This will be the thirteenth Doc Gumshoe pronouncement on the COVID-19 pandemic. Lucky or unlucky, I have no idea, but let’s get on with it.

To the question “Where are we now?” the answer depends enormously on exactly where, geographically, we are. The differences in the new case and fatality rates in among the different states in the US are nothing short of staggering. For example, the six states with the highest weekly rate of new cases per 100,000 population have new case rates more than ten times higher than the thirteen states with the lowest new case rates. The new case rates in Florida (the highest), Louisiana, Mississippi, Arkansas, Utah, and Nevada range between 100 and nearly 200 cases per 100,000 population, while the new case rates in the thirteen states with the lowest new case rates range between 8 and 11 new cases per 100,000 population. Those fortunate states are South Dakota, Minnesota, Wisconsin, Michigan, Ohio, Pennsylvania, New York, Connecticut, Rhode Island, Massachusetts, Vermont, New Hampshire, and Maine (the lowest).

The fatality rates also differ hugely between states. The two states with the highest weekly fatality rates per 100,000 population are Missouri and Arkansas, where the fatality rates are 1.6 per 100,000 and 1.2 per 100,000 respectively. This contrasts enormously with the weekly fatality rates in South Dakota (0.01 per 100,000), Iowa (0.01 per 100,000), New York (0.01 per 100,000), Connecticut (0 per 100,000) and Vermont (0 per 100,000).

The contrast between fatalities last week in the neighboring states of Iowa and Missouri is staggering. There were zero new deaths in Iowa compared with 52 new deaths in Missouri.

A number of factors account for the exceedingly large differences in both the rate of new cases and the rate of fatalities, but the principal factor appears to be the difference in vaccination rates. For example, Vermont leads the US in vaccination rates, with about 66% of its population having been fully vaccinated. And, perhaps as a consequence of having approached the vaccination level associated with herd immunity, Vermont is also among the leaders in the US in terms of the case rate in that state, an average of less than one new case per 100,000 people each day. This compares with an average of 7.8 new cases per day in those states that have vaccinated fewer than half of their residents.

Nationally, states that have fully vaccinated fewer than half of their residents have an average rate of new COVID-19 cases that is three times higher than in the states that have fully vaccinated more than half of their residents.

I need to point out that these new case rates, although higher now than just a few weeks ago, are far lower than during the pandemic’s huge surge in the fall and winter of 2020.

The ten states with the highest percentage of fully vaccinated residents are: Vermont, leading the nation with 66.17% of its population fully vaccinated, followed by Massachusetts (62.33%), Maine (62.2%), Connecticut (61.39%), Rhode Island (59.58%), New Hampshire (57.05%), Maryland (56.86%), New Jersey (56.03%), Washington (55.55%), and New Mexico (55.35%). (Data as of 07/09/21)

At the other end of the scale, the states with the lowest vaccination rates are West Virginia (38.61%), Utah (37.88%), Tennessee (37.77%), Georgia (37.12%), Idaho (36.45%), Louisiana (35.55%), Wyoming (35.55%), Arkansas (34.68%), Mississippi (33.28%), and bringing up the rear, Alabama (33.1%).

A great many factors come into play in trying to account for the differences in vaccination rates, new cases rates, and fatalities. Willingness to be vaccinated versus “vaccine hesitancy” (as it is politely termed – I would prefer “anti-vax stubbornness”) is only one. But there are obviously others – rural populations are much more difficult to get vaccinated, and the economic resources of the different states have a large impact. The unvaccinated population also tends to have a lower educational level, lower economic status, and include a larger proportion of persons of color.

The influence of well-known individuals, whether from the political or religious or popular culture spheres, is also a factor. For example, Michael Andrews, an ace swimmer who is competing in the Olympics in Tokyo, has stated publicly that he will not be vaccinated. How many of his fans back here in the US will go along with him and refuse to be vaccinated? And will some of those fans contract the deadly coronavirus?

We’re seeing a surge in new cases of COVID-19. Why might this be?

When I began writing this piece about ten days ago, I started out by saying that the recent increase in new COVID-19 cases was not getting as much attention as one might suppose. From where Doc Gumshoe sat in careful observation, it appeared that lot more attention was being focused on “getting back to normal.” However, since the recent surge in cases, mostly due to the Delta variant, there have been a number of statements (including from the CDC) that masks will be required indoors in all the parts of the US where the transmission rates are elevated. I’ve seen announcements that in New York, the Metropolitan Opera, having successfully concluded negotiations with stagehands and choristers, is planning to resume a full schedule of performances before (they hope!) well-attended houses. However, to attend performances at the Met, all audience members must provide proof of vaccination and be masked.

That fleeting sense of complacency was no doubt largely due to the “success” of the vaccination effort. By the middle of July, more than 160 million Americans had been fully vaccinated. That’s not bad, but it’s less than 50% of the US population.

Some of the big increase in new cases was no doubt due to a sense of complacency, the idea that “we’re on our way to beating this thing.” Or perhaps in part due to fatigue – “I’m sick and tired of wearing this damned mask.” Or, “I can’t wait to be in contact with my friends.” Or, speaking for myself and my wife, “We’re keenly looking forward to rehearsing and performing with our chorus.” (But we won’t do it unless we can be absolutely certain that every single member is fully vaccinated!)

All of this is going on at the same time as a surge in new cases. The average of new cases per day on June 30th was 11,000. By July 15th it had increased to 26,000 per day, and on July 29th there were almost 52,000 new cases. The current daily average of new cases is rising very steeply.

However, it seems pretty clear at this point that a major part of the increase in new cases is due to the spread of the variants, especially the one labeled the Delta variant. Let’s take a look at the variant picture as a whole.

The coronavirus variants – how big is that threat and what can we do about it?

A variant is a mutation of the virus that in some way benefits the virus and leads to increased survival – of the virus, but certainly not of the host. When viruses reproduce (which they can only do when they have taken residence in a host and appropriated some of the host’s cells to aid in their reproductive process), the process inevitably results in transcription errors. Most of these errors are meaningless. A few are fatal to the virus. But the occasional transcription error leads to a mutation that is beneficial to the virus, such as making it easier for the virus to infect another host. Those mutations form what we call “variants.”

Even though the coronavirus (SARS-CoV-2) arose in China, it seems that most of the first cases of infection in the US due to this virus came from a mutation that emerged in the UK back in December of 2019. That variant, initially designated B.1.1.7, has now been named the Alpha variant.

• Alpha (B.1.1.7). This variant emerged in the UK, and is responsible for most COVID-19 infections in the US. Alpha is the coronavirus strain against which the Pfizer and Moderna vaccines were initially tested and found to be about 95% effective.
• Beta (B.1.351). Emerged in Africa. Mutations in the spike protein help it bind more tightly to human cells and thus make it more infective. Beta also has the E484K mutation, which helps it avoid antibodies at least partially and thus makes it more resistant to vaccines. For example, the Pfizer vaccine is only 72% to 75% effective against Beta. In the US, Beta accounts for only about 0.1% of COVID-19 cases.
• Gamma (P.1) First identified among travelers from Brazil at the beginning of January 2021 during routine screening at an airport in Japan. Shortly after the initial identification of Gamma, it became the dominant strain in Brazil. It has now been identified in at least 37 different countries and in 31 states in the US. Gamma can be almost twice as transmissible as some of the other variants. Like Beta, Gamma contains the N501Y and K417T mutations, both of which give the virus a tighter grasp on human cells. It also carries E484K, a mutation known to help the virus evade certain types of antibodies. Vaccines, therefore, may offer less protection against the Gamma variant than others. In Washington State, Gamma was responsible for 16.3% of new COVID-19 cases.
• Delta (B.171.2) Emerged in India and was first detected in October 2020, but did not become a variant of concern until the surge in India in the spring of 2021. Delta spread globally very fast and is now by far the dominant strain in the US. As of 20 July, 83% of the new COVID-19 cases in the US that had been sequenced to determine the specific infective strain were due to Delta. This is up from about 50% of new cases at the beginning of July. Delta is considered responsible for the recent spike in new cases and fatalities. Delta has been found to be about 64% more transmissible than the Alpha strain, which was already estimated to be about 50% more transmissible than the original wild virus. According to a study in Scotland, the risk of hospital admission was 85% higher in patients with the Delta variant compared with the Alpha variant.
• Lambda (C.37) First identified in Peru in December 2020, and has since been reported in 29 countries. In Peru, 81% of new COVID-19 cases since April 2021 have been associated with Lambda. In Chile, Lambda accounts for about one third of cases sequenced in the past two months. The first US COVID-19 case identified as due to the Lambda variant was detected in Texas on July 21. WHO deemed Lambda a “variant of interest” on June 14, 2020. That designation means the resulting mutations are believed to affect the virus’s transmissibility and severity and are causing “significant community transmission or multiple COVID-19 clusters” in multiple countries, such that it appears to be “an emerging risk to global public health.” However, it is not yet considered a “variant of concern,” as are the four above-mentioned variants.

The question in everyone’s mind is, of course, how effective are vaccines in dealing with variants?

Vaccines vs variants

There isn’t and won’t be a simple quantitative answer to that question. The statements that the Pfizer and Moderna vaccines are about 95% effective in preventing infection were based on large clinical trials that yielded a clear yes or no answer to the question whether the vaccines prevented infection. Similar clinical trials yielded similar quantitative answers regarding the other vaccines such as Astra-Zeneca, Johnson & Johnson, and others.

Very few similar clinical trials have specifically focused on the larger question of the effectiveness of vaccines in “dealing with” the variants, by which we mean not just preventing infection, but preventing the consequences of infection, particularly serious illness, hospitalization, the need for supplementary oxygen, and death. The evidence for the effectiveness of the vaccines versus the variants has gradually emerged as the variants themselves spread and as larger percentages of populations in several countries have become vaccinated.

The general conclusion that has emerged is that vaccines are indeed effective in preventing the most serious consequences of COVID-19 due to variants, even if they are less effective in preventing infection.

Vaccines elicit an immune response on a broad front. The immediate reaction to vaccines is the generation of antibodies to the specific pathogen that the vaccine was developed to combat. In general, the quantity of antibodies that is produced far exceeds the amount needed to overwhelm the virus. Even if the antibodies are not an exact match to the specific virus, there are generally enough antibodies to prevent massive viral growth.

Beyond the immediate antibody response, vaccines produce what is termed “cellular immunity,” which means that there are cells that act as sentinels and recognize the virus, and there are also killer T-cells that seek out and destroy the virus. That form of immunity takes somewhat longer to emerge than antibodies, but it lasts much longer – years, and even in some cases, a lifetime. You may recall that persons who had the earlier SARS-CoV-1 disease about 18 years ago still demonstrate immunity to that pathogen.

One specific study conducted in Qatar found that the Pfizer vaccine prevented infection with the Beta variant about 75% of the time. However, it was successful in preventing severe, critical, or fatal disease by any variant that was then in circulation 97.4% of the time.

Information about the effectiveness of vaccines against the Delta variant has recently emerged in a study in the UK. Two doses of the Pfizer vaccine were 87.9% effective in preventing symptomatic disease with the Delta variant, while two doses of AstraZeneca’s vaccine had an efficacy of 59.8% in preventing symptomatic disease. The study sequenced 12,675 COVID-19 cases, 11,621 of which were due to the Alpha variant and 1,054 to the Delta variant. In comparison, two doses of the Pfizer vaccine were 93.4% effective in preventing symptomatic disease with the Alpha variant, and two doses of the AstraZeneca vaccine’s effectiveness was 66.1%.

According to researchers at Yale looking at all available data, the Pfizer vaccine is about 88% effective in preventing any symptomatic disease with the Delta variant and 96% effective against hospitalizations. They are still looking at data on the overall effectiveness of the Moderna vaccine, but believe it will be similar to that of Pfizer’s.

The overall statistics powerfully support the premise that vaccination prevents SARS-CoV-2 infection and, in particular, its most serious consequences. As of July 12, according to the CDC, 5,492 vaccinated individuals tested positive for the coronavirus and were either hospitalized or died. That’s out of 159 million fully vaccinated persons in the US. According to my calculations, that would come to about 0.035%, or an “effectiveness score” of 99.965%. And in Texas, 8,744 of the 8,787 COVID-19 deaths since February of this year have been among the unvaccinated. Only 43 of those fatalities occurred in vaccinated individuals. That’s would be a “score” of 99.86%. (Those “scores” are far from official, useful perhaps only as a basis of comparison.)

We should not be too quick to attribute the cause of death in persons who were infected with SARS-CoV-2 to COVID-19 itself. Many times, specifying a cause of death is a judgment call, and it can be somewhat arbitrary. It happens frequently that a person is admitted to the hospital with a severe condition such as an infection in a recent knee or hip replacement, but then develops a pulmonary infection in the hospital. Which infection was the cause of death? The hospital would far prefer the fatality not to be attributed to the hospital-acquired infection. Similarly, if a person with elevated cardiovascular risk factors such as congestive heart failure is admitted to the hospital with COVID-19, requires supplementary oxygen, and experiences a fatal heart attack in the hospital, the cause of death is likely to be attributed to COVID-19 and not to pre-existing conditions. Another person with a similar COVID-19 infection, but no CV risk factors, would more likely survive.

Do we need vaccine booster shots?

A couple of weeks ago, Pfizer executives met with high-level members of the Biden administration for a discussion of vaccine boosters. No decisions have as yet been announced, but there’s plenty of speculation. Pfizer, obviously, is pushing the idea. The argument in favor of boosters is that they would raise the antibody levels and help the patient reject the coronavirus infection more quickly. And, in general, the vaccinated cohort of the US public would favor getting boosters. If it improves our chances of fending off the infection, and if (like the original vaccines) the booster is free, then why in the world not?

The real question is, in terms of controlling the COVID-19 pandemic, what are the priorities? At present, the threat – not only in the US, but globally – comes from the emergence of new variants beyond those listed above. And those new variants will almost certainly emerge among the unvaccinated populations of the world. At present, the pandemic is raging in such nations as Indonesia, where as of July 15, 6% of the population was fully vaccinated. New cases were being diagnosed in Indonesia in mid-July at a rate seven times higher than that at the end of June.

In India, where the Delta variant emerged, the COVID-19 pandemic is raging. Reliable data on the number of cases is hard to come by. The official numbers are almost certainly a huge undercount, since the great majority of the Indian populace does not have direct access to the kind of medical care that can produce an accurate diagnosis. Avrid Sibranaian, who is the former chief economic advisor at the Center for Global Development (a Harvard think tank) estimates that the total number of deaths due to COVID-19 in India is somewhere between 3 and 4.7 million, which is between ten and fifteen times the official death toll. About 6% of India’s population is fully vaccinated.

In Africa, only about 1% of the population is fully vaccinated. This could rise to 6% at most by the end of 2021. Most of the available vaccines in Africa are Sinovac, Sinopharm, Can Sino, and CoVaxin, all Chinese vaccines. Smaller numbers of AstraZeneca and Pfizer vaccines have been delivered to Africa. However, it has been reported that when vaccines arrive in Africa they wind up in warehouses for months, rather than being used. Reportedly, there are 950 million available doses of those vaccines. The pandemic is very poorly controlled in Africa. The death rate from COVID-19 in Africa increased by 40% during a period of one month.

The question that needs to be asked in reference to boosters is this: where does the real threat to our population come from? Is it that current vaccines do not sufficiently protect us from serious illness and death?

A number of experts have expressed view that the greatest threat, not just to our population or the residents of the developed world, but to all the human inhabitants of planet earth, is that the relatively unchecked spread of the coronavirus is such places as Indonesia, India, and Africa is what will lead to the emergence of new and even more threatening variants. Another serious threat is the continuing spread of COVID-19 in the unvaccinated populations of the more developed countries, such as the US. For example, 40% of all the new COVID-19 cases in the US are occurring in just three states – Florida, Missouri, and Texas – with Florida alone accounting for 22% of all new cases nationally.

As you know, viruses cannot reproduce and mutate all on their own. SARS-CoV-2 requires a human host to reproduce, and it is in the human host that the virus mutates. The real threat to the vaccinated populations is the emergence of dangerous mutations as viruses reproduce in their human victims. And it will be in the unvaccinated populations that those mutations – and the dangerous variant strains of the coronavirus – will emerge. The simple fact is that the unvaccinated are the greatest threat to the rest of us.

Therefore, what we need is, not booster shots, but enough vaccines to get to those unvaccinated billions of people. The resources of Pfizer and other vaccine makers should go towards a global vaccination effort, which is what will best protect us.

Possible side effects with vaccines

Any time a foreign substance enters our bodies, there is a possibility that some harm may ensue. Currently, there is a focus on a possible link between the mRNA vaccines (Pfizer and Moderna) and myocarditis, which is inflammation of the heart muscle. In both children and adults, cases of myocarditis have been identified shortly after administration of these vaccines — typically 2 to 4 days after receiving the second dose — and appear to follow a relatively benign course. Patients have typically had symptoms of chest pain, and were subsequently found to have elevated levels of troponin, abnormal electrocardiograms, and cardiac MRI patterns consistent with myocarditis. Serious complications such as circulatory failure or dangerous arrhythmias appear to be exceptionally uncommon.

And in early July, the FDA added a warning that Johnson & Johnson’s COVID-19 vaccine may trigger Guillain-Barré syndrome (GBS) in a small number of people. Of the 12.5 million Americans who received this vaccine, about 100 people reported having GBS in the Vaccine Adverse Event Reporting System. Of these, 95 were serious and required hospitalization, and there was one reported death.

So, yes, it’s possible that getting vaccinated entails the risk of an adverse effect of some kind. But that risk is minuscule compared with the risk of getting COVID-19.

Most of our emphasis thus far has been on the race between the spread of the disease and the effort to get as much of the populace vaccinated. But when a person becomes infected with SARS-CoV-2, what do the healthcare workers have available for treatment?

What options are there currently for treating COVID-19?

Remdesivir (Veklury, from Gilead)

In the earliest days of this pandemic, in fact even before it was declared a pandemic and before it was given the name COVID-19, Doc Gumshoe noted that remdesivir was the first drug that purported to be at least somewhat effective in treating that disease. Here’s what I said back in January of 2020:

“Incidentally, Gilead is said to be considering trying remdesivir for this new coronavirus. Remdesivir was originally developed as a vaccine against the Ebola virus, but was dropped because a couple of other vaccines were somewhat more effective. It has shown efficacy against other coronaviruses, such as in MERS and SARS, and could be effective against the Wuhan virus.”

Remdesivir, now named Veklury, is currently the only FDA-approved therapy for COVID-19. It received emergency use authorization (EUA) in October 2020 for hospitalized COVID-19 patients aged 12 and older who weigh at least 88 pounds. This EUA has been revised to permit treatment of hospitalized pediatric patients under 12 who weigh at least 7.7 pounds.

The FDA also issued an EUA for the combination of remdesivir with baricitinib (Olumiant) for hospitalized patients.

The National Institutes of Health (NIH) recommends remdesivir for use in hospitalized patients who require supplemental oxygen. For patients who need either high-flow or noninvasive ventilation, NIH recommends remdesivir only in combination with dexamethasone.

The earliest evidence for the effectiveness of remdesivir was based on the case of a 35-year-old man who had returned to the US on January 15th, 2020, from a visit to his family in Wuhan. On January 19th, he presented to an urgent care facility in Snohomish County, Washington, with a four-day history of cough and fever. He reported that he had seen a health alert from the Centers for Disease Control and Prevention (CDC) about this novel coronavirus outbreak in China and decided to seek medical attention.

The patient was tested for the so-called Wuhan coronavirus, and the next day, January 20th, the report came back that the swab samples had tested positive for that virus. Those specimens as well as stool samples indicated a high viral load.

For the next four days, the patient remained relatively stable, although with a non-productive cough, intermittent fevers, and periods of abnormally fast heart rates. However, on hospital day five, radiographic findings showed evidence of pneumonia in the lower left lung. He was subsequently started on supplemental oxygen, plus antibiotics to prevent hospital-acquired pneumonia. On hospital day six, X-rays showed that the pneumonia had spread to the right lung as well.

In response to worsening symptoms which were consistent with reports of the symptoms of what was then called 2019-nCoV, the clinicians decided to initiate treatment with intravenous remdesivir.

On hospital day eight, after one full day of treatment with remdesivir, the patient’s clinical condition improved. It was possible to discontinue supplemental oxygen, and the patient’s oxygen saturation, while breathing ambient air, returned to normal levels.

Several clinical trials with remdesivir are currently under way. The results of some may be announced as early as March of 2022; others will not announce results until 2023. In vitro and animal studies have confirmed that remdesivir strongly inhibits the coronavirus. A Vanderbilt/University of North Carolina study showed that remdesivir inhibited the growth of SARS-CoV-2 in human lung cell tissue and also improved lung function in mice infected with that virus.

Dexamethasone (off-patent; sold under six different trade names)

Dexamethasone, a common steroid, is an active and effective anti-inflammatory and is used in a number of diseases characterized by inflammation, including arthritis, asthma, and cancer. It should not be used in the earlier stages of COVID-19 – the so-called “viremic” phase. During this phase, the patient’s essential immune response responds, mobilizing cellular agents to attack the invader. The host’s immune response has not ramped up to its maximum activity as yet, therefore in that phase an anti-inflammatory drug would potentially interfere with the patient’s immune response.

During the second phase the pulmonary symptoms of COVID-19 take hold. Patients entering this phase of the disease begin to experience difficulties in breathing, requiring supplementary oxygen. This phase is characterized by the increase in the patient’s immune response, although not yet to the level where the immune response causes harm to the patient.

The third phase, labeled the severe phase, is characterized by an inflammatory response as the patient’s immune system goes into high gear. Some researchers have called this the “cytokine storm.” Cytokines are a large class of proteins released by many different cells in the body. They play an important part in the normal immune response, but the release of a large amount of cytokines at one time can be extremely harmful and even fatal.

It is in this phase that dexamethasone is used. NIH recommends dexamethasone for use in many patients hospitalized with COVID-19, but not for those with mild-to-moderate disease who are not hospitalized. The NIH recommendation extends to hospitalized patients who need supplemental oxygen, high-flow or noninvasive ventilation, or extracorporeal membrane oxygenation (ECMO).

If dexamethasone is not available, NIH says other corticosteroids may be used, such as prednisone, methylprednisone, or hydrocortisone.

Tocilizumab (Actemra, from Roche)

On June 24, the FDA authorized tocilizumab for the treatment of hospitalized adult and pediatric patients on systemic corticosteroids and supplemental oxygen, non-invasive or mechanical ventilation, or ECMO. Tocilizumab is one of a class of drugs called monoclonal antibodies (mAbs). It is an inhibitor of interleukin-6 (IL-6) which can trigger an inflammatory response that contributes to rheumatoid arthritis (RA). It is widely used in the treatment of RA.

The NIH recommends using tocilizumab in combination with dexamethasone in certain hospitalized COVID patients exhibiting rapid respiratory decompensation. That includes those who have been admitted to the ICU within the previous 24 hours who require invasive mechanical ventilation, noninvasive mechanical ventilation, or high-flow nasal cannula oxygen.

Tocilizumab in combination with dexamethasone has been reported to reduce mortality by about one-third for COVID-19 patients requiring oxygen, and by almost one-half for patients requiring a ventilator. This is based on results from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial in the UK, which was established in March, 2020, to investigate treatments for COVID-19.

A French study found that in patients with moderate to severe cases of COVID-19 associated pneumonia with higher levels of C-reactive protein (CRP), the percentage who required mechanical ventilation or died was significantly lower in those receiving tocilizumab compared to the usual care group (18% vs 57%, respectively). Moreover, 90-day mortality rate was significantly lower for the tocilizumab group compared to the usual care group, at 9% versus 35%.

The NIH says there is no evidence supporting the use of other IL-6 inhibitors for the treatment of COVID-19.

Non-drug treatments

Guidelines for use of non-drug treatments are somewhat confusing.

NIH recommends that all adults hospitalized for COVID-19 who aren’t pregnant should receive prophylactic anticoagulation to prevent venous thromboembolism (VTE) – in other words, blood clots. Pregnant patients hospitalized for severe COVID-19 should also get prophylactic anticoagulation unless it’s contraindicated.

Convalescent plasma has an FDA emergency use authorization to treat hospitalized COVID-19 patients. Only high-titer plasma is now authorized, however, and is restricted to hospitalized patients who are early in their disease course or those who have impaired humoral immunity.

For hospitalized patients without impaired immunity, NIH guidelines recommend against plasma for those who are mechanically ventilated and against high-titer plasma for hospitalized patients not on a ventilator, except in a clinical trial.

As for hospitalized patients with impaired immunity, NIH says there are insufficient data to recommend for or against the therapy. There’s also insufficient evidence to make recommendations about plasma in non-hospitalized patients, according to NIH.

Vitamins and supplements

The official NIH view on vitamin C, vitamin D, and zinc is that there is insufficient evidence to recommend for or against the use of these in treating COVID-19. However, from the sidelines Doc Gumshoe wishes to remind the NIH that, by a considerable margin, persons with significant COVID-19 symptoms were found to be deficient in Vitamin D.

Ivermectin

Way back in January of this year, Doc Gumshoe dumped a lengthy discussion of ivermectin on his long-suffering readers. I reported NIH’s conclusion, which was that, in spite of the stubborn support for ivermectin by a group of healthcare providers called Front Line COVID-19 Critical Care Alliance (FLCCC), the real evidence supporting its use was exceedingly skimpy. The FLCCC group has developed a protocol for treating sepsis, using methylprednisolone, ascorbic acid, thiamine, and heparin, plus a statin, zinc, vitamin D, famotidine, melatonin, and magnesium. They adapted this protocol, labeled MATH+, as a treatment for COVID-19.

On January 14, the COVID-19 Treatment Guidelines Panel chimed in with much the same conclusion as NIH, specifically that “there are insufficient data to recommend either for or against the use of ivermectin for the treatment of COVID-19. Results from adequately powered, well-designed, and well-conducted clinical trials are needed to provide more specific, evidence-based guidance on the role of ivermectin for the treatment of COVID-19.”

An important point made by the panel is that “ivermectin doses up to 100-fold higher than those approved for use in humans would be required to achieve the plasma concentrations necessary to duplicate the drug’s antiviral efficacy in vitro.”

Meantime, a report on a large clinical trial in Egypt which the FLCCC group was counting on to support its use of ivermectin has been withdrawn by the preprint server Research Square because (in the words of the editor) “we were presented with evidence of both plagiarism and anomalies in the dataset associated with the study, neither of which could reasonably be addressed by the author issuing a revised version of the paper.”

Hydroxychloroquine (HCQ)

HCQ has the unusual distinction of having a negative recommendation from both WHO and NIH, both of whom recommended against the use of that antimalarial drug in any COVID-19 patients. This was based on findings from the RECOVERY trial that use of hydroxychloroquine did not reduce mortality among COVID-19 patients after 28 days, and in fact trended towards risk of death. Additionally, patients who received the drug had a longer median hospital stay than those who received standard of care.

The strong negative recommendation for HCQ was contrary to its being advocated by prominent persons having access to public forums.

Doc Gumshoe’s conclusions

I am not speaking for the CDC, NIH or WHO, but for myself, based as carefully as I am able on the news and the evidence.

First, the COVID-19 pandemic may be slightly tapering off in the more developed parts of the planet, but in the less developed parts it appears to be raging.

Second, despite the all-out efforts of healthcare workers everywhere, the best that can be done for patients with severe disease is to attempt to mitigate the worst of their symptoms. There is no cure, and in many places in the world the capacity of medical facilities to alleviate those symptoms is extremely limited. This is true even in wealthy nations, where some hospitals cannot provide support to the influx of new patients. In the less developed nations, medical facilities are greatly overwhelmed.

Third, persons in authority in the more developed nations have mostly come around to supporting the measures that have been shown to control the pandemic. That includes political figures who formerly were dubious about vaccines, but who have now come around in support of widespread vaccination.

Four, some nations and some regions may be approaching herd immunity. For example, in the UK, about 70% of the population is vaccinated. At the moment, caseloads in the UK are rising, but as increasing numbers of people are vaccinated, the rate of new cases is likely to diminish. In the US, the differences in case-loads and deaths between different states are huge and closely linked with vaccination rates.

Five, it is the immense number of non-vaccinated individuals that presents the greatest risks for all of us. Yes, a vaccinated person can be infected with SARS-CoV-2, but the odds are huge that the infection will be transmitted from an unvaccinated person. A vaccinated person can transmit the infection, but the viral load is likely to be much lower than the amount of virus from an unvaccinated person. And, as I pointed out earlier, it is in those unvaccinated multitudes that new and perhaps even more dangerous variants are likely to emerge.

So, as I see it, we’re far from out of the woods. Some of us, depending mostly on our location, but also on our underlying state of health, are a good deal luckier than others. We all need to continue to be very careful, and to understand the effect that our own behavior can have on our fellow humans.

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Many thanks for reading this long (but I hope not too tedious) Doc Gumshoe treatise. I have stored up a number of queries, hints, and suggestions from you and will be coming up with some information pretty soon. Best to all, Michael Jorrin (aka Doc Gumshoe)

[ed. note: Michael Jorrin is a longtime medical writer (not a doctor), who I dubbed “Doc Gumshoe” many years ago — he writes health and medicine-focused columns for our readers a couple times a month, and though he does not generally cover investment ideas he has agreed to our trading restrictions. You can find his past columns here.]