What We Dont Know About the Coronavirus – The New Yorker

Its not only the immune system that must maintain a delicate balance. The bloodstream, too, exists in a perpetual tug-of-war between bleeding and clotting. Too much bleeding, and the smallest trauma can cause hemorrhage, even to the point of death (the danger faced by people with hemophilia); too far in the other direction, and clots will form in the absence of trauma, potentially obstructing blood vessels and causing lethal damage if they travel to the heart, lungs, or brain.

By measuring a blood protein called D-dimer, doctors can get a rough sense of how much excess clotting is happening in the bloodstream. Many infections cause a rise in clotting. But in some COVID-19 patients doctors are seeing jaw-dropping spikes. A few patients appear to have widespread pathologic clotting. One of our patients, a healthy man in his fifties, arrived in our hospitals I.C.U. with a D-dimer level of a thousandelevated but unremarkable. But when a doctor attempted to put an I.V. into one of the mans femoral veinsthe largest veins in the legshe discovered, through use of a bedside ultrasound, that it was filled with clots. The second D-dimer test, performed just hours after the first, registered a level of over ten thousand. The man died several hours later.

Its possible that cytokine storms are causing overactive clotting. But, whatever the cause turns out to be, clinicians face a challenge. Doctors often give small doses of anticoagulant medication to patients who are admitted to the hospital, simply because lying in bed for an extended period makes clotting more likely. But more extreme levels of clotting demand more aggressive anticoagulationand doctors must figure out when to administer it and to whom. These medications carry their own risks. The patient suffering from femoral clotting was immediately put on aggressive anticoagulation medication. Yet his death, and the rapid increase in his D-dimer, suggest that successful anticoagulant interventions in other patients may need to come earlier.

Doctors often test critically ill patients for cardiac-specific troponinsproteins in the bloodstream that are normally found only in the muscles of the heart. The presence of such proteins in blood suggests heart damage. Some severe COVID-19 patients have elevated troponin levels; their hearts appear to be damaged. Were not entirely sure whats causing the damage, though, and so we dont know exactly how to treat it.

One major cause of heart damage is oxygen starvation: its what happens in a heart attack, when the sudden obstruction of a coronary artery prevents oxygen from reaching heart muscle. Starvation can also occur when failing lungs prevent oxygen from entering the bloodstream, or when sepsis causes such a drop in blood pressure that even properly oxygenated blood cant get to the heart fast enough. These problems are significant, and, in broad terms, doctors know how to respond to them. There are, however, other possibilities. Perhaps runaway clotting is choking off circulation vessel by vessel. Early reports from China, meanwhile, suggested that the coronavirus could be attacking the heart muscle directly, causing a syndrome known as myocarditis. No one knows for sure what the best treatment for this form of myocarditis might be. Some doctors have reported that steroids can helpand yet steroids also act as an immunosuppressant. In critical care, its often hard to bring one organ system into balance without destabilizing another.

A similar story appears to be unfolding around the kidneys. Kidneys serve as filters for the blood, weeding out certain compounds and excreting them in urine, while regulating the precise composition of electrolytes that allow cells to function. Complete kidney failure is a death sentence if its not quickly addressed. Unfortunately, many critically ill COVID-19 patients are developing it. Just as ventilators are substituting for failing lungs, so dialysis machines are taking over for failing kidneys. The hardest-hit areas of the country are facing shortages of the resources needed for dialysis: dialysis machines, the fluid used in the dialysis process, and dialysis-trained nurses.

We dont yet know how kidney injury plays out in COVID-19 patients. Its likely that some people will recover their kidney function, while others could lose it permanently. We also dont know why people are going into kidney failure in the first place. As with the heart, its possible that oxygen starvation is the problem. But some clinicians argue that the virus is attacking kidney cells directlyand there is biopsy data out of China that supports this thesis, too.

Still other organ systems may be involved in COVID-19. The ACE-2 receptor protein, which is used by the coronavirus to enter human cells, resides not just in the respiratory tract but also on cells in the stomach, intestines, liver, kidneys, and brain. There are reports of coronavirus patients with encephalitisa potentially fatal inflammation of the brainand signs of an increased incidence of stroke. In our hospital, we have seen several COVID-19 patients suffering from a severe complication of diabetes called diabetic ketoacidosis, despite having no history as diabetics.

Last month, we screened for COVID-19 by asking about fever and cough. Now we know that the disease manifests in other ways, or sometimes proceeds with no symptoms at all. One patient recently arrived in the E.R. reporting three days of watery diarrhea and a day of nausea and vomiting; she said that she felt weak but hadnt experienced fevers, chills, sweats, or respiratory symptoms. Her oxygen saturation was in the low nineties; her chest X-ray was consistent with COVID-19.

For us, and for many doctors we know, cases like these have become subjects of consuming fascination. During our few free moments, we share patients sky-high D-dimer levels and swap theories about the sources of their discordant oxygen readings. In the absence of data from randomized, prospective trials, we search for answers on colleagues Twitter accounts, in interviews with Chinese or Italian physicians, and in our patients charts. Our colleagues at Mount Sinai are actively embarking on dozens of research projects, ranging from ventilator-management strategies to social determinants of COVID-19 mortality, but months will pass before these projects give us objective insight into the disease. The desperate desire for clarity is evident at every level of the medical profession. Earlier this month, The New England Journal of Medicine published an observational, fifty-three-patient study of the antiviral drug remdesivir; many observers criticized the journal for publishing it, because the trial had neither a control group nor randomization, and so no meaningful statistical conclusions could be drawn from its results. (Even its authors noted that actual measurement of the drugs efficacy would require ongoing randomized, placebo-controlled trials.)

And yet, as the historian of science Lorraine Daston writes in a recent essay, its natural to cast about for answers at the dawn of a pandemic. At moments of extreme scientific uncertainty, Daston writes, observation, usually treated as the poor relation of experiment and statistics in science, comes into its own. Confronting a new disease, doctors have no choice but to turn to suggestive single cases, striking anomalies, partial patterns. Slowly, as our ideas about what works and what doesnt help tell us what to test, what to count, the picture clarifies. Until then, we are back in the seventeenth century, the age of ground-zero empiricism, and observing as if our lives depended on it. One patient at a time, we have to work our way into the present.

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What We Dont Know About the Coronavirus - The New Yorker