EFFECT OF FULL VACCINATION AND POST-COVID OLFACTORY DYSFUNCTION IN RECOVERED COVID-19 PATIENT. A RETROSPECTIVE LONGITUDINAL STUDY WITH PROPENSITY MATCHING.

Background Symptoms after Coronavirus Disease (COVID-19) infection affect the quality of life of its survivor especially to the special senses including olfactory function. It is important to prevent the disability at an earlier stage. Vaccination as key prevention has been proven to be effective in reducing symptomatic disease and severity. However, the effects of vaccination on post COVID symptoms have not been evaluated. This study aimed to evaluate the possible protection of full vaccination and the occurrence of post-COVID olfactory dysfunction, specifically anosmia, and hyposmia in patients who were diagnosed with COVID-19. Method A longitudinal analysis using the retrospective cohort of the Indonesian patient-based Post-COVID-19 survey collected from July 2021 until December 2021, involving COVID-19 Patients confirmed by Real-Time Polymerase Chain Reaction (RT-PCR) and/or Antigen test. Variables including demography, comorbidities, health behavior, type of vaccine, symptoms, and treatment were collected through an online questionnaire based on the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). Participants were matched (1:1) using propensity matching score into two exposure statuses, infected 1)>14 days of full vaccination and 2)<14 days or incomplete or unvaccinated. The olfactory dysfunction was assessed two weeks and four weeks after negative conversion with PCR using a self-measured olfactory questionnaire (MOQ). The Generalized Estimating Equation (GEE) was performed to assess the effect of full vaccination on post-COVID-19 olfactory dysfunction. The Receiver Operating Characteristic determined the sensitivity and specificity of the cutoff value of the days from fully vaccinated to diagnosis and the olfactory dysfunction. Results A total of 442 participants were extracted from the cohort and inoculated with the inactivated viral vaccine (99.5%). The prevalence of olfactory dysfunction in two weeks was 9.95% and 5.43% after four weeks. Adjusted by other variables, people who were infected >14 days after being fully vaccinated had a 69% (adjusted Odds Ratio / aOR 0.31 95% CI 0.102-0.941) probability of developing olfactory dysfunction. Longer days of fully vaccinated to infection are associated with increased risk (aOR 1.012 95% CI 1.002-1.022 p-value 0.015). A cut-off of 88 days of full vaccination-to-diagnosis duration has Area Under Curve (AUC) of 0.693 (p=0.002), the sensitivity of 73.9%, and specificity of 63.3% in differentiating the olfactory dysfunction event in two weeks after COVID-19 with a crude odds ratio of 4.852 (95% CI 1.831-12.855 p=0.001) Conclusion After 14 days of full vaccination, the protective effect could reduce the chance of post-COVID olfactory dysfunction although a longer full vaccination-to-diagnosis duration increases the risk. It is important to consider a booster shot starting from 89 days after the last dose in those who received the inactivated viral regimen.

Pediatric Urachal Anomalies: Monocentric Experience and Mini-Review of Literature

Background: Surgery is the current mainstay for the treatment of urachal anomalies (UA). Recent literature data support the theory of a spontaneous resolution within the first year of life. The aim of this study, comprising solely surgically treated children, was to identify age specific patterns regarding symptoms and outcomes that may support the non-surgical treatment of UA. Methods: Retrospective review on the clinico-laboratory characteristics of 52 children aged < 17 years undergoing resection of symptomatic UA at our pediatric surgical unit during 2006–2017. Data was dichotomized into age > 1 (n = 17) versus < 1 year (n = 35), and complicated (pre-/post-surgical abscess formation or peritonitis, n = 10) versus non-complicated course (n = 42). Results: Children aged < 1 year comprised majority (67%) of cohort and had lower complication rates (p = 0.062). Complicated course at surgery exclusively occurred in patients aged > 1 year (p = 0.003). Additionally, complicated group was older (p = 0.018), displayed leukocytosis (p < 0.001) and higher frequencies regarding presence of abdominal pain (p = 0.008) and abdominal mass (p = 0.034) on admission. Regression analysis identified present abdominal pain (OR (95% CI), 11.121 (1.152–107.337); p = 0.037) and leukocytosis (1.435 (1.070–1.925); p = 0.016) being associated with complicated course. Conclusions: This study provides evidence that symptomatic disease course follows an age-dependent complication pattern with lower complication rates at age < 1 year. Larger, studies have to clarify, if waiting for spontaneous urachal obliteration during the first year of life comprises a reasonable alternative to surgery.

Nosocomial Transmission of SARS-CoV-2 Involving Vaccinated Health Care Workers

COVID-19 vaccination has proven to be effective at preventing symptomatic disease but there are scarce data to fully understand whether vaccinated individuals can still behave as SARS-CoV-2 transmission vectors. Based on viral genome sequencing and detailed epidemiological interviews, we report a nosocomial transmission event involving two vaccinated health care-workers (HCWs) and four patients, one of them with fatal outcome.

Nocebo effect in multiple system atrophy: systematic review and meta-analysis of placebo-controlled clinical trials

Background Nocebo effect is prevalent among neurological diseases, resulting in low adherence and treatment outcome. We sought to examine the nocebo effect in randomized controlled trials (RCTs) in multiple system atrophy (MSA). Methods We searched RCTs in MSA from Medline since September, 2021. RCTs for drug treatment conducted in adult MSA patients with more than 5 cases in each treatment arm were included. We assessed the number of dropout due to placebo intolerance. We also did a symptomatic/disease-modifying subgroup analysis based on two different treatment purposes. The STATA software was used for statistical analysis. Overall heterogeneity was assessed using the Cochran Q and I2. Results Data were extracted from 11 RCTs fulfilling our search criteria. Of 540 placebo-treated patients, 64.2% reported at least one adverse event (AE) and 7.5% reported dropout because of AEs. The chance of dropping out because of an AE and experiencing at least one AE did not differ between placebo and active drug treatment arms. Besides, the pooled nocebo dropout rate in the symptomatic subgroup was similar to that of the disease-modifying subgroup. Conclusion In MSA RCTs, nocebo dropout rate was not at a low level among neurological disorders. Nocebo effect was an important reason of dropout because of AE in placebo and active drug treatment arms. Different treatment purposes may not influence nocebo effect.

Incidence of COVID-19 after pulmonary function tests: a retrospective cohort study

Introduction: It has been proposed that exposure to pulmonary function tests (PFT) could be associated with a higher risk of viral transmission. The risk of the Coronavirus Disease 2019 (COVID-19) transmission after performing PFT is unknown. We aimed to assess the incidence of COVID-19 after a PFT at an academic teaching facility in Buenos Aires, Argentina. Materials and methods: We conducted a retrospective cohort study including all consecutive adult patients that performed PFT between April 1, 2020 and September 30, 2020. Patients with prior COVID-19 were excluded. We defined a 15-day time window to ascertain PFT related COVID-19. The primary outcome was ascertained by consulting a national database, which has information on all patients with nasopharyngeal swabs for SARS-CoV-2 in Argentina. Results: We included 278 patients who performed a PFT. Fifty percent were women, the mean age was 54 years (SD 18), and the main comorbidities were obesity (31%), smoking (31%), hypertension (29%), and chronic lung disease (28%). The main indication for performing PFT was anesthetic preoperative risk assessment. Swabs were collected from 27 patients (10%). Twenty-two swabs (8%) were taken according to surgical protocols; five swabs (2%) were taken due to clinical suspicion of COVID-19, with only one testing positive. The cumulative incidence of COVID-19 after PFT was 0.36% (95% CI 0.01-20%). None of the technicians developed symptomatic disease. Conclusion: Given the right setting and strict adherence to international recommendations, the SARS-CoV-2 infection after having a PFT appears to be low, which follows that these procedures can be performed safely for both patients and staff.

Osteoarthritis Medication and Overview: A Narrative Review

Osteoarthritis, the most common form of joint disease, is primarily a disease of aging. Ninety percent of all people have radiographic features of osteoarthritis in weight-bearing joints by age 40. Symptomatic disease increases with age. Risk factors for this disorder include gender, genetics, obesity, and work history. Osteoarthritis develops in women more often than in men. This arthropathy is characterized by cartilage degeneration and bony hypertrophy at the articular margins. Inflammation is usually minimal. Hereditary and mechanical factors may be involved in the pathogenesis. This review provides an overview of counseling osteoarthritis and its treatment and management.

Potential SARS-CoV-2 infectiousness among asymptomatic healthcare workers

A majority of SARS-CoV-2 infections are transmitted from a minority of infected subjects, some of which may be symptomatic or pre-symptomatic. We aimed to quantify potential infectiousness among asymptomatic healthcare workers (HCWs) in relation to prior or later symptomatic disease. We previously (at the onset of the SARS-CoV-2 epidemic) performed a cohort study of SARS-CoV-2 infections among 27,000 healthcare workers (HCWs) at work in the capital region of Sweden. We performed both SARS-CoV-2 RT-PCR and serology. Furthermore, the cohort was comprehensively followed for sick leave, both before and after sampling. In the present report, we used the cohort database to quantify potential infectiousness among HCWs at work. Those who had sick leave either before or after sampling were classified as post-symptomatic or pre-symptomatic, whereas the virus-positive subjects with no sick leave were considered asymptomatic. About 0.2% (19/9449) of HCW at work were potentially infectious and pre-symptomatic (later had disease) and 0.17% (16/9449) were potentially infectious and asymptomatic (never had sick leave either before nor after sampling). Thus, 33% and 28% of all the 57 potentially infectious subjects were pre-symptomatic or asymptomatic, respectively. When a questionnaire was administered to HCWs with past infection, only 10,5% of HCWs had had no indication at all of having had SARS-CoV-2 infection (“truly asymptomatic”). Our findings provide a unique quantification of the different groups of asymptomatic, potentially infectious HCWs.

Progression of Myeloproliferative Neoplasms (MPN): Diagnostic and Therapeutic Perspectives

Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) are a heterogeneous group of hematologic malignancies, including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), as well as post-PV-MF and post-ET-MF. Progression to more symptomatic disease, such as overt MF or acute leukemia, represents one of the major causes of morbidity and mortality. There are clinically evident but also subclinical types of MPN progression. Clinically evident progression includes evolution from ET to PV, ET to post-ET-MF, PV to post-PV-MF, or pre-PMF to overt PMF, and transformation of any of these subtypes to myelodysplastic neoplasms or acute leukemia. Thrombosis, major hemorrhage, severe infections, or increasing symptom burden (e.g., pruritus, night sweats) may herald progression. Subclinical types of progression may include increases in the extent of bone marrow fibrosis, increases of driver gene mutational allele burden, and clonal evolution. The underlying causes of MPN progression are diverse and can be attributed to genetic alterations and chronic inflammation. Particularly, bystander mutations in genes encoding epigenetic regulators or splicing factors were associated with progression. Finally, comorbidities such as systemic inflammation, cardiovascular diseases, and organ fibrosis may augment the risk of progression. The aim of this review was to discuss types and mechanisms of MPN progression and how their knowledge might improve risk stratification and therapeutic intervention. In view of these aspects, we discuss the potential benefits of early diagnosis using molecular and functional imaging and exploitable therapeutic strategies that may prevent progression, but also highlight current challenges and methodological pitfalls.

Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern

Background A rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines. Methods We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunisation with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. Results Between 27 November and 06 December 2021, 581 and 56,439 eligible Omicron and Delta cases respectively were identified. There were 130,867 eligible test-negative controls. There was no effect against Omicron from 15 weeks after two ChAdOx1 doses, while VE after two BNT162b2 doses was 88.0% (95%CI: 65.9 to 95.8%) 2-9 weeks after dose 2, dropping to between 34 and 37% from 15 weeks post dose 2.From two weeks after a BNT162b2 booster, VE increased to 71.4% (95%CI: 41.8 to 86.0%) for ChAdOx1 primary course recipients and 75.5% (95%CI: 56.1 to 86.3%) for BNT162b2 primary course recipients. For cases with Delta, VE was 41.8% (95%CI: 39.4-44.1%) at 25+ weeks after two ChAdOx1 doses, increasing to 93.8% (95%CI: 93.2-94.3%) after a BNT162b2 booster. With a BNT162b2 primary course, VE was 63.5% (95%CI: 61.4 to 65.5%) 25+ weeks after dose 2, increasing to 92.6% (95%CI: 92.0-93.1%) two weeks after the booster. Conclusions Primary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.

Adolescent vaccination with BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine and effectiveness of the first dose against COVID-19: national test-negative case-control study, England

Adolescents in the UK were recommended to have their first dose of mRNA vaccine during a period of high community transmission due to the highly transmissible Delta variant, followed by a second dose at an extended interval of 8-12 weeks. We used national SARS-CoV-2 testing, vaccination and hospitalisation data to estimate vaccine effectiveness (VE) using a test-negative case-control design, against PCR-confirmed symptomatic COVID-19 in England. VE against symptomatic disease increased to 80% within two weeks of the first dose of BNT162b2 vaccine (higher than in adults aged 18-64 years) and then declines rapidly to 40% within 8 weeks (similar to adults). Early data in 16-17-year-olds also indicate high protection against hospitalisation and a rapid increase in VE against symptomatic COVID-19 after the second dose. Our data highlight the importance of the second vaccine dose for protection against symptomatic COVID-19 and raise important questions about the objectives of an adolescent immunisation programme. If prevention of infection is the primary aim, then regular COVID-19 vaccine boosters will be required.