Impact of COVID-19 Pandemic on Physical Activity, Pain, Mood, and Sleep in Adults with Knee Osteoarthritis.

Objective: To examine changes in physical activity, sleep, pain and mood in people with knee osteoarthritis (OA) during the ongoing COVID-19 pandemic by leveraging an ongoing randomized clinical trial (RCT). Methods: Participants enrolled in a 12-month parallel two-arm RCT (NCT03064139) interrupted by the COVID-19 pandemic wore an activity monitor (Fitbit Charge 3) and filled out custom weekly surveys rating knee pain, mood, and sleep as part of the study. Data from 30 weeks of the parent study were used for this analysis. Daily step count and sleep duration were extracted from activity monitor data, and participants self-reported knee pain, positive mood, and negative mood via surveys. Metrics were averaged within each participant and then across all participants for pre-pandemic, stay-at-home, and reopening periods, reflecting the phased re-opening in the state of Massachusetts. Results: Data from 28 participants showed small changes with inconclusive clinical significance during the stay-at-home and reopening periods compared to pre-pandemic for all outcomes. Summary statistics suggested substantial variability across participants with some participants showing persistent declines in physical activity during the observation period. Conclusion: Effects of the COVID-19 pandemic on physical activity, sleep, pain, and mood were variable across individuals with OA. Specific reasons for this variability could not be determined. Identifying factors that could affect individuals with knee OA who may exhibit reduced physical activity and/or worse symptoms during major lifestyle changes (such as the ongoing pandemic) is important for providing targeted healthcare services and management advice towards those that could benefit from it the most.

Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19: A Randomized Clinical Trial.

Importance: Effective treatments for patients with severe COVID-19 are needed. Objective: To evaluate the efficacy of canakinumab, an anti-interleukin-1ß antibody, in patients hospitalized with severe COVID-19. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled phase 3 trial was conducted at 39 hospitals in Europe and the United States. A total of 454 hospitalized patients with COVID-19 pneumonia, hypoxia (not requiring invasive mechanical ventilation [IMV]), and systemic hyperinflammation defined by increased blood concentrations of C-reactive protein or ferritin were enrolled between April 30 and August 17, 2020, with the last assessment of the primary end point on September 22, 2020. Intervention: Patients were randomly assigned 1:1 to receive a single intravenous infusion of canakinumab (450 mg for body weight of 40-<60 kg, 600 mg for 60-80 kg, and 750 mg for >80 kg; n = 227) or placebo (n = 227). Main Outcomes and Measures: The primary outcome was survival without IMV from day 3 to day 29. Secondary outcomes were COVID-19-related mortality, measurements of biomarkers of systemic hyperinflammation, and safety evaluations. Results: Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, -3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = .29). COVID-19-related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of -2.3% (95% CI, -6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Conclusions and Relevance: Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT04362813.

The Effect of IL-6 Inhibitors on Mortality Among Hospitalized COVID-19 Patients: A Multicenter Study.

BACKGROUND: The effectiveness of interleukin-6 inhibitors (IL-6i) in ameliorating coronavirus disease 2019 (COVID-19) remains uncertain. METHODS: We analyzed data for patients aged ≥18 years admitted with a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test at 4 safety-net hospital systems with diverse populations and high rates of medical comorbidities in 3 US regions. We used inverse probability of treatment weighting via machine learning for confounding adjustment by demographics, comorbidities, and disease severity markers. We estimated the average treatment effect, the odds of IL-6i effect on in-hospital mortality from COVID-19, using a logistic marginal structural model. RESULTS: Of 516 patients, 104 (20.1%) received IL-6i. Estimate of the average treatment effect adjusted for confounders suggested a 37% reduction in odds of in-hospital mortality in those who received IL-6i compared with those who did not, although the confidence interval included the null value of 1 (odds ratio = 0.63; 95% confidence interval, .29-1.38). A sensitivity analysis suggested that potential unmeasured confounding would require a minimum odds ratio of 2.55 to nullify our estimated IL-6i effect size. CONCLUSIONS: Despite low precision, our findings suggested a relatively large effect size of IL-6i in reducing the odds of COVID-19-related in-hospital mortality.