A total of 2,618,862 participants reported their potential symptoms of COVID-19 on a smartphone-based app. Among the 18,401 who had undergone a SARS-CoV-2 test, the proportion of participants who reported loss of smell and taste was higher in those with a positive test result (4,668 of 7,178 individuals; 65.03%) than in those with a negative test result (2,436 of 11,223 participants; 21.71%) (odds ratio = 6.74; 95% confidence interval = 6.31-7.21). A model combining symptoms to predict probable infection was applied to the data from all app users who reported symptoms (805,753) and predicted that 140,312 (17.42%) participants are likely to have COVID-19. COVID-19 is an acute respiratory illness caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its outbreak in China in December 2019, over 2,573,143 cases have been confirmed worldwide (as of 21 April 2020; https://www.worldometers.info/coronavirus/). Although many people have presented with flu-like symptoms, widespread population testing is not yet available in most countries, including the United States (https://www.cdc.gov/coronavirus/2019-ncov/ cases-updates/testing-in-us.html) and United Kingdom 1. Thus, it is important to identify the combination of symptoms most predictive of COVID-19, to help guide recommendations for self-isolation and prevent further spread of the disease 2. Case reports and mainstream media articles from various countries indicate that a number of patients with diagnosed COVID-19 developed anosmia (loss of smell) 3,4. Mechanisms of action for the SARS-CoV-2 viral infection causing anosmia have been postulated 5,6. Other studies indicate that a number of infected individuals present anosmia in the absence of other symptoms 7,8 , suggesting that this symptom could be used as screening tool to help identify people with potential mild cases who could be recommended to self-isolate 9. We investigated whether loss of smell and taste is specific to COVID-19 in 2,618,862 individuals who used an app-based symptom tracker 10 (Methods). The symptom tracker is a free smartphone application that was launched in the United Kingdom on 24 March 2020, and in the United States on 29 March 2020. It collects data from both asymptomatic and symptomatic individuals and tracks in real time how the disease progresses by recording self-reported health information on a daily basis, including symptoms, hospitalization, reverse-transcription PCR (RT-PCR) test outcomes, demographic information and pre-existing medical conditions.

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Both underweight and obesity have been associated with increased mortality1,2. Underweight, defined as body mass index (BMI) ≤ 18,5 kg/m2 in adults 3 and ≤ −2 standard deviations (SD) in children4,5, is the main sign of a series of heterogeneous clinical conditions such as failure to thrive (FTT) 6–8, feeding and eating disorder and/or anorexia nervosa9,10. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported 11, 12. We previously demonstrated that hemizygosity of a ~600 kb region on the short arm of chromosome 16 (chr16:29.5–30.1Mb), causes a highly-penetrant form of obesity often associated with hyperphagia and intellectual disabilities13. Here we show that the corresponding reciprocal duplication is associated with underweight. We identified 138 (132 novel cases) duplication carriers (108 unrelated carriers) from over 95,000 individuals clinically-referred for developmental or intellectual disabilities (DD/ID), psychiatric disorders or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight (mean Z-score −0.6; p=4.4×10−4) and BMI (mean Z-score −0.5; p=2.0×10−3). In particular, half of the boys younger than 5 years are underweight with a probable diagnosis of FTT, while adult duplication carriers have an 8.7-fold (p=5.9×10−11; CI_95=[4.5–16.6]) increased risk of being clinically underweight. We observe a significant trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive feeding behaviours and a significant reduction in head circumference (mean Z-score −0.9; p=7.8×10−6). Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus, correlating with changes in transcript levels for genes mapping within the duplication but not within flanking regions. The reciprocal impact of these 16p11.2 copy number variants suggests that severe obesity and being underweight can have mirror etiologies, possibly through contrasting effects on eating behaviour.

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