COVID-19: Coming to Our Senses

“When you arise in the morning, think of what a privilege it is to be alive—to breathe, to think, to enjoy, to love.” Marcus Aurelius

“I wish all the disinfecting fluids invented made such ‘an abominable smell’ that they forced you to admit fresh air. That would be a useful invention.” Florence Nightingale

The focus of this Germ Gem is on symptoms of SARS-CoV-2 (COVID-19), and more specifically on silent hypoxia, a condition where patients with perilously low blood oxygen levels paradoxically do not feel short of breath, and on the loss of taste and smell. Additionally, the role of another of our senses—common sense—in decision-making is discussed.

As we all know, saying that we are on a steep learning curve in the COVID-19 pandemic is a colossal understatement. The first information on the nature of the disease emerged like the pandemic itself from the epicenter, Wuhan, China. These reports described the clinical features of hospitalized patients. Based on their findings, supplemented by subsequent publications, the symptoms of COVID-19 that were initially highlighted were cough, fever, and shortness of breath.

Currently, the Center for Disease Control and Prevention (CDC) lists nine common symptoms that may appear in some combination within 2 to 14 days after exposure to the virus: cough, shortness of breath or difficulty breathing, fever, chills, repeated shaking chills, muscle pain, headache, sore throat, and new loss of taste or smell. (Fatigue and disturbances of the gastrointestinal tract and nervous system can also occur.) An important caveat on the presentation of COVID-19 in older adults, a group at increased risk of dying, is that they may have few or none of these symptoms. And as with other types of pneumonia, a change in their mental status, like confusion or increased sleepiness, can be a harbinger of death.

Because it was apparent from the outset of the pandemic that SARS-CoV-2 primarily attacks the respiratory tract, none of the symptoms listed by the CDC is particularly surprising with the exception of “loss of taste or smell.” And while “shortness of breath” isn’t unusual in patients with pneumonia and thus is an unsurprising symptom, some patients with COVID-19 experience a paradoxical phenomenon called “silent hypoxia”—an absence of the sense of being short of breath in the face of very low levels of blood oxygen—which is surprising as it is unexpected in patients with pneumonia.

Silent hypoxia. Frankly, I was unaware of the association of silent hypoxia and COVID-19 pneumonia until reading an April 20 New York Times article, “The Infection That’s Silently Killing Coronavirus Patients” by Richard Levitan. Dr. Levitan is an emergency medicine physician who volunteered to spend 10 days in March in the Emergency Department of Bellevue Hospital in New York City, where he found himself intubating patients with COVID-19 pneumonia who had remarkably low blood oxygen levels. What surprised him was that the patients “did not report any sensation of breathing problems, even though their chest X-rays showed diffuse pneumonia.”

The exact mechanism underlying silent hypoxia in COVID-19 pneumonia isn’t established. Dr. Levitan postulates that at the start of inflammation in the lungs, the tiny air sacs (alveoli) where gas exchange occurs fill with fluid that interferes first with oxygen transport. But because carbon dioxide levels don’t build up concomitantly, patients don’t feel short of breath. In this NYT article and subsequent reports it was suggested that using a device called a home pulse oximeter, which measures blood oxygen levels, could be a “game changer” in the early management of patients with COVID-19 pneumonia. As its name suggests, the device fits over a fingertip and measures the pulse as well as the blood oxygen level. (And many models are available via Amazon).

I was involved in the management of many patients with pneumonia over the past several decades. I don’t recall any of them having silent hypoxia. And the idea of using a home pulse oximeter to test your blood oxygen level at home never occurred to me. But that was in the pre-COVID-19 era. A home pulse oximeter could indeed be very useful as an aid in the early detection of COVID-19 pneumonia. I’m sure that we will see clinical research in the near future aimed not only at characterizing the mechanism underlying COVID-19-mediated silent hypoxia but also at determining whether a home oxygen pulse oximeter (perhaps sitting in the medicine cabinet next to a thermometer) is of value in detecting pneumonia, whether it be caused by SARS-CoV-2 or another pathogen.

Loss of the sense of taste and the sense of smell. Like the reports of silent hypoxia, I was surprised when I saw descriptions of patients with a distorted sense of taste (dysgeusia) and loss of the sense of smell (anosmia) as early clinical manifestations of COVID-19. I don’t remember ever encountering a patient with pneumonia who complained of these symptoms. The first association of these symptoms with COVID-19 came from studies in China, South Korea, and Italy, and then as the pandemic hit the United States, New York City.

One of the more interesting reports of this disorder appeared in an April 22 publication in the Journal of the American Medical Association, “Alterations in Smell or Taste in Mildly Symptomatic Outpatients with SARS-CoV-2 Infection.” In this study from Treviso Regional Hospital in Italy, 283 adult patients with mildly symptomatic COVID-19 were recruited over a four-day period in March. In a questionnaire administered during a telephone interview, 64.4% of the patients reported a sudden onset of an altered sense of smell or taste within two weeks before they tested positive for SARS-CoV-2.

To assess the severity of these symptoms a Sino-nasal Outcome Test 22 (SNOT-22) was used where a score of zero (0) indicates no symptoms through a score of five, which indicates as bad as it could be. The median SNOT-22 score of these COVID-19 patients was 4. If the results of this study are confirmed, the authors of this study suggest that consideration should be given to testing for COVID-19 and for self-isolation of patients who develop new onset of an altered taste or smell.

Through its spike protein, SARS-CoV-2 is now known to target cells in the lower respiratory tract that express ACE2 receptors. Relatively high levels of expression of this receptor are also found in the human olfactory epithelium, so in light of these findings, it’s perhaps not surprising that a loss of smell occurs in COVID-19, and because olfaction and taste are tightly linked, development of distorted taste may follow.

On the topic of the sense of smell, in an April 29 New York Post article, “Dogs could ‘revolutionize’ coronavirus testing by sniffing out the disease,” research is described at the University of Pennsylvania and London School of Hygiene & Tropical Medicine in which dogs are being trained to detect the odor of SARS-CoV-2 in saliva and urine samples. While this might seem far-fetched, the average dog’s nose is tens of thousands of times more sensitive to odors than ours, and as you know, dogs are frequently used to sniff out minute amounts of all kinds of things, including contraband at airports. And incredibly, dogs have been trained to sniff out a variety of cancers and Parkinson’s disease, as well as another infectious disease—malaria.

COVID-19 and common sense. Over the course of my several decades-long clinical career, I often suggested to medical trainees and patients, alike that common sense is a valuable guide to making medical decisions. With the help of several infectious diseases colleagues, I even developed what came to be called the “Ten Rules of Internal Medicine.” All ten rules are rooted in common sense, and as my family and many friends know, I often cite these rules in guiding everyday decisions.

During the course of the COVID-19 pandemic, I’ve often thought that many of the same ten rules could be applied to public health decisions. As this Germ Gem is about symptoms, an example is “Rule 5: If you don’t have any symptoms your doctor can’t make you feel better.” This rule makes the point that if a medicine is recommended and you don’t have any symptoms of illness (that is, you’re asymptomatic), you want to be sure there is solid evidence of its beneficial effects.

From a public health perspective, the decision about wearing a mask to stop the spread of SARS-CoV-2 remains controversial. While there is uniform agreement that patients with symptomatic COVID-19 should wear a mask, for asymptomatic people the decision is less clear. But because we know now that asymptomatic carriers of SARS-CoV-2 can transmit the virus, wearing a mask is recommended for everyone.

And when you stop and think about it, most of the recommendations about prevention of COVID-19—washing your hands frequently, covering your cough and sneezes, avoiding touching your face, and maintaining a distance of at least 6 feet from others—make sense. So too do the suggestions to stay at home if you’re ill and to seek medical advice if you develop fever, cough, and difficulty breathing. After reading this Germ Gem, you should add to this list a sudden loss of taste or smell and for older adults, any change in mental status.

Because COVID-19 is a new disease and our knowledge base is rapidly evolving, it makes sense to follow the advice of trusted public health experts and medical authorities at the CDC and National Institutes of Allergy and Infectious Diseases regarding when you can return to work, school, and entertainment venues. Finally, consider Rule 9 of Internal Medicine: “Timing is everything, and sometimes time is the cure.” Although nobody knows for sure when, COVID-19 will pass. And hopefully, our community, country, and world will emerge much smarter, wiser, and better prepared for the future.