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Chemical Senses Jan 2023Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with... (Meta-Analysis)
Meta-Analysis
Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms.
Topics: Male; Adult; Middle Aged; Female; Humans; COVID-19; Ageusia; SARS-CoV-2; Olfaction Disorders; Taste Disorders; Smell; Taste
PubMed: 38100383
DOI: 10.1093/chemse/bjad043 -
BMC Infectious Diseases Dec 2023Persistent headache is a frequent symptom after coronavirus disease 2019 (COVID-19) and there is currently limited knowledge about its clinical spectrum and predisposing...
BACKGROUND
Persistent headache is a frequent symptom after coronavirus disease 2019 (COVID-19) and there is currently limited knowledge about its clinical spectrum and predisposing factors. A subset of patients may be experiencing new daily persistent headache (NDPH) after COVID-19, which is among the most treatment-refractory primary headache syndromes.
METHODS
We conducted a cross-sectional study in Latin America to characterize individuals with persistent headache after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify factors associated with NDPH. Participants over 18 years old who tested positive for SARS-CoV-2 infection and reported persistent headache among their symptoms completed an online survey that included demographics, past medical history, persistent headache clinical characteristics, and COVID-19 vaccination status. Based on participants' responses, NDPH diagnostic criteria were used to group participants into NDPH and non-NDPH groups. Participant data was summarized by descriptive statistics. Student's t and Mann-Whitney U tests were used according to the distribution of quantitative variables. For categorical variables, Pearson's chi-square and Fisher's exact tests were used according to the size of expected frequencies. Binomial logistic regression using the backward stepwise selection method was performed to identify factors associated with NDPH.
RESULTS
Four hundred and twenty-one participants from 11 Latin American countries met the inclusion criteria. One in four participants met the NDPH diagnostic criteria. The mean age was 40 years, with most participants being female (82%). Over 90% of the participants reported having had mild/moderate COVID-19. Most participants had a history of headache before developing COVID-19 (58%), mainly migraine type (32%). The most predominant clinical characteristics in the NDPH group were occipital location, severe/unbearable intensity, burning character, and radiating pain (p < 0.05). A higher proportion of anxiety symptoms, sleep problems, myalgia, mental fog, paresthesia, nausea, sweating of the face or forehead, and ageusia or hypogeusia as concomitant symptoms were reported in participants with NDPH (p < 0.05). Palpebral edema as a concomitant symptom during the acute phase of COVID-19, occipital location, and burning character of the headache were risk factors associated with NDPH.
CONCLUSION
This is the first study in Latin America that explored the clinical spectrum of NDPH after SARS-CoV-2 infection and its associated factors. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH.
Topics: Humans; Female; Adult; Adolescent; Male; COVID-19; Cross-Sectional Studies; Latin America; SARS-CoV-2; COVID-19 Vaccines; Headache Disorders; Headache
PubMed: 38097988
DOI: 10.1186/s12879-023-08898-2 -
American Journal of Otolaryngology 2024
Topics: Humans; COVID-19; Olfaction Disorders; SARS-CoV-2; Risk Factors; Smell; Taste Disorders
PubMed: 38029533
DOI: 10.1016/j.amjoto.2023.104114 -
Frontiers in Immunology 2023A series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context of various infections, such as COVID-19....
INTRODUCTION
A series of symptoms, including fever, widespread pain, fatigue, and even ageusia, have frequently been reported in the context of various infections, such as COVID-19. Although the pathogenic mechanisms underlying an infection causing fever and pain have been well established, the mechanisms of fatigue induced by infection in specific brain regions remain unclear.
METHODS
To elucidate whether and how the peripheral infection cause fatigue via regional neuroinflammation, we performed a brain-wide investigation of neuroinflammation in a peripheral pseudoinfection rat model using [F]DPA-714 positron emission tomography (PET) imaging analysis, in which the polyriboinosinic: polyribocytidylic acid (poly I:C) was intraperitoneally injected.
RESULTS
Transient fever lasting for several hours and subsequent suppression of spontaneous activity lasting a few days were induced by poly I:C treatment. Significant increase in plasma interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α were observed at 2 and 4 h following poly I:C treatment. PET imaging analysis revealed that the brain uptake of [F]DPA-714 was significantly increased in several brain regions one day after poly I:C treatment, such as the dorsal raphe (DR), parvicellular part of red nucleus (RPC), A5 and A7 noradrenergic nucleus, compared with the control group. The accumulation of [F]DPA-714 in the DR, RPC and A5 was positively correlated with subsequent fatigue-like behavior, and that in the A7 tended to positively correlate with fever.
DISCUSSION
These findings suggest that peripheral infection may trigger regional neuroinflammation, which may cause specific symptoms such as fatigue. A similar mechanism might be involved in COVID-19.
Topics: Rats; Animals; Neuroinflammatory Diseases; Positron-Emission Tomography; Pain; COVID-19; Poly I
PubMed: 38022622
DOI: 10.3389/fimmu.2023.1261256 -
Biomolecules Oct 2023COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19... (Review)
Review
COVID-19 patients can exhibit a wide range of clinical manifestations affecting various organs and systems. Neurological symptoms have been reported in COVID-19 patients, both during the acute phase of the illness and in cases of long-term COVID. Moderate symptoms include ageusia, anosmia, altered mental status, and cognitive impairment, and in more severe cases can manifest as ischemic cerebrovascular disease and encephalitis. In this narrative review, we delve into the reported neurological symptoms associated with COVID-19, as well as the underlying mechanisms contributing to them. These mechanisms include direct damage to neurons, inflammation, oxidative stress, and protein misfolding. We further investigate the potential of small molecules from natural products to offer neuroprotection in models of neurodegenerative diseases. Through our analysis, we discovered that flavonoids, alkaloids, terpenoids, and other natural compounds exhibit neuroprotective effects by modulating signaling pathways known to be impacted by COVID-19. Some of these compounds also directly target SARS-CoV-2 viral replication. Therefore, molecules of natural origin show promise as potential agents to prevent or mitigate nervous system damage in COVID-19 patients. Further research and the evaluation of different stages of the disease are warranted to explore their potential benefits.
Topics: Humans; COVID-19; Neuroprotective Agents; SARS-CoV-2; Nervous System Diseases; Encephalitis
PubMed: 38002267
DOI: 10.3390/biom13111585 -
Food Science & Nutrition Nov 2023Dietary creatine has been recently put forward as a possible intervention strategy to reduce post-COVID-19 fatigue syndrome yet no clinical study so far evaluated its...
Dietary creatine has been recently put forward as a possible intervention strategy to reduce post-COVID-19 fatigue syndrome yet no clinical study so far evaluated its efficacy and safety for this perplexing condition. In this parallel-group, randomized placebo-controlled double-blind trial, we analyzed the effects of 6-month creatine supplementation (4 g of creatine monohydrate per day) on various patient- and clinician-reported outcomes, and tissue creatine levels in 12 patients with post-COVID-19 fatigue syndrome. Creatine intake induced a significant increase in tissue creatine levels in vastus medialis muscle and right parietal white matter compared to the baseline values at both 3-month and 6-month follow-ups ( < .05). Two-way analysis of variance with repeated measures revealed a significant difference (treatment vs. time interaction) between interventions in tissue creatine levels ( < .05), with the creatine group was superior to placebo to augment creatine levels at vastus medialis muscle, left frontal white matter, and right parietal white matter. Creatine supplementation induced a significant reduction in general fatigue after 3 months of intake compared to baseline values ( = .04), and significantly improved scores for several post-COVID-19 fatigue syndrome-related symptoms (e.g., ageusia, breathing difficulties, body aches, headache, and difficulties concentrating) at 6-month follow-up ( < .05). Taking creatine for 6 months appears to improve tissue bioenergetics and attenuate clinical features of post-COVID-19 fatigue syndrome; additional studies are warranted to confirm our findings in various post-COVID-19 cohorts.
PubMed: 37970399
DOI: 10.1002/fsn3.3597 -
Expert Review of Clinical Pharmacology 2023This trial aimed to monitor the outcomes of persistent post-covid-19 smell and taste disorders after cerebrolysin therapy, a NTF, and olfactory and gustatory trainings. (Randomized Controlled Trial)
Randomized Controlled Trial
The effectiveness of cerebrolysin, a multi-modal neurotrophic factor, for treatment of post-covid-19 persistent olfactory, gustatory and trigeminal chemosensory dysfunctions: a randomized clinical trial.
BACKGROUND
This trial aimed to monitor the outcomes of persistent post-covid-19 smell and taste disorders after cerebrolysin therapy, a NTF, and olfactory and gustatory trainings.
RESEARCH DESIGN AND METHODS
This was a prospective randomized trial. It included 250 patients (male = 93, female = 157; age: 31.3 ± 8.9 years). Patients were randomized into group 1 ( = 150): received cerebrolysin [5 ml/d (IM), 5d/week] and practiced olfactory and gustatory trainings, and group 2 ( = 100): practiced olfactory and gustatory trainings only, for ≥ 8-24 weeks. Measures of outcomes were: a clinical questionnaire; sniffin' odor, taste and flavor identification tests; and global rating scales for smell and taste.
RESULTS
The duration of disorders was 11.7 ± 3.7mo (range: 6-24mo). The majority ( = 167; 66.8%) developed parosmia within months (3.6 ± 2.7mo) after anosmia. Objective testing showed anosmia in all and taste, flavor, and trigeminal sensory losses in 18% ( = 45). Analyses for secondary outcome were done on 202 patients (group 1 = 130; group 2 = 72). Recovery was complete in 61.5% ( = 80) with cerebrolysin therapy and partial in 17% ( = 22). There was no recovery with trainings only. There were no predictors for recovery.
CONCLUSIONS
Cerebrolysin had fast, promising, and constant effect, with cure rate of > 60%. This might be due to its ability to initiate and enhance neuronal regeneration and reorganization of sensory epithelia.
TRIAL REGISTRATION
NCT04830943.
Topics: Humans; Male; Female; Young Adult; Adult; Smell; COVID-19; Anosmia; Prospective Studies; Nerve Growth Factors
PubMed: 37950370
DOI: 10.1080/17512433.2023.2282715 -
Journal of Korean Medical Science Nov 2023Coronavirus disease 2019 (COVID-19) is known to have a high incidence of loss of smell and taste. However, studies in the early stages of the COVID-19 pandemic have...
BACKGROUND
Coronavirus disease 2019 (COVID-19) is known to have a high incidence of loss of smell and taste. However, studies in the early stages of the COVID-19 pandemic have evaluated these symptoms using subjective surveys and simple olfactory tests only. Hence, we compared the olfactory and gustatory characteristics of patient groups with COVID-19 olfactory dysfunction (C19OD) and non-COVID-19 postinfectious olfactory dysfunction (PIOD) using an objective olfactory test and evaluated the significance of olfactory training in both patient groups.
METHODS
We retrospectively analyzed the medical records of 14 patients with a decreased sense of smell after having positive COVID-19 polymerase chain reaction results, and 56 patients with PIOD with no history of confirmed COVID-19. Participants were evaluated using the Korean version of the Sniffin' stick (KVSS) II, and chemical gustometry and olfactory training was assessed during their first visit. Olfactory training was then re-evaluated after an average of 8 (± 6) weeks.
RESULTS
The average age of participants in the C19OD group was lower than in those in the non-COVID-19 PIOD group. The proportion of men in the C19OD group was higher than in the non-COVID-19 PIOD group. At baseline assessment, the C19OD group had better olfactory and gustatory functions. After olfactory training, the non-COVID-19 PIOD patient group showed a significant increase in all KVSS II Total, T, D, and I scores, but there was a non-significant increase in all scores in the C19OD group.
CONCLUSION
The C19OD group had better olfactory and gustatory function than the non-COVID-19 PIOD group at the initial assessment. After olfactory training, there was an increase in olfactory function test scores in both groups. Olfactory training may be helpful in C19OD, as in non-COVID-19 PIOD.
Topics: Male; Humans; Smell; COVID-19; Olfaction Disorders; Pandemics; Retrospective Studies
PubMed: 37935167
DOI: 10.3346/jkms.2023.38.e352 -
Cureus Sep 2023Introduction COVID-19 involvement in the nervous system has been reported in many cases. Viral neuroinvasion has multiple routes of entry. Neurological manifestations...
Neurological Manifestations in Hospitalized Geriatric Patients With COVID-19 at King Abdulaziz Medical City in Jeddah, Western Region, Saudi Arabia From 2020 to 2021: A Cross-Sectional Study.
Introduction COVID-19 involvement in the nervous system has been reported in many cases. Viral neuroinvasion has multiple routes of entry. Neurological manifestations of COVID-19 can be divided into ones of the central nervous system (CNS), such as headache, dizziness, altered mental status, ataxia, and seizure, and of the peripheral nervous system (PNS), including ageusia, anosmia, acute illness demyelinating polyneuropathy, and neuralgia. Aim and objectives This study aims to observe and report the neurological manifestations in geriatric patients who were diagnosed with COVID-19 at KAMC-J and report the duration of admission to the in-patient and ICU wards. Methods This was a cross-sectional study conducted on admitted geriatric patients with PCR-confirmed COVID-19 from April 1, 2020 to June 30, 2021 at KAMC-J. Using Raosoft®, the sample size was estimated with a CI of 95% and a 36.4% prevalence of neurological symptoms in COVID-19 patients to be 289. Convenience sampling was used, and the data were collected from BESTCare EMRs. IBM SPSS Statistics for Windows, Version 20 (Released 2011) was used for descriptive and inferential statistical analysis. Results In this study, a total of 290 patients' data were collected, 161 (55.5%) of which were males. In addition, the median age was 71 (Q1-Q3: 65-78) years; furthermore, the median body mass index (BMI) was 30(Q1-Q3: 25-34) kg/m. In descending order, the most prevalent comorbidities were hypertension (HTN) (70.3%), diabetes mellitus (DM) (68.6%), cardiac disease (42.1%), chronic kidney disease (26.6%), neurological disease (23.6%), cancer malignancy (13.1%), and finally chronic respiratory disease (11.4%). Regarding typical COVID-19 manifestations, 181 patients claimed to have experienced cough (62.4%), dyspnea by 164 (56.7%), fever by 154 (53.5%), fatigue by 93 (32.3%), a reading of anoxia by 68 (23.4%), abdominal pain by 58 (20.0%), diarrhea by 56 (19.4%), and finally throat pain by 19 (6.6%). Manifestations and pathologies of the CNS included headache (25.4%), dizziness (21.5%), impaired consciousness (17.2%), delirium (6.6%), ischemic stroke (4.1%), focal cranial nerve dysfunction (2.8%), seizure (2.8%), intracerebral hemorrhage (ICH) (0.3%), and ataxia (0.3%). Moreover, pathologies of the PNS manifested as taste impairment in 46 patients (15.9%), smell impairment in 33 (11.4%), nerve pain in 7 (24%), visual impairment in 5 (1.7%), Bell's palsy in 2 (0.7%), and Guillain-Barre syndrome in 1 (0.3%). Moreover, the majority of patients who developed an ischemic stroke or ICH, or required admission to the ICU had either DM or HTN. In addition, 17 (25.4%) of the 67 patients admitted to the ICU developed impaired consciousness. All-cause mortality in our study was 31 (10.71%) cases. Conclusion Neurological manifestations of COVID-19 are common and can result in serious complications if not detected and managed early, especially in the elderly. These complications are mostly seen in severely ill patients and may be the only symptoms in COVID-19 patients. In addition, patients' clinical conditions could deteriorate rapidly and result in significant morbidity and mortality. Therefore, a high index of suspicion is required among healthcare providers when dealing with such cases. Moreover, we recommend systematically collecting data on the short- and long-term neurological complications of COVID-19 globally and documenting the functional long-term outcomes after these complications.
PubMed: 37876390
DOI: 10.7759/cureus.45759 -
The European Journal of General Practice Dec 2023Early in the COVID-19 pandemic, GPs had to distinguish SARS-CoV-2 from other aetiologies in patients presenting with respiratory tract infection (RTI) symptoms on... (Observational Study)
Observational Study
BACKGROUND
Early in the COVID-19 pandemic, GPs had to distinguish SARS-CoV-2 from other aetiologies in patients presenting with respiratory tract infection (RTI) symptoms on clinical grounds and adapt management accordingly.
OBJECTIVES
To test the diagnostic accuracy of GPs' clinical diagnosis of a SARS-CoV-2 infection in a period when COVID-19 was a new disease. To describe GPs' management of patients presenting with RTI for whom no confirmed diagnosis was available. To investigate associations between patient and clinical features with a SARS-CoV-2 infection.
METHODS
In April 2020-March 2021, 876 patients (9 countries) were recruited when they contacted their GP with symptoms of an RTI of unknown aetiology. A swab was taken at baseline for later analysis. Aetiology (PCR), diagnostic accuracy of GPs' clinical SARS-CoV-2 diagnosis, and patient management were explored. Factors related to SARS-CoV-2 infection were determined by logistic regression modelling.
RESULTS
GPs suspected SARS-CoV-2 in 53% of patients whereas 27% of patients tested positive for SARS-CoV-2. True-positive patients (23%) were more intensively managed for follow-up, antiviral prescribing and advice than true-negatives (42%). False negatives (5%) were under-advised, particularly for social distancing and isolation. Older age (OR: 1.02 (1.01-1.03)), male sex (OR: 1.68 (1.16-2.41)), loss of taste/smell (OR: 5.8 (3.7-9)), fever (OR: 1.9 (1.3-2.8)), muscle aches (OR: 2.1 (1.5-3)), and a known risk factor for COVID-19 (travel, health care worker, contact with proven case; OR: 2.7 (1.8-4)) were predictive of SARS-CoV-2 infection. Absence of loss of taste/smell, fever, muscle aches and a known risk factor for COVID-19 correctly excluded SARS-CoV-2 in 92.3% of patients, whereas presence of 3, or 4 of these variables correctly classified SARS-CoV-2 in 57.7% and 87.1%.
CONCLUSION
Correct clinical diagnosis of SARS-CoV-2 infection, without POC-testing available, appeared to be complicated.
Topics: Humans; Male; COVID-19; SARS-CoV-2; Pandemics; COVID-19 Testing; Ageusia; Primary Health Care; Pain
PubMed: 37870070
DOI: 10.1080/13814788.2023.2270707