The Grim Reaper has his game face on.
On July 27th, the Journal of the American Medical Association published research by a German team which had examined 100 people who had recovered from COVID-19 infections and discovered that most of them showed continuing effects on their hearts.
They examined 100 people who tested positive for antibodies to SARS CoV-2, all between 47 and 53 years old, roughly evenly split between male and female. One-third had been hospitalized, two-thirds had not. The exams included MRI examination of heart structure, and detailed blood work. The average time between original diagnosis and the MRI was 71 days. The results were unsettling, to say the least: “Cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.”
Yikes. These were not elderly people in poor health. This study strongly suggests that cardiovascular damage may be a widespread consequence of COVID-19 infection, a significant cost above and beyond the death toll. More study is urgently required and will provide deeper, broader data, but as first looks go, this was a jarring result.
ON July 28th, an expert in viral persistence (William Petri) warned that SARS CoV-2 may “hang around” in the body after active symptoms are gone, in what are termed “immune privileged” sites. Much is unknown, but there are red flags around such sites as the testes, the brain, and the placenta in pregnant women.
Also on July 28th, Axios recorded an interview with President Trump by journalist Jonathan Swan (aired on HBO on August 3rd), in which the President continued to argue that we report so many confirmed cases because we do so much testing. He kept deflecting the question of our catastrophic death toll, as if deaths are not also a test of the presence of infection. When he did acknowledge deaths, he waved bar charts showing that the ratio of confirmed deaths to confirmed cases in the US wasn’t as bad as in some countries. He resisted Swan’s attempts to get him to acknowledge that deaths relative to total population was very high in the US. He questioned whether other countries are accurately reporting their cases and deaths (as if South Korea, with 300 total deaths, might be lying so badly that the US, with 158,000 deaths, is actually doing well by comparison), and he claimed that death rate is “going down” in the United States, when in fact it went down and has since risen again.
He also consistently used a lower-than-true figure for total deaths and lied blatantly about the prevalence of the virus in Tulsa, Oklahoma before his rally there. Once again, he gave the impression of a man who is such a domineering, relentless bullshitter that it’s impossible to have a coherent, fact-based conversation with him and not come away needing a shower. Swan brought his A game but is still going to need strong soap.
On the morning of August 2nd, the Trump administration’s Coronavirus Response Coordinator (Dr. Deborah Birx) warned CNN viewers that the US is in a “new phase” of our hapless battle with the coronavirus, wherein the virus is widespread and out of control. She didn’t dispute the possibility of 300,000 dead by year-end, a number recently suggested by former FDA Commissioner Scott Gottlieb.
Also on the morning of August 2nd, over on CBS, the President and CEO of the Federal Reserve Bank of Minneapolis (Neel Kashkari) called for an immediate “hard shutdown” of the US for 4-6 weeks for the sake of the US economy, citing his belief that regaining control of the virus was an economic necessity.
On the afternoon of August 2nd, veteran pandemic-fighter Fred Brown warned (in a personal email) that if we don’t implement a lockdown for about 100 days and use the time to build up our test/trace/quarantine infrastructure, we could see not only ~300,000 dead by the end of this year, but another ~500,000 next year, despite whatever vaccine(s) may arrive.
Early on August 3rd, the head of the World Health Organization (Tedros Adhanom Ghebreyesus) told reporters in Geneva, Switzerland that there was “no silver bullet at the moment – and there might never be.” He lauded remarkable progress toward vaccines, with several now entering Phase III testing, but warned that there’s no guarantee that any will prove useful, and begged people to practice the non-pharmaceutical protocols (distancing, masks, hands…) that are the only way to reduce the damage and death toll of the virus.
Also on August 3rd, President Trump tweeted a reaction to Dr. Birx’ warning. He called her “pathetic.”
It was not a very comforting week.
From Now to Inauguration Day.
How likely is it, do you think, that President Trump is going to go all-in for a hard lockdown from now until election day, with an all-out federal effort to build a test/trace/quarantine infrastructure? Such an infrastructure would require, among many other moving parts, hiring, training, deploying, managing and supporting roughly 1.3 million full-time employees (thanks for that calculation to Fred Brown). Even if Trump were to shock everyone by getting behind (and staying behind) such a program, could his belittled, flunky-managed, brain-drained federal agencies even pull it off?
The model-builders are not optimistic. University of Washington-based IHME projects 231,000 dead by November 1. MIT projects 223,000 dead by October 15. Other models vary, but the thrust is similar—the death rate will be high for the foreseeable future. It’s no wonder Dr. Birx was not willing to dismiss Gottlieb’s estimate of 300,000 by year’s end. As a frame of reference, consider the number 291,557. That’s the official total number of US combat deaths in World War II. Those deaths accrued over 44 months. COVID-19 could exceed that number of American deaths in a span of just 10 months, and keep going through much of next year, at least.
Meanwhile, the US has become Vaccine Nation: fixated like a cargo cult on the devoutly wished-for arrival of a vaccine to save us all. However, as scientists keep warning, the vaccine candidates might not survive Phase III, and those which survive, if any, may only offer partial or short-term protection. Moreover, the logistics of huge-scale administration are unsolved, and the usual fixer in this area, the CDC, is apparently missing in action, a broken shadow of its former self.
Fred Brown, mentioned above and in other articles I’ve written, gives the following educated guesses: the first vaccines will be ~50% effective, and reach ~50% of the US population by the end of 2021. That much vaccine use will make a difference, but it won’t bring a sudden end to the pandemic. Brown’s estimate of ~500,000 dead next year assumes this level of vaccine effectiveness and availability. To further complicate matters, the share of Americans who express skepticism about even accepting vaccination is very high—around 50%. The cost of terrible leadership from now until Joe Biden’s hoped-for inauguration will be hundreds of thousands of additional needless deaths, many of them after Trump has left office.
There seems to be no way to avoid this dark period of continuing loss and grief. However, help is on the way. In the short run, we cannot escape awful consequences. In the long run, the pandemic in the US will be controlled, and the extreme death and damage tolls will end. How will this happen?
The dogs in the fight.
The battle against the virus is taking place in four arenas:
- Preventing transmission
- Reducing severity
- Preventing death
- Preventing long-term damage
Here’s a snapshot of the progress in each arena:
Most of our attention has been focused here: statewide shutdowns, travel restrictions, social distancing, masks, hand washing, testing/tracing, and vaccine development are all efforts at reducing transmission of what has turned out to be a fiendishly infectious virus. Looking ahead, the great vaccine race is on center stage with 165 candidates in development, 27 in human trials, and a half-dozen candidates already entering Phase III (large-scale in-the-wild testing). This is a spectacular achievement, but there’s no certainty yet about how large the benefits will be, or how soon they will arrive. One thing is known, however: vaccination is the ONLY weapon with the potential to end or at least greatly attenuate the pandemic. If we get very lucky, we could have a “sanitizing” vaccine as soon as next year. That’s unlikely, but the odds of a very effective vaccine in five years are pretty good, and the odds keep rising after that.
Beyond vaccines, the next-most-encouraging development might be the potential for widespread personal testing with real-time results. Even without a vaccine, this virus could be brought under much better control, bringing substantial economic and social relief, if it were possible for individuals to test themselves (or be tested) in a quick, easy, inexpensive process every day or two. Imagine getting up in the morning, testing yourself, and having the result automatically read into your phone within a few minutes. If you test negative, your phone will create a time-stamped, good-for-24-hours or good-for-48-hours QR code (or whatever) that can be shown to get you into your workplace, retailers, restaurants, and so forth. Such establishments would also be able to test on the spot and return positive or negative results to you within a few minutes. There are companies working on such personal testing systems. Fred Brown estimates the first of them could be in use within 18 months.
The so-called NPIs—non-pharmaceutical interventions—have been our first defense, and at first, out of ignorance, we’ve been trying everything. They have been much maligned, and the economic cost has been high, but they have saved literally millions of lives around the world so far. We’re learning as we go, and there’s reason to hope we’ll get better at it. As we better understand SARS CoV-2 transmission, we may be better able to disrupt it by how we go about our daily lives. For example, there seems to be a lot of opportunity to make a difference by improving indoor ventilation.
This is also a good place to mention heterogeneity—the degree of variation in something. For example, the degree of variation between individual humans in susceptibility to SARS CoV-2 virus infection. We know that different demographic groups are at different degrees of risk of dying from COVID-19: older vs. younger, male vs. female, HWP vs. obese, etc. There are also variations based on environment and behavior—working at home vs. working in a meat-packing plant, or masking up and social distancing vs. not doing so. Some scientists speculate that there may also be innate, gene-based differences between people in their susceptibility to infection by this virus.
If heterogeneity in susceptibility to infection by this virus is high among humans, we’ll start to see a tapering off of the new infection rate sooner than we would expect, and the proportion of the population that needs to have systemic immunity (from vaccines or from having had the disease) in order for herd immunity to kick in might be lower. If this were true, we’d begin to get more bang for our buck from wearing masks, banning super-spreader events, and so forth, and we might see the pandemic’s power begin to weaken when the share of the population with antibodies is as low as 20-30%.
There’s no proof whatsoever that this theory is true, but the hypothesis comes from serious scientists, and models which assume that it’s true show a significant slowing of new infections at lower levels of antibody presence in the population than expected. Think of this as a blind quarterback throwing a Hail Mary pass to a blind receiver in a snowstorm, for the national championship. It would be really cool if he caught it.
COVID-19 can be mild or even asymptomatic, but it can also be a hellacious experience. Bad cases absorb great amounts of healthcare resources, require procedures that increase the danger to healthcare workers, and highly correlate with bad outcomes. Intervening to reduce severity, therefore, can have multiple benefits. The first approved drug for COVID-19 use, Remdesivir, is a therapeutic agent which can reduce severity. In other diseases (HIV being a salient example) “cocktails” of several therapeutics have proven effective at protecting patients from severe consequences of infection, and they make it harder for the virus to gain resistance. These agents can work in several ways: they can disrupt the reproduction cycle of the virus, speed up immune response, stand in for immune response, or even suppress immune response to minimize the risk that immune overkill will harm the patient. Many therapeutics approved for other uses are currently being tested for efficacy against COVID-19.
One severity response is to use antibodies generated by other patients. This treatment comes in two flavors: one method—called convalescent plasma therapy—solicits blood donations from recovered COVID-19 patients, separates out their antibody-laden plasma, and injects it into patients in the early stages of fighting the disease. One donation provides enough antibodies for three treatments. There are many types of antibody, so the degree of “fit” between the donor’s antibodies and the recipient’s immediate needs are variable, but the treatment is safe and seems to be somewhat effective. Obviously, this is not going to be a cheap, universal treatment, but it could make a critical difference for some patients. So far, supplies are limited and campaigns to recruit donors are underway. The second flavor of antibody treatment—monoclonal antibodies—takes a COVID-19 antibody from a recovered patient and then manufactures an enormous number of copies. Unlike convalescent plasma therapy, this is a scalable treatment: if certain cocktails of monoclonal antibodies are discovered to be effective, manufacturing can be spun up to create large numbers of doses. Anthony Fauci’s group at NIH is currently running a global testing program on monoclonal antibodies.
Anything which reduces severity is also likely to prevent death. In addition, as our healthcare system gains COVID-19 experience, it develops better patient care protocols, which can also prevent some deaths. Protecting the healthcare system from overload prevents deaths, as overloads in Lombardy and New York have proved, so the NPIs which “flattened the curve” prevented deaths. It would also help if we solved our preexisting national healthcare crisis, which leaves many people without insurance and therefore afraid to seek care when they feel sick.
Preventing long-term damage
The correlation between severity and long-term damage is not clear at this point. Although it’s true that people who have been very seriously ill from this virus are more likely to suffer damage to their cardiovascular systems and a variety of organs, it’s not clear that milder cases can’t also inflict lasting damage. As pointed out above, German researchers found evidence of heart damage in people who had antibodies to the disease but had never entered the hospital. As also mentioned above, there’s reason to suspect that in some cases the virus itself lingers in some people well after symptoms have cleared. Long-term damage is the least-understood part of the COVID-19 puzzle, because we haven’t yet had a long term with this virus during which to study long-term effects. So far, preventing long-term damage falls back on preventing transmission in the first place, and then on reducing severity. We know enough about the prevalence of long-term damage to know that a high rate of infections in the near term could leave us with a long tail of deleterious effects.
So here we are.
We are well on the path through the valley of the shadow of death. In a country of 330 million people, 330,000 deaths works out to 1 person in a thousand. We’ll pass that milestone at some point in the next 4-6 months, and it seems unlikely that we’ll be able to avoid going well beyond it. The forces marshalled against the virus, though grievously hampered by the current administration, are formidable and determined. Over the next two years, along with the appalling death rate for a while, we will see initial vaccines, personal testing, and refined NPI protocols to reduce transmission and thereby improve the economic outlook, and we’ll see, inch by inch, better therapeutics and protocols to reduce disease severity and deaths. Fixing the healthcare system could take a little longer.
We could have avoided most of the tragedy that currently engulfs us through better leadership, and Trump’s “comorbidity” (Ed Yong’s term in The Atlantic) will prolong the disaster until he is gone. Nevertheless, we will climb out of this, so long as we wear masks and change Presidents.
About heart damage in recovered COVID-19 patients:
About the virus lingering in the body:
Jonathan Swan’s interview with President Trump:
About Birx’ characterization of “new phase” of pandemic:
About Kashkari’s call for a hard lockdown:
About Fred Brown:
About WHO’s “no silver bullet” warning:
Trump attacking Birx:
IHME’s projected deaths:
MIT’s projected deaths:
About vaccine progress:
About instant self-testing:
About heterogeneity and the possibility of herd immunity sooner:
About preventing transmission with better ventilation:
About convalescent plasma therapy:
About monoclonal antibody trials:
Ed Yong’s excellent overview of how the US botched the pandemic: