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, and generally lacked quantitative measurements. 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.

In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using 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 univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. 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 univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<OR<10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.

Although situated ∼400 km from the east coast of Africa, Madagascar exhibits cultural, linguistic, and genetic traits from both Southeast Asia and Eastern Africa. The settlement history remains contentious; we therefore used a grid-based approach to sample at high resolution the genomic diversity (including maternal lineages, paternal lineages, and genome-wide data) across 257 villages and 2,704 Malagasy individuals. We find a common Bantu and Austronesian descent for all Malagasy individuals with a limited paternal contribution from Europe and the Middle East. Admixture and demographic growth happened recently, suggesting a rapid settlement of Madagascar during the last millennium. However, the distribution of African and Asian ancestry across the island reveals that the admixture was sex biased and happened heterogeneously across Madagascar, suggesting independent colonization of Madagascar from Africa and Asia rather than settlement by an already admixed population. In addition, there are geographic influences on the present genomic diversity, independent of the admixture, showing that a few centuries is sufficient to produce detectable genetic structure in human populations.

In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population.

Background: Sudden smell loss is a specific early symptom of COVID-19, which, prior to the emergence of Omicron, had estimated prevalence of ~40% to 75%. Chemosensory impairments affect physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. The aim of this cohort study was to characterize smell function and recovery up to 11 months post COVID-19 infection. Methods: This 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 survey (S1) about respiratory symptoms, chemosensory function and COVID-19 diagnosis between April and September 2020, were invited to complete 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. Results: At 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 illness. The ability to smell during COVID-19 was rated slightly lower by those who did not eventually recover their pre-illness ability to smell at S2. Conclusions: While smell ability improves for many individuals who lost it during acute COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is associated with broader persistent symptoms of COVID-19, and may last for many months following acute COVID-19. 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 even 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.

While admixed populations offer a unique opportunity to detect selection, the admixture in most of the studied populations occurred too recently to produce conclusive signals. By contrast, Malagasy populations originate from admixture between Asian and African populations that occurred ~27 generations ago, providing power to detect selection. We analyze local ancestry across the genomes of 700 Malagasy and identify a strong signal of recent positive selection, with an estimated selection coefficient >0.2. The selection is for African ancestry and affects 25% of chromosome 1, including the Duffy blood group gene. The null allele at this gene provides resistance to Plasmodium vivax malaria, and previous studies have suggested positive selection for this allele in the Malagasy population. This selection event also influences numerous other genes implicated in immunity, cardiovascular diseases, and asthma and decreases the Asian ancestry genome-wide by 10%, illustrating the role played by selection in recent human history.

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<OR<4), especially when viral lab tests are impractical or unavailable.

Importance: Sudden 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. Objective: To characterize smell function and recovery up to 11 months post COVID-19 infection. Settings, Participants: This 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 & Measures: Primary 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. Results: On 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 Relevance: While 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.