Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Upadacitinib, a Janus kinase inhibitor, has been shown to be effective in patients with ankylosing spondylitis. We aimed to assess the efficacy and safety of upadacitinib in non-radiographic axial spondyloarthritis. METHODS: The SELECT-AXIS 2 non-radiographic axial spondyloarthritis study was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 113 sites across 23 countries (Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Japan, Mexico, Poland, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey, Ukraine, and the USA). Eligible adults had active non-radiographic axial spondyloarthritis, with objective signs of inflammation based on MRI or elevated C-reactive protein and an inadequate response to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1) to receive oral upadacitinib 15 mg once daily or placebo using interactive response technology. Random treatment assignment was stratified by MRI inflammation in the sacroiliac joints and screening high-sensitivity C-reactive protein status (MRI-positive and C-reactive protein-positive, MRI-positive and C-reactive protein-negative, and MRI-negative and C-reactive protein-positive) and previous exposure to biologic disease-modifying antirheumatic drugs (yes vs no). Treatment assignment was masked from patients, investigators, study site personnel, and the study sponsor. The primary endpoint was the proportion of patients with an Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Analyses were performed on the full analysis set of patients, who underwent random allocation and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04169373. FINDINGS: Between Nov 26, 2019, and May 20, 2021, 314 patients with active non-radiographic axial spondyloarthritis were enrolled into the study, and 313 received study drug (156 in the upadacitinib group and 157 in the placebo group); 295 (94%) patients (145 in the upadacitinib group and 150 in the placebo group) received treatment for the full 14 weeks. A significantly higher ASAS40 response rate was achieved with upadacitinib compared with placebo at week 14 (70 [45%] of 156 patients vs 35 [23%] of 157 patients; p<0·0001; treatment difference 22%, 95% CI 12-32). The rate of adverse events up to week 14 was similar in the upadacitinib group (75 [48%] of 156 patients) and placebo group (72 [46%] of 157 patients). Serious adverse events and adverse events leading to discontinuation of study drug occurred in four (3%) of 156 patients in the upadacitinib group and two (1%) of 157 patients in the placebo group. Few patients had serious infections or herpes zoster in either treatment group (each event occurred in two [1%] of 156 patients in the upadacitinib group and one [1%] of 157 patients in the placebo group). Five (3%) of 156 patients in the upadacitinib group had neutropenia; no events of neutropenia occurred in the placebo group. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, or deaths were reported with upadacitinib treatment. INTERPRETATION: Upadacitinib significantly improved the signs and symptoms of non-radiographic axial spondyloarthritis compared with placebo at week 14. These findings support the potential of upadacitinib as a new therapeutic option in patients with active non-radiographic axial spondyloarthritis. FUNDING: AbbVie.

Spatial-temporal clustering of an outbreak of SARS-CoV-2 Delta VOC in Guangzhou, China in 2021.

Background: In May 2021, the SARS-CoV-2 Delta variant led to the first local outbreak in China in Guangzhou City. We explored the epidemiological characteristics and spatial-temporal clustering of this outbreak. Methods: Based on the 153 cases in the SARS-CoV-2 Delta variant outbreak, the Knox test was used to analyze the spatial-temporal clustering of the outbreak. We further explored the spatial-temporal clustering by gender and age groups, as well as compared the changes of clustering strength (S) value between the two outbreaks in Guangzhou. Results: The result of the Knox analysis showed that the areas at short distances and brief periods presented a relatively high risk. The strength of clustering of male-male pairs was higher. Age groups showed that clustering was concentrated in cases aged ≤ 18 years matched to 18-59 years and cases aged 60+ years. The strength of clustering of the outbreak declined after the implementation of public health measures. The change of strength of clustering at time intervals of 1-5 days decreased greater in 2021 (S = 129.19, change rate 38.87%) than that in 2020 (S = 83.81, change rate 30.02%). Conclusions: The outbreak of SARS-CoV-2 Delta VOC in Guangzhou has obvious spatial-temporal clustering. The timely intervention measures are essential role to contain this outbreak of high transmission.

Reduced binding activity of vaccine serum to omicron receptor-binding domain.

Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). However, the emergence and rapid transmission of the SARS-CoV-2 variant Omicron raise a concern about the efficacy of the current vaccination strategy. Here, we expressed monomeric and dimeric receptor-binding domains (RBDs) of the spike protein of prototype SARS-CoV-2 and Omicron variant in E. coli and investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to these recombinant RBDs. In 106 human blood samples collected from 91 participants from Jiangxi, China, 26 sera were identified to be positive for SARS-CoV-2 spike protein antibodies by lateral flow dipstick (LFD) assays, which were enriched in the ones collected from day 7 to 1 month post-boost (87.0%) compared to those harvested within 1 week post-boost (23.8%) (P < 0.0001). A higher positive ratio was observed in the child group (40.8%) than adults (13.6%) (P = 0.0073). ELISA results showed that the binding activity of anti-SARS-CoV-2 antibody-positive sera to Omicron RBDs dropped by 1.48- to 2.07-fold compared to its homogeneous recombinant RBDs. Thus, our data indicate that current SARS-CoV-2 vaccines provide restricted humoral protection against the Omicron variant.

Reduced binding activity of vaccine serum to omicron receptor-binding domain

Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). However, the emergence and rapid transmission of the SARS-CoV-2 variant Omicron raise a concern about the efficacy of the current vaccination strategy. Here, we expressed monomeric and dimeric receptor-binding domains (RBDs) of the spike protein of prototype SARS-CoV-2 and Omicron variant in E. coli and investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to these recombinant RBDs. In 106 human blood samples collected from 91 participants from Jiangxi, China, 26 sera were identified to be positive for SARS-CoV-2 spike protein antibodies by lateral flow dipstick (LFD) assays, which were enriched in the ones collected from day 7 to 1 month post-boost (87.0%) compared to those harvested within 1 week post-boost (23.8%) (P < 0.0001). A higher positive ratio was observed in the child group (40.8%) than adults (13.6%) (P = 0.0073). ELISA results showed that the binding activity of anti-SARS-CoV-2 antibody-positive sera to Omicron RBDs dropped by 1.48- to 2.07-fold compared to its homogeneous recombinant RBDs. Thus, our data indicate that current SARS-CoV-2 vaccines provide restricted humoral protection against the Omicron variant.

Telehealth and the Digital Divide: Identifying Potential Care Gaps in Video Visit Use.

In recent years, telehealth visits have surged in response to the COVID-19 pandemic. However, existing structural inequities impact the access and use of information technology based on social and geographical characteristics, which is referred to as the digital divide. This has created disparities between patients with access to video visits vs. telephone visits. Previous telehealth research has focused on the completion of video visits. However, further research is needed to understand patients who decline video visits and rely on phone visits. We conducted semi-structured interviews (n = 13) of older patients (n = 9) and clinical support staff (n = 4) to understand the barriers in accessing virtual care. Most patients reported feeling left behind with telehealth, despite having access to a computer or smartphone. Clinical staff identified access to reliable technology and the ability for patients to navigate the technology as primary barriers to accessing virtual care. Many patients indicated an interest in video visits, but wanted low tech solutions and at-the-elbow support to build confidence with the technology.

Co-benefits of nonpharmaceutical intervention against COVID-19 on infectious diseases in China: A large population-based observational study.

Background: Nonpharmaceutical interventions (NPIs) are public health measures that aim to suppress the transmission of infectious diseases, including border restrictions, quarantine and isolation, community management, social distancing, face mask usage, and personal hygiene. This research aimed to assess the co-benefits of NPIs against COVID-19 on notifiable infectious diseases (NIDs) in Guangdong Province, China. Methods: Based on NID data from the Notifiable Infectious Diseases Surveillance System in Guangdong, we first compared the incidence of NIDs during the emergency response period (weeks 4-53 of 2020) with those in the same period of 2015-2019 and then compared that with the expected incidence during the synchronous period of 2020 for each city by using a Bayesian structural time series model. Findings: A total of 514,341 cases of 39 types of NIDs were reported in Guangdong during the emergency response period in 2020, which decreased by 50·7% compared with the synchronous period during 2015-2019. It was estimated that the number of 39 NIDs during the emergency response in 2020 was 65·6% (95% credible interval [CI]: 64·0% - 68·2%) lower than expected, which means that 982,356 (95% CI: 913,443 - 1,105,170) cases were averted. The largest reduction (82·1%) was found for children aged 0-14 years. For different categories of NIDs, natural focal diseases and insect-borne infectious diseases had the greatest reduction (89·4%), followed by respiratory infectious diseases (87·4%), intestinal infectious diseases (59·4%), and blood-borne and sexually transmitted infections (18·2%). Dengue, influenza, and hand-foot-and-mouth disease were reduced by 99·3%, 95·1%, and 76·2%, respectively. Larger reductions were found in the regions with developed economies and a higher number of COVID-19 cases. Interpretation: NPIs against COVID-19 may have a large co-benefit on the prevention of other infectious diseases in Guangdong, China, and the effects have heterogeneity in populations, diseases, time and space. Funding: Key-Area Research and Development Program of Guangdong Province.

The time-varying transmission dynamics of COVID-19 and synchronous public health interventions in China.

OBJECTIVES: We aimed to estimate the time-varying transmission dynamics of COVID-19 in China, Wuhan City, and Guangdong province, and compare to that of severe acute respiratory syndrome (SARS). METHODS: Data on COVID-19 cases in China up to 20 March 2020 was collected from epidemiological investigations or official websites. Data on SARS cases in Guangdong Province, Beijing, and Hong Kong during 2002-3 was also obtained. We estimated the doubling time, basic reproduction number (R0), and time-varying reproduction number (Rt) of COVID-19 and SARS. RESULTS: As of 20 March 2020, 80,739 locally acquired COVID-19 cases were identified in mainland China, with most cases reported between 20 January and 29 February 2020. The R0 value of COVID-19 in China and Wuhan was 5.0 and 4.8, respectively, which was greater than the R0 value of SARS in Guangdong (R0 = 2.3), Hong Kong (R0 = 2.3), and Beijing (R0 = 2.6). At the start of the COVID-19 epidemic, the Rt value in China peaked at 8.4 and then declined quickly to below 1.0 in one month. With SARS, the Rt curve saw fluctuations with more than one peak, the highest peak was lower than that for COVID-19. CONCLUSIONS: COVID-19 has much higher transmissibility than SARS, however, a series of prevention and control interventions to suppress the outbreak were effective. Sustained efforts are needed to prevent the rebound of the epidemic in the context of the global pandemic.