Booster dose of self-amplifying SARS-CoV-2 RNA vaccine vs. mRNA vaccine: a phase 3 comparison of ARCT-154 with Comirnaty (preprint)

Background Licensed mRNA vaccines demonstrated initial effectiveness against COVID-19 but require booster doses to broaden the anti-SARS-CoV-2 response. There is an unmet need for novel highly immunogenic and broadly protective vaccines. We compared immunogenicity and tolerability of ARCT-154, a novel self-amplifying mRNA vaccine with the mRNA vaccine, Comirnaty. Methods We compared immune responses to ARCT-154 and Comirnaty booster doses in healthy 18-77-year-old Japanese adults initially immunised with two doses of mRNA COVID-19 vaccine (Comirnaty or Spikevax) then a third dose of Comirnaty at least 3 months previously. Neutralising antibodies were measured before and 28 days after booster vaccination. The primary objective was to demonstrate non-inferiority of the immune response against Wuhan-Hu-1 SARS-CoV-2 virus as geometric mean titre (GMT) ratios and seroresponse rates (SRR) of neutralising antibodies; key secondary endpoints included the immune response against the Omicron BA.4/5 variant and vaccine tolerability assessed using participant-completed electronic diaries. Findings Between December 13, 2022 and February 25, 2023 we enrolled 828 participants randomised 1:1 to receive ARCT-154 (n = 420) or Comirnaty (n = 408) booster doses. Four weeks after boosting, ARCT-154 induced higher Wuhan-Hu-1 neutralising antibodies GMTs than Comirnaty (5641 [95% CI: 4321-7363] and 3934 [2993-5169], respectively), a GMT ratio of 1.43 (95% CI: 1.26-1.63), with SRR of 65.2% (60.2-69.9) and 51.6% (46.4-56.8) meeting the non-inferiority criteria. Respective anti-Omicron BA.4/5 GMTs were 2551 (1687-3859) and 1958 (1281-2993), a GMT ratio of 1.30 (95% CI: 1.07-1.58), with SRR of 69.9% (65.0-74.4) and 58.0% (52.8-63.1), meeting the superiority criteria for ARCT-154 over Comirnaty. Booster doses of either ARCT-154 or Comirnaty were equally well-tolerated with no causally-associated severe or serious adverse events; 94.8% and 96.8% of ARCT-154 and Comirnaty vaccinees reported local reactions and 65.7% and 62.5% had solicited systemic adverse events. Events were mainly mild in severity, occurring and resolving within 3-4 days of vaccination. Interpretation Immune responses four weeks after an ARCT-154 booster dose in mRNA-immunised adults were higher than after a Comirnaty booster, meeting non-inferiority criteria against the prototype Wuhan-Hu-1 virus, and superiority criteria against the Omicron BA.4/5 variant.

Psychological distance and user engagement in online exhibitions: Visualization of moiré patterns based on electroencephalography signals

The COVID-19 pandemic has significantly affected the exhibition of artworks in museums and galleries. Many have displayed their collection online. In this context, experiencing an online exhibition is essential for visitors to appreciate and understand the artwork. Compared with offline exhibitions, visitors to online exhibitions are often unable to communicate their experiences with other visitors. Therefore, in this study, by facilitating communication via Zoom call, we established a system that allows two people to visit the museum together through the Google Arts and Culture (GA&C) website. To reduce the psychological distance between online visitors and help increase user engagement, we designed and developed a media device based on moiré pattern visualization of electroencephalography (EEG) signals. The participants were divided into two groups to visit the online museum, communicating remotely through Zoom. The objective of this study was to test whether a real-time EEG signal visualization device could help close the psychological distance between participants and whether it could increase user engagement with the online exhibition. Participants were randomly assigned to either the normal online exhibition experience (NOEE) group or EEG signal visualization device (ESVD) group. Participants in the NOEE group experienced four online exhibitions (Task1, Task2, Task3, and Task4) together (two participants per test unit). The conditions for participants in the ESVD group remained the same, apart from adding a media device to enable them to visualize EEG signals. A total of 40 university students participated in this study. Independent samples t-tests revealed that participants in the ESVD group perceived a significantly closer psychological distance between themselves and the participants on the opposite side than those in the NOEE group (t = −2.699;p = 0.008 < 0.05). A one-way ANOVA revealed that participants experienced Task3 with significantly closer psychological distance assessments than Task1 (p = 0.002 < 0.05), Task2 (p = 0.000 < 0.05), and Task4 (p = 0.001 < 0.05). Repeated ANOVAs revealed that participants in the ESVD group had higher overall user engagement than those in the NOEE group, with marginal significance (p = 0.056 < 0.1). Thus, this study shows that EEG visualization media devices can reduce the psychological distance between two participants when experiencing an online exhibition. Moreover, it can increase user engagement to some extent.

Risk factors for mortality of coronavirus disease-2019 (COVID-19) patients in two centers of Hubei province, China: A retrospective analysis.

PURPOSE: Since the outbreak in late December 2019 in Wuhan, China, coronavirus disease-2019 (COVID-19) has become a global pandemic. We analyzed and compared the clinical, laboratory, and radiological characteristics between survivors and non-survivors and identify risk factors for mortality. METHODS: Clinical and laboratory variables, radiological features, treatment approach, and complications were retrospectively collected in two centers of Hubei province, China. Cox regression analysis was conducted to identify the risk factors for mortality. RESULTS: A total of 432 patients were enrolled, and the median patient age was 54 years. The overall mortality rate was 5.09% (22/432). As compared with the survivor group (n = 410), those in the non-survivor group (n = 22) were older, and they had a higher frequency of comorbidities and were more prone to suffer from dyspnea. Several abnormal laboratory variables indicated that acute cardiac injury, hepatic damage, and acute renal insufficiency were detected in the non-survivor group. Non-surviving patients also had a high computed tomography (CT) score and higher rate of consolidation. The most common complication causing death was acute respiratory distress syndrome (ARDS) (18/22, 81.8%). Multivariate Cox regression analysis revealed that hemoglobin (Hb) <90 g/L (hazard ratio, 10.776; 95% confidence interval, 3.075-37.766; p<0.0001), creatine kinase (CK-MB) >8 U/L (9.155; 2.424-34.584; p = 0.001), lactate dehydrogenase (LDH) >245 U/L (5.963; 2.029-17.529; p = 0.001), procalcitonin (PCT) >0.5 ng/ml (7.080; 1.671-29.992; p = 0.008), and CT score >10 (39.503; 12.430-125.539; p<0.0001) were independent risk factors for the mortality of COVID-19. CONCLUSIONS: Low Hb, high LDH, PCT, and CT score on admission were the predictors for mortality and could assist clinicians in early identification of poor prognosis among COVID-19 patients.

Nearly One In Five Skilled Nursing Facilities Awarded Positive Incentives Under Value-Based Purchasing.

Medicare's Skilled Nursing Facility Value-Based Purchasing Program, which awards value-based incentive payments based on hospital readmissions, distributed its first two rounds of incentives during fiscal years 2019 and 2020. Incentive payments were based on achievement or improvement scores-whichever was better. Incentive payments were as low as -2.0 percent in both program years and as high as +1.6 percent in FY 2019 and +3.1 percent in FY 2020. In FY 2019, 26 percent of facilities earned positive incentives and 72 percent earned negative incentives, compared with 19 percent positive and 65 percent negative incentives in FY 2020. Larger, rural, and not-for-profit facilities were more likely to earn positive incentives, as were those with the highest registered nurse staffing levels. Although these findings indicate the potential to reward high-quality care at skilled nursing facilities, intended and unintended outcomes of this new value-based purchasing program should be monitored closely for possible program refinements, particularly in light of the disproportionate impacts of coronavirus disease 2019 (COVID-19) on nursing facilities.

Discrimination in the Venture Capital Industry: Evidence from Two Randomized Controlled Trials (preprint)

This paper examines discrimination based on startup founders' gender, race, and age by early-stage investors using two complementary field experiments with real U.S. venture capitalists. The first experiment invites investors to evaluate multiple randomly generated startup profiles, which they know to be hypothetical, in order to be matched with real, high-quality startups from collaborating incubators. Investors can also donate money to randomly displayed startup teams to show their anonymous support during the COVID-19 pandemic. The second experiment consists of sending hypothetical pitch emails with randomized startups' information to global venture capitalists and comparing their email behaviors by utilizing a new email technology that tracks investors' detailed information acquisition behaviors. These experiments provide the following findings. (i) In the contact stage, investors are biased towards female, Asian, and older founders of relatively low-quality startups, while they are biased against female, Asian, and older founders of relatively high-quality startups. This result provides a potential reconciliation of the contradictory results in the extant literature. (ii) Among multiple coexisting sources of bias identified, statistical discrimination and implicit bias are important reasons for investors' "anti-minority" behaviors. A consistent estimator is developed to measure the polarization of investors' biases and their separate driving forces. And finally, (iii) there was a temporary, stronger bias against Asian founders during the COVID-19 outbreak, which started to fade in April 2020.

Heat inactivation of serum interferes with the immunoanalysis of antibodies to SARS-CoV-2 (preprint)

The detection of serum antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a new tool for the coronavirus disease-2019 (COVID-19) diagnosis. Since many coronaviruses are sensitive to heat, heating inactivation of samples at 56 prior to testing is considered a possible method to reduce the risk of transmission, but the effect of heating on the measurement of SARS-CoV-2 antibodies is still unclear. By comparing the levels of SARS-CoV-2 antibodies before and after heat inactivation of serum at 56 for 30 minutes using a quantitative fluorescence immunochromatographic assay, we shown that heat inactivation significantly interferes with the levels of antibodies to SARS-CoV-2. The IgM levels of all the 34 serum samples (100%) from COVID-19 patients decreased by an average level of 53.56%. The IgG levels were decreased in 22 of 34 samples (64.71%) by an average level of 49.54%. Similar changes can also be observed in the non-COVID-19 diseases group (n=9). Of note, 44.12% of the detected IgM levels were dropped below the cut-off value after heating, suggesting heat inactivation can lead to false-negative results of these samples. Our results indicate that heat inactivation of serum at 56 for 30 minutes interferes with the immunoanalysis of antibodies to SARS-CoV-2. Heat inactivation prior to immunoanalysis is not recommended and the possibility of false-negative results should be considered if the sample was pre-inactivated by heating.