When I go to the grocery store these days, I see only a few people wearing masks, and in our chorus, my wife and I are among the handful of masked singers. I acknowledge that wearing a mask is a nuisance, and singing through a mask is not much fun. But at the same time I need to pay attention to the unfortunate reality that (as the NYTimes said a week or so ago) “The Pandemic Rolls On For a Certain Group.” That group, as you surely know, consists of people over the age of 65, and I am definitely a member of that group.
In the United States, about three out of four COVID deaths have occurred in people over that age, and the greatest number of fatalities has been in persons over the age of 75. And the death rate continues to rise as we age. The overall death rate in the month of January declined somewhat after a December spike, but was substantial, particularly among that segment of the population discretely termed “seniors.” There were 2,100 fatalities in persons aged 65 to 74, more than 3,500 in the 75 to 84 group, and nearly 5,000 fatalities in those 85 years of age or older. Those deaths amounted to more than 90% of the nation’s COVID deaths this past January.
Hospital admissions of patients with COVID can be taken as an indication of more severe illness. In spite of the very welcome news that, on balance, the more recent variants tend to result in milder symptoms and that the total number of hospitalizations is dropping, there continue to be individuals who develop symptoms severe enough to require hospitalization. Five times as many persons over the age of 70 require hospitalization as do those under the age of 50.
And hospitalization itself can entail risks. The illness that caused the individual patient to be hospitalized can be treated, usually successfully, but the patient can be exposed to other risks. Patients endure inactivity and sleep deprivation, and may be exposed to other diseases. Simply being bedridden increases the risks of any pulmonary disease.
All this is taking place in an overall environment where the risks from COVID are being minimized, mostly due to a steep decline in the number of new cases and in the number of deaths. According to the Centers for Disease Control, the decline in the number of new cases went from a weekly high as of January 19th, 2022 of 5,630,722 cases to 259,639 cases the week ending February 15th, 2023. The 2/15/23 figures are 4.6% of the 01/19/22 figures. That’s a decline of 95.4% according to my primitive arithmetic.
The weekly death figures went from a high of 23,378 as of January 15th, 2021 to 2,838 deaths the week ending February 15th, 2023, 12.1% of the 01/15/21 figures, a decline of 87.9%.
The highest peak in new cases by far occurred in early 2022, but there were peaks in deaths in early 2020, then again in the winter of 2020 – 2021, and late fall and winter 2021 -2022. Since spring 2022, the reported death rate has stayed fairly constant, between 350 and 450 deaths per day.
However, those good tidings have not been evenly distributed among the entire population. As you saw, seniors have borne the brunt of the pandemic. But it has also not been evenly distributed geographically. A map of the US, based on census data, shows that in most of the country the case rate is fairly low – mostly less than 25 new cases per 100,000 population. There are hot spots here and there, where the case rate is more than 100 new cases per 100,000, such as in Texas, Missouri, and South Dakota. Overall, Alabama and Louisiana have the highest case rates.
The case rates and the death rates are in inverse proportion to the vaccination rates – those rates are highest in states with the lowest vaccination rates, and vice-versa. For example, among the states with the lowest vaccination rates – below 50% – are some of the states with the highest case rates, such as Mississippi, Alabama, Louisiana, and Tennessee.
Despite their being at higher risk from the coronavirus, seniors tend to have a lower vaccination rate. Only 40.8% of seniors have received a bivalent booster, according to a CDC survey posted in January. Many seniors are confident that they already have strong protection, and others distrust the effectiveness of the booster or worry about the side effects. And another factor is that many elders have difficulties in getting the booster, including finding a site, making online appointments, and travelling to the location where they can actually get the booster shot.
Even in nursing homes, which as you remember got hammered in the early days of the pandemic, just slightly over half of nursing home residents were up to date on vaccination, and a disgracefully low – 23%! – of staff members had received boosters. In the beginning months of the pandemic, the Federal government sent healthcare workers into nursing homes to deliver vaccines, but since then nursing homes have been on their own.
The benefits of masking are questioned
In the February 22nd New York Times there was a short opinion piece by Bret Stephens entitled “ ‘Do Something’ Is Not Science.” He was referring to a review in the Cochrane Library entitled “Physical interventions to interrupt or reduce the spread of respiratory viruses.” Stephens quotes the lead author of the Cochrane review, Tom Jefferson: “There is just no evidence that they” – the masks – “make any difference. Full stop.”
Cochrane reviews are not original research. What they do is assemble the content of large numbers of studies and clinical trials and attempt to arrive at general conclusions. Jefferson was not the author of any of the studies reviewed in that paper, and in my opinion, even though he was the lead author, his statement as quoted by Bret Stevens does not come close to reflecting the actual content of the Cochrane review.
As you can tell by the title, the review covered the whole range of physical interventions, including masking of course, but also hand washing, not touching the eyes or mouth, wiping surfaces with disinfectant, wearing gloves or protective gowns, distancing, and screening. All in all, the Cochrane review identified 78 relevant studies. Of these, six were completed during the COVID-19 pandemic. And of those six studies, two were conducted in Mexico, and one each in Denmark, Bangladesh, England, and Norway. Cochrane judged the evidence in these studies to be “moderate certainty” and stated that the risk of bias was “mostly high or unclear.” It was noted that “adherence with interventions was low in many studies” and that “harms were rarely measured and poorly reported (very low-certainty evidence).”
In other words, even though these studies were supposedly comparing mask-wearing with the absence of masks, adherence to that intervention was “low in many studies.” Meaning that in many cases they were comparing a group that wore masks with a group that maybe wore masks some of the time, and that “harms” – i.e., getting infected with COVID – were rarely measured and poorly reported.
So what does it mean when Tom Jefferson makes that absolute statement that there is no evidence that masks make any difference? What it really means is that the Cochrane review failed to find clear evidence that masks did make a difference. The Cochrane review, from my perspective, failed to find evidence of any kind whatever. Pretty clearly, Jefferson is speaking as a mask skeptic, and he is taking failure to find evidence as evidence of failure.
As for the masks themselves, we do know that they effectively capture respiratory droplets, which transport fairly hefty doses of viruses. They are not as effective in capturing aerosols. Since mask-wearing became the norm (yes, it’s the norm no longer) the incidence of flu has plummeted. And I haven’t caught cold in three years. For sure, masks are doing something.
Coronavirus variants
The coronavirus, SARS-CoV-2, is an unusually shifty creature, an evil-doer with a great many disguises. When it first emerged, it was generally labeled “the Wuhan virus,” based on the assumption that Wuhan was where it emerged from being a virus that infected animals and developed the ability to infect humans. Since then, the coronavirus has mutated many, many times, and some of the mutations have been labeled as “variants of interest” and “variants of concern.” Variants of interest are those that are expected to affect transmission or treatment, while variants of concern show evidence of being more contagious, causing more severe disease, or being less susceptible to public health measures – essentially, being more dangerous. If the changes that emerge due to mutation are advantageous to the virus, the variant tends to spread more, and will gradually replace other variants.
In May of 2021, the World Health Organization began labeling new variants of interest or concern with letters of the Greek alphabet. The purpose was to make them easier to remember, but also to avoid the stigma that was associated with referring to them by the country where they were first detected. Some of these variants, such as Eta, Iota, and Kappa, have been taken off WHO’s watchlist because they are no longer thought to be a threat. The Greek letter “Nu” is not used, because it sounds like “new.” And “Xi” would appear to point to the leader of China as somehow associated with a particular strain of the coronavirus.
Alpha
The first named mutation was Alpha (B.1.1.7), detected in the UK in December of 2020, about a year after the Wuhan strain was recognized, and by December 2021 it had spread to 192 locations worldwide. It carries several mutations in the spike protein, which is the instrument that the virus uses to gain entry to human cells. Alpha is thought to be about 50% more contagious than the original Wuhan strain, and perhaps results in more severe disease. One of the mutations in an Alpha variant, the E484K mutation, may help the virus escape the neutralizing antibodies that the human body generates as a result of vaccination or previous infection.
Beta
Beta (B.1.351) was detected in South Africa, also in December 2020, and since then has been detected in 139 locations worldwide. In addition to three of the mutations observed in the Alpha variant, Beta contains a K417N mutation which may help the virus avoid neutralizing antibodies. It is thought to be somewhat more transmissible than Alpha or the original Wuhan virus, but there is no evidence that Beta produces a more severe disease. Recent data from Canada suggest that one dose of the Oxford/AstraZeneca vaccine is about 82% protective against hospitalization or death from Beta, and two doses of the Pfizer/BioNTech or Moderna vaccines provide very strong protection against Beta. The global prevalence of the Beta variant diminished markedly when the Delta variant appeared and became the most prevalent variant.
Gamma
Gamma (P.1) was first detected in Brazil, in January of 2021 and declared a variant of concern. It shares many of the same mutations as Beta including the K417T mutation which may make it easier for this variant to spread. The existing vaccines seem to work well against Gamma.
Delta
Delta (B.1.617.2) was first detected in India in May of 2021 and rapidly spread to 176 countries worldwide, overtaking existing variants to become the dominant variant in many countries. It is estimated that Delta caused more than twice as many infections as previous variants—in Connecticut, it was estimated to have been 80 to 90% more transmissible than the Alpha variant. In the US in June 2021, after a steady decline in COVID-19 cases and hospitalizations, the arrival of Delta coincided with a rapid reversal of that trend. In the fall of 2021, there were surges even in the most vaccinated states, prompting experts to urge people to get their booster shots.
Delta contains the D614G mutation, plus many additional ones not seen in other variants of concern, including mutations that may increase infectivity, that help it avoid recognition by the immune system, and that are associated with an enhanced ability to trigger severe disease. Some data from Scotland suggest that in unvaccinated persons, Delta is associated with approximately double the risk of hospitalization as Alpha. Data suggests that vaccines are slightly less effective against preventing infection with Delta, but they remain strongly protective against severe disease.
Omicron
The original Omicron strain (BA.1) was first identified from a specimen collected in Gauteng province in South Africa on November 9th, 2021. It evidently spread from South Africa with remarkable rapidity. By December 3, 2021, it had been verified in 22 locations worldwide, including parts of North and South America, Europe, Africa, Asia and Australia. By January 2022 Omicron was causing daily case numbers in the US to skyrocket to over a million. In 2022, it spawned a number of subvariants, including BA.5, BQ.1, and BQ.1.1. In January 2023, a new Omicron subvariant called XBB.1.5 was causing the most infections in the US.
According to the World Health Organization, it is not yet clear whether Omicron is more easily spread from person to person compared to other variants, or whether infection with it causes more severe disease. There is currently no information to suggest that symptoms associated with Omicron are different from those from other variants. There is preliminary evidence that persons infected with Omicron are more likely to be reinfected if they are exposed. At this point, there are concerns in the healthcare community that the Omicron variants may be more likely to evade current COVID vaccines. Tests to assess this risk are currently ongoing, but there are some indications that while vaccinated individuals may become infected, they continue to be well-protected against disease severe enough to require hospitalization.
Meanwhile, experts are still learning about several newer Omicron strains circulating in the US, each of which, as of mid-December, were causing less than 6% of infections. They include BF.7, XBB, BN.1, BF.11, and others. Omicron’s subvariants are considered to be especially efficient spreaders of the disease, and while scientists are still learning about XBB.1.5, they say it is the most transmissible strain of the virus so far.
Will Omicron be the last named variant of concern? Almost certainly not. Viruses mutate, some more frequently than others, and the coronavirus seems to be one of the most frequently mutating viruses. The relevant question is whether the newly mutated viruses will be more transmissible and – more crucial – cause more serious disease. Thus far, the pattern has been that they are more transmissible, but cause less – rather than more – serious disease.
If you look at this from the point of view of what’s best for the virus, that makes perfect sense. The virus “wants” to infect as many hosts as possible, because that’s where the virus reproduces (remember, viruses can’t reproduce on their own the way bacteria do – they can only reproduce inside a living host.) But after it invades the host, it “wants” the host to go about its life so that it comes into contact with other potential hosts, and so that the virus can infect those new hosts as well. And that’s how the disease spreads.
From the perspective of survival and spread of the virus, the ideal model for viral survival is HIV. Patients with HIV can survive for years transmitting the virus without knowing that they are infected. On the other hand, a virus that quickly kills the host is doing itself no favors.
So, while there will continue to be new SARS-CoV-2 variants, my guess is that as they continue to mutate, the disease they cause will in general be less severe. That doesn’t mean that we have nothing to worry about, but it does mean that we aren’t looking forward to something worse.
The Omicron subvariants exhibit resistance to neutralizing antibodies
Neutralizing antibodies are one of the ways that vaccines generate protection against infections. The antibodies are generated quickly in response to the elements of the vaccine that closely mimic the antigens – the parts of the virus that attack the host. Vaccines can also generate protection by contributing to another kind of immunity – cellular immunity – in which some cells learn to recognize and remember the characteristics of the invading pathogen and summon up the troops of killer T cells to get rid of the pathogen. But while cellular immunity protects against illnesses resulting from infection, antibody-mediated immunity attempts to prevent infection in the first place by neutralizing the invading pathogen.
It seems that some of the Omicron subvariants are able to evade the action of the neutralizing antibodies, and as a result, are able to infect the host in some cases despite vaccination. The specific Omicron subvariants that have been shown to have this evil capability are XXB.1.5, CA.3.1, and CH.1.1.
The subvariants demonstrated resistance to the neutralizing antibodies generated by vaccines, in particular the monovalent vaccines that were originally developed. However, the more recent bivalent mRNA vaccines induce up to eight times higher levels of neutralizing antibodies than the older monovalent vaccines, providing a much stronger wall for the virus to breach. This is not the final answer to the battle against SARS-CoV-2; it will keep on mutating and scientists will have to keep working to keep the vaccines current.
In case you’re a bit confused …
Yes, the naming of the coronavirus variants is confusing. Once you get past the obvious Greek letter names – Delta, Omicron, and so forth – there are all those variants named with plain old fashioned Roman letters and Arabic numbers – BA.5, XXB.1 and their ilk. Those names are the so-called “Pango lineage”; Pango standing for Phylogenetic Assignment of Named Global Outbreak Lineages. But there’s yet another naming convention, which keeps track of the changes in the individual spike proteins of the coronavirus, e.g., G339D, S371L, S373P, S375F, K417N, etc.
I suspect – strongly suspect – that the “Pango lineage” system of naming COVID subvariants was given its name with a somewhat covert reference to the possibility that the coronavirus might have jumped species from pangolins to humans. Somebody then cobbled together the “Philogenetic Assignment” name to fit the acronym. Scientists naming clinical trials do this all the time. They pick a nifty name and then figure out what they can actually title the trial to fit the nifty name. Researchers have to have a bit of entertainment.
Three new studies point to good performance by the bivalent COVID vaccine
One study, published in The New England Journal of Medicine, compared the monovalent vaccines effectiveness over 99 days from late May 2022 to the end of August with the effectiveness of the bivalent vaccine over 99 days from September through late November 2022. In subjects aged 12 and older, the monovalent vaccine’s effectiveness against disease severe enough to require hospitalization was 25%. The effectiveness of the bivalent vaccine was 58.7%. Vaccine effectiveness against severe infection that resulted in hospitalization or death was 24.9% for the monovalent vaccine and 61.8% for the bivalent vaccine. It should be pointed out that the bivalent vaccine targeted earlier Omicron variants, BA.4 and BA.5, but the prevailing variants during the period of the study were BQ.1 and BQ.1.1.
The second study examined the effectiveness of the bivalent booster against the newer variants XBB and XBB.1. The study, published in the CDC journal, Morbidity and Mortality Weekly Report, looked at data from COVID tests conducted at pharmacies from December 1, 2022, to January 13, 2023. Vaccine effectiveness against symptomatic infection was similar against the XXB and XXB.1 variants as against BA.5. For the 18 to 49 age group, the effectiveness against XXB and XXB.1 was 49% versus 52% against the BA.5 variant. Effectiveness against these variants was slightly lower in older age groups, with similar differences between the XXB/XXB.1 and BA.5 variants. Persons vaccinated with the bivalent booster had double the protection of death due to COVID than did persons who had received only the monovalent vaccine. And the bivalent booster conferred about thirteen times the protection from death compared to the risks in the unvaccinated.
…and the original monovalent vaccine reduces the risk of long COVID
A third study, published online by the journal Antimicrobial Stewardship & Healthcare Epidemiology, analyzed vaccine data for 1.6 million people, focusing on COVID symptoms lasting longer than three to four weeks. They found that people who got a single dose of the monovalent vaccine had a 35% lower risk of developing long COVID compared with unvaccinated people. And unvaccinated persons who contracted COVID, recovered, and then received the monovalent vaccine, reduced their risk of long COVID by 27%. The study did not evaluate the impact of boosters on long COVID.
Treatment for long COVID?
So far, there is no form of treatment that is specific for long COVID. In spite of the intense focus on the pandemic these past years, long COVID has not gotten much attention. In November 2021, the CDC estimated that three to five million adults were experiencing long COVID, and a more recent CDC estimate was that 15% of all adults who contracted COVID had symptoms that lasted more than a month. But long COVID has not been the subject of much research by pharmaceutical companies or by the healthcare system in general.
Part of the problem is funding. Many big pharmaceutical outfits have taken in big sums related to COVID, but very few are looking at ways to address long COVID.
Companies like Ampligen and AIM Immunotech have potential candidates for long COVID treatment, but lack the funds to carry out the necessary clinical trials.
One major outlier is Pfizer, which is trying out its approved COVID treatment Paxlovid as a long COVID therapy, with two individual trials underway in conjunction with Stanford and Yale.
The Japanese pharma Shionogi is similarly testing its COVID treatment, ensitrelvir, for long COVID remedy. Exploratory data from the company’s phase 3 trial found that 125 mg of ensitrelvir reduced the risk of long COVID by 45% compared to placebo
Another issue is that federal attention on COVID-19 is winding down. The national public health emergency is set to end in May, and while that will not explicitly impact the FDA’s ability to issue emergency use authorizations, the agency has reduced its level of attention to COVID-related matters.
Long COVID does not appear to present an elevated risk of death, but the symptoms are not trivial. The most common symptom is fatigue that interferes with normal daily activities, but persons with long COVID may also experience a great many significant symptoms including shortness of breath, cough, chest pain, heart palpitations, headaches, difficulty sleeping, depression, and other symptoms.
The desire to stop thinking and worrying about COVID is pervasive, but long COVID deserves more attention than it’s getting.
The US Department of Energy has a notion about where COVID came from
They think, but aren’t a hundred percent sure, that it escaped from a laboratory in China. The evidence, which they said was of “low confidence,” most likely came from the department’s network of laboratories, some of which do biomedical research. They caution that it may be difficult or impossible to verifying their conjecture, because of the fixed Chinese opposition to further investigation and research.
The FBI also has concluded that the virus escaped from a Chinese laboratory, but four other US agencies continue to maintain (with limited confidence) that the virus was first transmitted from an animal to a human host.
We’ll never know for sure.
… and, while we’re talking about China…
China’s COVID tsunami after it relaxed restrictions in December 2022
As we remember (or ought to remember), China went into an unprecedented national lockdown in early 2020, right after the Wuhan outbreak. Entire cities went into quarantine. Infected individuals were removed from their homes to quarantine centers. Travel was restricted. The lockdown had significant impacts on the Chinese economy. But the results were that case rates and fatalities remained very low – that is, until restrictions were lifted in December last year. At that point, case rates and death rates soared.
Even after China eliminated mass testing, health officials in several parts of China continued to test. Hundreds of thousands of people around the country were tested between mid-December and mid-January. Based on those testing results, researchers estimated that 90% of the Chinese population had been infected in a short period after restrictions were lifted. And (according to the New York Times) a leading government epidemiologist stated, on Weibo, a Chinese social media web platform, that 80% of the population had been infected.
China’s official count was 83,150 deaths. This is widely thought to be a colossal undercount. For a start, China has an exceedingly narrow definition of what counts as a COVID fatality. As crematories were swamped in December, Chinese officials only reported as COVID fatalities those deaths that had taken place as a result of respiratory failure. Deaths as a result of liver, kidney, or cardiac failure were excluded. Moreover, the only deaths that were included in the official count were those that occurred in a hospital.
Estimates as to the actual number of COVID deaths in China range from a low of a bit under 1 million, based on travel patterns, to a high of about 1.6 million deaths, based on a model following an outbreak in Shanghai. If the death rate for people infected in China was similar to that rate in the US (that is 1 in 650 persons, or about 0.15%), and if the 90% infection rate of China’s approximately 1.4 billion population were correct, the death count would be about 1.9 million. The actual death rate in China is not known; we only have estimates, and these estimates vary a great deal.
However we attempt to calculate the impact of the COVID resurgence in China, it was and continues to be exceedingly serious.
What can that tell us about China’s COVID policy, which was highly restrictive initially, and then all restrictions removed? Would China have fared better with a more moderate policy initially, followed by gradual relaxation of those restrictions? In spite of the recent surge in case and death rates, the total death rate in China may still be lower than that in the US. Most of that difference would probably be due to the difference in forms of government – the highly restrictive policies imposed on the Chinese people from the beginning of the pandemic would have been impossible in the US.
A threat to the rest of the world from the Chinese outbreak is that it will be in those billion or so infected people that the coronavirus will continue to mutate and spawn new variants. We hope and trust that those new variants, which are surely coming, will be less deadly.
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In the meantime, as I’ve been focused on all matters related to COVID, plenty of other interesting news items have been trickling into my inbox, and I will try to bring them to your attention in the next Doc Gumshoe epistle. And I will also do a bit of sleuthing on your suggestion and questions. I hope you will keep sending these along with your comments, for which I thank you. Best to all, Michael Jorrin (aka Doc Gumshoe)
[ed note: Michael Jorrin, who I dubbed “Doc Gumshoe” many years ago, is a longtime medical writer (not a doctor) and shares his commentary with Gumshoe readers once or twice a month. He does not generally write about the investment prospects of topics he covers, but has agreed to our trading restrictions. Past Doc Gumshoe columns are available here.]