Most of this Doc Gumshoe posting was ready to go a couple of days before Thanksgiving. But then, you know what happened: the new variant (now named Omicron) surfaced in South Africa. So I finished up another Doc Gumshoe epistle that I had been working on and quickly got it to Travis so I could take a little time and try to present a more complete picture of the present state of the pandemic, including the Omicron variant.

I will preface this piece with a statement that has been repeated numerous times by all kinds of eminent authorities: we can at best make educated guesses about how the Omicron variant will ultimately affect us. The scientists have examined the virus itself and have enumerated the mutations – as many as 50. About 32 mutations are located in the spike protein, which is the part of the virus that grabs onto cells in the host and initiates infection. But how this variant will affect us, both individually and as a society, is an open question.

The Omicron variant (or B.1.1.529), was first detected in Botswana on November 11, and then identified in South Africa three days later. It was also detected on November 13 in Hong Kong in a national returning from South Africa. By that time there were six known COVID cases in Botswana due to Omicron. By November 24, the new variant had been sequenced in Botswana, at the Harvard HIV Reference Laboratory in Gaborone. Current reports from South Africa indicate that most recent COVID-19 cases in that nation are due to the Omicron variant.

Cases have appeared in a number of countries beyond the African continent, including (as of December 1) the first case reported in the US. The patient had returned from South Africa on November 22 to San Francisco, and tested positive for Omicron on November 29. This patient was fully vaccinated, but had not received a booster. The patient’s symptoms thus far have been mild.

The spread of cases has been rapid and concerning. For example, on Friday, November 26, a KLM flight from South Africa to Amsterdam carried a number of passengers who tested positive for the Omicron variant. According to Dutch officials, more than 60 passengers on that KLM flight plus one other flight tested positive for COVID, and of those 60, 14 had the Omicron variant. The 60 passengers who tested positive were quarantined. However, the other passengers, all of whom had been exposed to the virus during the flight, were permitted to go on their way. It was reported that during the KLM flight, masking was haphazard.

A passenger on that flight was quoted in the NY Times as follows: “We were in the same place, the same room. I felt like a pig in a pen. They were completely spreading the virus around us.”

Below is a list of the nations where Omicron has emerged as of December 1 and the percentage of total cases caused by Omicron.

That was as of December 1. As of today (December 7) as I am writing this, the number of cases in the US has grown very rapidly, with cases in 30 states. Other nations where Omicron has been sequenced include Belgium, Brazil, Canada, Czech Republic, Denmark, Finland, France, Iceland, India, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Nigeria, Norway, Portugal, Réunion, Saudi Arabia, Singapore, South Korea, Spain, Sri Lanka, Sweden, Switzerland, and the United Arab Emirates. On Monday, December 6, the UK had 336 cases and Denmark reported 261 cases.

In South Africa, the surge in new COVID-19 cases has occurred very quickly. A month ago, South Africa had about 300 new cases a day, but on Friday December 3 and again on Saturday, the figure was more than 16,000. It is not known how many of these new cases were due to Omicron, but the sense among South African scientists is that most of the new cases are due to that variant.

All of this is to say that in all likelihood, the Omicron variant will spread quickly.

Whether it will frequently result in severe illness and death is not known for certain at this time, but some data from South Africa suggest that the variant will cause milder disease than previous coronavirus variants. A report from the Steve Biko/Tshwane District Hospital Complex in Pretoria said that of the 42 people hospitalized with COVID on December 2, 29 (70%) were not oxygen-dependent. Of the 13 patients on supplementary oxygen, four required it due to causes other than COVID. Only one of those 42 hospitalized patients was on intensive care.

Fareed Abdullah, MD, director of the office of AIDS and TB research at the South African Medical Research Council, said “What’s interesting this time around – and we want to be cautiously optimistic about it – is that most patients in the hospital are what we are calling ‘incidental COVID.’  Two-thirds of our COVID patients over the last two weeks are there for another diagnosis. That’s unusual, that’s different from previous waves.”

The overall data from South Africa supports those findings. In spite of the very large surge in new cases, only 106 patients were in intensive care over the past two weeks. Most of the patients were admitted for reasons unrelated to COVID. A report stated that their infection is an incidental finding in these patients and is largely driven by hospital policy requiring testing in all patients.

Experts in other parts of the world have not jumped on the optimism bandwagon. Even if Omicron turns out not to be as deadly as previous variant, Delta is still out there killing people. Caution continues to be the guiding principle.

What do we know about the mutations in the Omicron variant?

This variant carries many more mutations than did the previous variants. As we said earlier, Omicron has about 50 mutations, 32 of which are in the spike protein. In contrast, the Alpha, Beta, Gamma, and Delta variants had about 8 to 10 mutations in the spike protein. That the mutations are in the spike protein is highly significant, since it is the spike that the antibodies recognize and inactivate. Therefore it is likely that the antibody response to the Omicron variant will be considerably reduced.

However, the antibody-mediated immunity is not the only form of immunity that protects us. In vaccinated individuals and in persons who have recovered from COVID, there is a persistent degree of cellular immunity, mediated by B-cells and T-cells. The neutralizing antibodies form the first line of defense, so to speak. These antibodies are generated in response to exposure to the virus or to the vaccine, and they are specific to that virus or vaccine. The effect of the antibodies is to prevent the virus from finding an accommodating environment in the host. The virus cannot replicate in the presence of a sufficient amount of antibodies, and therefore cannot infect the host. To put it simply, antibodies prevent infection.

Cellular immunity is not so rapid. B-cells and T-cells are not specific antagonists of any single pathogen; however, they are able to recognize and attack a wide range of invaders. Anna Durbin, director of the Center for Immunization Research at Johns Hopkins Bloomberg School of Public Health, said T-cells may not be enough to prevent infection with the Omicron variant, but should help shut down the disease it triggers, if infection occurs. “You will have some protection if you were vaccinated. Our immune systems have seen parts of that spike protein before.”

Barney Graham, former deputy director of the Vaccine Research Center at the National Institutes of Health, said he too would expect people with some pre-existing immunity to the coronavirus will have T-cells that cross-react with the new variant; they will kick into gear if the person contracts the virus. “We’re not a blank slate anymore. We have a lot of complex, nuanced immunity that may not be perfectly matched, but it is going to overall give us an advantage that we didn’t have two years ago.”

So, while the fully vaccinated may not be fully protected from infection with the Omicron variant, they will likely benefit from a degree of protection from serious illness. This will probably not be a repetition of the initial outbreak of the coronavirus in March 2020.

Other matters relating to the COVID-19 pandemic

Just about a year ago, Doc Gumshoe posted a piece headlined by a question about the COVID-19 pandemic, to wit, “Where are we now, and where are are we headed?” That is still the question. Now, a year later, we’re in possession of a great deal more information and perhaps a bit more clarity, even though the emergence of the Omicron variant has attracted most of the attention since the first cases were detected and the cause was identified. Some of the information appears contradictory, at least as it pops out of the news media and hits us between the eyes. But perhaps that seemingly contradictory information contains valuable clues about where we’re headed.

Is the COVID-19 pandemic going to become endemic?

That’s what a number of the experts seem to think, and on careful consideration, I’ll go along with them. The coronavirus is not going to disappear. In some parts of the world it will become relatively rare, while in other parts it will be a common presence – i.e., endemic.

That does not imply anything relating to the severity of the illness caused by the virus. As the virus mutates, the variants that arise from these constant mutations will have an enormous range of characteristics. The characteristics that are most favorable to the survival of the coronavirus are that it can easily invade the human host, and that it does not affect the host in such a way as to prevent the host from transmitting the virus to other potential hosts. The ideal survival characteristic is that, once having invaded the host and employed the host’s cellular system to reproduce, the host maintains normal contact with other human beings and transmits the coronavirus to those persons. If the coronavirus quickly made its host very ill, with severe symptoms, that host would be much less likely to transmit the virus to others. Therefore, making its hosts severely ill is not a survival characteristic for the coronavirus, or any other virus.

So, from the perspective of the virus, the ideal pattern is to be highly infective but not highly sick-making. Like the common cold – it’s hard not to catch cold from time to time, but when you catch it, it’s not going to make you terribly sick.

That’s in the future, or at least, that’s what I hope the future of COVID-19 will look like: present in many parts of the world, but not highly dangerous.

As for the present, the attention-demanding news item is that the COVID-19 pandemic has taken the lives of at least 5 million of us earthlings. That was confirmed on Monday, 1 November, by the Johns Hopkins Center for Systems Science and Engineering, which has been keeping a highly detailed dashboard of new and total cases and new and total deaths by nations and regions since the beginning of the pandemic. Now, a month later, the total number is 5,267,917.

That figure is at best an estimate. Many countries, such as India and African nations, have been unable to keep an accurate count of their fatalities. The veracity of fatality numbers from some other countries (like Russia) has been questioned. Some experts have suggested that the true number of global fatalities could be double that estimate – 10 million, or even more.

The pace of fatalities has been increasing. It took nine months for the coronavirus to kill its first one million victims. The next million met their fate in three and a half months, another three months to get to three million, and two and a half months to reach four million.

The US (shamefully) leads the world in COVID-19 deaths, with 785,912 as of December 3, 2021. The US is followed in this appalling contest by Brazil, with 615,279 deaths, India, with 470,115 deaths, Mexico, with 294,715 deaths, and Russia, with 273,463 deaths.

While we’re looking at statistics, it’s interesting that the first and steepest peak in both cases and deaths came in January of 2021. As of 10 January 2021, the weekly average for new cases was 1,735,000, and for deaths the peak weekly average was 23,415 as of 17 January 2021. The second peak came in September, 2021, with a weekly average of new cases of 1,149,000 as of 5 September, and a weekly average of new deaths of 14,452 as of 26 September 2021.

The rates both of new cases and new deaths declined significantly after September, but the curve started to go the other way in mid-November, perhaps due to the season, with more people congregating indoors. We’ll almost certainly see the upward curve become steeper as Omicron spreads.

Might there be something to be learned from India’s recent experience with COVID?

COVID-19 in India: a huge spike and then a huge decline: what’s happening?

When the Delta variant hit India, the spike was colossal. At one point the rate of new cases in India amounted to just about half of the global total. The surprise around this event was that after the Delta spike, the steep decline in new cases was unprecedented, and highly surprising to many expert observers.

As you may remember, when COVID first hit India, the government had put in place a number of very strict protocols. Many of these turned out to be not just ineffective, but harmful and conducive to further transmission of the virus. For example, many workplaces were shut down. As a result, a huge number of their employees had no choice but to go back home to their villages. They rode on crowded trains and took the virus back to their home villages. Quarantines were enacted in crowded slums, which meant packing even more people into confined places. Restricting the hours of grocery stores and other shops simply meant that during the hours when these little businesses were open, they were more crowded than ever. The measures that had been seen as effective in other countries simply did not work in India, with its 1.4 billion population crowded into a relatively small space.

After that first surge eased back a little, restrictions were loosened, and people returned to a more or less “normal” round of activities. Of course, there continued to be new cases and deaths, but the trend didn’t seem to be straight up as it had been initially.

Then came Delta and another huge spike, initially followed by a seemingly “normal” tailing off of the spike. However, after the first downward turn of the curve, the decline in new cases was very large and very swift.

The Delta spike was referred to by some epidemiologists as a “virus inferno.” By some estimates, over 70% of the entire population of India were to some degree infected with the coronavirus. The reason that there was no marked resurgence of the virus after that enormous increase in new cases is that the virus had “no place to go,” in the words of Bhramar Mukherjee, PhD, of the University of Michigan School of Public Health in Ann Arbor.

It has been emphatically pointed out that the absence of a new surge in COVID-19 cases should not be taken as evidence that the pandemic is over in India. The biggest festival, Diwali, took place on 4 November. Many millions of people crowd together to observe the festival, and precautions have been thrown to the winds, creating a situation ideal for the transmission of the virus. However, the degree of immunity acquired through the widespread exposure to the virus will have a major dampening effect on the transmissibility of the coronavirus.

Might India have taken the first step on the way to herd immunity?

And might something similar be happening in Florida?

The cooling off of a hot spot

The surprise is that Florida at this time has the lowest new COVID-19 case rate in the US. The Florida case rate has made an extremely rapid U-turn. About 14 weeks ago, in mid-August, Florida was averaging 25,000 new cases of COVID-19 per day. This comes to 116 cases for every 100,000 residents, which was easily the worst case rate in the US, and one of the worst in the world. Since then, Florida’s daily average for new cases has dropped by more than 90%, to about 1,700 cases per day, which comes to 7 cases per 100,000 residents. Louisiana is the only other state with a similar daily case rate. In contrast, Connecticut’s daily case rate is 10 per 100,000 residents, and New York’s is 20 new cases per 100,000 residents.

Of those four states, however, Florida has by far the highest death rate: 0.49 deaths per 100,000 residents. The death rate in Connecticut is a quarter as high, with 0.12 deaths per 100,000 residents. New York’s is 0.17 deaths per 100,000 residents, and Louisiana, whose daily case rate is about the same as Florida’s, has a death rate that’s about one half of Florida’s, at 0.24 deaths per 100,000 residents.

So, as we see, the decline in the new case rates has not been accompanied by a decline in the death rate. It can be argued that the new case rate is a leading indicator, and that if there are fewer new cases now, there will be fewer deaths in a month or so. For the sake of the worthy citizens of Florida (and the unworthy as well), I hope so. But we haven’t seen it yet.

It’s not quite as if Florida has anything to congratulate itself about in relation to its handling of the pandemic. The vaccination rate is low, and the governor has specifically encouraged vaccine opponents. For example, he offered hiring bonuses to policemen who have lost their jobs rather than be vaccinated, so as to induce them to move to Florida and join the police forces there. And he has vocally opposed requiring students to wear masks.

Is it possible that the combination of the very large number of people who got infected during the Delta peak and those who actually did get the vaccine in the state of Florida added up to something approaching herd immunity? That, after all, is the hope of the epidemiologists.

Is it a sign that the COVID pandemic may be evolving into endemic COVID?

Here’s some information that is highly encouraging for the vaccinated population.

Even though protection from infection wanes, vaccination confers powerful protection from death.

Some highly interesting data come from Scotland, where 3,273,336 people are fully vaccinated. That’s out of a total population of about 5,470,000, including children. Of these, 1,205,642 received the Pfizer vaccine, and 2,026,198 the AstraZeneca vaccine. In those two cohorts, there were a total of 236 deaths, which amounted to a mortality rate of 0.007%. There were no deaths in the 41,476 persons receiving the Moderna vaccine.

In the segment of the population older than 80 years, there was a large difference in the mortality rate due to COVID-19 between the vaccinated and unvaccinated. In the unvaccinated, the death rate was 420 per 10,000 person-years, while in the vaccinated that death rate was 14 per 10,000 person-years. In the next younger cohort, 65 – 80 years, those rates were 64.8 in the unvaccinated versus 4.2 in the vaccinated.

It should be noted that of the 236 deaths attributed to COVID-19, 230 individuals had more than one cause of death listed on the death certificates.

Data from the US similarly supports the conclusion that vaccination against SARS-CoV-1 is highly protective against severe illness and death. However, the protectiveness of the vaccines against infection dipped to some degree in mid-year, as the antibodies generated by the vaccine waned, and also as the Delta variant surged.

CDC data reported 6,587 COVID-19 breakthrough cases as of July 26, 2021, and 1,263 deaths. At that time, more than 163 million people in the US had been fully vaccinated. According to those figures, fewer than 0.001% of fully vaccinated people died as a result of a breakthrough COVID-19 infection.

A study tracking vaccine effectiveness in 780,000 US veterans getting treatment at Veterans Health Facilities found that overall vaccine efficacy against all types of infection with the coronavirus dropped dramatically between February and October, 2021, from 87.9% in February to 48.1% in October. However, effectiveness is preventing death remained fairly robust. In the period from July to October, vaccine effectiveness against death among veterans under 65 years who had sustained breakthrough infections was 73% for the Johnson and Johnson vaccine, 81.5% for Moderna, and 84.3% for Pfizer’s.

If those effectiveness figures look weak in comparison with the tiny percentage figures cited above with regard to Scotland and the CDC data reporting that fewer than 0.001% of the fully vaccinated had died from COVID as of last July, it’s largely because they are a percentage of a percentage. In the veterans study, efficacy against infection is stated as the number of infected divided by the total number of vaccinated, while efficacy against death is the number of deaths divided by the number of infected. In the Scotland data, the data cited was the percentage of the total population.

All the same, these data strongly support the need for booster shots. Immunity does wane, and the risks of serious illness and death rise.

Another factor to consider in evaluating the data in the veterans study is that the study population was largely male, and included a higher proportion of minorities. Both of these groups tend to have more serious disease and a higher death rate.

Which country is experiencing the highest COVID-19 death rate?

Although the US leads the world in COVID deaths, at this moment the country with the highest death rate on a per capita basis is Romania. According to the NY Times, Romania’s death rate relative to population is almost seven times higher than that in the US, and almost 17 times higher than that in Germany. The Romanian death rate is part of the COVID surge that has overwhelmed several countries in Eastern Europe, likely due to the very low rate of vaccination that prevails there. This sharp increase in the case load has placed a colossal burden on the Romanian health system, such that several ambulances at a time are frequently waiting outside of the biggest infectious disease hospital until a space can be found for the acutely ill patients they are carrying.

Statements by elevated members of the Eastern Orthodox clergy have aggravated the situation. A bishop in Southern Romania attempted to comfort his flock by saying “Don’t be fooled by what you see on TV. Don’t be afraid of COVID.” On October 14, another bishop, Ambrose of Giurgiu specifically told worshipers in this small town not to rush to get vaccinated. Many clerics and some influential bishops have denounced vaccines as the Devil’s work.

A statement by an elected member of Romania’s parliament led a protest that blocked the opening of a vaccination center, denouncing the COVID pandemic as “the biggest lie of the century.”

Romania has the second-lowest vaccination rate in Europe, with only 44% of adults having received at least one shot. Bulgaria’s rate is the lowest, at 29%. Overall, in the European Union, the vaccination rate is over 80% and several countries have a 90% rate of vaccination in adults.

Health workers in Romania are extremely distressed about the situation, especially because, as they say, it could easily have been prevented.

COVID-19 vaccines protect recipients from death from other causes

There seems to be another totally unrelated benefit from the COVID vaccine. This was based on data from 11 million people enrolled in the CDC’s Vaccine Safety Datalink from December 2020 through July 2021. They compared mortality rates in vaccinated individuals with those in an unvaccinated cohort. The unvaccinated cohort consisted of people who had received at least one influenza vaccine in the previous two years, so as to ensure that the two populations had comparable health-seeking behavior. Non-COVID-19 deaths were defined as those that did not occur within 30 days of a positive SARS-CoV-2 test via RT-PCR or rapid test or a COVID-19 diagnosis.

The study population consisted of 6.4 million vaccinated subjects and 4.6 million unvaccinated subjects. Of these, about 3.5 million received the Pfizer vaccine, 2.6 million the Moderna vaccine, and 350,000 the J & J vaccine.

After excluding COVID-19-associated deaths, the standardized mortality rates were 0.35 and 0.34 per 100 person-years for Pfizer and Moderna recipients and 0.84 per 100 person-years for the J & J vaccine. This compared with 1.11 per 100 person-years for unvaccinated individuals.

To put this in simple terms, it looks as though the non-COVID death rate in unvaccinated persons was about triple the death rate in the people who got the Pfizer or Moderna vaccines. The people who got the J & J vaccine were not quite as fortunate.

It seems to me that there are three possible ways to look at this data:

• One, the COVID vaccines in some way contribute to our overall immune response, and not just to immunity from the evil coronavirus.
• Two, the unvaccinated cohort, all of whom had received flu shots, were essentially unhealthy, and that’s why they all went and got flu shots.
• Or three, it was those flu shots that did them in!

Doc Gumshoe hopes that the correct answer is Number One.

What do antibody levels really mean?

As we’ve learned by now, what the vaccines do initially is boost our levels of antibodies to the coronavirus. Vaccines also stimulate the creation of specific cells that recognize and remember features of the coronavirus. These are memory B-cells, which have the capacity both to mobilize antibodies and also to summon up killer T-cells. The T-cells constitute a sort of standing army whose mission is to attack and kill invaders. Cellular immunity – B-cells and T-cells – last a long time. As we have said, cellular immunity to the first coronavirus has been detected in persons who had that disease almost 20 years ago. In contrast, antibody-mediated immunity tends to wane in less than a year.

In terms of action, antibodies work much faster than the B-cell/T-cell duo. Perhaps we could simplify by putting it this way: antibodies prevent the coronavirus from causing infection, while the B-cell/T-cell duo acts to prevent illness once the virus has entered the body.

Some people have sought to determine just what their antibody levels were and how much they had waned in order to come to a decision as to getting a booster shot. Most commercially-available antibody tests are useful only in answering a simple yes/no question: did you or did you not have COVID? If antibodies are present, you had COVID; if not, then not. But they don’t tell you much about how much antibody-conferred immunity you have going forward.

To get the answer to that question, a neutralization assay is needed. Dr Nathaniel Landau, a virologist in the department of microbiology at NYU Grossman School of Medicine, said that the neutralization assay is the gold standard. In these tests, serum from an infected or vaccinated person is diluted to varying levels, then mixed with a set amount of virus. A dilution of 1:100, for instance, means that 50% of virus was killed when 1 mL of serum was mixed with 99 mL of saline. The more the serum can be diluted and still kill 50% of virus, the stronger the level of immunity provided by the antibody.

Dr Landau said that natural infection with wild-type virus generally confers a titer of 1:400. With the Delta variant, that gets bumped down to 1:100 — which is still pretty good, he noted. Immunity conferred by the mRNA vaccines – Pfizer/BioNTech and Moderna – on the other hand, typically generates a titer of 1:1,000, which is significantly better than immunity generated by infection with the virus itself. Why this is the case is at this time uncertain, but the findings are very positive.

When tested against the Delta variant, protection was diminished for the mRNA vaccines. With Delta, mRNA vaccinated immunity falls to a titer of about 1:250. Dr Landau observed that naturally infected people have been fairly well protected against reinfection, so a titer of 1:100 gives quite good – though not perfect – protection from infection. The mRNA vaccines should still give strong protection against variants.

Similar data should shortly emerge regarding neutralization assays of the Omicron variant versus antibodies. Scientists have been wary of predicting how the antibodies would hold up against the variant, whether the antibodies had been generated through vaccination or previous infection.

A vaccine-related subject that Doc Gumshoe has so far not discussed is the possibility that there may be significant side effects related to the SARS-CoV-2 vaccine – by which I do not mean soreness at the injection site or a day or so of feeling distinctly sub-par. About the only side effect of any consequence is myocarditis.

Myocarditis: what is it and what are the possible causes?

Myocarditis is inflammation of the heart muscle. In many cases, a person with myocarditis is unaware that he/she has the condition, and it often resolves spontaneously. Factors that can cause myocarditis include a number of common viruses and bacteria, including hepatitis C, herpes, HIV, streptococci and staphylococci, as well as alcohol, lead poisoning, spider and wasp bites, chemo and radiation therapy, and any disease that causes inflammation throughout the body, such as rheumatoid arthritis.

Treatment for myocarditis ranges from simple rest for mild cases, treatment of the underlying cause for more acute cases (e.g., anti-inflammatories for rheumatoid arthritis), to heart transplants for the most acute and refractory cases.

Myocarditis has been reported in relation to the COVID-19 mRNA vaccines. When it occurs, it is usually after the second dose, and mostly in males under 30 years of age. Even in this population, myocarditis is rare. The CDC has reported a total of 877 cases of myocarditis in the US, where more than 80 million people have been totally vaccinated.

As to what the mechanism through which the mRNA vaccines might cause myocarditis, so far there are no clear answers, but considerable speculation. One possibility is that when the vaccine is administered, the injection accidentally hits a vein, and the vaccine travels directly to the heart, where it triggers an inflammatory response. This theory has been tested in Hong Kong, where researchers found that intravenous injection of the Pfizer/BioNTech vaccine into mice induced myocarditis and also pericarditis, which is inflammation of the tissue lining the heart.

Another possibility has to do with the similarity of the coronavirus spike protein to heart muscle proteins. Neutralizing antibodies created in response to vaccination may start attacking those heart muscle proteins due to that similarity. Researchers at the Mayo Clinic are looking into whether heart muscle cells link with the mRNA and produce the spike protein, thereby triggering an immune response against those heart muscle cells.

Some researchers have speculated that testosterone may also play a role. Younger males (of course!) have much higher levels of testosterone, and it can magnify the inflammatory response.

If it is indeed the case that a person can have myocarditis and be unaware of it, I would guess that a great many more people than the 877 reported by the CDC had episodes of myocarditis as a reaction to the vaccine. However, the weight of the evidence is that overall, the possible incidence of myocarditis as a reaction to the coronavirus vaccine does not significantly detract from the benefit side of the benefit-to-risk equation.

And now, shifting our focus away from vaccination issues to treatment of the actual disease….

The COVID-19 pills from Merck and Pfizer are very promising

Merck’s oral treatment for COVID-19 popped onto the scene a bit earlier than Pfizer’s, with their application for Emergency Use Authorization submitted to the FDA on November 4th. Molnupiravir is a polymerase inhibitor, and the way it attacks the coronavirus is by inserting errors into the virus’s genetic material, such that the virus does not survive. The virus essentially mutates itself to death.

When given within five days of the onset of symptoms, molnupiravir was initially reported to be about 50% effective in preventing hospitalization or death. However, a more recent analysis reduced this effectiveness level to about 30%. The treatment regimen consists of 4 capsules twice a day for 5 days, adding up to a total of 40 pills for the complete course of treatment. The estimate cost of treatment with molnupiravir is about $700 per patient.

Also on November 4th, molnupiravir received approval from the UK medicines regulator. Molnupiravir will be marketed under the trade name Lagevrio. It was developed by Merck in collaboration with Ridgeback Therapeutics. Originally, the drug was developed by Emory University as a treatment for influenza.

Pfizer’s pill, to be called Paxlovid, holds out the promise of superior efficacy. The drug is a combination of ritonavir (an old HIV drug) with a new agent designated as PF-07321332, which is a protease inhibitor specifically designed to target SARS-CoV-2. (By the way, I have noticed several mentions in the media in which Pfizer’s new combination is referred to simply as “ritonavir,” without mentioning PF-07321332. This is the kind of error that could cause a great many people, including some health workers, to demand treatment with the old HIV drug, which by itself would be useless.)

A clinical trial with the new combination therapy was conducted in 1,219 adults who had contracted COVID-19 and had at least one underlying condition that put them at risk of severe COVID. The Pfizer pill registered an efficacy level of  89% in the trial subjects who initiated treatment within three days after onset of symptoms. In the trial subjects who started treatment on the fourth or fifth day after symptom onset, the efficacy level was very slightly diminished, to about 85%. In an interim analysis, 0.8% of patients in the Paxlovid group who received the drug within three days of symptom onset were hospitalized through day 28 (three hospitalizations, no deaths) compared to 7.0% of patients who received placebo in this time frame (27 hospitalizations and seven deaths).

The rates of adverse events were similar between the treatment and placebo groups, with the placebo groups reporting a very slightly higher rate, suggesting that the COVID-19 symptoms were more troubling that the drug side effects.

The treatment course consists of a total of 30 pills taken over a period of five days.

Just one day after Merck received Emergency Use Authorization for molnupiravir, on November 5th, Pfizer applied to the FDA for EUA and registered Paxlovid as a trade name for the ritonavir/ PF-07321332 combination.

The US government has struck a deal with Pfizer for enough pills for 1.7 million courses of treatment, and negotiations for another 3.3 million courses of treatment are going on currently.

A last minute addition to the list of available COVID-19 treatments: as of December 3, the UK regulatory authorities have authorized a treatment from Glaxo SmithKline – sotrovimab (Xevudy) which reportedly cuts hospital admission and death by 79%.

A word of caution regarding those treatment options: for these pills to be available for use, patients need to be tested quickly, as soon as any symptoms emerge. Their efficacy has been demonstrated only when treatment is started soon after the first suspicious symptoms emerge. Insisting on getting the results of a PCR test, which may take as long as a week, would greatly reduce the effectiveness of these pills.

The health-care community has received the news of these oral medications with relief, and a degree of enthusiasm. This is not only because of the demonstrated effectiveness of these drugs in preventing the worst outcomes of the coronavirus infection, but because they take a huge load off the health-care system. Let me remind you, these drugs are pills. Plain, old-fashioned pills. All one needs to administer these drugs is a glass of water. In contrast, the alternatives, such as antibody serum or the drug remdesivir (regardless of their claimed efficacy) need to be delivered in a medical facility by a health-care worker. They are given intravenously or by infusion. Also, these pills are relatively inexpensive.

All in all, the arrival of the Merck, GSK, and particularly the Pfizer pills, is one of the best bits of news that we have had regarding the COVID-19 pandemic.

*****

I have no doubts whatever that Doc Gumshoe will be revisiting the COVID topic in future missives, but perhaps we can together take a time-out and consider other happenings in the general health-care area. Do please let me know if there are topics you would like to know more about. I myself might or might not know anything of value, but I will pledge to do some sleuthing for our mutual benefit. And keep those comments coming! Thanks and be well, Michael Jorrin (aka Doc Gumshoe)

[ed. note: Michael Jorrin, who I call Doc Gumshoe, is a longtime medical writer (not a doctor) who writes for us about medicine and health a couple times a month. He has agreed to our trading and disclosure restrictions, but does not generally write directly about investments. His ideas, thoughts and words are his own, and you can see all his past pieces here.]