key: cord-0871622-dxxubbwb authors: Fernández-de-las-Peñas, César; Martín-Guerrero, José D.; Navarro-Pardo, Esperanza; Cancela-Cilleruelo, Ignacio; Moro-López-Menchero, Paloma; Pellicer-Valero, Oscar J. title: Exploring Trajectory Curves from Loss of Smell and Taste in Previously Hospitalized COVID-19 Survivors: the LONG-COVID-EXP-CM Multicenter Study date: 2022-02-22 journal: J Gen Intern Med DOI: 10.1007/s11606-022-07459-8 sha: 9f65dad7dcb9c033e735bd338e79b093c8d3c4dc doc_id: 871622 cord_uid: dxxubbwb nan Self-reported loss of smell (anosmia) and taste (ageusia) have a prevalence of 19% and 23% in COVID-19 patients at the acute phase 1 and a prevalence of 15% in a post-COVID phase 2, 3 . Altered taste and smell may lead to disruption to basic daily living activities; nevertheless, almost 80% of patients may expect spontaneous recovery after 6 months 4 . Most studies investigating loss of smell/taste have used crosssectional designs assessing their presence just once. Understanding longitudinal patterns of loss of smell/taste could have significant implications for determining comprehensive plans for prevention and management of these post-COVID complications. 5 This study explores the recovery trajectory of loss of smell/taste symptom in previously hospitalized COVID-19 survivors by using mosaic and exponential model bar plots for showing the long-term evolution of these symptoms. The LONG-COVID-EXP-CM is a multicenter cohort study including patients with a positive diagnosis of SARS-CoV-2 hospitalized during the first wave of the pandemic in five urban hospitals of Madrid (Spain). From all hospitalized patients, a sample of 400 individuals from each hospital was randomly selected. The study was approved by all the Ethics Committees (HUF/EC1517, HCSC20/495E, HSO25112020, HUIL/092-20, HUFA 20/126). Informed consent was obtained from all participants. Patients were scheduled for two telephone interviews at two follow-ups with a 5-month period in between. We used the AAO-HNS Anosmia Reporting Tool 6 for collecting data about smell/taste disturbances. Clinical (i.e., age, gender, height, weight, medical comorbidities) and hospitalization (e.g., symptoms at hospital admission, days at the hospital, intensive care unit admission) data were collected from medical records and used as adjusted covariables. Python's library statsmodels 0.11.1 was used for producing the mosaic plots, while the bar plots were done with Matplotlib 3.3.4. The exponential curves were fitted to the data according to the formula y = Ke ct , where y represents the modeled prevalence of a symptom (anosmia or ageusia) at time t (in months), and K and c are the parameters of the model. From a total of 2000 randomly selected individuals from the five hospitals, finally 1593 (45% women, age: 61, SD: 16 years) were assessed at T0 (hospital admission), T1 (mean: 8.4, range 6-10 months), and T2 (mean: 13.2, range 11-15 months) after discharge. The mosaic plots revealed that prevalence of loss of smell decreased from 8.1% (n = 130) at T0, to 4.0% (n = 64) at T1, to 3.1% (n = 49) at T2. Looking the figure, 91% of those patients (n = 119/130) experiencing anosmia at hospitalization (T0) had recovered 7 months after (T1). Further, 82% (53/64) of those with anosmia at T1 had developed it "de novo" (did not experience anosmia at T0). The prevalence of ageusia decreased from 7.1% (n = 114) at T0, to 3.0% (n = 48) at T1, to 1.75% (n = 28) at T2. Again, 90% of individuals (103/114) experiencing ageusia at hospitalization (T0) had recovered 7 months after (T1), whereas 77% (37/48) patients with ageusia at T1 had developed it "de novo." The trajectory analysis revealed fitted exponential curves with a decreased prevalence trend (Fig. 1) . To the best of the authors' knowledge, this is the first trajectory curve of recovery of post-COVID loss of smell/taste. The mosaic plots revealed that patients with anosmia or ageusia at T0 had mostly recovered by T1. In fact, most cases at T1 corresponded to individuals who had developed the symptoms "de novo." Since there are more individuals recovering than developing loss of smell/taste symptoms, the overall trend is descending. Considering the long regenerate time of olfactory/ gustatory neurons, the recovery of loss of smell/taste could be longer than expected. The exponential recovery trend identified here suggests that these symptoms could be present at least 3 years after the infection. This may be related to the fact that 80% of COVID-19 survivors developed "de novo" loss of smell/taste the following months after hospitalization. We acknowledge some weaknesses of this study. First, only hospitalized patients aged 60 years old were included. Loss of smell/taste were self-reported. Third, we just focused on these two post-COVID symptoms. Interaction between different post-COVID symptoms is common. In conclusion, post-COVID loss of smell/taste tends to spontaneously recover during the 3 years after COVID-19 in previously hospitalized survivors. The recovery rate is higher than the rate of "de novo" symptoms. Author Contribution All authors contributed to the study concept and design. CFdlP, JDMG, and OPV conducted literature review and did the statistical analysis. All authors recruited participants and collected data. OPV supervised the study. All authors contributed to interpretation of data. All authors contributed to drafting the paper. All authors revised the text for intellectual content and have read and approved the final version of the manuscript. Funding The LONG-COVID-EXP-CM is supported by a grant of Comunidad de Madrid y la Unión Europea, a través del Fondo Europeo de Desarrollo Regional (FEDER), Recursos REACT-UE del Programa Operativo de Madrid 2014-2020, financiado como parte de la respuesta de la Unión a la pandemia de COVID-19. The sponsor had no role in the design, collection, management, analysis, or interpretation of the data, draft, review, or approval of the manuscript or its content. The authors were responsible for the decision to submit the manuscript for publication, and the sponsor did not participate in this decision. Consent to Participate: Participants provided informed consent before collecting data. Self-reported loss of smell and taste in SARS-CoV-2 patients: Primary care data to guide future early detection strategies Prevalence of symptoms more than seven months after diagnosis of symptomatic COVID-19 in an outpatient setting Prevalence of post-COVID-19 symptoms in hospitalized and nonhospitalized COVID-19 survivors: A systematic review and meta-analysis Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients Planning for the post-COVID syndrome: How payers can mitigate long-term complications of the pandemic American Academy of Otolaryngology-Head and Neck Surgery Anosmia Reporting Tool for Clinicians The authors declare that they do not have a conflict of interest.