04/08/2020:
* testing for new infections  - the U.S. has been tragically slow to get this going.
* Testing for antibodies show who has recovered and acquired immunity.
  Recovered cases may allow us to start getting back to business. Good News on this front!
* Vaccines - when?
* Update 4/9/2020: A link to detailed discussion of treatment Remdesvir and a vaccine from Novavax

04/06/2020: The Science of the SARS2-CoV-2 virus
* The genetics of SARS-CoV-2 and how it should affect everyone's responses
* Latest news of treatment: Remdesivir and Hydrochloroquine
* Quick news: You have an 3 extra months to file Federal and Vermont income taxes. To speed up your $1,200 one time (?) Federal payment, set up direct funds transfer to your bank and be sure you have filed taxes for either 2018 or 2019. Register at https://www.eftps.gov/eftps/

 04/03/2020:  What comes next?
* When and how can we expect this to end?
* LATEST NEWS!   Gilead's remdesivir OK'd in Europe for compassionate use in COVID-19
2:31 pm, Fri, Apr. 3, 2020. Whether or not this means it is effective as opposed to just safe is still a question.

3/24/2020: The Pandemic in Vermont.
*  Worldwide spread is just getting going: 
*  New York's cases are rapidly accelerating - should we keep New Yorkers out of Vermont?
*  Vermont's rural culture of mutual help and caring for each other helps to slow the spread.
*  We don't really know how many are infected; people without symptoms can be infectious carriers.
*  Economic consequences in small town Vermont.
*  Social isolation, flattening the curve to reduce deaths and give our medical delivery systems time to catch up.
*  Avoiding contagion: recommended precautions and understanding the virus
*  Recommended cleaners and disinfectants
* Where and how did COVID-19 start? A quick look.

04/08/2020:
* testing for new infections and recovered cases may allow a gradual re-start of economy
* Vaccines - when?
* Update 4/9: Novavax (NASDAQ:NVAX) announces that it has identified a coronavirus vaccine candidate, NVX-CoV2373. A Phase 1 study in ~130 healthy volunteers will launch in mid-May. Safety and preliminary immunogenicity data should be available in July.
* Update 4/9: A detailed discussion on Remdesivir's efficacy and early implementation as a treatment.

Testing for active infections
     PCR tests, which look for genetic material related to the virus, indicate an active infection. More widespread testing than is now available would identify new cases before they show symptoms. Individuals testing positive could be quarantined, and their contacts traced and tested. This would greatly slow the spread of the virus. At present, the U.S. still requires active symptoms of COVID-19 and/or a note from a doctor before a test can be administered.
     Some version of these tests have been in use worldwide since the outbreak started. The U.S. has been slow to make the supply of such tests widely available. One problem has been rules that required test kits to be developed by the U.S. Centers for Disease Control, with a centralized distribution. In Germany, where early and widely available testing was implemented, a high infection rate has been accompanied by a very low death rate. Germany has a decentralized production and distribution of tests. They are currently (April 2) testing more than 50,000 people a day. South Korea was also one of several countries that rapidly made test kits available.

What you can do: Call your senators and representatives, and flood the White House with demands that the U.S. government immediately implement a unified, national program of testing, instead of the state-by-state policy that has the states competing for kits (and protective gear).

Antibody testing will get many of us back to work much faster.
     The next step in national and global recovery will be widespread testing for antibodies. Antibodies are made by our immune system to respond to a specific pathogen, like a bacterium or virus. If you get sick from a germ and you get better, you now have antibodies that your immune system created for the specific invader. Next time the virus attacks, these antibodies are ready to shut down the infection before it does any real damage.
     Scientists believe that antibodies to SARS coronaviruses are retained for a fairly long time. Recovered patients will likely retain their immunity long enough for us to develop a vaccine. So far, it does not look like the SARS-Cov2 virus is evolving very fast, so antibodies, created either by infection and recovery or a vaccine, will probably remain active for an extended period, thus protecting the person who has them.
     When we have an accurate, rapid, and widely available test for the SARS-CoV2 virus, we can identify all those of who were infected and recovered. These people can safely return to life as usual. Right now, anyone who was sick, tested positive for corona virus, and recovered, can probably resume all their activities.
     
     Scientists appear to be making rapid progress in developing an antibody test. On APRIL 3, 2020, the FDA granted Emergency Use Authorization (EUA) for the qSARS-CoV-2 IgG/IgM Rapid Test, made by Cellex Company (Durham, NC). This the first antibody test for COVID-19.
     The test measures immunoglobulins G and M antibodies against SARS-CoV-2 in serum, plasma or venipuncture whole blood samples. It measure a the strength of a patient’s acquired immune response to the virus that causes COVID-19. The serological test uses only a couple of droplets of blood and a small strip, similar to blood glucose monitors. Results should be available in about 20 minutes.
It is available only by prescription.
     The FDA warned that it may not be able to detect virus very early in the course of infection.
https://www.idse.net/Covid-19/Article/04-20/New-SARS-CoV-2-Antibody-Test-Other-Diagnostics-Receive-EUAs/57838

A vaccine for SARS-CoV-2 - the end of the pandemic, but when?
      CEPI - the Oslo, Norway-based Coalition for Epidemic Preparedness Innovations - had already signed funding agreements with three groups racing to develop vaccines by the third week of January. Since then, its portfolio has grown to eight, with more on the way.
     The organization has raised $430 million toward its $2 billion funding goal. Norway recently announced it is providing roughly $220 million. The pharmaceutical giants Sanofi, Pfizer and Johnson & Johnson are working on vaccine candidates.
     J&J and Sanofi are working with BARDA (the U.S. Biomedical Advanced Research and Development Authority), which will develop vaccines to address U.S. requirements. These vaccines can also be manufactured outside the United States and they can contribute to a global solution. However, many the companies capable of developing a vaccine have had some negative experiences developing them in the past.

     It will take a lot of government money to support the multi-billion dollar research. Drug makers “have very clearly articulated that … the current way of approaching this — to call them during an emergency and demand that they do this and that they reallocate resources, disrupt their daily operations in order to respond to these events — is completely unsustainable,” said Richard Hatchett, CEO of CEPI. The only real expertise in the world to make these vaccines in quantity in a safe environment is in the private sector. 
     After developing vaccines, the companies often face a public that has lost interest in using them, leaving the developers with vast and expensive unused inventory. Public perception of the costs and burdens on companies and the commitments of national governments will have to support any successful effort.

     This time around, governments, especially in the U.S., will have to provide adequate guarantees to the developers of a successful vaccine. Hatchett say that if we want vaccines as fast as we possibly can and we don’t want to compromise safety, i.e. we want to have a rational clinical development program, we’re going to have to take an awful lot of financial risk, which means investing in manufacturing capacity for everything, scaling it up right now, and even beginning full-scale manufacturing before we know if the vaccine even works.
A lot of platforms are going to fail because that’s just been the experience with vaccine development.
https://www.statnews.com/2020/04/07/pandemic-expert-calls-for-making-coronavirus-vaccines-before-we-know-they-work/

March 16, 2020: The National Institute of Allergy and Infectious Diseases (NIAID) is funding a trial of a vaccine called mRNA-1273 at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle. The open-label trial will enroll 45 healthy adult volunteers ages 18 to 55 years over approximately 6 weeks. The first participant received the investigational vaccine on March 16.
     The vaccine was developed by NIAID scientists and their collaborators at the biotechnology company Moderna, Inc., based in Cambridge, Massachusetts. The study is evaluating different doses of the experimental vaccine for safety and its ability to induce an immune response in participants.
https://www.niaid.nih.gov/news-events/nih-clinical-trial-investigational-vaccine-covid-19-begins

04/06/2020: The virus that is causing the COVID-19 pandemic is much more infectious than its closest genetic relative, the SARS virus that caused the pandemic in 2003-2004. 
 
     During the 2003 SARS pandemic, a total of 8,098 people worldwide became sick. Of these, 774 died. In the United States, only eight people had laboratory evidence of SARS-CoV infection. All of these people had traveled to other parts of the world where SARS was spreading. SARS did not spread more widely in the community in the United States.

     By comparison, 1,289,380 cases have been identified worldwide as of April 6 at 11:30 AM EDT, along with 270,372 recovered and 70,590 deaths.

     The new virus is approximately 98% identical to the original SARS-CoV of 2003; both are believed to have originated in bats.

     The big difference with the SARS2 virus is the little spikes that cover the surface. These spikes allow the virus to connect to the target cell and break through the cell membrane. Like similar viruses, SARS2 needs to find a substance in the host cell to accomplish this. Several human organs, including the lungs, intestines, and liver, and heart contain an enzyme called Furin, which binds to the viral spikes and provides this function very effectively. SARS-CoV and coronaviruses in the same family do not have the same furin activation site.

     People most likely to develop severe forms of COVID-19 are those with pre-existing illnesses and the elderly, according to data from China in February. While less than 1 percent of people who were otherwise healthy died from the disease, the fatality rate for people with cardiovascular disease was 10.5 percent. That figure was 7.3 percent for diabetes patients and around 6 percent for those with chronic respiratory disease, hypertension, or cancer. About 1 percent of cases overall have been fatal so far.

     SARS2 virus is a more efficient and powerful pathogen. It takes much less of it to successfully overwhelm a naive host's immune defenses than previous viruses. This is why it is spreading so quickly. 
     It can also cause an exaggerated immune response, which can be life threatening. Some people—especially the elderly and sick—may have dysfunctional immune systems that fail to keep the response to particular pathogens in check. This could cause an uncontrolled immune response, triggering an overproduction of immune cells and their signaling molecules.
More on this topic.

     Because this new virus is such a perfect predator, the calls for continued distancing and the use of masks must be heeded. You can spread the virus by talking and breathing, not just sneezing and coughing. Six feet is enough distance for the droplets of saliva and mucus in everyone's breath to fall out of the air, although dry mists of finer particles (aerosols) can spread it farther than that.  For this reason, it is also important to wear some kind of mask to keep your breath, sneezes, and coughs close to you.  

     Masks don't do very much to protect you.  They protect other people in your general vicinity.  You can infect others even if you feel fine and have no signs of illness. especially if you come into close contact with anyone who goes out in public, or has a high risk job (police, medical, food stores, social service, corrections and inpatient medical services), WEAR A MASK if you are anywhere close to other people!
How far does the virus travel in the air?  Perhaps this will convince you. Read
 https://www.theatlantic.com/health/archive/2020/04/coronavirus-pandemic-airborne-go-outside-masks/609235/   All about masks!
    
Further reading:
The science:
https://www.nature.com/articles/s41418-020-0530-3
https://www.sciencedirect.com/science/article/pii/S0042682212004187
https://www.medicalnewstoday.com/articles/why-does-sars-cov-2-spread-so-easily
https://www.livescience.com/coronavirus-can-spread-as-an-aerosol.html
The complete genome and structure with nice illustrations (if you really want to know):
https://www.nytimes.com/interactive/2020/04/03/science/coronavirus-genome-bad-news-wrapped-in-protein.html?utm



Treatment: medicines to kill the virus and treat the symptoms

     An effective drug that gets people out of hospitals faster will help reduce the burden on health care systems. Knowing there is something that can aid people who do get sick could also help countries feel more comfortable reopening their economies. In a way, effective therapies can buy the world time before a vaccine is approved. The two most widely discussed candidates have been Choroquine & Remdesivir,

CDC report on Choroquine & Remdesivir
https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html

     Remdesivir is an investigational intravenous drug with broad antiviral activity that inhibits viral replication. It is currently in trials worldwide. Some patients have experienced nausea, vomiting, rectal bleeding, and elevated liver enzymes.
     Chloroquine has been used to treat Malaria and autoimmune disorders such as rheumatoid arthritis, lupus, and psoriasis. Few, relatively small trials have been conducted to evaluate its effectiveness in treating COVID-19, indicating that it is effective. It can produce a large number of potentially serious side effects.

Chloroquine:
     Chloroquine has been used for malaria treatment ; hydroxychloroquine is used for treatment of rheumatoid arthritis and lupus. Both drugs have in-vitro activity against SARS-CoV, SARS-CoV-2, and other coronaviruses, with hydroxychloroquine having relatively higher potency against SARS-CoV-2.
     Hydroxychloroquine has been administered to hospitalized COVID-19 patients on an uncontrolled basis in multiple countries, including in the United States. One small study reported that hydroxychloroquine alone or in combination with azithromycin reduced detection of SARS-CoV-2 RNA in upper respiratory tract specimens compared with a non-randomized control group but did not assess clinical benefit (improvement in blood oxygenation and reduction of fever). No large controlled clinical trials have been done.

     Chloroquine is know to have a long list of potentially serious side effects, including back, leg, or stomach pains, darkening, blistering, peeling, or loosening of the skin, problems with vision such as difficulty in focusing the eyes and possible eye damage, chest discomfort or pain, irregular or pounding heartbeat, and potentially serious problems including heart failure (high doses), hair loss, diarrhea, permanent loss of visions, and many more.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/009768s041lbl.pdf 

Chloroqine trials in France:
     In a small French clinical trial of COVID-19 patients, 70% of 20 patients treated with hydroxychloroquine had a significant reduction in the virus within 6 days compared to 12.5% of untreated controls. A Chinese study conducted in 30 patients showed no significant differences between patients treated with 400 mg per day and controls (N=15).

     A study was conducted at the University Hospital Institute Méditerranée Infection in Marseille, France. 80 patients patients received treatment with hydroxychloroquine and azithromycin (to control opportunistic bacterial infections). 81.3% of patients had favourable outcome and were discharged. The study reports that adverse events were rare and minor.
https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdf .
     This study did not include a control group treated with placebo, and as such is only a proof of concept.

Controlled clinical trials, China
     The study was small and limited to patients who were mildly or moderately ill, helped to speed the recovery of a small number of patients who were mildly ill from the coronavirus, doctors in China reported this week. earlier reports from France and China drew criticism because they did not include control groups to compare treated versus untreated patients.
     The new study, of 62 patients with an average age of about 45, did have a control group. None of the treated group became severely ill, vs 4 in the control group. This resuslt may be due to Hydrochloroquine's ability to dial back the immune system, which is why it is used for autoimmune disorders. Severe immune reactions are involved in the worst coronavirus cases, resulting in organ damage and death.
https://www.nytimes.com/2020/04/01/health/hydroxychloroquine-coronavirus-malaria.html



Remdesivir
     This month (April 2020), the world should get the first results from a clinical trials in China. The drug is designed to interfere with the process the virus SARS-CoV-2 uses to make copies of itself. The resulting copies of the virus lack their full RNA genome, so they can’t go on to replicate themselves or infect other cells.

     Results from the China studies could signal whether the drug is effective. Results may come as soon as mid-April. The primary goal is to show that the drug is better than placebo at improving symptoms - fever, respiratory rate, oxygen saturation and alleviation of cough - within 28 days. Patients must do 20% better on remdesivir than placebo for the drug to be successful.

     Clinical improvement is measured with a six-point scoring system ranging from hospital discharge (a score of 1) to death (a score of 6). In order to count as someone who responded to the drug, a patient must improve by at least two points. Patients can remain hospitalized at the end of the 28-day period of the clinical trial but still improve enough clinically — no longer needing intubation or supplemental oxygen, for example — to count as a responder.

     Generally, antivirals are most effective if they are given soon after a person is infected. This allows them to slow the replication of the virus while it is still at low levels. If a treatment is given too late, and the virus has had a full chance to proliferate, it’s possible that the cascade of health consequences cannot be stopped.
     One problem: Remdesivir may be more effective if given early, but since it is given intravenously, it may be easier to administer in a hospital after patients are already very sick. How and when to treat is still a question.

     In the U.S., clinical trials are underway with severely and moderately ill goups. Completion date of study estimated in May, 2020, but may be available in April.

     Remdesivir was rapidly pushed through clinical trials due to the West African Ebola virus epidemic of 2013–2016, eventually being used in at least one human patient despite its early development stage at the time. Preliminary results were promising and it was used in the emergency setting during the Kivu Ebola epidemic that started in 2018 along with further clinical trials, until August 2019, when Congolese health officials announced that it was significantly less effective than monoclonal antibody treatments such as mAb114 https://en.wikipedia.org/wiki/MAb114 and REGN-EB3.
https://en.wikipedia.org/wiki/REGN-EB3. The trials, however, established its satisfactory safety profile.

     A journal pre-print (not peer reviewed) offered online March 9, 2020, 3 of the first 12 U.S. patients in the U.S.were treated in January, 2020, with Remdesivir. There was not a “clear temporal association” between treating patients with remdesivir and improvements in oxygen requirements, fever, and viral results, compared with hospitalized patients who did not receive the investigational drug. Data regarding drug efficacy is inconclusive.
https://www.medrxiv.org/content/10.1101/2020.03.09.20032896v1.full.pdf

     Gilead has been ramping up production of the drug since January. It now has 1.5 million doses, which is enough for 140,000 patients. They have cut production times by as much as 50%, but end-to-end manufacturing still takes about six months. The The company’s goal is to have 1 million treatment courses available by the end of the year.
More at https://www.statnews.com/2020/04/06/gilead-remdesivir-data-coming-soon/ 

   
04/03/2020

What comes next: How will COVID-19 end?
     A consensus is emerging regarding the ultimate course of the COVID-19 Pandemic: before the waves of infection will recede, a critical number of humans will have to be removed from the pool of available hosts worldwide. This can happen through infection and either the death of the patient or recovery with acquired immunity, or the development and global implementation of an effective vaccination program.

      Gabriel Leung, Dean of Medicine at Hong Kong Univ and founding director of the WHO Collaborative center for infectious diseases, has made a rough calculation that the spread of the coronavirus will not stop until at least half the global human population has either been sick and acquired immunity, dies, or been successfully vaccinated. 

     Ed Yong, in The Atlantic , 3/25/20, writes:

     "Even a perfect response won’t end the pandemic. As long as the virus persists somewhere, there’s a chance that one infected traveler will reignite fresh sparks in countries that have already extinguished their fires. This is already happening in China, Singapore, and other Asian countries that briefly seemed to have the virus under control."

      Under these conditions, there are three possible endgames: one that’s very unlikely, one that’s very dangerous, and one that’s very long.
     The first would have been a fast, perfect response, wheres every nation works simultaneously to bring the epidemic under control. 
     According to Dr. Michael Levy, professor of epidemiology at the University of Pennsylvania College of Medicine, if everyone on the planet had observed with absolute perfection all the social distancing, shutdown of all activity, testing and quarantine, and disinfecting that we are even now still struggling to get used to, the problem could have been over in two weeks. Too late for that.
     Given how widespread the coronavirus pandemic is, and how badly many countries are faring, the odds of worldwide synchronous control are nearly zero at this point.

      The second is that the virus does what past flu pandemics, especially the Spanish Flu of 1918, have done: It burns through the world and leaves behind enough immune survivors that it eventually struggles to find viable hosts. This “herd immunity” scenario would be quick, and thus tempting. But it would also kill many millions of people, and destroy the healthcare systems worldwide.  The United Kingdom initially considered this herd-immunity strategy, but reconsidered when models revealed the dire consequences. President Trump essentially supported this plan [3/25], but is now (4/3) supporting an extended shutdown.

     The third scenario - what we are doing now - is that the world plays a protracted game of whack-a-mole with the virus, stamping out outbreaks here and there until a vaccine can be produced. It is the longest, most expensive, and most complicated.

     There is a fourth scenario -  development of a cure or treatment  - that will reduce the severity of the disease number of deaths until we reach herd immunity. 
     One good candidate is Gilead Corporation's (GILD) Remdesivir, an antiviral drug which has been successfully used to treat Ebola. Early indications are that it is effective. [update 4/4/2020: Remdesivir is useful in treating Ebola, but not as effective as two other treatments that have been used.] Gilead is the company that developed successful treatments for HIV and a 12-week cure (not just treatment) for hepatitis. Distribution of Remdesivir has been approvde for compassionate use for COVID-19 in Europe.
     President Trump has said that Hydroxy Chloroquine, a medicine with potentially dangerous side effects that is in widespread use to treat malaria, is a "beautiful" treatment for COVID-19. This idea has been widely discredited by the medical community. 
     However, there is one clinical study, conducted in France, indicating the efficacy of Chloroquine to treat COVID-19. 
https://www.mediterranee-infection.com/wp-content/uploads/2020/03/COVID-IHU-2-1.pdf
     A treatment will not by itself shorten the pandemic or reduce the total number of people who get infected, but it will save lives.

     The wild card in this whole game is the likelihood - the eventual certainty - that 21st century medical science will develop an effective vaccine. There are a number of biotech companies working on vaccines, each with their own novel technology.
     Novovax (NVAX) is working on vaccines for viral diseases, including the flu, with a technology that allows rapid production more quickly.
     British Tobacco Company's (BAT/BTI) U.S. subsidiary, Kentucky BioProcessing (KBP, is developing a novel plant-based vaccine for COVID-19, and is now in pre-clinical testing. According to BAT, "if testing goes well, BAT is hopeful that, with the right partners and support from government agencies, between 1 and 3 million doses of the vaccine could be manufactured per week, beginning in June."