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https://www.newyorker.com/science/medical-dispatch/how-to-understand-trumps-evolving-condition

How to Understand Trump’s Evolving Condition
Day to day, the news can be confusing. But the treatment of COVID-19 has steps, phases, and milestones that can tell us a lot about how the President is doing.
By Dhruv Khullar

October 4, 2020

The days since Donald Trump tested positive for the coronavirus have been more confusing than usual. Consider this exchange from Saturday’s news conference with Sean Conley, the White House physician:

reporter: Has he also experienced difficulty breathing?

conley: No, no, he has not. Never did. He had a little cough. He had the fever. More than anything he’s felt run-down.

A seemingly straightforward answer. And yet later it emerged that Trump’s oxygen levels had already dipped low enough to warrant supplementary oxygen. Was the President not short of breath when that happened? No one who wasn’t there can say for sure, because the Administration hasn’t been communicating clearly and in a detailed way about Trump’s illness. If the President had a fever, then what was his temperature? Has he sustained any lung damage? When did he last test negative for the virus? One might have hoped that Conley, having been roundly criticized for his evasiveness after his first briefing, would be more forthright at his second, on Sunday. Instead, he dodged again. When asked if Trump had received a second round of supplementary oxygen, he pleaded ignorance: “I’d have to check with the nursing staff,” he said.

The vagueness of the communications we’ve received so far may be intentional: in particular, the question of when and how the President was first diagnosed has become freighted with clinical, epidemiological, and ethical implications. Most reports have placed his first positive test sometime between Wednesday morning and Thursday evening. Clinically, knowing the precise time line would tell us how far into the illness Trump has progressed, and when he will enter the window, usually beginning about a week after the onset of symptoms, in which he’s at the greatest risk for deterioration. Epidemiologically, the timing matters for the many people Trump may have exposed to the virus: the President held campaign events throughout the week, including a fund-raiser in New Jersey on Thursday where he met with dozens of donors—an event that featured a buffet. And, ethically, it affects our judgment of his actions. It’s possible that Trump knew that he had been exposed to the virus, or had even received a diagnosis himself, and yet continued to meet with staff and donors, consciously placing their health at risk.

These possibilities may be adding to the Administration’s caginess. In any event, the coronavirus is already confusing. In the months since the pandemic started, I’ve cared for scores of patients with covid-19, many of whom, like Trump, have been advanced in age. Doctors speak of the “course” of a disease; my patients’ disease courses have been unpredictable, with long plateaus interrupted by sudden reversals. Now that Trump himself has covid-19, the country as a whole faces the diagnostic challenge with which doctors like me have grown familiar. We must figure out where Trump is in the landscape of clinical possibility and try to guess where he’s headed. In a sense, our task is harder: we must do it without an organized, comprehensive overview of what’s happening, piecing together the scattered information as it emerges.

Doctors now recognize two broad and somewhat overlapping phases of covid-19. In the first phase, it’s the replication of the virus that causes problems, such as shortness of breath; especially in the lungs, the virus has hijacked the body’s cells to multiply exponentially, and the immune system is fighting to tamp it down. It’s during this phase that antiviral drugs are thought to have their greatest effect; they are like reinforcements for the immune system, and they help to slow the replication of the virus. In the second phase, it’s the immune system itself that starts to become a problem. The virus provokes an immunological storm that wreaks havoc on many organs; the lungs are still at the center of the disease, but other systems get damaged, too. The body must now fight the virus while weathering its own overreaction. Most patients never enter this second, more dangerous phase, but those who do can grow seriously ill.

To evaluate patients with covid-19, therefore, one must start by determining where in the process they find themselves: are they in the first phase, the second, or the transition between? It’s not unusual for people to be admitted to the hospital during the first phase. Because their lungs are under attack, they often have trouble breathing and need some supportive oxygen; in many cases, an insufficient blood-oxygen level is the primary rationale for hospitalization. (This seems likely to have been true in Trump’s case.) Such patients are monitored closely for changes in oxygen levels and also for other problems that can arise, such as blood clots, heart-muscle damage, bacterial pneumonia, and worsening kidney function. They are likely to receive remdesivir, an antiviral drug, and perhaps the steroid dexamethasone, if their oxygen levels dip low enough. (According to the RECOVERY Trial, a large biostatistical effort in the U.K., dexamethasone may help people who need supplemental oxygen.) We now know that the President has received both remdesivir and dexamethasone; in general, the administration of steroids suggests that a patient is approaching, or has already entered, the second, immune-focused phase of the disease. Still, at this level of illness, a patient might spend a few days on and off small doses of oxygen, delivered through a nasal cannula—a hose with prongs for the nostrils. All this is nerve-racking for patients and their doctors and families, but many people go through this experience and then recover enough to be discharged home.

In some cases, however, oxygen levels continue to fall. The immune system hasn’t been able to subdue the virus, and has started to overreact, causing collateral damage to blood vessels or organs. Once this happens, the second phase has fully arrived. Doctors monitoring a patient in this situation would be especially concerned if lab tests showed that inflammation was surging within the body, or if a CT scan uncovered a blood clot in the lungs or widespread injury to delicate lung tissue. If a steroid had not already been started, it would be administered now. Doctors might also prescribe a blood-thinning medication to treat or prevent a clot, or antibiotics to kill bacteria that are adding insult to viral injury. They could also introduce more sophisticated oxygen-delivery devices—powerful high-flow nasal cannulas, or “non-rebreather” masks—that can provide much higher doses of oxygen to the lungs. The air we breathe normally is about twenty-one per cent oxygen, and a regular nasal cannula might increase this proportion by a few percentage points—but a high-flow nasal cannula can shoot nearly a hundred per cent oxygen up your nose, at sixty litres a minute.

If these maneuvers aren’t enough to maintain blood-oxygen levels above ninety per cent, then doctors turn to mechanical ventilators. A tube is snaked down a patient’s throat and into the lungs. All intubated patients are transferred to an I.C.U. The ventilator takes over the work of breathing; doctors treat what they can and hope for the best. Precise estimates of the likelihood that a person will progress from infection to hospitalization to I.C.U. to death are hard to come by, and vary widely. But a recent meta-analysis suggests that about a third of patients with severe covid-19 end up in the I.C.U., and about a third of those in the I.C.U. go on to die. Although mortality rates for patients requiring I.C.U.-level care have declined since the start of the pandemic, they remain distressingly high.

Because of the scary mortality statistics, the discussion of the President’s illness has often had mortal stakes. The truth, though, is that there’s a vast middle ground of survival, in which patients can beat the virus only to experience residual symptoms and, in some cases, ongoing physical or cognitive deficits. For many covid-19 patients—even those who never move beyond the first phase of the disease—problems such as fatigue and shortness of breath can linger for weeks or months. The risks are much higher for those with severe illness, especially those who end up in the I.C.U. Some patients who recover from covid-19 report fatigue, headaches, memory issues, and breathing and gastrointestinal problems for months after their initial symptoms. Surviving illness and returning to good health are not one and the same.

From a medical perspective, many questions remain about Trump’s illness; some may be answered in the coming days. One set of questions concerns diagnostic tests that could give us a clearer understanding of the seriousness of the President’s condition and the possibility of decline. Disclosure of a CT scan, for example, could offer meaningful information about whether the coronavirus has injured his lungs. (Conley indicated that the President’s scans have shown “expected findings,” but it wasn’t clear what this meant; notably, he did not say the imaging was normal.) Blood tests that analyze inflammatory molecules could reveal the degree of inflammation in Trump’s body, and offer clues about whether the President has crossed from the first phase of illness to the second. Much of the incomplete diagnostic information provided so far has just raised more questions. Conley has said, for instance, that Trump is getting daily ultrasounds, which is not standard medical practice. Ultrasounds of what, and why? If one of them reveals a blood clot in the legs, or damage to the heart—both relatively common complications of covid-19—that would portend a more serious course for the President. In that case, he might be facing a systemic illness, rather than one confined to the lungs; his immune system may have failed to contain the virus and now be contributing to damage of the blood vessels and other organs.

A second set of questions revolves around the treatments Trump is receiving. In the absence of clear communication from his medical team, we can try to work backward, using new steps in his treatment to guess at developments in his illness. For now, we know that the President got a dose of REGN-COV2, Regeneron’s experimental antibody drug, on Friday. The drug has not completed Phase III clinical trials, and hasn’t been approved by the F.D.A. or authorized for emergency use; instead, Trump received the medication under a “compassionate use” request. Last week, Regeneron issued a press release indicating that REGN-COV2 has shown promise for reducing the amount of circulating virus in the body and for alleviating symptoms in non-hospitalized patients. Preliminary results suggest that it is relatively safe, and that patients early in the disease course, who haven’t yet mounted their own immune responses, are more likely to benefit from it. (The average age of trial patients, however, was forty-four—thirty years younger than the President.) The company is still testing to find out whether REGN-COV2 helps hospitalized patients, and whether it can prevent infection in those exposed to the virus. The fact that Trump’s team decided to use an unproven drug suggests something about the perceived seriousness of his disease as early as Friday morning.

The use of dexamethasone is also striking. It likely means that his illness is serious and could be worsening. Dexamethasone can lessen the chances of death for covid-19 patients who are on ventilators or who require supplemental oxygen—but it can be harmful in those without a need for respiratory support. Administering it to someone who isn’t firmly in the second phase of the illness, therefore, involves a careful balancing of risks and trade-offs. It’s a medicine for those with severe disease.

At this point, it’s not clear what the future holds for the President or the country. covid-19 is dangerous and capricious. If we take the White House physician at his word, Trump’s current condition appears stable—but Conley’s evasiveness has created more uncertainty than understanding. In the meantime, we should prepare for a trickle of unsatisfactory, and sometimes contradictory, information from the President’s team. There may be days with no changes, and they may be followed by sudden positive or negative developments. The daily drama of ferreting out Trump’s oxygen levels and test results is worthwhile, but there are key shifts in his clinical care that will be much more telling: the need for a more powerful oxygen-delivery device, for example, or a transfer to a higher level of care, such as the I.C.U. A relatively long hospital stay, even outside the I.C.U., would also be cause for concern. Alternatively, from here, the President could quickly improve and, as Conley suggested on Sunday, be discharged home. These big shifts are far more medically revelatory than whether the President needed two litres of supplemental oxygen or three, and whether he needed them in the morning or the afternoon.

In the hospital, when patients with covid-19 ask me about their prognoses, I respond honestly. Together, we talk through the evidence we have and acknowledge the information we lack. For patients of Trump’s age, and at his stage of the disease, I’m usually able to say that there’s a good chance we’ll get the full recovery we hope for. But I also have to be truthful about the uncertainty we face. I try to choose my words carefully. “It’s hard to predict how things will go,” I often say. “We should prepare for a range of possible outcomes.”