Viral dynamics and duration of PCR positivity of the SARS-CoV-2 Omicron variant

Background. The Omicron SARS-CoV-2 variant is responsible for a major wave of COVID-19, with record case counts reflecting high transmissibility and escape from prior immunity. Defining the time course of Omicron viral proliferation and clearance is crucial to inform isolation protocols aiming to minimize disease spread. Methods. We obtained longitudinal, quantitative RT-qPCR test results using combined anterior nares and oropharyngeal samples (n = 10,324) collected between July 5th, 2021 and January 10th, 2022 from the National Basketball Association's (NBA) occupational health program. We quantified the fraction of tests with PCR cycle threshold (Ct) values <30, chosen as a proxy for potential infectivity and antigen test positivity, on each day after first detection of suspected and confirmed Omicron infections, stratified by individuals detected under frequent testing protocols and those detected due to symptom onset or concern for contact with an infected individual. We quantified the duration of viral proliferation, clearance rate, and peak viral concentration for individuals with acute Omicron and Delta variant SARS-CoV-2 infections. Results. A total of 97 infections were confirmed or suspected to be from the Omicron variant and 107 from the Delta variant. Of 27 Omicron-infected individuals testing positive ≤1 day after a previous negative or inconclusive test, 52.0% (13/25) were PCR positive with Ct values <30 at day 5, 25.0% (6/24) at day 6, and 13.0% (3/23) on day 7 post detection. Of 70 Omicron-infected individuals detected ≥2 days after a previous negative or inconclusive test, 39.1% (25/64) were PCR positive with Ct values <30 at day 5, 33.3% (21/63) at day 6, and 22.2% (14/63) on day 7 post detection. Overall, Omicron infections featured a mean duration of 9.87 days (95% CI 8.83-10.9) relative to 10.9 days (95% CI 9.41-12.4) for Delta infections. The peak viral RNA based on Ct values was lower for Omicron infections than for Delta infections (Ct 23.3, 95% CI 22.4-24.3 for Omicron; Ct 20.5, 95% CI 19.2-21.8 for Delta) and the clearance phase was shorter for Omicron infections (5.35 days, 95% CI 4.78-6.00 for Omicron; 6.23 days, 95% CI 5.43-7.17 for Delta), though the rate of clearance was similar (3.13 Ct/day, 95% CI 2.75-3.54 for Omicron; 3.15 Ct/day, 95% CI 2.69-3.64 for Delta). Conclusions. While Omicron infections feature lower peak viral RNA and a shorter clearance phase than Delta infections on average, it is unclear to what extent these differences are attributable to more immunity in this largely vaccinated population or intrinsic characteristics of the Omicron variant. Further, these results suggest that Omicron's infectiousness may not be explained by higher viral load measured in the nose and mouth by RT-PCR. The substantial fraction of individuals with Ct values <30 at days 5 of infection, particularly in those detected due to symptom onset or concern for contact with an infected individual, underscores the heterogeneity of the infectious period, with implications for isolation policies.

Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials

Background and Objectives:Detailed study of tenecteplase (TNK) in patients greater than 80 years of age is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients greater than 80 years with large vessel occlusion.Methods:A pooled analysis of the EXTEND-IA TNK randomized controlled trials (n=502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25mg/kg, TNK 0.40mg/kg, and alteplase 0.90mg/kg, stratifying for patient age (>80 years). Outcomes evaluated include 90-day modified Rankin scale (mRS), all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIHSS, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models.Results:In patients >80 years (n=137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs. 4, adjusted common OR=2.70, 95% CI: 1.23-5.94) and reduced mortality (aOR=0.34, 95% CI: 0.13-0.91) versus 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs. 4, acOR=2.28, 95% CI: 1.03-5.05) versus alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, one patient treated with alteplase and zero patients treated with TNK 0.25 mg/kg. In patients ≤ 80 years, no differences in 90-day mRS, mortality, or symptomatic ICH was observed between TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg.Conclusions:TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients greater than 80 years of age. No differences between the doses were observed in younger patients.Classification of Evidence:This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients >80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.Trial Registration:ClinicalTrials.gov Identifiers: NCT02388061, NCT03340493https://www.clinicaltrials.gov/ct2/show/NCT02388061https://www.clinicaltrials.gov/ct2/show/NCT03340493

Scn1a gene reactivation after symptom onset rescues pathological phenotypes in a mouse model of Dravet syndrome

Dravet syndrome is a severe epileptic encephalopathy caused primarily by haploinsufficiency of the SCN1A gene. Repetitive seizures can lead to endurable and untreatable neurological deficits. Whether this severe pathology is reversible after symptom onset remains unknown. To address this question, we generated a Scn1a conditional knock-in mouse model (Scn1a Stop/+) in which Scn1a expression can be re-activated on-demand during the mouse lifetime. Scn1a gene disruption leads to the development of seizures, often associated with sudden unexpected death in epilepsy (SUDEP) and behavioral alterations including hyperactivity, social interaction deficits and cognitive impairment starting from the second/third week of age. However, we showed that Scn1a gene re-activation when symptoms were already manifested (P30) led to a complete rescue of both spontaneous and thermic inducible seizures, marked amelioration of behavioral abnormalities and normalization of hippocampal fast-spiking interneuron firing. We also identified dramatic gene expression alterations, including those associated with astrogliosis in Dravet syndrome mice, that, accordingly, were rescued by Scn1a gene expression normalization at P30. Interestingly, regaining of Nav1.1 physiological level rescued seizures also in adult Dravet syndrome mice (P90) after months of repetitive attacks. Overall, these findings represent a solid proof-of-concept highlighting that disease phenotype reversibility can be achieved when Scn1a gene activity is efficiently reconstituted in brain cells.

Lysophosphatidic Acid May Be a Novel Biomarker for Early Acute Aortic Dissection

Background: Misdiagnosis and delayed diagnosis of acute aortic dissection (AAD) significantly increase mortality. Lysophosphatidic acid (LPA) is a biomarker related to coagulation cascade and cardiovascular-injury. The extent of LPA elevation in AAD and whether it can discriminate sudden-onset of acute chest pain are currently unclear.Methods: We measured the plasma concentration of LPA in a cohort of 174 patients with suspected AAD chest pain and 30 healthy participants. Measures to discriminate AAD from other acute-onset thoracalgia were compared and calculated.Results: LPA was significantly higher in AAD than in the AMI, PE, and the healthy (344.69 ± 59.99 vs. 286.79 ± 43.01 vs. 286.61 ± 43.32 vs. 96.08 ± 11.93, P &lt; 0.01) within 48 h of symptom onset. LPA level peaked at 12 h after symptom onset, then gradually decreased from 12 to 48 h in AAD. LPA had an AUC of 0.85 (0.80–0.90), diagnosis threshold of 298.98 mg/dl, a sensitivity of 0.81, specificity of 0.77, and the negative predictive value of 0.85. The ROC curve of LPA is better than D-dimer (P = 0.041, Delong test). The decision curve showed that LPA had excellent standardized net benefits.Conclusion: LPA showed superior overall diagnostic performance to D-dimer in early AAD diagnosis may be a potential biomarker, but additional studies are needed to determine the rapid and cost-effective diagnostic tests in the emergency department.

IMPACT OF GENDER ON THE CLINICAL FEATURES, ANGIOGRAPHIC FINDINGS, AND OUTCOMES OF YOUNG PATIENTS PRESENTED WITH ACUTE CORONARY SYNDROME

Objectives: Acute coronary syndrome (ACS) at a younger age is now becoming a crucial problem. This study determined the effect of gender on the clinical findings and outcomes of young patients (≤ 45 years) with ACS. Methodology: In this descriptive cross sectional study, young patients (≤45 years) who presented with ACS and underwent coronary angiography were recruited. The comparison of clinical profile, angiographic findings, in-hospital, and 90-days mortality between genders were made. Results: A total of 335 young patients with ACS were included, 80.6% of whom were men. A significant difference was found between men and women in terms of mean age: 38±6 vs. 40±5 (p=0.014), hypertension: 37.8% vs. 58.5% (p=0.002), diabetes: 17.4% vs. 35.4% (p=0.001), smoking: 50.4% vs. 6.2% (p≤0.001), use of smokeless tobacco: 14.1% vs. 4.6% (p=0.037), median time from symptom onset to first medical contact: 270 [420–165] minutes vs. 346 [499.5–240] minutes (p=0.047), ST-segment elevation myocardial infarction (STEMI) 89.6% vs. 78.5% (p=0.015), non-ST-elevation myocardial infarction (NSTEMI) 8.5% vs. 18.5% (p=0.019), and three-vessel disease (3VD) 10.7% vs. 21.5% (p=0.019), respectively. In-hospital and 90-day mortality rates were 0.4% vs. 3.1% (p=0.097) and 1.5% vs. 4.6% (p=0.136) for men and women, respectively. Conclusion: Women tended to have a higher age at presentation, more frequent traditional risk factors, late presentation after symptom onset, frequent NSTEMI, and 3VD, whereas men were distinct with frequent STEMI and higher tobacco use. In addition, women trended to have a higher in-hospital as well as short-term mortality than men did.

Baseline clinical features of COVID-19 patients, delay of hospital admission and clinical outcome: A complex relationship

Introduction Delay between symptom onset and access to care is essential to prevent clinical worsening for different infectious diseases. For COVID-19, this delay might be associated with the clinical prognosis, but also with the different characteristics of patients. The objective was to describe characteristics and symptoms of community-acquired (CA) COVID-19 patients at hospital admission according to the delay between symptom onset and hospital admission, and to identify determinants associated with delay of admission. Methods The present work was based on prospective NOSO-COR cohort data, and restricted to patients with laboratory confirmed CA SARS-CoV-2 infection admitted to Lyon hospitals between February 8 and June 30, 2020. Long delay of hospital admission was defined as ≥6 days between symptom onset and hospital admission. Determinants of the delay between symptom onset and hospital admission were identified by univariate and multiple logistic regression analysis. Results Data from 827 patients were analysed. Patients with a long delay between symptom onset and hospital admission were younger (p<0.01), had higher body mass index (p<0.01), and were more frequently admitted to intensive care unit (p<0.01). Their plasma levels of C-reactive protein were also significantly higher (p<0.01). The crude in-hospital fatality rate was lower in this group (13.3% versus 27.6%), p<0.01. Multiple analysis with correction for multiple testing showed that age ≥75 years was associated with a short delay between symptom onset and hospital admission (≤5 days) (aOR: 0.47 95% CI (0.34–0.66)) and CRP>100 mg/L at admission was associated with a long delay (aOR: 1.84 95% CI (1.32–2.55)). Discussion Delay between symptom onset and hospital admission is a major issue regarding prognosis of COVID-19 but can be related to multiple factors such as individual characteristics, organization of care and severe pathogenic processes. Age seems to play a key role in the delay of access to care and the disease prognosis.

Detection of IgG and IgM Levels in Patients with COVID-19 in Mosul Province, Iraq

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has become the most dangerous viral infection worldwide. Since its identification in late 2019, the number of medical trials to combat the infection has sharply increased. Here, we investigated the profiles of IgG and IgM in 85 patients with confirmed SARS-CoV-2 infection from day 1 after symptom onset until day 35 with 5-day intervals. Serum samples were collected and stored until use. We observed that IgM levels were detectable on day 5 post symptom onset and increased sharply, with the highest rate detected in moderate cases (32.332 ± 4.32, n=10). Subsequently, a significant reduction in IgM was observed until it was undetectable on day 35 after symptom onset. Meanwhile, IgG levels were detected on day 10 post symptom onset, and the highest rate was observed in moderate cases (8.232 ± 2.3, n=10). A significant increase in IgG rate was observed in all patients, with the highest rate in moderate cases (42.432 ± 4.34, n=67) on day 35 post symptom onset. The statistical difference between the case and control groups was significant (p≤0.001). Two out of 85 patients died during the study.

Imaging markers of intracerebral hemorrhage expansion in patients with unclear symptom onset

Background: Hematoma expansion (HE) is common and associated with poor outcome in intracerebral hemorrhage (ICH) with unclear symptom onset (USO). Aims: We tested the association between non-contrast computed tomography (NCCT) markers and HE in this population. Methods: Retrospective analysis of patients with primary spontaneous ICH admitted at five centers in the United States and Italy. Baseline NCCT was analyzed for presence of the following markers: intrahematoma hypodensities, heterogeneous density, blend sign, and irregular shape. Variables associated with HE (hematoma growth > 6 mL and/or > 33% from baseline to follow-up imaging) were explored with multivariable logistic regression. Results: Of 2074 patients screened, we included 646 subjects (median age = 75, 53.9% males), of whom 178 (27.6%) had HE. Hypodensities (odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.79–3.98), heterogeneous density (OR = 2.16, 95% CI = 1.46–3.21), blend sign (OR = 2.28, 95% CI = 1.38–3.75) and irregular shape (OR = 1.82, 95% CI = 1.21–2.75) were independently associated with a higher risk of HE, after adjustment for confounders (ICH volume, anticoagulation, and time from last seen well (LSW) to NCCT). Hypodensities had the highest sensitivity for HE (0.69), whereas blend sign was the most specific marker (0.90). All NCCT markers were more frequent in early presenters (time from LSW to NCCT ⩽ 6 h, n = 189, 29.3%), and more sensitive in this population as well (hypodensities had 0.77 sensitivity). Conclusion: NCCT markers are associated with HE in ICH with USO. These findings require prospective replication and suggest that NCCT features may help the stratification of HE in future studies on USO patients.

Duration of antibody responses following severe acute respiratory syndrome coronavirus 2 infection

Background Little is known on the duration of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibodies in patients following SARS-CoV-2 infection. Aims We aimed to determine the duration of the immunoglobulin G (IgG) and M (IgM) antibody responses following SARS-CoV-2 infection and to evaluate the risk factors for a short duration of anti-SARS-CoV-2 IgG. Methods We measured antibody responses in 94 patients who had recovered from SARS-CoV-2 infection. The chi-square test and multivariable logistic regression analysis were used to identify risk factors for a short duration (< 6 months) of anti-SARS-CoV-2 IgG. Results IgG antibodies were detectable in all patients until 4 months; 19 (21.8%) convalescent patients reverted to IgG negative 4–6 months after symptom onset. IgM antibodies decreased significantly to 5.7% at 4–6 months after symptom onset. Patient characteristics were not associated with a short duration of detectable IgG. Conclusions A substantial fraction of convalescents may exhibit a transient IgG response following SARS-CoV-2 infection. Our findings suggest that patients who have recovered from SARS-CoV-2 infection should also be vaccinated if their anti-SARS-CoV-2 IgG antibodies are undetectable.