Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19.

BACKGROUND: The Ad26.COV2.S vaccine is a recombinant, replication-incompetent human adenovirus type 26 vector encoding full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in a prefusion-stabilized conformation. METHODS: In an international, randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned adult participants in a 1:1 ratio to receive a single dose of Ad26.COV2.S (5×1010 viral particles) or placebo. The primary end points were vaccine efficacy against moderate to severe-critical coronavirus disease 2019 (Covid-19) with an onset at least 14 days and at least 28 days after administration among participants in the per-protocol population who had tested negative for SARS-CoV-2. Safety was also assessed. RESULTS: The per-protocol population included 19,630 SARS-CoV-2-negative participants who received Ad26.COV2.S and 19,691 who received placebo. Ad26.COV2.S protected against moderate to severe-critical Covid-19 with onset at least 14 days after administration (116 cases in the vaccine group vs. 348 in the placebo group; efficacy, 66.9%; adjusted 95% confidence interval [CI], 59.0 to 73.4) and at least 28 days after administration (66 vs. 193 cases; efficacy, 66.1%; adjusted 95% CI, 55.0 to 74.8). Vaccine efficacy was higher against severe-critical Covid-19 (76.7% [adjusted 95% CI, 54.6 to 89.1] for onset at ≥14 days and 85.4% [adjusted 95% CI, 54.2 to 96.9] for onset at ≥28 days). Despite 86 of 91 cases (94.5%) in South Africa with sequenced virus having the 20H/501Y.V2 variant, vaccine efficacy was 52.0% and 64.0% against moderate to severe-critical Covid-19 with onset at least 14 days and at least 28 days after administration, respectively, and efficacy against severe-critical Covid-19 was 73.1% and 81.7%, respectively. Reactogenicity was higher with Ad26.COV2.S than with placebo but was generally mild to moderate and transient. The incidence of serious adverse events was balanced between the two groups. Three deaths occurred in the vaccine group (none were Covid-19-related), and 16 in the placebo group (5 were Covid-19-related). CONCLUSIONS: A single dose of Ad26.COV2.S protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe-critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of Covid-19 vaccines. (Funded by Janssen Research and Development and others; ENSEMBLE ClinicalTrials.gov number, NCT04505722.).

Systematic Review of Shoulder Imaging Abnormalities in Asymptomatic Adult Shoulders (SCRUTINY): Abnormalities of the glenohumeral joint.

OBJECTIVE: The primary objective was to determine the population prevalence of glenohumeral joint imaging abnormalities in asymptomatic adults. METHOD: We systematically reviewed studies reporting the prevalence of X-ray, ultrasound (US), computed tomography, and magnetic resonance imaging (MRI) abnormalities in adults without shoulder symptoms (PROSPERO registration number CRD42018090041). This report presents the glenohumeral joint imaging findings. We searched Ovid MEDLINE, Embase, CINAHL and Web of Science from inception to June 2023 and assessed risk of bias using a tool designed for prevalence studies. The primary analysis was planned for the general population. The certainty of evidence was assessed using a modified Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) for prognostic studies. RESULTS: Thirty-five studies (4 X-ray, 10 US, 20 MRI, 1 X-ray and MRI) reported useable prevalence data. Two studies were population-based (846 shoulders), 15 studies included miscellaneous study populations (1715 shoulders) and 18 included athletes (727 shoulders). All were judged to be at high risk of bias. Clinical diversity precluded pooling. Population prevalence of glenohumeral osteoarthritis ranged from 15% to 75% (2 studies, 846 shoulders, 1 X-ray, 1 X-ray and MRI; low certainty evidence). Prevalence of labral abnormalities, humeral head cysts and long head of biceps tendon abnormalities were 20%, 5%, 30% respectively (1 study, 20 shoulders, X-ray and MRI; very low certainty evidence). CONCLUSION: The population-based prevalence of glenohumeral joint imaging abnormalities in asymptomatic individuals remains uncertain, but may range between 30% and 75%. Better estimates are needed to inform best evidence-based management of people with shoulder pain.

Incidence and Prognostic Significance of Silent Coronary Disease in Asymptomatic Patients with Severe Aortic Stenosis.

Background and Objectives: The aim of this study was to estimate the prevalence of silent coronary artery disease (CAD) in asymptomatic patients with severe aortic stenosis (AS) and assess long-term prognosis in terms of major adverse cardiovascular event (MACE)-free survival. Materials and Methods: This was a prospective study conducted at the Clinic for Cardiac Surgery, University Clinical Center of Serbia, in asymptomatic patients with severe AS, normal LVEF and stress test without signs of myocardial ischemia. Adverse cardiovascular events (cardiac death, myocardial infarction and any hospitalization due to heart disease) was monitored during one year of follow up. Results: A total of 116 asymptomatic patients with severe AS were included in the study. The average age was 67.3 ± 9.6 years, and 56.9% of patients were men. The most common cause of AS was degenerative valvular disease (83.5%). The incidence of significant CAD was 30 out of 116 patients (25.9%). The median Society for Thoracic Surgeons (STS) predicted risk of mortality score was 1.62% (25th to 75th percentile: 1.15-2.76%). The overall mean gradient across aortic valve (Pmean) was 52.30 mmHg ± 12.16, and the mean indexed AVA (AVAi) was 0.37 ± 0.09 cm2/m2. The mean LVEF was 68.40% ± 8.01%. Early surgery for aortic valve replacement was performed in 55 patients (55.2%), while 52 (44.8%) patients received conservative treatment. Twenty-two patients (42.3%) in the conservative treatment group underwent surgery during follow up. There were a total of 44 (37.9%) patients with MACE during one year of follow up. Univariate Cox regression analyses identified the following significant risk factors for MACE-free survival: presence of CAD and early conservative treatment (p = 0.004), age (p = 0.003), diabetes mellitus (p = 0.016) and STS score (p = 0.039). According to multivariate analysis, the presence of CAD with early conservative treatment was the most important predictor of MACE-free survival in asymptomatic patients with severe aortic stenosis (p ≤ 0.001). Conclusions: Early surgery for aortic valve replacement in asymptomatic patients with severe AS and concomitant CAD is beneficial for long-term survival.

An adjusted Asia-Pacific colorectal screening score system to predict advanced colorectal neoplasia in asymptomatic Chinese patients.

PURPOSE: The Asia-Pacific Colorectal Screening (APCS) score and its derivatives have been used to predict advanced colorectal neoplasia (ACN). However, it remains unknown whether they apply to the current Chinese population in general clinical practice. Therefore, we aimed to update the APCS score system by applying data from two independent asymptomatic populations to predict the risk of ACN in China. METHODS: We developed an adjusted APCS (A-APCS) score by using the data of asymptomatic Chinese patients undergoing colonoscopies from January 2014 to December 2018. Furthermore, we validated this system in another cohort of 812 patients who underwent screening colonoscopy between January and December 2021. The discriminative calibration ability of the A-APCS and APCS scores was comparatively evaluated. RESULTS: Univariate and multivariate logistic regression were applied to assess the risk factors for ACN, and an adjusted scoring system of 0 to 6.5 points was schemed according to the results. Utilizing the developed score, 20.2%, 41.2%, and 38.6% of patients in the validation cohort were classified as average, moderate, and high risk, respectively. The corresponding ACN incidence rates were 1.2%, 6.0%, and 11.1%, respectively. In addition, the A-APCS score (c-statistics: 0.68 for the derivation and 0.80 for the validation cohort) showed better discriminative power than using predictors of APCS alone. CONCLUSIONS: The A-APCS score may be simple and useful in clinical applications for predicting ACN risk in China.

Multiomic blood correlates of genetic risk identify presymptomatic disease alterations.

Transitions from health to disease are characterized by dysregulation of biological networks under the influence of genetic and environmental factors, often over the course of years to decades before clinical symptoms appear. Understanding these dynamics has important implications for preventive medicine. However, progress has been hindered both by the difficulty of identifying individuals who will eventually go on to develop a particular disease and by the inaccessibility of most disease-relevant tissues in living individuals. Here we developed an alternative approach using polygenic risk scores (PRSs) based on genome-wide association studies (GWAS) for 54 diseases and complex traits coupled with multiomic profiling and found that these PRSs were associated with 766 detectable alterations in proteomic, metabolomic, and standard clinical laboratory measurements (clinical labs) from blood plasma across several thousand mostly healthy individuals. We recapitulated a variety of known relationships (e.g., glutamatergic neurotransmission and inflammation with depression, IL-33 with asthma) and found associations directly suggesting therapeutic strategies (e.g., Ω-6 supplementation and IL-13 inhibition for amyotrophic lateral sclerosis) and influences on longevity (leukemia inhibitory factor, ceramides). Analytes altered in high-genetic-risk individuals showed concordant changes in disease cases, supporting the notion that PRS-associated analytes represent presymptomatic disease alterations. Our results provide insights into the molecular pathophysiology of a range of traits and suggest avenues for the prevention of health-to-disease transitions.

Risk factors for mortality within 5 years of carotid endarterectomy for asymptomatic stenosis.

OBJECTIVE: The current Society for Vascular Surgery guidelines for the treatment of patients with asymptomatic carotid stenosis recommend endarterectomy for patients with >70% stenosis and acceptable surgical risk. The reduced rate of stroke with modern medical therapy has increased the importance of careful selection in deciding which patients should undergo elective carotid endarterectomy (CEA) for asymptomatic disease. It would, therefore, be very prudent to investigate preexisting variables predictive of 5-year mortality for patients meeting the criteria to undergo CEA. METHODS: The Vascular Quality Initiative was queried from 2003 onward for all cases of CEA. Inclusion in the study required the following: (1) documentation of survival status; (2) complete data on all incorporated demographic study variables; and (3) asymptomatic neurologic status. The variables present at surgery were investigated using binary logistic regression to identify multivariate predictors of 5-year mortality. The highest risk variables were then interrogated for an additive effect regarding long-term mortality. A subanalysis was performed for patients aged >80 years. RESULTS: A total of 30,615 patients met the inclusion criteria, 5414 (18%) of whom had died within 5 years. The highest risk variables were classified as those that had had an adjusted odds ratio >1.25, P < .001, and beta coefficient of ≥0.25. These included a body mass index <20 kg/m2, diabetes mellitus, a history of congestive heart failure, renal insufficiency, end-stage renal disease, chronic obstructive pulmonary disease, living status other than home, prior lower extremity bypass, prior major amputation, Black race relative to other races combined, hemoglobin <10 mg/dL, a history of neck irradiation, and a history of smoking. Age had an annual odds ratio of 1.04 (P < .001). Other variables that achieved a statistically significant (P < .05) association with 5-year mortality were coronary artery disease, a positive stress test or the occurrence of myocardial infarction within 2 years, lower extremity arterial intervention, aneurysm repair, and P2Y12 inhibitor therapy at surgery. The use of statin and aspirin therapy at surgery were both protective against 5-year mortality (P < .001). CONCLUSIONS: We identified 12 particularly high-risk variables, which, in combination, progressively predicted for increasing mortality within 5 years of CEA performed for asymptomatic stenosis. Special attention should be given to patients aged >80 years and patients with any history of congestive heart failure regardless of current symptoms, chronic obstructive pulmonary disease, renal insufficiency or end-stage renal disease, peripheral artery disease, diabetes, and variables associated with frailty (BMI under 20, anemia, assisted living status).

Disease-Based Risk Stratification of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis for Common Bile Duct Stones.

BACKGROUND: Risk stratification of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) for common bile duct (CBD) stones is needed for clinicians to adequately explain to patients regarding the risk of PEP in advance of ERCP and to proactively take preventive measures in high-risk patients. AIMS: To stratify the risk of PEP for CBD stones based on CBD-related diseases. METHODS: A total of 1551 patients with naïve papilla who underwent ERCP for CBD stones were divided into three groups: Group A: asymptomatic CBD stones, Group B: obstructive jaundice and elevated liver test values without cholangitis, and Group C: mild, moderate, and severe cholangitis. We stratified the risk of PEP by comparing its incidence among the three groups using the Holm's method. Furthermore, we performed one-to-one propensity score matching between Group A and the other groups to examine the risk of PEP in Group A. RESULTS: The incidence rates in Groups A, B, and C were 13.7%, 7.3%, and 1.8%, respectively. The Holm-adjusted p values between Groups A and B, Groups A and C, and Groups B and C were 0.023, < 0.001, and < 0.001, respectively. Propensity score matching revealed that the incidence of PEP was significantly more in Group A than in the other groups (13.3% vs. 1.5%; p < 0.001). CONCLUSIONS: The risk of PEP for CBD stones was stratified into low risk (Group C), intermediate risk (Group B), and high risk (Group A). This simple disease-based risk stratification may be useful to predict the risk of PEP in advance of ERCP.

Cerebral blood volume Alberta Stroke Program Early Computed Tomography Score predicts intracranial hemorrhage after thrombectomy in patients with acute ischemic stroke in an extended time window.

BACKGROUND: Higher baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was associated with a lower probability of hemorrhagic transformation in patients with acute ischemic stroke (AIS). PURPOSE: To investigate the predictive value of cerebral blood volume (CBV)-ASPECTS of intracranial hemorrhage (ICH) in AIS treated with thrombectomy selected by computed tomographic perfusion (CTP) in an extended time window. MATERIAL AND METHODS: A total of 91 consecutive patients with AIS with large vessel occlusion in the anterior circulation after thrombectomy in an extended time window were enrolled between January 2018 and September 2019. ICH was diagnosed according to Heidelberg Bleeding Classification. CBV-ASPECTS was assessed by evaluating each ASPECTS region for relatively low CBV value compared with the mirror region in the contralateral hemisphere. Demographic characteristics, clinical data, CBV-ASPECTS, and procedure process and results were compared between patients with ICH and those without. RESULTS: ICH occurred in 31/91 (34.1%) patients with AIS. Symptomatic ICH (sICH) was observed in 4 (4.4%) patients, while asymptomatic ICH (aICH) was seen in 27 (29.7%). In univariate analysis, both ICH and aICH were associated with high admission NIHSS score (P<0.001 and P<0.001, respectively), more passes of retriever (P = 0.007 and P = 0.019, respectively), low NCCT-ASPECTS (P = 0.013 and P = 0.034, respectively), and low CBV-ASPECTS (P < 0.001 and P < 0.001, respectively). After multivariable analysis, low CBV-ASPECTS remained an independent predictor of ICH (odds ratio [OR] 0.521, 95% confidence interval [CI] 0.371-0.732, P < 0.001) and aICH (OR 0.532, 95% CI 0.376-0.752, P < 0.001), respectively. CONCLUSION: Low CBV-ASPECTS independently predicts ICH in patients with AIS treated with thrombectomy selected by CTP in an extended time window.

Derivation and validation of a predictive model for advanced colorectal neoplasia in asymptomatic adults.

OBJECTIVE: Knowing risk for advanced colorectal neoplasia (AN) could help patients and providers choose among screening tests, improving screening efficiency and uptake. We created a risk prediction model for AN to help decide which test might be preferred, a use not considered for existing models. DESIGN: Average-risk 50-to-80-year olds undergoing first-time screening colonoscopy were recruited from endoscopy units in Indiana. We measured sociodemographic and physical features, medical and family history and lifestyle factors and linked these to the most advanced finding. We derived a risk equation on two-thirds of the sample and assigned points to each variable to create a risk score. Scores with comparable risks were collapsed into risk categories. The model and score were tested on the remaining sample. RESULTS: Among 3025 subjects in the derivation set (mean age 57.3 (6.5) years; 52% women), AN prevalence was 9.4%. The 13-variable model (c-statistic=0.77) produced three risk groups with AN risks of 1.5% (95% CI 0.72% to 2.74%), 7.06% (CI 5.89% to 8.38%) and 27.26% (CI 23.47% to 31.30%) in low-risk, intermediate-risk and high-risk groups (p value <0.001), containing 23%, 59% and 18% of subjects, respectively. In the validation set of 1475 subjects (AN prevalence of 8.4%), model performance was comparable (c-statistic=0.78), with AN risks of 2.73% (CI 1.25% to 5.11%), 5.57% (CI 4.12% to 7.34%) and 25.79% (CI 20.51% to 31.66%) in low-risk, intermediate-risk and high-risk subgroups, respectively (p<0.001), containing proportions of 23%, 59% and 18%. CONCLUSION: Among average-risk persons, this model estimates AN risk with high discrimination, identifying a lower risk subgroup that may be screened non-invasively and a higher risk subgroup for which colonoscopy may be preferred. The model could help guide patient-provider discussions of screening options, may increase screening adherence and conserve colonoscopy resources.

Analysis of Asymptomatic and Presymptomatic Transmission in SARS-CoV-2 Outbreak, Germany, 2020.

We determined secondary attack rates (SAR) among close contacts of 59 asymptomatic and symptomatic coronavirus disease case-patients by presymptomatic and symptomatic exposure. We observed no transmission from asymptomatic case-patients and highest SAR through presymptomatic exposure. Rapid quarantine of close contacts with or without symptoms is needed to prevent presymptomatic transmission.

Efficacy and Safety of Etrasimod in a Phase 2 Randomized Trial of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: Etrasimod (APD334) is an oral, selective sphingosine 1-phosphate receptor modulator in development for immune-mediated inflammatory disorders. We assessed the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis (UC). METHODS: In a phase 2, proof-of-concept, double-blind, parallel-group study, adult outpatients with modified Mayo Clinic scores (MCSs) (stool frequency, rectal bleeding, and endoscopy findings) of 4-9, endoscopic subscores of 2 or more, and rectal bleeding subscores of 1 or more were randomly assigned to groups given once-daily etrasimod 1 mg (n = 52), etrasimod 2 mg (n = 50), or placebo (n = 54) for 12 weeks. The study was performed from October 15, 2015, through February 14, 2018, at 87 centers in 17 countries. The primary endpoint was an increase in the mean improvement in modified MCS from baseline to week 12. Secondary endpoints included the proportion of patients with endoscopic improvement (subscores of 1 or less) from baseline to week 12. Exploratory endpoints, including clinical remission, are reported in the article, although the study was statistically powered to draw conclusions only on the primary endpoint. RESULTS: At week 12, the etrasimod 2 mg group met the primary and all secondary endpoints. Etrasimod 2 mg led to a significantly greater increase in mean improvement in modified MCS from baseline than placebo (difference from placebo, 0.99 points; 90% confidence interval, 0.30-1.68; P = .009), and etrasimod 1 mg led to an increase in mean improvement from baseline in modified MCS of 0.43 points more than placebo (90% confidence interval, reduction of 0.24 to increase of 1.11; nominal P = .15). Endoscopic improvement occurred in 41.8% of patients receiving etrasimod 2 mg vs 17.8% receiving placebo (P = .003). Most adverse events were mild to moderate. Three patients had a transient, asymptomatic, low-grade atrioventricular block that resolved spontaneously all patients had evidence of atrioventricular block before etrasimod exposure. CONCLUSIONS: In patients with moderately to severely active ulcerative colitis, etrasimod 2 mg was more effective than placebo in producing clinical and endoscopic improvements. Further clinical development is warranted. Clinicaltrials.gov, Number: NCT02447302.

Rationale and design of a digital trial using smartphones to detect subclinical atrial fibrillation in a population at risk: The eHealth-based bavarian alternative detection of Atrial Fibrillation (eBRAVE-AF) trial.

Current guidelines recommend opportunistic screening for subclinical atrial fibrillation (AF) taking advantage of e-health-based technologies. However, the efficacy of a fully scalable e-health-based strategy for AF detection in a head-to-head comparison with routine symptom-based screening is unknown. eBRAVE-AF is an investigator-initiated, digital, prospective, randomized, siteless, open-label, cross-over study to evaluate an e-health-based strategy for detection of AF in a real-world setting. 67,488 policyholders of a large German health insurance company (Versicherungskammer Bayern, Germany) selected by age ≥ 50 years and a CHA2DS2-VASc score ≥ 1 (females ≥2) are invited to participate. Subjects with known AF or on treatment with oral anticoagulation are excluded. After obtaining electronic informed consent, at least 4,400 participants will be randomly assigned to an e-health-based screening strategy or routine symptom-based screening. The e-health-based strategy consists of repetitive one-minute photoplethysmographic (PPG) pulse wave assessments using a certified smartphone app (Preventicus Heartbeats, Preventicus, Jena, Germany), followed by a confirmatory 14-day ECG patch (CardioMem CM 100 XT, Getemed, Teltow, Germany) in case of abnormal findings. After 6 months, participants are crossed over to the other study arm. Primary endpoint is the incidence of newly diagnosed AF leading to oral anticoagulation indicated by an independent physician. Clinical follow-up will be at least 12 months. In both groups, follow-up is performed by 4-week app-based questionnaires, personal contact in case of abnormal findings, and matching with claim-based insurance data and medical reports. At time of writing enrollment is completed. First results are expected to be available in mid-2021.

The association of healthcare disparities and patient-specific factors on clinical outcomes in peripheral artery disease.

BACKGROUND: PAD increases the risk of cardiovascular mortality and limb loss, and disparities in treatment and outcomes have been described. However, the association of patient-specific characteristics with variation in outcomes is less well known. METHODS: Patients with PAD from Duke University Health System (DUHS) between January 1, 2015 and March 31, 2016 were identified. PAD status was confirmed through ground truth adjudication and predictive modeling using diagnosis codes, procedure codes, and other administrative data. Symptom severity, lower extremity imaging, and ankle-brachial index (ABI) were manually abstracted from the electronic health record (EHR). Data was linked to Centers for Medicare and Medicaid Services data to provide longitudinal follow up. Primary outcome was major adverse vascular events (MAVE), a composite of all-cause mortality, myocardial infarction (MI), stroke, lower extremity revascularization and amputation. RESULTS: Of 1,768 patients with PAD, 31.6% were asymptomatic, 41.2% had intermittent claudication (IC), and 27.3% had chronic limb-threatening ischemia (CLTI). At 1 year, patients with CLTI had higher rates of MAVE compared with asymptomatic or IC patients. CLTI and Medicaid dual eligibility were independent predictors of mortality. CLTI and Black race were associated with amputation. CONCLUSIONS: Rates of MAVE were highest in patients with CLTI, but patients with IC or asymptomatic disease also had high rates of adverse events. Black and Medicaid dual-eligible patients were disproportionately present in the CLTI subgroup and were at higher risk of amputation and mortality, respectively. Future studies must focus on early identification of high-risk patient groups to improve outcomes in patients with PAD.

Screening Students and Staff for Asymptomatic Coronavirus Disease 2019 in Chicago Schools.

OBJECTIVES: To assess rates of asymptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positivity in K-8 schools with risk mitigation procedures in place, and to evaluate SARS-CoV-2 transmission in school and household contacts of these positive individuals. STUDY DESIGN: In this prospective observational study, screening testing for SARS-CoV-2 was performed by oropharyngeal swabbing and polymerase chain reaction (PCR) analysis in students and staff at K-8 private schools in high-risk Chicago ZIP codes. New coronavirus disease 2019 (COVID-19) diagnoses or symptoms among participants, household contacts, and nonparticipants in each school were queried. RESULTS: Among 11 K-8 private schools across 8 Chicago ZIP codes, 468 participants (346 students, 122 staff members) underwent screening testing. At the first school, 17 participants (36%) tested positive, but epidemiologic investigation suggested against in-school transmission. Only 5 participants in the subsequent 10 schools tested positive for an overall 4.7% positivity rate (1.2% excluding school 1). All but 1 positive test among in-person students had high PCR cycle threshold values, suggesting very low SARS-CoV-2 viral loads. In all schools, no additional students, staff, or household contacts reported new diagnoses or symptoms of COVID-19 during the 2 weeks following screening testing. CONCLUSIONS: We identified infrequent asymptomatic COVID-19 in schools in high-risk Chicago communities and did not identify transmission among school staff, students, or their household contacts. These data suggest that COVID-19 mitigation procedures, including masking and physical distancing, are effective in preventing transmission of COVID-19 in schools. These results may inform future strategies for screening testing in K-8 schools.

Immune response against SARS-CoV-2 in pediatric patients including young infants.

Pediatric cases of the coronavirus disease 2019 (COVID-19) are generally mild or asymptomatic, and are usually detected by virological examination following close contact with COVID-19 patients, often the children's parents. The detailed clinical features and virological data of pediatric patients with COVID-19, particularly young infants, remain unclear. Here, the clinical and virological characteristics of four children with COVID-19 including two young infants were investigated. One- and 4-month-old boys with COVID-19 were both asymptomatic, and seroconversion was demonstrated. These findings suggest that even young infants can mount an immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), despite having weaker immune defenses than adolescents and adults. Three-year-old boy, who was SARS-CoV-2-negative, was admitted to the same room as his SARS-CoV-2-positive father due to the lack of caregivers. Although he was asymptomatic, he had seroconverted to SARS-CoV-2. Eleven-year-old boy, who was sibling of the 3-year-old boy, was also SARS-CoV-2-negative. He was isolated in his own room and did not seroconvert. If young children are SARS-CoV-2 negative, they should be isolated from their SARS-CoV-2-positive parents. This may be difficult in practice, if parents with COVID-19 are the only available caregivers. In such situations, the most appropriate measures should be taken for each patient.

Clinical characteristics of pediatric SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) in Kuwait.

Clinical presentation of coronavirus disease-2019 (COVID-19) ranges from asymptomatic to severe and life-threatening. National-level registries found that children, generally, have less severe disease when compared with adults. However, most asymptomatically infected children will not present to hospital and may be missed. We aimed to describe the clinical characteristics in pediatric COVID-19 patients in Kuwait, and to estimate the potential duration of viral shedding. A retrospective cohort study was performed in Jaber Alahmad Hospital (JAH) from February 29 to April 30, 2020. During the study period and as part of the public health measures, all severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients from 1 month to 18 years old, regardless of symptoms, were hospitalized at JAH, and were included. Polymerase chain reaction (PCR) negativity was defined as having two consecutive negative PCR results from a respiratory specimen. Descriptive statistics and multivariable regression analyses were performed. We found that 67.9% (95% CI, 59.4%-75.3%) of 134 SARS-CoV-2-infected children were asymptomatic. Median PCR positivity was 15 days and did not vary with symptoms. Among patients who had laboratory investigations and chest imaging, symptomatic infection was associated with elevated C-reactive protein and procalcitonin, and radiographic pneumonia. Asymptomatic SARS-CoV-2 infection is very common in children. Among symptomatic patients, the disease seems to be mild. Children exhibit substantial duration of viral shedding, regardless of symptoms.

Asymptomatic common extensor tendon pathology in patients with carpal tunnel syndrome.

INTRODUCTION/AIMS: Carpal tunnel syndrome (CTS) and lateral epicondylitis are both highly prevalent conditions. Our objective was to determine the prevalence of B-mode ultrasound abnormalities of the common extensor tendon (CET) in patients with CTS and establish the relationship between CET stiffness, as measured by shear wave elastography (SWE) and CTS severity. METHODS: Patients without symptoms or signs of lateral epicondylitis were recruited from referrals to a neurophysiology laboratory for possible CTS. These patients were examined for clinical features of CTS before undergoing electrodiagnostic testing followed by an ultrasound examination, consisting of B-mode, power Doppler, and SWE. RESULTS: Thirty-nine limbs with clinically diagnosed CTS and 20 control limbs were included. Of the CTS limbs, 61.5% had sonographically abnormal CET compared with 35% of the controls. The mean CET sonographic abnormality score was higher in CTS patients compared with controls (P = .006). CTS patients with sonographically abnormal CET had more severe CTS by electrophysiological criteria. The mean CET stiffness in CTS patients was lower than in controls (P = .033). DISCUSSION: Sonographic abnormalities of the CET are common in CTS patients with no clinical evidence of lateral epicondylitis and may relate to common pathogenetic mechanisms. These findings suggest that isolated ultrasound abnormalities in the CET are not diagnostically useful in patients presenting with upper limb pain unless there are clinical features of lateral epicondylitis.

Postvaccination SARS-CoV-2 Infections Among Skilled Nursing Facility Residents and Staff Members - Chicago, Illinois, December 2020-March 2021.

Early studies suggest that COVID-19 vaccines protect against severe illness (1); however, postvaccination SARS-CoV-2 infections (i.e., breakthrough infections) can occur because COVID-19 vaccines do not offer 100% protection (2,3). Data evaluating the occurrence of breakthrough infections and impact of vaccination in decreasing transmission in congregate settings are limited. Skilled nursing facility (SNF) residents and staff members have been disproportionately affected by SARS-CoV-2, the virus that causes COVID-19 (4,5), and were prioritized for COVID-19 vaccination (6,7). Starting December 28, 2020, all 78 Chicago-based SNFs began COVID-19 vaccination clinics over several weeks through the federal Pharmacy Partnership for Long-Term Care Program (PPP).† In February 2021, through routine screening, the Chicago Department of Public Health (CDPH) identified a SARS-CoV-2 infection in a SNF resident >14 days after receipt of the second dose of a two-dose COVID-19 vaccination series. SARS-CoV-2 cases, vaccination status, and possible vaccine breakthrough infections were identified by matching facility reports with state case and vaccination registries. Among 627 persons with SARS-CoV-2 infection across 75 SNFs since vaccination clinics began, 22 SARS-CoV-2 infections were identified among 12 residents and 10 staff members across 15 facilities ≥14 days after receiving their second vaccine dose (i.e., breakthrough infections in fully vaccinated persons). Nearly two thirds (14 of 22; 64%) of persons with breakthrough infections were asymptomatic; two residents were hospitalized because of COVID-19, and one died. No facility-associated secondary transmission occurred. Although few SARS-CoV-2 infections in fully vaccinated persons were observed, these cases demonstrate the need for SNFs to follow recommended routine infection prevention and control practices and promote high vaccination coverage among SNF residents and staff members.

Towards the use of a smartphone imaging-based tool for point-of-care detection of asymptomatic low-density malaria parasitaemia.

BACKGROUND: Globally, there are over 200 million cases of malaria annually and over 400,000 deaths. Early and accurate detection of low-density parasitaemia and asymptomatic individuals is key to achieving the World Health Organization (WHO) 2030 sustainable development goals of reducing malaria-related deaths by 90% and eradication in 35 countries. Current rapid diagnostic tests are neither sensitive nor specific enough to detect the low parasite concentrations in the blood of asymptomatic individuals. METHODS: Here, an imaging-based sensing technique, particle diffusometry (PD), is combined with loop mediated isothermal amplification (LAMP) on a smartphone-enabled device to detect low levels of parasitaemia often associated with asymptomatic malaria. After amplification, PD quantifies the Brownian motion of fluorescent nanoparticles in the solution during a 30 s video taken on the phone. The resulting diffusion coefficient is used to detect the presence of Plasmodium DNA amplicons. The coefficients of known negative samples are compared to positive samples using a one-way ANOVA post-hoc Dunnett's test for confirmation of amplification. RESULTS: As few as 3 parasite/µL of blood was detectable in 45 min without DNA extraction. Plasmodium falciparum parasites were detected from asymptomatic individuals' whole blood samples with 89% sensitivity and 100% specificity when compared to quantitative polymerase chain reaction (qPCR). CONCLUSIONS: PD-LAMP is of value for the detection of low density parasitaemia especially in areas where trained personnel may be scarce. The demonstration of this smartphone biosensor paired with the sensitivity of LAMP provides a proof of concept to achieve widespread asymptomatic malaria testing at the point of care.