Stress, intertemporal choice, and mitigation behavior during the COVID-19 pandemic.

Delayed gratification is an important focus of research, given its potential relationship to forms of behavior, such as savings, susceptibility to addiction, and pro-social behaviors. The COVID-19 pandemic may be one of the most consequential recent examples of this phenomenon, with people's willingness to delay gratification affecting their willingness to socially distance themselves. COVID-19 also provides a naturalistic context by which to evaluate the ecological validity of delayed gratification. This article outlines four large-scale online experiments (total N = 12, 906) where we ask participants to perform Money Earlier or Later (MEL) decisions (e.g., $5 today vs. $10 tomorrow) and to also report stress measures and pandemic mitigation behaviors. We found that stress increases impulsivity and that less stressed and more patient individuals socially distanced more throughout the pandemic. These results help resolve longstanding theoretical debates in the MEL literature as well as provide policymakers with scientific evidence that can help inform response strategies in the future. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial.

Importance: It is unknown whether ivermectin, with a maximum targeted dose of 600 µg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19. Objective: To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19. Design, Setting, and Participants: The ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1206 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022. Interventions: Participants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 µg/kg (n = 602) daily, or placebo (n = 604) for 6 days. Main Outcomes and Measures: The primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28. Results: Among 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 µg/kg daily for 6 days, compared with placebo did not improve time to sustained recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530.

Lower Risk of Multisystem Inflammatory Syndrome in Children (MIS-C) with the Delta and Omicron variants of SARS-CoV-2.

Little is known about the MIS-C risk with different SARS-CoV-2 variants. In Southeast England, MIS-C rates per confirmed SARS-CoV-2 infections in 0-16 years-olds were 56% lower (rate ratio, 0.34; 95%CI, 0.23-0.50) during pre-vaccine Delta, 66% lower (0.44; 0.28-0.69) during post-vaccine Delta and 95% lower (0.05; 0.02-0.10) during the Omicron period.

Spleen tyrosine kinase inhibition restores myeloid homeostasis in COVID-19.

Spleen tyrosine kinase (SYK) is a previously unidentified therapeutic target that inhibits neutrophil and macrophage activation in coronavirus disease 2019 (COVID-19). Fostamatinib, a SYK inhibitor, was studied in a phase 2 placebo-controlled randomized clinical trial and was associated with improvements in many secondary end points related to efficacy. Here, we used a multiomic approach to evaluate cellular and soluble immune mediator responses of patients enrolled in this trial. We demonstrated that SYK inhibition was associated with reduced neutrophil activation, increased circulation of mature neutrophils (CD10+CD33-), and decreased circulation of low-density granulocytes and polymorphonuclear myeloid-derived suppressor cells (HLA-DR-CD33+CD11b-). SYK inhibition was also associated with normalization of transcriptional activity in circulating monocytes relative to healthy controls, an increase in frequency of circulating nonclassical and HLA-DRhi classical monocyte populations, and restoration of interferon responses. Together, these data suggest that SYK inhibition may mitigate proinflammatory myeloid cellular and soluble mediator responses thought to contribute to immunopathogenesis of severe COVID-19.

Parallels between our response to COVID-19 and approach to patient safety.

The response to the COVID-19 pandemic and the approach to patient safety share three important concepts: the challenges of preventing rare events, use of rules, and tolerance for uncertainty. We discuss how each of these ideas can be utilised in perioperative safety to create a high-reliability system.

mRNA or ChAd0x1 COVID-19 Vaccination of Adolescents Induces Robust Antibody and Cellular Responses With Continued Recognition of Omicron Following mRNA-1273.

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant.

Utility of Esophageal Ultrasound-guided Biopsy of Mediastinal Lymph Nodes in Diagnosis of Childhood Tuberculosis.

A 6-year-old boy with autistic spectrum disorder was diagnosed with tuberculosis infection following contact tracing of his mother who had isoniazid-resistant pulmonary tuberculosis. He progressed to develop mediastinal lymphadenopathy causing a persistent cough. He was too small to undergo endobronchial ultrasound-guided biopsy. As an alternative, he underwent esophageal endoscopic ultrasound-guided biopsy, leading to confirmation of the diagnosis. We believe this approach to diagnostic biopsy is underrecognized in pediatric practice, and highlight its utility with this case and a brief literature review.

Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: Non-antiviral therapeutic options are required for the treatment of hospitalised patients with COVID-19. CD24Fc is an immunomodulator with potential to reduce the exaggerated inflammatory response to tissue injuries. We aimed to evaluate the safety and efficacy of CD24Fc in hospitalised adults with COVID-19 receiving oxygen support. METHODS: We conducted a randomised, double-blind, placebo-controlled, phase 3 study at nine medical centres in the USA. Hospitalised patients (age ≥18 years) with confirmed SARS-CoV-2 infection who were receiving oxygen support and standard of care were randomly assigned (1:1) by site-stratified block randomisation to receive a single intravenous infusion of CD24Fc 480 mg or placebo. The study funder, investigators, and patients were masked to treatment group assignment. The primary endpoint was time to clinical improvement over 28 days, defined as time that elapsed between a baseline National Institute of Allergy and Infectious Diseases ordinal scale score of 2-4 and reaching a score of 5 or higher or hospital discharge. The prespecified primary interim analysis was done when 146 participants reached the time to clinical improvement endpoint. Efficacy was assessed in the intention-to-treat population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT04317040. FINDINGS: Between April 24 and Sept 22, 2020, 243 hospitalised patients were assessed for eligibility and 234 were enrolled and randomly assigned to receive CD24Fc (n=116) or placebo (n=118). The prespecified interim analysis was done when 146 participants reached the time to clinical improvement endpoint among 197 randomised participants. In the interim analysis, the 28-day clinical improvement rate was 82% (81 of 99) for CD24Fc versus 66% (65 of 98) for placebo; median time to clinical improvement was 6·0 days (95% CI 5·0-8·0) in the CD24Fc group versus 10·0 days (7·0-15·0) in the placebo group (hazard ratio [HR] 1·61, 95% CI 1·16-2·23; log-rank p=0·0028, which crossed the prespecified efficacy boundary [α=0·0147]). 37 participants were randomly assigned after the interim analysis data cutoff date; among the 234 randomised participants, median time to clinical improvement was 6·0 days (95% CI 5·0-9·0) in the CD24Fc group versus 10·5 days (7·0-15·0) in the placebo group (HR 1·40, 95% CI 1·02-1·92; log-rank p=0·037). The proportion of participants with disease progression within 28 days was 19% (22 of 116) in the CD24Fc group versus 31% (36 of 118) in the placebo group (HR 0·56, 95% CI 0·33-0·95; unadjusted p=0·031). The incidences of adverse events and serious adverse events were similar in both groups. No treatment-related adverse events were observed. INTERPRETATION: CD24Fc is generally well tolerated and accelerates clinical improvement of hospitalised patients with COVID-19 who are receiving oxygen support. These data suggest that targeting inflammation in response to tissue injuries might provide a therapeutic option for patients hospitalised with COVID-19. FUNDING: Merck & Co, National Cancer Institute, OncoImmune.

Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. RESULTS: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ±â€…0.3 vs -2.6 ±â€…0.4, P = .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, P = .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group. CONCLUSION: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT04579393.

Organ donation in the time of COVID-19: the Israeli experience one year into the pandemic-ethical and policy implications.

PURPOSE: To present the response of the Israel National Transplantation Center (NTC) to the evolving challenge of COVID-19, the impact on deceased organ donation and living organ kidney donation during 2020, and resultant policy and ethical implications. METHODS: Data collected included (i) for deceased donors, the total number of potential organ donors, if hospitalized in ICU or general ward, cause of death, number of family authorizations and refusals, number of actual donors, number of organs transplanted/donor and total number of transplants performed; (ii) for living-kidney-donors (related or altruistic), the number of procedures performed; and (iii) the number of patients registered on the national organ waiting-list. RESULTS: Following the first case (February 2020), deceased organ donation continued uninterrupted. The total number of potential donors was similar to 2019 (181 vs. 189). However, the number of families approached for donation decreased significantly (P = 0.02). This may be attributed to COVID-19-imposed limitations including fewer brain death determinations due to limited possibilities for face-to-face donor coordinator-donor family interactions providing emotional support and visual explanations of the medical situation. Fewer donors were admitted to ICU (P = 0.1) and the number of organs retrieved/donor decreased (3.8/donor to 3.4/donor). The overall result was a decrease of 24.2% in the number of transplant procedures (306 vs. 232). Living kidney donation, initially halted, resumed in May and the total number of procedures increased compared to 2019 due to a significant increase in altruistic donations (P < 0.0001), while the number of related-living donations decreased. CONCLUSION: This study of organ donation during a crisis has informed the introduction of policy changes in the NTC including the necessity to mobilize rapidly a "war room", the use of innovative virtual tools for contact-less communication, and the importance of cooperation with hospital authorities in allocating scarce health-care resources. Finally, the pandemic highlighted and intensified ethical considerations, such as under what circumstances living kidney donation be continued in the face of uncertainty, and what information to provide to altruistic donors regarding a prospective recipient, in particular whether all options for related living donation have been exhausted. These should be addressed now.

Making it Real: The Role of Parasocial Relationships in Enhancing Perceived Susceptibility and COVID-19 Protective Behavior

Formation of accurate risk perceptions and adoption of protective measures play a key role in reducing transmission and stopping the spread of infectious diseases. Extant research, however, has shown that perceptions of risk are not necessarily correlated with the level of actual risk, including that of COVID-19. Informed by the social amplification of risk framework (SARF), we test whether having a parasocial relationship with a celebrity who has COVID-19 makes the risk of contracting the virus more real, thus amplifying the perceived susceptibility to the virus and reducing the biased sense of optimism that one is safe. Findings from Study 1, a national survey (N = 493), suggest that having a parasocial friend contract COVID-19, is related to increased perceived susceptibility, especially for those for whom it would otherwise seem and vague. Study 2 (N = 228) complements these findings by identifying a potential underlying mechanism for the observed relationship between PSR and perceived susceptibility – attenuation of the optimism bias. Findings are discussed in terms of their contribution to understanding the underlying mechanisms of the potential role played by celebrities in health and risk communication. [ FROM AUTHOR] Copyright of Media Psychology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Local and systemic responses to SARS-CoV-2 infection in children and adults.

It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

Keep Calm and Stay Safe: The Relationship between Anxiety and Other Psychological Factors, Media Exposure and Compliance with COVID-19 Regulations.

The COVID-19 pandemic has led many countries to employ public health regulations to achieve behavioral change and stop the transmission of the virus. The factors influencing compliance with these regulations may differ from "classic" predictors for medical compliance. This study attempted to assess the effect of social communication and psychological factors on intention to comply. A cross-sectional online survey was conducted on healthy adults living in Israel (n = 697). The survey assessed the intention to comply with the state COVID-19 regulations and explored possible correlations with demographic and psychosocial factors. Data were collected during May 2020 using a Qualtrics online survey. Data were analyzed to find correlations between anxiety, uncertainty, media exposure and other variables and the level of intention to comply as self-reported. Moderation and mediation effects were studied by an integrative model of influencing factors. We found that media exposure change, trust in responsible agencies and anxiety were positively correlated with compliance, while uncertainty was correlated with noncompliance. The effect of media exposure on compliance had two components. First, media exposure was positively correlated with compliance. On the other hand, media exposure was positively correlated with uncertainty, and uncertainty was negatively correlated with compliance. Interestingly, anxiety, which was positively correlated with media exposure, also moderated the negative correlation between uncertainty and compliance. Our results highlight the important role of uncertainty and anxiety as moderators between media exposure and compliance. To increase public compliance with COVID-19 regulations, efforts should be directed at decreasing uncertainty and anxiety.

Gastrointestinal endoscopy during the coronavirus pandemic in the New York area: results from a multi-institutional survey.

Background and study aims The coronavirus disease 2019 (COVID-19), and measures taken to mitigate its impact, have profoundly affected the clinical care of gastroenterology patients and the work of endoscopy units. We aimed to describe the clinical care delivered by gastroenterologists and the type of procedures performed during the early to peak period of the pandemic. Methods Endoscopy leaders in the New York region were invited to participate in an electronic survey describing operations and clinical service. Surveys were distributed on April 7, 2020 and responses were collected over the following week. A follow-up survey was distributed on April 20, 2020. Participants were asked to report procedure volumes and patient characteristics, as well protocols for staffing and testing for COVID-19. Results Eleven large academic endoscopy units in the New York City region responded to the survey, representing every major hospital system. COVID patients occupied an average of 54.5 % (18 - 84 %) of hospital beds at the time of survey completion, with 14.5 % (2 %-23 %) of COVID patients requiring intensive care. Endoscopy procedure volume and the number of physicians performing procedures declined by 90 % (66 %-98 %) and 84.5 % (50 %-97 %) respectively following introduction of restricted practice. During this period the most common procedures were EGDs (7.9/unit/week; 88 % for bleeding; the remainder for foreign body and feeding tube placement); ERCPs (5/unit/week; for cholangitis in 67 % and obstructive jaundice in 20 %); Colonoscopies (4/unit/week for bleeding in 77 % or colitis in 23 %) and least common were EUS (3/unit/week for tumor biopsies). Of the sites, 44 % performed pre-procedure COVID testing and the proportion of COVID-positive patients undergoing procedures was 4.6 % in the first 2 weeks and up to 19.6 % in the subsequent 2 weeks. The majority of COVID-positive patients undergoing procedures underwent EGD (30.6 % COVID +) and ERCP (10.2 % COVID +). Conclusions COVID-19 has profoundly impacted the operation of endoscopy units in the New York region. Our data show the impact of a restricted emergency practice on endoscopy volumes and the proportion of expected COVID positive cases during the peak time of the pandemic.