**5. Using "olfaction" to detect COVID-19 and the subsequent sensory-cognitive deficits**

Having been one of the first symptoms to be affected in COVID-19, our sense of smell became an important and a robust tool to be utilized for detecting if an individual is infected [100]. This became much more beneficial in detecting "asymptomatic" or "paucisymptomatic" patients, i.e., those who did not develop other visible symptoms of the disease [101–103]. Since 2020, many empirical tests that could previously assess olfactory detection and sensitivity and acted as biomarker indicators of neurodegenerative disorders, have been also utilized as early screening tools for COVID-19. Brief Smell Identification test (BSIT), a revised version of University of Pennsylvania Smell Identification test (UPSIT), was among the first self-administered tests, which was utilized during first wave of COVID-19 [104, 105]. Briefly, it consisted of 12 scented strips (encapsulated odors), which are to be scratched by a pencil to release the odor. It is a forced-choice test, and the subject needed to choose one of the four choices which smelled like the tested odor. A high score indicated normal olfactory performance. Using this test, olfactory dysfunction was observed in 40% of the patients. Indeed, in those patients with just olfactory-related problems, other symptoms flared up ~2 days later [105]. Another study used the Persian version of the full 40-odor UPSIT and found out that 98% of the 60 patients had olfactory dysfunctions. In total, 58% of these were either anosmic or severly microsmic [106]. Hummel's quick olfactory sniffing Sticks (q-Sticks) test was also administered in COVID-19 patients, which consisted of asymptomatic individuals as well [107]. This test consisted of recognition of groups of three odors emanating from refill sticks. Although only 14% of the total patients reported smell loss before

the test administration, q-Sticks test revealed that 81% of total patients suffered from anosmia or hyposmia [108]. Since the outbreak, such objective tests that can quantitatively measure olfactory detection, such as Quick-Smell Identification test (Q-SIT), SAFER scent cards, *SCENTinel* 1.0 among others have gained traction [109–111]. However, these traditional tests offer simplistic handle on determining odor detection abilities.

Based on the neurotropic potential of CoV-2, olfactory dysfunctions cannot just be restricted to sensory detection and threshold capacities. Rather, COVID-19 can cause both sensory and cognitive deficits, and efforts are being made to diagnose those too. To this end, highly automated tests with precise stimulus delivery are important.

#### **Figure 2.**

*"Olfaction" as a tool to detect COVID-19. (A) Objective tools such as University of Pennsylvania Smell Identification test (UPSIT), Sniffing stick tests among others have been utilized to evaluate the olfactory detection and discrimination capabilities. These tests consist of delivery of odors to the subject via reservoirs/pen refills/ microencapsulations [104, 106, 115]. (B) An automated odor delivery system, Olfactory-action meter (OAM) has been utilized to precisely calculate odor detection at the threshold levels and olfactory matching skills, i.e., both sensory and cognitive capabilities of symptomatic, asymptomatic, and healthy individuals [101, 112]. (C) Sense of smell, i.e., electronic noses, trained canines, and organic semiconducting sensors are also deployed to using the body odor (BO) of individuals to detect COVID-19 [116–119].*

#### *Neurotropic SARS-CoV-2: Causalities and Realities DOI: http://dx.doi.org/10.5772/intechopen.108573*

Olfactory-action meter (OAM), an automated machine with custom-written software that can generate odor pulses of varying complexities, has been utilized to assess olfactory detection abilities at differing concentration ranges as well as olfactory matching skills in asymptomatic carriers, symptomatic patients, and those who have recovered from the disease [101, 112, 113]. Compared with normal healthy subjects, up to 81% of the asymptomatic carriers failed at detecting odors at low concentrations (9% (v/v)). In total, 65% of these carriers depicted significantly lower detection at three low-concentration ranges (9–23.1%). Upon administering an olfactory matching task of determining whether the two odors delivered at a set inter-stimulus interval of 5 s are "same" or "different," they found out olfactory working memory deficits in the patients [101]. Not only that, upon carrying out this test with individuals who had recovered from COVID-19 (4–18 months after infection), persistent sensorycognitive deficits were found out when this paradigm was employed over 5 days [112]. These studies point to the persistence of sensory-cognitive impairments in longhaulers (those suffering from Long-COVID) and also calls for further interrogation of CNS functioning. This also exhibits the importance of monitoring neurocognitive skills during post-infection periods in a pandemic-struck world. These results display the necessity of developing accurate noninvasive methods, which can precisely quantify cognitive deficits in Long COVID [112, 114].

Usage of electronic noses (eNoses) also became popular in detecting COVID-19-infected individuals. eNoses are machines that can mimic animal olfaction and can thus be applied as specific smell detectors of target volatile organic compounds. Usage of an eNose at a drive-through testing station that can detect COVID-19 in real time using body odor that has a nasal passage carried out in an attempt to use them as fast, reliable detectors of this disease [118]. Organic semiconducting sensors could also capture the scent of the asymptomatic carriers of the diseases, suggesting that they can also be deployed at large scale [119]. Finally, dogs can supposedly be our best friends, even during a pandemic. Multiple studies have reported using canines to detect the body odors of the infected patients. Axillary sweat samples of patients may well be successfully discriminated from the normal subjects at a success rate of 76–100% for trained dogs [117]. All these studies thus indicate that sense of smell can be utilized at different levels and scales for diagnosing COVID-19 and furthering the research on cognitive blunting due to this disease (**Figure 2**).
