Combined analyses of within-host SARS-CoV-2 viral kinetics and information on past exposures to the virus in a human cohort identifies intrinsic differences of Omicron and Delta variants.

The emergence of successive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) during 2020 to 2022, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics-such as varying levels of immunity-can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform Coronavirus Disease 2019 (COVID-19) planning and response and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both interindividual variation in Ct values and complex host characteristics-such as vaccination status, exposure history, and age-we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least 5 prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs. Trial Registration: The Legacy study is a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening for SARS-CoV-2 at University College London Hospitals or at the Francis Crick Institute (NCT04750356) (22,23). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469). The Legacy study was approved by London Camden and Kings Cross Health Research Authority Research and Ethics committee (IRAS number 286469) and is sponsored by University College London Hospitals. Written consent was given by all participants.

Biased signalling in analgesic research and development.

Ligand bias offers a novel means to improve the therapeutic profile of drugs. With regard to G protein-coupled receptors involved in analgesia, it could be advantageous to develop such drugs if the analgesic effect is mediated by a different cellular signalling pathway than the adverse effects associated with the drug. Whilst this has been explored over a number of years for the µ receptor, it remains unclear whether this approach offers significant benefit for the treatment of pain. Nevertheless, the development of biased ligands at other G protein-coupled receptors in the CNS does offer some promise for the development of novel analgesic drugs in the future. Here we summarise and discuss the recent evidence to support this.

Radiologic and Clinical Evaluation of Posterolateral Versus Transforaminal Interbody Fusion in Degenerative Lumbar Spondylolisthesis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The primary objective is to compare foraminal height (FH) and disk height (DH) differences in posterolateral (PLF) and transforaminal interbody fusions (TLIFs) and secondarily correlate these measurements with patient-reported outcomes. BACKGROUND: The impact FH has on patient outcomes in degenerative lumbar spinal fusion surgery is unknown. Postoperative FH change and how it relates to patient-reported outcomes in posteriorly based procedures has not been well evaluated. METHODS: A retrospective review of a subset of patients from a prospective cohort from the Canadian Spine Outcomes and Research Network was undertaken. Radiographic assessment preoperatively, at 3 months and 1 year, with standing lumbar spine radiographs were completed. FH and DH were recorded at each time interval, differences between groups were compared, and correlations with patient-reported outcomes were assessed. RESULTS: One hundred nine patients were included (23 PLF and 86 TLIF). At 3-month follow-up, the change in FH was greater in the TLIF group (mean difference =2.3; 95% CI: 0.8-3.5, P =0.002). The change in FH remained significantly different at 12 months (mean difference=1.6, 95% CI: 0.2, 3.0 mm, P =0.028). The change in DH was greater in the TLIF group, with a mean difference between groups of 4.1 mm (95% CI: 2.5, 5.7, P <0.001) and 3.6 mm (95% CI: 2.0, 5.3, P <0.001). A positive change in FH correlated with less back pain, less disability, and improved physical function in the TLIF group ( P <0.05). CONCLUSIONS: Patients treated with PLF lost FH over time. An increased difference in FH at 1 year was associated with improved function and less back pain in the TLIF group.

Characterizing mJOA-defined post-surgical recovery patterns in patients with degenerative cervical myelopathy.

Background: Degenerative cervical myelopathy is a spinal disorder resulting in progressive cord compression and neurological deficits that are assessed using the modified Japanese Orthopedic Association (mJOA) questionnaire. It is difficult to predict which patients will recover neurological function after surgery, making it challenging for clinicians to set postoperative patient expectations. In this study, we used mJOA subscores to identify patterns of recovery and recovery timelines in patients with moderate and severe myelopathy. Methods: Fifty-three myelopathy patients were enrolled and completed the mJOA questionnaire both pre-surgery, and six weeks and six months post-surgery. Pearson chi-square tests were performed to assess relationships of both recovery patterns and recovery timelines with severity of disease. Results: Moderate myelopathy patients were significantly more likely than severe myelopathy patients to experience full recovery of upper extremity, lower extremity, and sensory domains. Disease severity did not significantly impact the timeline during which recovery occurs. Overall, >90% of patients experienced at least partial recovery by six months post surgery, 80% of which demonstrated it within the first six weeks. Conclusions: This study shows the more severe the disease experienced by myelopathy patients, the more likely they will be left with permanent disabilities despite surgery. Early identification and treatment are therefore necessary to prevent worsening quality of life and increased costs of functional dependence. The recovery timelines for each subscore are similar and provide new values to guide patient expectations in their potential post-operative recovery. The overall recovery timeline is more generalizable though potentially lacking the specificity patients seek.

Is the level of consent to a national research registry associated with patient outcomes following traumatic spinal cord injury? A population-based study from the Rick Hansen Spinal Cord Injury Registry (RHSCIR).

OBJECTIVE: We examined the impact of consenting to the Rick Hansen Spinal Cord Injury Registry (RHSCIR) on outcomes: acute length of stay (LOS), in-hospital mortality, medical complications (pressure injuries and pneumonia), and the final discharge destination following a spinal cord injury (SCI) using the national RHSCIR dataset. DESIGN: A retrospective cohort study was conducted using RHSCIR participant data from 2014 to 2019. Participants approached for enrollment were grouped into 1) PC: provided full consent including community follow-up (CFU) interviews, 2) DWC: declined CFU interviews but accepted minimal data collection that may include initial/final interviews and/or those who later withdrew consent, and 3) DC: declined consent to any participation. As no data was collected for the DC group, descriptive, bivariate, and multivariable regression analysis was limited to the PC and DWC groups. RESULTS: Of 2811 participants, 2101 (74.7%) were PC, 553 (19.7%) were DWC, and 157 (5.6%) were DC. DWC participants had significantly longer acute LOS, more acute pneumonias/pressure injuries, and were less likely to be discharged home than PC participants. All these associations - except pneumonia - remained significant in the multivariable analyses. CONCLUSION: Not participating fully in RHSCIR was associated with more complications and longer hospital stays.

COVID-19 in non-hospitalised adults caused by either SARS-CoV-2 sub-variants Omicron BA.1, BA.2, BA.4/5 or Delta associates with similar illness duration, symptom severity and viral kinetics, irrespective of vaccination history.

BACKGROUND: SARS-CoV-2 variant Omicron rapidly evolved over 2022, causing three waves of infection due to sub-variants BA.1, BA.2 and BA.4/5. We sought to characterise symptoms and viral loads over the course of COVID-19 infection with these sub-variants in otherwise-healthy, vaccinated, non-hospitalised adults, and compared data to infections with the preceding Delta variant of concern (VOC). METHODS: In a prospective, observational cohort study, healthy vaccinated UK adults who reported a positive polymerase chain reaction (PCR) or lateral flow test, self-swabbed on alternate weekdays until day 10. We compared participant-reported symptoms and viral load trajectories between infections caused by VOCs Delta and Omicron (sub-variants BA.1, BA.2 or BA.4/5), and tested for relationships between vaccine dose, symptoms and PCR cycle threshold (Ct) as a proxy for viral load using Chi-squared (χ2) and Wilcoxon tests. RESULTS: 563 infection episodes were reported among 491 participants. Across infection episodes, there was little variation in symptom burden (4 [IQR 3-5] symptoms) and duration (8 [IQR 6-11] days). Whilst symptom profiles differed among infections caused by Delta compared to Omicron sub-variants, symptom profiles were similar between Omicron sub-variants. Anosmia was reported more frequently in Delta infections after 2 doses compared with Omicron sub-variant infections after 3 doses, for example: 42% (25/60) of participants with Delta infection compared to 9% (6/67) with Omicron BA.4/5 (χ2 P < 0.001; OR 7.3 [95% CI 2.7-19.4]). Fever was less common with Delta (20/60 participants; 33%) than Omicron BA.4/5 (39/67; 58%; χ2 P = 0.008; OR 0.4 [CI 0.2-0.7]). Amongst infections with an Omicron sub-variants, symptoms of coryza, fatigue, cough and myalgia predominated. Viral load trajectories and peaks did not differ between Delta, and Omicron, irrespective of symptom severity (including asymptomatic participants), VOC or vaccination status. PCR Ct values were negatively associated with time since vaccination in participants infected with BA.1 (ß = -0.05 (CI -0.10-0.01); P = 0.031); however, this trend was not observed in BA.2 or BA.4/5 infections. CONCLUSION: Our study emphasises both the changing symptom profile of COVID-19 infections in the Omicron era, and ongoing transmission risk of Omicron sub-variants in vaccinated adults. TRIAL REGISTRATION: NCT04750356.