Coronavirus is an elusive enigma

How did coronavirus become so widespread? By the time Dr. Zhang Jixian first reported the cases, it is thought that 180 patients were already infected.

The problem with this is that SARS-CoV-2 and the disease it causes, COVID-19, presents in many different ways and spreads in patients with no symptoms. By the time we were even able to identify that a novel virus was infecting humans, it was already too late. The cases were most likely far too numerous for us ever to be able to identify. This is because the coronavirus moves in silence. By the time a case has been confirmed, it has most likely already spread to numerous individuals who may or may not show symptoms. Making the virus even more elusive is that our testing is missing cases(a lot of cases). This causes contact tracing to be insufficient and behind any advancement of the virus, especially in densely populated cities.

How do we identify the coronavirus? We have no gold standard. Since medicine began, we have always relied on clinical presentations. In the case of COVID-19, there is ambiguity because it can range from asymptomatic to mild or severe. It is extremely difficult to diagnose an asymptomatic COVID-19 patient.

Let us consider a patient who actually does get symptoms. What symptoms are we looking for? That is also ambiguous.

Fever, cough, and shortness of breath have been the triad of findings repeatedly advertised by most major organizations, but these findings are turning out to be quite insensitive.

One study from China in the New England Journal of Medicine showed that even patients presenting to the hospital with symptoms had a fever only 43.8% of the time (understand that we are often using fevers as a screening tool for workers). In other words, even when they had severe symptoms, fever was not seen in the majority of patients. A mere 18.7% of patients reported shortness of breath as a symptom. We are now learning that patients can present with a headache, conjunctivitis, muscle aches, runny nose, sore throat, abdominal pain, diarrhea, nausea, vomiting, or even difficulty tasting or smelling. Just recently news articles have surfaced relating COVID-19 to acute stroke and tender red toes, sometimes being their main symptom.

We have placed a lot of focus on symptomatic patients, but many patients are not and were not symptomatic, at least at some point in their clinical course, but were still infectious. To show how well this virus can deceive, we can look at a study from Japan concerning the
Princess Cruise Lines
. Of the 1723 passengers, 454 of them were recognized as SARS-CoV-2 carriers. This includes 189 people who were not symptomatic and even had an initial negative RT-PCR but were subsequently found to have the virus. We now know with certainty that these asymptomatic carriers can transmit the virus to other unsuspecting individuals. That means they harbor enough virus to infect someone else, despite not having symptoms and possibly testing negative. Also, in the study, it showed that 54% of these asymptomatic cases had severe enough disease to show lung opacities on a CT scan.

This study involved a lot of patients that were older, a category we expect to have more severe disease (more virus, more easily found on testing).

We also know that asymptomatic patients can test positive for the virus by RT-PCR, again confirming viral presence (whether viable or not) in these patients. A recent article in the New England Journal of Medicine proved this even further with asymptomatic screening in the nursing home population. This showed that 56% of the positive cases were asymptomatic at the time of testing.

Let us imagine we have some intuitive sixth sense when we come across an asymptomatic patient who has COVID-19. How could we prove it? Currently, we are relying on a real-time polymerase chain reaction test that amplifies any strand of SARS-CoV-2 RNA that it is able to detect. We are learning that these tests, in a lab, do a reliable job of identifying this RNA.

Despite that, clinically, the sensitivity or the ability of the test to identify the disease is, honestly, terrible.

In one study, 48% of patients with negative RT-PCR for the virus showed lung findings on a CT scan that were determined to be highly likely from COVID-19. Additionally, 33% that tested negative were determined to probably have COVID-19. Of course, we do not have a gold standard for testing, so it is unclear whether this was COVID-19 or a different lung disease, but other studies have also shown that the test is missing a lot of cases including severe, intensive care level cases where we would expect viral replication and RNA levels to be highest.

A study from the Journal of the American Medical Association (JAMA) showed us that patients requiring oxygen can test positive on day 3 or 4 of their illness, but then test negative for four straight days, and then test positive again on day 9 with their subsequent results continuing to fluctuate.

This is becoming increasingly troublesome as negative testing is leading to false reassurance. Reopening sports and other large gatherings are relying on these tests. Some hospitals and treatment teams are making important decisions about stopping strict isolation and moving patients into none COVID departments based on the RT-PCR and clinical suspicion. Outpatient surgery centers are using negative results to clear patients for surgeries with a high risk of transmission.

We need to start looking at this virus as the novel pandemic virus it is, with all its novel characteristics. These deceptive characteristics allowed the virus to flourish, permitting it to get on an airplane and travel throughout the world. At the same time, sick patients were isolated in their local hospital being intensely studied. Our focus was always on them — and it should be — but we must understand the contribution of carriers and asymptomatic patients if we are to halt the spread of the virus.

Cameron Harrison is an emergency medicine resident.

Image credit: Shutterstock.com

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