Long COVID Clusters of Symptoms Persist beyond Two Years after Infection: Insights from the CARDIO COVID 20-21 Registry.

Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a two-year follow-up. We characterized the included patients and performed a cluster analysis of symptoms through multiple correspondence analysis and hierarchical clustering. A total of 199 patients with long COVID were included. The median age was 58 years (48-69), 56% were male, and the median follow-up time since the COVID-19 diagnosis was 26 months (IQR: 25, 27). Three symptom clusters were identified: Cluster 1 is characterized by fatigue, myalgia/arthralgia, a low prevalence of symptoms, and a lack of specific symptoms; Cluster 2 is defined by a high prevalence of fatigue, myalgia/arthralgia, and cardiorespiratory symptoms, including palpitations, shortness of breath, cough, and chest pain; and Cluster 3 is demonstrated a high prevalence of ageusia, anosmia, fatigue, and cardiorespiratory symptoms. Our study reinforces the concept of symptom clustering in long COVID, providing evidence that these clusters may persist beyond two years after a COVID-19 diagnosis. This highlights the chronic and debilitating nature of long COVID and the importance of developing strategies to mitigate symptoms in these patients.

Performance of a cost-effective olfactory test to evaluate hyposmia in Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) causes motor and non-motor symptoms such as hyposmia, which is evaluated through olfactory tests in the clinical practice. OBJECTIVE: To assess the feasibility of using the modified Connecticut Chemosensory Clinical Research Center (mCCCRC) olfactory test and to compare its performance with the Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Germany) test. METHODS: A transversal case-control study in which the patients were divided into the PD group (PDG) and the control group (CG). The cost and difficulty in handling substances to produce the mCCCRC test kits were evaluated. Sociodemographic characteristics, smoking habits, past coronavirus disease 2019 (COVID-19) infections, self-perception of odor sense, and cognition through the Montreal Cognitive Assessment (MoCA) were also evaluated. The PDG was scored by part III of the Unified Parkinson's Disease Rating Scale (UPDRS-III) and the Hoehn and Yahr Scale (H&Y) scale. Correlations were assessed through the Spearman rank correlation coefficient test (ρ, or rho). RESULTS: The mCCCRC test was easily manufactured and handled at a cost ten times lower compared with the SS-12. The groups (PDG: n = 34; CG: n = 38) were similar in terms of age, sex, level of schooling, smoking habits, and history of COVID-19. The tests results showed moderate correlation (rho = 0.65; p < 0.0001). The CG presented better cognitive performance and scored better in both tests (p < 0.0001). There was a tendency for a negative correlation with age, but good correlation with the MoCA (p = 0.0029). The results of the PDG group showed no correlation with olfactory results and motor performance or disease duration. The self-perception of hyposmia was low in both groups. CONCLUSION: The mCCCRC is an easy-to-apply and inexpensive method that demonstrated a similar performance to that of the SS-12 in evaluating olfaction in PD patients and healthy controls.

ANTECEDENTES: A doença de Parkinson (DP) cursa com sintomas motores e não motores como a hiposmia, que é avaliada por diferentes testes olfativos na prática clínica. OBJETIVO: Avaliar a viabilidade do teste olfatório Connecticut Chemosensory Clinical Research Center modificado (mCCCRC) e compará-la à do teste Sniffin' Sticks-12 (SS-12, Burghart Messtechnik GmbH, Wedel, Alemanha). MéTODOS: Estudo transversal de caso-controle em que os pacientes foram divididos no grupo DP (GDP) e no grupo controle (GC). O custo e as dificuldades no manuseio das substâncias necessárias para a produção dos kits do teste mCCCRC foram avaliados. Características sociodemográficas, tabagismo, histórico de infecção por doença do coronavírus 2019 (coronavírus disease 2019, COVID-19, em inglês), autopercepção do olfato e cognição pelo Montreal Cognitive Assessment (MoCA) também foram avaliados. O GDP foi avaliado pela parte III da Unified Parkinson's Disease Rating Scale (UPDRS-III) e pela escala de Hoehn and Yahr (H&Y). As correlações utilizaram o teste do coeficiente de correlação de postos de Spearman (ρ, ou rho). RESULTADOS: O mCCCRC foi facilmente poroduzido e manipulado com custo dez vezes inferior ao do SS-12. Os grupos (GDP: n = 34; GC: n = 38) eram similares em termos de idade, sexo, escolaridade, tabagismo e histórico de COVID-19. Os resultados obtidos em ambos os testes mostraram excelente correlação (rho = 0.65; p < 0.0001). O GC teve um desempenho cognitivo melhor e pontuou melhor nos dois testes (p < 0.0001). Houve uma tendência a uma correlação negativa com a idade, mas boa correlação com a pontuação no MoCA (p = 0.0029). Os resultados olfativos do GDP não mostraram correlação com desempenho motor ou duração da doença. A autopercepção de hiposmia foi baixa em ambos os grupos. CONCLUSãO: O mCCCRC é um teste de fácil aplicação, baixo custo, e apresentou um desempenho semelhante ao do SS-12 na avaliação olfativa de pacientes com DP e controles saudáveis.

Longitudinal Exploration of Cortical Brain Activity in Cognitive Fog: An EEG Study in Patients with and without Anosmia.

BACKGROUND: Long-Covid, characterized by persistent symptoms following acute Covid-19 infection, represents a complex challenge for the scientific community. Among the most common and debilitating manifestations, cognitive fog is a neurological disorder characterized by mental confusion and cognitive difficulties. In this study, we investigated the long-term effects of previous Covid-19 infection on cortical brain activity in patients experiencing cognitive fog symptoms in the medium and long term. METHODS: A total of 40 subjects (20 females and 20 males) aged between 45 and 70 years (mean age (M) = 59.78, standard deviation (SD) = 12.93) participated in this study. This sample included individuals with symptoms of cognitive fog, both with and without anosmia, and a control group comprised of healthy subjects. All electroencephalography (EEG) data were collected in two sessions, 1 month and 8 months after recovery from Covid-19, to measure the neurophysiological parameters of P300 and beta band rhythms. RESULTS: The results revealed significant differences in the neurophysiological parameters of P300 and beta band rhythms in subjects affected by cognitive fog, and these alterations persist even 8 months after recovery from Covid-19. Interestingly, no significant differences were observed between the participants with anosmia and without anosmia associated with cognitive fog. CONCLUSIONS: These findings provide a significant contribution to understanding the long-term effects of Covid-19 on the brain and have important implications for future interventions aimed at managing and treating brain fog symptoms. The longitudinal assessment of cortical brain activity helps highlight the persistent impact of the virus on the neurological health of Long-Covid patients.

[Features of olfactory impairment connected with trigeminal nerve system]. / Osobennosti narusheniya obonyaniya v aspekte sistemy troinichnogo nerva.

Data on the state of sense of smell in patients who had a new coronavirus infection caused by the SARS-CoV-2 virus are currently reduced because of the impairment of the olfactory nerve system. There are practically no results in studies of disorders in the trigeminal nerve system. OBJECTIVE: Qualitative assessment of olfactory disorders after COVID-19 according to the system of olfactory and trigeminal nerves with a targeted assessment of the functional component of olfactory disorders. MATERIAL AND METHODS: We examined 40 patients aged 19 to 66 who had a coronavirus infection. All patients underwent neurological, otorhinolaryngological examinations, olfactometry, filled out the hospital anxiety and depression scale. RESULTS: Anosmia was diagnosed in 5 (12.5%) patients, hyposmia in 21 (52.5%) patients, and normosmia in 14 (35%) patients. Formed: the 1st group - 14 patients (35%) with normogram according to olfactometry; the 2nd group - 26 patients (65%) with anosmia/hyposmia. In the 1st group, disorders of the anxiety-depressive spectrum were significantly more common. In the 2nd group, a low identification of odors was found, lying in the spectrum of fresh, sharp, unpleasant, irritating, compared with sweet and pleasant or neutral, which indicates a predominant lesion of the trigeminal system. CONCLUSION: In patients with complaints of impaired sense of smell after undergoing COVID-19, the possible functional nature of anosmia/hyposmia should be taken into account, which requires the referral of such patients to psychotherapeutic specialists, and the possible entry of olfactory disorders into the 'trigeminal' spectrum.

Post-Covid Conditions and their Effects on the Cardiovascular System.

Background: Rising global concerns about COVID-19 recently gained more research attention due to the ease of person-to-person transmission, various symptoms after healing, and the shortage of effective antiviral therapy. The study aims to analyze post-COVID conditions and clinical manifestations of cardiovascular lesions in patients recovering from COVID-19 infection. Methods: A practical examination of post-COVID conditions manifestation was conducted in a prospective cohort study, involving 250 patients diagnosed with COVID-19 between June 1, 2021, and August 31, 2021. The study specifically focused on analyzing the cardiovascular effects of COVID-19, utilizing data from a subgroup of 200 patients previously discharged from the hospital with elevated troponin levels. The cardiovascular variables assessed included tachycardia, ischemia, heart attack, myocarditis, hypertension, blood clots, and heart failure. Results: It has been observed that among surviving patients, the following symptoms persisted: anosmia/ageusia (59%), severe dyspnea (36.7%), palpitations and complaints related to the cardiovascular sys-tem (15.8%), headaches (13.2%), arthralgia (11.7%), myalgia (9.8%), and hair problems (≥5%). By the 60th day, a reduction in symptoms by 5-10% was noted, and by the 90th day, a decrease in activity by 25-35% was observed. Patients aged 40-60 years exhibited the highest percentage of cardiovascular diseases (75%). Conclusions: Consequently, the SARS-CoV-2 virus underscores the critical importance of cardiological attention in patient care. Cardiac screening results in individuals with COVID-19 reveal a significant prevalence of serious heart problems, affecting over half of the patients. This emphasizes the necessity for heightened vigilance and specialized cardiac care when managing patients with COVID-19.

Long-COVID impacts taste and olfactory in individuals with substance use disorder: A retrospective cohort study from the TriNetX US Collaborative Networks.

Substance use disorder (SUD) exacerbates the impact of Long-COVID, particularly increasing the risk of taste and olfactory disorders. Analyzing retrospective cohort data from TriNetX and over 33 million records (Jan 2020-Dec 2022), this study focused on 1,512,358 participants, revealing that SUD significantly heightens the likelihood of experiencing taste disturbances and anosmia in Long-COVID sufferers. Results indicated that individuals with SUD face a higher incidence of sensory impairments compared to controls, with older adults and women being particularly vulnerable. Smokers with SUD were found to have an increased risk of olfactory and taste dysfunctions. The findings underscore the importance of early screening, diagnosis, and interventions for Long-COVID patients with a history of SUD, suggesting a need for clinicians to monitor for depression and anxiety linked to sensory dysfunction for comprehensive care.

Cognition and Other Non-Motor Symptoms in an At-Risk Cohort for Parkinson's Disease Defined by REM-Sleep Behavior Disorder and Hyposmia.

Background: REM-sleep behavior disorder (RBD) and other non-motor symptoms such as hyposmia were proposed by the Movement Disorder Society as research criteria for prodromal Parkinson's disease (P-PD). Global cognitive deficit was later added. Objective: To compare non-motor symptoms, focusing on cognition, between a P-PD group and a matched control group. Methods: In this cross-sectional, case-control study, in a first set of analyses, we performed extensive cognitive testing on people with (n = 76) and a control group without (n = 195) probable RBD and hyposmia. Furthermore, we assessed motor and non-motor symptoms related to Parkinson's Disease (PD). After propensity score matching, we compared 62 P-PD with 62 age- and sex-matched controls. In addition, we performed regression analyses on the total sample (n = 271). In a second set of analyses, we used, a.o., the CUPRO to evaluate retrograde procedural memory and visuo-constructive functions. Results: People with P-PD showed significantly poorer performances in global cognition, visuo-constructive and executive functions, mainly in mental flexibility (p < 0.001; p = 0.004; p = 0.003), despite similar educational levels (p = 0.415). We observed significantly more motor and non-motor symptoms (p < 0.001; p = 0.004), higher scores for depression (p = 0.004) and apathy (p < 0.001) as well as lower quality of life (p < 0.001) in P-PD. CONCLUSIONS: Our findings confirm that global cognitive, executive, and visuo-constructive deficits define the P-PD group. In addition, depression, apathy, and lower quality of life were more prevalent in P-PD. If replicated in other samples, executive and visuo-constructive deficits should be considered in non-motor P-PD. Determining specific patterns will support early recognition of PD, secondary prevention of complications and the development of neuroprotective treatments.

Hyposmia correlates with axial signs and gait disorder in Parkinson's disease: an Italian Olfactory Identification Test study.

BACKGROUND: Olfactory dysfunction is a non-motor symptom and an important biomarker of Parkinson's disease (PD) because of its high prevalence (> 90%). Whether hyposmia correlates with motor symptoms is unclear. In the present study, we aim to investigate the relationship between olfactory impairment with both motor and non-motor features and disease variables (disease duration, stage, and severity). METHODS: One-hundred fifty-four PD patients were evaluated. Odor identification ability was tested using Italian Olfactory Identification Test (IOIT). A comprehensive spectrum of motor and non-motor features was assessed. Cognitive function was investigated through MMSE. Patients were divided into 3 different clinical phenotypes using UPDRS-III: tremor-dominant type (TDT), akinetic-rigid type (ART), and mixed type (MXT). RESULTS: Three of the 33 IOIT items were most frequently misidentified: basil (74.3%), coffee (66.9%), and mushroom (59.6%). Hyposmia was found in 93%. Hyposmic patients were older than controls (p = 0.01). Hoehn & Yahr (H&Y) score of 2 or greater was associated with higher probability of being hyposmic (OR = 5.2, p = 0.01). IOIT score did not significantly differ between TDT, ART, and MXT of analyzed PD patients. Performance to IOIT inversely correlated with age (p < 0.01), disease duration (p = 0.01), and H&Y score of 2 or higher (p < 0.01). Clinical features that associated with higher IOIT score were freezing of gait (FOG) (p < 0.001) and camptocormia (p < 0.05). CONCLUSIONS: In our cohort, IOIT scores showed a positive correlation with axial motor signs, but not with non-motor symptoms. IOIT may be a useful tool not only for supporting PD diagnosis but also for providing prognostic information about motor function.

Persistent COVID-19 parosmia and olfactory loss post olfactory training: randomized clinical trial comparing central and peripheral-acting therapeutics.

PURPOSE: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment. METHODS: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia. RESULTS: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated. CONCLUSIONS: umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.

COVID-19 associated anosmia in pediatric patients: subject publications review.

OBJECTIVE: Aim: To review the publications subject to the problem of COVID-19 associated anosmia incidence in pediatric patients as well as its pathogenesis, diagnostics, treatment and recovery. The peculiarity of pediatric COVID-19 anosmia is due to children accounting for very low percentage of COVID-19 patients (comparing to one in adults), mostly with milder course of the disease. Awareness of anosmia and its proper diagnostics is crucial in children and adolescents, considering it can be the only manifestation in COVID-19 positive pediatric patients. PATIENTS AND METHODS: Materials and Methods: In order to achieve this goal a meta-analysis of information from databases followed by statistical processing and generalisation of the obtained data was carried out. CONCLUSION: Conclusions: Publications on COVID-19 anosmia in children and adolescents are less numerous than those concerning adult patients, so it is important to use every single trustworthy one. Anosmia/ageusia may be the only symptom, early identifier and the strongest predictor of COVID-19 infection in pediatric patients. Prospects for further scientific researches. Further researches regarding differential diagnostics of COVID-19 and other infections, including seasonal influenza, manifesting with both olfactory and taste dysfunction as well as anosmia diagnostics in children and adolescents with autistic spectrum and different types of mental disorders are possible.

Longitudinal brain changes in Parkinson's disease with severe olfactory deficit.

INTRODUCTION: Olfactory dysfunction and REM sleep behavior disorder (RBD) are associated with distinct cognitive trajectories in the course of Parkinson's disease (PD). The underlying neurobiology for this relationship remains unclear but may involve distinct patterns of neurodegeneration. This study aimed to examine longitudinal cortical atrophy and thinning in early-stage PD with severe olfactory deficit (anosmia) without and with concurrent probable RBD. METHODS: Longitudinal MRI data over four years of 134 de novo PD and 49 healthy controls (HC) from the Parkinson Progression Marker Initiative (PPMI) cohort were analyzed using a linear mixed-effects model. Patients were categorized into those with anosmia by the University of Pennsylvania Smell Identification Test (UPSIT) score ≤ 18 (AO+) and those without (UPSIT score > 18, AO-). The AO+ group was further subdivided into AO+ with probable RBD (AO+RBD+) and without (AO+RBD-) for subanalysis. RESULTS: Compared to subjects without baseline anosmia, the AO+ group exhibited greater longitudinal declines in both volume and thickness in the bilateral parahippocampal gyri and right transverse temporal gyrus. Patients with concurrent anosmia and RBD showed more extensive longitudinal declines in cortical volume and thickness, involving additional brain regions including the bilateral precuneus, left inferior temporal gyrus, right paracentral gyrus, and right precentral gyrus. CONCLUSIONS: The atrophy/thinning patterns in early-stage PD with severe olfactory dysfunction include regions that are critical for cognitive function and could provide a structural basis for previously reported associations between severe olfactory deficit and cognitive decline in PD. Concurrent RBD might enhance the dynamics of cortical changes.

Anosmia or Ageusia Following COVID-19 Vaccination: A Systematic Review.

Aim: To systematically review the cases of anosmia or ageusia after receiving the coronavirus disease 2019 (COVID-19) vaccine. Methods: A systematic search was conducted in electronic databases, including Web of Science, Scopus, Embase, and PubMed, to identify any published study that evaluated the anosmia or ageusia after receiving the COVID-19 vaccine, including case reports, case series, letter to editor articles with reported cases regarding our topic, or observational studies with at least 1 eligible patient consisted with our criteria. We excluded the studies that reported anosmia or ageusia due to COVID-19 infection and non-COVID-19 vaccines. Results: Five studies consisting of 11 patients were included in this systematic review. Of the 11 patients, 5 patients had received the Pfizer COVID-19 vaccine and 6 patients received the Oxford-AstraZeneca COVID-19 vaccine, of which 6 patients developed symptoms after the first dose of vaccination and 5 patients were symptomatic after the second vaccine dose. Most of the patients developed symptoms within 1 week after the vaccination. The disorders of the patients included partial or total anosmia, parosmia, phantosmia, hyposmia, ageusia, and dysgeusia. Also, the patients had symptoms other than smell or taste disorders, including arthralgia, fever, chills, rhinorrhea, myalgia, abdominal pain, fatigue, muscle weakness, altered bowel pattern, aural fullness, tinnitus, and headache. Most of the evaluated patients did not receive any treatment as for their disorders. However, in some cases, treatment with oral corticosteroids or dietary supplementation was required. Conclusion: Anosmia and ageusia are important symptoms of COVID-19 vaccination. These symptoms will resolve without any treatment in most cases, although some interventions may be needed in some patients.

Diagnosed and subjectively perceived long-term effects of COVID-19 infection on olfactory function assessed by supervised machine learning.

Loss of olfactory function is a typical acute coronavirus disease 2019 (COVID-19) symptom, at least in early variants of SARS-CoV2. The time that has elapsed since the emergence of COVID-19 now allows for assessing the long-term prognosis of its olfactory impact. Participants (n = 722) of whom n = 464 reported having had COVID-19 dating back with a mode of 174 days were approached in a museum as a relatively unbiased environment. Olfactory function was diagnosed by assessing odor threshold and odor identification performance. Subjects also rated their actual olfactory function on an 11-point numerical scale [0,…10]. Neither the frequency of olfactory diagnostic categories nor olfactory test scores showed any COVID-19-related effects. Olfactory diagnostic categories (anosmia, hyposmia, or normosmia) were similarly distributed among former patients and controls (0.86%, 18.97%, and 80.17% for former patients and 1.17%, 17.51%, and 81.32% for controls). Former COVID-19 patients, however, showed differences in their subjective perception of their own olfactory function. The impact of this effect was substantial enough that supervised machine learning algorithms detected past COVID-19 infections in new subjects, based on reduced self-awareness of olfactory performance and parosmia, while the diagnosed olfactory function did not contribute any relevant information in this context. Based on diagnosed olfactory function, results suggest a positive prognosis for COVID-19-related olfactory loss in the long term. Traces of former infection are found in self-perceptions of olfaction, highlighting the importance of investigating the long-term effects of COVID-19 using reliable and validated diagnostic measures in olfactory testing.

The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

The burden of persistent symptoms after COVID-19 (long COVID): a meta-analysis of controlled studies in children and adults.

BACKGROUND: Previous meta-analyses estimating the prevalence of the post-COVID-19 condition (PCC) were confounded by the lack of negative control groups. This may result in an overestimation of the prevalence of those experiencing PCC, as these symptoms are non-specific and common in the general population. In this study, we aimed to compare the burden of persistent symptoms among COVID-19 survivors relative to COVID-19-negative controls. METHODS: A systematic literature search was conducted using the following databases (PubMed, Web of Science, and Scopus) until July 2023 for comparative studies that examined the prevalence of persistent symptoms in COVID-19 survivors. Given that many of the symptoms among COVID-19 survivors overlap with post-hospitalization syndrome and post-intensive care syndrome, we included studies that compare the prevalence of persistent symptoms in hospitalized COVID-19 patients relative to non-COVID-19 hospitalized patients and in non-hospitalized COVID-19 patients relative to healthy controls that reported outcomes after at least 3 months since infection. The results of the meta-analysis were reported as odds ratios with a 95% confidence interval based on the random effects model. RESULTS: Twenty articles were included in this study. Our analysis of symptomatology in non-hospitalized COVID-19 patients compared to negative controls revealed that the majority of symptoms examined were not related to COVID-19 infection and appeared equally prevalent in both cohorts. However, non-COVID-19 hospitalized patients had higher odds of occurrence of certain symptoms like anosmia, ageusia, fatigue, dyspnea, and brain fog (P < 0.05). Particularly, anosmia and ageusia showed substantially elevated odds relative to the negative control group at 11.27 and 9.76, respectively, P < 0.05. In contrast, analysis of hospitalized COVID-19 patients compared to those hospitalized for other indications did not demonstrate significantly higher odds for the tested symptoms. CONCLUSIONS: The persistent symptoms in COVID-19 survivors may result from hospitalization for causes unrelated to COVID-19 and are commonly reported among the general population. Although certain symptoms exhibited higher odds in non-hospitalized COVID-19 patients relative to controls, these symptoms are common post-viral illnesses. Therefore, the persistent symptoms after COVID-19 may not be unique to SARS-CoV-2. Future studies including well-matched control groups when investigating persistent symptoms in COVID-19 survivors are warranted to draw a firm conclusion.

Trigeminal function in patients with COVID-associated olfactory loss.

PURPOSE: Olfactory dysfunction (OD) can be a long-term consequence of various viral infections, including COVID-19. Dysfunction includes hyposmia/anosmia and parosmia (odor distortions). Interactions of the virus with the olfactory nerve have been extensively researched, but little is known about the interactions of the intranasal trigeminal nerve system in modulating this sensory loss. METHODS: We investigated intranasal trigeminal function across COVID-19 OD patients with and without parosmia compared to normosmic controls, to determine whether (1) post-viral hyposmia and/or (2) post-viral hyposmia with parosmia is associated with altered trigeminal function. OD patients (n = 27) were tested for olfactory function using the extended Sniffin' Sticks olfactory test and for trigeminal function through three methods-odor lateralization, subjective ratings of nasal patency, and ammonium vapor pain intensity ratings. This group was subsequently compared to controls, normosmic subjects (n = 15). RESULTS: Our findings revealed that post-COVID OD patients without parosmia experienced decreased sensitivity in ammonium vapor pain intensity ratings and odor lateralization scores-but similar nasal patency ratings-compared to normosmic controls. There were no significant differences in trigeminal function between OD patients with and without parosmia. CONCLUSIONS: Based on our results, we conclude that the trigeminal nerve dysfunction may partially explain post-viral OD, but does not seem to be a major factor in the generation of parosmia pathophysiology.

Assessment of anosmia/hyposmia in post-COVID-19 patients: a cross-sectional study in an eastern province of Saudi Arabia.

Background and aim It has been shown that olfactory dysfunction is one of Coronavirus disease-2019 (COVID-19)common and puzzling symptoms that may persist weeks after the infection. This study aimed for the objective assessment of persisting olfactory dysfunction in post-COVID-19 patients. It also investigated the factors associated with the development of such symptoms in the Eastern Province of Saudi Arabia. METHODS: A cross-sectional study that was conducted in the Department of Physiology, College of Medicine, Imam Abdulrahman bin Faisal University, Khobar, Saudi Arabia. One hundred and forty-seven participants were included in this study, and sixty of them agreed  to participate in the objective testing using the Connecticut Chemosensory Clinical Research Center (CCCRC) olfaction test. RESULTS: There was a significant correlation between the following factors: (1) Persistence of anosmia/hyposmia and the time of onset of anosmia/hyposmia (P=0.015). (2) Persistence of anosmia/hyposmia and the duration of anosmia/hyposmia (P=0.012). (3) Duration of anosmia/hyposmia and the duration of COVID-19 symptoms (P=0.010). Interestingly, there was a significant association between the subjective participants' claim of anosmia/hyposmia and the score of their objective assessment (P=0.026). CONCLUSION: The current study demonstrated that post-COVID-19 participants with delayed onset of anosmia/hyposmia and/or longer duration of either anosmia/hyposmia or COVID-19 symptoms were prone to have persistent olfactory dysfunction. Further studies are necessary to uncover the underlying pathophysiology and management of this olfactory dysfunction in COVID-19 patients.

Association between SARS-CoV-2 variants and post COVID-19 condition: findings from a longitudinal cohort study in the Belgian adult population.

BACKGROUND: While many studies on the determinants of post-COVID-19 conditions (PCC) have been conducted, little is known about the relationship between SARS-CoV-2 variants and PCC. This study aimed to assess the association between different SARS-CoV-2 variants and the probability of having PCC three months after the infection. METHODS: This study was a longitudinal cohort study conducted between April 2021 and September 2022 in Belgium. In total, 8,238 adults with a confirmed SARS-CoV-2 infection were followed up between the time of their infection and three months later. The primary outcomes were the PCC status three months post infection and seven PCC symptoms categories (neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, anosmia and/or dysgeusia, and other manifestations). The main exposure variable was the type of SARS-CoV-2 variants (i.e. Alpha, Delta, and Omicron), extracted from national surveillance data. The association between the different SARS-CoV-2 variants and PCC as well as PCC symptoms categories was assessed using multivariable logistic regression. RESULTS: The proportion of PCC among participants infected during the Alpha, Delta, and Omicron-dominant periods was significantly different and respectively 50%, 50%, and 37%. Participants infected during the Alpha- and Delta-dominant periods had a significantly higher odds of having PCC than those infected during the Omicron-dominant period (OR = 1.61, 95% confidence interval [CI] = 1.33-1.96 and OR = 1.73, 95%CI = 1.54-1.93, respectively). Participants infected during the Alpha and Delta-dominant periods were more likely to report neurocognitive, respiratory, and anosmia/dysgeusia symptoms of PCC. CONCLUSIONS: People infected during the Alpha- and Delta-dominant periods had a higher probability of having PCC three months after infection than those infected during the Omicron-dominant period. The lower probability of PCC with the Omicron variant must also be interpreted in absolute figures. Indeed, the number of infections with the Omicron variant being higher than with the Alpha and Delta variants, it is possible that the overall prevalence of PCC in the population increases, even if the probability of having a PCC decreases.

[Olfactory impairment in patients of the older age group with COVID-19 in the acute period and in the period of convalescence.]

Complete or partial loss of sense of smell significantly reduces the quality of life and in some cases is life-threatening. A new coronavirus infection in some cases leads to hypo- or anosmia. The defeat of the olfactory epithelium, swelling of the mucous membrane, the presence of discharge in the nasal cavity complicate the effect of odorants on the neuroepithelium. With COVID-19, anosmia may be the first and leading symptom. The restoration of the sense of smell occurs more often during the first weeks, but in some cases it is persistent. A special group of patients are older patients, older than 60 years. The course of a new coronavirus infection due to concomitant pathology proceeds in a more severe form. We present the experience of olfactory training with a set of essential oils (juniper, turmeric, eucalyptus and rose). Aromatherapy was preceded by irrigation of the nasal cavity with isotonic saline solution. In the absence of a clear clinical effect for 3 weeks, the set of oils was changed to fir oil, rosemary oil, monarda and lavender. The course of treatment continued for an average of 2 months. The technique included physiotherapy (endonasal electrophoresis with 0,25% zinc sulfate solution № 10), zinc preparations, pumpkin seeds 20-30 g per day, B vitamins (B6 and B12).

Post COVID-19 syndrome. Severity and evolution in 4673 health care workers.

BACKGROUND: The evolution of post COVID syndrome has been variable and we lack information on its impact on healthcare professionals, particularly in Latin America. METHODS: We conducted a survey through a social network in health professionals on post COVID-19 syndrome cases confirmed with PCR. In a web-based questionnaire, we asked about 21 symptoms, their severity, duration, degree of activity impairment and return to work. RESULTS: 4673 health professionals from 21 countries responded, mean age of 47.8 years, 64.2% women. The initial course was asymptomatic in 9.1%, mild symptoms 36.8%, moderate symptoms without hospitalization 40.8% or with hospitalization 11.7%, and severe symptoms with respiratory assistance 1.6%. The most prevalent symptoms were fatigue (67%), insomnia (44.2%), anxiety (42.3%), myalgia (41.9%) and anosmia (41.2%). Considering only severe symptoms (grades 3-4 on a subjective index from 1 to 4), the most prevalent were slowness (36.3%), impaired concentration (33.1%), anosmia (20.4%), fatigue (19.1%), impaired memory (18.1%) and dyspnea (15.9%). Prevalence dropped by half in the first 5 five months, but in many cases, it lasted for more than a year. In the multivariate analysis, symptoms tended to be grouped into clusters (cognitive, neuropsychiatric, cardiorespiratory, digestive, others). The need to change the work area was 16% and lack of return to work 7.8%, related to older age, number of symptoms and severity of the initial course. CONCLUSION: In conclusion, in many cases the persistence of post-COVID symptoms can be prolonged and have an occupational impact on healthcare professionals, requiring the adoption of specific policies to reduce harm.

Introducción: La evolución del síndrome post COVID ha sido variable y carecemos de información sobre su impacto en los profesionales de la salud. Métodos: Realizamos una encuesta a través de una red social en profesionales de la salud sobre casos de síndrome post COVID-19 confirmados con PCR. En un cuestionario web, preguntamos sobre 21 síntomas, su gravedad, duración, grado de afectación de la actividad y reincorporación al trabajo. Resultados: Respondieron 4673 profesionales sanitarios de 21 países, edad media de 47 años, 64% mujeres. El curso inicial fue asintomático en el 9%, síntomas leves en el 36%, síntomas moderados sin hospitalización en el 40% o con hospitalización en el 11%, y síntomas graves en el 1%. Los síntomas más prevalentes fueron fatiga (67%), insomnio (44%), ansiedad (42%), mialgia (41%) y anosmia (41%). La prevalencia se redujo a la mitad en los primeros 5 cinco meses, pero en muchos casos se prolongó durante más de un año. En el análisis multivariado los síntomas tendieron a agruparse en clusters (cognitivos, neuropsiquiátricos, cardiorrespiratorios, digestivos, otros). La necesidad de cambiar de área de trabajo fue del 16% y la falta de reincorporación al trabajo del 7%, relacionadas con la mayor edad, el número de síntomas y la gravedad del curso inicial. Conclusión: En muchos casos la persistencia de los síntomas post-COVID puede ser prolongada y tener un impacto laboral en los profesionales sanitarios, requiriendo la adopción de políticas específicas para reducir el daño.