Pericytes may facilitate SARS-CoV-2 entry into the nervous system

Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Method(s): We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Result(s): The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion(s): Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes. Additionally, SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Mechanisms and implications of COVID-19 transport into neural tissue

The neuropathogenicity of COVID-19 was reported shortly after detection of the virus when patients began reporting symptoms of diminished taste and smell, headaches, mental status changes, and more. As the virus spread, increasing data on viral symptoms in conjunction with novel theories on COVID-19 virulence factors indicated that the virus had neurotropic properties. Several mechanisms have been proposed detailing severe acute respiratory syndrome coronavirus disease 2019 (SARS-CoV-2) transport past the blood–brain barrier and into neural tissue. This chapter offers a comprehensive review of possible neurotropic mechanisms including transport via the angiotensin-converting enzyme 2 (ACE-2) receptor, transportation directly past or through the blood–brain barrier, transsynaptic neuronal transfer, and olfactory conduction. © 2023 Elsevier Inc. All rights reserved.

Imbalanced brain connectome: A possible link behind functional somatic disorders, multiple chemical sensitivity, and long COVID patients

Background: Functional Somatic Disorders (FSDs) are characterized by persistent physical symptoms that cannot be explained by other somatic or psychiatric conditions. Multiple Chemical Sensitivity (MCS) is a non-allergic FSD characterized by odour intolerance and various somatic symptoms being attributed to the influence of toxic environmental chemicals in low, usually harmless doses. The pathophysiology of FSDs are still not clear. Smell and taste complaints were also among the notable symptoms characterizing the covid epidemic and the latest evidence suggests overlaps between long COVID and FSDs. Method(s): The study includes advanced analysis of MRI-derived functional and structural connectomes acquired on a 3 T MR scanner. Furthermore, it includes questionnaires and paraclinical tests, e.g. the Sniffin' Stick olfactory test, Mini-Mental State Examination, and Sino-Nasal Outcome test 22. The pilot part of the project included 6 MCS patients who were compared with 6 matched healthy participants. Later follow-up included analysis of 8 multiorgan FSD and 4 post-COVID patients. Result(s): The MCS group showed important brain structural connectivity differences in 34 tracts. Notably, for MCS patients, the olfactory cortex (especially in the right hemisphere) showed decreased connectivity with regions in the emotional system. Conclusion(s): We plan to extend these findings with whole-brain modelling of the functional connectivity in the patient groups. Long-term this could be used as a 'fingerprint' which could help with diagnosis and treatment monitoring in FSDs as well as with new diagnoses such as long-COVID.Copyright © 2023

Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial.

INTRODUCTION: The current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss. METHODS: This multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT] ≤ 33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale. RESULTS: A total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p = 0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported. CONCLUSION: Olfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy.

Olfactory Cleft Length: A Possible Risk Factor for Persistent Post-COVID-19 Olfactory Dysfunction.

INTRODUCTION: To date, little is known about predisposing factors for persistent COVID-19-induced olfactory dysfunction (pCIOD). The objective was to determine whether olfactory cleft (OC) measurements associate with pCIOD risk. MATERIAL AND METHODS: Three subgroups were recruited: group A included patients with pCIOD, group B included patients without olfactory dysfunction following SARS-CoV-2 infection (ntCIOD), and group C consisted in controls without past history of SARS-CoV-2 infection (noCOVID-19). Olfactory perception threshold (OPT) and visual analog scale for olfactory impairment (VAS-olf) were obtained. OC measurements were obtained through computed tomography scans. Results were subsequently compared. RESULTS: A total of 55 patients with a mean age of 39 ± 10 years were included. OPT was significantly lower in pCIOD patients (group A: 4.2 ± 2.1 vs. group B: 12.3 ± 1.8 and group C: 12.2 ± 1.5, p < 0.001). VAS-olf was significantly higher in pCIOD (group A: 6 ± 2.6 vs. group B: 1.7 ± 1.6 and group C: 1.6 ± 1.5, p < 0.001). OC length was significantly higher in group A (42.8 ± 4.6) compared to group B (39.7 ± 3.4, p = 0.047) and C (39.8 ± 4, p = 0.037). The odd of pCIOD occurring after COVID-19 infection increased by 21% (95% CI [0.981, 1.495]) for a one unit (mm) increase in OC length. The odd of pCIOD occurring was 6.9 times higher when OC length >40 mm. CONCLUSION: Longer OC may be a predisposing factor for pCIOD. This study is expected to encourage further research on OC morphology and its impact on olfactory disorders.

Management of Post-Infectious Anosmia and Hyposmia: A Systematic Review.

BACKGROUND: Anosmia and hyposmia significantly affect patients' quality of life and have many etiologies, including trauma, inflammatory conditions including chronic rhinosinusitis, neoplasm, and viral infections, such as rhinovirus and SARS-CoV-2. OBJECTIVE: Our purpose was to establish whether a consensus exists regarding optimal management of olfactory dysfunction and to provide insight into the treatment of anosmia in the current climate of increased prevalence secondary to COVID-19. Thus, we aimed to systematically review the literature on the management of non-Chronic-rhinosinusitis- related anosmia/hyposmia. METHODS: PubMed, EMBASE, and Cochrane databases were searched for articles published since January 1990 using terms combined with Medical Subject Headings (MeSH). We included articles evaluating management of anosmia and hyposmia written in the English language, with original data, a minimum of 3 months of follow-up except for COVID-related studies, at least 2 patients, and well-defined and measurable outcomes. RESULTS: A total of 3013 unique titles were returned upon the initial search. Of these, 297 abstracts were examined, yielding 19 full texts meeting inclusion criteria (8 with level 1 evidence, 3 with level 2, 1 with level 3, and 7 with level 4). The studies included a total of 1522 subjects, with follow up ranging from 3 to 72 months, with an exception for COVID related studies. Endpoints were based on clinically significant improvements of olfactory functions as measured through validated smell tests. Treatments with the most robust data were intranasal corticosteroids and olfactory training. CONCLUSION: The literature on the treatment of anosmia and hyposmia includes randomized trials showing the efficacy of a few modalities. While further research is needed to expand therapeutic options for this debilitating condition, the current literature supports the use of olfactory training and topical corticosteroids.

Smell and Taste Loss Associated with COVID-19 Infection.

OBJECTIVE: The aim of this study was to quantify the impact of COVID-19 on olfactory and gustatory function in US adults. METHODS: From the 2021 Adult National Health Interview Survey, demographic and survey-specific module data concerning COVID-19 diagnoses, testing and disease severity, and data quantifying disturbances and eventual recovery of smell and taste were extracted. Sample weights were applied to obtain nationally representative statistics. The overall rate of COVID-19 infection was determined, and those diagnosed with COVID-19 were analyzed with respect to disease severity, smell and taste disturbance, and respective recoveries. RESULTS: In 2021, 35.8 million or 14% of the adult population (95% CI 13.5-14.7%; mean age, 43.9 years; 53.8% female) had been diagnosed with COVID-19. Among those, 60.5% (58.6-62.5%) and 58.2% (56.2-60.1%) reported accompanying losses  in smell or taste, respectively; there was a significant association between overall COVID-19 symptom severity and smell (p < 0.001) and taste disturbance (p < 0.001). Following infection, 72.2% (69.9-74.3%), 24.1% (22.2-26.2%), and 3.7% (3.0-4.6%) of the patients experienced complete, partial, and no smell recovery, respectively. Recovery rates for gustatory function paralleled olfaction, with 76.8% (74.6-78.9%), 20.6% (18.7-22.7%), and 2.6 (1.9-3.4%) reporting complete, partial, and no recovery of taste, respectively. When sensory disturbance was present, severity of overall symptomatology was negatively associated with smell and taste recovery (p < 0.001 for each). CONCLUSION: The majority of adults infected with COVID-19 in 2021 experienced olfactory or gustatory dysfunction with a non-negligible population reporting incomplete or no near-term sensory recovery. Our results are useful for providers counseling patients and suggest that interventions lessening overall COVID-19 symptom burden may prevent prolonged sensory dysfunction. LEVEL OF EVIDENCE: IV. Laryngoscope, 2023.

Diagnosis and Treatment Strategy of Nasogenic Olfactory Dysfunction.

Since the global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a symptom of the onset of SARS-CoV-2, olfactory dysfunction (OD), has attracted tremendous attention. OD is not only a negative factor for quality of life but also an independent hazard and early biomarker for various diseases, such as Parkinson's and Huntington's diseases. Therefore, early identification and treatment of OD in patients are critical. Many etiological factors are responsible for OD based on current opinions. Sniffin'Sticks are recommended to identify the initial position (central or peripheral) for OD when treating patients clinically. It is worth emphasizing that the olfactory region in nasal cavity is recognized as the primary and critical olfactory receptor. Many nasal diseases, such as those with traumatic, obstructive and inflammatory causes, can lead to OD. The key question is no refined diagnosis or treatment strategy for nasogenic OD currently. This study summarizes the differences in medical history, symptoms, auxiliary examination, treatment and prognosis of different types of nasogenic OD by analyzing the current studies. We propose using olfactory training after 4-6 weeks of initial treatment for nasogenic OD patients with no significant improvement in olfaction. We hope that our research can provide valuable clinical guidance by systematically summarizing the clinical characteristics of nasogenic OD.

Omega-3 Fatty Acid Supplementation for the Treatment of Persistent COVID-Related Olfactory Dysfunction.

OBJECTIVE: To evaluate the efficacy of omega-3 fatty acid (O3FA) supplementation in the treatment of COVID-related olfactory dysfunction (OD). METHODS: Patients with laboratory-confirmed or clinically-suspected COVID-19 infection and new-onset OD from August 2020 to November 2021 were prospectively recruited. Patients with quantitative OD, defined as a brief smell identification test (BSIT) score of 9 or less, were eligible for study inclusion. The experimental group received 2 g of O3FA supplementation, while the control group received an identical placebo to be taken daily for 6 weeks. The primary outcome was a change in BSIT score between the initial and 6-week follow-up tests. RESULTS: One hundred and seventeen patients were included in the analysis, including 57 patients in the O3FA group and 60 in the placebo group. O3FA group patients demonstrated a mean BSIT improvement of 1.12 ± 1.99 compared to 0.68 ± 1.86 in the placebo group (p = 0.221). Seventy-seven patients, 42 within the O3FA group and 35 in the placebo group, completed a follow-up BSIT survey at an average of 717.8 days from study onset. At long-term follow-up, there was an average BSIT score improvement of 1.72 within the O3FA group compared to 1.76 within the placebo group (p = 0.948). CONCLUSION: Among patients with persistent COVID-related OD, our study showed no clear evidence of relative short-term or long-term olfactory recovery among patients receiving high doses of O3FA supplementation.

Prevalence and 24-month recovery of olfactory dysfunction in COVID-19 patients: A multicentre prospective study.

OBJECTIVE: To investigate the prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients 24 months after the infection. METHODS: From 22 March 2020 to 5 June 2022, 251 COVID-19 patients were followed in three European medical centres. Olfactory function was assessed with subjective patient-reported outcome questionnaires and odour identification tests at baseline, 6, 12, 18 and 24 months postinfection. The predictive values of epidemiological and clinical data were investigated with multivariate analysis. RESULTS: One hundred and seventy-one patients completed the evaluations. The odour identification test revealed that 123 patients (50.8%) had OD at baseline. The prevalence of persistent psychophysical abnormalities at 6, 12, 18 and 24 months post-COVID-19 was 24.2%, 17.9%, 5.8% and 2.9%, respectively (p = 0.001). Parosmia occurred in 40 patients (23.4%) and lasted 60 ± 119 days. At 2 years, 51 patients (29.8%) self reported that their olfaction was unnormalised. Older patients had better odour identification evaluations at baseline (p < 0.001) but those with OD reported lower odour identification test scores at the end of the follow-up. Parosmia occurred more frequently in young patients. The olfactory training was significantly associated with higher values of Sniffin' Sticks tests at 18 months postinfection (rs = 0.678; p < 0.001). CONCLUSION: Two years post-COVID-19, 29.8% of patients reported persistent OD, but only 2.9% had abnormal identification psychophysical evaluations.

[Interpretation of the 2021 American Academy of Allergy, Asthma and Immunology expert consensus on the treatment of postinfectious olfactory dysfunction].

Respiratory tract viruses are the second leading cause of olfactory dysfunction. Between 2019 to 2022, the world has been plagued by the problem of olfaction caused by the COVID-19. As we learn more about the impact of severe acute respiratory syndrome coronavirus 2（SARS-CoV-2）, with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction（PIOD）. The Clinical Olfactory Working Group has proposed theconsensus on the roles of PIOD. This paper is the detailed interpretation of the consensus.

Recovery from olfactory and gustatory dysfunction following COVID-19 acquired during Omicron BA.1 wave in Italy.

BACKGROUND: Despite alterations in the sense of smell and taste have dominated the symptoms of SARS-CoV-2 infection, the prevalence and the severity of self-reporting COVID-19 associated olfactory and gustatory dysfunction has dropped significantly with the advent of the Omicron BA.1 subvariant. However, data on the evolution of Omicron-related chemosensory impairment are still lacking. OBJECTIVE: The aim of the present study was to estimate the prevalence and the recovery rate of self-reported chemosensory dysfunction 6-month after SARS-CoV-2 infection acquired during the predominance of the Omicron BA.1 subvariant in Italy. METHODS: Prospective observational study based on the sino-nasal outcome tool 22 (SNOT-22), item "sense of smell or taste" and additional outcomes conducted in University hospitals and tertiary referral centers in Italy. RESULTS: Of 338 patients with mild-to-moderate COVID-19 completing the baseline survey, 294 (87.0 %) responded to the 6-month follow-up interview. Among them, 101 (34.4 %) and 4 (1.4 %) reported an altered sense of smell or taste at baseline and at 6 months, respectively. Among the 101 patients with COVID-19-associated smell or taste dysfunction during the acute phase of the disease, 97 (96.0 %) reported complete resolution at 6 months. The duration of smell or taste impairment was significantly shorter in vaccinated patients (p = 0.007). CONCLUSIONS: Compared with that observed in subjects infected during the first wave of the pandemic, the recovery rate from chemosensory dysfunctions reported in the present series of patients infected during the predominance of the Omicron BA.1 subvariant was more favorable with a shorter duration being positively influenced by vaccination.

COVID-19 olfactory dysfunction, evaluation of onset, and persistence.

Olfactory dysfunction (OD) is a common feature of COVID-19. The goal of the study was to define the modes of onset of OD in the clinical course of the disease and to follow the cases for 12-18 months in order to estimate the differences in the recovery time from OD over the course of the disease. We managed to follow a total of 325 patients (females: 198, males: 127) in the Babylon governorate in Iraq. All were COVID-19 patients who should have OD during the course of the disease. COVID-19 infection was established in all patients by swab test, i.e. polymerase chain reaction (PCR) and/or chest computed tomography findings of pneumonia compatible with COVID-19. Detailed medical records were obtained directly from the patients or their relatives. The patients were then followed up by telephone and questioned with structured questionnaires concentrating upon general clinical features and the sense of olfaction. Information about the presence of olfactory disorders, their occurrence, and development was recorded. Based on the onset of OD, the patients were categorized into three groups. Olfactory functions were assessed primarily by face-to-face interview and then (if necessary) by a telephone questionnaire assessing self-reported olfactory function and olfactory-related quality of life, which measures the subjective olfactory capability (SOC). In the first 2 weeks, 148 (45.5%) patients reported complete recovery from OD, of which 90 (73.2%) patients joined at the end of the 1st month. OD persistence was observed in 11 (3.3%) patients toward the end of the 1st year, in 5 (1.5%) patients at the end of the 15th month, and only in two (0.6%) patients at the end of the 18th month. We found no significant correlation between the type of onset of OD and the duration and persistence of OD. Most sufferers of COVID-associated OD recover their sense of smell within the 1st month.

Mechanisms of olfactory impairment in COVID-19: a systematic review

One of the symptoms of a new coronavirus infection (COVID-19) is a complete or partial violation of the sense of smell. The aim of the work is to analyze the published results of scientific research on the mechanisms of olfactory impairment in COVID-19. Material and methods. Research was conducted for publications in Pubmed on the problem of olfactory impairment in COVID-19 using terms indexed by MeSH. The systematic review was compiled in accordance with the checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Results. Publication's analysis has shown that the existing ideas about conductive anosmia are insufficient to explain the causes of olfactory impairment caused by SARS-CoV-2. It has been established that ACE2 and TMPRSS2 receptors located on the surface of target cells are necessary for the penetration of a new coronavirus. It is known that these receptors are mainly located on the cells of the olfactory epithelium. The main hypothesis of olfactory impairment in COVID-19 is that anosmia/hyposmia is caused by damage not to neuronal cells (as previously assumed), but to the olfactory epithelium. There is no confirmation of the point of view about the damage of SARS-CoV-2 olfactory bulbs and olfactory neurons, since they do not express receptor proteins for the virus on their surface.Copyright © 2022 by the authors.

The olfactory bulb - gateway for SARS-Cov-2?

Introduction. Anosmia and ageusia are one of the most common and characteristic symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, with a frequency of almost 50% in patients in Western countries. Hypotheses proposing that the virus potentially affects the central nervous system (CNS) are on the rise. One hypothesis suggests that the virus enters via nasal mucosa and then enters the olfactory bulb via cribriform plate, with further dissemination to the CNS. Case report. A 34-year-old female patient experienced the loss of the sense of smell and taste about two months before testing positive for SARS-Cov-2. Coronavirus disease 2019 (COVID- 19) presented with minor pneumonia and worsening anosmia and ageusia. After treatment, the patient recovered well, but anosmia and ageusia appeared again, varying in intensity, and since February 2021, they have become persistent. The case was evaluated by an otorhinolaryngologist, pulmonologist, and finally, a neurologist. In the meantime, the patient tested negative for SARS-Cov-2 and received two doses of the Sputnik V vaccine. Brain magnetic resonance imaging (MRI) was performed, and it clearly showed severe bilateral olfactory bulb atrophy. The patient has had anosmia and ageusia up to this day, and future MRI follow- up is planned. Conclusion. Loss of sense of smell and taste may be a predictor of further CNS dissemination of the virus and possible neurological complications (which is still a subject of consideration). The olfactory bulb could be a gateway to COVID-19 intrusion into the CNS, and its atrophy could be an indicator of the process. Further investigation on this topic is required, including a wide application of MRI, in order to come to definite conclusions.

Smell disorders associated with COVID-19 infection

Background: We performed a search in the PubMed databases, Web of Science, LILACS, MEDLINE, SciELO, and Cochrane Library using the keywords COVID-19, Novel coronavirus, corona, 2019-nCoV, SARS-CoV-2, ENT, nose, anosmia, hyposmia, smell, olfactory, ORL, different ENT related symptoms. We reviewed published and peer-reviewed studies that reported the ENT manifestations in COVID-19 laboratory-confirmed positive patients. Main text: Within the included 2549 COVID-19 laboratory-confirmed positive patients, smell affection was reported in 1453 patients (57%). The other reported ENT manifestations were taste disorder (49.2%), headache (42.8%), nasal blockage (26.3%), sore throat (25.7%), runny nose or rhinorrhea (21.3%), upper respiratory tract infection (URTI) (7.9%), and frequent sneezing (3.6%). Conclusion(s): Smell affection in COVID-19 is common and could be one of the red flag signs in COVID-19 infection. With a sensitivity of utilized questionnaire in smell identification, a homogenous universal well-defined COVID-19 questionnaire is needed to make the COVID-19 data collection more sensible.Copyright © 2021, The Author(s).

Neuropathogenesis and Neurological Manifestations of SARS-CoV-2

Neurological complications of COVID-19 contribute significantly to mortality in the intensive care unit (ICU). Preventive therapy, though discussed in literature, is limited for COVID-19 neurological manifestations and treatment algorithms continue to rely on evidence from previous pandemics. Thus, in this chapter we evaluate current in vitro, in vitro, histopathological studies to ascertain the most likely mechanisms of SARS-CoV-2 central nervous system entry. From this understanding, we determine probable mechanisms for neurological compilations observed in COVID-19 as relevant to the clinician. SARS-CoV-2 infection of nasal epithelium and the respiratory tract may allow for a systemic inflammatory response that results in neuroinflammation. While most neurological complications are inflammatory in etiology, rarely, SARS-CoV-2 may enter into the central nervous system and mediate neuronal damage. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

The Retrospective Pilot Study of the Prevalence of Olfactory Dysfunction or Loss of Smell, Loss of Taste and Oral Manifestations Among COVID-19 Positive Health Workers in Muscat, Oman.

A retrospective study evaluating the prevalence of loss of smell, loss of taste and oral manifestations was carried out by framing an online questionnaire and disseminated among the health care workers including medical and dental students, who were afflicted with COVID-19. The objective of this study was to find out the prevalence of the loss of smell, loss of taste (LOST) and oral manifestations and whether these (LOST & oral manifestations) can be the premonitory manifestations and also whether these can predict the prognosis of COVID-19 disease. Our study showed that the loss of smell, loss of taste and dry mouth did occur before the other symptoms considerably in the COVID-19 infected health workers. All the infected health workers were in home quarantine phase and not hospitalized during the occurrence of COVID-19. The loss of smell, loss of taste and oral manifestations can be the prodromal signs of COVID-19 and may be used as a screening tool to predict the severity of the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03293-w.