Dexamethasone has demonstrated efficacy in reducing mortality in COVID‐19. However, its practical use is badly defined. We aimed to investigate factors associated with dexamethasone efficacy in real ...life. Our retrospective study was conducted in two university hospitals between September and November 2020 and included all the consecutive hospitalized patients with a laboratory‐confirmed SARS‐CoV‐2 infection assessed by RT‐PCR, treated with intravenous dexamethasone (6 mg/day). Among 111 patients, 10.6% necessitated a transfer into the intensive care unit (ICU) and the 28‐day mortality rate was 17.1%. The 28‐day mortality rate was significantly lower in patients who demonstrated improvement at 48 h (hazard ratio HR: 0.17, 95% confidence interval CI: 0.04–0.78, p = 0.02) and 96 h (HR: 0.07, 95% CI: 0.02–0.31, p = 0.0005) after dexamethasone initiation. Apart from well‐known risk factors (age, hypertension, active cancer, severe lesions on chest computed tomography CT scan), we found that a high viral load in nasopharyngeal swab (Cycle threshold <30) at dexamethasone initiation was associated with higher 28‐day mortality (66.6% vs. 36.7%, p = 0.03). Patients who did not receive antibiotics at dexamethasone initiation had a higher rate of transfer into the ICU (55.6% vs. 23.5%, p = 0.045) with a trend towards higher mortality in case of severe or critical lesions on CT scan (75.0% vs. 25.0%, p = 0.053). Patients who did not improve within 2–4 days after steroid initiation have a bad prognosis and should receive additional anti‐inflammatory drugs. Our data suggest better efficacy of dexamethasone in patients with a low or negative viral load, receiving broad‐spectrum antibiotics.
Highlights
At dexamethasone initiation, a high viral load was associated with higher mortality.
Patients without antibiotics were more transferred into the ICU.
Mortality was lower when improvement 48 h and 96 h after dexamethasone initiation.
What makes humans moral beings? This question can be understood either as a proximate “how” question or as an ultimate “why” question. The “how” question is about the mental and social mechanisms ...that produce moral judgments and interactions, and has been investigated by psychologists and social scientists. The “why” question is about the fitness consequences that explain why humans have morality, and has been discussed by evolutionary biologists in the context of the evolution of cooperation. Our goal here is to contribute to a fruitful articulation of such proximate and ultimate explanations of human morality. We develop an approach to morality as an adaptation to an environment in which individuals were in competition to be chosen and recruited in mutually advantageous cooperative interactions. In this environment, the best strategy is to treat others with impartiality and to share the costs and benefits of cooperation equally. Those who offer less than others will be left out of cooperation; conversely, those who offer more will be exploited by their partners. In line with this mutualistic approach, the study of a range of economic games involving property rights, collective actions, mutual help and punishment shows that participants’ distributions aim at sharing the costs and benefits of interactions in an impartial way. In particular, the distribution of resources is influenced by effort and talent, and the perception of each participant’s rights on the resources to be distributed.
During SARS-CoV-2 infection, eosinopenia may reflect a hyperactive immune response. In this study of hospitalized COVID-19 patients, we aimed to better understand the prognostic value of severe ...eosinopenia (absolute eosinophil count = 0 G/L) and decipher its underlying mechanisms. We retrospectively analyzed the records of COVID-19 patients hospitalized from March to June 2020 in three university hospitals in Marseille, France. We assessed the association between severe eosinopenia and a composite poor outcome in these patients, including the need for oxygen supplementation at >6 L/min, ICU admission, and in-hospital death. Among the 551 COVID-19 patients included in this study, severe eosinopenia was found in 228 (51%) of them on admission to hospital and was associated with a composite poor outcome using multivariate analysis (OR = 2.58; CI95 1.77−3.75; p < 0.0001). We found a significant association between the presence of severe eosinopenia on admission and the elevation in C-reactive protein, ferritin, IP-10, and suPAR. The histological findings in a series of 37 autopsies from patients who died from severe COVID-19 and presented with severe eosinopenia showed no pulmonary eosinophil trapping. Severe eosinopenia can be a reliable biomarker associated with a composite poor outcome in hospitalized COVID-19 adult patients. It may reflect the magnitude of immune hyperactivation during severe-to-critical COVID-19.
This paper focuses on a class of reinforcement learning problems where significant events are rare and limited to a single positive reward per episode. A typical example is that of an agent who has ...to choose a partner to cooperate with, while a large number of partners are simply not interested in cooperating, regardless of what the agent has to offer. We address this problem in a continuous state and action space with two different kinds of search methods: a gradient policy search method and a direct policy search method using an evolution strategy. We show that when significant events are rare, gradient information is also scarce, making it difficult for policy gradient search methods to find an optimal policy, with or without a deep neural architecture. On the other hand, we show that direct policy search methods are invariant to the rarity of significant events, which is yet another confirmation of the unique role evolutionary algorithms has to play as a reinforcement learning method.
Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus ...anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra.
Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation.
Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4%
31.2%, p = 0.76), the in-hospital mortality (31.7%
33.0%, p = 0.83), the high-flow oxygen requirement (17.5%
18.3%, p = 0.86), the intensive care unit admission rate (30.8%
22.2%, p = 0.30), and the mechanical ventilation rate (15.4%
11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1%
30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1%
21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3%
9.2%, p = 0.44).
Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.
Addressing global environmental crises such as anthropogenic climate change requires the consistent adoption of proenvironmental behavior by a large part of a population. Here, we develop a ...mathematical model of a simple behavior-environment feedback loop to ask how the individual assessment of the environmental state combines with social interactions to influence the consistent adoption of proenvironmental behavior, and how this feeds back to the perceived environmental state. In this stochastic individual-based model, individuals can switch between two behaviors, ‘active’ (or actively proenvironmental) and ‘baseline’, differing in their perceived cost (higher for the active behavior) and environmental impact (lower for the active behavior). We show that the deterministic dynamics and the stochastic fluctuations of the system can be approximated by ordinary differential equations and a Ornstein-Uhlenbeck type process. By definition, the proenvironmental behavior is adopted consistently when, at population stationary state, its frequency is high and random fluctuations in frequency are small. We find that the combination of social and environmental feedbacks can promote the spread of costly proenvironmental behavior when neither, operating in isolation, would. To be adopted consistently, strong social pressure for proenvironmental action is necessary but not sufficient—social interactions must occur on a faster timescale compared to individual assessment, and the difference in environmental impact must be small. This simple model suggests a scenario to achieve large reductions in environmental impact, which involves incrementally more active and potentially more costly behavior being consistently adopted under increasing social pressure for proenvironmentalism.
While necessary parts of the puzzle, cultural technologies are insufficient to explain peace. They are a form of second-order cooperation - a cooperative interaction designed to incentivize ...first-order cooperation. We propose an explanation for peacemaking cultural technologies, and therefore peace, based on the reputational incentives for second-order cooperation.
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