia and hypomagnesemia: HRS says this ALWAYS a good idea.
- Potassium levels >4mEq/L
- Magnesium levels >2mg/dL
- Avoiding other QTc prolonging agents whenever feasible:
- These may include quinolones, antifungals, atypical antipsychotics, antidepressants and opioids, among others.
See, also, alkaline and dietary suggestions in the Preventive Medicine Center Considerations below.
As of 4/10/20, the population of the USA is 330 million Americans with 505,000 known CASES of CoV2-19; 17,000 have died from this disease. Some of these deaths labeled as due to corona virus are actually due other causes but the patient ALSO had a corona virus infection and so is counted as a corona virus death, even though was not be the actual cause of death. Worldwide there are 1,600,000 reported 2019 corona virus/CoV2-19 cases with 95,000 deaths: 5% of cases are labelled as “serious”. Documented risk factors for developing CoV2-19 are obesity, diabetes, air pollution, and asthma, … which are more prevalent in the African American and Latino communities. Europe, which is about the same size and population as the USA, is now the world-wide epicenter of corona cases and deaths. As of 4/9/30 Europe has 700,000 corona virus cases with 65,000 deaths. On 4/10/20 the USA death rate is 3.4 % vs 1.5% in South Korea and 4% in China. A report based on ANTIBODIES from GERMANY states that “One in Seven May Be Immune”: that reduces COVID lethality from 2% to 0.37%, still nearly 4 times that of of the flu. Early on, most of those cases in the USA were elderly nursing home residents in Washington state. Now New York state leads, followed by New Jersey. In the USA there are 500,000 FLU hospitalizations per YEAR, and 35,000 flu deaths per YEAR. Both the flu and CoV2-19 cause PNEUMONIA, “the old man’s friend”, and that is the usual cause of death for CoV2-19. It can affect the heart and elsewhere. 7500 Americans die of all causes every DAY normally.
Here is an article that discusses the POSSIBLE need for 44 days of LOCKDOWN to DEFEAT CoV2-19. This below article does NOT TAKE INTO ACCOUNT the diagnosis and treatment developments that are rapidly happening in the USA: ANTIBIOTICS, CELLULAR ALKALINIZATION, IMMUNE ENHANCEMENT, TRANSFUSED ANTBODIES, VACCINES, and INTERFERING RNA, etc. Gerard J. Tellis et al. “How Long Should Social Distancing Last? Predicting Time to Moderation, Control, and Containment of COVID-19”, SSRN Electronic Journal (2020). DOI: 10.2139/ssrn.3562996
Here is the plan for how Germany plans to REOPEN/ · the country after Covid-19: https://www.ifo.de/en/publikationen/2020/monograph-authorship/making-fight-against-coronavirus-pandemicsustainable
A COUGH can send infected droplets 15 feet. A strong SNEEZE can send infected droplets 25 feet. The virus can live in the air for three hours, on wet surfaces for three days, 24 hours on cardboard, and 3 days on plastic: after 45 minutes the viral count is reduced by half on copper. The half-life of the virus in infected droplets is 5 hours on stainless steel. The virus count decreases by half every 7 hours on plastic so that by day 2 there is only 1/100th of the original viral count on plastic.
In China, with their strong QUARANTINE and ISOLATION procedures, new cases have REPORTEDLY slowed to a trickle. This is exactly similar to the reaction of certain, but not all, USA cities to the 1918 SPANISH FLU that killed millions. This USA cities that most effectively “locked down” with what we now call “social isolation” had the best health and economic recoveries then. There is a major difference: once widespread testing, detection, isolation, and treatment begin, such isolation will be much less necessary in the USA. Presently, South Korea has been the best and most effective country in dealing with this infection by using strong QUARANTINE and GPS TRACKING of contacts: “acceptance of (relevant public) surveillance” is the key. Their success occurred with high frequency testing of the public, tracing of contacts of those who are test-positive, and treating based on risk profile. Israel has developed such a tracking app called Hamagen. Oxford University’s Professor Christopher Fraser developed a similar app that can also assist in reducing transmission and resurgence of CoV2-19 infections. South Korea has drive-through testing which is ramping up in the USA. Unfortunately, South Korea, Hong Kong and Taiwan are seeing a SECOND WAVE of CoV2-19 infections as infected returnees come back to these areas from elsewhere. False negative testing and re-infection may be possibilities. Sweden is not doing our strong social distancing. Korean S D Biosensor is now making 350,000 test a day and ramping up to 1.5 million tests a day to be exported to the USA and other countries.
An excellent WEBSITE to follow the virus world-wide is by 17-year-old self-taught prodigy Avi Schiffman: http://ncov2019.live/data . Johns Hopkins University website is also excellent. https://coronavirus.jhu.edu/map.html The website www.bing.com has excellent data. For optimism, check out the twitter of a garbage man whose handle I lost: it had 3 letters in caps at the end. Another fine source of information & perspective on CoV2-19 is Harvard’s infectious disease specialist Dr. Lindsey R. Baden of Brigham and Women’s Hospital.
Here is a link to what life is like in Wuhan, China:
A rather remarkable interview with world famous VIROLOGIST David Ho, MD
Here is a very MODERATE, EVENHANDED, optimistic yet sober STATISTICIAN’s perspective on this corona CoV2-19 virus:
A GENETECIST discusses what a virus is, what it does inside a cell, and what CoV2-19 is.
Stanford University EPIDEMIOLOGIST John IOANNIDIS, MD, has published a profound article that says that the USA and all other countries simply lack reliable evidence to draw accurate conclusions regarding the seriousness of CoV2-19 infections. This is because the vast majority of cases are MISSED due to limited testing availability of the general public so far. He states that “short term lockdowns may be bearable” with the implication that long-term lockdowns likely will not be tolerable because of “profound financial and social consequences”. I believe he is exactly correct.
In the American population there are 950,000 HOSPITAL BEDS, 45,000 ICU beds and
150,000 available VENTILATORS. Ventilators have 150 parts and those new to that manufacturing will need to become expert in production of all. Continuous positive airway Pressure = CPAP is a halfway step developed by the Mercedes F1 racing team that can reduce the need for ventilators. “…low sat’ “happy hypoxics” comfortably walking around did well with just high flow nasal cannulas and had no need for ventilators
Low cost compact ventilators designed by Southern Miss from hardware store parts now produced by Howard Industries can alleviate shortages and be used in various settings because of its size and ease of use. This new bag-based ventilator could be produced very quickly,” said Dr. Joe Campbell, Forrest General’s chief anesthesiologist.
Adapt sleep apnea machines: 4/8/20 scientists have developed a way to turn a sleep apnea machine into a ventilator to treat people with COVID-19. The modification of a Nippy3+ began at Leeds Teaching Hospitals at the University of Leeds. The modification is straightforward and involves changes to the device’s settings and reconfiguring the supply of oxygen so it flows to the face mask worn by the patient. The machine operates in a mode called CPAP: constant positive airway pressure. That means the pressure inside the mask is slightly raised, keeping the patient’s airway open and making it easier for them to breathe. It provides enriched oxygen of between 40 to 60 percent and because it is a modification to a device, it does not have to go through a full regulatory approval process. Last week, engineers at University College London and Mercedes announced that they had successfully reversed engineered a CPAP device that had widely been used in China. They said they have a device that has regulatory approval and can be rapidly manufactured. More information: A technical note written by the expert team has been submitted to MedRxiv, an online platform that allows researchers t orapidly disseminate important findings ahead of peer review. The technical note can be downloaded from AlphaGalileo: www.alphagalileo.org/DTControl … ntrol/Images/pdf.png
Based on a robust body of clinical evidence, including studies published in the New England Journal of Medicine, a TIDAL VOILUME of around 6 cc per kilogram of patient body weight is the general standard of care for patients with Acute Respiratory Distress Syndrome/ARDS as part of “lung-protective” ventilation. SNORKLE/diving MASKS are being adapted as respirators. Prone positioning & inhaled nitric oxide are recommended, but not steroids. However, some are using 60 mg/day PREDNISONE for 3 days, 40 mg for 2 days, and 20 mg for 1 day. MIT created an inexpensive and simple respirator using Ambu bags. A very experienced respirator designer puts already FDA approved parts together to make a simple respirator that avoids VILY = Ventilator Induced Lung Injury—yet to be cleared by the FDA:
COMING OFF THE VENTILATOR can be problematic. In 2017 FDA approved SUGGAMMADEX which reverses the effect of muscle relaxants differently. In a new U of Michagan study, Kheterpal et al compared the rates of serious lung complications in patients who received neostigmine vs sugammadex. The newer drug was associated with significantly reduced rates of complications.
“We saw a 37% decrease across all pulmonary complications and 55 % decrease in respiratory failure,” says Kheterpal. “In many practices, neostigmine is no longer used in high risk patients or procedures,” he says.
More information: Sugammadex versus Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications (STRONGER): A Multicenter Matched Cohort Analysis. Anesthesiology. (2020) DOI: 10.1097/ALN.0000000000003256
“Cough Sync” is a newly developed tool for aspirating thick lung secretions more effectively. 85% of medicines/pharmaceuticals are manufactured in China and India; all of USA’s required rare earth metals for manufacturing come from China.
TRAVEL bans have been set up by Saudi Arabia, Russia, Poland, Kenya, Morocco, Argentina, Brazil, Canada, Denmark, the Netherlands, Germany, the European Union, and many others as well as the quite appropriately, the USA beginning on 1/31/20. That quarantine was supported by the NIH’s infectious disease chief Dr. A. Fauci.
At the present time almost all of us feel OFF BALANCE because of the inability to find out if we are (+) or (-) for the CoV2-19. There has been a general LOSS OF JOY across the United States. Being “shut-ins” has led to “cabin fever.” The stock market is responding to FUD: fear, uncertainty, doubt—all of which translates as ANXIOUS UNCERTAINTY. And although I believe allowing oneself to panic is largely a personal responsibility, the nationwide information atmosphere seems responsible for predisposing the susceptible to panic. A psychiatrist trenchantly said this national stressor will make “those not well put together, go over the edge”. In balance, it must also be asked what will be the psychological and economic cost of not returning to our more normal lives sooner than the various quarantines permit? Domestic violence, drug usage, worsening diet, and suicide will increase. People will eventually adjust out of reason and/or necessity. It is important to be careful, but not to be paranoid.
Early on the CDC (Centers for Disease Control) did not allow TESTING development outside of its requirements. The recent CDC tests had a technical flaw and proved unreliable. Independent test development by D S Chugh, MD, of Washington state allowed the recognition of the first USA case of coronavirus 19/CoV2-19 on 1/21/20 which, remarkably, was in a teenager–as it was felt then and afterwards that those of that age group were relatively immune to the serious consequences of corona 19/CoV2-19. Despite initially being held back by CDC regulations, she eventually decided on her own correctly to develop accurate testing by NOT adhering to the guidelines. The CDC & FDA are reported to still be slowing acceptance and release of new innovative testing kits and those for home testing. WHO test kits were made available to lower income countries without testing capability, not the USA. Better PREPARATION for this current viral pandemic after the much more dangerous 2003 SARS, 2007 Zika, 2014 Ebola, and 2012 MERS crises could have been accomplished. The federal Pandemic Office was not eliminated as some suggest, but was merged with other governmental groups.
TINY IRON OXIDE NANOPARTICLES coated with SILICA have a strong affinity for the RNA genetic material inside the virus that causes COVID-19/CoV2-19.
Norwegian U of Science & Technology NTNU’s & St. Olavs Hospital’s new test uses the nanoparticles to extract RNA from a solution containing a sample from the patient. The solution contains substances that crack the virus open so that its RNA genetic material can be extracted.
“We can then identify the genetic code from the RNA and compare it to the coronavirus,” Bjørås said. The researchers tested the accuracy of their method by running tests from patients in parallel with commercial tests. Bjørås said the new method is more sensitive than commercial tests.
Bjørås said the lab at NTNU’s Department of Chemical Engineering that is making the magnetic particles can make 30-40,000 tests a day, a rate that can be increased after Easter. The plan is to scale up to be able to produce a minimum of 150,000 tests per week,
From Trends-In-Medicine 4/2/20: TESTING. The list of available/approved/cleared Covid-19 tests continues to grow. Most of the tests are laboratory or point-of-care tests for diagnosing Covid-19. The rapid 5-15 minute Abbott ID NOW test is starting to be used and even FDA Commissioner Stephen Hahn, MD, called it a game changer. It is a one-at-a-time test for individuals, not for larger populations. However, what is needed next is a serologic (ELISA) test that can detect who has been exposed to SARS-CoV-2 and developed antibodies – and therefore can’t get sick and can’t transmit the virus. Those are the people whose blood may be therapeutic and who could go back to work immediately. Dr. Deborah Birx said she has tasked researchers at the major universities in the country to develop a simple ELISA test, saying, “It is easy to do. In a day or two they could SCREEN AN ENTIRE HOSPITAL. I call on every university in every state to develop Elisas. You can buy antigens and controls online. Get to work to test healthcare communities in your state… Our universities can do that by Friday [April 3]. I put that challenge out to them. We are not waiting. We are asking for help now. It could happen this month if the universities help us.” She said this was done with HIV, and it is exactly the same concept and process for SARS-CoV-2. “
As published in Trends-In-Medicine 4/2/20: “Among the newest DIAGNOSTIC TESTS to be cleared:
- AusDiagnostics’ multiplex PCR assay, which can detect influenza, respiratory syncytial virus, and SARS-CoV-2, was granted a CE Mark for use in Europe.
- Avellino Labs’ AvellinoCoV2 test, which detects SARS-CoV-2 nucleic acid using oropharyngeal and nasopharyngeal swab samples, was granted emergency use authorization (EUA) by the FDA. The test can only be performed by Avellino’s CLIA laboratory.
- BGI Genomics/BGI Americas’ BGI Real-Time Fluorescent RT-PCR Kit, which can detect SARS-CoV-2 from bronchoalveolar lavage fluid and throat swabs in 3 hours, was granted EUA by the FDA.
- Luminex’s NxTAG CoV Extended Panel, a multiplex panel that can detect SARS-CoV-2 from nasopharyngeal swab samples, was granted EUA by the FDA.
- NeuMoDx Molecular’s SARS-CoV-2 Test Strip, which can deliver results in around 80 minutes and runs on the NeuMoDx 288 and NeuMoDx 96 molecular systems, was granted EUA by the FDA.
- Novacyt/Primerdesign’s Genesig Real-Time PCR assay, which can deliver results within 2 hours, was granted EUA by the FDA.
- Rendu Biotechnology’s SARS-CoV-2 nucleic acid detection kit, which can deliver results within 90 minutes, was given emergency approval by China’s National Medical Products Administration.
Among the tests still in development are: Cue Health got a $13 million grant from the U.S. Biomedical Advanced Research and Development Authority (BARDA) to create, validate, and gain approval for a fast and portable SARS-CoV-2 point-of-care test. GenMark Diagnostics got a grant for up to $749,000 from BARDA to develop and seek EUA for a diagnostic panel that combines a new SARS-CoV-2 viral target with the company’s ePlex Respiratory Pathogen panel.”
The current lack of preparedness was due to governmental and the wider society not having the necessary vision to understand the implications of what was happening then and then not preparing the appropriate response that could have been used now. CDC regulations are now updated. Now cities, states, and the private market are allowed independently to create their own testing. The Roche pharmaceutical company has developed a simplified and automated technology that will increase testing from 30 to 1,000 tests per day and Roche said it will be quickly able to upscale its production and distribution of this simpler and accurate CoV2-19 virus testing. AS ABOVE, ABBOTT has developed the ID NOW test that is a small, convenient, and easier to perform “point of care self-swab” that gives the answer in 5-15 minutes. Its disadvantage is that a one at-a-time test that cannot screen large populations effectively.
The PROPER SAMPLE culture areas are nasopharyngeal, oropharyngeal, and sputum samples, but not urine, blood, or stool. Companies that are making TEST KITS: ABBOT’s ID NOW is the quickest and most convenient presently. However, it only tests 1 sample at a time, so an army of those machines will be necessary at any one location. Cepheid is a quick test providing positive or negative results for the virus in 45 minutes. S D Biosensor of Korea is ramping up making test kits. GeneMatrix, Chembiao Diagnostics, Hologic, GenMark, Integrated DNA, Pharma Mar, Thermo Fisher are all developing tests. 3M is scaling up producing N95 face masks. Construction and other companies are donating their N95 mask and gown stockpiles while the federal government is shipping ventilators and other stockpiled necessities to infection hot spots.
“Pipeline: Investigations therapies of COVID-19/CoV2-19
Diana Ernst, RPh of MPR wrote on March 11, 2020:
“Currently, there are no antivirals licensed by the FDA to treat patients with COVID-19. While no specific treatment for corona 2019 (COVID-19/CoV2-19) is currently available, several therapies are being investigated globally.”
“A FIVE day treatment with CHLOROQUINE or HYDROXYCHLOROQUINE (Plaquenil) COMBINED with AZITHROMYCIN seems QUITE EFFECTIVE for COV2-19. An open-label study investigated hydroxychloroquine in hospitalized patients with confirmed COVID-19 at The Méditerranée Infection University Hospital Institute in Marseille, France. (The study was run by epidemiologist Didier Raoult, MD.) Patients received oral HYDROXYCHLOROQUINE 200 mg 3 times daily for 10 days (n=20) vs control group (n=16). Patients were age 12 years and older, and had PCR documented SARS-CoV-2 in nasopharyngeal samples at admission. Treatment with the antibiotic AZITHROMYCIN was also provided. The end point was virological clearance at day 6. (There have been no cardiac complications due to the medicine combination in an experience now exceeding1,000 patients.)
Results showed that by day 6 post-inclusion, 70% of HYDROXYCLOROQUINE-only treated patients were cured of the virus vs 12.5% in the control group (p =.001). At day 6, 100% of patients treated with hydroxychloroquine + AZITHROMYCIN was cured of the virus compared with 57.1% of patients treated with hydroxychloroquine only, and 12.5% of the control group (p <.001). A significant difference between the hydroxychloroquine and control groups was reported as early as day 3.” Similar results were found at the University of Minnesota.
High dose intravenous vitamin C 4-12,000 mg per day is already being used in New York hospitals.
COLCHICINE may reduce the lung inflammation.
IVERMECTIN is a safe single dose treatment effective in reducing the virus. The ScienceDirect journal, Antiviral Research, research from Monash U’s K Wagstaff, MD, in Melbourne, Australia. The approved and safe common anti-parasite Ivermectin has broad spectrum antiviral activity and is effective inhibiting the coronavirus that causes COVID-19. Ivermectin is an inhibitor of the COVID-19 causative virus (SARS-CoV-2) in the TEST TUBE. A single treatment was able to effect ∼5000-fold reduction in virus at 48h in cell culture.
AVIGAN (FAVIPIRAVIR): 14 days of the Japanese flu drug shortens the illness.
Trends-In-Medicine 4/2/20: TREATMENT: The drugs currently getting the most attention as a treatment for Covid-19 are hydroxychloroquine (HCQ) and chloroquine (with or without other medications, usually azithromycin). New developments with these include:
- A 62-patient Chinese study in preprint found: üCompared to control, there were significant improvements at Day 5 in time to clinical recovery (TTCR), cough (2.0 days vs. 3.1 days), and fever (2.2 days vs. 3.2 days). üPneumonia was improved in 80.6% of HCQ patients vs. 54.8% of control. üAll four patients who progressed to severe illness were in the control group.
- The White House reportedly is working on a platform using Oracle software to track patient outcomes with off-label drugs used to treat Covid-19 patients (mostly hydroxychloroquine, at least to start).
- New York has treated ~1,100 patients with HCQ, and Henry Ford Health System (along with 4 other Michigan sites) has treated another 800. Other drugs currently getting attention as treatments for Covid-19 include:
- Antibody-rich blood products taken from blood donated by people recovered from Covid-19.
- Antiviral – e.g., Gilead Sciences’ remdesivir. Data on two patients given this drug was reported. The first patient developed ALT elevation 3xULN and a rash, and remdesivir was discontinued on Day 4. The next day the patient became asymptomatic, and he was discharged on Day 14. The second patient was given a loading dose of remdesivir in the ICU on illness Day 15, followed by 9 days of maintenance treatment. He recovered completely and was discharged on Day 30.
- Convalescent plasma. · Hyperimmune globulin – GigaGen is working on this.
- IL-6 receptor inhibitors, e.g. tocilizumab
- Monoclonal antibodies – e.g., Brii Biosciences, Tsinghua University, and 3d People’s Hospital of Shenzhen which are collaborating on developing fully human neutralizing monoclonal antibodies against Covid-19. FDA. To speed development of potentially safe and effective treatments of Covid-19, the FDA set up a new program – the Coronavirus Treatment Acceleration Program (CTAP) – which uses all the tools the Agency has to help get therapies to patients quickly. Health and Human Services Secretary Alex Azar said, “As part of this new program, the FDA is cutting red tape, redeploying staff, and working day and night to review requests from companies, scientists, and doctors who are working toward therapies.” FDA staff in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) are providing regulatory advice, guidance, and technical assistance as quickly as possible. And the FDA is triaging requests from developers and scientists working on new drugs and biologics. Other drugs worth watching include:
- Fujifilm/Toyama Chemical’s Avigan (favipiravir) – The company started a Phase III trial in Japan of this antiviral flu drug, an RNA polymerase inhibitor, to see if it shortens Covid-19 recovery time. TRENDS-IN-MEDICINE April 1, 2020/Coronavirus
- NeuroRx and Relief Therapeutics’ aviptadil – The FDA gave the green light for the start of a Phase II trial of this erectile dysfunction drug to treat acute respiratory distress in Covid-19 patients.
- Roche’s Activase (alteplase, tPA) – An article, published in the Journal of Trauma and Acute Care Surgery, suggests that this stroke drug might be useful in Covid-19-associated acute respiratory distress syndrome (ARDS), particularly in patients who need a ventilator but can’t get one. Their reasoning: “The risk of adverse events…is far outweighed by the certainty of death in patients meeting the eligibility criteria for this treatment.” A 12-patient compassionate-use study is planned.
- Vitamin C – A meta-analysis of 8 studies, published in the Journal of Intensive Care, found that giving vitamin C to ICU patients on a ventilator reduced the length of time on the ventilator by 14% vs. control. The patients with the most benefit from vitamin C were those on the ventilator the longest. A person in good health maintains a normal plasma vitamin C level with an intake of ~0.1g/day. Critically ill ventilator patients may need much higher doses – grams/day.”
Preventive Medicine Center general suggestions and thoughts based on fact, judgment, reasoning, and experience:
Avoid MILK-DAIRY products 100 (100!!!) %. My belief is that ANY MILK-DAIRY thickens the mucus reducing clearance of the invading virus, allowing it to “settle in and invade.” It is my belief-knowledge that a single drop of any milk dairy begins this allergic type adverse pathway. It is 100% milk-dairy avoidance or incorrectly have as much as you want. SWEETS, including dried fruits, and juices except for Pom Wonderful pomegranate juice, function as sweets = sugar = reduce/immobilize immune functioning at multiple levels. Basically, consume an organic unprocessed whole foods diet, ideally “macrobiotic” grains-vegetables-beans-fruit-nuts-seeds = GVBfns. See the www.thepmc.org website for general wellness information + this paper + how to prevent and/or reverse where possible high blood pressure, diabetes, high triglycerides, overweight at the 95+% level and the need for open heart surgery, angioplasty.
Read http://williamspear.com/2020/03/12/covid-19/ Bill Spear’s summary letter on CoV2-19 & his Macrobiotics Primer: Bill states in a personal letter to me (minimally edited) 4/5/20: “As we know, the virus isn’t actually “living”, it’s just anxious to find a host in your lungs, and when it gets there all hell breaks loose. So, the real job of prevention is to strengthen the host’s blood supply to cells, i.e., alkalinity (HRS states that is similar to the hydroxychloroquine discussion above). My layman’s point of view is that just as the fatty outer coating is broken by sudsy, soapy wash (and stronger) externally, acidic blood breaks that cellular fatty wall internally releasing the cascade of inflammation and lung damage that ensues. Whether that’s accurate or not, relevantly I know of long- time macrobiotic people who are caring for CoV2-19 positive non-macrobiotic family members in the same house, and they all have experienced only very minor symptoms. That may not be causal insofar as their seeming “immunity” but such an interpretation is reasonable”-HRS agrees.
For cooking, rely on “The Changing Seasons Cookbook”. Make 1 recipe EXACTLY according to directions-avoid as many processed foods, and wheat products as possible therein. Organic miso, tamari, rice noodles are processed and acceptable/even desired. Take the recipe with you to the natural food store. Be sure to get the exact ingredients in that one recipe. Miso soup with kombu, millet + cauliflower, scallions and daikon; brown rice with pickled shiso are specifically recommended for now as is live refrigerated organic sauerkraut. CLEANING solutions: 4 teaspoons of bleach in a quart of water, 0.125% peroxide, 80% ethanol, and 75% isopropyl alcohol are effective cleaners that kill the virus.
MEDICINE, SUPPLEMENT, AND GENERAL CONSIDERATIONS HERE ARE TO BE SPECIFICALLY DECIDED ON BETWEEN YOU AND YOUR PHYSICIAN: These Preventive Medicine Center thoughts are “invitations to consider” and require your personal judgment. If there are questions or concerns, please contact the Preventive Medicine Center. Usual suggestions are that supplements be taken daily for 2 weeks and then 5 DAYS A WEEK thereafter. Chew gum to keep your throat lubricated in order to “wash out” the virus. For colds or CoV2-19: the PMC position is to take vitamin C 500 mg 3 times a day, and in treatment 1-6 grams IV vitamin C per day reduced respirator use 25%, vitamin D3 5.000 units a day 5 days a week, Immune Renew (a yeast based immune stimulating beta glucan) 2 twice a day (Host Defense & OM manufacturers) also have beta glucan immune stimulating products), as is Brewer’s yeast. AHCC 2 twice a day (as just said, 5 days a week) is the top selling supplement in Japan. Manuka honey has anti-bacterial and possibly anti-viral properties. Pau d’arco is an herbal anti-inflammatory as is nano-curcumin. Berberine functions similarly to metformin, spirulina is the origin of phycocyanobilin -> anti-inflammatory heme oxygenase production, & glucosamine. Singulair (montelukast) is a lung leukotriene inhibitor that reduces lung inflammation and is worth considering in the armamentarium. If you are taking high blood pressure medication, try to have it be an ARB (angiotensin receptor blocker such as losartan). If on cholesterol lowering medicine, Livalo/pitavastatin seems more beneficial than Crestor/rosuvastatin or Lipitor/atorvastatin. Personally, my guess is that the gout treatment medication allopurinol would be helpful for serious CoV2-19 infection.
An excellent air purifier company: https://www.airpurifiersandcleaners.com/sun-pure-sp-20-portable-air-purifier. Dulera inhaler for bronchial cough issues. Zantac (or Pepcid as famotidine once daily) is off market + Zyrtec (for complete histamine blockade) twice a day for nasal congestion. Immediate (!) use of these combined antihistamines can actually stop the development of “colds.” Fish oil is generally anti-inflammatory: Carlson’s Cod Liver Oil (2 teaspoons = “a swig”) once or twice a day. Elderberry capsules for further immune enhancement. For a bothersome cough for my patients I recommend elderberry syrup 2 tsp 3 times a day. Generic or trade Robitussin DM 2 teaspoons 3 times a day as necessary also only for a bothersome cough. For chest issues, the glutathione supporting antioxidant NAC 600 mg 2 or 3 a day. If there is a deep cough, in order to prevent scarring due to fibrosis/scarring consider taking anti-fibrosis serrapeptase 2 capsules three times a day. If there is bacterial invasion in the lungs = pneumonia development, antibiotics should be chosen based on sensitivity. HYDROXYCHLOROQUINE + AZITHROMYCIN would be the first choice. Otherwise, if treatment is begun without a culture, doxycycline + azithromycin would be my antibiotics of choice as they also have an anti-inflammatory effect.
Read the 2020 Progress in Cardiovascular Diseases article by Mark McCarty et al regarding nutraceuticals inhibiting NOX2, thereby stimulating type 1 interferon response via Toll Receptor 7 (TLR7). HO-1 (heme oxygenase-1) enhancement to treat RNA viruses. Discussed/ “recommended” in that article are alpha lipoic acid, sulforaphane, ferulic acid, resveratrol, spirulina (phycocyanobilin). EGCG as capsules or as green tea, with white tea for its high antioxidant content.
New vaccine platform for CoV2-19 4/8/20 by University of Bristol Edited for concision
COVID-19/CoV2-19 SPIKE PROTEIN mediates cell entry. Imophoron’s ADDomer-based vaccine presents exactly (just) these parts to the immune system, giving rise to SPECIFIC antibodies in order to neutralize the virus/protect against infection.
Most COVID-19 vaccines present the ENTIRE SPIKE to the immune system, which reacts by making antibodies. This usual approach RISKS inducing antibodies that bind to the WRONG parts of the spike and could make the disease even worse. In vaccines for SARS-CoV-1 (note “1”), this sometimes resulted in severe lung tissue damage. Imophoron’s vaccine presents only very SPECIFIC parts of the spike essential for cell entry and are much less prone to this risk.
This Imophoron ADDomer platform is a new, highly adaptable, easy-to-manufacture, rapid-response platform for vaccines to combat present and future infectious diseases. It is a synthetic, self-assembling, nature-inspired virus-like particle (VLP). This type of vaccine is extremely stable and requires no refrigeration, enabling unrestricted distribution world-wide.
Frederic Garzoni, Founder/CEO at Imophoron: “We … can design and roll-out potential vaccines in about two weeks …& contribute to resolving the major health and economic threats caused by emerging viruses such as COVID-19.”
More information: Charles Vragniau et al. Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display, Science Advances (2019). DOI: 10.1126/sciadv.aaw2853
AIM ImmunoTech: developing Ampligen, a broad-spectrum antiviral that will be tested as a potential treatment for COVID-19 in Japan. A significant survival effect was observed in a trial evaluating mice infected with the earlier Severe Acute Respiratory Syndrome (SARS) coronavirus.
Gilead: developing remdesivir, a broad-spectrum intravenous antiviral agent that is being investigated in a double-blinded, placebo-controlled study sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH). In addition, Gilead is initiating two phase 3 trials to evaluate the safety and efficacy of remdesivir in adults diagnosed with COVID-19, following a rapid review and acceptance by the Food and Drug Administration (FDA) of the investigational new drug filing for the novel antiviral.
Immunotherapies and other investigational therapies:
The Israeli company MIGAL (see further below) says it HAS A VACCINE that will be finalized in 2 weeks and ready for distribution in 80 days. J Craig VENTER, the team leader who first sequenced the human genome and an originator of chromosome insertion, has his own California institute that in all probability more quickly than anyone else in the USA will develop an efficient CoV2-19 testing and the relevant & an effective CoV2-19 vaccine. Distributed Bio/Dr Jacob GLANVILLE is using computational-guided immune-engineering to create an antibody that neutralizes the virus in 20 minutes. It binds the spot that the virus uses to gain entry into your cells. “We have generated extremely potent picomolar antibodies that block known neutralizing ACE2 epitopes, blocking the novel coronavirus-19 from infecting human cells.”
Algernon Pharmaceuticals: developing ifenprodil, an N-methyl-d-aspartate (NDMA) receptor glutamate receptor antagonist, which is being prepared for US clinical trials for COVID-19 based on results of an animal study that showed the investigational therapy significantly reduced acute lung injury and improved survivability in H5N1 infected mice.
CEL-SCI: developing an immunotherapy using LEAPS, a patented T cell modulation peptide epitope delivery technology, to stimulate protective cell-mediated T cell responses and reduce viral load.
Innovation Pharmaceuticals: developing brilacidin, a defensin-mimetic, that mimics the human innate immune system and causes disruption of the membrane of pathogens, leading to cell death. It has already been tested in humans in phase 2 trials for other indications.
Mesoblast Limited: investigating remestemcel-L, an allogeneic mesenchymal stem cell (MSC) product candidate, as a treatment for patients with acute respiratory distress syndrome caused by COVID-19. Remestemcel-L, which is comprised of culture-expanded MSCs derived from the bone marrow of an unrelated donor, is administered in a series of intravenous infusions and is believed to have immunomodulatory properties to counteract inflammatory processes.
Q BioMed: partnering with Mannin Research to develop a potential treatment that addresses vascular leakage and endothelial dysfunction, which may potentially help patients with severe cases of COVID-19.
Takeda: developing an anti-SARS-CoV-2 polyclonal hyperimmune globulin (H-IG) to treat high-risk individuals with COVID-19 (TAK-888). Pathogen-specific antibodies from plasma will be collected from recovered patients (or vaccinated donors in the future) and will be transferred to sick patients to improve the immune response to the infection and increase the chance of recovery.
Tiziana: developing TZLS-501, which has been shown to rapidly deplete circulating levels of interleukin-6 (IL-6) in the blood, a key driver of chronic inflammation. Excessive production of IL-6 is believed to be associated with severe lung damage observed with COVID-19 infections.
University of Pittsburgh in EBioMedicine “Band Aid” Vaccine
Researchers at the U of Pittsburgh published in EBioMedicine has created a mouse tested and easily scalable vaccine for coronavirus-19 that is “delivered through a fingertip-sized patch” with “a microneedle array” that would inject the vaccine through 400 small needles applied like a Band-Aid. The vaccine created “a surge of antibodies” sufficient to eliminate the coronavirus but hasn’t been followed long term. This U of P vaccine has potential advantages over the vaccine being tested developed by Moderna which uses a more experimental method. This U of P vaccine was developed along the line of the flu shots, “using lab-made pieces of viral protein to build immunity.”
From Trends -In-Medicine: Altimmune Inc: developing a single-dose, intranasal vaccine against COVID-19 using its proprietary NasoVAX technology. The vaccine is moving toward animal testing.
Applied DNA Sciences: collaborating with Takis Biotech to develop a DNA vaccine candidate using PCR-based DNA (“LinearDNA”) manufacturing systems; preclinical testing in animals is expected to begin in the second quarter of 2020.
Codagenix Inc: co-developing a live-attenuated vaccine with the Serum Institute of India using viral deoptimization.
GlaxoSmithKline: collaborating with Clover Biopharmaceuticals to develop a protein-based corona virus vaccine candidate (COVID-19 S-Trimer) using Clover’s proprietary technology (Timer-Tag©) and combining it with GSK’s pandemic adjuvant system.
Inovio Pharmaceuticals: developing a DNA vaccine (INO-4800) to address COVID-19; human trials to begin in the US in April.
Johnson & Johnson: partnering with the Biomedical Advanced Research and Development Authority (BARDA) to develop a vaccine using Janssen’s AdVac® and PER.C6® technology, which provide the ability to rapidly upscale production of an optimal vaccine candidate.
Moderna Inc: vials of the Company’s mRNA vaccine (mRNA-1273) have been shipped to the National Institute of Allergy and Infectious Diseases to be used in a phase 1 study in the US.
Novavax: currently evaluating multiple recombinant nanoparticle vaccine candidates in animal models; initiation of phase 1 testing is expected in late spring of 2020. The COVID-19 vaccine candidates will likely include the saponin-based Matrix-M™ adjuvant to enhance immune responses.
Sanofi: collaborating with BARDA to develop a vaccine using Sanofi’s recombinant DNA platform. The DNA sequence encoding the antigen will be combined into the DNA of the baculovirus expression platform and used to produce large quantities of the coronavirus antigen which will be formulated to stimulate the immune system to protect against the virus.
*This list is not all inclusive.
Israel: a Covid 19/CoV2-19 VACCINE
by Howard Richman 3/15/20
“Israeli scientists at the MIGAL Galilee Research Institute had worked for four years and had successfully developed a Coronavirus vaccine for chickens which passed clinical trials. When they saw the genetic sequencing of the COVID-19 virus, they realized that they could quickly adapt their chicken vaccine to the human virus. Ella Dagan, a spokesman for MIGAL told Europorter:
When the genetic sequence of the new coronavirus COVID-19 was published, the researchers realized that the two viruses have the same infection mechanism similarities so they can use it, with small amount of adaptation, to achieve an effective human vaccine in a very short period of time.
Dr. Shahar, one of the scientists told nocamels.com:
It’s a little bit like fate that we were working on this coronavirus vaccine at the same time that the world was suddenly hit by this epidemic of coronavirus for humans.
MIGAL created its vaccine by synthesizing two proteins. Unlike vaccines that are created by injecting a dead or weakened disease-causing virus, there is little danger that synthetic virus protein segments will give patients a disease.
Its vaccine creates antibodies in the mucosal immune system of the body which consists of thin permeable barriers to infection in the lungs, gut, eyes, nose, throat, uterus, and vagina. Dr. Chen Katz, MIGAL’s biotechnology group leader, gave Europorter a detailed cellular-level description of how MIGAL’s vaccine works:
The scientific framework for the vaccine is based on a new protein expression vector, which forms and secretes a chimeric soluble protein that delivers the viral antigen into mucosal tissues by self-activated endocytosis (a cellular process in which substances are brought into a cell by surrounding the material with cell membrane, forming a vesicle containing the ingested material), causing the body to form antibodies against the virus.
Israel’s Minister of Science and Technology, Ofir Akunis, is expediting the human vaccine through Israel’s approval process. According to Europorter:
The minister has instructed the Director General of the Ministry of Science and Technology to fast-track all approval processes with the goal of bringing the human vaccine to market as quickly as possible.
Dr. Katz of MIGAL told Times of Israel that Israel’s approval process only involves about two months of actual testing:
The clinical testing experiments themselves are not so long, and we can complete them in 30 days, plus another 30 days for human trials. Most of the time is bureaucracy — regulation and paperwork.
CEO David Zigdon of MIGAL told Europorter that MIGDAL’s goal is to get their vaccine approved in just three months:
Given the urgent global need for a human Coronavirus vaccine, we are doing everything we can to accelerate development. Our goal is to produce the vaccine during the next 8-10 weeks, and to achieve safety approval in 90 days.
There are at least two American COVID-19 vaccines in the works:
- Moderna Therapeutics has developed a synthetic virus vaccine made from mRNA and has gotten it approved by NIAID (National Institute of Allergy and Infectious Diseases) for testing with human subjects. Those tests began until April.
- Regeneron Pharmaceuticals will soon have a treatment that will serve as a vaccine for those who don’t have coronavirus and a treatment for those who do. They will inject corona virus antibodies directly into the bloodstream instead of relying upon a vaccine to create those antibodies. They used a similar treatment to prevent and cure Ebola.
The Israeli government could approve the Israeli vaccine in as little as three months. President Trump may have to intervene in order to get NIAID moving just as fast with an American vaccine.”
These are thoughts as of 4/10/20