Taste Loss in Covid-19: What Do We Really Know About It?
Possible reasons for why some Covid-19 patients have taste loss but an intact sense of smell.
Google and PubMed (a biomedical database) mostly return hits on smell loss, or combined smell and taste loss, as a symptom of Covid-19 that may take weeks to resolve. But how much do we really know about Covid-19 taste loss itself?
Smell loss alone cannot explain it
We know how SARS-CoV-2, the novel coronavirus that causes Covid-19, induces smell loss. It infects and damages the olfactory sensory epithelium that serves to maintain the health of olfactory neurons. As a result, the olfactory neurons lose their supporting structure and malfunction. And electrical signals carrying smell data into the brain gets hampered.
“Isolated taste dysfunctions are reported in Covid-19 which shows other mechanisms are involved.”
As smell and taste systems are interlaced, many believed that taste loss in Covid-19 is just the aftereffect of smell loss. While that is a valid reason, it is not the full picture. As a July review in the Journal of Craniofacial Surgery pointed out, “Isolated taste dysfunctions are reported in Covid-19 which shows other mechanisms are involved.”
A meta-analysis of 27 studies, published September in Otolaryngology Open, calculated that smell and taste disorders occurred in 48% and 41% of Covid-19 patients, respectively. But this number is only 35% for combined smell and taste disorders. This means that at least 6% had taste problems not attributed to smell. Why?
1. Zinc depletion
In people with no known medical history that may impair taste function, zinc deficiency is often the culprit. Gustin, a saliva component that contains zinc, maintains the health of taste buds (or taste receptors). As follows, zinc therapy has been reported to improve gustin levels and taste function in humans with a reduced sense of taste. A small randomized controlled trial has also supported the use of zinc to treat taste disorders.
Immune cells require zinc to function. And zinc itself is an antiviral that disrupts the replication machinery of coronaviruses (and other RNA viruses). So, as the body fights against Covid-19, its zinc stores may become exhausted.
And Covid-19 patients are likely zinc-deficient for two reasons, leading to compromised taste buds or receptors:
- Poor zinc status is a risk factor for hospitalization and death from Covid-19. And zinc treatment could prevent the worsening of Covid-19 if administered early. Thus, Covid-19 patients are probably already deficient in zinc, even before the infection.
- Immune cells require zinc to function. And zinc itself is an antiviral that disrupts the replication machinery of coronaviruses (and other RNA viruses). So, as the body fights against Covid-19, its zinc stores may become exhausted.
“We hypothesize that changes in localized cellular zinc homeostasis in oral gustatory cells resulting from immune responses to SARS-CoV-2 viral replication may result in dysgeusia,” said a Septemeber research review of Francina Lozada-Nur, a professor of clinical oral medicine at the University of California San Francisco. (Dysgeusia: an altered sense of taste.)
More Studies Shed Light on the Value of Zinc in Covid-19
Evidence suggests that zinc could protect against Covid-19 — how?
2. Infected salivary glands and taste buds
Studies have detected that ACE2 receptors — the entry point of SARS-CoV-2 — in the taste buds and salivary glands of humans (also mice and monkeys) are highly expressed. In rhesus monkeys, a study showed that one of the earliest infection sites of SARS-1 is the salivary glands.
As SARS-CoV-2 and SARS-1 use the same ACE2 receptor to infect cells, Prof. Lozada-Nur suspects that “human salivary glands may be affected early on by SARS-CoV-2 infection, resulting in salivary gland dysfunction with subsequent salivary flow impairment, in both quality and quantity…”
The salivary glands are also an immune-privileged site, where the immune system is less vigilant. Salivary glands have been called a reservoir or hidden source of SARS-CoV-2 for this reason. Indeed, high amounts of infectious virus particles are present in the saliva of most Covid-19 patients.
When cranial nerves are infected and injured, the transfer of neural information, such as taste, from the taste buds to the brain would be jeopardized.
The same may happen with taste buds, where coronavirus infection causes its damage. Besides, taste buds have an abundance of toll-like receptors (TLRs) that recognize pathogens and then mount an inflammatory response against it. As taste buds get infected by viruses like SARS-CoV-2 and become inflamed, the professor theorized, taste bud cells could be damaged or lost.
3. Infected taste buds — cranial nerve — brainstem neural connection
Others have speculated that cranial nerves may also be a target of SARS-CoV-2, given its capacity to replicate efficiently in cultured neurons, brain organoids, or animal brains. When cranial nerves are infected and injured, the transfer of neural information, such as taste, from the taste buds to the brain would be jeopardized.
Brain MRI on Covid-19 patients has suggested that cranial nerves are affected — either by direct infection or generalized neuroinflammation. More robust evidence comes from an autopsy study, published in October in The Lancet Neurology, where researchers identified the presence of SARS-CoV-2 proteins in the cranial nerves and brainstem.
Most of the cranial nerves are linked to the brainstem, where neural signals are processed. The brainstem is rich in ACE2 receptors, which could explain the extensive brainstem damage seen in brain autopsies of deceased Covid-19 patients. SARS-1 and MERS also have a preference to attack the brainstem. How SARS-CoV-2 reach the brainstem, or the brain for that matter, could be either via neuronal hijack or blood-brain-barrier invasion.
While scientists have decoded how SARS-CoV-2 causes smell loss, much lesser is known about taste. As smell and taste systems are interlinked, is it assumed that taste loss in Covid-19 is a result of smell loss. But Covid-19 patients can experience taste disorders while having an intact sense of smell, suggesting other mechanisms at play. These include zinc deficiency and infection of the salivary glands, taste buds, and neuronal connections between taste buds, cranial nerves, and the brainstem.
Although these mechanisms are largely theoretical, considering that the scientific community overlooked taste disorders related to Covid-19, they could help inform better medical decisions. For instance, Covid-19 patients could try zinc supplementation to restore taste function if taste loss persists.