Persisting Chemosensory Impairments in 366 Healthcare Workers Following COVID-19: An 11-Month Follow-up. (preprint)

Background and Objectives: Olfactory and gustatory dysfunctions (OD, GD) are prevalent symptoms following COVID-19 and persist in 6%-44% of individuals in the first months after the infection. As only few reports have described their prognosis more than 6 months later, the main objective of this study was to assess the prevalence of OD and GD 11 months after COVID-19. We also aimed to determine test-retest reliability of subjective chemosensory ratings for the follow-up of chemosensory sensitivity, as this measure is often used for remote follow-up. Methods: Inclusion criteria included a PCR-confirmed SARS-CoV-2 infection; exclusion criteria were the presence of other respiratory infections and chronic sinusitis. To assess whether OD and GD had changed compared to pre-pandemic levels, we designed an observational study and distributed an online questionnaire assessing quantitative chemosensory function to healthcare workers 5 and 11 months after COVID-19. Specifically, we assessed olfaction, gustation, and trigeminal sensitivity (10-point visual analog scale) and function (4-point Likert scale) separately. We further assessed clinically relevant OD using the Chemosensory Perception Test, a psychophysical test designed to provide a reliable remote olfactory evaluation. Qualitative chemosensory dysfunction was also assessed. Results: We included a total of 366 participants (mean age of 44.8 years old (SD: 11.7)). They completed the last online questionnaire 10.6 months (SD: 0.7) after the onset of COVID-19 symptoms. Of all participants, 307 (83.9%) and 301 (82.2%) individuals retrospectively reported lower olfactory or gustatory sensitivity during the acute phase of COVID-19. Eleven months later, 184 (50.3%) and 163 (44.5%) indicated reduced chemosensory sensitivity, 32.2% reported impairment of olfactory function while 24.9% exhibited clinically relevant OD. Three variables predicted OD at follow-up, namely chest pain and GD during COVID-19 and presence of phantosmia at 5 months. Olfactory sensitivity ratings had a high test-retest reliability (intraclass correlation coefficient: 0.818 (95% CI: 0.760 - 0.860)) Discussion: This study suggests that chemosensory dysfunctions persist in a third of COVID-19 patients 11 months after COVID-19. Subjective measures have a high test-retest reliability and thus can be used to monitor post-COVID-19 OD. OD appears to be a common long-term symptom of COVID-19 important to consider when treating patients.

COVID-19 Has Long Term Effects on Chemosensory Functions (preprint)

Importance: A number of studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Objective: To describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution at 3 to 7 months after infection. Design, Setting, and Participants: A follow-up study of 704 health care workers with a RT-PCR confirmed SARS-CoV-2 infection between 28/2/2020 and 14/6/2020 was conducted 3 to 7 months after onset of symptoms. Data were collected with an online questionnaire. Participant had to be [≥]18 years old without respiratory illness in the 2 weeks prior to questionnaire completion. Main outcomes and measures: Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Results: Among the 704 health care worker participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities were reported by 81.3%, 81.5% and 48.0% respectively. Three to seven months later, reduced sensitivity was still reported by 52.0%, 41.9% and 23.3% respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. Conclusions and relevance: A significant proportion of COVID-19 cases have persistent chemosensory impairments at 3 to 7 months after their infection but the majority of those who had completely lost their olfactory, gustatory and trigeminal sensitivity have improved. Given the possible neurological underpinnings of this observation and the important number of individuals infected with SARS-CoV-2, further longitudinal studies are needed to better characterize this phenotype and to report eventual post-COVID-19 neurological sequelae.

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

Background: COVID-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. Methods: This 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. Results: Both 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 no significant 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. Conclusions: As 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 (10

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

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.

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

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.