Increasing incidence of parosmia and phantosmia in patients recovering from COVID-19 smell loss

ImportanceSudden smell loss is a specific early symptom of COVID-19, with an estimated prevalence of ~40% to 75%. Smell impairment affects physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. ObjectiveTo characterize smell function and recovery up to 11 months post COVID-19 infection. Settings, ParticipantsThis longitudinal survey of individuals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial respiratory symptoms, chemosensory function and COVID-19 diagnosis survey (S1) between April and September 2020 and completed a follow-up survey (S2) between September 2020 and February 2021; 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. Main Outcomes & MeasuresPrimary outcomes are ratings of smell and taste function on a visual analog scale, and self-report of parosmia (smell distortions) and phantosmia (unexplained smells). Secondary outcomes include a checklist of other COVID-19 symptoms. ResultsOn follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID. During COVID-19 illness, the ability to smell was slightly lower among those who did not recover their pre-illness ability to smell at S2. Conclusions and RelevanceWhile smell loss improves for many individuals who lost it due to COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is also associated with wider COVID-19 symptoms and may persist for many months after COVID-19 onset. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long term sequelae; more research into treatment options is strongly warranted given that conservative estimates suggest millions of individuals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health. Trial registrationThis project was pre-registered at OSF: https://osf.io/3e6zc. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/21262763v2_ufig1.gif" ALT="Figure 1"> View larger version (22K): org.highwire.dtl.DTLVardef@b2aceforg.highwire.dtl.DTLVardef@77a539org.highwire.dtl.DTLVardef@1004dbborg.highwire.dtl.DTLVardef@ef5c9c_HPS_FORMAT_FIGEXP M_FIG C_FIG Key PointsO_ST_ABSQuestionC_ST_ABSWhat are the characteristics of smell and taste recovery of COVID-19 patients? FindingsIn this preregistered observational study of 1,468 participants, smell loss is associated with a higher number of COVID-19 symptoms, and may persist for at least 11 months following disease onset. While a majority of participants report quantitative improvement in their ability to smell, the prevalence of parosmia and phantosmia increases substantially at follow-up. Taste recovers faster than smell, suggesting taste and smell recover separately and can be distinguished by the respondents. MeaningOlfactory dysfunction appears to be a component of long-COVID, with parosmia as a prominent symptom in almost half of those with smell loss. More research into treatment is needed, especially given that olfactory dysfunction is associated with depression and loss of appetite. Health professionals should be aware of these common and long lasting effects.

Onset, duration, and persistence of taste and smell changes and other COVID-19 symptoms: longitudinal study in Israeli patients

ObjectivesThe multifaceted manifestation of COVID-19 requires longitudinal characterization of symptoms, to aid with screening and disease management. MethodsPhone interviews and follow-ups were completed with 112 mostly mild COVID-19 RT-PCR-positive adult patients, over a six-months period. ResultsMore than one symptom at disease onset was experienced by [~]70% of the patients. About 40% of the patients experienced fever, dry cough, headache, or muscle ache as the first symptom. Fatigue, if reported, usually was the first to appear. Smell and taste changes were experienced 3.9 {+/-} 5.4 and 4.6 {+/-} 5.7 days (mean {+/-} SD) after disease onset and emerged as first symptom in 15% and 18% of patients, respectively. Fever had the shortest duration (5.8 {+/-} 8.6 days), and taste and smell changes were the longest-lasting symptoms (17.2 {+/-} 17.6 and 18.9 {+/-} 19.7 days, durations censored at 60 days). Longer smell recovery correlated with smell change severity. Cough, taste change and smell change persisted after negative RT-PCR tests (in 20%, 26% and 29% of the patients in total). At six-months follow-up, 46% of the patients had at least one unresolved symptom, most commonly fatigue (21%), chemosensory changes (14%) or breath difficulty (9%). ConclusionsMore than one symptom typically occurred at disease onset. Chemosensory changes and cough persisted after negative RT-PCR in a quarter of the patients. Almost half of the patients reported at least one unresolved symptom at six-months follow up, mainly fatigue, smell changes and breath difficulty. Our findings highlight the prevalence of long-lasting effects of COVID-19.

Self-rated smell ability enables highly specific predictors of COVID-19 status: a case control study in Israel

BackgroundClinical diagnosis of COVID-19 poses an enormous challenge to early detection and prevention of COVID-19, which is of crucial importance for pandemic containment. Cases of COVID-19 may be hard to distinguish clinically from other acute viral diseases, resulting in an overwhelming load of laboratory screening. Sudden onset of taste and smell loss emerge as hallmark of COVID-19. The optimal ways for including these symptoms in the screening of suspected COVID-19 patients should now be established. MethodsWe performed a case-control study on patients that were PCR-tested for COVID-19 (112 positive and 112 negative participants), recruited during the first wave (March 2020 - May 2020) of COVID-19 pandemic in Israel. Patients were interviewed by phone regarding their symptoms and medical history and were asked to rate their olfactory and gustatory ability before and during their illness on a 1-10 scale. Prevalence and degrees of symptoms were calculated, and odds ratios were estimated. Symptoms-based logistic-regression classifiers were constructed and evaluated on a hold-out set. ResultsChanges in smell and taste occurred in 68% (95% CI 60%-76%) and 72% (64%-80%), of positive patients, with 24 (11-53 range) and 12 (6-23) respective odds ratios. The ability to smell was decreased by 0.5{+/-}1.5 in negatives, and by 4.5{+/-}3.6 in positives, and to taste by 0.4{+/-}1.5 and 4.9{+/-}3.8, respectively (mean {+/-} SD). A penalized logistic regression classifier based on 5 symptoms (degree of smell change, muscle ache, lack of appetite, fever, and a negatively contributing sore throat), has 66% sensitivity, 97% specificity and an area under the ROC curve of 0.83 (AUC) on a hold-out set. A classifier based on degree of smell change only is almost as good, with 66% sensitivity, 97% specificity and 0.81 AUC. Under the assumption of 8% positives among those tested, the predictive positive value (PPV) of this classifier is 0.68 and negative predictive value (NPV) is 0.97. ConclusionsSelf-reported quantitative olfactory changes, either alone or combined with other symptoms, provide a specific and powerful tool for clinical diagnosis of COVID-19. The applicability of this tool for prioritizing COVID-19 laboratory testing is facilitated by a simple calculator presented here.

Recent smell loss is the best predictor of COVID-19: a preregistered, cross-sectional study

BackgroundCOVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. MethodsThis preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery. ResultsBoth C19+ and C19-groups exhibited smell loss, but it was significantly larger in C19+ participants (mean{+/-}SD, C19+: -82.5{+/-}27.2 points; C19-: -59.8{+/-}37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for [~]50% of participants and was best predicted by time since illness onset. ConclusionsAs smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings [≤]2 indicate high odds of symptomatic COVID-19 (4

More than just smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, generally lacked quantitative measurements, were mostly restricted to data from single countries. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change {+/-}100) revealed a mean reduction of smell (-79.7 {+/-} 28.7, mean {+/-} SD), taste (-69.0 {+/-} 32.6), and chemesthetic (-37.3 {+/-} 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.

Utility and limitations of Google searches on sensory loss as markers for new COVID-19 cases

Web tools are widely used among population to obtain health related information, and these data are often employed for public health monitoring. Here we analyzed searches related to smell loss and taste loss, recently linked to COVID-19, as well as sight loss and hearing loss, not included in the COVID-19 symptoms list. Google Trends results per region (Italy) or state (United States) over several weeks were compared to the number of new cases prevalence in that geographical area. Taste and smell loss searches were correlated with each other, and, during a limited time window, with new COVID-19 cases. However, this correlation decreased with time, attributable, at least in part, to media coverage. As new symptoms are being discovered for COVID-19 and the pandemic continues to spread around the globe, the lesson learned here, that correlation between public interest in novel symptoms of infectious disease has an initial spike (the "surprise rise") and subsequently goes to a new baseline due to "knowledge saturation", is of general and practical value for the public.