The Morning Jolt


Why Hydroxychloroquine Didn’t Turn Out to Be a Miracle Pill

A scientist holds a sample during coronavirus testing at New York City’s health department during the coronavirus, April 23, 2020. (Brendan McDermid/Reuters)

A lot to chew over today: why the drug hydroxychloroquine will prove to be a life-saver for some coronavirus patients and useless or even a life-ender for others; why the country needs to “embrace the suck” and be able to accept, process, and respond to bad news; why we are likely to be forced into a reopening plan that lots of Americans will vehemently dislike; and the 2020 campaign’s forgotten man.

We Need to Stop Expecting a Miracle Pill

Part of the frustration in dealing with a really bad situation is a ravenous hunger for magic bullet solutions. One reader wrote in, contending that hydroxychloroquine is effective 100 percent of the time if it’s administered early enough, so why not reopen society and give everyone a prescription for hydroxychloroquine at the first sign of the virus?

Chloroquine and hydroxychloroquine actually slow down parts of a patient’s immune system by “interfere with lysosomal activity and autophagy, interact with membrane stability and alter signalling pathways and transcriptional activity, which can result in inhibition of cytokine production and modulation of certain co-stimulatory molecules” — which is a jargon-heavy way of saying it makes your immune system’s cells not work as well together.

People might wonder why anyone would want to take a drug that weakens their immune system. Hydroxychloroquine can be an effective drug for lupus, because with lupus, the body’s immune system becomes overactive and starts attacking healthy, normal cells. It is also used to treat arthritis, because in patients with rheumatoid arthritis, their immune system attacks the lining of their joints. With patients suffering from malaria, the parasite actually can send out “messages” that distract the body’s immune system, causing it to attack healthy red blood cells and ignore the real threat: “While the immune system is busy defending the organism against fake danger, the real infection proceeds inside red blood cells, allowing the parasite to multiply unhindered at dizzying speed. By the time the immune system discovers its mistake, precious time has been lost, and the infection is much more difficult to contain.” Hydroxychloroquine effectively calms down the immune system and along the way binds to the malaria parasite, breaking it apart.

The coronavirus identified as SARS-CoV-2 can generate a “cytokine storm” — when the body’s immune system kicks into overdrive and starts attacking healthy cells in important organs. Dr. Randy Cron, an expert on cytokine storms at the University of Alabama at Birmingham, told the New York Times last month that in about 15 percent of coronavirus patients, the body’s defense mechanism of cytokines fight off the invading virus, but then attack multiple organs including the lungs and liver, and may eventually lead to death. As the patient’s body fights its own lungs, fluid gets into the lungs, and the patient dies of acute respiratory distress syndrome.

From this, you can get a sense of how and why hydroxychloroquine might be effective in some circumstances and not others. If the patient’s immune system is strong enough to fight off the coronavirus, but is at risk of going into overdrive and setting off a cytotkine storm, administering the right amount of hydroxychloroquine might put their immune system back in the Goldilocks zone — strong enough to fight off and defeat the virus, but not so strong that it starts attacking vital organs by mistake. It’s also easy to see why we would only want people taking this drug under a doctor’s recommendation and possibly supervision — take the drug too early, and you suppress the body’s immune system just when it needs that system functioning well to fight off the invading virus. Take the drug too late, and the damage to the vital organs can’t be overcome.

Tocilizumab is another immunosuppressant drug that is being used in trials to treat the coronavirus. Because President Trump hasn’t mentioned it, you’re hearing almost nothing about it, and no one is writing angry op-eds about it.

In Order to Get Through This, We Need to Be Able to Handle Bad News

“Embrace the suck” is a military slang term meaning, “The situation is bad, but deal with it.”

One of the recurring points in discussing this virus over the past — ugh, has it only been three months? It feels like three years — has been American culture’s difficulty in accepting and processing bad news and responding to it. We don’t want the situation to be so terribly bad, so we either flatly insist that the situation can’t be so bad, or we look for any sign that the situation might not be as bad.

In January, we saw many inaccurate reassurances that Americans should be more worried about the common flu than this new virus that emerged in Wuhan, China. Back on January 30, former Obama White House health advisor Dr. Ezekiel Emanuel told CNBC: “Everyone in America should take a very big breath, slow down, and stop panicking and being hysterical. We are having a little too much histrionics on this.” (Now Emanuel believes that Americans will not return to large events until “fall 2021 at the earliest.”) And Emanuel was far from alone in his assessment that the coronavirus was not much of a threat.

In reading the debates about the virus and how to handle the ongoing outbreak, you get the sense that some people placed bets early on and are determined to see those early assessments turn out right. Some people insist that because the CDC’s website has the official death count at 39,910 that the more commonly cited numbers from Johns Hopkins or Worldometers must be a widespread, sinister effort to overstate the virus’ toll. Never mind that right there on the CDC website, at the bottom, it says, “data during this period are incomplete because of the lag in time between when the death occurred and when the death certificate is completed, submitted to NCHS and processed for reporting purposes. This delay can range from 1 week to 8 weeks or more, depending on the jurisdiction, age, and cause of death.”

I can’t begrudge someone for recoiling from the thought that more than 71,000 Americans have succumbed to the virus. But that doesn’t mean that a smaller number must be the more accurate one, particularly when the source tells you that the data are incomplete. And for everyone reading this who jumped out of their chair eager to write me about the factors that could be contributing to an undercount or overcount, I wrote about them in the Corner yesterday.

Reopening Society with Manageable, but Still Existent, Risk

By the way, as much as I enjoy reminding Ezekiel of his terribly wrong early assessments, he’s also willing to tell the New York Times that a functioning American society requires some acceptance of some level of risk:

Bazelon: Should we make reopening school the highest priority, even though there are going to be trade-offs, and maybe some increase in deaths?

Emanuel: Well, I think as long as teachers can opt in and administrators can opt in and parents can opt in. Maybe I’m crazy, but I think a lot of parents would consider it and be willing to run some risk to themselves.

He’s not crazy — or at least not on this particular point.

With no enthusiasm, I contend that the United States is going to have to enact some version of the evolving plan laid out by Lanhee Chen, Bob Kocher, Avik Roy, and Bob Wachter; with additional contributions from Mark Dornauer, Gregg Girvan, and Dan Lips. (I keep calling it “the Avik Roy plan” because I know him.)

I’m not going to lie to you. This plan stinks. It just happens to stink less than all of the other options. The Avik Roy plan assumes we can’t create a vaccine in the coming year, we can’t test everyone as often as we would like, and that we won’t get a miraculous treatment that mitigates the danger of the virus.

You should read the whole thing — a shorter version was in the Wall Street Journal — but here’s probably the most controversial decision: 

To start, states and localities should work as quickly as possible to reopen pre-K and K-12 schools. Children have a very low risk of falling seriously ill due to Covid-19, and the majority can and should return to school this academic year. Switzerland, for example, is planning to reopen schools on May 11, based on research showing that school closures were among the least effective measures at reducing European Covid-19 cases.

Children who live with the elderly or other at-risk individuals should continue to stay home. Teachers and staff from vulnerable populations should stay home as well, with paid leave. School districts should immediately begin to develop virtual lesson plans for those who must remain home.

(Keep in mind, some state government officials are already saying that distance learning may continue at the beginning of the school year in late August and early September.) The plan continues . . .

Similarly, we should reopen workplaces to healthy, non-elderly individuals who don’t live with vulnerable people. At-risk individuals with jobs should continue to have opportunities to work from home or to receive paid medical leave.

If you’re wondering about whom the plan means when they say “at-risk individuals” . . .

Individuals between the ages of 40 and 65 should consider continuing to stay home if they have any underlying conditions that make them more susceptible to death or hospitalization with COVID-19, such as cardiovascular disease, high blood pressure, diabetes, severe asthma, chronic obstructive pulmonary disease (COPD), kidney failure, severe liver disease, immunodeficiency, and malignant cancer. It is worth noting that a large percentage of the over-40 population has one of these conditions, and so it will be essential to monitor COVID-19 cases over time for evidence that helps us narrow the categories of risk, and also evidence regarding the relationship between positive antibody tests and immunity.

That’s a lot of Americans to leave working at home, continuing social distancing, avoiding groups, parties, and strangers more or less indefinitely.

But some version of this is probably going to be the least-bad way to establish a sufficiently reopened society and economy, while protecting those most at risk to succumbing to the virus.

ADDENDUM: Maybe it’s just me, because I’m hip-deep in medical journals these days, but . . . is anyone else periodically forgetting that Joe Biden is running for president? Like, “Oh yeah, this is a presidential election year, I forgot about that . . .”


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