Covid Update XIV

Featured

General Course of the Pandemic

The daily number of new cases, both in the US and worldwide, is twice what it was in April. Vietnam, the exemplary country, has posted its first three deaths, while it tries to manage an outbreak in Da Nang (a foremost tourist destination). Almost every country in Southeast Asia is going through this “second wave” anxiety. Australia is closing Melbourne down. Spain has seen daily increases in its numbers. Italy has been given a respite, so far.

Almost every country in the world has seen a decline in the rate at which infected people are hospitalized, get admitted to ICU, or die. There are many potential explanations: all of them probably valid. Younger (healthier) people are getting infected. Doctors have learned a lot about how to deal with and prevent complications. Remdesivir and dexamethasone have helped. There is more convalescent plasma available. Maybe the virus has mutated into something less deadly (don’t tell that to Herman Cain).

Inexplicably, mask-wearing continues to be a source of controversy, not only in the US. Even worse, it has been universally appropriated as a battle emblem by right-wing, totalitarian heads of state. I figured it may be a good idea to identify masks as fashion accessories. Cool things to have.

Testing

We may be finally accepting pool testing as an adequate solution for the delays that we currently experience in getting results back.

The UK just bought millions of test kits that check for influenza and Covid-19 in the same specimen. They have promised that results will take 90 minutes, and they expect excellent accuracy. They plan to deploy these in facilities that care for the elderly.

There is a growing chorus that wants to accelerate the deployment of home kits that only need saliva to obtain an accurate result. I may have more solid information on this next week.

Treatment and Vaccines

There is nothing new on this front. As I have warned in the past, we are beginning to see people taking sides on which group of citizens will get to receive the vaccine when and if a successful candidate is approved. This “noise” will only get louder as we come closer to the rollout.

I want to use the rest of this space to rant against my fellow citizens of all stripes. To your eternal shame, you have used an unprecedented tragedy to try to make your political opponent look bad. Yes, all of you. One news station says that our death rate is the worst among wealthy countries. This is not true. The other side says that we have the best results in hospitalized patients. Also false. One side claims the current administration is disastrously incompetent. If this were the case, we would not have ramped up three years’ worth of vaccine work into three months. The other claims that we are the world leaders in innovation: not true; there are many contributors. It goes on and on.

Few politicians seem to be interested in working together to come up with a coherent effort at the state, city, and neighborhood level. I understand that the current national leadership has been absent from most of these efforts, but looking at how irrational people can be when all of them are grouped into a large cohort, maybe it was a good idea to try to handle this county by county. Now it is too late: we will have to take our lumps and see if we can make it to the other side with the least damage possible.

Let us talk about what “the other side” will look like, and when we can expect to reach it. Barring divine intervention or egregious political corruption, approval of a successful vaccine will not take place before November. Most likely it will be January before high-risk individuals are given their first dose. Most vaccines under investigation will require a second dose a month after the first one. It will take four to six weeks after that for patients to generate enough of an immune response. This gets us into late March, and only for the small percentage of the population that is at high risk. To vaccinate everyone will not happen before June 2021.

That is the best-case scenario. If the new vaccines only provide 50% protection, or if a serious side effect is identified after 200,000 people have been immunized, we can be in the same situation that we are in now twelve months from now. Unless someone comes up with an inexpensive, oral, effective treatment regimen. Do not hold your breath waiting for that to happen.

This should not be hard to understand. You, that means you, cannot continue to expose yourself to potential contagion because you are sure that our smart doctors will come up with an answer. That this plague will go away; that it has to, must go away. Not so.

The next issue is our schools; high schools; colleges. I wish that everyone will just stop screaming about this and take a deep breath. Read what I wrote above. We cannot keep children and adolescents out of school for another year. People who advocate closing the schools now are somehow delusional that this will be only a temporary state of affairs. All of the evidence points out otherwise. A large percentage (I think 30% is large) of our citizens will refuse to wear a mask and ignore suggestions to be judicious. We cannot even get millionaire baseball players who are under close supervision to grow common sense. It is unrealistic to assume that contagion will soon decrease enough to make it safer to open schools.

What to do? We need to treat this as the true emergency that it is. Hundreds of billions of dollars need to be spent on new ventilation systems, bigger classrooms, in-school nursing help, small dispensaries within easy reach, etc. We need to come up, now, with a rapid test that uses saliva or a mouth swab. Something that can be done daily. We have to give our teachers and other school employees “combat pay,” like we give our fighter pilots. We must have an agreement on how to make sure that no one is worried about liability in case a teacher or student gets sick. We must keep schools open twelve hours a day, twelve months a year, until our students catch up.

This is a huge undertaking. The alternative is much easier: we keep screaming at each other, we keep blaming the opposing party for anything that goes wrong, and we, all of us, get sucked into the whirlpool as we get flushed down the drain. Do not think that your job, your home, your investments, and your currency are safe. Do not, for a minute, assume that this is somebody else’s problem to solve. This is about you, it is happening now, and you better get to work on it.

Have I made myself clear?

Covid Update XIII

Our Arch; illuminated, on better days.

General Course of the Pandemic

Cases in the “hotspots” of Arizona, Texas, and Florida are leveling off, although at a high level. California is still on an upward slope. Many other states have increasing caseloads; they do not show up in bright red because they have smaller populations. For a more “granular” report go to the latest map and case count from the New York Times.

On the international front:

Some countries that had the outbreak under control have noticed upswings in the number of cases. Spain is concerned enough to have reinstituted restrictions throughout, mot prominent in Catalonia. Vietnam, the world leader in control of the virus, had one case appear in Da Nang: a city heavy on tourism. If you were there on vacation yesterday, you just earned two extra weeks of stay, whether you planned it this way or not. Hong Kong; Australia; South Korea have the same story. Africa and the rest of the Americas are doing poorly. S

School reopenings:

We have, again, managed to turn a conversation on how to best serve our children into political chaos and disarray. This one hurts me to the bone, because if there is anything that all of us agree on is that we want our kids to learn and grow up healthy. The CDC has modified its guidelines for safe operation of schools.

Unemployment benefits expired three days ago. The ban on evictions, and the temporary suspension of penalties for being late on student loans, expire in a few days. In Missouri, the ban on evictions never existed. We are soon to see thousands of people thrown out on the street. The bipartisan law that gave everyone an extra $600 a week did a lot to keep people fed and warm; it also lowered the number of people who qualified as being in a state of poverty. Republicans want that extra $600 to be lowered to $200, because there were (many) people who were making more money on unemployment than they were while working. This is true. It is also true that all of these people were very low-income earners; the ones that use extra money to spend it, not save it. These are the same people who will remain unemployed if restaurants and hotels continue to operate at little or no capacity. No chance that these people will refuse to go to work: their place of employment cannot hire them. It is also true that nobody can live on unemployment (about half your “normal” pay) plus $200 a week.

Many people made fun of our president for suggesting that UV light be used to treat people afflicted with the virus. There is an interesting TED talk about using UVC light to sterilize indoor spaces, thus making it less likely that there will be transmission in places like bars and restaurants. The UVC light does not penetrate human skin or eyes, so it is deemed safe. This is not, I repeat, not a treatment. Just a theoretical preventive.

Testing

There are many ideas on how to increase the efficiency and number of tests performed. This week there is nothing new on using multiple specimens to run one test, or on testing sewage. I found these suggestions on how to ramp up what we have interesting.

Treatment

The British company Synairgen reported last week that their inhaled interferon therapy markedly reduced the shortness of breath provoked by the virus, while decreasing mortality and length of hospital stay.

Vaccines

The three main (Western) candidates will go into large-scale (Phase III) testing now. As I have said in the past, several large problems have to be dealt with. While Phase II studies recruit a few young and healthy people, Phase III studies must enroll a larger sample (about 30,000 volunteers) that represent the population as a whole. That means that the study directors must find thousands of people with chronic diseases (like diabetes and hypertension) to agree to participate AND remain available for follow-up for months and even years. It may well turn out that those who agree to participate consider themselves healthier than the average diabetes or asthma patient. If that happens, we will not get a good idea if the vaccine works for the sicker people. Underserved populations, that have a well-deserved mistrust of medical researchers, have to be convinced that this time they will not be taken advantage of. It is likely that the three vaccines tested will have different degrees of “success.” We will, for sure, be subjected to claims from all three that they are the best, and that the only reason that Vaccine A showed better numbers is that they recruited fewer old people, or failed to record deaths properly, and so forth. The studies are more likely to come up with a valid conclusion when they are conducted in areas where there is a lot of ongoing contagion. If, through some coincidence, the number of infections in a population sharply decreases once the study starts, it may take years to come up with a sign that the vaccine works (or not).

I saw a YouTube profile on Sarah Gilbert, the lead researcher for the Oxford group. I found it almost as engaging as watching a movie about a medical hero. Her lab was close to having no money to continue to operate. Now they stand to be the first vaccine to finish their trials. To give hope to billions of human beings. Hope that you enjoy it.

I hope that you like the new format to the updates. The reason for the change is to try to reach a wider audience. I very much want to read your comments and suggestions. If you want to do me a huge favor, forward this content to everyone that you are linked to. I promise that I will remain objective, and that I will continue to scour everything that comes out in order to give you a readable summary.

Be kind. Wear a mask. Say “thank you” a lot.

COVID Update XII

Walking over the clouds in Teide Mountain, Canary Islands

General Course of the Pandemic

Cases in the United States have reached the 70,000-daily plateau. Although the bulk of the new cases reside in Arizona, California, Texas, and Florida, this apparent skewing is likely due to the fact that these are the most populous and urbanized states outside New England. Most experts agree that it is only a matter of time before the rural areas become enmeshed in the sticky web that this has become. I already see sporadic stories from relatively isolated areas in Kansas and other “rural” states detailing the misery that is generated when half of the people that you know are in danger.

Many states have agreed to pass mandatory mask ordinances. A few remain resistant. The reason these governors give for refusing to concede the obvious is twofold: “The people” will know what is best for them, and “The people” want to keep their freedom to choose. So far, they have not rescinded the mandatory use of seat belts, or the requirement that every vehicle stop at a red light. But you never know; they may surprise us.

Last week we discussed that it was only a matter of time before the death count rose. Right on schedule, we have seen a sharp rise in the number of casualties. Again, please remember that it is not only the dead that we should mourn. There are tens of thousands of individuals that have survived, only to enter an alternative universe where it is hard for them to comb their hair every morning. How, as a nation, we intend to nurse these people back to health remains a problem that is barely mentioned by federal authorities. It took two years, on the average (before Covid-19), for social security to adjudicate disability claims. Can these people remain without a salary, or health insurance, for that long? I have read nothing; I mean nothing, on what the plans to deal with this issue are.

Scientific data that shows the value of wearing a mask accumulates. Two Missouri hair stylists that unknowingly exposed 143 customers to their virus wore masks while at work, as did most of their customers. There was no contagion reported. Another study that used a mannequin’s head powered by an atomizer showed that even a handkerchief placed over the mannequin’s “mouth” proved effective at limiting the distance that particles traveled when expelled. Of course, a cloth mask with a good fit worked even better.

Small outbreaks in China, Australia, Spain (Catalonia), and South Korea have precipitated prompt response from their authorities. Vietnam is still, by far, the world leader in safely handling the outbreak. Africa and every country south of Texas is suffering.

Testing

My wife got tested last week because she had fever, muscle aches, and gastrointestinal issues. It took five days for her results to come back. These delays are the rule for the past month. Which means that, from a preventive standpoint, getting tested is useless. A few weeks ago, Dr. Fauci mentioned that the government was looking at grouping tests: running ten samples on one test, as they do in China. Just yesterday I read that maybe they would start doing this with four specimens at a time. This approach will only work in areas where the virus is not very prevalent yet. It is beyond my understanding why we have not pursued antigen testing with more vigor. Although antigen tests are only about 80% accurate, they cost less than five dollars each (as opposed to $100 for a PCR), and results are available within minutes. We could afford to open schools and test children daily because they use saliva or a cheek swab. Also, no reason as to why they have not pursued testing sewage, which is cheap and screens hundreds of people at a time.

I listened to a TED talk today that mentioned Ginkgo Bioworks. A fascinating story of bioengineering. They are going all-in on Covid-19 testing; the CEO thinks that within 2-3 weeks they will be able to run 500,000 tests a day using their PCR technology. They have recently received more than a billion dollars in venture capital funding. No mention of what they intend to charge for their tests.

Treatment

The major story here is that there is not enough remdesivir to go around, even for the wealthy countries. Forget about Africa and the Middle East. As I mentioned before, the Regeneron monoclonal antibody results are due to be published soon. The promise that there could be a safe and effective oral treatment was probably not founded on reality. No recent upgrades on the llama nanoantibodies.

Vaccines

The study on the Oxford/ Astra Zeneca vaccine was published today on The Lancet. This study was done in Wuhan. The vaccine starts with an adenovirus, which is a common virus that causes respiratory symptoms. The viral DNA is manipulated so that, when it enters a human cell, it is forbidden from making copies of itself. They have found a way to take the Covid-19 virus and strip it of part of its RNA; the one that codes for the “spike” protein. They take this RNA and piggyback it onto the adenovirus DNA. Then they inject the mix into some very trusting people who feel well.

This approach was tried on Ebola. I am not sure how it worked. My understanding (I could be wrong; have had no time to check on this) is that no vaccine that uses this technology has ever been licensed. In any case, all people who were so inoculated developed good antibodies against Covid-19. We do not know if this will translate into preventing or decreasing the severity of the infection. Two encouraging signs: there was also a good T cell response (Helper T cells help, as their name implies, to augment immune responses), and seven out of eight ferrets treated with this vaccine avoided infection even when the virus was flushed up their noses.

The Chinese Army vaccine also published their results today. Not as good an antibody response, and a higher frequency of side effects, but no worry: they will start immunizing their troops in August. There are advantages to a totalitarian regime, if only they incur to the scientists and higher-ups. As far as the unfortunate Chinese Army conscripts… Hey, they have a job, right?

I cannot overemphasize how cautious we need to be about this vaccine issue. There has been so much money (and effort) poured into this quest, that people in the middle of this project may ignore warning signals because they so desperately want (need?) this to work. If the majority of the population decides that they will not agree to getting the vaccine, it will not work no matter how safe and effective it is (see recent measles cases in the US). If politicians decide that launching a not fully tested vaccine is going to help them in the elections, we may be told false information about it, and launch it they will, most likely shortly before the elections, too much fanfare.

Stay tuned. Wear masks. Be generous.

Covid Update XI

13 Jul 2020

General Course of the Pandemic

The US has reached daily highs of new cases during the past week. Hospitalizations and ICU stays are taking off; close to a vertical asymptote (I was a math major; I could not resist using this word). For a long time, the number of deaths did not spike, but the upward trend is beginning. Experts say that deaths usually lag behind new cases by three weeks or more, which makes sense if we consider that people who die in ICU, for the most part, have been there for a while. Although the virus by itself can and will kill you, the complications of prolonged ICU stays, particularly in people who have preexisting issues with diabetes, heart failure, etc., take a few days to appear and are a major reason that these patients die.

Much attention is being paid to autopsy findings on those who die of Covid-19, and to the myriad manifestations of the disease outside its respiratory complications. Blood clotting has emerged as a common and potentially crippling complication, even in younger patients. Many, if not most of the patients who recover report significant symptoms that last weeks, even months. Even if we accept that the death rate for all infected people is a bit less than 1%, think about this: The US has a population of 330 million. If we propose to infect 70% of all US citizens in order to obtain the maybe mythical “herd immunity,” that means that 231 million people will get infected, and 2.3 million will die. Are we ready to accept this horrible burden?

South America, Africa, and India seem headed into disaster. It is not just medical: poverty, hunger, and crime are likely to claim as many victims as the virus. We should not trust the number of cases that are reported by most governments in these areas. Even if they mean well, and many of these countries do not, they do not have the medical infrastructure to fully account for all of the affected population. There have been scattered outbreaks in China, and Europe, but for the most part they are controlled, and their economies are reopening carefully. I find it bitterly ironic that an American citizen who wants to lower her chances of getting infected is better off moving to China. Of course, she would not be allowed in.

Testing

Despite the five months that we have had to make sure that everyone who needs a test gets one, we are not close to that goal. Many cities in the southern US report a delay of 5 days to 3 weeks in getting results back. This nullifies any value that identifying and tracing contacts may have. It is not just one issue with testing. Lack of swabs, reagents, tubes, machines to read the tests, PPE for personnel to use… All of these have been identified; not all in the same places. One state could have enough tests but not enough swabs; another may have the opposite problem. A national strategy that directs supplies and personnel where needed would be helpful. But no…

Treatment

I hear through the grapevine that the Regeneron monoclonal antibody studies are progressing. Final results are expected mid- to late September.

There was another study on remdesivir published. This is larger, better put together, and more definitive than the initial one. There was significant evidence that it helps. Because this is an IV treatment, because it is expensive, and because we do not have enough remdesivir for the whole world, you should only receive this drug if you are seriously ill.

A study that showed a beneficial effect of hydroxychloroquine on mild cases was published. A number of people have found fault with the study design. The WHO has stopped all hydroxychloroquine studies. Further information is not likely to be generated.

No further news on the protease and kinase inhibitors being tested.

Vaccines

The Chinese government has developed its own vaccine; the Western world has three major candidates going through studies. Many nations are sponsoring their own versions. It seems to me that the smaller countries are afraid that the wealthier nations will hoard all of the supply if a vaccine is found to be effective. I read in the Spanish newspaper that they have their own vaccine candidate. It would make much more sense for everyone to work together and pool funds and testing sites. The US, as a renowned world leader in research and humanitarian assistance, is uniquely positioned to lead this charge. Do not, I repeat, do not hold your breath.

Please wear your masks. Be nice to every stranger. Tip generously.

Covid Update X

8 Jul 2020

  1. General Course of the Pandemic
    There has been a sharp spike of cases in the United States. At least half of the new cases are bunched in our most populous states. Texas, California, Florida, and other states have felt obligated to walk back some of the “reopenings” that they had approved. Hospitals in many states are feeling a certain sense of urgency. I have heard a couple of reports that there is concern that we will have still another shortage of PPE to protect all essential workers. Part of the surge in positive tests is due to the increased number of people being tested. By no means does this account for all of the increase. Death rates per 1,000 population and per case have decreased. Experts attribute the decline to several factors: An increased proportion of the positive cases come from younger people, who tend to have milder disease; we have gotten better at treating those people who require hospital stays; there is better follow-up of those who test positive.
    The rest of the world remains split. The European Union is successfully reopening. All member countries have had flares of outbreaks here and there. They are being handled forcefully. All of the Americas south of Texas are doing poorly. They will probably get worse. Africa shows signs of worsening. Australia and New Zealand are doing well, and Southeast Asia continues to be a model for all of us.
    Most experts believe that the death rate from infection (this counts people who are probably positive but have not been tested) is a bit less than 0.7%. Although this sounds (and is) encouraging, we have to remember that:
    a. This does not mean, like our president says, that 99% of cases are “mild.” The president fails to count those people who were infected, ended up in the hospital, and took weeks to recover. Many of these people, although they are out of mortal danger, still feel like crap and are nowhere near close to functional.
    b. We do not have accurate numbers as to what the death rate is for people who have preexisting conditions. It is at least 7%.
    There has been a recent report from a scientist that felt that the WHO and CDC were not paying enough attention to transmission of the virus via aerosol droplets. He advocates that buildings should have more efficient filtering systems for recycled air. A brief lesson on droplets: Sneezing; coughing; singing and loud talking; all generate larger size droplets. Because they weigh more, they fall to the ground or floor faster (please do not remind me of Galileo and his Tower of Pisa experiment; larger particles do fall faster because they do not float as well). Also because of their size, they carry a higher number of virus particles. Aerosols remain suspended for much longer but are only able to carry a few copies of virus per droplet. In theory, it is possible that you could walk into an empty room and still be prone to getting infected if there are a few “infected” droplets hanging around from the last time that the room was used. This reinforces the need to use masks whenever you are indoors. But to be realistic, the chances of any person becoming seriously ill from such an exposure is vanishingly low.
  2. Testing
    One report that I read today says that many workplaces have given up on testing employees. At $100 a test, with dwindling supplies, and the need to repeat tests at least once a week, this frustration is understandable. I cannot understand why we have not fully thrown ourselves into testing ten people with one test, or examining sewage, which are much cheaper alternatives. Tracing of contacts of people who have positive tests is in its infancy, and therefore in need of much improvement. One report that I read said that half of contacts did not answer their phone (which is what I do when I get called by a number that I do not recognize). Use of social media looks like a good alternative, but we are so obsessed (I do not use this word in a negative sense) with privacy and individual rights that a facebook/Instagram solution to the problem, although likely to work, may never be adopted.
  3. Treatment
    An article published in Cell, a very respected journal, says that inhibition of a class of enzymes known as kinases inhibited the reproduction of covid-19 viral particles in the lab. This could be a game changer. There are many oral, once a day, kinase-inhibiting medications available. They are mostly used to treat cancers and autoimmune conditions, but what we call their “therapeutic repertoire” is potentially vast. Side effects are minimal. Since there are many kinase enzymes in our bodies, the next step is to figure out which enzymes the virus most depends on, and then to see which of the medicines that we have now best inhibits this particular protein. The most promising part of this scenario is that we already have these pills available, and that safety studies would therefore not be necessary (or would not need to be as exhaustive as what “new” medicines are subjected to).
    I listened to a TED talk with Bill Gates; a recent one. Like me, he thinks that monoclonal antibodies are our best hope in the near future. Using these antibodies is like cheating on a test: we figure out what protein our bodies make in response to an infection or a vaccine. Instead of getting injected with a vaccine and hoping that we make enough “good” antibody to protect us from the virus, we make this “good” antibody in the lab and give it to everybody. In this way we do not have to worry if the vaccine will work or not. The problem is that monoclonal antibodies are a lot more expensive than vaccines, so we would have to restrict their use to people who are at high risk. Because we have vast experience in dealing with antibody injections or infusions, we expect side effects to be minimal.
  4. Vaccines
    My favorite sport these days is making up a list of how many vaccine candidates are in development. I have read numbers ranging from 120 to “more than 180.” For sure someone, whom I will call “Vaccine God,” knows what the exact number of vaccine candidates is, give or take 1%. But so far this “Vaccine God” has chosen to remain silent, so we depend on people who think that they know what they are talking about, and in good faith spread their own brand of gospel. I make light of this, because it does not matter if we have 120 or 180 candidates. My gripe is that there should be an international consortium that is given this task, and that we have failed; all of us; to grasp this golden chance that we had of finding ONE THING that we could agree to work on together.
    Progress on the Moderna and Astra Zeneca vaccines continues. Large-scale testing is due to start soon. It is a bit disconcerting to hear that the US has agreed to pay Astra Zeneca four times as much per vaccine as the UK has agreed to pay. This after we have funded much of the research and the money needed to ramp up the factories. Also disconcerting to see that Moderna stock has tripled in value, thus making its CEO an instant billionaire, even though Moderna has never made anything that has been approved by the FDA. Although just about everyone has promised to keep the vaccine affordable for all of humanity, we have not heard a peep of promise as to what they will charge if a yearly, or biyearly, “booster” is needed. The commercialization of medicine in this country has reached the pinnacle of obscenity. I do not know what it will take for our citizens to begin to demonstrate about this matter with as much fervor as they have about income and racial inequality. The stakeholders have done an excellent job of convincing a majority of the population that they will be subjected to death panels, years of waiting to be seen for a sore throat, and emasculation of physician independence to diagnose and treat as best fits the situation. Hard to tell where to start fixing things because there is a lot to fix.
    Keep wearing your masks. Be nice to essential workers; tip when you can.