The psychoneuroendocrine response of aggression due to COVID-19 social isolation

The pandemic caused by the SARS-COV-2 virus in the years 2020-2022 altered the emotional behavior of humans. The restrictive feeling caused by the isolation and the change of life habits that demanded a social separation promoted anxiety, distress, apathy, domestic violence, educational problems, and economic instability, among other aspects. Erroneous statistics, and social media information about the number of people infected by the coronavirus SARS-COV-2, aggravated human anxiety and depression. This review compares the main psychological effects caused by pandemic isolation compared to other isolated social contexts. We studied the primary central nervous system areas involved in human reactive aggressiveness behavior. We examine this behavior in relationship with catecholamines and hormones during social isolation. We do not measure or analyze any hormone in our laboratory and only describe the circuits involved in the neuroendocrine response to the aggressive behavior. (English) [ FROM AUTHOR] La pandemia causada por el virus Sars-Cov-2 durante los años 2020 a 2022, alteró la conducta emocional de los humanos. El sentimiento de restricción causado por el aislamiento y el cambio de hábitos de vida que demandaron una separación social promovieron: ansiedad, estrés, apatía, violencia doméstica, problemas educativos e inestabilidad económica, entre otros aspectos. Estadísticas erróneas y de los medios de información acerca del número de personas infectadas por el Coronavirus Sars-Cov-2 agravaron la ansiedad y la depresión humana. Esta revisión compara los principales efectos psicológicos causados por el aislamiento durante la pandemia comparado con otros contextos de aislamiento social. Nosotros estudiamos las áreas primarias involucradas en la conducta de agresión reactiva en los humanos y analizamos esta conducta en relación con las catecolaminas y hormonas durante el aislamiento social. No medimos ni analizamos ninguna hormona en nuestro laboratorio solo describimos los circuitos involucrados en la respuesta neuroendocrina a la conducta agresiva. (Spanish) [ FROM AUTHOR] Copyright of Revista Mexicana de Neurociencia is the property of Academia Mexicana de Neurologia 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.)

Return and volatility spillovers among global assets: Comparing health crisis with geopolitical crisis

This study investigates the dynamic mechanism across equity, cryptocurrency, and commodity markets before and during health and geopolitical crisis (Covid-19 and the Ukrainian war). We apply the (TVP-VAR) based extended joint connectedness methodology, to understand return and volatility connectedness of financial markets for 2010–2023 period. The empirical results indicate that spillovers were particularly high during the Covid-19 and Russia-Ukraine war. First, health and geopolitical risks considerably impact the return and volatility system. Second, the value of total joint connectedness during the COVID-19 period was greater than during Russia-Ukraine war crisis. Also, evidence suggests that Commodity markets, received the highest shocks from other markets after Russia-Ukraine war and wheat was the main commodity receiving chocks from both health and geopolitical crisis. Our findings indicate that spillover channels differ depending on the type of crisis. Specifically, low-frequency components are the main transmission channels during the health crisis, whereas high-frequency components are the main transmission channels during the geopolitical crisis. Finally, results indicate that, cryptocurrency markets played some minor role in transmitting risks between markets. Our results are important in understanding how assets affect return and volatility spillover during geopolitical and health crises and are of particular importance to policymakers, market regulators, investors, and portfolio managers.

Trajectories of the socioeconomic gradient of mental health: Results from the CLSA COVID-19 Questionnaire Study

As the coronavirus disease (COVID-19) pandemic prolongs, documenting trajectories of the socioeconomic gradient of mental health is important. We describe changes in the prevalence and absolute and relative income-related inequalities of mental health between April and December 2020 in Canada. We used data from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study and the pre-pandemic CLSA Follow-up 1. We estimated the prevalence proportion, the concentration index (relative inequality), and the generalized concentration index (absolute inequality) for anxiety and self-reported feeling generally unwell at multiple points in April-December 2020, overall, by sex and age group, by region, and among those who reported poor or fair overall health and mental health pre-pandemic. Overall, the prevalence of anxiety remained unchanged (22.45 to 22.10%, p=0.231), but self-reported feeling generally unwell decreased (9.83 to 5.94%, p=0.004). Relative and absolute income-related inequalities were unchanged for both anxiety and self-reported feeling generally unwell, with exceptions of an increased concentration of self-reported feeling generally unwell among the poor, measured by the concentration index, overall (-0.054 to -0.115, p=0.004) and in Ontario (-0.035 to -0.123, p=0.047) and British Columbia (-0.055 to -0.141, p=0.044). The COVID-19 pandemic appeared to neither exacerbate nor ameliorate existing income-related inequalities in mental health among older adults in Canada between April and December 2020. Continued monitoring of inequalities is necessary.

An investigation of SMART Recovery: protocol for a longitudinal cohort study of individuals making a new recovery attempt from alcohol use disorder.

INTRODUCTION: Alcohol use disorder (AUD) remains one of the most pervasive of all psychiatric illnesses conferring a massive health and economic burden. In addition to professional treatments to address AUD, mutual-help organisations such as Alcoholics Anonymous (AA) and newer entities like Self-Management and Recovery Training (SMART Recovery) play increasingly important roles in many societies. While much is known about the positive effects of AA, very little is known about SMART. Hence, this study seeks to estimate real-world patterns of utilisation and benefit from SMART Recovery as well as explore for whom (moderators) and how (mechanisms) SMART confers recovery benefits. METHODS AND ANALYSIS: Naturalistic, longitudinal, cohort study (n=368) of individuals with AUD recruited between February 2019 and February 2022, initiating a new recovery attempt who self-select into one of four groups at study entry: (1) SMART Recovery; (2) AA; (3) SMART+AA; (4) Neither SMART nor AA; (stratified by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) severity markers), with assessments conducted at intake, and 3 months, 6 months, 9 months, 12 months, 18 months and 24 months. Primary outcomes are: frequency of SMART and AA meetings attendance; per cent days abstinent and per cent days heavy drinking. Secondary outcomes include psychiatric distress; quality of life and functioning. Moderator variables include sex/gender; race/ethnicity; spirituality. Mediational variables include social networks; coping skills; self-efficacy; impulsivity. Multivariable regression with propensity score matching will test for patterns of attendance and effects of participation over time on outcomes and test for mechanisms and moderators. ETHICS AND DISSEMINATION: This study involves human participants and was approved by the Massachusetts General Hospital Institutional Review Board (Protocol #: 2017P002029/PHS). Results will be published in peer-reviewed journals and presented at conferences. REGISTRATION: This is a non-randomised, naturalistic, longitudinal, cohort study, and thus was not registered in advance. Results, therefore, should be considered exploratory.

Causes, survival rates, and short-term outcomes of preterm births in a tertiary hospital in a low resource setting: An observational cohort study.

Background: Prematurity is the most important cause of death among children under the age of five years. Globally, most preterm births occur in Sub-Saharan Africa. Subsequent prematurity leads to significant neonatal morbidity, mortality and long-term disabilities. This study aimed to determine the causes, survival rates and outcomes of preterm births up to six weeks of corrected age in Ghana. Materials and methods: An observational prospective cohort study of infants born preterm was conducted in a tertiary hospital in Accra, Ghana from August 2019 to March 2020. Inclusion was performed within 48 h after birth of surviving infants; multiple pregnancies and stillbirths were excluded. Causes of preterm birth were categorized as spontaneous (including preterm pre-labour rupture of membranes) or provider-initiated (medically indicated birth based on maternal or fetal indications). Survival rates and adverse outcomes were assessed at six weeks of corrected age. Recruitment and follow-up were suspended due to the COVID-19 outbreak. Descriptive statistics and differences between determinants were calculated using Chi-squared tests or Kruskal-Wallis test. Results: Of the 758 preterm deliveries, 654 (86.3%) infants were born alive. 179 were enrolled in the cohort and were analyzed. Nine (5%) were extremely preterm [gestational age (GA) < 28 weeks], 40 (22%) very preterm (GA 28-31 weeks), and 130 (73%) moderate to late preterm (GA 32-37 weeks) births. Most deliveries (n = 116, 65%) were provider-initiated, often due to hypertensive disorders in pregnancy (n = 79, 44.1%). Sixty-two infants were followed-up out of which fifty-two survived, presenting a survival rate of 84% (n = 52/62) at six weeks corrected age in this group. Most infants (90%, n = 47/52) experienced complications, predominantly consisted of NICU admission (92%) and interval illnesses (21%) including jaundice and sepsis. Conclusions: The incidence of adverse outcomes associated with preterm birth in a tertiary facility with NICU capacity is high. Larger longitudinal studies are needed for an in-depth understanding of the causes and longer-term outcomes of preterm birth, and to identify effective strategies to improve outcomes in resource constrained settings.

Professional Challenges for United States Hematology/Oncology Trainees during COVID-19.

COVID-19 has been devastating for patients with cancer. In this commentary, we chronicle the pandemic's downstream impacts on United States hematology/oncology trainees in terms of professional development and career advancement. These include loss of access to clinical electives and protocol workshops, delays in research approval and execution, mentor shortages due to academic burnout, and obstacles with career transitions (most notably the post-fellowship job search). While certain silver linings from the pandemic have undoubtedly emerged, continued progress against COVID-19 will be essential to fully overcome the professional challenges it has created for the future hematology/oncology workforce.

Trajectories of the socioeconomic gradient of mental health: Results from the CLSA COVID-19 Questionnaire Study.

As the coronavirus disease (COVID-19) pandemic prolongs, documenting trajectories of the socioeconomic gradient of mental health is important. We describe changes in the prevalence and absolute and relative income-related inequalities of mental health between April and December 2020 in Canada. We used data from the Canadian Longitudinal Study on Aging (CLSA) COVID-19 Questionnaire Study and the pre-pandemic CLSA Follow-up 1. We estimated the prevalence proportion, the concentration index (relative inequality), and the generalized concentration index (absolute inequality) for anxiety and self-reported feeling generally unwell at multiple points in April-December 2020, overall, by sex and age group, by region, and among those who reported poor or fair overall health and mental health pre-pandemic. Overall, the prevalence of anxiety remained unchanged (22.45 to 22.10%, p = 0.231), but self-reported feeling generally unwell decreased (9.83 to 5.94%, p = 0.004). Relative and absolute income-related inequalities were unchanged for both anxiety and self-reported feeling generally unwell, with exceptions of an increased concentration of self-reported feeling generally unwell among the poor, measured by the concentration index, overall (-0.054 to -0.115, p = 0.004) and in Ontario (-0.035 to -0.123, p = 0.047) and British Columbia (-0.055 to -0.141, p = 0.044). The COVID-19 pandemic appeared to neither exacerbate nor ameliorate existing income-related inequalities in mental health among older adults in Canada between April and December 2020. Continued monitoring of inequalities is necessary.

COVID-19 and transtympanic injections for sudden sensorineural hearing loss.

BACKGROUND: Multiple reports have linked COVID-19 infection with sudden sensorineural hearing loss (SSNHL), although other studies have failed to demonstrate this association. The current study was conceived to examine the rates of SSNHL across a large, principally national, population by characterizing the rate of transtympanic injections for SSNHL during the pandemic. METHODS: Retrospective review of all patients that underwent transtympanic injection from 2019 to 2020. RESULTS: Covering a unique beneficiary population of 9.6 million individuals of all ages in the United States, a statistically significant decrease in transtympanic injections for SSNHL was performed from 2019 to 2020 (p = 0.04, IRR = 0.91, 95 % CI = 0.84-0.99). No patient receiving a transtympanic injection also had a COVID-19 diagnosis. CONCLUSIONS: These findings support the idea that COVID-19 infections do not clinically significantly increase patients' risk of developing SSNHL. In fact, the decreased exposure through social isolation to other common viruses implicated in causing SSNHL may have actually led to a lower rate of SSNHL during the pandemic.

Goals of Care Conversations in Long-Term Care during the First Wave of the COVID-19 Pandemic.

Goals of care discussions typically focus on decision maker preference and underemphasize prognosis and outcomes related to frailty, resulting in poorly informed decisions. Our objective was to determine whether navigated care planning with nursing home residents or their decision makers changed care plans during the first wave of the COVID-19 pandemic. The MED-LTC virtual consultation service, led by internal medicine specialists, conducted care planning conversations that balanced information-giving/physician guidance with resident autonomy. Consultation included (1) the assessment of co-morbidities, frailty, health trajectory, and capacity; (2) in-depth discussion with decision makers about health status and expected outcomes; and (3) co-development of a care plan. Non-parametric tests and logistic regression determined the significance and factors associated with a change in care plan. Sixty-three residents received virtual consultations to review care goals. Consultation resulted in less aggressive care decisions for 52 residents (83%), while 10 (16%) remained the same. One resident escalated their care plan after a mistaken diagnosis of dementia was corrected. Pre-consultation, 50 residents would have accepted intubation compared to 9 post-consultation. The de-escalation of care plans was associated with dementia, COVID-19 positive status, and advanced frailty. We conclude that during the COVID-19 pandemic, a specialist-led consultation service for frail nursing home residents significantly influenced decisions towards less aggressive care.

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.

Importance: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. Objective: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. Design, Setting, and Participants: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. Exposures: SARS-CoV-2 status (positive or negative test result) at enrollment. Main Outcomes and Measures: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. Results: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (ß = 3.32; 95% CI, 1.84-4.80; P < .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: ß = 3.90; 95% CI, 1.75-6.05; P < .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: ß = 4.16; 95% CI, 2.12-6.20; P < .001). Conclusions and Relevance: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19.

Prevalence and Outcomes of COVID-19 among Hematology/Oncology Patients and Providers of a Community-Facing Health System during the B1.1.529 ("Omicron") SARS-CoV-2 Variant Wave.

(1) Background: the SARS-CoV-2 (COVID-19) pandemic continues, and patients actively receiving chemotherapy are known to be at enhanced risk for developing symptomatic disease with poorer outcomes. Our study evaluated the prevalence of COVID-19 among patients and providers of our community-facing county health system during the B1.1.529 ("Omicron") COVID-19 variant wave. (2) Methods: We retrospectively analyzed patients that received care and clinical providers whom worked at the Jackson Memorial Hospital Hematology/Oncology clinic in Miami, Florida, USA, from 1 December 2021 through 30 April 2022. We assessed demographic variables and quality outcomes among patients. (3) Results: 1031 patients and 18 providers were retrospectively analyzed. 90 patients tested positive for COVID-19 (8.73%), while 6 providers tested positive (33.3%) (p = 0.038). There were 4 (10.3%) COVID-19-related deaths (and another outside our study timeframe) and 39 non-COVID-19-related deaths (89.7%) in the patient population (p = 0.77). COVID-19 accounted for 4.44% of our clinic's total mortality, and delayed care in 64.4% of patients. (4) Conclusions: The prevalence of COVID-19 positivity in our patient cohort mirrored local, state, and national trends, however a statistically significant greater proportion of our providers tested positive. Almost two-thirds of patients experienced a cancer treatment delay, significantly impacting oncologic care.

Risk connectedness between energy and stock markets: Evidence from oil importing and exporting countries

The surmounted environmental and energy challenges have motivated this study to explore the connectedness nexus between oil/renewable energy and stock markets for oil-exporting (importing) countries. We utilize the dynamic conditional correlation (DCC-GARCH) connectedness framework to compare the connectedness of oil/renewable energy with stock markets. Our results showcase higher total connectedness between renewable energy and stock markets. We find increased connectedness during three major pandemics (Swine Flu, EBOLA, and COVID-19). We performed a regression analysis that highlighted the impact of economic and financial uncertainties on connectedness as an additional analysis. The addition of dummy variables for three major pandemics indicates that COVID-19 significantly impacted the connectedness between oil/renewable energy and stock markets. For the robustness of our results, we employed time-varying vector autoregressions (TVP-VAR) connectedness framework to showcase that our results remain qualitatively similar and robust to different specifications. We draw useful implications for oil exporting and oil importing countries in particular, and we draft ramifications for investors, portfolio managers, policymakers, and macroprudential bodies in general.

Abatacept for Treatment of Adults Hospitalized with Moderate or Severe Covid-19 (preprint)

Background: We investigated whether abatacept, a selective costimulation modulator, provides additional benefit when added to standard-of-care for patients hospitalized with Covid-19. Methods: We conducted a master protocol to investigate immunomodulators for potential benefit treating patients hospitalized with Covid-19 and report results for abatacept. Intravenous abatacept (one-time dose 10 mg/kg, maximum dose 1000 mg) plus standard of care (SOC) was compared with shared placebo plus SOC. Primary outcome was time-to-recovery by day 28. Key secondary endpoints included 28-day mortality. Results: Between October 16, 2020 and December 31, 2021, a total of 1019 participants received study treatment (509 abatacept; 510 shared placebo), constituting the modified intention-to-treat cohort. Participants had a mean age 54.8 (SD 14.6) years, 60.5% were male, 44.2% Hispanic/Latino and 13.7% Black. No statistically significant difference for the primary endpoint of time-to-recovery was found with a recovery-rate-ratio of 1.14 (95% CI 1.00-1.29; p=0.057) compared with placebo. We observed a substantial improvement in 28-day all-cause mortality with abatacept versus placebo (11.0% vs. 15.1%; odds ratio [OR] 0.62 [95% CI 0.41-0.94]), leading to 38% lower odds of dying. Improvement in mortality occurred for participants requiring oxygen/noninvasive ventilation at randomization. Subgroup analysis identified the strongest effect in those with baseline C-reactive protein >75mg/L. We found no statistically significant differences in adverse events, with safety composite index slightly favoring abatacept. Rates of secondary infections were similar (16.1% for abatacept; 14.3% for placebo). Conclusions: Addition of single-dose intravenous abatacept to standard-of-care demonstrated no statistically significant change in time-to-recovery, but improved 28-day mortality. Trial registration: ClinicalTrials.gov (NCT04593940).

Infliximab for Treatment of Adults Hospitalized with Moderate or Severe Covid-19 (preprint)

BackgroundImmune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care. MethodsWe conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants hospitalized with Covid-19 pneumonia. We report results for infliximab (single dose infusion) versus shared placebo both with standard of care. Primary outcome was time to recovery by day 29 (28 days after randomization). Key secondary endpoints included 14-day clinical status and 28-day mortality. ResultsA total of 1033 participants received study drug (517 infliximab, 516 placebo). Mean age was 54.8 years, 60.3% were male, 48.6% Hispanic or Latino, and 14% Black. No statistically significant difference in the primary endpoint was seen with infliximab compared with placebo (recovery rate ratio 1.13, 95% CI 0.99-1.29; p=0.063). Median (IQR) time to recovery was 8 days (7, 9) for infliximab and 9 days (8, 10) for placebo. Participants assigned to infliximab were more likely to have an improved clinical status at day 14 (OR 1.32, 95% CI 1.05-1.66). Twenty-eight-day mortality was 10.1% with infliximab versus 14.5% with placebo, with 41% lower odds of dying in those receiving infliximab (OR 0.59, 95% CI 0.39-0.90). No differences in risk of serious adverse events including secondary infections. ConclusionsInfliximab did not demonstrate statistically significant improvement in time to recovery. It was associated with improved 14-day clinical status and substantial reduction in 28- day mortality compared with standard of care. Trial registrationClinicalTrials.gov (NCT04593940).

Double-stranded RNA drives SARS-CoV-2 nucleocapsid protein to undergo phase separation at specific temperatures.

Nucleocapsid protein (N-protein) is required for multiple steps in betacoronaviruses replication. SARS-CoV-2-N-protein condenses with specific viral RNAs at particular temperatures making it a powerful model for deciphering RNA sequence specificity in condensates. We identify two separate and distinct double-stranded, RNA motifs (dsRNA stickers) that promote N-protein condensation. These dsRNA stickers are separately recognized by N-protein's two RNA binding domains (RBDs). RBD1 prefers structured RNA with sequences like the transcription-regulatory sequence (TRS). RBD2 prefers long stretches of dsRNA, independent of sequence. Thus, the two N-protein RBDs interact with distinct dsRNA stickers, and these interactions impart specific droplet physical properties that could support varied viral functions. Specifically, we find that addition of dsRNA lowers the condensation temperature dependent on RBD2 interactions and tunes translational repression. In contrast RBD1 sites are sequences critical for sub-genomic (sg) RNA generation and promote gRNA compression. The density of RBD1 binding motifs in proximity to TRS-L/B sequences is associated with levels of sub-genomic RNA generation. The switch to packaging is likely mediated by RBD1 interactions which generate particles that recapitulate the packaging unit of the virion. Thus, SARS-CoV-2 can achieve biochemical complexity, performing multiple functions in the same cytoplasm, with minimal protein components based on utilizing multiple distinct RNA motifs that control N-protein interactions.