As I write this, both the US and the world are seeing an upsurge in COVID-19. There has been a 46% spike in hospitalized patients, and in the past seven days more than a half-million more Americans have contracted the coronavirus. According to the Johns Hopkins dashboard that tracks COVID-19 cases all over the world, as of today, the number of US cases is 9,982,054. And the number of deaths is 237,608. The daily totals have set new records: 103,369 new cases on November 8th, and 1,096 deaths. I cite Johns Hopkins data because it is generally thought to be the most accurate and timely data. All the same, there are holes in the data – it’s only as good as the sources, and some of the sources clearly may not report complete data.
This is the third spike in morbidity and mortality that the US has sustained since the pandemic hit us back in March of this year. About two weeks ago, epidemiologists predicted that the number of new cases per day would “soon reach 100,000.” That number was surpassed in just about a week. They also predicted that we would likely see another 100,000 fatalities by the end of the year. We’ll see how long it takes to reach that number.
In my previous Doc Gumshoe offering, I discussed the Great Barrington Declaration, which proposed limiting the measures currently being used to attempt to quell the infection rate to those persons most at risk, and greatly loosening the restrictions on the rest of the community, while herd immunity was allowed to do its work. This meant that a large enough fraction of the general population would contract COVID-19, but experience relatively mild cases and survive, contributing to herd immunity. I stated that I strongly disagreed with that position, and cited a few experts to support my position.
Several members of the Gumshoe congregation took issue with my response to that declaration. One parishioner went so far as to say that Dr Fauci (one of the experts I cited) should be locked up. Another, referring to the year and a half life expectancy (on average) of nursing home residents, said, “If they lose 6 months to a year of that (esp. with the quality of life being pretty low by this point) is that really that drastic compared to the economic fallout of never ending lockdowns?”
I strongly object to the notion that our society has to make a choice between combating the pandemic and supporting the economy (never mind that it’s not just nursing home patients that have contracted COVID-19 and perished). Without any doubt, the damages to the economy that the COVID-19 restrictions have caused are real and major. But the pandemic itself has serious economic consequences entirely independent of the restrictions. Even without the restrictions, many people would be loath to put themselves at risk of contracting the coronavirus. They would refrain from going to the movies or attending sports events; prefer doing a lot of their shopping on-line rather than going into crowded stores; postpone travelling on crowded buses, trains, or planes; and in general avoid putting themselves needlessly at risk from contagion. Most of the restrictions put in place by “authorities” of all types encourage careful behavior by the careful sector of the community, and attempt to require careful behavior from the not-so-careful remainder.
The rationale behind The Great Barrington Declaration assumes that the current restrictions also have the effect of interfering with the emergence of herd immunity. That would be a genuine concern if the only path to herd immunity were increasing the number of individuals in the community who had developed COVID-19 and recovered, thus having acquired a degree of immunity and no longer potentially transmitting the disease to others. But that is not the only path to herd immunity. The question about vaccines is not “if” but “when”. At some point there will be a vaccine. It will reduce the number of potential transmitters of the coronavirus. Herd immunity will be achieved though both avenues.
There continues to be a flood of interesting data and stimulating discussion related to COVID-19 that may have escaped the notice some of the Gumshoe tribe. In my previous piece I mentioned a few topics. Here are some:
The relationship between viral load and the severity of symptoms
This would appear to be fairly obvious – the poison is in the dose. A big dose will likely kill you, but a small dose won’t do much harm. That proposition is questionable with pathogens like viruses, which have the capacity to multiply rapidly, so that a tiny dose can quickly become an overwhelmingly large dose. Evidently, however, our natural immune systems are able to spot the invader and muster the resources to mount an effective battle against that invader. But it does depend on the size of the invading force.
An interesting perspective on that matter came from a very recent paper in The New England Journal of Medicine (Ghandi M. N Engl J Med 2020; 383:e101 DOI: 10.1056/NEJMp2026913). The paper cited examples of COVID-19 hot spots where large majorities of the individuals were infected by the coronavirus but did not develop any symptoms. On a closed Argentinean cruise ship, passengers were provided with surgical masks and the crew with N95 masks. Among those who were infected, the rate of asymptomatic infection was 81%, which was compared with a 20% rate of asymptomatic infection on a previous cruise ship where neither passengers nor crew had masks. Other examples included two US food processing plants, where all workers were issued masks each day and were required to wear them. A total of 500 persons were infected with the coronavirus in the two plants, but 95% of these were asymptomatic and the remaining 5% had mild to moderate symptoms. The CDC had estimated in mid-July of this year that about 40% of persons infected with the coronavirus would essentially be asymptomatic, but more recent evidence suggests that in settings where mask-wearing is universal, the observed rate of asymptomatic infections is closer to 80%.
These examples support the hypothesis that facial masking reduces the severity of disease among those individuals that do become infected, and also the concept that severity of symptoms is proportionate to the viral load or inocculum.
The authors of the paper speculate that widespread asymptomatic infection with SARS-CoV-2 would mimic a practice known as variolation. This was a process in which people were inoculated with material from a vesicle of a person with smallpox, with the intent of causing a mild infection and resulting in immunity. This practice was abandoned when the smallpox vaccine was introduced, making even the mild infections resulting from variolation unnecessary. Until a vaccine against the coronavirus becomes widely available, a near-universal use of face masks would not only decrease the proportion of severe or fatal COVID-19 cases, but would also increase the proportion of asymptomatic and mild cases, resulting in rising levels of immunity in the population. To quote from the paper,
“While we await the results of vaccine trials, however, any public health measure that could increase the proportion of asymptomatic SARS-CoV-2 infections may both make the infection less deadly and increase population-wide immunity without severe illnesses and deaths. Reinfection with SARS-CoV-2 seems to be rare, despite more than 8 months of circulation worldwide and as suggested by a macaque model. The scientific community has been clarifying for some time the humoral and cell-mediated components of the adaptive immune response to SARS-CoV-2 and the inadequacy of antibody-based seroprevalence studies to estimate the level of more durable T-cell and memory B-cell immunity to SARS-CoV-2. Promising data have been emerging in recent weeks suggesting that strong cell-mediated immunity results from even mild or asymptomatic SARS-CoV-2 infection, so any public health strategy that could reduce the severity of disease should increase population-wide immunity as well.”
Doc Gumshoe took the liberty of putting that last sentence in bold, because that’s the message in a nutshell.
The range of treatment options for COVID-19: no cures, but relief of symptoms
As you probably remember, about the time the coronavirus started to make headlines, the first drug that attracted attention – including my own – was Gilead’s remdesivir. About two weeks ago, October 22nd, the FDA approved remdesivir – now trade-named Veklury – for treatment of COVID-19 in patients requiring hospitalization. The terms of approval state that remdesivir should only be given in a hospital or a healthcare stetting capable of providing acute care comparable to acute hospital care. Remdesivir is the first drug to receive regular FDA approval for the treatment of COVID-19. The approval does not include the entire population that had been authorized for treatment with remdesivir under the previous Emergency Use Authorization, which included hospitalized pediatric patients less than 12 years of age.
The FDA approval was announced just a few days after an interim report on a large trial with remdesivir was made public. This was a study conducted by the World Health Organization (WHO). At 28 days, the death rate in patients being treated with remdesivir barely differed from that in other patients with COVID-19. And there were no advantages for remdesivir in the secondary outcomes – initiation of ventilation and duration of the hospital stay.
The trial was observational, rather than the double-blind placebo-controlled trial that is thought to give the most reliable results. From March 22 to October 4, WHO investigators compiled data from 405 hospitals in 30 countries, in a trial that comprised 11,266 adults: 2,750 receiving remdesivir, 954 were on hydroxychloroquine (HCQ), 1,411 on lopinavir, 651 on interferon plus lopinavir, 1,412 on interferon only, and 4,088 on standard care without any of the above. Within the study, HCQ was discontinued for futility on June 18 and lopinavir on July 4. Interferon was discontinued on October 16.
It was noted that the WHO study was based on data from many different settings around the world, and included a lot of different approaches to the care of hospitalized COVID-19 patients. In contrast, the FDA approval was largely based on the NIH Phase 3 trial showing that patients with mild, moderate, and severe disease who were treated with up to 10 days of remdesivir recovered about 5 days more quickly than those on placebo, and about 7 days sooner in those requiring oxygen at baseline.
In other words, not a cure, but significant relief of symptoms.
Two more possibilities