COVID-19 and Smell Loss: What is Known about Mechanism and Recovery?
How the novel coronavirus robs your sense of smell, and what can be done about it.
For generations to come, there is no doubt that 2020 will be branded as the year of the pandemic. Perhaps 2020 will also make us realize how little we know about the coronavirus and post-viral smell loss. It took us by surprise when the majority of COVID-19 patients reported this unusual symptom, and we hardly know what to do about it.
Although it is established that COVID-19 (the disease), specifically, SARS-CoV-2 (the virus), causes respiratory symptoms (shortness of breath) by primarily infecting one’s lungs; an insidious finding has been reported in more than 50% of COVID-19 patients: anosmia (the loss of smell). Anosmia is also frequently accompanied by dysgeusia, a distortion of taste.
This makes sense if you think about the nose being linked to the windpipe, down the lungs, right?
Here are three possible mechanisms describing how SARS-CoV-2 causes anosmia, as well as potential treatment options to restore the sense of smell.
How does SARS-CoV-2 invade cells? 👽
In gist, SARS-CoV-2 has spike proteins on its surface. These spike proteins bind onto ACE-2 receptors present on the human cell membranes, facilitating cellular entry and infection, leading to the shedding of new virions. These ACE-2 receptors are abundant in a number of organs such as the lungs, small intestine and blood vessels, as well as cells present in the nasal cavity.
Infection mechanism may influence recovery speed 📈
I. Nasal congestion 😷
Imagine having a stuffy/runny nose from catching a cold. It’s difficult to pick up the smell of your mom’s cooking, and your favorite food doesn’t taste the same. Nasal congestion may contribute to a temporary loss of smell. However, this is the least likely cause of anosmia given the high incidence of COVID-19 patients reporting an absent stuffy/runny nose.
As such, researchers proposed that SARS-CoV-2 may instead target cells involved in scent detection as well as the neurons that perceive them.
II. Cellular damage 😡
This study investigated the expression of ACE-2 receptors in the scent detection region of the nasal cavity: the olfactory epithelium, comprising of olfactory sensory neurons (short for OSNs, which are responsible for detecting and transmitting odor information to the brain) and a group of supporting cells (i.e., basal stem cells and sustentacular cells).
Mouse models and human autopsies revealed that ACE-2 receptors are highly abundant in supporting cells, in contrast to OSNs, where none are present. This prompts a strong possibility that SARS-CoV-2 infect supporting cells, which in turn damages the OSNs, resulting in transient anosmia. This is a temporary phenomenon as supporting cells do regenerate.
Another proposed mechanism contributing to anosmia is the inflammatory response elicited by vascular cells upon SARS-CoV-2 infection. This causes collateral damage to the olfactory bulb neurons due to diffused vascular inflammation. As seen in the image below, the vascular cells and neurons are in close proximity. Once the inflammation resolves, patients gradually recover their sense of smell.
On a molecular level, this inflammatory response may also occur in supporting cells within the olfactory epithelium, where inflammation triggers the release of certain molecules (e.g., type I interferon) that down-regulate the expression of odor receptors in OSNs.
Without these odor receptors, the OSNs can’t detect scent particles that have entered the nose — this information won’t be delivered to the brain, resulting in anosmia. Similarly, once inflammation resolves, patients gradually regain their sense of smell.
III. Cell death 💀
If the infection is severe enough, it’ll cause cell death to either OSNs or supporting cells, which is the mechanism hypothesized in patients with long-term anosmia lasting longer than 4 months.
However, data from this study reassuringly reported that more than 90% of their patients eventually regain their sense of smell after 6 months.
What does this mean for COVID-19 patients? 👃
Interestingly, the majority of COVID-19 patients (85%) presented with anosmia tend not to develop severe respiratory symptoms, although some may experience mild bouts of dry cough. Note that they are still contagious at this stage and ought to follow self-isolation and mask-wearing regulations.
Despite the fact the olfactory epithelium has one of the fastest regenerating cells in the human body, ranging from days to weeks, reports have shown that, on average, COVID-19 patients recover their sense of smell within 3 weeks, while some as long as 6 months.
Don’t they regenerate super fast? Why does it take so long to recover?
Researchers have narrowed this phenomenon down to two reasons: Genetic predisposition of the host and genetic variation of the virus.
The former hypothesized that individuals with different genetic polymorphisms of SARS-CoV-2 entry proteins (i.e., ACE-2 and TMPRSS-2 receptors) in cells lining the olfactory epithelium are predisposed to the virus, resulting in larger viral loads and more cell deaths. This is highly plausible given the dense concentration of SARS-CoV-2 entry receptors present in supporting cells of the olfactory epithelium. With more cell deaths, it would take longer for these cells to regenerate, hence a longer period of anosmia.
The latter suggested that mutated SARS-CoV-2 viruses may have a stronger affinity to olfactory epithelium cells, leading to severe inflammation that inhibits the regeneration process, leading to prolonged anosmia.
Studies on Recovery 🔬🌷
Although olfactory impairment is not life-threatening, it could cripple one’s quality of life, especially to patients who rely on them for their livelihoods, such as chefs.
Presently, experts are looking into treatment modalities such as olfactory training to strengthen the remaining olfactory function. Olfactory training involves repeatedly sniffing a set of essential oils (e.g., lemon, rose, eucalyptus and clove scents) for 20–30 seconds, twice a day, to stimulate various olfactory receptors and establish new neural pathways to the brain’s olfactory center, essentially retraining how the brain perceives odors.
Previous studies have shown promising results of substantial olfactory improvement in (non-COVID-19) post-infectious patients who underwent 3 months of olfactory training.
In addition, given the inflammatory havoc SARS-CoV-2 is notorious for, researchers are investigating the role of systemic and intranasal corticosteroids in COVID-19 patients to mitigate inflammation. Without inflammatory components flooding the nasal epithelium, the regeneration process will no longer be inhibited, which by theory, should gradually restore one’s sense of smell.
Other medications previously used in post-infectious patients that are now under investigation for patients with anosmia due to COVID-19 include:
- Intranasal sodium citrate spray that was trialed to improve olfactory function by modulating cellular signal transduction cascades.
- Adjuvant use of intranasal vitamin A to promote neuron growth.
- Omega-3, as an adjunct to olfactory training, for its anti-inflammatory properties.
Given the magnitude of this pandemic and the high prevalence of COVD-19-related anosmia, of which at least 10% of these patients continue to suffer from anosmia longer than 6 months, finding effective therapeutics capable of restoring olfactory function is all the more important now.
This is my first time attempt at writing a scientific topic on Medium. Hopefully, you found it as interesting as I did!😄 On that note, I would like to end this post with a quote by UN Secretary-General Antonio Guterres:
“We are in this together — and we will get through this, together.”
Please, take care.⭐
Love, Alice
P.S.: I have another interesting COVID-19 related topic lined up.💩💩
