Persistence of SARS-CoV-2 Antigens in the Nasal Mucosa of Eight Patients with Inflammatory Rhinopathy for over 80 Days following Mild COVID-19 Diagnosis.

The nasal mucosa is the main gateway for entry, replication and elimination of the SARS-CoV-2 virus, the pathogen that causes severe acute respiratory syndrome (COVID-19). The presence of the virus in the epithelium causes damage to the nasal mucosa and compromises mucociliary clearance. The aim of this study was to investigate the presence of SARS-CoV-2 viral antigens in the nasal mucociliary mucosa of patients with a history of mild COVID-19 and persistent inflammatory rhinopathy. We evaluated eight adults without previous nasal diseases and with a history of COVID-19 and persistent olfactory dysfunction for more than 80 days after diagnosis of SARS-CoV-2 infection. Samples of the nasal mucosa were collected via brushing of the middle nasal concha. The detection of viral antigens was performed using immunofluorescence through confocal microscopy. Viral antigens were detected in the nasal mucosa of all patients. Persistent anosmia was observed in four patients. Our findings suggest that persistent SARS-CoV-2 antigens in the nasal mucosa of mild COVID-19 patients may lead to inflammatory rhinopathy and prolonged or relapsing anosmia. This study sheds light on the potential mechanisms underlying persistent symptoms of COVID-19 and highlights the importance of monitoring patients with persistent anosmia and nasal-related symptoms.

Solitary Anosmia/Ageusia in Prison: Results From a COVID-19 Cluster.

A prison setting with its congregate environment is at high risk for widespread transmission of respiratory illnesses. Identifying COVID-19 cases as early as possible and isolating cases and tracing contacts is critical to halting the spread of this disease. The Centers for Disease Control and Prevention (CDC) added new loss of taste or smell to its list of symptoms and, initially, only if associated with at least one of six other symptoms. The CDC has since updated the guidance to remove this qualifier as of May 13, 2020. New loss of taste or smell, alone, can help to identify COVID-19 cases. Solitary anosmia/ageusia should be strongly considered in routine symptom screening protocols for COVID-19.

Proof-of-concept: SCENTinel 1.1 rapidly discriminates COVID-19-related olfactory disorders.

It is estimated that 20%-67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia.

Loss of olfactory sensitivity is an early and reliable marker for COVID-19.

Detection of early and reliable symptoms is important in relation to limiting the spread of an infectious disease. For COVID-19, the most specific symptom is either losing or experiencing reduced olfactory functions. Anecdotal evidence suggests that olfactory dysfunction is also one of the earlier symptoms of COVID-19, but objective measures supporting this notion are currently missing. To determine whether olfactory loss is an early sign of COVID-19, we assessed available longitudinal data from a web-based interface enabling individuals to test their sense of smell by rating the intensity of selected household odors. Individuals continuously used the interface to assess their olfactory functions and at each login, in addition to odor ratings, recorded their symptoms and results from potential COVID-19 test. A total of 205 COVID-19-positive individuals and 156 pseudo-randomly matched control individuals lacking positive test provided longitudinal data which enabled us to assess olfactory functions in relation to their test result date. We found that odor intensity ratings started to decline in the COVID-19 group as early as 6 days prior to the test result date (±1.4 days). Symptoms, such as sore throat, aches, and runny nose appear around the same point in time; however, with a lower predictability of a COVID-19 diagnosis. Our results suggest that olfactory sensitivity loss is an early symptom but does not appear before other related COVID-19 symptoms. Olfactory loss is, however, more predictive of a COVID-19 diagnosis than other early symptoms.

Revealing the mystery of persistent smell loss in Long COVID patients.

COVID-19 is hopefully approaching its end in many countries as herd immunity develops and weaker strains of SARS-CoV-2 dominate. However, a new concern occurs over the long-term effects of COVID-19, collectively called "Long COVID", as some symptoms of the nervous system last even after patients recover from COVID-19. This review focuses on studies of anosmia, i.e., impairment of smell, which is the most common sensory defect during the disease course and is caused by olfactory dysfunctions. It remains mysterious how the olfactory functions are affected since the virus can't invade olfactory receptor neurons. We describe several leading hypotheses about the mystery in hope to provide insights into the pathophysiology and treatment strategies for anosmia.

Signs and symptoms to determine if a patient presenting in primary care or hospital outpatient settings has COVID-19.

BACKGROUND: COVID-19 illness is highly variable, ranging from infection with no symptoms through to pneumonia and life-threatening consequences. Symptoms such as fever, cough, or loss of sense of smell (anosmia) or taste (ageusia), can help flag early on if the disease is present. Such information could be used either to rule out COVID-19 disease, or to identify people who need to go for COVID-19 diagnostic tests. This is the second update of this review, which was first published in 2020. OBJECTIVES: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19. SEARCH METHODS: We undertook electronic searches up to 10 June 2021 in the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We used artificial intelligence text analysis to conduct an initial classification of documents. We did not apply any language restrictions. SELECTION CRITERIA: Studies were eligible if they included people with clinically suspected COVID-19, or recruited known cases with COVID-19 and also controls without COVID-19 from a single-gate cohort. Studies were eligible when they recruited people presenting to primary care or hospital outpatient settings. Studies that included people who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards. DATA COLLECTION AND ANALYSIS: Pairs of review authors independently selected all studies, at both title and abstract, and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and assessed risk of bias using the QUADAS-2 checklist, and resolved disagreements by discussion with a third review author. Analyses were restricted to prospective studies only. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic (ROC) space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary prospective studies were available, and whenever heterogeneity across studies was deemed acceptable. MAIN RESULTS: We identified 90 studies; for this update we focused on the results of 42 prospective studies with 52,608 participants. Prevalence of COVID-19 disease varied from 3.7% to 60.6% with a median of 27.4%. Thirty-five studies were set in emergency departments or outpatient test centres (46,878 participants), three in primary care settings (1230 participants), two in a mixed population of in- and outpatients in a paediatric hospital setting (493 participants), and two overlapping studies in nursing homes (4007 participants). The studies did not clearly distinguish mild COVID-19 disease from COVID-19 pneumonia, so we present the results for both conditions together. Twelve studies had a high risk of bias for selection of participants because they used a high level of preselection to decide whether reverse transcription polymerase chain reaction (RT-PCR) testing was needed, or because they enrolled a non-consecutive sample, or because they excluded individuals while they were part of the study base. We rated 36 of the 42 studies as high risk of bias for the index tests because there was little or no detail on how, by whom and when, the symptoms were measured. For most studies, eligibility for testing was dependent on the local case definition and testing criteria that were in effect at the time of the study, meaning most people who were included in studies had already been referred to health services based on the symptoms that we are evaluating in this review. The applicability of the results of this review iteration improved in comparison with the previous reviews. This version has more studies of people presenting to ambulatory settings, which is where the majority of assessments for COVID-19 take place. Only three studies presented any data on children separately, and only one focused specifically on older adults. We found data on 96 symptoms or combinations of signs and symptoms. Evidence on individual signs as diagnostic tests was rarely reported, so this review reports mainly on the diagnostic value of symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. RT-PCR was the most often used reference standard (40/42 studies). Only cough (11 studies) had a summary sensitivity above 50% (62.4%, 95% CI 50.6% to 72.9%)); its specificity was low (45.4%, 95% CI 33.5% to 57.9%)). Presence of fever had a sensitivity of 37.6% (95% CI 23.4% to 54.3%) and a specificity of 75.2% (95% CI 56.3% to 87.8%). The summary positive likelihood ratio of cough was 1.14 (95% CI 1.04 to 1.25) and that of fever 1.52 (95% CI 1.10 to 2.10). Sore throat had a summary positive likelihood ratio of 0.814 (95% CI 0.714 to 0.929), which means that its presence increases the probability of having an infectious disease other than COVID-19. Dyspnoea (12 studies) and fatigue (8 studies) had a sensitivity of 23.3% (95% CI 16.4% to 31.9%) and 40.2% (95% CI 19.4% to 65.1%) respectively. Their specificity was 75.7% (95% CI 65.2% to 83.9%) and 73.6% (95% CI 48.4% to 89.3%). The summary positive likelihood ratio of dyspnoea was 0.96 (95% CI 0.83 to 1.11) and that of fatigue 1.52 (95% CI 1.21 to 1.91), which means that the presence of fatigue slightly increases the probability of having COVID-19. Anosmia alone (7 studies), ageusia alone (5 studies), and anosmia or ageusia (6 studies) had summary sensitivities below 50% but summary specificities over 90%. Anosmia had a summary sensitivity of 26.4% (95% CI 13.8% to 44.6%) and a specificity of 94.2% (95% CI 90.6% to 96.5%). Ageusia had a summary sensitivity of 23.2% (95% CI 10.6% to 43.3%) and a specificity of 92.6% (95% CI 83.1% to 97.0%). Anosmia or ageusia had a summary sensitivity of 39.2% (95% CI 26.5% to 53.6%) and a specificity of 92.1% (95% CI 84.5% to 96.2%). The summary positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.55 (95% CI 3.46 to 5.97) and 4.99 (95% CI 3.22 to 7.75) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The summary positive likelihood ratio of ageusia alone was 3.14 (95% CI 1.79 to 5.51). Twenty-four studies assessed combinations of different signs and symptoms, mostly combining olfactory symptoms. By combining symptoms with other information such as contact or travel history, age, gender, and a local recent case detection rate, some multivariable prediction scores reached a sensitivity as high as 90%. AUTHORS' CONCLUSIONS: Most individual symptoms included in this review have poor diagnostic accuracy. Neither absence nor presence of symptoms are accurate enough to rule in or rule out the disease. The presence of anosmia or ageusia may be useful as a red flag for the presence of COVID-19. The presence of cough also supports further testing. There is currently no evidence to support further testing with PCR in any individuals presenting only with upper respiratory symptoms such as sore throat, coryza or rhinorrhoea. Combinations of symptoms with other readily available information such as contact or travel history, or the local recent case detection rate may prove more useful and should be further investigated in an unselected population presenting to primary care or hospital outpatient settings. The diagnostic accuracy of symptoms for COVID-19 is moderate to low and any testing strategy using symptoms as selection mechanism will result in both large numbers of missed cases and large numbers of people requiring testing. Which one of these is minimised, is determined by the goal of COVID-19 testing strategies, that is, controlling the epidemic by isolating every possible case versus identifying those with clinically important disease so that they can be monitored or treated to optimise their prognosis. The former will require a testing strategy that uses very few symptoms as entry criterion for testing, the latter could focus on more specific symptoms such as fever and anosmia.

Olfactory dysfunction in COVID-19, new insights from a cohort of 353 patients: The ANOSVID study.

Olfactory disorders (OD) pathogenesis, underlying conditions, and prognostic in coronavirus disease 2019 (COVID-19) remain partially described. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from March 1 2020 to May 31 2020. The aim was to compare COVID-19 patients with OD (OD group) and patients without OD (no-OD group). A second analysis compared patients with anosmia (high OD group) and patients with hyposmia or no OD (low or no-OD group). The OD group presented less cardiovascular and other respiratory diseases compared to the no-OD group (odds ratio [OR] = 0.536 [0.293-0.981], p = 0.041 and OR = 0.222 [0.056-0.874], p = 0.037 respectively). Moreover, history of malignancy was less present in the high OD group compared with the low or no-OD group (OR = 0.170 [0.064-0.455], p < 0.001). The main associated symptoms (OR > 5) with OD were loss of taste (OR = 24.059 [13.474-42.959], p = 0.000) and cacosmia (OR = 5.821 [2.246-15.085], p < 0.001). Most of all ORs decreased in the second analysis, especially for general, digestive, and ENT symptoms. Only two ORs increased: headache (OR = 2.697 [1.746-4.167], p < 0.001) and facial pain (OR = 2.901 [1.441-5.842], p = 0.002). The high OD group had a higher creatinine clearance CKD than the low or no-OD group (89.0 ± 21.1 vs. 81.0 ± 20.5, p = 0.040). No significant difference was found concerning the virological, radiological, and severity criteria. OD patients seem to have less comorbidity, especially better cardiovascular and renal function. Associated symptoms with OD were mostly neurological symptoms. We did not find a significant relationship between OD and less severity in COVID-19 possibly due to methodological bias.

Testing for anosmia and ageusia in patients presenting to the emergency department with suspected coronavirus disease 2019 in Saudi Arabia.

OBJECTIVE: This study investigated the role of objective olfactory dysfunction (OD) and gustatory dysfunction (GD) testing among patients with suspected coronavirus disease 2019 (COVID-19) who presented with respiratory symptoms. METHODS: A prospective, blinded, observational study was conducted in the emergency units of two tertiary hospitals. Participants were asked to identify scents in the pocket smell test (PST) and flavors in four different solutions in the gustatory dysfunction test (GDT). We assessed the level of agreement between objective findings and self-reported symptoms. We evaluated the diagnostic accuracy of chemosensory dysfunction for diagnosing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: Of 250 participants, 74 (29.6%) were SARS-CoV-2-positive. There was slight agreement between self-reported symptoms and objective findings (kappa = 0.13 and 0.10 for OD and GD, respectively). OD assessed by the PST was independently associated with COVID-19 (adjusted odds ratio = 1.89, 95% confidence interval, 1.04-3.46). This association was stronger when OD was combined with objective GD, cough, and fever (adjusted odds ratio = 7.33, 95% confidence interval, 1.17-45.84). CONCLUSIONS: Neither the PST nor GDT alone are useful screening tools for COVID-19. However, a diagnostic scale based on objective OD, GD, fever, and cough may help triage patients with suspected COVID-19.

Performance of formal smell testing and symptom screening for identifying SARS-CoV-2 infection.

BACKGROUND: Altered sense of smell is a commonly reported COVID-19 symptom. The performance of smell testing to identify SARS-CoV-2 infection status is unknown. We measured the ability of formal smell testing to identify SARS-CoV-2 infection and compared its performance with symptom screening. METHODS: A convenience sample of emergency department patients with COVID-19 symptom screening participated in smell testing using an eight odor Pocket Smell Test (PST). Participants received a SARS-CoV-2 viral PCR test after smell testing and completed a health conditions survey. Descriptive analysis and receiver operating characteristic (ROC) curve models compared the accuracy of smell testing versus symptom screening in identifying SARS-CoV-2 infection. RESULTS: Two hundred and ninety-five patients completed smell testing and 87 (29.5%) had a positive SARS-CoV-2 PCR test. Twenty-eight of the SARS-CoV-2 positive patients (32.2%) and 49 of the SARS-CoV-2 negative patients (23.6%) reported at least one of seven screening symptoms (OR = 1.54, P = 0.13). SARS-CoV-2 positive patients were more likely to have hyposmia (≤5 correctly identified odors) than SARS-CoV-2 negative patients (56.1% vs. 19.3%, OR = 5.36, P<0.001). Hyposmia was 52.9% (95% CI 41.9%-63.7%) sensitive and 82.7% (95% CI 76.9%-87.6%) specific for SARS-CoV-2 infection. Presence of ≥1 screening symptom was 32.2% (95% CI 22.6%-43.1%) sensitive and 76.4% (70.1%-82.0%) specific for SARS-CoV-2 infection. The ROC curve for smell testing had an area under the curve (AUC) of 0.74 (95% CI 0.67-0.80). The ROC curve for symptom screening had lower discriminatory accuracy for SARS-CoV-2 infection (AUC = 0.55, 95% CI 0.49-0.61, P<0.001) than the smell testing ROC curve. CONCLUSION: Smell testing was superior to symptom screening for identifying SARS-CoV-2 infection in our study.

"Anosmia" the mysterious collateral damage of COVID-19.

COVID-19 pandemic spreads worldwide, with more than 100 million positive cases and more than 2 million deaths. From the beginning of the COVID-19 pandemic, several otolaryngologists described many cases of a sudden loss of smell (anosmia) associated with the disease with or without additional symptoms. Anosmia is often the first and sometimes the only sign in the asymptomatic carriers of COVID-19. Still, this disorder is underestimated, and it is not life-threatening. However, it significantly decreases the quality of life. This olfactory dysfunction continues in several cases even after the nasopharyngeal swab was negative. The occurrence of anosmia can be used as a screening tool for COVID-19 patients and can be used to identify these patients to accomplish the isolation and tracking procedures. In this review, we highlighted the possible mechanisms of anosmia in COVID-19 patients, major pathologies and features of anosmia, implications of anosmia in early diagnosis of COVID-19, evaluation of the smell function during COVID-19, and management and treatment options of COVID-19 anosmia.

Olfactory sensory and perceptual evaluation in newborn infants: A systematic review.

Fetuses are able to process olfactory stimuli present in the womb and continue to show a preference for these odors for months after birth. Despite the accumulated knowledge about their early ability to perceive odors, there is a lack of validated scales for odor response in newborns. The evaluation of reactions of the olfactory system to environmental stimuli in infants has been defined by methodological theoretical approaches of experimental and clinical assessment tools. These approaches are mainly based on psychophysical approaches and predominantly use behavioral and physiological measures. Examples can be found in studies describing early abilities of newborn babies for behaviors or heart rate variability showing memory of maternal food preferences or mother's breast milk. This systematic review aimed to determine whether validated odor assessment tools can be feasibly used in studies. Particularly in light of the current COVID-19 pandemic and evidence of associated olfactory impairment resulting from SARS-COV-2 infection, the study is also motivated by the need for tools to assess olfactory function in neonates.

[Clinical manifestations of COVID-19 in children]. / Nevrologicheskie proyavleniya COVID-19 u detei.

The neurological symptoms of COVID-19 in children (in Dyurtyuli area, Republic of Bashkortostan) are analyzed and brief review of the literature is undertaken in the paper. 137 children underwent swab test for COVID-19. The disease was diagnosed in 9 of them. Only respiratory symptoms were observed in 3 children, a combination of respiratory with anosmia or/and headache - in 3, asymptomatic form - in another 3. A case of a 7-years old girl suffering from COVID-19 with respiratory symptoms as well as anosmia and headache is presented. According to the review of the literature, COVID - 19 in children is usually milder than in adults, but in some cases may lead to neurological consequences. Multisystem inflammatory syndrome may lead to the development symptoms of encephalopathy (altered mental status, headache) and stroke. Autoimmune complications such as Gillian-Barre syndrome develop simultaneously or after resolving of the infectious process. The development of viral meningoencephalitis in COVID-19 is questionable.

Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people.

BACKGROUND: Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type. METHODS AND FINDINGS: We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2-7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2-7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England. CONCLUSIONS: Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage.

Olfactory dysfunction at six months after coronavirus disease 2019 infection.

OBJECTIVE: This study aimed to assess olfactory dysfunction in patients at six months after confirmed coronavirus disease 2019 infection. METHODS: Coronavirus disease 2019 positive patients were assessed six months following diagnosis. Patient data were recoded as part of the adapted International Severe Acute Respiratory and Emerging Infection Consortium Protocol. Olfactory dysfunction was assessed using the University of Pennsylvania Smell Identification Test. RESULTS: Fifty-six patients were included. At six months after coronavirus disease 2019 diagnosis, 64.3 per cent of patients (n = 36) were normosmic, 28.6 per cent (n = 16) had mild to moderate microsmia and 7 per cent (n = 4) had severe microsmia or anosmia. There was a statistically significant association between older age and olfactory dysfunction. Hospital or intensive care unit admission did not lead to worse olfactory outcomes compared to those managed in the out-patient setting. CONCLUSION: At six months after coronavirus disease 2019 diagnosis, approximately two-thirds of patients will be normosmic. This study is the first to describe six-month outcomes for post-coronavirus disease 2019 patients in terms of olfactory dysfunction.

Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia.

The year 2020 became the year of the outbreak of coronavirus, SARS-CoV-2, which escalated into a worldwide pandemic and continued into 2021. One of the unique symptoms of the SARS-CoV-2 disease, COVID-19, is the loss of chemical senses, i.e., smell and taste. Smell training is one of the methods used in facilitating recovery of the olfactory sense, and it uses essential oils of lemon, rose, clove, and eucalyptus. These essential oils were not selected based on their chemical constituents. Although scientific studies have shown that they improve recovery, there may be better combinations for facilitating recovery. Many phytochemicals have bioactive properties with anti-inflammatory and anti-viral effects. In this review, we describe the chemical compounds with anti- inflammatory and anti-viral effects, and we list the plants that contain these chemical compounds. We expand the review from terpenes to the less volatile flavonoids in order to propose a combination of essential oils and diets that can be used to develop a new taste training method, as there has been no taste training so far. Finally, we discuss the possible use of these in clinical settings.

Is loss of smell an early predictor of COVID-19 severity: a systematic review and meta-analysis.

Anecdotal evidence suggests that the severity of coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is likely to be distinguished by variations in loss of smell (LOS). Thus, we conducted a meta-analysis of 45 articles that include a total of 42,120 COVID-19 patients from 17 different countries to demonstrate that severely ill or hospitalized COVID-19 patients have a lesser chance of experiencing LOS than non-severely ill or non-hospitalized COVID-19 patients (odds ratio = 0.527 [95% CI 0.373-0.744; p < 0.001] and 0.283 [95% CI 0.173-0.462; p < 0.001], respectively). We also proposed a possible mechanism underlying the association of COVID-19 severity with anosmia, which may explain why patients without sense of smell develop severe COVID-19. Variations in LOS according to the severity of COVID-19 is a global phenomenon, with few exceptions. Since severely ill patients have a lower rate of anosmia, patients without anosmia should be monitored more closely in the early stages of COVID-19, for early diagnosis of severity of illness. An understanding of how the severity of COVID-19 infection and LOS are associated has profound implications for the clinical management and mitigation strategies for the disease.

Correlations Between Olfactory Psychophysical Scores and SARS-CoV-2 Viral Load in COVID-19 Patients.

OBJECTIVES/HYPOTHESIS: The aim of this study was to evaluate the correlations between the severity and duration of olfactory dysfunctions (OD), assessed with psychophysical tests, and the viral load on the rhino-pharyngeal swab determined with a direct method, in patients affected by coronavirus disease 2019 (COVID-19). STUDY DESIGN: Prospective cohort study. METHODS: Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and determination of the normalized viral load on nasopharyngeal swab within 10 days of the clinical onset of COVID-19. RESULTS: Sixty COVID-19 patients were included in this study. On psychophysical testing, 12 patients (20% of the cohort) presented with anosmia, 11 (18.3%) severe hyposmia, 13 (18.3%) moderate hyposmia, and 10 (16.7%) mild hyposmia with an overall prevalence of OD of 76.7%. The overall median olfactory score was 50 (interquartile range [IQR] 30-72.5) with no significant differences between clinical severity subgroups. The median normalized viral load detected in the series was 2.56E+06 viral copies/106 copies of human beta-2microglobulin mRNA present in the sample (IQR 3.17E+04-1.58E+07) without any significant correlations with COVID-19 severity. The correlation between viral load and olfactory scores at baseline (R2  = 0.0007; P = .844) and 60-day follow-up (R2  = 0.0077; P = .519) was weak and not significant. CONCLUSIONS: The presence of OD does not seem to be useful in identifying subjects at risk for being super-spreaders or who is at risk of developing long-term OD. Similarly, the pathogenesis of OD is probably related to individual factors rather than to viral load and activity. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2312-2318, 2021.

Modeling the effectiveness of olfactory testing to limit SARS-CoV-2 transmission.

A central problem in the COVID-19 pandemic is that there is not enough testing to prevent infectious spread of SARS-CoV-2, causing surges and lockdowns with human and economic toll. Molecular tests that detect viral RNAs or antigens will be unable to rise to this challenge unless testing capacity increases by at least an order of magnitude while decreasing turnaround times. Here, we evaluate an alternative strategy based on the monitoring of olfactory dysfunction, a symptom identified in 76-83% of SARS-CoV-2 infections-including those with no other symptoms-when a standardized olfaction test is used. We model how screening for olfactory dysfunction, with reflexive molecular tests, could be beneficial in reducing community spread of SARS-CoV-2 by varying testing frequency and the prevalence, duration, and onset time of olfactory dysfunction. We find that monitoring olfactory dysfunction could reduce spread via regular screening, and could reduce risk when used at point-of-entry for single-day events. In light of these estimated impacts, and because olfactory tests can be mass produced at low cost and self-administered, we suggest that screening for olfactory dysfunction could be a high impact and cost-effective method for broad COVID-19 screening and surveillance.

Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial.

The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, <0.001, <0.001, <0.001, respectively). The analyses also showed significant within-group differences from baseline. Nevertheless, the changes were not significant between the two groups (P: 0.444, 0.402, 0.267, 0.329). There was no significant difference between the two groups in terms of the UPSIT results (p > 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P < 0.001). Compared to olfactory training, mometasone furoate nasal spray combination with olfactory training showed a higher improvement in severe chronic anosmia by COVID-19.