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1.
Nat Med ; 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1773989

ABSTRACT

Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of cases and continues to circulate globally. To establish a novel SARS-CoV-2 human challenge model that enables controlled investigation of pathogenesis, correlates of protection and efficacy testing of forthcoming interventions, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally in an open-label, non-randomized study (ClinicalTrials.gov identifier NCT04865237 ; funder, UK Vaccine Taskforce). After inoculation, participants were housed in a high-containment quarantine unit, with 24-hour close medical monitoring and full access to higher-level clinical care. The study's primary objective was to identify an inoculum dose that induced well-tolerated infection in more than 50% of participants, with secondary objectives to assess virus and symptom kinetics during infection. All pre-specified primary and secondary objectives were met. Two participants were excluded from the per-protocol analysis owing to seroconversion between screening and inoculation, identified post hoc. Eighteen (~53%) participants became infected, with viral load (VL) rising steeply and peaking at ~5 days after inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log10 copies per milliliter (median, 95% confidence interval (8.41, 9.53)). Viable virus was recoverable from the nose up to ~10 days after inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected participants, beginning 2-4 days after inoculation, whereas two (11%) participants remained asymptomatic (no reportable symptoms). Anosmia or dysosmia developed more slowly in 15 (83%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs present even in asymptomatic infection. All infected individuals developed serum spike-specific IgG and neutralizing antibodies. Results from lateral flow tests were strongly associated with viable virus, and modeling showed that twice-weekly rapid antigen tests could diagnose infection before 70-80% of viable virus had been generated. Thus, with detailed characterization and safety analysis of this first SARS-CoV-2 human challenge study in young adults, viral kinetics over the course of primary infection with SARS-CoV-2 were established, with implications for public health recommendations and strategies to affect SARS-CoV-2 transmission. Future studies will identify the immune factors associated with protection in those participants who did not develop infection or symptoms and define the effect of prior immunity and viral variation on clinical outcome.

2.
Int Forum Allergy Rhinol ; 2022 Mar 14.
Article in English | MEDLINE | ID: covidwho-1756550

ABSTRACT

BACKGROUND: The aim of this study was to estimate the prevalence of self-reported chemosensory dysfunction in a study cohort of subjects who developed a mild-to-moderate coronavirus disease 2019 (COVID-19) in the period from January 17, 2022, to February 4, 2022 (Omicron proxy period) and compared that with a historical series of patients testing positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection between March and April, 2020 (comparator period). METHODS: Prospective study based on the 22-item Sino-Nasal Outcome Tool (SNOT-22), item "sense of smell or taste" and additional outcomes. RESULTS: Patients' characteristics and clinical presentations of COVID-19 were evaluated and compared in 779 patients, 338 of the study cohort and 441 of the historical series. The prevalence of self-reported chemosensory dysfunction during the proxy Omicron period (32.5%; 95% confidence interval [CI], 27.6-37.8) was significantly lower from that during the comparator period (66.9%; 95% CI, 62.3-71.3) (p < 0.001). Nearly one-quarter of patients (24.6%; 95% CI, 20.1-29.5) reported an altered sense of smell during the proxy Omicron period compared to 62.6% (95% CI, 57.9-67.1) during the comparator period (p < 0.001). Similarly, the prevalence of an altered sense of taste dropped to 26.9% (95% CI, 22.3-32.0) during the proxy Omicron period from 57.4% (95% CI, 52.6-62.0) during the comparator period (p < 0.001). The severity of chemosensory dysfunction was lower in the proxy Omicron period compared to the comparator period (p < 0.001). CONCLUSION: The prevalence and the severity of COVID-19-associated smell and taste dysfunction has dropped significantly with the advent of the Omicron variant but it still remains above 30%.

3.
The Cochrane database of systematic reviews ; 2021(3), 2021.
Article in English | EuropePMC | ID: covidwho-1728547

ABSTRACT

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID‐19 infection. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach.

4.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328567

ABSTRACT

To establish a novel SARS-CoV-2 human challenge model, 36 volunteers aged 18-29 years without evidence of previous infection or vaccination were inoculated with 10 TCID 50 of a wild-type virus (SARS-CoV-2/human/GBR/484861/2020) intranasally. Two participants were excluded from per protocol analysis due to seroconversion between screening and inoculation. Eighteen (~53%) became infected, with viral load (VL) rising steeply and peaking at ~5 days post-inoculation. Virus was first detected in the throat but rose to significantly higher levels in the nose, peaking at ~8.87 log 10 copies/ml (median, 95% CI [8.41,9.53). Viable virus was recoverable from the nose up to ~10 days post-inoculation, on average. There were no serious adverse events. Mild-to-moderate symptoms were reported by 16 (89%) infected individuals, beginning 2-4 days post-inoculation. Anosmia/dysosmia developed more gradually in 12 (67%) participants. No quantitative correlation was noted between VL and symptoms, with high VLs even in asymptomatic infection, followed by the development of serum spike-specific and neutralising antibodies. However, lateral flow results were strongly associated with viable virus and modelling showed that twice-weekly rapid tests could diagnose infection before 70-80% of viable virus had been generated. Thus, in this first SARS-CoV-2 human challenge study, no serious safety signals were detected and the detailed characteristics of early infection and their public health implications were shown. ClinicalTrials.gov identifier: NCT04865237.

5.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-327748

ABSTRACT

Background The aim of this study was to estimate the prevalence of self-reported chemosensory dysfunction in a study cohort of subjects who developed a mild-to-moderate COVID-19 in the period from January 17, 2022 to February 4, 2022 (Omicron proxy period) and compared that with a historical series of patients tested positive for SARS-CoV-2 infection between March and April, 2020 (comparator period). Methods Prospective study based on the sinonasal outcome tool 22 (SNOT-22), item “sense of smell or taste” and additional outcomes. Results Patients’ characteristics and clinical presentations of COVID-19 were evaluated and compared in 779 patients, 338 of the study cohort and 441 of the historical series. The prevalence of self-reported chemosensory dysfunction during the proxy Omicron period (32.5%;95% CI, 27.6-37.8) was significantly lower from that during the comparator period (66.9%;95% CI, 62.3-71.3) ( p <.001). 24.6% (95% CI, 20.1-29.5) of patients reported an altered sense of smell during the proxy Omicron period compared to 62.6% (95% CI, 57.9-67.1) during the comparator period ( p <.001). Similarly, the prevalence of an altered sense of taste dropped from 57.4% (95% CI, 52.6-62.0) during the comparator period to 26.9% (95% CI, 22.3-32.0) during the proxy Omicron period ( p <.001). The severity of chemosensory dysfunction was lower in proxy Omicron period compared to comparator period ( p <.001). Conclusions The prevalence and the severity of COVID-19 associated smell and taste dysfunction has dropped significantly with the advent of the Omicron variant.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323293

ABSTRACT

• Telephone interviews were conducted with 19 MACRO trial participants from 5 ENT sites across the UK. • Trial participants experienced mixed levels of communication during the COVID period and some felt uninformed about the trial status and their clinical situation. • Participants were most concerned about getting COVID through interactions with other patients in hospital settings. Conversely, there was a high level of trust in healthcare professionals. • Pre-visit COVID-safety information, minimising contact with other patients, and strict waiting room management can facilitate the restart of the MACRO trial from the patient perspective. • Patient confidence in trial participation is likely to continue improving with COVID vaccination roll out.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323144

ABSTRACT

Background: Interleukin 6 (IL-6) is a proinflammatory cytokine that is secreted by cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is widely recognized as a negative prognostic factor. The purpose of this study was to analyze the correlations between the olfactory scores determined by psychophysical tests and the serum levels of IL-6 in patients affected by coronavirus disease 2019 (COVID-19) Methods: : Patients underwent psychophysical olfactory assessment with Connecticut Chemosensory Clinical Research Center test and IL-6 plasma level determination within 10 days of the clinical onset of COVID-19. Results: : Seventy-four COVID-19 patients were included in this study. COVID-19 staged as mild in 34 patients, moderate in 26 and severe in 14 cases. There were no significant differences in olfactory scores across the different COVID-19 severity groups In the patient series, the median plasma level of IL-6 was 7.7 pg/mL (IQR 3.7 – 18.8). The concentration of IL-6 was found to be significantly correlated with the severity of COVID-19 with a directly proportional relationship. The correlation between IL-6 plasma concentrations and olfactory scores was weak (r s =0.182) and not significant (p=0.12). Conclusions: : In COVID-19 patients, psychophysical olfactory scores did not show significant correlations with the plasma levels of a well-recognized negative prognostic factor such as IL-6. This observation casts some shadows on the positive prognostic value of olfactory dysfunctions

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-307197

ABSTRACT

Purpose: To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2 positive patients. Methods: Cross sectional study based on ad hoc questions. Results: Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (p<0.001). Conclusion: Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2 positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection.

10.
Life (Basel) ; 12(2)2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1625852

ABSTRACT

(1) Background: Persistent olfactory (POD) and gustatory (PGD) dysfunctions are one of the most frequent symptoms of long-Coronavirus Disease 2019 but their effect on the quality of life (QoL) of patients is still largely unexplored. (2) Methods: An online survey was administered to individuals who reported to have had SARS-CoV-2 infection at least 6 months prior with persisting COVID-19 symptoms (using the COVID symptom index), including ratings of POD and PGD, and their physical (PCS) and mental (MCS) components of quality of life were assessed using the standardized short form 12 questionnaire (SF-12). (3) Results: Responses from 431 unique individuals were included in the analyses. The most frequent persistent symptoms were: fatigue (185 cases, 42.9%), olfactory dysfunction (127 cases, 29.5%), gustatory dysfunction (96 cases, 22.3%) and muscle pain (83 cases, 19.3%). Respondents who reported persisting muscle pain, joint pain, fatigue, headache, gastrointestinal disturbances, and dyspnea had significantly worse PCS. Those experiencing persistent fatigue and dyspnea also showed significantly lower MCS. Respondents reporting POD or PGD showed significantly worse QoL, but only pertaining to the MCS. Multiple regressions predicted MCS based on olfactory and marginally on gustatory ratings, but not PCS. Age significantly affected the prediction of PCS but not MCS, and gender and temporal distance from the COVID-19 diagnosis had no effect. (4) Conclusions: POD and PGD are frequent symptoms of the long-COVID-19 syndrome and significantly reduce QoL, specifically in the mental health component. This evidence should stimulate the establishment of appropriate infrastructure to support individuals with persistent CD, while research on effective therapies scales up.

11.
Curr Opin Otolaryngol Head Neck Surg ; 30(1): 19-25, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1612726

ABSTRACT

PURPOSE OF REVIEW: This article reviews the literature on COVID-19 related anosmia, focusing on the epidemiology, pathophysiology recovery rates, current available treatment options, and research regarding novel treatments. RECENT FINDINGS: Loss of sense of smell is one of the most prevalent symptoms reported by patients after COVID-19 infection. Even though there is a high self-reported recovery rate, recent studies have demonstrated that up to 7% of the patients remain anosmic more than 12 months after onset, leaving millions worldwide with severe olfactory dysfunction. Olfactory training remains the first line recommended treatment. Given the paucity of effective medical treatments options researchers are exploring novel therapeutic options. SUMMARY: Olfactory dysfunction remains a significant and persistent legacy of the COVID-19 pandemic, but heightened awareness may stimulate research that leads to the development of much-needed treatment options.


Subject(s)
COVID-19 , Olfaction Disorders , Humans , Olfaction Disorders/diagnosis , Olfaction Disorders/epidemiology , Olfaction Disorders/etiology , Pandemics , SARS-CoV-2 , Smell
13.
JMIR Form Res ; 5(12): e29086, 2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572235

ABSTRACT

BACKGROUND: The impact of qualitative olfactory disorders is underestimated. Parosmia, the distorted perception of familiar odors, and phantosmia, the experience of odors in the absence of a stimulus, can arise following postinfectious anosmia, and the incidences of both have increased substantially since the outbreak of COVID-19. OBJECTIVE: The aims of this study are to explore the symptoms and sequalae of postinfectious olfactory dysfunction syndrome using unstructured and unsolicited threads from social media, and to articulate the perspectives and concerns of patients affected by these debilitating olfactory disorders. METHODS: A thematic analysis and content analysis of posts in the AbScent Parosmia and Phantosmia Support group on Facebook was conducted between June and December 2020. RESULTS: In this paper, we identify a novel symptom, olfactory perseveration, which is a triggered, identifiable, and usually unpleasant olfactory percept that persists in the absence of an ongoing stimulus. We also observe fluctuations in the intensity and duration of symptoms of parosmia, phantosmia, and olfactory perseveration. In addition, we identify a group of the most common items (coffee, meat, onion, and toothpaste) that trigger distortions; however, people have difficulty describing these distortions, using words associated with disgust and revulsion. The emotional aspect of living with qualitative olfactory dysfunction was evident and highlighted the detrimental impact on mental health. CONCLUSIONS: Qualitative and unsolicited data acquired from social media has provided useful insights into the patient experience of parosmia and phantosmia, which can inform rehabilitation strategies and ongoing research into understanding the molecular triggers associated with parosmic distortions and research into patient benefit.

15.
Curr Opin Otolaryngol Head Neck Surg ; 30(1): 19-25, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1566100

ABSTRACT

PURPOSE OF REVIEW: This article reviews the literature on COVID-19 related anosmia, focusing on the epidemiology, pathophysiology recovery rates, current available treatment options, and research regarding novel treatments. RECENT FINDINGS: Loss of sense of smell is one of the most prevalent symptoms reported by patients after COVID-19 infection. Even though there is a high self-reported recovery rate, recent studies have demonstrated that up to 7% of the patients remain anosmic more than 12 months after onset, leaving millions worldwide with severe olfactory dysfunction. Olfactory training remains the first line recommended treatment. Given the paucity of effective medical treatments options researchers are exploring novel therapeutic options. SUMMARY: Olfactory dysfunction remains a significant and persistent legacy of the COVID-19 pandemic, but heightened awareness may stimulate research that leads to the development of much-needed treatment options.


Subject(s)
COVID-19 , Olfaction Disorders , Humans , Olfaction Disorders/diagnosis , Olfaction Disorders/epidemiology , Olfaction Disorders/etiology , Pandemics , SARS-CoV-2 , Smell
16.
Otolaryngol Head Neck Surg ; : 1945998211061511, 2021 Nov 23.
Article in English | MEDLINE | ID: covidwho-1528640

ABSTRACT

The purpose of this multicenter case-control study was to evaluate a group of patients at least 1 year after coronavirus disease 2019 (COVID-19) with Sniffin' Sticks tests and to compare the results with a control population to quantify the potential bias introduced by the underlying prevalence of olfactory dysfunction (OD) in the general population. The study included 170 cases and 170 controls. In the COVID-19 group, 26.5% of cases had OD (anosmia in 4.7%, hyposmia in 21.8%) versus 3.5% in the control group (6 cases of hyposmia). The TDI score (threshold, discrimination, and identification) in the COVID-19 group was significantly lower than in the control group (32.5 [interquartile range, 29-36.5] vs 36.75 [34-39.5], P < .001). The prevalence of OD was significantly higher in the COVID-19 group, confirming that this result is not due to the underlying prevalence of OD in the general population.

17.
Laryngoscope ; 132(2): 419-421, 2022 02.
Article in English | MEDLINE | ID: covidwho-1527451

ABSTRACT

The aim of this study is to investigate the clinical profile of patients who developed coronavirus disease 2019 (COVID-19) after full vaccination. Demographic, epidemiological and clinical data were collected through medical records and online patient-reported outcome questionnaire from patients who developed symptomatic SARS-CoV-2 infection, confirmed by nasopharyngeal swab, at least 2 weeks after completion of vaccination. A total of 153 subjects were included. The most frequent symptoms were: asthenia (82.4%), chemosensory dysfunction (63.4%), headache (59.5%), runny nose (58.2%), muscle pain (54.9%), loss of appetite (54.3%), and nasal obstruction (51.6%). Particularly, 62.3% and 53.6% of subjects reported olfactory and gustatory dysfunction, respectively. Symptom severity was mild or moderate in almost all cases. Chemosensory dysfunctions have been observed to be a frequent symptom even in subjects who contracted the infection after full vaccination. For this reason, the sudden loss of smell and taste could continue to represent a useful and specific diagnostic marker to raise the suspicion of COVID-19 even in vaccinated subjects. In the future, it will be necessary to establish what the recovery rate is in these patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:419-421, 2022.


Subject(s)
Ageusia/epidemiology , Anosmia/epidemiology , COVID-19 Vaccines , COVID-19/physiopathology , SARS-CoV-2 , Adult , Ageusia/virology , Anosmia/virology , COVID-19/complications , COVID-19/prevention & control , Female , Humans , Male , Middle Aged , Patient Reported Outcome Measures , Smell/drug effects , Surveys and Questionnaires , Taste/drug effects , Vaccination
18.
PLoS One ; 16(9): e0256998, 2021.
Article in English | MEDLINE | ID: covidwho-1438345

ABSTRACT

BACKGROUND: Qualitative olfactory (smell) dysfunctions are a common side effect of post-viral illness and known to impact quality of life and health status. Evidence is emerging that taste and smell loss are common symptoms of Covid-19 that may emerge and persist long after initial infection. The aim of the present study was to document the impact of post Covid-19 alterations to taste and smell. METHODS: We conducted exploratory thematic analysis of user-generated text from 9000 users of the AbScent Covid-19 Smell and Taste Loss moderated Facebook support group from March 24 to 30th September 2020. RESULTS: Participants reported difficulty explaining and managing an altered sense of taste and smell; a lack of interpersonal and professional explanation or support; altered eating; appetite loss, weight change; loss of pleasure in food, eating and social engagement; altered intimacy and an altered relationship to self and others. CONCLUSIONS: Our findings suggest altered taste and smell with Covid-19 may lead to severe disruption to daily living that impacts on psychological well-being, physical health, relationships and sense of self. More specifically, participants reported impacts that related to reduced desire and ability to eat and prepare food; weight gain, weight loss and nutritional insufficiency; emotional wellbeing; professional practice; intimacy and social bonding; and the disruption of people's sense of reality and themselves. Our findings should inform further research and suggest areas for the training, assessment and treatment practices of health care professionals working with long Covid.


Subject(s)
Anosmia , COVID-19 , Olfactory Perception , SARS-CoV-2 , Taste Disorders , Taste Perception , Adult , Anosmia/etiology , Anosmia/physiopathology , Anosmia/psychology , COVID-19/complications , COVID-19/physiopathology , COVID-19/psychology , Female , Humans , Male , Middle Aged , Taste Disorders/etiology , Taste Disorders/physiopathology , Taste Disorders/psychology , Time Factors
19.
Ear Nose Throat J ; : 1455613211044770, 2021 Sep 26.
Article in English | MEDLINE | ID: covidwho-1438188
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