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ORIGINAL ARTICLE Table of Contents  
Ahead of print publication
Study to evaluate the effect of COVID-19 on the sensory perception and the nervous system of an individual: A cross-sectional study


1 Department of Physiology, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India
2 Department of General Medicine, Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India

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Date of Submission29-Mar-2022
Date of Decision29-Apr-2022
Date of Acceptance13-May-2022
Date of Web Publication21-Sep-2022
 

  Abstract 

Purpose: The recent COVID-19 pandemic has caused temporary or permanent anosmia and ageusia in thousands of people. It was occasionally associated with a loss of nociception in the mouth too. A specific pattern of sensory loss or alteration is imperative to understand and predict the modality of the infection. Materials and Methods: A cross-sectional study was performed, which included 252 participants of all age groups and communities. A questionnaire was circulated on social media through the means of a Google Form. Consent was obtained before posing the participants with questions. Results: The sensory loss was found to be the most prevalent in people with mild symptoms. About 65.2% of the participants showed a partial or a total loss in olfaction and 59.5% of them showed a loss in one or more tastes. About 44% of the participants showed a partial or a total loss of nociception. All of the altered sensations came back to normalcy after 2 weeks of the loss of sensation in the majority of the population. Besides the other symptoms, 15.5% of the participants experienced altered mental alertness. Conclusion: SARS-CoV-2 infection was found to affect the olfaction, gustation, and nociception in the oral cavity (spice sensation). Mental alertness was also found to be altered in a small fraction of the population affected with SARS-CoV-2.

Keywords: Anosmia, COVID-19, nociception, SARS-CoV-2, sensory profile


How to cite this URL:
Harindra G, Kour H, Prabhu M. Study to evaluate the effect of COVID-19 on the sensory perception and the nervous system of an individual: A cross-sectional study. APIK J Int Med [Epub ahead of print] [cited 2022 Sep 25]. Available from: https://www.ajim.in/preprintarticle.asp?id=356504



  Introduction Top


It is known that the COVID-19 pandemic, caused by SARS-CoV-2, causes multiple sensory alterations. Although smell and taste sense alterations are the most common symptoms in viral infections, the nociceptive loss was also noted in a few due to which capsaicin could not be sensed. Physical pain remains unaffected despite spice and physical pain being carried by the same neural pathway.

Nociception is known to be sensed by the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, which is transmitted by the branches of the trigeminal nerve. This is a completely different pathway than that of the taste. It could also mean that the pain receptor (TRPV1) is blocked due to inflammation or a chemical change, which leads to the loss of secretion of substance P. This substance P is a polymodal nociceptive detector undecapeptide that is released from sensory nerve endings. Thus, a lack of substance P secretion would lead to the loss of pain sensation.[1],[2]

The anosmia has been speculated to be due to the action of the coronavirus on the angiotensin-converting enzyme 2 (ACE2) receptor proteins. This blocks the action of ACE2, thus preventing the conversion of angiotensin II to angiotensin, causing the prolonged inflammatory response in the olfactory epithelium. Another speculation is the effect of the anosmia on the gustation. The prolonged loss of smell is said to cause a negative effect on the gustatory senses, causing a loss in taste. However, none of these hypotheses have concrete evidence in their favor.[3],[4]

Apart from this, there have been instances where SARS-CoV-2 has caused neural damage, mainly to the brain, causing conditions such as stroke, dementia, encephalomyelitis, meningoencephalitis, and so on. However, this has been observed in those patients who were critically ill during the infection.[5]

With this background, the current study was designed to draw the comparisons between the loss of senses and the effect on the nervous system in SARS-CoV-2 infection. It is designed to arrive at a hypothesis of the pattern of loss of smell and taste loss in SARS-CoV-2 and to gather more information on the effect of the virus on the nervous system.

Aims and objectives

  1. This study aimed to evaluate the sensory perception of patients who were diagnosed and treated with SARS-CoV-2 (COVID-19) in the past
  2. To find the pattern of the occurrence of loss of nociception (spice sensation) along with ageusia
  3. To find the variables that affect the duration of the regaining the sense that was lost during COVID-19; and
  4. To provide more information on the effect of SARS-CoV-2 on the nervous system.



  Materials and Methods Top


A validated, questionnaire-based cross-sectional study was conducted, where the general public answered a set of multiple-choice questions based on sensory loss. The study was conducted by a prestructured Google Form, which was circulated through various platforms. This study targeted people between the ages of 8 and 102 years. The participants were eligible only if they had tested positive for COVID-19 at least once in the past 2 years by any form of diagnosis. However, participants who suffered from other viral infections apart from COVID-19 affecting the sensory perception and nervous system have been excluded. The questionnaire collected the data from the post-COVID patients about the loss of sensations during the infection. All the participants could take part in the questionnaire only after they gave informed consent. The study was carried out over 4 months from October 2021 to January 2022. A total of 252 participants took part in the questionnaire. The data obtained from the questionnaire were analyzed statistically through a spreadsheet and graphs. Classification and tabulation of the data of participants who were asymptomatic, mild (symptoms such as fever, cough, tiredness, and malaise), moderate (symptoms such as body aches, rashes, pneumonia with no signs of disease, and SpO2 <94% on room air), or severe symptoms (symptoms such as difficulty in breathing, severe pneumonia, confusion, and SpO2 <90% on room air) were also made based on their loss of senses and nociception.[6] Ethical clearance was obtained before the conduct of the study Ref. MDC/DOME/209 dated October 5, 2021.


  Results Top


A total of 252 people responded to the Google Survey, of which, 51.6% were female and 48.4% were male [Table 1], [Table 2], [Table 3].
Table 1: Demographic distribution of the participants

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Table 2: Information on vaccination, mode of diagnosis, and infection

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Table 3: Information on sensory profile

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From the above [Table 4], it was observed that loss of complete olfaction was the most prevalent in patients who suffered from moderate symptoms (56.52%), followed by severe symptoms (50%) and mild symptoms (45.51%). Furthermore, the majority of the people who suffered from weakened olfaction suffered from mild symptoms (20.1%) or severe symptoms (20%). It was also observed that smell returned within 2 weeks after loss in majority of the cases.
Table 4: Relation between severity of the infection and the symptoms: Olfaction*

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From the above [Table 5], it was observed that loss of multiple tastes was the most prevalent in patients who experienced moderate symptoms of COVID-19 (66.66%), followed by severe symptoms (60%) and mild symptoms (52.41%). Loss of one taste was the most prevalent in asymptomatic patients (9.75%), who was closely followed by mild symptoms (9.65%). It was also observed that taste returned within 2 weeks after loss in majority of the cases.
Table 5: Relation between severity of the infection and the symptoms: Gustation*

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From the above [Table 6], it was observed that loss of nociception (spice sensation) was the most prevalent in patients with moderate symptoms (45.65%), followed by severe symptoms (35%), mild symptoms (28.96%), and asymptomatic patients (17.07%). Altered nociception was the most prevalent in patients with mild symptoms (15.17%), followed by moderate symptoms (10.86%), severe symptoms (10%), and asymptomatic patients (7.31%). It was also observed that smell returned within 2 weeks after loss in majority of the cases.
Table 6: Relation between severity of the infection and the symptoms: Nociception*

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Thus, from the above results, a rough prediction of the symptoms pertaining to the loss of smell, taste, and spice sensation (nociception) can be made, based on the severity of the other presenting symptoms. This can help people to prepare themselves in advance, to obtain the best recovery of all their lost senses.


  Discussion Top


There have been a few theories that try to explain the reason behind the loss of these senses, although none of them have been proven with evidence yet.

One of the studies showed that 70.1% of the COVID-19-positive population experienced a loss of smell and 65% of them lost taste. This percentage is significantly larger than the loss of senses caused by other viral infections.[6],[7] In January 2020, it was hypothesized that SARS-CoV-2 uses the ACE-2 receptor to enter the human body. These receptors are present in the central nervous system (CNS).[8] The virus uses the ACE2 receptor proteins to enter the host cells, which prevent the cessation of the inflammation. However, it is unclear if the coronavirus causes inflammation through a direct pathway or a peripheral pathway.

Another study also states that the SARS-CoV-2 targets chemical senses, which is why olfaction and gustation are frequently lost. It states that SARS-CoV-2 can cause direct infection to the TMPRSS2 and ACE2, causing a change in composition and ionic balance of the mucus. This could lead to loss of smell and taste. It also states the possibility of the involvement of inflammatory cytokines that may cause the loss of olfaction. Taste may be affected when the cells of the tongue are directly infected by the virus.[3]

It has recently been discovered that SARS-CoV-2 binds to the sialic acid receptors in the mouth, similar to the mechanism of action of the Middle East respiratory syndrome coronavirus virus. Sialic acid is an important constituent of salivary mucin which plays an important role in cellular communication and also helps in the survival of the salivary cells during infection.[9] It also helps in the protection of glycoproteins that transport gustatory molecules into the taste pores from premature enzymatic degradations.[10] Thus, a reduction in the receptors of sialic acid leads to decreased sialic acid levels in the salivary mucin. This leads to an increase in gustatory threshold, which, in turn, leads to ageusia.[11]

Apart from the loss of smell and taste as the presenting symptoms, there have been reports of neurological manifestations in patients with COVID-19. However, no studies have comprehensively researched the clinical characteristics of the involvement of the nervous system.

It has been found that, among 1099 patients that were tested. A whopping 74% of them developed some sort of neurological issues. Impaired consciousness and stroke were frequently observed.[5]

In a cross-specialty survey of 125 patients from the UK, it was observed that 62% of the patients presented with stroke. Alerted mental status (31%), encephalopathy, and neuropsychiatric issues were also observed. It also states that neural disorders are seen more often in the younger age group.[12]

In another survey conducted in the Philippines, 36.4% of patients displayed neurological manifestations of the CNS and peripheral nervous system. These included altered mental status, headache, cognitive impairment, agitation, dysexecutive syndrome, seizures, corticospinal tract signs, dysgeusia, extraocular movement abnormalities, and myalgia.[13]

It has been found that the diet of an individual has been affected due to loss of gustation or olfaction. Altered eating habits and behaviors have been observed in people with anosmia or dysgeusia. This may be attributed to the lack of stimulation of certain centers in the brain, which are responsible for proper feeding habits.[14] This could lead to further health problems such as malnourishment or deficiency diseases.

Alterations in smell or taste were frequently reported by mildly symptomatic patients with SARS-CoV-2 infection and often were the first apparent symptom in many patients. The results must be interpreted with caution due to study limitations: data were self-reported and based on a cross-sectional survey, the sample was relatively small and geographically limited, more severe patients were not included, and data regarding the subsequent course of the disease was not available. Although the SNOT-22 questionnaire has been shown to correlate with objective testing of olfactory function, patients may have difficulty quantifying olfactory function; objective tests should be included in future studies. If these results are confirmed, consideration should be given to testing and self-isolation of patients with new onset of altered taste or smell during the COVID-19 pandemic.[15]


  Conclusion Top


We conclude this study by stating that the majority of the people who complained of loss of smell and taste experienced mild-to-moderate infections of the SARS-CoV-2 virus. Furthermore, the senses came back to normalcy within 2 weeks of its loss in the majority of the people. The findings were, however, surprising and varied, and therefore require a more detailed analysis of a bigger sample space. This could predict the onset of the symptoms, and the duration of the loss of symptoms.

Another conclusion that this study obtained was that loss of spice sensation was not as frequent as ageusia, which means that there is little correlation between the two senses.

It has been observed from the above results that recovery from loss of olfaction, gustation, and nociception in patients suffering from COVID-19 is delayed, as compared to other viral infections, in which it returns to normalcy within a week of infection. This can be considered a valid point to ponder upon for future studies in this regard.

Finally, the study concluded that a small fraction of the population suffered from altered mental alertness and a smaller fraction of the population suffered from dementia. Thus, this symptom needs to be researched more rigorously as it could be a future manifestation of the novel virus.

Limitations

The main limitation of this study was the lack of a molecular level of examination in the patients who experienced a loss of senses or mental alertness. This study was limited to a subjective evaluation of the population who were diagnosed with COVID-19 in the past 2 years. The study did not focus on how early the sensory disturbances appeared. It concentrated on its return after the disturbance. The study did not go into the depths of the pathology of the symptoms. Thus, to understand the virus and the symptoms associated with it on a better level, more targeted studies need to take place. Another limitation may be the inaccuracy of the reported symptoms due to the varying viral strands of SARS-CoV-2, causing different degrees of symptoms in the population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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2.
Govindarajan VS, Satyanarayana MN. Capsicum-production, technology, chemistry and quality. Part V impact on physiology, pharmacology, nutrition and metabolism; structure, pungency, pain and desensitization sequences. CRC Rev Food Sci Nutr 1991;29:447.  Back to cited text no. 2
    
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Rojas-Lechuga MJ, Izquierdo-Domínguez A, Chiesa-Estomba C, Calvo-Henríquez C, Villarreal IM, Cuesta-Chasco G, et al. Chemosensory dysfunction in COVID-19 out-patients. Eur Arch Otorhinolaryngol 2021;278:695-702.  Back to cited text no. 8
    
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Milanetti E, Miotto M, Di Rienzo L, Nagaraj M, Monti M, Golbek TW, et al. In-silico evidence for a two receptor based strategy of sARS-CoV-2. Front Mol Biosci 2021;8:690655.  Back to cited text no. 9
    
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Witt M, Miller IJ Jr. Comparative lectin histochemistry on taste buds in foliate, circumvallate and fungiform papillae of the rabbit tongue. Histochemistry 1992;98:173-82.  Back to cited text no. 10
    
11.
Pushpass RG, Pellicciotta N, Kelly C, Proctor G, Carpenter GH. Reduced salivary mucin binding and glycosylation in older adults influences taste in an in vitro cell model. Nutrients 2019;11:2280.  Back to cited text no. 11
    
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Varatharaj A, Thomas N, Ellul MA, Davies NW, Pollak TA, Tenorio EL, et al. Neurological and neuropsychiatric complications of COVID-19 in 153 patients: A UK-wide surveillance study. Lancet Psychiatry 2020;7:875-82.  Back to cited text no. 12
    
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Espiritu AI, Sy MC, Anlacen VM, Jamora RD; Philippine CORONA Study Group Investigators. COVID 19 outcomes of 10,881 patients: Retrospective study of neurological symptoms and associated manifestations (Philippine CORONA Study). SSRN Electron J June, 2021;19-22. [doi: 10.2139/ssrn. 3862533].  Back to cited text no. 13
    
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15.
Lechien JR, Cabaraux P, Chiesa-Estomba CM, Khalife M, Hans S, Calvo-Henriquez C, et al. Objective olfactory evaluation of self-reported loss of smell in a case series of 86 COVID-19 patients. Head Neck 2020;42:1583-90.  Back to cited text no. 15
    

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Correspondence Address:
Gaurav Harindra,
Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajim.ajim_43_22




 
 
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  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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    -  Kour H
    -  Prabhu M


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