Covid Update IX

29 Jun 2020

1. General Course of the Pandemic
   The United States continues on a hyperbolic path that is likely to continue for months. The three most populous states in the union (and I use that term very loosely) have record increases in cases, hospitalizations, and ICU bed use. It is as bad as it sounds. It seems a certainty that there will be overflow contagion into other parts of the country.
   Because there is more than one manufacturer that makes tests, and because the criteria for whether to accept a test as “Accurate” are not well defined, there is the likelihood that many of the negative tests that we see are early positives. Our CDC head recently said that the number of infected people could be as high as ten times what we are recording. If you are thinking of “herd immunity,” disassociate yourself from that pipe dream. Even if Dr. Redfield’s estimate is accurate, this “positivity” would mean 20% of us are or have been infected. Not nearly enough to qualify as a herd.
   Other than Europe, China, and Southeast Asia, the rest of the world seems on the edge of a cliff. The emerging African Middle Class has been shattered. Poverty and a sense of hopelessness will multiply. No remedy in sight. International efforts to help are feeble and not well coordinated.
2. Testing
   See the paragraph above. Not only is it impossible to tell which tests are responsible for how many cases; it is extremely difficult to get a test done in the areas that most need them. Five months after we got the news that we needed to prepare, the country remains paralyzed like the proverbial deer in the headlights. The federal government stopped funding several test sites, leaving the states with some money and all responsibility. Countries that have a tenth of our knowhow and financial resources are feeling sorry for us. One positive side effect of this epidemic may be that we will no longer be branded as capitalist imperialists. We are objects of pity. And dread: the EU has extended the ban on travel from the US (to be fair, we also ban them).
3. Treatment
   Nothing exciting on this front. Remdesivir remains the only medicine that has shown an effect, and it is minimal. It involves IV administration for five days. Gilead, the makers of this drug, recently announced that they will charge $2,000 for a five-day course for Medicare patients; $3,000 for private insurance. For a medication that barely cleared the bar as an effective therapy; that was already developed and did not entail hundreds of millions of dollars in research expenditures. People wonder why the pharma industry is so maligned.
4. Vaccines
   Clinical trials continue. We keep getting reassurances that provided that an effective vaccine is found, it will be available and affordable to all. A new technology to develop RNA vaccines has come up; it has generated a fair amount of excitement. The caveat: we have no idea if any of the vaccines in development will help to prevent illness. And if they do, we do not know how long this immunity will last.
   Some researchers are looking into unrelated vaccines in order to enhance what we call the innate immune system. Let us use polio vaccine as an example. It is given by mouth; it is extremely safe. Some experts feel that a dose or two of polio vaccine will place our immune systems on an enhanced alert mode, so that we will be primed to crush anything that comes knocking at our door, even if it is not polio. An oversimplified explanation, but it will do. Of course, we have little if any polio vaccine in the US because this disease has been largely eradicated in developed countries. We would have to go to some poor country, the kind that our president once referred to as “___holes” and beg for some of the stuff they have.
   The social consequences of the lockdown will soon be felt in devastating force. Hundreds of thousands of people are due to be evicted from their homes on July 1. There was an order to prevent evictions, but the law forgot to cover rent payments. In other words, on July 1 people will have to come up with four months’ worth of rent, instead of one. Landlords have been filing eviction notices in court since April. The federal order only said that people could not be evicted; not that papers could not be filed. If something is not done quick, we will have hundreds of thousands of newly homeless people wandering about. I will give you one guess; one; as to how upset they will be.
   As you may have gleaned, I am very discouraged. Six weeks ago, I was optimistic as to where all of this was going. It seems that someone in a position of leadership read the textbook on how to deal with pandemics, and then did the opposite of what was recommended.
   Hang tough. Watch more movies. Tip generously.
   Bonus round: The verb “to glean” comes from the medieval practice of allowing impoverished peasants to sift through whatever wheat was left to lie on the fields after the regular harvest. This was an important source of nutrition for people who had nothing. Late in the 19th century some landlords decided to charge for this privilege, which provoked strong protests. One wonders why Jesus said something about camels going through the eyes of needles before rich people were allowed into Heaven.

Covid Update VIII

22 Jun 2020

1. General Course of the Pandemic
   The United States Has seen the number of cases rise almost daily. The original “hot spots” on the East Coast have decreasing caseloads. Many southern and western cases have experienced a sharp rise. The governor of Florida says that the numbers are higher because we are testing more people. If this were true, the percentage of positive cases should remain the same or drop. They have been increasing. Hospital admissions and ICU occupancy have also gone up. Arizona and Alabama may face a shortage of ICU beds soon. Several public health officials in the most affected states have had their lives threatened, because they have promoted social distancing and wearing of masks. There have been some resignations. A great way to reward bright people who choose to work for lower government wages because they want to help humanity.
   There is much talk about what a “second wave” may look like. Common sense dictates that there will be no second wave if we are not done with the first wave. The way things are going in the US, current levels of infection and medical disasters may continue unabated for another year.
   In the rest of the world the situation is just as diverse. Europe has emerged from the most draconian measures, but their fingers remain crossed. Most European countries heavily depend on tourism. There is widespread concern about what might happen when the borders reopen. China had a small hot spot in Beijing. They have taken draconian measures, and no one has protested, as expected. New Zealand had a few cases; so did Korea, but in general, Asia has done much better that the Americas. Africa and South America are doing poorly.
2. Tests
   There is no information on what kind of tests are being done. There are many reports of contradictory results from antibody testing. A logical consequence of having approved all tests without knowing if they were accurate first. Most disturbing: we still do not know if people who have antibodies will be immune when they are re-challenged by the virus.
3. Treatments
   A lot of publicity was given to the British study that showed that severely ill people (Low oxygen; ICU; ventilators) had a lower death rate when they were treated with dexamethasone. This is a form of cortisone. In the US, the trade name is Decadron, although almost everyone uses the generic drug, because it is effective and inexpensive. Cortisone compounds decrease inflammation. They have been used in low doses to treat inflammatory and autoimmune diseases for decades. They suppress the immune system. Most lung specialists feel that an exaggerated surge of the immune system, called a cytokine storm, is responsible for a large percentage of the complications that seriously ill patients with covid-19 develop. Blunting this response proved useful in the British study.
   NOBODY should take it upon themselves to procure their own supply of dexamethasone. I have prescribed this medicine a lot over the last five decades. The side effects are significant and serious. Please do not do anything stupid.
   No news on oral drugs. In my opinion, this means that none of the combinations being used are jaw-droppingly effective. When a study is done, safeguards are put in place so that, if a drug is found to be effective, the study is ended, so that no patients remain on placebo. So far, no studies have been stopped.
   No new developments on antibody treatments.
4. Vaccines
   Phase III studies are underway in the EU, US, China, and maybe Russia. It will take months for any results to emanate. We have been told that there will be enough vaccine for the whole world if one or more of the candidates being tested pan out. It will probably come to having to use three or four different vaccines. Which will make it more difficult to ascertain which is the most effective one.
   On one hand, humanity should be proud of what has been accomplished. This is a new and vexing disease, and we have halted its spread in many places. We are getting better at finding ways to treat its complications. On the other hand, the lack of coordination between sovereign states, the chronic underfunding of the WHO and all national public health entities, and the scandalous neglect of our elderly, our prisoners, and our food processors will earn us points to go to hell immediately; do not pass GO. One hopes that maybe we will not let this happen again.

Covid Update VII

15 Jun 2020

1. General course of the Pandemic
   There is uniform agreement that at least twenty states are in an upward swing. It is unclear if most of the new cases are centered in prisons, meat packing plants, and nursing homes because there are states that are no longer making this information available. From my viewpoint it does not matter, because there are people who work in these facilities that go home at the end of their workday, and they carry with them whatever infection they have been exposed to. But there are people in the media who feel that a nursing home case should not be counted, because these people are not circulating among the rest of us. I think that this argument is flawed.
   Worldwide, we have most European and Asian countries demonstrating a good grasp on the virus, even though victory cannot be declared (except New Zealand, that claims to be rid of it). Brazil has passed everyone except the US in total cases and deaths. Perú, which tried its best, has a serious problem anyway. The rest of the Americas are doing poorly and scheduled to do worse. Africa should be the next epicenter. It is clear that the virus is going nowhere.
   Those who hoped that warm weather and outdoor exposure would help are a bit disappointed. Texas and Arizona are plenty warm this time of year, and they have the steepest curves.
   There was another report, this time from the US, that maybe the virus had mutated and was not as dangerous anymore. Yes, the virus has mutated. One of these mutations had made it more infectious, not less. Maybe the reason that deaths as a percentage of infections has gone down is because we are testing more asymptomatic people, and we are much better at treating them if they get sick.
2. Testing
   We are doing in the neighborhood of 500,000 tests per day. I have not been able to find any information as to whether these are PCR or antigen tests. Those people who figured that a positive antibody test would give them an “immunity passport” to go wherever they please have been disappointed. There is no proof; none; that a positive antibody test protects us from a new infection. Which is interesting, because every expert that I have read says that those people who had covid with symptoms are not getting sick again when re-exposed.
   A lot written about the “asymptomatic” carriers. It has been the gospel so far that the reason that the virus spreads so fast is because many people who pass it on to others have no symptoms. This past week the WHO put out a bulletin that said that asymptomatic transmission was “rare.” Which goes against the prevailing gospel. It only took a day for retractions to come left and right. Now they say that there is a new category of infected people called “presymptomatic.” They say that while it is true that people without symptoms spread the virus, most of these people will have at least one tiny teensy weensy symptom if you sit on them, hold a baseball bat over their heads, and force them to confess to minimal loose bowels, or an itchy eye, or being a bit tired two days ago. This splitting of hairs is a bit disappointing coming from the WHO.
3. Treatment
   Hydroxychloroquine back in the news. The scientific papers that said that it was not effective, and that it may increase the chances of death, have been retracted. Retracting a paper that has been published in a prestigious journal is a very unusual and particularly humiliating step. It appears that both papers used information provided by an organization that has taken down its web site and is unable to explain where they got their numbers. This is one of the hazards that we encounter when there is a rush to get information out as soon as possible. The review process suffers. Today the FDA retracted its approval of hydroxychloroquine for covid-19 treatment anyway. There are many studies ongoing, and none has shown an early “signal” that it is effective. Do not take it.
   No more news on oral treatments. We should have had some preliminary result by now if any of the candidate medicines had shown prompt cures.
   Antibody treatments are back in a positive light. Before we go into the news, some explanations are needed.
   For today’s purposes (and only for today), there are two kinds of antibodies that are developed in response to an infection. Binding antibodies, made by B lymphocytes (also known as B cells), stick to the infectious agent (virus or bacteria), but do not prevent this agent from attacking your cells. It is helpful, as we said weeks ago, to imagine the virus-antibody “mating” as a three-dimensional jigsaw puzzle. The antibody can attach (bind) to the tail of the virus, but if the virus does not use its tail to invade our cells, this antibody is not as helpful. It does help some, because when the binding takes place a host of immune cells are summoned, and they will ingest the virus and break it down IF it has not entered any cells yet.
   Neutralizing antibodies stick to the part of the virus that the virus needs to get into our cells. In covid-19’s case this is called the “spike” protein. If there is antibody sticking to the spike, the spike is unable to attach itself to our cells. Our immune soldiers will soon find this invader with this huge protein sticking out of its crown. The invader has no chance.
   Neutralizing antibodies are also made by B lymphocytes. Within hours of the manufacture of a neutralizing antibody, our bodies learn if this protein is of so-so efficacy, or if it is really powerful stuff. The so-so B cells are asked to kill themselves, and our bodies make billions of the best B cells. To be very correct about this, it is not B cells that end up making the bulk of neutralizing antibodies. The “winning” B cells turn into something called plasma cells, and it is them who generate the industrial amounts of good antibody. Just in case a doctor is reading this; I had to clarify.
   Good neutralizing antibodies against Covid-19 have been hard to come by. The paper that I read today says that less than 5% of covid-exposed people have been shown to make the premium stuff. Researchers at Stanford have been able to isolate one of these ultra-successful B cells. They have induced these cells to have trillions of babies; now they are harvesting good antibody from this mix.
   How this COULD translate into practice: Getting an as of yet undetermined amount of this anti-covid antibody could protect you from infection for weeks or months. Provided that the spike protein fails to mutate in any significant way. It would work as a vaccine, but instead of your immune system making its own antibody, you would get it ready-made, like a TV dinner. OK; that was an unappetizing simile. But you get it. Stay tuned.
4. Vaccines
   Astra Zeneca announced today that all of the European Union will get its adenovirus (Oxford) vaccine; there will be no shortages. The US will also be provided for. Large-scale human testing will begin in September. I hope that the process will not be rushed because of commercial or political reasons. Other vaccines are on schedule.
   For now, masks are still needed; keep washing your hands; read some poetry.

Covid Update VI

8 Jun 2020

1. General Course of the Pandemic
   The United States continues to have a fragmented course. There is wide variation between states, even counties, on number of active cases, ICU admissions, and deaths. Reporting is still sketchy. There have been noticeable outbreaks in places where crowds accumulated, yet in other places (like our Lake of the Ozarks) there has not been a huge surge following crowded revelry. We may get a better idea on the effects of gatherings in 2-3 weeks following the large demonstrations.
   The rest of the world is a similar mishmash. Brazil’s president decided to ignore the virus; not much data is being collected. People who live there describe hospital crowding and mass graves being dug. Russia is doing poorly, but hard information is hard to come by. Iran may have had a flareup; again no one knows for sure. South America is beginning to descend into mass disease. I do not know much about Africa. Asia has seen minor flares in Korea and Singapore. Vietnam has (still) not reported a single death. It has become a source of national pride; rightfully so. What this tells us is that we are likely to get another round of epidemic when we begin to open the country to foreign travel.
2. Testing
   Another disappointing story. Diagnostic testing continues to ramp up. This week the New England Journal of Medicine reported that nasal patient-collected samples are almost as good as having a trained health care worker slip the long swab up our noses. This would save a lot of PPE and would make expansion of testing more available. Unfortunately, there is still no standard on what constitutes a positive, and which test is more accurate. This means that you could test negative with Test A and positive with Test B two hours later. It seems like it would be an easy bar to clear, but no.
   Two exciting reports: Testing of sewage is at the point where it is accurate and reliable. As an example, if you lived in a large building, as I do, our sewage can be tested to see if there is any virus in it. This way you can test a hundred families at once, cheaply. If virus were found in the sewage, of course everyone would be asked to submit to an individual test. Sewage testing started out as a public health measure (germs), then moved on to looking for illegal drugs, not to arrest people, but to decide where to concentrate public health interventions. I am excited about the potential for this technology.
   The next breakthrough comes from China, where they did millions of tests in ten days in one of their cities. They found a way to run ten specimens through one test. If a positive comes out, again, individual testing must be done, but the cost of doing things this way is way lower.
3. Treatment
   Two more studies on hydroxychloroquine, showing no benefit on prevention or treatment. We will have to endure a rash of these studies coming out, because they were started weeks ago, when people thought it may have helped. If you hear that I have died suddenly in the next few weeks, it is probably because a positive study was reported on hydroxychloroquine, and I had a massive heart attack. I am that dead set against it.
   No more news on oral antivirals. There are persistent reports that Pepcid (yes, the acid medicine) may help to treat infected people. So many anecdotes came in, that controlled studies were started. The generic name is famotidine; it is cheap; it has minimal side effects; it is sold without a prescription. I am not asking you to take it; just giving information. What you do is up to you.
4. Vaccines
   If there is any light at the end of the tunnel, this may be it. Phase 2 studies are ongoing for the two major candidates, and there are more than a hundred others. My concern is that the process will be rushed by political considerations. In order for us to be sure that a vaccine is effective, we need to give it to tens of thousands of people and sit back and wait a few months. We calculate how many people who got the vaccine developed the disease, and we compare to how many people who got the placebo got sick. In order for the vaccine to be deemed safe, you need to triple the prior number of vaccine recipients and sit back and wait a year or two. We have an election coming up in November. It would not be beyond some people to interrupt the “normal” flow of events that have to happen before a vaccine is approved, in order to be able to tell the world that we have a vaccine and that it will be great. The best. Proof that we have the best country, with the best doctors, and the best pharma corporations. It would not be beyond some people to not give a damn if it turns out that the vaccine turns out to be ineffective, or dangerous, as long as some people get elected to the office they seek. We need to be careful when we get to October. Please do not believe everything that you hear from any politician or any of the agencies that are under the influence of politicians.
   Wear your masks; take a walk every day; laugh a lot.

Covid Update V

2 Jun 2020

1. General Course of the Pandemic
   It is hard to tell where we are. There are states that have sharply lower numbers of cases. There are states that show a flat course. The same goes for counties, cities, neighborhoods, different businesses. There is no single set of numbers that applies to everyone. For your local stats contact your state health department, but don’t expect much. The jumble of antigen tests, PCR tests, and antibody tests with different degrees of accuracy continues. Still no national policy on testing or contact tracing.
   No one knows if the massive demonstrations going on will increase the number of cases. It is clear that open air is better than closed rooms as far as diminishing transmission is concerned. It is also clear that shouting increases the chances that you will share your virus with others.
   There was one report from an Italian physician, who said that he thought the virus was losing its “potency.” The correct term is virulence, and there is no scientific proof that the virus is any nicer to us now. What may have happened is that hospitals have gained a lot of experience in treating the extremely sick people. Possible that we have gotten better at managing difficult cases.
2. Testing
   We have increased testing; up to 400,000 a day. Unclear which tests these numbers represent. I read that we need to get up to 900,000 a day in order to be able to open all businesses fully. I do not think that adequate numbers of contact tracers have been trained. Admiral Giroir, the testing “czar,” has been removed from his duties. We have been told that he is no longer needed, and that other people will take over from him. As is so often the case with our current public health personnel, no specific individual will be in charge.
3. Treatment
   There was one report from China that used one oral antiviral medicine with promising results. I have read nothing else new on the triple oral therapy or the Regeneron antibodies. Early June was supposed to be the time when many of these studies began to report their findings. We hope that the coming week will be busy in this front.
4. Vaccines
   The Chinese have developed their own adenovirus vaccine, with results as promising as the Oxford vaccine has shown. Both the Oxford and the Moderna vaccines are in Phase II studies. The usual progression in these cases is that, if no safety “signals” come up, tens of thousands of people will receive a vaccine in September. These will (and should) be limited to health care workers and others who are at high risk. This is not a way to discriminate against anyone. When we test for vaccine efficacy, it is important to first give it to people who are likely to be exposed to the virus. If we begin by giving it to people who mostly stay at home, it may take us five years to find out if it is effective. I read that we are ramping up at least four factories to make these vaccines, now, even if we do not know if they will work. We are making stuff that we may have to pour down the drain later on. The government has accepted the financial liability if it turns out that we will have to ditch any product.
   Please continue to wear your masks. Risk is small if you go take a walk in the park and have a cup of coffee in your favorite haunts, preferably with outdoor seating. Tip exceedingly generously. Be nice to people, even if they are barefaced. We can do this.