Onset Of Initial Symptoms Research Articles

Plasma p-tau181 associated with structural changes in mild cognitive impairment.

Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dementia and is a serious concern for the health of individuals and government health care systems worldwide. Gray matter atrophy and white matter damage are major contributors to cognitive deficits in AD patients, as demonstrated by magnetic resonance imaging (MRI). Many of these brain changes associated with AD begin to occur about 15years before the onset of initial clinical symptoms. Therefore, it is critical to find biomarkers reflective of these brain changes associated with AD to identify this disease and monitor its prognosis and development. The increased plasma level of hyperphosphorylated tau 181 (p-tau181) has been recently considered a novel biomarker for the diagnosis of AD, preclinical AD, and mild cognitive impairment (MCI). In the current study, we examined the association of cerebrospinal fluid (CSF) and plasma levels of p-tau181 with structural brain changes in cortical thickness, cortical volume, surface area, and subcortical volume in MCI patients. In this cross-sectional study, we included the information of 461 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The results of voxel-wise partial correlation analyses showed a significant negative correlation between the increased levels of plasma p-tau181, CSF total tau, and CSF p-tau181 with structural changes in widespread brain regions. These results provide evidence for the use of plasma p-tau181 as a diagnostic marker for structural changes in the brain associated with the early stages of AD and neurodegeneration.

A rare case of recurrent group A streptococcal vulvovaginitis in a premenopausal woman.

A rare case of recurrent group A streptococcal vulvovaginitis in a premenopausal woman.

Pediatric vestibular schwannoma without evidence of neurofibromatosis: consecutive 18 microsurgical experiences.

Sporadic vestibular schwannoma (VS) is rare in children in contrast to adults, and detailed investigations of case series of these patients using a single fixed protocol are scarce. This study presents our surgical experience of pediatric VSs without clinical evidence of neurofibromatosis type 2 (NF2) at the initial diagnosis. Among 1385 consecutive sporadic VS surgeries, 18 pediatric patients (1.3%; 11-18years old) were retrospectively investigated. The most common initial symptom was hearing disturbance (72.2%), and 6 patients (33.3%) experienced a delayed diagnosis (over 2years after initial symptom onset). Preoperative image characteristics of these tumors included a solid tumor, hypervascularity, and significant extension into the internal acoustic meatus, when compared with adults. Preoperative embolization was successfully accomplished for 2 recent hypervascular tumors. The tumor resection rate was 95-100% under sufficient intraoperative neuromonitoring, and no additional surgery was required during the follow-up period (average: 57.9months). No patients experienced permanent facial nerve palsy, and serviceable hearing function was preserved in 6 of 11 patients. Signs of NF2, such as bilateral VSs, were not identified in any patients during the follow-up. Safe and sufficient tumor resection was achieved under detailed neuromonitoring in pediatric patients with sporadic VS, although this tends to be difficult owing to hypervascularity, a small cranium, and significant meatal extension. Preoperative embolization may help safe resection of hypervascular tumors. Subsequent development of NF2 has not been observed up to the most recent follow-up, but careful observation is essential for these younger patients.

Relationship between Initial CT Value, Inflammatory Markers, and Onset of Clinical Symptoms with Outcomes of Treatment Outcomes of COVID-19 Patients at Dr. M. Djamil General Hospital Padang

Background: Treatment given for COVID-19 includes the provision of antiviral, anti-inflammatory, immunomodulatory, anticoagulant, and treatment of comorbidities and complications. The success of treatment in COVID-19 patients does not only depend on the drug given but is also influenced by clinical manifestations, clinical phase, and the presence or absence of complications and comorbidities. This study aims to assess the relationship between initial CT values, inflammatory markers, and symptom onset on treatment outcomes for COVID-19 patients at Dr. M. Djamil General Hospital Padang.
 Methods: This study is an observational analytic study with a retrospective cohort approach in confirmed COVID-19 patients treated at Dr. M. Djamil General Hospital Padang between 1st January – and 31st May 2021. The sample is the population that meets the inclusion criteria; confirmed COVID-19 from the results of RT PCR/TCM SARS-CoV-2, aged > 18 years, including the clinical degree of moderate, severe, critical illness. Exclusion criteria were patients with incomplete medical record data. Univariate analysis is intended to describe each research variable so that the distribution and percentage of each variable are presented in tabular form. Bivariate analysis using Chi-Square statistical test to see the relationship between variables.
 Results: COVID-19 patients being treated at Dr. M. Djamil General Hospital Padang were mostly in the age group above 50 years, namely 59.6%, and the female sex was treated more than the male, namely 55.5%. The moderate clinical grade is the highest proportion of hospitalized patients, namely 64.3%, followed by critical clinical 30.0% and severe clinical 5.6%. There is no relationship between the initial CT value and the outcome of COVID-19 patients. There is a relationship between IL-6 levels (initial) with the outcome of Covid-19 patients at Dr. M. Djamil General Hospital Padang. There is no relationship between the onset of clinical symptoms and the outcome of Covid-19 patients at Dr. M. Djamil General Hospital Padang.
 Conclusion: There is a relationship between IL-6 levels (initial) with patient outcomes, need for oxygen therapy, ferritin levels with the incidence of sepsis, initial albumin levels with initial D-Dimer levels, and IL-6 levels with D-dimers in COVID-19 patients at Dr. M. Djamil General Hospital Padang.

Avoiding Misdiagnosis and Missed Diagnosis for Appropriately Treating Spinal Osteoid Osteomas: A Single-Center Experience.

ObjectivesTo analyze the causes of misdiagnosis and missed diagnosis in spinal osteoid osteoma, and to put forward solutions to improve diagnosis accuracy and treatment efficacy in patients.MethodsWe performed a retrospective cohort study on patients with spinal osteoid osteoma in Beijing Jishuitan Hospital from January 1983 to September 2019. All patients underwent surgery. The outcome measures were the extent of local pain, nocturnal pain, radicular symptoms of extremities after surgery, and reduction or disappearance of lesions on CT after surgery.ResultsThirty‐seven patients with spinal osteoid osteoma were recruited in the study. A total of 27% were female, and the mean (SD) age at diagnosis was 21.3 (8.7) years. A total of 87.0% of patients presented with nocturnal pain, and 94.7% of patients were responsive to NSAIDS treatment. The mean (SD) time from the initial onset of symptoms to the final diagnosis was 14.7 (12.5) months. Only four of 37 (10.8%) patients were correctly diagnosed with spinal osteoid osteoma on the first visit to the local hospital. CT is associated with a higher diagnosis rate than X‐ray or MRI on the first visit. Surgical navigation was used in 88.9% of patients who underwent curettage resection, and in 10% of patients who underwent en bloc resection. A total of 37 of 37 patients (100%) reported relief of local pain and radicular symptoms of extremities after surgery, and no recurrence of tumors was found during follow‐ups.ConclusionsSpinal CTs are recommended to be performed if osteoid osteoma is suspected based on clinical manifestation, including nocturnal pain and responsiveness to NSAIDS treatment, to avoid misdiagnosis and missed diagnosis of spinal osteoid osteoma.

Factors Associated With Prehospital Delay Among Patients With Acute Myocardial Infarction in the Era of Percutaneous Coronary Intervention - Insights From the OACIS Registry.

The Japan Circulation Society launched the STOP-MI campaign in 2014, focusing on immediate hospital arrival for acute myocardial infarction (AMI) treatment. This study aimed to determine the factors influencing longer prehospital time among patients with AMI in Japan. This study analyzed a total of 4,625 AMI patients enrolled in the Osaka Acute Coronary Insufficiency Study registry from 1998 to 2014. The prehospital time delay was defined as the time interval from the onset of initial symptoms to hospital arrival time ≥2 h. Among eligible patients, 2,927 (63.3%) had a prehospital time ≥2 h. In multivariable analyses, age 65-79 years (adjusted odds ratio [AOR] 1.19, 95% confidence interval [CI] 1.02-1.39), age ≥80 years (AOR 1.42, 95% CI 1.13-1.79), diabetes mellitus (AOR 1.33, 95% CI 1.16-1.52), and onset time of 0:00-5:59 h (AOR 1.63, 95% CI 1.37-1.95) were positively associated with prehospital time ≥2 h, whereas smoking (AOR 0.78, 95% CI 0.68-0.90) and ambulance use (AOR 0.37, 95% CI 0.32-0.43) were negatively associated with prehospital time ≥2 h. Older age, diabetes mellitus, and nighttime onset were associated with prehospital time delay for AMI patients, whereas smoking and ambulance use were associated with no prehospital time delay. Healthcare providers and patients could help reduce the time to get to a medical facility by being aware of these findings.

Epstein-Barr virus and multiple sclerosis: supporting causality

Epstein-Barr virus (EBV) is a γ-herpes virus that infects around 95% of individuals worldwide. Although the infection is generally asymptomatic when acquired in childhood, EBV can cause infectious mononucleosis in adolescents and several tumours, like lymphomas and nasopharyngeal carcinoma, in adults. EBV has also been associated with multiple sclerosis, the most common chronic inflammatory disease of the CNS. Robust evidence indicates that the risk of multiple sclerosis is nearly absent in EBV-seronegative individuals, increases considerably after EBV infection, and increases even more after infectious mononucleosis. 1 Jacobs BM Giovannoni G Cuzick J Dobson R Systematic review and meta-analysis of the association between Epstein-Barr virus, multiple sclerosis and other risk factors. Mult Scler. 2020; 26: 1281-1297 Crossref PubMed Scopus (22) Google Scholar Furthermore, people with multiple sclerosis have an increased antibody response to EBV that becomes detectable years before disease onset. 2 Levin LI Munger KL Rubertone MV et al. Temporal relationship between elevation of Epstein-Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA. 2005; 293: 2496-2500 Crossref PubMed Scopus (334) Google Scholar , 3 Sundström P Juto P Wadell G et al. An altered immune response to Epstein-Barr virus in multiple sclerosis: a prospective study. Neurology. 2004; 62: 2277-2282 Crossref PubMed Scopus (246) Google Scholar These findings suggest that multiple sclerosis might develop in susceptible individuals due to an alteration of the EBV–host homoeostasis that ordinarily ensures a life-long, pacific coexistence under continuous immune surveillance in healthy EBV carriers. 4 Läderach F Münz C Epstein Barr virus exploits genetic susceptibility to increase multiple sclerosis risk. Microorganisms. 2021; 92191 Crossref Scopus (4) Google Scholar To date, however, most of the available evidence has been correlative in nature and it has been difficult to prove that EBV causes multiple sclerosis. 5 Olsson T Barcellos LF Alfredsson L Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017; 13: 25-36 Crossref PubMed Scopus (458) Google Scholar

Exploring New Characteristics: Using Deep Learning and 3D Reconstruction to Compare the Original COVID-19 and Its Delta Variant Based on Chest CT.

Purpose: Computer-aided diagnostic methods were used to compare the characteristics of the Original COVID-19 and its Delta Variant. Methods: This was a retrospective study. A deep learning segmentation model was applied to segment lungs and infections in CT. Three-dimensional (3D) reconstruction was used to create 3D models of the patient’s lungs and infections. A stereoscopic segmentation method was proposed, which can subdivide the 3D lung into five lobes and 18 segments. An expert-based CT scoring system was improved and artificial intelligence was used to automatically score instead of visual score. Non-linear regression and quantitative analysis were used to analyze the dynamic changes in the percentages of infection (POI). Results: The POI in the five lung lobes of all patients were calculated and converted into CT scores. The CT scores of Original COVID-19 patients and Delta Variant patients since the onset of initial symptoms were fitted over time, respectively. The peak was found to occur on day 11 in Original COVID-19 patients and on day 15 in Delta Variant patients. The time course of lung changes in CT of Delta Variant patients was redetermined as early stage (0–3 days), progressive and peak stage (4–16 days), and absorption stage (17–42 days). The first RT-PCR negative time in Original COVID-19 patients appeared earlier than in Delta Variant patients (22 [17–30] vs. 39 [31–44], p < 0.001). Delta Variant patients had more re-detectable positive RT-PCR test results than Original COVID-19 patients after the first negative RT-PCR time (30.5% vs. 17.1%). In the early stage, CT scores in the right lower lobe were significantly different (Delta Variant vs. Original COVID-19, 0.8 ± 0.6 vs. 1.3 ± 0.6, p = 0.039). In the absorption stage, CT scores of the right middle lobes were significantly different (Delta Variant vs. Original COVID-19, 0.6 ± 0.7 vs. 0.3 ± 0.4, p = 0.012). The left and the right lower lobes contributed most to lung involvement at any given time. Conclusion: Compared with the Original COVID-19, the Delta Variant has a longer lung change duration, more re-detectable positive RT-PCR test results, different locations of pneumonia, and more lesions in the early stage, and the peak of infection occurred later.

Cardiac MRI in Suspected Acute Myocarditis After COVID-19 mRNA Vaccination.

To evaluate cardiac MRI characteristics in patients with suspected hypersensitivity myocarditis following mRNA COVID-19 vaccination. Patients clinically suspected of acute myocarditis after COVID-19 vaccination were retrospectively analyzed and compared against a healthy control group. Cardiac MRI protocol included parameters such as T1 and T2 relaxation times, extracellular volume (ECV), T2 signal intensity ratio, and late gadolinium enhancement (LGE). Lymph node size was assessed in the patient group on the injection side. Student t-test, analyses of variance (ANOVA) with Tukey post-hoc test, and χ2 test were used for statistical analysis. 20 patients with clinically suspected post-vaccine myocarditis (28 ± 12 years; 12 men) and 40 controls (31 ± 11years; 25 men) were evaluated. According to the 2018 Lake Louise criteria (LLC), patients with clinically suspected myocarditis were further subdivided into an LLC-positive group (n = 9) and an LLC-negative group (n = 11). The mean time of symptom onset after vaccination was 1.1 ± 1.2 days (LLC-positive) and 6.5 ± 9.2 days (LLC-negative). Group differences in inflammatory variables between myocarditis patients and control subjects were more pronounced in the LLC-positive group (e. g., T1 relaxation time: 1041 ± 61 ms [LLC positive] vs. 1008 ± 79 ms [LLC-negative] vs. 970 ± 25 ms [control]; p <.001; or T2 signal intensity ratio 2.0 ± 0.3 vs. 1.6 ± 0.3 [LLC-negative] and vs. 1.6 ± 0.3 [control], p = .012). LLC-positive patients were significantly faster in receiving an MRI after initial symptom onset (8.8 ± 6.1 days vs. 52.7 ± 33.4 days; p = .001) and had higher troponin T levels (3938 ± 5850 ng/l vs. 9 ± 11 ng/l; p <.001). LGE lesions were predominantly located at the subepicardium of the lateral wall. Axillary lymphadenopathy was more frequent in the LLC-positive group compared to the LLC-negative group (8/9 [89 %] vs. 0/11 [0 %], p < 0.001). Vaccine-induced myocarditis should be considered in patients with acute symptom onset after mRNA vaccination, especially if elevated serum troponin T is observed. Imaging findings of vaccine-induced myocarditis are similar to virus-induced myocarditis, allowing for the use of the Lake Louise Criteria for diagnostic purposes. · Vaccine-induced hypersensitivity myocarditis can be confirmed with cardiac MRI. · Especially patients with sudden onset of symptoms and elevated serum troponin T had positive cardiac MRI findings. · Cardiac MRI characteristics of vaccine-induced myocarditis are similar to those in virus-induced myocarditis. · Kravchenko D, Isaak A, Mesropyan N et al. Cardiac MRI in Suspected Acute Myocarditis After COVID-19 mRNA Vaccination. Fortschr Röntgenstr 2022; 194: 1003 - 1011.

High-Dose Convalescent Plasma for Treatment of Severe COVID-19.

To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.

Zika Virus Infection of Sertoli Cells Alters Protein Expression Involved in Activated Immune and Antiviral Response Pathways, Carbohydrate Metabolism and Cardiovascular Disease.

Zika virus (ZIKV), a re-emerging virus, causes congenital brain abnormalities and Guillain–Barré syndrome. It is mainly transmitted by Aedes mosquitoes, but infections are also linked to sexual transmissions. Infectious ZIKV has been isolated, and viral RNA has been detected in semen over a year after the onset of initial symptoms, but the mode of long-term persistence is not yet understood. ZIKV can proliferate in human Sertoli cells (HSerC) for several weeks in vitro, suggesting that it might be a reservoir for persistent ZIKV infection. This study determined proteomic changes in HSerC during ZIKV infections by TMT-mass spectrometry analysis. Levels of 4416 unique Sertoli cell proteins were significantly altered at 3, 5, and 7 days after ZIKV infection. The significantly altered proteins include enzymes, transcription regulators, transporters, kinases, peptidases, transmembrane receptors, cytokines, ion channels, and growth factors. Many of these proteins are involved in pathways associated with antiviral response, antigen presentation, and immune cell activation. Several immune response pathway proteins were significantly activated during infection, e.g., interferon signaling, T cell receptor signaling, IL-8 signaling, and Th1 signaling. The altered protein levels were linked to predicted activation of immune response in HSerC, which was predicted to suppress ZIKV infection. ZIKV infection also affected the levels of critical regulators of gluconeogenesis and glycolysis pathways such as phosphoglycerate mutase, phosphoglycerate kinase, and enolase. Interestingly, many significantly altered proteins were associated with cardiac hypertrophy, which may induce heart failure in infected patients. In summary, our research contributes to a better understanding of ZIKV replication dynamics and infection in Sertoli cells.

Human Nasal Epithelial Cells Sustain Persistent SARS-CoV-2 Infection In Vitro, despite Eliciting a Prolonged Antiviral Response.

ABSTRACTThe dynamics of SARS-CoV-2 infection in COVID-19 patients are highly variable, with a subset of patients demonstrating prolonged virus shedding, which poses a significant challenge for disease management and transmission control. In this study, the long-term dynamics of SARS-CoV-2 infection were investigated using a human well-differentiated nasal epithelial cell (NEC) model of infection. NECs were observed to release SARS-CoV-2 virus onto the apical surface for up to 28 days postinfection (dpi), further corroborated by viral antigen staining. Single-cell transcriptome sequencing (sc-seq) was utilized to explore the host response from infected NECs after short-term (3-dpi) and long-term (28-dpi) infection. We identified a unique population of cells harboring high viral loads present at both 3 and 28 dpi, characterized by expression of cell stress-related genes DDIT3 and ATF3 and enriched for genes involved in tumor necrosis factor alpha (TNF-α) signaling and apoptosis. Remarkably, this sc-seq analysis revealed an antiviral gene signature within all NEC cell types even at 28 dpi. We demonstrate increased replication of basal cells, absence of widespread cell death within the epithelial monolayer, and the ability of SARS-CoV-2 to replicate despite a continuous interferon response as factors likely contributing to SARS-CoV-2 persistence. This study provides a model system for development of therapeutics aimed at improving viral clearance in immunocompromised patients and implies a crucial role for immune cells in mediating viral clearance from infected epithelia.

Retinal findings of COVID-19 patients using ocular coherence tomography angiography two to three months after infection: Ocular appearance recovered COVID-19 patient

PurposeThe aim of this study was to evaluate the ocular disorders in COVID-19 patients, two to three months after infection. MethodsIn this cross-sectional, historically controlled study, fifty-one COVID-19 patients were compared with thirty-seven age, and gender-matched healthy individuals. After complete ophthalmological examination, all participants underwent peripapillary and macular optical coherence tomography, and optical coherence tomography angiography (OCTA) measurements (OptoVue Inc, Freemont, CA, USA). ResultsThe time between the initial onset of symptoms, and ophthalmologic examination was 63.31±15.21 (40–95 days). Ophthalmic examination of all the recovered COVID-19 patients was within normal range. None of the peripapillary and macular OCTA parameters were significantly different between the two groups with pairwise comparisons, but after adjusting for age, gender, axial length, and signal strength index (SSI), recovered COVID-19 eyes showed a significant increase in peripapillary retinal nerve fiber (RNFL) thickness, superficial, and deep macular vessel densities in parafoveal and perifoveal regions compared with healthy control eyes (p<= 0.05). Inner retinal thickness overall is higher in recovered COVID-19 eyes compared to healthy eyes after adjustment. ConclusionPatients with moderate-intensity SARS-CoV-2 pneumonia had altered peripapillary and macular vessel density compared to healthy subjects. Further investigation is warranted to analyze the correlation of these changes with disease severity as well as evolution of these changes over time.

Peripheral Blood Mononuclear Cell Cytokine mRNA Profiles in Acute Respiratory Infection Patients.

Respiratory infections, collectively, are one of the World's most common and serious illness groups. As recent observations have shown, the most severe courses of acute respiratory infection, often leading to death, are due to uncontrolled cytokine production (hypercytokinemia). The study involved 364 patients with respiratory illness being treated in clinics in St. Petersburg (Russia) in 2018-2019 and 30 healthy controls. Cytokine analysis was carried out in the acute phase of illness (2-3 days from onset of initial symptoms) and in the stage of recovery (days 9-10). The research presented is devoted to the assessment of mRNA expression of specific cytokines (interleukin [IL]-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α [TNF-α], and interferon-λ) and MxA in whole blood leukocytes, by means of real-time polymerase chain reaction. In 70% of patients, bacterial or viral pathogens were identified, with influenza viral infections (types A and B) prevailing. Significant increases in the expression of IL-18, TNF, and IL-10 were observed, relative to controls, only with influenza viral infections. We have shown a difference in IL-6 mRNA expression in patients with bacterial or viral pathogens. No statistically significant difference was found in white blood cells IL-4 expression levels between patients and healthy controls. Investigation of the nuances of systemic cytokine production, in response to specific viral and bacterial pathogens, makes it possible to assess the risks of developing hypercytokinemia during respiratory infection with agents circulating in the human population and to predict the pathogenicity and virulence of circulating threats.

Increased Healthcare Delays in Tuberculosis Patients During the First Wave of COVID-19 Pandemic in Korea: A Nationwide Cross-Sectional Study.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems, consequently endangering tuberculosis (TB) control. We investigated delays in TB treatment among notified patients during the first wave of the COVID-19 pandemic in Korea.MethodsWe systemically collected and analyzed data from the Korea TB cohort database from January to May 2020. Groups were categorized as ‘before-pandemic’ and ‘during-pandemic’ based on TB notification period. Presentation delay was defined as the period between initial onset of symptoms and the first hospital visit, and healthcare delay as the period between the first hospital visit and anti-TB treatment initiation. A multivariate logistic regression analysis was performed to evaluate factors associated with delays in TB treatment.ResultsProportion of presentation delay > 14 days was not significantly different between two groups (48.3% vs. 43.7%, P = 0.067); however, proportion of healthcare delay > 5 days was significantly higher in the during-pandemic group (48.6% vs. 42.3%, P = 0.012). In multivariate analysis, the during-pandemic group was significantly associated with healthcare delay > 5 days (adjusted odds ratio = 0.884, 95% confidence interval = 0.715–1.094).ConclusionThe COVID-19 pandemic was associated with healthcare delay of > 5 days in Korea. Public health interventions are necessary to minimize the pandemic’s impact on the national TB control project.

289. Post COVID Syndrome Cohort Characterization

BackgroundPost COVID Syndrome (PCS) is significant morbidity following COVID-19. This study aims to identify biomarkers that predict PCS in a Gulf Coast cohort known for poor health outcomes.MethodsSince March 2020 the study Collection of Serum and Secretions for SARS CoV-2 Countermeasure Development (aka ClinSeqSer) has been enrolling subjects with confirmed acute COVID-19, with initial visit at 1 month and follow up every three months from symptom onset. At follow-up, subjects complete symptom questionnaire, physical examination, nasopharyngeal swab/saliva collection, blood draw. Subjects with >= one symptom new since COVID are PCS, remainder are Non-PCS experienced at initial one month visit and six months or longer. Univariate and bivariate analysis was carried out to study significant associations of currently available dataset (N=60).Figure 1. Post-COVID Symptoms Included if “new since covid”. For 60 subjects consented post-covid with completed questionnaire, results were analyzed. Most common symptoms reported were fatigue/tiredness or exhaustion (52%), muscle aches (38%), difficulty concentrating (33%) and headache (32%) as the most common symptoms during one month prior to their initial follow-up visit. The persistent symptoms experienced for six months or longer were fatigue/tiredness or exhaustion (25%), forgetfulness (22%), muscle aches (18%), and sleep difficulties (18%).ResultsCohort is 36 (60%) female, 24 (40%) male, age group of 49 (82%) 18-64 years, 11 (18%) 65+ years, 33 (55%) African American, 27 (45%) Caucasian. Median follow-up time after symptom onset: 290 days. Study cohort reported fatigue (52%), myalgias (38%), difficulty concentrating (33%), headache (32%) as most common symptoms during first month from initial symptom onset. Persistent symptoms ( >=6 months) are fatigue (25%), forgetfulness (22%), myalgias (18%), sleep difficulties (18%). Bivariate analysis shows that gender (female, P=0.04), past stroke/transient ischemic attack (P=0.04), deep venous thrombosis (P=0.02), abnormal kidney function (P=0.01) associate with PCS. Convalescent antibodies (ReSARS N IgG, S-RBD IgG) were measured and percentage inhibition of ACE2 spike interaction was recorded. Plasma inflammatory protein levels were measured using multiplex ELISA and Proximity Extension Assay technology during follow-up visit. Increased antibody ReSARS N IgG (2.91, 0.74-10.93; P=0.02) response and higher convalescent IL-10 (P=0.04) was associated with PCS. Percent inhibition of ACE2: spike interaction was not associated (P=0.79) with PCS. Nasal swab/saliva SARS-COV-2 sequencing has not identified a specific SARS-CoV-2 virus mutation predictive of PCS. Table 1. Demographic and Clinical Characteristics The bivariate analysis results showed that the gender (female, P=0.0354), history of stroke or transient ischemic attack (P=0.0382), chest pain from narrow heart vessels (P=0.0479), deep venous thrombosis (P=0.0241) and abnormal kidney function (P=0.0142) were associated with Post-COVID syndrome.Table 2. Antibodies and ACE2 spike inhibition. The convalescent antibodies, ReSARS N IgG and S-RBD IgG were measured in U/mL and percentage inhibition of ACE2 spike interaction was recorded during follow-up visit for PCS vs Non-PCS subjects. The increased antibody ReSARS N IgG (2.91, 0.74-10.93; P=0.0159) response was associated with Post-COVID syndrome. Percent inhibition of ACE2: spike interaction was not associated (P=0.7932) with PCS.Table 3. Plasma inflammatory protein levels. Plasma inflammatory protein levels were measured using multiplex ELISA (MSD) and Proximity Extension Assay technology (Olink) recorded during follow-up visit for PCS vs Non-PCS subjects, revealing IL-10 (P=0.0379) was associated with development of PCS.ConclusionThis study identifies initial clinical and biomarker predictors of PCS in a cohort that is 55% African American.Figure 2. Antibody ReSARS N IgG ReSARS N IgG measured in post-covid patients is significantly associated with post-COVID syndrome(P=0.0159). X axis: number of months from symptom onset to blood draw. Y axis: N IgG U/mL.Figure 3. Spike amino acid mutations Spike amino acid mutations detected in SARS-CoV-2 from acute-phase respiratory isolates. Nasal swab/saliva samples were collected from subjects with acute COVID-19 at time of enrollment into ClinSeqSer, stored at -80°C followed by RNA isolation and SARS-CoV-2 qRT-PCR. Samples with Ct value of ≤30 were then sequenced using NextSeq (Illumina). All sequences are deposited on GISAID and under BioProject (ID PRJNA681020). X axis: subject ID, with ID number increasing chronologically. Y axis: amino acid position of each mutation moving from N- to C-terminus.Disclosures Robert Garry, PhD, Zalgen Labs (Shareholder)

Intracompartmental pressure in lower leg muscles and tibial nerve in healthy volunteers correlate to the stiffness measured using shear wave elastography

BackgroundAcute compartment syndrome in the lower leg is a painful condition characterized by an increase in intracompartmental pressure. To prevent misdiagnosis and delay in the recognition of the condition, which can lead to severe complications, continuous monitoring of intracompartmental pressure for at least 24 h. from the onset of initial symptoms has been recommended. The purpose of the current study was to establish shear wave elastography as a potential imaging biomarker for the observed increase in pressure in four compartments of the lower leg. MethodsEighteen healthy participants (9 males) without any injury in their leg muscles were recruited for the study after internal review board approval. Subjects were instructed to sit on a table and pressures at 60, 90, and 120 mmHg were applied using a pressure cuff placed above the proximal pole of the patella. Shear wave elastography-measured stiffness outcomes at baseline (0 mmHg) and at each cuff pressure level were obtained from the tibialis anterior, the peroneus longs, gastrocnemius medialis, and tibialis posterior muscles, as well as the tibial nerve. FindingsSpearman's rank correlation coefficient showed strong correlations between shear wave elastography-measured stiffness from all four muscles and cuff pressure levels (r > 0.80, P < 0.05). Stiffness from the tibial nerve was also significantly correlated with cuff pressure levels (r > 0.99, P < 0.05). InterpretationShear wave elastography imaging of lower leg muscles and nerve can be useful to non-invasively monitor intracompartmental pressure in patients suspected of acute compartment syndrome.

508 The Early Use of Intratympanic Steroid Injections in the Treatment of Labyrinthitis Obliterans – A Case Report

Abstract Introduction Labyrinthitis Obliterans is an inner ear condition characterised by pathological sclerosis and ossification of the membranous labyrinth as a response to inflammatory insult. It is associated with profound sensorineural hearing loss and occasionally dizziness and/or vertigo.In this case report, we describe the use of intratympanic steroid injections in a patient presenting with sudden sensorineural hearing loss (SSNHL) with a radiological diagnosis of Labyrinthitis Obliterans. Whilst many studies suggest the role of oral steroids in SSNHL, there is no current evidence regarding the role of intratympanic steroid injections specifically for the treatment of this condition. Case Presentation A 60-year-old gentleman was referred to ENT with a 3-day history of sudden right sided hearing loss. There was no improvement in his Pure Tone Audiometry (PTA) results after 7 days of oral Prednisolone. Subsequently, an MRI Internal Acoustic Meatus showed evidence of right sided Labyrinthitis Obliterans. The patient was initiated on a course of intratympanic Methylprednisolone injections 10 days after initial onset of symptoms. A significant improvement in his baseline hearing of over 60dB was demonstrated after 4 courses of injections over a 3-month period. Discussion Our findings reveal that despite a diagnosis of Labyrinthitis Obliterans, the early use of intratympanic steroid injections can significantly improve hearing threshold and quality of life of the patient. The biggest hurdle in the management of Labyrinthitis Obliterans is establishing the diagnosis early and ensuring timely treatment, therefore we would advocate the early use of MRI and early intervention with intratympanic steroid injections.

Chronic bee paralysis virus - quo vadis? Incidence in Bavaria and consideration of therapeutic measures

Chronic bee paralysis virus (CBPV), a so far unclassified RNA virus that may cause neurological signs and hairless black syndrome in honey bees, has become increasingly prevalent in various European countries in recent years. The disease occasionally leads to immense losses of worker bees and a significant drop in performance, especially in strong colonies. The aim of this retrospective study was to analyse the spread of CBPV in Bavaria from 2018 to 2020 as well as to evaluate therapeutic measures. In part 1 of the study, analysis results of the Tiergesundheitsdienst Bayern e. V. (Bavarian Animal Health Service) from 302 bee colonies were examined with regard to virus diagnostics and clinical signs with a focus on CBPV. In part 2, data collected with the help of a questionnaire regarding 105 CBPV-positive and symptomatic colonies were evaluated. In part 1, a significant (p = 0.004) increase in CBPV-positive samples from 2018 to 2020 was detected within Bavaria. In addition, the number of cases with clinical signs also increased during the last 2 years. Part 2 of the study showed a clustering of reports of initial onset of CBPV symptoms during springtime. The colonies mostly with a combination of symptoms recovered from the disease in 57 % of the cases. Therapeutic intervention was one decisive factor. A large number of different combinations of measures led to survival, and a lack of intervention mostly resulted in the death of the colony. In 62 % of the diseased and isolated colonies, isolation prevented further spread in the apiary. Based on the results, CBPV occurred more frequently in connection with clinical signs in Bavaria in recent years. Due to the large number of applied combinations of measures, no evidence-based therapy recommendation may be derived based on the current evaluations. However, it has been shown that any therapeutic intervention is superior to withholding treatment. For precise therapy recommendations, trials with treatment under standard conditions are necessary.

Incidence and duration of self-reported hearing loss and tinnitus in a cohort of COVID-19 patients with sudden chemosensory loss: A STROBE observational study

AimsTo investigate the self-reported audiological symptoms in a cohort of coronavirus disease 2019 (COVID-19) patients and monitor improvement or recovery. Material and methodsFollowing the STROBE guidelines for observational studies, a retrospective questionnaire concerning audio-vestibular symptoms was conducted in a cohort of Danish COVID-19 patients with self reported chemosensory loss. Data regarding demographics, symptoms onset, duration and remission was registered in a REDCap database. ResultsOf the 225 respondents with chemosensory loss, 59 (26.2%) reported concomitant hearing loss (10.7%) or tinnitus (16.4%). In a follow-up questionnaire focused on ear-symptoms, severity, and duration (n=31), 17 reported hearing loss and 21 reported tinnitus. Debut of hearing loss and tinnitus were on average 10 and 30 days respectively, after onset of initial symptoms. Among the hearing loss patients, only two patients experienced full recovery, whereas 15 had partial or no recovery after on average 266 days from COVID-19 symptom onset. Among the tinnitus patients, 7/21 had full recovery, while 14 had partial or no recovery after on average 259 days from COVID-19 symptom onset. ConclusionIn a large Danish cohort of COVID-19 patients, a significant proportion experienced concomitant audiological symptoms which seem long lasting and with negative impact on quality of life. This study warrants further investigation of the association between COVID-19 and audio-vestibular symptoms, and the need for rehabilitation among convalescents.