The Pandemic Will End: How and Why

David C. Weisman, MD
Director, ANA Clinical Research Center

In many ways we’ve been fortunate. Despite a pandemic, society has not broken down. The supply lines have held. The essential workers go to work. They raise food, transport it, stock shelves, clean the carts, man cashiers, staff ERs, ICUs, and hospital floors. Profiles of grace and courage emerge daily. These are the heroes of the pandemic and a just society will one day raise monuments to them.

The scientific, bioinformatic, and mathematic experts staffing obscure posts in academics and civil service are also essential workers. They modeled data of the infectious spread. They warned us to “flatten the curve” and explained why. At the onset we were powerless against the viral spread, but we quickly figured out how to slow it down. The virus is small, it does not move itself. Humans can reduce transmission by staying at home and prevent the medical system from being overwhelmed. We can protect the most vulnerable: our friends, colleagues, and loved ones. These are seniors, or young people with cancer, heart disease, or diabetes. Or those who are just unlucky. They may have a genetic quirk that responds to this viral pneumonia with death. One of those people could be you. Unless you have the virus and survive, there’s no telling. No one knows their personal risk, or their children’s, parent’s, or friend’s. Unlike most diseases, the range here is non-symptomatic to fatal.

The essential workers risk exposure and disease by going to work. Thanks to them, thanks to our society, and thanks to the citizens, we’ve listened to the experts, not the charlatans. The wall has held, the curve is flattening. But cracks have always been there. Those with darker impulses expand the cracks into chasms. They come in various forms, like Dr. Drew Pinsky’s denialism, calling this “less virulent than the flu” when we knew it was around ten times more deadly. Dr. Mehmet Oz not only dismissed possible fatal side effects of an untested medication he was promoting with no evidence (which is bad enough), but suggested that opening up schools “may only cost us 2 to 3% in terms of total mortality.” Finding an acceptable trade-off between social clustering and thousands of lives lost is not compatible with being a doctor. Both later backpedaled, but other false prophets continue to widen the cracks.

But these dark impulses find their way into our hearts. We are at risk of betraying those who may die of the disease, turning against our brothers and sisters. Humans are social, and the main competing interest, the economy, must get back eventually. Flattening the curve won’t hold much weight when new cases start decreasing, but the risk of a rebound will remain. So now what?

We cannot look to political leaders to solve a biological crisis. Even the competent ones, even those who have already saved lives by making the hard choices of closing schools, bars, and golf courses, cannot legislate the virus away. Laws cannot defeat the virus. The virus is a biologic phenomenon and the solution must be biological.

At this point, as the curve turns flat then downwards, we must wage a difficult war, one that defies an easy slogan. Yes, we must flatten the curve, although we might have to revise it: ‘Keep the downslope down’ comes to mind. But the downslope only measures new cases. Slope measures deceleration, not speed. The virus still spreads, it is slowing down only when compared to the maximal acceleration. Slowing down does not mean gone.

Why does it slow down? Biology 101: as people get the disease, they recover and become immune. Many do not know they are immune. In Iceland, 43% of positive cases had no symptoms. You might be one of them. Over time, more and more people develop an immune response against the virus. Immunity makes it impossible for them to be infected with the virus and thus impossible to shed the virus or spread it. They then become dampeners, reducing the transmission.

Imagine an immune person as an essential worker. Three weeks ago, Susan was asymptomatic but infected, shedding viral particles as she delivered groceries. But now Susan’s immune system recognizes the virus. The instant Susan gets re-exposed, antibodies in her blood and nasal passages bind to the virus, killing it. Susan is immune. And since she no longer sheds the virus, she cannot serve as a vector. She can no longer infect others. Now imagine Susan as a caretaker for her elderly parents. She can freely tidy their homes, cut their hair, get them groceries. She serves as a wall. The virus cannot pass.

Now imagine thousands of Susan’s immunologic brothers and sisters in arms, all around us, immune and protecting us, like the mortar between floor tiles, preventing us from spreading the contamination. This is how the curve naturally bends and new cases drop. This is called herd immunity.

We can use this phenomenon by testing for the antibodies. Up until now, we tested for viral shedding, so when doctors called patients “positive” it meant that they were actively shedding viral particles. This was the test that the CDC botched and the FDA over-regulated, so there was essentially no meaningful early testing (except perhaps for the well connected). It is a tragedy, a blunder for the history books, but we must press onward.

We now must focus on tests for immunity. We can test blood for the antibodies that stick to and destroy coronavirus. We can find Susan! And more like her! We can discern between tile and mortar. By identifying people like Susan, we can allow members of our society to return to work without fear. While there are some unknowns (we don’t know how long people will be immune), we can restart the economy and keep the downslope.

Why bother? Why not create more Susans by allowing the virus to spread naturally? Because out of thousands, some will die. The virus is not predictable. When antibody testing becomes available, and our society permits the immune to return to work, willful self-infection may gain traction. Many people will be willing to take a risk to become immune and get to work. Self-infection has historical precedent. Before the smallpox vaccine, inoculations were fairly standard and carried risk of death (just less risk than normal transmission). If antibody testing is widely adopted and jobs are tied to immunity, there will almost certainly be corona-parties.

We must develop better treatments and vaccines to defeat the virus. The medical community is already getting better at figuring out how to treat the disease, prevent clotting that seems to occur, whom to intubate and when.

For some reason, attention first gravitated to an old drug called hydroxyquinine. We don’t know if it works, but we do know it can cause fatal heart rhythms. Early, non-randomized data does not look promising.

Convalescent plasma means taking blood from people like Susan, who has antibodies against the coronavirus, taking out her serum (and the antibodies it contains), and then infusing it into sick people. This is an exciting prospect. Antibodies are also being developed against the coronavirus spike protein.

Gilead, the company who first cured patients of hepatitis C, is developing a drug called remdesivir, a molecule that sabotages the way the virus replicates. The mechanism is so beautiful that it seems it must work, but biology is complex.

Drugs are fragile. They look promising until they meet biological complexity and many break into shards. Only a few drugs become medications. We can’t get hopes up based on mechanism, or anecdotes, or case reports. We need randomized controlled trials to show drugs work and are safe. In these trials, some get the drug, some do not. Then we compare the groups. In that way we become certain, we can know. Pretending to know outside evidence is stupid and evil. It is perhaps the deepest, darkest of the black cracks. It harms the very method by which we come to know: clinical research.

These treatments and others may take the teeth out of the disease. If we make COVID19 into a disease with a higher survival rate, then fear diminishes. But the disease remains.

COVID19 will be crushed by immunity, natural or man-made. Nature gives immunity after the disease, like Susan. Medicine gives immunity with a vaccine. Two dozen biotech, pharma companies, and public-private partnerships are in a race to prove safety and efficacy of their vaccine. But this is a novel virus. The timeline for success is unknown. Currently there is talk of an “accelerated” 6-18 months. The range alone tells the story of over-optimism. Even with the greatest project managers in the world, even with permissive safety considerations, 18 months is a sprint. How long to deploy many millions of vaccine doses and provide herd immunity? Another unknown, but it will likely take years.

Previous plagues in human history show us the way. Humanity wins the war, but suffers losses. Plagues pierce our delusion of control, of dominion over nature. They remind us that we are part of nature, that very tiny bits of nature rules over us, that our delusion of control was always exactly that. COVID19 is no different.

When the Black Death came to humans in the 1300s, our ancestors were fully in its thrall. Humans exactly like us watched as it killed between 1-2 people out of three. But they did not know their plague was due to a bacterium, that it was harbored by rats, that it spread to humans by fleas. They had no knowledge of germ theory, of possible treatments. They had no methods by which to study the infectious cause, the transmission, and develop valid treatments.

What a difference 700 years makes. Humanity raised ourselves out of the muck of false beliefs like bloodletting for infection, exorcisms for seizures. It didn’t come effortlessly. We now stand on the shoulders of millions. We must honor their efforts by reaching further.

Over the past few months it took scientists weeks to isolate the cause of COVID19, sequence its DNA, and study its transmission. It will take weeks and months to test for the prevalence of natural immunity in our friends and neighbors. It will take many months for the medical community to develop better treatments and even more months to years to develop vaccines. Please take the long view. Humanity has some control, some hope.

Let us be wise enough to use the tools we have. Adopting a stepwise approach is the only way forward to open the economy, while staying mindful of advances in testing and therapy; each individual’s workplace and home; and each individual’s immune status and tolerance for risk. Get ready for a long and bumpy road. We may find that re-opening results in worse outcomes, so we will find ourselves accelerating, then braking, using off-ramps, and even reversals.

Be well. Stay safe.