Anosmia, ?happy hypoxia,? and blood clots: What scientists know and don?t know

The Covid-19 pandemic is an unprecedented event in modern medical practice, and health care providers are seeing extraordinary numbers of severely ill people. Many providers think the novel coronavirus is causing the human body to behave in weird ways. In some cases, they may be right ? but not in all of them.

Some of the side effects associated with Covid-19 are unusual symptoms for a respiratory infection while others are simply being observed by doctors more often because of the sheer number of people infected. As the pandemic unfolds, both physicians and the public are struggling to differentiate between the two as a way to better understand the virus. Below are three symptoms that have received recent attention.

Easily clotting blood

One symptom that has been described as a mysterious complication of Covid-19 infection is the presence of blood clots in people with more severe forms of the disease.

In a prepublication study recounting the autopsy findings of 20 people in Louisiana who died from Covid-19, the authors described clotting in the small blood vessels of many patients? lungs. A group of Dutch scientists also described a series of hospitalized people who had clotting complications; most of those complications were in the veins of the lungs.

The process of clot formation in human blood involves hundreds, if not thousands, of proteins and cells. Doctors who specialize in blood diseases can usually identify the cause of a clotting disorder by looking for patterns in blood tests that measure those proteins and cells? abundance.

But the clotting that accompanies many severe Covid-19 infections evades that effort. Blood tests in people with these infections ?don?t fit into the usual patterns,? says Adrienne Phillips, MD, a specialist in hematology and oncology at Weill Cornell Medicine in New York City. This makes it hard to determine the root cause of clotting in these people, which in turn makes it difficult to make broad recommendations for preventing or treating those clots.

Another unusual feature of the clotting associated with Covid-19 is related to the size of the blood vessels where the clots are found. Critically ill people who do not have Covid-19 often develop clots in large blood vessels as a side effect of not moving much and having disease-related inflammation in their bodies. These factors make clotting so likely that for years, most critically ill people have received clot-preventing medication as a matter of course while they?re in the hospital.

But many people with Covid-19 who are on clot-preventing medications are nevertheless developing clots in their lungs ? and not just in the large blood vessels but in very small ones, too. ?That?s what makes this clotting unique,? says Phillips. The unusual locations of these clots raise the concern that clotting is not just a side effect of a Covid-19 infection but is actually a feature of it.

Because these clots? characteristics are so unusual, and because of the growing concern that clotting is responsible for much of the havoc the infection wreaks, several studies are underway to investigate whether drugs that prevent or bust clots can help people infected with the novel coronavirus.

While this set of symptoms might feel unusual, it?s really the number of people experiencing it that?s unusual rather than the symptom itself.

?Happy hypoxia?

The presence of ?happy hypoxia,? a phenomenon in which people with low blood oxygen levels do not actually feel short of breath, has also been treated in news reports as a clinical conundrum. Although the spectrum of lung disease that Covid-19 causes is still not completely understood, this particular symptom is nothing new, says Martin Tobin, a professor of pulmonary and critical care medicine at Loyola University.

When it comes to the ways lungs work in the setting of Covid-19 infection, ?our understanding of how the body reacts to major challenges remains the same,? he says.

At baseline, human bodies need a steady supply of fresh oxygen to live, and so people constantly produce carbon dioxide waste as a side effect of normal metabolism. Healthy lungs exchange oxygen for carbon dioxide in the lungs? many tiny air sacs.

When a portion of the lungs has a complete blockage of air or blood flow, that exchange doesn?t happen and oxygen levels drop. But carbon dioxide, which exchanges more readily than oxygen, can still escape the lungs as long as the rest of the lung tissue is relatively healthy and not stiffened by age or disease, like uncontrolled asthma or severe pneumonia.

That results in low oxygen levels and low carbon dioxide levels ? and people can actually feel pretty comfortable with low oxygen levels if they are not exerting themselves, says Tobin. Before this pandemic, doctors occasionally saw this same pattern in people with healthy lungs who had developed a bacterial pneumonia called ?lobar? pneumonia.

?This is an extraordinarily contagious virus that is affecting people in the thousands, tens of thousands, hundreds of thousands,? says Tobin. Doctors aren?t used to evaluating people with respiratory problems in these numbers nor ?having to make decisions about large numbers in a very short period of time.? So while this set of symptoms might feel unusual, it?s really the number of people experiencing it that?s unusual rather than the symptom itself.

Covid-19-associated smell loss may be unusual in that it is reported by so many people relatively early in the course of their infection, often without nasal passage inflammation.

Loss of smell and taste

There are some relatively common Covid-19 complications that are less common in other infections. The loss of smell and taste are among them. A prepublication study from a group of German authors compared smell in 45 people diagnosed with Covid-19 with 45 uninfected people and found that 40% of infected people and none of the uninfected people had lost their sense of smell. Another peer-reviewed French study found a loss of smell lasting an average of nine days in nearly half of all people infected with Covid-19; 85% of those people who lost smell also lost their sense of taste. Although anecdotal reports often highlight the absence of other symptoms accompanying loss of smell, the French investigators noted 60% of people who lost their sense of smell had a runny nose.

Well before Covid-19 was on the scene, doctors understood smell could be impaired by a variety of conditions, infections among them. A Japanese study of people who reported problems smelling after head colds identified a virus in 15 of 24 participants? nasal discharge: Most were rhinoviruses ? among the most common causes of runny noses ? and one was a coronavirus.

When head colds cause loss of smell, it is often thought to be a result of swelling and mucus in the nasal passages that block smell receptors. However, it is also thought that persistent swelling of these passages can kill the nerve cells that conduct smell sensation to the brain, resulting in the inability to smell even well after the swelling is gone (they usually grow back, though).

Covid-19-associated smell loss may be unusual in that it is reported by so many people relatively early in the course of their infection, often without nasal passage inflammation or discharge. Those features make some scientists wonder if Covid-19 is directly affecting the nerves involved in sensing smell or other cells in the lining of the nasal passages. But as with all weird symptoms associated with the infection, further research is needed before we really understand what?s going on.