A Drumbeat of Disturbing Reports
- On April 15th, NIH let us know that the COVID-19 virus (SARS CoV-2) attacks the lining of blood vessels everywhere in the body. Or maybe instead it damages the cardiovascular system by attacking oxygen regulation in unknown ways. Or maybe the vessels are damaged by the immune system. So much to learn, so little time. In any case, vascular damage is common in serious COVID-19 cases. This may be a reason for the early evidence that the virus can damage multiple organs: heart, lungs, brain, intestines, liver, and kidneys.
- Also on April 15th, Researchers in the US and China reported evidence that this virus can attack T-cells in a manner similar to HIV. T-cells are an important component of the immune system. Unlike HIV, which replicates within T-cells, this virus merely disarms T-cells, so they cannot do their job of killing other cells infected with the virus.
- On April 20th, the New York Times reported that the way COVID-19 causes pneumonia prevents patients from realizing that they have pneumonia until their blood oxygen levels are already low. This increases their chances of dying from it, and greatly increases the burden on hospitals trying to keep them alive.
- On April 22nd, according to the South China Morning Post, a team of Chinese researchers using a less-common analytical technique observed a higher rate of substantial mutations in the virus than was first thought. Viruses that perform substantial mutations more readily can evolve in response to the selection pressure created by a vaccine, making it harder to create a long-lasting vaccine.
- Also on April 22nd, the Washington Post reported that US doctors are discovering a high rate of abnormal blood clotting in COVID-19 patients—and that this clotting may in fact be a significant cause of death. As with COVID-19 pneumonia, COVID-19 clotting doesn’t behave as doctors expect, and they don’t know why.
- On April 24th, The Washington Post reported an alarming nationwide pattern of major strokes among young and middle-aged people with COVID-19. Doctors dealing with these unexpected strokes among healthy younger people with mild COVID-19 symptoms speculate that the strokes may be related to the clotting problem mentioned above.
- Also on April 24th, the World Health Organization warned that thus far there’s been no evidence that having antibodies to the disease confers immunity. They urge caution in assuming otherwise until more data is available.
- On April 26th, the Korea Centers for Disease Control and Prevention reported that the number of relapsed cases in the country has reached 222, which is about 2.5% of all patients who had been declared fully recovered and free of the disease. They don’t yet know if this means that people can be quickly re-infected (meaning they gained little or no immunity by having the disease), or if it means that the virus managed to hide in the body after their first round, only to reemerge a few weeks after they were declared virus-free. Neither explanation is good news.
A Difficult Enemy
With each new story, the SARS CoV-2 virus is revealed to be a more enigmatic and dangerous adversary. It first presented as a respiratory virus, but appears to have broader skills with darker consequences that don’t always resolve when the respiratory symptoms do. As the dark side of this virus becomes clearer, the idea that perhaps we should just “let nature take its course” and pay the price in extra deaths in the uncertain hope of achieving herd immunity becomes harder to defend, and the case for continued aggressive control through social distancing, despite the high cost, grows stronger.
The reports cited above are from rough-and-ready early science: data is limited, and peer reviews have largely not been performed. Even so, the data so far shows us a viral enemy that is far more dangerous than its nearest relatives, SARS and MERS. It may kill at a lower rate, but it spreads at a much higher rate, and seems to create a disturbing corona of long-term effects. Moreover, we don’t know yet how much useful immunity having the disease will confer, or how long such immunity will last.
In Pursuit of a Magic Bullet
As COVID-19 spreads, our urgent longing for a quick solution grows in proportion. There is an unprecedented global race to develop vaccines, and much hope is attached to these efforts. The most commonly stated target date for deployment is 12-18 months. Bill Gates, in a recent Vox interview, said he thinks it’s “very likely” that we’ll have an effective, scaled-up vaccine within two years. He cautions, however, that much uncertainty remains. A team at Oxford University plans to begin scaled-up human testing on a vaccine candidate next month. Since it’s based on a previously, tested vaccine, it’s considered safe enough. They will be testing for efficacy. (It works in Rhesus Monkeys, so good news for them already)
There has been less discussion about how we will manage to cross the wide chasm from our initial shutdown to our eventual healthy new normal, even if there IS a new and effective vaccine two years from now. Two years is too long to shut down the world economy and hope, and two years appears to be the best case scenario. There has been very little discussion of the odds that an effective vaccine might not be deployable until long after 2022, and how we’ll manage that if need be.
The Battle-Scarred Veteran
I’ve been talking to Fred Brown about this. Fred is a veteran epidemic fighter, educated by his battles with HIV-AIDS, Zika Virus, Malaria, and H5N1 Flu, among others. He has led pharmaceutical teams creating and deploying vaccines and antivirals on a large scale: hundreds of millions of people and doses, billions of dollars. These days, he’s advising political leaders across the country and around the world (free of charge) from his socially distanced domestic hideaway near Ann Arbor, Michigan, and he’s built a decision support tool for political leaders who must navigate complexities of interwoven biological, medical, and economic issues (also free of charge). (Disclosure: I’ve helped Fred organize his communications tools.)
He’s obsessed now with this virus. He believes that the odds of a broadly effective vaccine becoming widely deployable in less than 18 months is perhaps 20%. It would be even lower were it not for the monumental global effort by Gates and other being made to develop a vaccine. Brown believes that there’s also a roughly 20% chance that it will take at least ten years to develop such a vaccine, and perhaps it will never happen. This is not an extreme view: historically, the average time required to develop a virus vaccine is over 13 years. We still don’t have one for HIV (“ten more years,” says Fred), and our flu vaccines are only partially effective.
The most likely scenario in Fred’s view—he gives it a 60% chance—is that the development of a reasonably complete vaccine becomes odds-on by 2025 or so. Between now and then, he believes, we’re going to be “running a marathon” against this virus to hold off a runaway pandemic. In his view, if this virus “gets away from us,” the global death toll could reach or exceed 120 million over the course of a year or two, and that would not be the end of it. At present, we have no idea what the additional toll might be in long-term damage to the health of some survivors, but the early indicators give reason for concern.
At this point, I must report that Fred is an exceptionally upbeat person. He seems boundlessly energetic, and so eager to help people understand what we are up against and how we can fight it that the words tumble out at warp speed. When his audience is knocked over by the fire hose, he apologizes, tweaks the nozzle, and turns the water back on. To Fred Brown, it’s very good news that we have it in our power to avoid the worst, even if the solution requires that we live our lives very differently for at least several years. Like many pandemic experts, he’s been waiting fretfully for years for this kind of a pandemic-ready virus to emerge. We’re lucky, he says, that it waited this long to arrive; our capacity to analyze this virus and design vaccines and therapeutics to control it have improved markedly with each passing decade.
The Yo-Yo Marathon
If we’re in for a protracted fight to preserve some degree of good health AND a somewhat functional economy, what might that look like? Whether Bill Gates is right and we get a vaccine in 2022, or Fred Brown is right and it’s more like 2025, we need to cope with a period of time far too long to just stay shut down, yet the virus is too dangerous to just turn loose. How can we solve this conundrum?
Neil Ferguson, a noted modeler at the Imperial College in the UK, predicts that if we succeed in deeply suppressing the virus by social distancing this first time and then relax, we’ll get a window of relatively low-risk time, and then a second wave of viral infection. This pattern would repeat—we’d deploy social distancing each time the virus starts to rise, and then relax restrictions when the virus population collapses, 3-5 times a year.
Fred Brown proposes that the best way to run our yo-yo marathon is to get really good at managing this saw-toothed cycle of viral surges and suppressions: shutting our economies down at just the right times to let the air out of each viral rebound, and cracking them back open again at just the right times to let some air into our struggling economies. In this scenario, each viral outbreak would be more modest than the initial one we’re living through today. This will feel weird: shutting down when everything seems fine isn’t going to be an easy political sell. To get good at it, we’ll need to develop a gusher of real-time data about the virus’s activities, which means an unprecedented (and uncomfortably invasive) regime of testing and contact tracing—also a tough political sell.
The reward for this effort will be that our economies will oscillate more predictably between relatively open and relatively closed, and we’ll gradually learn how to spend more time open and less time closed. Over time, we’ll learn more about what works best, and be able to trim the severity, duration, and frequency of the closings. As we develop expertise in walking this tightrope across the wide chasm, we can aspire to having our economies “open” two-thirds of the time and “closed” one-third of the time. At first it will probably be the reverse.
Along the way, we’ll get some help. Antiviral medications are likely to emerge: they are no substitute for a strong vaccine, but they can, perhaps, reduce the severity of many cases and therefore reduce the death rate, and perhaps provide protection for the most vulnerable workers, such as healthcare workers. This week, the National Institute of Allergy and Infectious Diseases reported that preliminary data show patients who received Gilead’s antiviral drug remdesivir recovered faster than similar patients who received placebo, an encouraging development. With experience, our healthcare practitioners will learn more about caring for patients in ways that reduce the death rate and reduce the chances of long-term damage, and we may get better at controlling the overreaction of the immune system that is a significant cause of COVID-19 deaths.
Although the pathway to a so-called “complete” vaccine could be long and uncertain, it’s possible that partial vaccines will emerge along the way, and function like our current system of annually optimized flu vaccines. We don’t know yet how much immunity recovered patients will have, but if they have some degree of lasting immunity, their increasing presence in the population will incrementally contribute to the effort to contain the virus. In a brutal calculus, we’ll also inevitably lose many of the most extremely vulnerable in the early rounds, leaving the surviving population just a bit more resistant on average.
As each of these nudges kicks in, we can further reduce the extent, duration, and frequency of economic closings. Fred estimates we might see six cycles of the virus/economy dance in the next 18 months, so even if we get very lucky and have a magic bullet vaccine available in two years, we still need to perfect our dance steps. In the event that we’ll have to keep dancing for five or ten more years, we’d better practice dancing like our lives and livelihoods depended on it.
A Crisis Not to Waste
This is a seemingly bleak prospect: years of elevated health risks, years of reduced economic vitality, and years of constraints on personal privacy and freedom of movement. Bleak now, yes, but over time we can make it better, bit by bit, vaccine or no vaccine, and much better with a vaccine, whenever it arrives. We’ll learn to revise the ways we work, learn, and play in order to reduce risk across most economic and social sectors. We can also learn how to get much better at stopping the next pandemic much sooner. We will not lack for motivation.
Is there a silver lining? Well, a sliver of silver. Perhaps the experience will persuade us to rebalance our social contract: This virus is a vivid reminder that nobody’s perfectly safe unless everybody’s fairly safe. Even with infinite money, the 1% can’t wall their lives off from this and proceed as usual. If we come out of this with reduced inequality (historically, epic global catastrophes do that), a stronger social safety net (especially in health care), a restored appreciation for the virtues of competent government, and a new chance to addresses the climate crisis more effectively, it would almost make our trip to hell and back worth it. Perhaps that’s why Fred Brown retains his upbeat demeanor, and his obsession with helping people understand our options for surviving and prevailing. As for Bill Gates, his pragmatic optimism seems to be an innate trait, and we can trust it will continue.
Attacks beyond respiratory:
The Oxford Vaccine:
Thank you, Tom for writing this very important, beautifully written and factual article. I hope it will be widely read. It reminds that learned, experienced people are aggressively working on solutions for dealing with this pandemic and that eventually we’ll figure it out. I especially liked the sliver of a silver lining. Be Well!
Thanks Tom, you always lay out strong thoughts.
I wonder if there is more room for optimism in the treatment side of the story. We may, as you say, have to wait years for a vaccine, but there is a strong market to develop treatments, making coronavirus less lethal and less ruinous.
There’s room for optimism. The real challenge is that the case for optimism can’t be quantified yet, but there’s enough data to know that the situation could get really bad if we lose control. Hence, we’re facing the mother of all “hope for the best but prepare for the worst” problems. Even if we think that “the best” is 90% likely to happen, we still have to prepare for the worst, because that other 10% is so bad. Specifically regarding antiviral medications, quite possibly they will prove helpful–hope for the best–but we can’t be at all sure yet whether that will be the case–prepare for the worst. If we look at a parallel case, influenza antivirals, we see that the drugs (there are 4) are considered, on average, to provide greater benefit than risk. If taken early, they can reduce the course of the disease (for example, taken immediately upon presentation of symptoms, they can reduce the duration of symptoms by 0.5 to 1.5 days, in 60-90% of patients). All the data is soft-edged, though: effective for some people but not others; reduce symptoms by modest amounts; more effective when taken early; more effective is the person has also been vaccinated; efficacy varies between types of flu, and from year to year. The combination of flu vaccines and flu antivirals has made the flu a “livable” disease for us most years. COVID-19 appears to be significantly more infectious (especially before the onset of symptoms), and more lethal than the flu. There is no companion vaccine. Under those circumstances, antivirals are likely to be meaningfully helpful, but probably not enough to free us from the economically momentous cycle of viral surges and periods of distancing. We can hope that antivirals will provide relief, but we have to prepare to soldier on for several years understanding that that relief, if and when it comes, is likely to be modest.
Beautifully-written science writing. Bravo.