I decided to add the year to my title in the event that this thing goes on for another full year, and I have to do an update in May 2021. I pray fervently that such an eventuality will not come to pass, but it’s certainly possible. Having said that, your obedient servant Doc Gumshoe continues to be an optimist, more or less, and continues on the alert for positive developments and hopeful bits of news.
Well, all I know is what I see on the internet, as Will Rogers would have said if he were around these days. But here are some topics that Doc Gumshoe has looked at carefully, and which I hope you will think deserving of attention.
The first, and likely most important and most hopeful of these is the emergence of herd immunity.
When, and how, will herd immunity emerge to protect us from the coronavirus?
The “herd” I am referring to here is not cows or sheep, but us – the human population. The way it works, and the reason it works, is that viruses are not able to survive on their own. They can exist for a limited time outside of a host. The duration of that limited time varies among different viruses; in the corona virus (now designated SARS-CoV-2) under normal circumstances it may be as long as 48 hours, but usually much shorter. It depends, as probably you have heard, on its specific environment; for example, on steel or hard plastic, it might still be present and a possible source of infection 48 hours after it was first deposited there by a cough or a sneeze. On some other metals, such as copper, not more than about 6 hours. On paper, cardboard, textiles, and other absorbent surfaces, a considerably shorter time. Of course, researchers have their ways of keeping the virus alive and active for longer.
Therefore, in order to survive, a virus needs to penetrate a living being and kidnap the resources it needs to reproduce, which it manages with considerable efficiency. Multitudes of viral particles can take up residence in a single living cell, appropriate the cell’s own functions, kill the cell, and emerge to invade other cells. In the case of the novel corona virus, the spikes on the exterior of the virus have the special ability to attach to receptors on the exterior of living cells in the host. These spikes, by the way, are what give corona viruses their name – they resemble a crown.
When it penetrates the living cell, the virus is recognized as an invader, and the innate immune system of the living being that the virus has invaded (the host) will produce antibodies, which at the same time can attach to the viral particles and alert the immune system’s defense forces to attack the virus. The host that the virus has invaded – human or animal – uses its immune response to combat and eliminate the virus. An all-out war has been declared, and the host is the battlefield. This is not necessarily agreeable for the host. We – the human hosts that have been invaded by the virus – develop fevers, inflammation, aches, and other symptoms that we may interpret as signs that we are sick, but are in reality signs that we’re desperately fighting off a severe disease.
But even after the virus’s host wins this war – which we fervently hope the host does win – the antibodies remain, and act as sentries in case the virus should invade again. It’s not known at this moment what degree of immunity those persons have who have been infected with the evil corona virus and fought off the COVID-19 disease, but what is known about viruses strongly suggests that some immunity will be present in those individuals. How powerful that immunity will be and how long it will last is a matter of speculation at this time.
Vaccines are the other pathway to immunity. At present, more than 100 potential COVID-19 vaccines are in development. We’ll take a look at a few of the more promising candidates later on in this piece, but despite a certain person’s promise to have 300 million doses of a vaccine available by January of 2021, that timetable seems a stretch.
A vaccine is carefully crafted to produce an immune response without causing the actual disease. Frequently vaccines do cause some mild symptoms, and the symptoms do vary among the many vaccines. The smallpox vaccine usually produced a single little pox on the skin at the site of the inoculation. Many vaccines cause aching arms at the injections site, and mild headaches or a mild sickish feeling. (What Doc Gumshoe can state with total conviction is that vaccines do not cause autism.)
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In any case, those mild symptoms are manifestations of an immune reaction, which is what the vaccine is meant to trigger. The immune reaction essentially means that the vaccinated individual now has a troop of sentinels which are primed to recognize the invasion of the specific pathogens and summon a militia of phagocytes and lymphocytes. In the case of viruses, the most effective militia are a class of lymphocytes called T-cells, sometimes called natural killer cells, which are highly effective against most viruses.
(Exceptions to this are retroviruses like the human immunodeficiency virus (HIV) that causes AIDS. These are particularly successful in terms of viral life, because they do not trigger an immune response. Instead, they take over the host’s immune system, disabling T-cells. Individuals infected with HIV can live for years without exhibiting any symptoms. However, during those years they continue to carry and transmit HIV. This is good for the virus, but catastrophic for the human hosts.)
At this point, no one can say with certainty whether individuals who have been infected with SARS-CoV-2 and recovered have immunity to the virus, and if so, how strong that immunity is and how long it will last. The assumption is that those individuals will have some immunity, and the hope is that the immunity will persist long enough to protect those individuals from infection in at least the near future. The same hope applies to the effects of a vaccine.
The hope, essentially, is that enough persons – either because they have had the disease or been vaccinated, or both – will possess a degree of immunity such that the virus cannot spread like wildfire through the population. The percentage of individuals in the community necessary to provide immunity to the entire herd of humanity is not precisely known, but it is quite high. The human race was protected from smallpox by herd immunity because almost everybody had been vaccinated against smallpox. (That herd immunity has vanished at this point, since people are no longer routinely vaccinated against smallpox, but the disease itself has also vanished.) Up until quite recently, herd immunity kept the measles totally under control, but then a few parents decided that vaccinating their children against the measles violated their principles, with the result that the measles reappeared, and there were even deaths from the measles.
The way herd immunity works is by depriving the pathogen of a site to which it can spread and reproduce. If in a class of 30 children, all are vaccinated, even if one child gets the measles despite being vaccinated, it doesn’t spread. (Since no vaccine is 100% effective, some children who have been vaccinated may also get the measles.) The child recovers; the measles virus expires since it has no place to hide. But if a sizeable number of children are not vaccinated, the measles will spread.
In brief: the transmission of a disease, whether bacterial or viral, is in inverse proportion to the percentage of the population that has immunity. The more people that are immune, the less the disease spreads; the fewer people that are immune, the more the disease spreads.
I deeply hope that herd immunity rises in our country and the world because of the availability of a vaccine and the widespread use of the vaccine, and not because the corona virus itself has infected most of the world’s population. And I also deeply hope that when this vaccine becomes available, the vaccine deniers don’t try to quash it by manufacturing rumors that the vaccine itself causes some dire disease. A great deal depends on widespread vaccination – not less than the future of humanity and civilization.
So, when will a vaccine become generally available?
That depends on whom you ask, and also where you’re asking from. The White House proclaims that a vaccine will be available to one and all (at least here in the good old USA) by January, 2021. To that end, a project has been announced whose objective is having 300,000,000 doses – that’s 300 million, by next January. The project, dubbed Operation Warp Speed, is headed by Moncef Slaouli, who was chairman of vaccines at GlaxoSmithKline. General Gustave F. Perna, who is in charge of the Army Matériel Command, will be the chief operating officer, tasked with getting those 300 million doses of the hoped-for vaccine manufactured and distributed.
The plan is that the fruit of their labors will be an effective vaccine against SARS-CoV-2 which will be exclusively reserved for Americans. The plan, according to sources familiar with the plan, is to have 100 million doses available this November and the other 200 million in December and January of next year.
The project initially focused on 14 candidates selected from the 110 or so possible vaccines that have emerged in the past few months. That list of 14 was narrowed to eight, chosen in part because they represent different technologies, or platforms, as they are called. Much of the focus thus far has been on just two technologies. One constructed with the messenger RNA encoding the corona virus surface proteins that form the spike, or crown. The other uses an adenovirus (one of the viruses that causes the common cold) to carry a protein that has the capacity to disable the corona virus. However, other pathways to disable or eliminate the corona virus are being investigated, and the Operation Warp Speed project will consider these as well.
An official speaking for the project made the point that Warp Speed will not consider pushing any potential vaccines made in China or based on Chinese research, such as the inactivated virus vaccine which was recently shown to protect monkeys from the virus. However, the winning candidate might well be manufactured by a company that is not headquartered in the United States.
Warp Speed’s plan, based perhaps as much on hope as on careful preparation, is to have all candidate vaccines in human trials by July of this year. At the same time, the plan is to conduct large-scale investigations of safety in hamsters and monkeys, in order to winnow out any vaccine that produces significant adverse events.
In the meantime, the National Institutes of Health (NIH) has an initiative called Accelerating COVID-19 Interventions and Vaccines (ACTIV). It’s relationship with Warp Speed remains unclear. ACTIV plans to coordinate clinical trial of several COVID-19 vaccines, and is also considering human challenge studies, in which vaccines would be fast-tracked by immunizing healthy subjects (volunteers, of course) and then deliberately infecting them with SARS-CoV-2 or a weakened version of it. This, I should hardly need to point out, is highly controversial. However, a phalanx of courageous volunteers has already come forward.
One promising candidate is a vaccine in development by Moderna, Inc (MRNA). In early trials it was found that the vaccine, mRNA-1273 produced levels of antibodies in trial subjects similar to those found in blood samples from persons who have recovered from COVID-19. Moderna is planning to start late stage trials in July.
Other efforts to develop a vaccine include the Coronavirus Global Response, organized by the European Commission. The World Health Organization (WHO) and other groups have formed the Access to COVID-19 Tools Accelerator. And the Bill and Melinda Gates Foundation is watching about 15 vaccine candidates and will support the most promising among them. These initiatives aim to achieve equitable worldwide distribution of vaccines when they become available. Many experts have expressed concern that the Warp Speed plan, which would restrict any resulting vaccines for use in the US only, would deny access to such vaccines to the most vulnerable populations outside the US. These concerns led more than 140 world leaders to sign an open letter asking governments to consider Covid-19 vaccines to be a “global good” and ensure equal access when the resource does become available.
What is the real fatality rate?
As of today, May 18, when I am writing this, the total number of confirmed cases of COVID-19 on the planet is 4,758,937, with 316,277 fatalities. These numbers are certainly inaccurate, since every country tracks these numbers somewhat differently. They are also certain to constitute a considerable undercount, because not every person was tested who had possible COVID-19 symptoms, nor was every person tested who died in the period since COVID-19 emerged.
Ecuador stands out as a prime example. Despite its relatively youthful and generally healthy population, Ecuador experienced a high rate of infection and death due to COVID-19, even based on the official confirmed figures. However, consider this: between March 1st and April 15th, there were 7,600 more deaths in Ecuador than the average number during that span of time in the pre-COVID-19 years. The number of deaths that the government had officially attributed to the corona virus during that period was 503. If many or most of those 7,600 excess deaths were due to COVID-19, it would suggest that the actual COVID-19 fatality rate in Ecuador was as much 15 times higher than the official published rate. (The term “excess deaths” is the epidemiologists’ terminology for the gap between the observed and normal number of deaths; the rest of us probably consider any deaths at all to be in excess of what is desirable.)
In the US, the indications are that in at least nine states the excess fatality rate has been far above normal. These include California, Colorado, Illinois, Maryland, Massachusetts, New Jersey, New York, Vermont, and Washington. New York City alone has reported 13,831 confirmed COVID-19 deaths as well as another 5,408 probably related to COVID, but the excess death gap totaled 24,172, suggesting that there may have been nearly 5,300 unreported COVID deaths,
New York State has so far tested about 7,500 for corona virus antibodies. Statewide, nearly 1 in 7 tested positive for the antibodies, and in New York City, the number was higher – 1 in 5 New York City residents tested positive for coronavirus antibodies. Those results suggest that about 2.7 million people in the state of New York have at this point been infected with the corona virus.
When I look at the ratio between confirmed COVID-19 cases and fatalities in various communities in my part of the country, the discrepancies are quite large, and surprising. For instance, as of May 13th:
|Putnam County, NY||1,108||7||0.6|
|Westchester County ,NY||31,611||1,245||3.4|
|Fairfield County. CT||13,636||1,068||7.8|
|New Haven, CT||9,570||745||7.8|
These differences probably reflect genuine environmental factors that affect infection rates and fatality rates. Putnam County is a good deal more rural than Westchester County, thus making it easier for people to maintain social distancing. In Connecticut, Hartford is more congested than New Haven or Fairfield County. However, it’s also likely that there are differences in the availability of testing between various areas.
The COVID-19 fatality rate has hit certain populations particularly hard. For example, in a veteran’s care facility in New Jersey, 72 people died, more than 10% of the residents – not 10% of the confirmed cases, as we were discussing above, but 10% of the entire population of the facility. Nursing homes and some hospitals have been disproportionately hit, no doubt due to the extreme difficulty (not to say impossibility) of maintaining distancing between persons, as well as the compromised health of the residents. For example, 70% of the COVID-19 deaths in the state of Connecticut have occurred in nursing homes or senior care facilities. The town where I live in Fairfield County has reported about 40 COVID-19 fatalities to date, but 38 of these have been in senior assisted living facilities.
Housing conditions and living arrangements clearly affect the fatality rate, likely due to difficulties in maintaining distancing. A person living in a multiple-story apartment building or housing project may have no choice but to ride in crowded elevators and walk in hallways that do not permit distancing.
It has been clearly established that COVID-19 has affected some ethnic/racial groups more severely than others. The fatality rate among black and Hispanic populations is significantly higher than among the white population, and this difference is largely attributable to economic disparities that are reflected in living conditions. More crowding, sometimes resulting in several persons sharing one room, lead to a higher fatality rate, for obvious reasons. It is also likely that there are more deaths from COVID-19 that have not been specifically attributed to the virus.
The factors that point to a significantly higher fatality rate from COVID-19 than the confirmed deaths almost certainly apply to the rest of the world. My source of information about the global spread of the disease is the John Hopkins website, which as of today shows that in 104 countries the number of fatalities has only attained double digits, and in about 11 of these, the number of fatalities is in the single digits. For example, Botswana has reported one single fatality. Those low fatality figures are almost certainly due to low testing rates. Deaths in individuals who have not been confirmed as infected with the corona virus are not counted as COVID-19 fatalities, so it’s a virtual certainty that both the number of cases and the number of deaths are greatly underreported, especially in the less-developed world.
There are also differences in the rates of infection and death stemming from the way the disease is managed in different places. An example is a comparison between fatalities in Sweden compared with Norway, neighboring countries with similar cultures and economic conditions. However, while Norway has practiced the social distancing and restriction of a great many businesses and entertainment enterprises, Sweden has mostly skipped those restrictions, concentrating on the elderly population, based on the reports that it’s the elderly that the virus most impacts. However, the fatality figures cast doubt on that calculation. Sweden’s population is not quite double Norway’s, but the fatality rate is three and a half times that of Norway’s.
What this might imply about the ultimate toll of the COVID-19 pandemic is a matter of speculation. Comparison with the influenza pandemic of 1918 – 1919 is inevitable but not necessarily enlightening. That pandemic was perhaps the second deadliest pandemic in history, second only to the bubonic plague that may have caused the deaths of a hundred million (or more!) during the 14th century, when the global population was a tiny fraction of what it is today. The flu pandemic killed about 50 million people globally, and 675,000 people in the US. There were more deaths due to that pandemic than to World War I. Many of the measures used at that time were similar to the ones we have adopted today, including closing schools and places of public entertainment, requiring people to wear masks in public, and enforcing “no spitting” ordinances.
Estimates vary enormously on the number of infected and the number of deaths before the corona virus is tamed. Most knowledgeable authorities project a rate of infection and fatality that will ultimately reach major multiples of current levels, particularly in less developed parts of the world. Ultimately, a great deal depends on immunity, whether as a result of a vaccine or because of the numbers of infected people around the globe who have recovered and retained immunity.
How can we tell whether or not we have immunity to the corona virus?
As of about a week ago, a test for antibodies to SARS-CoV-2 has received FDA Emergency Use Authorization. This test, developed by Abbott, analyzes serum from a blood sample for immunoglobulin G I(IgG) and takes about three to five days for a result. According to Abbott, this assay has specificity of 99.6% and sensitivity of 100%. The specificity figure indicates a very low likelihood of false positives, meaning that a person receiving a positive result with this test can be almost certain that he/she was indeed infected with the corona virus. The sensitivity figure indicates that if the test result is negative, meaning that the assay did not detect IgG related to the corona virus, the person can be entirely certain that he/she was not infected.
The value of an antibody test is that a person with positive corona virus antibodies is likely, but not certain, to have at least a degree of immunity. Does that mean that this person can totally ignore the precautions that the rest of us careful folk are taking every day? At this point, we do not know for sure. However, knowing that in all likelihood we had the infection and have some immunity must surely ease our minds. Wearing the face mask and washing our hands is no big deal. Hugging and kissing our friends and acquaintances might need to be deferred for a while. We can probably go out to dinner, but it would make sense to pick a restaurant where the tables are not too scrunched together. I would be skeptical about going to the movies. And if you run into a guy who’s sneezing his head off, give him wide berth.
The Abbott antibody test, which is used by Quest Labs and a number of other sites, is not to be confused with the rapid test for the presence of the virus itself, also made by Abbott. That test, Abbott Laboratories’ ID NOW molecular COVID-19 rapid test, supposedly could deliver positive results in as little as five minutes. Because of the speedy results, this test was adopted for use at the White House, and in one case apparently caused considerable confusion. Vice President Pence’s press secretary, Katie Miller, tested negative on the ID NOW test, but a few days was tested again and tested positive. She is one of two White House staff personnel who have tested positive and are now in quarantine.
The ID NOW test was examined closely by New York University’s Langone Labs, using samples from 101 patients. Those test results were compared with the result of the Cepheid Xpert Xpress test, and the NYU researchers found that the ID NOW test missed detecting the corona virus in a large percentage of the samples that the Cepheid test had found positive. The false negatives rate ran from about 33% to 48%, depending on the way the test samples were stored before analysis. The ID NOW test, by the way, is not a blood test, but a nasal swab test. Abbott, as might be expected, strongly disagreed with the results of the NYU lab’s investigation, asserting that their analysis was not properly conducted and that their own research had put the false negative rate at about 0.02%.
Some conclusions, put forward with some hesitation
A Doc Gumshoe reader commented recently that it would be a good idea for me to put my main take-aways in bullet form at the end of these pieces. I hesitate to do this, because those “conclusions” are less conclusive when stripped from the context. But I can see that it might make some sense to do that, so here goes…
- One, first and foremost, our salvation lies in herd immunity. It’s possible, of course, that the evil coronavirus will just peter out, but we humans (by which I mean all of us) can absolutely not rely on that. Herd immunity, whether because huge numbers of us have had mild cases of COVID-19 or because all of us have been vaccinated, is what will bring an end to this pandemic.
- Two, it is absolutely imperative that, when a vaccine becomes available, we all get vaccinated.
- Three, it is highly likely that the total toll, disease and death, due to SARS-CoV-2, will be much, much higher than it has been to date. As bad as it has been, it will – at least in some parts of the world – get worse.
If you think this is a departure from my usual optimistic self, you are mistaken. I remain an optimist. I have confidence in the resourcefulness and resolve of our researchers and of at least some of our leaders. I also think that most of us humans are pretty good folk, and will hang together to see this through.
Thanks for your comments, and, to all of you, be well and stay well. Michael Jorrin, (aka Doc Gumshoe)
(Ed. Note: Michael Jorrin, who I dubbed “Doc Gumshoe” many moons ago, is a longtime medical writer (not a doctor) who shares his thoughts on health and medicine with our readers a couple times a month. He does not offer personal health or investment advice, and does not generally write about investment ideas, but has agreed to our trading and disclosure rules. You can see all of his past columns here.)