Post-COVID Parosmia in Women May be Associated with Low Estradiol Levels.

We aimed to investigate the effects of female gender hormones on post-COVID parosmia in females. Twenty-three female patients aged 18-45 who had COVID-19 disease in the last 12 months were included in the study. Estradiol (E2), prolactin (PRL), luteotrophic hormone (LH), follicular stimulating hormone (FSH), and thyroid stimulating hormone (TSH) values were measured in the blood of all participants and a parosmia questionnaire was applied for the subjective evaluation of olfactory function. Values between 4 and 16 were obtained as parosmia score (PS), and the lowest PS showed the most severe complaint. The mean age of the patients was 31 (18-45). According to the PS, patients with a score of 10 or less were classified as Group 1, and patients above 10 were considered Group 2. The age difference between Groups 1 and 2 was statistically significant and younger patients were found to have more complaints of parosmia (25 and 34, respectively, p-value 0.014). It was found that patients with severe parosmia had lower E2 values and there was a statistically significant difference (p-value 0.042) between groups 1 and 2 in terms of E2 values (34 ng/L and 59 ng/L, respectively). There was no significant difference between the two groups in terms of PRL, LH, FSH, TSH levels, or FSH/LH ratio. It may be recommended to measure E2 values in female patients whose parosmia continues after COVID-19 infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03612-9.

Natural trajectory of recovery of COVID-19 associated olfactory loss.

IMPORTANCE: Prevalence of post-viral olfactory loss has increased dramatically due to the frequency and severity of olfactory dysfunction associated with infection by the SARS-CoV-2 virus. OBJECTIVE: To determine the trajectory of COVID-19 olfactory loss over a six-month period. A key secondary objective is to assess predictive factors associated with the recovery of olfaction. DESIGN: Longitudinal repeated-measures study that enrolled from May 5, 2020 to February 2, 2021, with the last date of data collection on June 15, 2021. SETTING: Barnes-Jewish HealthCare/Washington University School of Medicine facilities (Saint Louis, Missouri, USA). PARTICIPANTS: Individuals who tested positive for SARS-CoV-2 by real-time polymerase chain reaction on nasopharyngeal swab and indicated olfactory loss on COVID-19 screening questionnaire. Individuals were excluded if they had previously diagnosed history of olfactory loss, neurodegenerative disorders, <18 years of age, admitted to hospital service, unable to read, write, and understand English, or lacked computer or internet access. INTERVENTIONS/EXPOSURES: Watch and wait for spontaneous recovery. MAIN OUTCOME(S) AND MEASURE(S): Participants completed olfactory assessments every 30 days for six months. Each assessment consisted of the University of Pennsylvania Smell Identification Test (UPSIT), an objective "scratch-and-sniff" test, and Clinical Global Impressions (CGI), a subjective Likert rating scale. RESULTS: The mean age was 41 years old (SD = 16). 39 (80 %) were female and 42 (86 %) white. At baseline assessment of objective olfaction, 18 (36 %) participants had anosmia or severe hyposmia. Subjective, complete recovery at six months was 81 % (95 % CI 74 % to 88 %). Likelihood of recovery was associated with age <50 years (aHR = 8.1 (95 % CI 1.1 to 64.1)) and mild olfactory loss at baseline (UPSIT = 30-33 for males and 31-34 for females) (aHR 6.2 (95 % CI 1.2 to 33.0)). CONCLUSIONS AND RELEVANCE: The trajectory of olfactory recovery among adults with COVID-19 olfactory loss illustrated rapid recovery within 2-3 weeks of infection, and by six months 81 % had recovered based on self-report. Age <50 years old and mild severity of olfactory loss at baseline were associated with increased likelihood of recovery of olfaction. These findings can be used to inform shared decision-making with patients.

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.

The Effects of Olfactory Loss and Parosmia on Food and Cooking Habits, Sensory Awareness, and Quality of Life-A Possible Avenue for Regaining Enjoyment of Food.

Olfactory dysfunction often has severe consequences on patients' quality of life. The most common complaint in these patients is their reduced enjoyment of food in both patients with olfactory loss and parosmia. How the different types of olfactory dysfunction differ in relation to food and cooking habits, sensory awareness, and food-related quality of life has not yet received much attention. By applying questionnaires on cooking, food, olfactory function, weight changes, sensory awareness, and food-related quality of life, we investigated how various aspects of eating differ between participants with olfactory loss (n = 271), parosmia (n = 251), and normosmic controls (n = 166). Cooking habits in olfactory dysfunction revealed pronounced differences as compared with normosmic controls. Cooking with olfactory dysfunction was associated with, e.g., a lack of comfort and inspiration for cooking and an inability to make new foods successfully. Significant differences in cooking were also found between olfactory loss and parosmia. Food items were less familiar in participants with olfactory loss and parosmia, while the ratings of liking food items differed between olfactory loss and parosmia, indicating the importance of adapting ingredients in meals separately for olfactory loss and parosmia. Parosmia was associated with a higher incidence of weight loss, but we found no difference in food-related quality of life between participants with olfactory loss and parosmia. While olfactory loss and parosmia have wide-ranging consequences on patients' cooking and food habits, adapting meals to include 'safer food items' and integrating multisensory stimulation may be a possible avenue for improving the enjoyment of food.

SARS-CoV-2 Leads to Significantly More Severe Olfactory Loss than Other Seasonal Cold Viruses.

The aim of this study was to investigate whether COVID-associated olfactory impairment differs from olfactory disorders due to other upper respiratory tract infections. We investigated the frequency of a SARS-CoV-2 infection among subjects presenting with a subjective olfactory impairment to a corona outpatient clinic between October 2020 and March 2021. Olfactory and gustatory loss were tested psychophysically, and the type of infection, SARS-CoV-2 versus 14 other common cold viruses, was assessed with nasopharyngeal swabs. Differences between the smell impairment caused by the pathogens were compared. Out of the 2120 patients, 314 reported sudden smell and/or taste loss (14%). In 68.9% of them, olfactory and in 25.6%, gustatory dysfunction could be confirmed by psychophysical testing. Of those with a psychophysically determined loss of smell, 61% were tested positive for SARS-CoV-2. SARS-CoV-2 led to a significantly more severe loss of smell and more qualitative olfactory disorders than other pathogens. Apart from rhinorrhea, shortness of breath and sore throat accompanying cold symptoms do not differ significantly between the viruses indicating the particular importance of smell loss in the differential diagnosis of seasonal colds. Multiplex-PCR in non-COVID patients revealed that only 27% of them had rhinoviruses, whereas the remainder were no further identified pathogens. Olfactory screening significantly increases diagnostic accuracy in COVID-19 patients compared to subjective assessment of olfactory loss.

Olfactory Impairment and Close Social Relationships. A Narrative Review.

Olfactory impairment is one of the more unique symptoms of COVID-19 infection and has therefore enjoyed increased public attention in recent months. Olfactory impairment has various implications and consequences ranging from difficulty detecting dangerous pathogens to hindering social functioning and social behaviors. We provide an overview of how olfactory impairment can impact 3 types of close social relationships: family relationships, friendships, and romantic relationships. Evidence is divided into several categories representing potential mechanisms by which olfactory impairment can impact close social relationships: bonding disruptions, decreased social support, missed group-eating experiences, hygiene concerns, and altered sexual behaviors. We conclude with a discussion of emerging future research questions.

Olfactory Cleft Opacification in COVID-19 Related Smell Loss: CT Findings and Correlation With Objective Testing.

OBJECTIVES: Besides the common symptoms of the coronavirus disease 2019 (COVID-19) including fever, shortness of breath, and cough, a "sudden loss of smell" has recently been added as a diagnostic symptom. The relationship between paranasal sinus computed tomography (PNS CT) and sudden loss of smell in COVID-19 was examined. MATERIALS AND METHODS: Two groups were selected for the study, the COVID-19 and the control groups. The control group consisted of 40 patients who applied to our clinic with headache and therefore underwent PNS CT. The other group consisted of 40 patients with COVID-19 who were diagnosed with sudden loss of smell with the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test. Clinical and demographic characteristics, tomography results, and olfactory test scores of patients with COVID-19 loss of smell and control group patients were recorded. The relationship between CT changes in the olfactory cleft and the degree of loss of smell was evaluated. The "Opacification in the olfactory cleft" was accepted as a positive CT finding. RESULTS: Comparison of patients with COVID-19 who had a loss of smell and the control group indicated that a significant difference was observed in terms of CT findings (P = .022). When we evaluated the paranasal CTs obtained from our patients with loss of smell, the CT of 13 patients showed pathological findings (P < .05). As the COVID-19 progressed (pneumonia and respiratory failure), the degree of loss of smell increased (P < .05). A statistically significant relationship was found between the CCCRC score and the presence of PNS CT findings (P = .0012). CONCLUSION: The PNS CT findings are significant in patients with COVID-19 with a loss of smell and were significantly associated with the degree of loss of smell. In patients with olfactory loss due to COVID-19, PNS CT can help in diagnosis. However, for this imaging to be diagnostic, a larger patient series is needed.

Sudden olfactory loss as an early marker of COVID-19: a nationwide Italian survey.

PURPOSE: The presence of many asymptomatic COVID-19 cases may increase the risks of disease dissemination, mainly for physicians. There are numerous reports on the frequent findings of sudden anosmia or hyposmia, before or at the same time of the typical COVID-19 symptoms onset. The aim of this study was to verify the association of olfactory impairment and COVID-19, providing a basis for subsequent research in the field of COVID-19 clinical heterogeneity. METHODS: We developed a 15-item online questionnaire on "Sudden Olfactory Loss (SOL) and COVID-19" that was administered during March 2020 to Italian general practitioners registered to a social media group. RESULTS: One hundred and eighty responses were received. SOL was identified as a significant sign of infection in COVID-19 patients, mainly aged between 30 and 40 years, even in the absence of other symptoms. SOL was present as an initial symptom in 46.7% of subjects, and in 16.7%, it was the only symptom. Among the COVID-19 confirmed cases, SOL occurred as the only symptom in 19.2% of patients. CONCLUSION: SOL could represent a possible early symptom in otherwise asymptomatic COVID-19 subjects. Subjects affected by SOL should be considered as potential COVID-19 cases. LEVEL OF EVIDENCE: 4.

More that ACE2? NRP1 may play a central role in the underlying pathophysiological mechanism of olfactory dysfunction in COVID-19 and its association with enhanced survival.

Three mechanisms have been proposed to account for COVID-19 associated olfactory dysfunction; obstruction of the olfactory cleft; epithelial injury and infection of the sustentacular supporting cells, which are known to express ACE2, or injury to the olfactory bulb due to axonal transport through olfactory sensory neurones. The absence of ACE2 expression by olfactory sensory neurones has led to the neurotropic potential of COVID-19 to be discounted. While an accumulating body of evidence supports olfactory epithelial injury as an important mechanism, this does not account for all the features of olfactory dysfunction seen in COVID-19; for example the duration of loss in some patients, evidence of changes within the olfactory bulb on MRI imaging, identification of viral particles within the olfactory bulb in post-mortem specimens and the inverse association between severity of COVID-19 and the prevalence of olfactory loss. The recent identification of a second route of viral entry mediated by NRP1 addresses many of these inconsistencies. Expression by the olfactory sensory neurones and their progenitor cells may facilitate direct injury and axonal transport to the olfactory bulb as well as a mechanism for delayed or absent recovery. Expression by regulatory T cells may play a central role in the cytokine storm. Variability in expression by age, race or gender may explain differing morbidity of infection and inverse association between anosmia and severity; in the case of higher expression there may be a higher risk of olfactory function but greater activation of regulatory T cells that may suppress the cytokine storm.

Systematic Review and Meta-analysis of Smell and Taste Disorders in COVID-19.

OBJECTIVE: Loss of smell and taste are considered potential discriminatory symptoms indicating triaging for coronavirus disease 2019 (COVID-19) and early case identification. However, the estimated prevalence essential to guide public health policy varies in published literature. This meta-analysis aimed to estimate prevalence of smell and taste loss among COVID-19 patients. DATA SOURCES: We conducted systematic searches of PubMed, Embase, Web of Science, and Google Scholar databases for studies published on the prevalence of smell and taste loss in COVID-19 patients. REVIEW METHODS: Two authors extracted data on study characteristics and the prevalence of smell and taste loss. Random-effects modeling was used to estimate pooled prevalence. Subgroup analysis and meta-regression were conducted to explore potential heterogeneity sources. This study used PRISMA and MOOSE guidelines. RESULTS: Twenty-seven of 32 studies reported a prevalence of loss of smell, taste, or both from a combined sample of 20,451 COVID-19 patients. The estimated global pooled prevalence of loss of smell among 19,424 COVID-19 patients from 27 studies was 48.47% (95% CI, 33.78%-63.29%). Loss of taste was reported in 20 studies and 8001 patients with an estimated pooled prevalence of 41.47% (95% CI, 3.13%-31.03%), while 13 studies that reported combined loss of smell and taste in 5977 COVID-19 patients indicated a pooled prevalence of 35.04% (95% CI, 22.03%-49.26%). CONCLUSIONS: The prevalence of smell and taste loss among COVID-19 patients was high globally, and regional differences supported the relevance of these symptoms as important markers. Health workers must consider them as suspicion indices for empirical diagnosis of severe acute respiratory syndrome coronavirus 2 infection.

Olfactory Dysfunction in COVID-19 Patients: Prevalence and Prognosis for Recovering Sense of Smell.

While olfactory dysfunction associated with coronavirus disease 2019 (COVID-19) has attracted considerable interest, few studies have tracked outcomes at serial time points or beyond 2 weeks. Furthermore, data are conflicting regarding whether COVID-19 severity correlates with degree of olfactory dysfunction. This prospective case-control study analyzed prevalence and severity of subjective loss of smell in outpatients (n = 23) and inpatients (n = 20) with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vs healthy controls (n = 25). Olfactory dysfunction was reported more commonly in COVID-19 patients than in healthy controls (P < .001), and outpatients paradoxically reported loss of smell more commonly than inpatients (P = .02). Headaches were present in 52% of patients with olfactory dysfunction. Anosmia or hyposmia persisted beyond 5 days but most of the patients recovered by 30 days, suggesting favorable prognosis for olfaction. Differences between inpatients and outpatients are potentially reflective of timeline of olfactory symptoms and contextual factors, underscoring the importance of corroborative objective testing, coupled with careful tracking of temporal relationships.

Predictive Value of Sudden Olfactory Loss in the Diagnosis of COVID-19.

INTRODUCTION: Recent reports suggest that sudden smell loss might be a symptom of SARS-CoV-2 infection. The aim of this study was to investigate the frequency of olfactory loss in an outpatient population who presented to a coronavirus testing center during a 2-week period and to evaluate the diagnostic value of the symptom "sudden smell loss" for screening procedures. METHODS: In this cross-sectional controlled cohort study, 500 patients who presented with symptoms of a common cold to a corona testing center and fulfilled corona testing criteria completed a standardized diagnostic questionnaire which included the patients' main symptoms, time course, and an additional self-assessment of the patients' current smell, taste function, and nasal breathing compared to the level before the onset of symptoms. RESULTS: Out of the 500 patients, 69 presented with olfactory loss. Twenty-two of them subsequently tested positive for SARS-CoV-2. Only 12 out of the patients without olfactory loss tested positive, resulting in a frequency of 64.7% for the symptom "sudden smell loss" in COVID-19 patients. Compared to COVID-19 patients without smell loss, they were significantly younger and less severely affected. Changes in nasal airflow were significantly more pronounced in SARS-CoV-2 negative patients with olfactory complaints compared to the patients with smell loss who tested positive for SARS-CoV-2. By excluding patients with a blocked nose, the symptom "sudden smell loss" can be attested a high specificity (97%) and a sensitivity of 65% with a positive predictive value of 63% and negative predictive value of 97% for COVID-19. CONCLUSION: Considering the high frequency of smell loss in non-hospitalized COVID-19 patients, acute olfactory impairment should be recognized as an early symptom of the disease and should be tested for on a regular basis. In contrast to other acute viral smell impairment, COVID-19-associated smell loss seems to be only rarely accompanied by a severely blocked nose.