Early Surge Research Articles

Money Matters: Broad Divisia Money and the Recovery of the US Nominal GDP From the COVID‐19 Recession

ABSTRACTThe rise of inflation in 2021 and 2022 surprised many macroeconomists who ignored the earlier surge in money growth because of past instability in the demand for simple‐sum monetary aggregates. We find that the demand for more theoretically based Divisia aggregates can be modeled and that these aggregates provide useful information about nominal GDP. Unlike M2 and Divisia‐M2, whose velocities do not internalize shifts in liabilities across commercial and shadow banks, the velocities of broader Divisia monetary aggregates are stable and can be empirically modeled through the Covid‐19 pandemic. In the long run, these velocities depend on regulation and mutual fund costs that affect the substitutability of money for other financial assets. In the short run, we control for swings in mortgage activity and use vaccination rates and the stringency of government pandemic restrictions to control for the unusual pandemic effects. The velocity of broad Divisia money declines during crises like the Great and COVID Recessions but later rebounds. In these recessions, monetary policy lowered short‐term interest rates to zero and engaged in quantitative easing of about $4 trillion. Nevertheless, broad money growth was more robust in the COVID Recession, reflecting a less impaired banking system that promoted rather than hindered deposit creation. Our framework implies that nominal GDP growth and inflation rebounded more quickly from the COVID Recession versus the Great Recession. Our different scenarios for future Divisia money growth and the unwinding of the pandemic have different implications for medium‐term nominal GDP growth and inflationary pressures.

Hypertension and Cognitive Disorders.

Systemic hypertension is possibly the most important modifiable risk factor for the development of cognitive decline, both for mild cognitive impairment (MCI) and dementia. For effective blood pressure (BP) control, it requires proper assessment, using brachial, central, and ambulatory measurements, and monitoring with a focus on different BP parameters. Different BP parameters like pulse pressure, mean arterial pressure, BP variability, and circadian parameters, like nondippers and early morning surge, should be considered in the evaluation for the risk of cognitive decline due to hypertension in middle age and older adults. Chronic hypertension causes vascular remodeling in the brain and leads to brain failure or cognitive decline. Achieving specific BP goals can improve clinical outcomes and possibly slow down cognitive decline for patients with comorbid hypertension and cognitive impairment.

Kinetics of viral hemorrhagic septicemia virus (VHSV) and immune response in olive flounder (Paralichthys olivaceus) at altered temperature

Viral hemorrhagic septicemia virus (VHSV) is a pathogen that causes hemorrhagic septicemia in olive flounder at water temperatures below 15 °C, leading to symptoms such as abdominal swelling due to ascites and muscle hemorrhaging, and in severe cases, mortality. In this study, we investigated the proliferation of NCCs, the transcriptional analysis of CD4 and CD8, and the expression of pro-inflammatory cytokines (IL-1β, IL6, TNFα) and the cytokines (IL12, IL15, IFN-1β, IFNγ) involved in cytotoxic cell activation in the kidney of olive flounder during VHSV infection at suboptimal temperature (17 °C) and following a shift to optimal temperature (10 °C). Following viral infection, the population of NCCs and CD8 gene expression steadily increased. Meanwhile, IL12, IL15, and IFN-1β levels exhibited an early surge, reaching their peak within 1–2 days post-challenge at 17 °C. Notably, in olive flounder that were re-challenged with VHSV at 10 °C after an initial challenge at 17 °C, there was a rapid and robust expansion of NCCs and increased CD4 and CD8 gene expression, demonstrating the mounting of immune memory by NCCs and an efficient adaptive immune response from CD4+ and CD8+ T cells against VHSV infection.

Compressor Surge Identification in Innovative Heat-Pump Systems Equipped by Vaned Diffuser Centrifugal Compressor

Abstract In the present energy scenario, heat-pumps play an important role to improve energy efficiency in reversible cooling systems. In case of industrial size plants, centrifugal compressors are preferred with respect to other solutions; nonetheless, they work in variable operation and therefore they must withstand off-design conditions. Carrier provided the University of Genoa with a small size chiller rig equipped with an innovative high speed centrifugal compressor driven by a variable speed motor to study unstable operation of refrigerant closed loop systems. To this aim, vibro-acoustic signature analysis of such closed loop rig is performed mainly focusing on compressor mechanical response. This experimental characterization is firstly conducted in system stable operation. Afterwards, surge transients are obtained by acting on plant feeding lines valves; meanwhile, experimental signals are acquired at relevant plant locations to investigate system response just before instability onset. Indeed, system dynamics is affected by interposed volumes, and therefore the effect of heat exchangers in system response may be relevant. Therefore, system dynamics is analysed both in sub-synchronous frequency range and in high frequency region to assess how its vibro-acoustic response varies when moving from stable conditions towards surge. By doing so, suitable surge precursors can be defined by relying only on vibro-acoustic signals both in low and high frequency ranges to perform early surge detection in such chiller systems. The proposed approach main advantage is to exploit non-intrusive probes, which allow to define diagnostic indicators without interacting directly with the working fluid.

Comparison of fixed and flexible progestin-primed ovarian stimulation in women classified in patient-oriented strategies encompassing individualized oocyte number (POSEIDON) group 4.

This study aimed to compare the fixed and flexible protocols for progestin-primed ovarian stimulation (PPOS) in poor ovarian responders. This retrospective study included 95 poor ovarian responders classified using the Patient-Oriented Strategies Encompassing Individualized Oocyte Number group 4 criteria. Treatment involved assisted reproductive medicine using fixed and flexible PPOS protocols at Shiga University of Medical Science between July 2019 and August 2023. PPOS cycles were assigned to the fixed and flexible groups at the discretion of attending physicians. The results of assisted reproductive medicine were compared between groups. The fixed and flexible groups included 68 and 27 patients, respectively. The flexible group obtained more retrieved oocytes and two pro-nuclei than the fixed group, without an early luteinizing hormone surge. Multiple linear regression analysis demonstrated that differences in protocols and anti-müllerian hormone (AMH) levels were related to the number of retrieved oocytes. The differences in protocols were more strongly correlated with the number of oocytes than with the AMH levels. Among poor ovarian responders, the flexible PPOS protocol provided more retrieved oocytes than the fixed PPOS protocol, possibly because the total dosage of progestins was lower in the flexible group and progestins were not administered at the time when ovarian stimulation was initiated.

Modeling COVID-19 spread and non-pharmaceutical interventions in South Africa: A stochastic approach

The COVID-19 pandemic has exerted a pervasive worldwide influence, including on South Africa, which stands out as one of the African nations most substantially impacted. As of March 20, 2021, the nation has encountered a multitude of obstacles in its efforts to contain the virus’s transmission. Conventional approaches to forecasting the transmission of contagious illnesses frequently prove inadequate when it comes to comprehending the intricate dynamics of COVID-19, specifically with regard to stochastic disruptions and the efficacy of non-pharmaceutical interventions. The deficiency in predictive modeling has impeded the capacity to effectively evaluate and execute measures to reduce the spread of the virus. The principal objective of this study is to construct a novel stochastic model, denoted as SEIHR, that can effectively forecast the transmission of COVID-19 in South Africa while also assessing the efficacy of diverse non-pharmacological interventions. By conducting an extensive data analysis spanning from April 17, 2020, to September 13, 2021, this research endeavors to provide a comprehensive and nuanced comprehension of the dynamics of the epidemic, with a particular focus on its early surges. Using the idea of stochastic Lyapunov function theory, this study aims to find out if there is and is not a solution in the given model. It also wants to find out what conditions must be met in order to get rid of diseases when there are random disturbances, such as white noise. Using this model, the efficacy of interventions such as lockdowns in preventing the spread of the virus during the epidemic will also be critically evaluated. The primary objective is to furnish policymakers and health authorities with invaluable insights and tools that will enable them to more effectively manage and alleviate the COVID-19 crisis in South Africa and comparable settings.

Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19: Evidence from the US National COVID Cohort Collaborative (N3C).

The coronavirus disease 2019 (COVID-19) pandemic has been an unprecedented healthcare crisis, one that threatened to overwhelm health systems and prompted an urgent need for early treatment options for patients with mild-to-moderate COVID-19 at high risk for progression to severe disease. Randomised clinical trials established the safety and efficacy of monoclonal antibodies (mAbs) early in the pandemic; in vitro data subsequently led to use of the mAbs being discontinued, without clear evidence on how these data were linked to outcomes. In this study, we describe and compare real-world outcomes for patients with mild-to-moderate COVID-19 at high risk for progression to severe COVID-19 treated with sotrovimab versus untreated patients. Electronic health records from the National COVID Cohort Collaborative (N3C) were used to identify US patients (aged ≥ 12 years) diagnosed with COVID-19 (positive test or ICD-10: U07.1) in an ambulatory setting (27 September 2021-30 April 2022) who met Emergency Use Authorization (EUA) high-risk criteria. Patients receiving the mAb sotrovimab within 10 days of diagnosis were assigned to the sotrovimab cohort, with the day of infusion as the index date. Untreated patients (no evidence of early mAb treatment, prophylactic mAb or oral antiviral treatment) were assigned to the untreated cohort, with an imputed index date based on the time distribution between diagnosis and sotrovimab infusion in the sotrovimab cohort. The primary endpoint was hospitalisation or death (both all-cause) within 29 days of index, reported as descriptive rate and adjusted [via inverse probability of treatment weighting (IPTW)] odds ratio (OR) and 95% confidence interval (CI). Of nearly 2.9 million patients diagnosed with COVID-19 during the analysis period, 4992 met the criteria for the sotrovimab cohort, and 541,325 were included in the untreated cohort. Before weighting, significant differences were noted between the cohorts; for example, patients in the sotrovimab cohort were older (60 years versus 54 years), were more likely to be white (85% versus 75%) and met more EUA criteria (mean 3.1 versus 2.2) versus the untreated cohort. The proportions of patients with 29-day hospitalisation or death were 3.5% (176/4992) and 4.5% (24,163/541,325) in the sotrovimab and untreated cohorts, respectively (unadjusted OR: 0.78; 95% CI: 0.67, 0.91; p = 0.001). In adjusted analysis, sotrovimab was associated with a 25% reduction in the odds of hospitalisation or death compared with the untreated cohort (IPTW-adjusted OR: 0.75; 95% CI: 0.61, 0.92; p = 0.005). Sotrovimab demonstrated clinical effectiveness in preventing severe outcomes (hospitalisation, mortality) in the period 27 September 2021-30 April 2022, which included Delta and Omicron BA.1 variants and an early surge of Omicron BA.2 variant.

Barrel cortex development lacks a key stage of hyperconnectivity from deep to superficial layers in a rat model of Absence Epilepsy

During development of the sensory cortex, the ascending innervation from deep to upper layers provides a temporary scaffold for the construction of other circuits that remain at adulthood. Whether an alteration in this sequence leads to brain dysfunction in neuro-developmental diseases remains unknown. Using functional approaches in a genetic model of Absence Epilepsy (GAERS), we investigated in barrel cortex, the site of seizure initiation, the maturation of excitatory and inhibitory innervations onto layer 2/3 pyramidal neurons and cell organization into neuronal assemblies. We found that cortical development in GAERS lacks the early surge of connections originating from deep layers observed at the end of the second postnatal week in normal rats and the concomitant structuring into multiple assemblies. Later on, at seizure onset (1 month old), excitatory neurons are hyper-excitable in GAERS when compared to Wistar rats. These findings suggest that early defects in the development of connectivity could promote this typical epileptic feature and/or its comorbidities.

Progestin-primed ovarian stimulation with letrozole using different doses of medroxyprogesterone acetate per day: a retrospective cohort study.

In the progestin-primed ovarian stimulation protocol, the oral administration of medroxyprogesterone acetate has been observed to effectively inhibit the LH surge during ovarian stimulation in patients experiencing infertility. Nevertheless, the use of utilizing medroxyprogesterone acetate during ovarian stimulation can result in more pronounced pituitary suppression, potentially necessitating increased doses of gonadotropins and extended treatment durations. Therefore, it is necessary to determine the optimal dose of medroxyprogesterone acetate, aiming to use relatively lower concentrations of medroxyprogesterone acetate to effectively and safely suppress early LH surges. This retrospective cohort study included 710 patients who underwent cycles of in vitro fertilization or intracytoplasmic sperm injection and were subjected the progestin-primed ovarian stimulation protocol utilizing letrozole between from 1st January 2021 to 31st December 2021. The study population was divided into low, medium, and high concentration groups based on the daily dosage of medroxyprogesterone acetate.The primary focus of this investigation was on the cumulative live birth rate. Secondary outcomes encompassed the occurrence of a premature surge in luteinizing hormone, the quantity of retrieved oocytes, viable embryos, and high-quality embryos, as well as clinical pregnancy rate, abortion rate, ectopic pregnancy rate, and multiple pregnancy rate. In this study, significant differences were observed among three groups in various parameters including body mass index, baseline levels of Anti-Müllerian hormone and luteinizing hormone, antral follicle count, total dose of gonadotropin, and duration of gonadotropin administration (p<0.05). The number of oocytes and viable embryos were significantly higher in medium group and higher than those in the low dose group. Following adjustments for confounding factors related to medroxyprogesterone acetate for various outcome measures, we conducted multiple regression analysis to investigate the independent effects of daily medroxyprogesterone acetate dosage within the combined progestin-primed ovarian stimulation and letrozole protocol. Following multivariable regression analysis, no disparities were found in embryo characteristics (number of oocytes retrieved, number of available embryos, number of high-quality embryos) or pregnancy outcomes (clinical pregnancy rate, cumulative live birth rate) among the three groups. Progestin-primed ovarian stimulation with letrozole using different dose of medroxyprogesterone acetate per day was comparable in terms of the number of oocytes retrieved, the number of high-quality embryos, clinical pregnancy rate and cumulative live birth rate after frozen embryo transfer.

2475. Admissions Screening for Influenza and RSV Among a Highly Immunosuppressed Patient Population

Abstract Background During the Fall/Winter 2022-23, the U.S. experienced an early surge of Influenza and RSV cases, while SARS-CoV-2 cases persisted. With concerns of a potential “tripledemic” on the horizon, the NIH Clinical Center, a clinical research hospital with a heavily immunosuppressed patient population, implemented Influenza and RSV testing, in addition to SARS-CoV-2, for all patients on admission to facilitate early detection and prompt isolation of infected patients. Methods Nasopharyngeal (NP) swabs (n=1213) were collected on admission from 11/2022 to 4/2023 and tested for Influenza and RSV by PCR. 1213 NP swabs from 985 unique patients were tested (some patients had multiple admissions); 1100 were tested on the Panther Fusion® SARS-CoV-2 Assay (Hologic, Inc.) and 113 using the SARS-CoV-2 RT-PCR Xpert® Xpress test. Medical chart reviews and discussions with patient care providers elucidated whether cases identified on admission were asymptomatic. Results Of 1213 NP swabs collected from patients admitted to our hospital, 5 (0.41%) were identified with Influenza A infection, 4 (0.33%) RSV infection and no patients were identified with Influenza B. Two (0.16%) had a known history of RSV infection, 3 (0.25%) screened negative for symptoms but subsequently disclosed symptoms, 1 (0.08%) was asymptomatic on admission but disclosed a recent history of an upper respiratory infection, and 3 were asymptomatic. All infections were detected between late November 2022 to mid-January 2023, when community transmission was high, yielding a 2-month positivity rate of 2.3% during this time of peak community spread. Conclusion Admission surveillance for Influenza and RSV during a respiratory virus surge in our community allowed us to isolate nine patients on admission who would likely not have been appropriately isolated, as symptom screening alone is not reliable. Surveillance is important to be able to identify infected patients promptly when respiratory infections are rampant in the community, and especially for institutions serving immunosuppressed patients. Disclosures All Authors: No reported disclosures

Alarming Trends in Dengue Incidence and Mortality in Bangladesh.

Bangladesh is currently experiencing the country's largest and deadliest dengue outbreak on record. This year's outbreak has been characterized by an early seasonal surge in cases, rapid geographic spread, and a high fatality rate. The alarming trends in dengue incidence and mortality this year is an urgent wake-up call for public health policymakers and researchers to pay closer attention to dengue dynamics in South Asia, to strengthen the surveillance system and diagnostic capabilities, and to develop tools and methods for guiding strategic resource allocation and control efforts.

The role of ATG5 beyond Atg8ylation and autophagy

ABSTRACT ATG5 plays a pivotal role in membrane Atg8ylation, influencing downstream processes encompassing canonical autophagy and noncanonical processes. Remarkably, genetic ablation of ATG5 in myeloid cells leads to an exacerbated pathological state in murine models of tuberculosis, characterized by an early surge in mortality much more severe when compared to the depletion of other components involved in Atg8ylation or canonical autophagy. This study shows that in the absence of ATG5, but not other core canonical autophagy factors, endolysosomal organelles display a lysosomal hypersensitivity phenotype when subjected to damage. This is in part due to a compromised recruitment of ESCRT proteins to lysosomes in need of repair. Mechanistically, in the absence of ATG5, the ESCRT protein PDCD6IP/ALIX is sequestered by the alternative conjugate ATG12–ATG3, contributing to excessive exocytic processes while not being available for lysosomal repair. Specifically, this condition increases secretion of extracellular vesicles and particles, and leads to excessive degranulation in neutrophils. Our findings uncover unique functions of ATG5 outside of the autophagy and Atg8ylation paradigm. This finding is of in vivo relevance for tuberculosis pathogenesis as modeled in mice.

Vibro-Acoustic Responses and Pressure Signal Analysis for Early Surge Detection in a Turbocharger Compressor

Abstract High-speed centrifugal compressors may be exploited to pressurize fuel cell systems. Nonetheless, due to fuel cells significant interposed volumes, compressor behavior can lead to severe vibrations related to fluid-dynamic instabilities during part load operating conditions. In particular, surge strongly limits centrifugal compressors stable operating region when moving toward low mass flow rates due to a change in system working point. Therefore, compressor dynamic response must be adequately characterized for early surge detection. To this aim, a dedicated experimental activity was conducted on a vaneless diffuser turbocharger coupled to a solid oxide fuel cell emulator plant; compressor evolution toward surge was investigated. Several signal processing techniques were applied to pressure signals as well as vibro-acoustic responses to better predict compressor behavior and classify its status as stable or unstable. Cepstrum, cross-correlation, and wavelet transform have been identified as suitable techniques to define precursors able to early detect surge. By means of cross-correlation function, propagation phenomena in the ducts can be investigated to assess how they interact near compressor low-mass flowrate unstable conditions. Cepstrum provides a convenient way to determine pressure signal spectrum distortion in terms of further periodic components onset. These harmonic components are due to complex system responses generated by transient phenomena; indeed, cepstrum allows to identify hidden anomalous contributions in system response spectra which may arise in incipient surge conditions. Wavelet transform was performed on both structural and pressure response signals to observe their dominant energy contents temporal evolution; indeed, such spectral pattern time-dependent variation can detect the rise of unstable conditions. By exploiting all these techniques, a complete system identification is performed which allows a deeper investigation of the physical phenomena involved; moreover, a more complete set of surge precursors extracted from different probes' physical signals were defined. The results obtained provide original diagnostic insights for monitoring systems suited to perform early surge detection. Compressor instability prevention can extend its operating range, performance, and reliability to allow better integration with other plant components. Finally, cepstrum application for compressor instability identification can be regarded as a novel method in the fluid machinery field.

Release, Reentry, and Reintegration During COVID-19: Perspectives of Individuals Recently Released from the Federal Bureau of Prisons.

The COVID-19 pandemic had a large negative impact on people in U.S. prisons. Expedited releases from prison were one strategy used to decrease morbidity and mortality from COVID-19. However, little is known about the reentry experiences of those being rapidly released from custody early in the pandemic. We aimed to examine the perspectives of former residents in the Federal Bureau of Prisons (BOP) regarding release, reentry, and reintegration into their respective communities. We conducted semistructured interviews with 21 recently released individuals primarily recruited through legal aid organizations between September and October 2021. Subjects were incarcerated before and during the early surge in the COVID-19 pandemic. We coded transcripts thematically with domains developed a priori in which we revised iteratively and inductively based on the data. Several major themes emerged. Participants reported that they needed to advocate for themselves to take advantage of the early release process. Compared with normal circumstances, they reported a lack of reentry planning and preparation before participants were released. Finally, experiences with reintegration varied but were often more challenging due to COVID-19. Residents released during COVID-19 reported many challenges with reentry that could have been mitigated by support and guidance from the BOP. Reentry is a process that should begin prelease and continues postrelease to ensure individuals have adequate structural and social supports. Inadequate reentry support has significant impacts on the health and well-being of recently released individuals and contributes to the broader context of achieving health equity for minitorized groups who are disproportionately overrepresented in prisons. Policy and practice reform is needed to address the time-sensitive, life-threatening challenges individuals face when transitioning from prison to community.

Investigational medications in 9,638 hospitalized patients with severe COVID-19: lessons from the “fail-and-learn” strategy during the first two waves of the pandemic in 2020

BackgroundThe early surge of the novel coronavirus disease 2019 (COVID-19) pandemic introduced a significant clinical challenge due to the high case-fatality rate in absence of evidence-based recommendations. The empirical treatment modalities were relegated to historical expertise from the traditional management of acute respiratory distress syndrome (ARDS) in conjunction with off-label pharmaceutical agents endorsed under the “emergency use authorization” (EUA) paradigm by regulatory agencies. This study was designed to evaluate the insights from the “fail-and-learn” strategy in 2020 before the availability of COVID-19 vaccines and access to reliable insights from high-quality randomized controlled trials.MethodsA retrospective, multicenter, propensity-matched, case-control study was performed on a data registry comprising 186 hospitals from a national health care system in the United States, designed to investigate the efficacy of empirical treatment modalities during the early surge of the COVID-19 pandemic in 2020. Reflective of the time-windows of the initial two surges of the pandemic in 2020, patients were stratified into “Early 2020” (March 1–June 30) versus “Late 2020” (July 1–December 31) study cohorts. Logistic regression was applied to determine the efficacy of prevalent medications (remdesivir, azithromycin, hydroxychloroquine, corticosteroids, tocilizumab) and supplemental oxygen delivery modalities (invasive vs. non-invasive ventilation) on patient outcomes. The primary outcome measure was in-hospital mortality. Group comparisons were adjusted for covariates related to age, gender, ethnicity, body weight, comorbidities, and treatment modalities pertinent to organ failure replacement.ResultsFrom a total of 87,788 patients in the multicenter data registry screened in this study, 9,638 patients were included who received 19,763 COVID-19 medications during the first two waves of the 2020 pandemic. The results showed a minimal, yet statistically significant, association with hydroxychloroquine in “Early 2020” and remdesivir in “Late 2020” with reduced odds of mortality (odds ratios 0.72 and 0.76, respectively; P = 0.01). Azithromycin was the only medication associated with decreased odds of mortality during both study time-windows (odds ratios 0.79 and 0.68, respectively; P < 0.01). In contrast, the necessity for oxygen supply showed significantly increased odds of mortality beyond the effect of all investigated medications. Of all the covariates associated with increased mortality, invasive mechanical ventilation had the highest odds ratios of 8.34 in the first surge and 9.46 in in the second surge of the pandemic (P < 0.01).ConclusionThis retrospective multicenter observational cohort study on 9,638 hospitalized patients with severe COVID-19 revealed that the necessity for invasive ventilation had the highest odds of mortality, beyond the variable effects observed by administration of the prevalent EUA-approved investigational drugs during the first two surges of the early 2020 pandemic in the United States.

COVID-19 Associated Pulmonary Aspergillosis in Patients on Extracorporeal Membrane Oxygenation Treatment-A Retrospective Study.

The incidence and outcome of pulmonary aspergillosis in coronavirus disease (COVID-19) patients on extracorporeal membrane oxygenation (ECMO) are unknown and have not been fully addressed. We investigated the incidence, risk factors and outcome of pulmonary aspergillosis in COVID-19 ECMO patients. In addition, the diagnostic utility of bronchoalveolar lavage fluid and CT scans in this setting were assessed. We conducted a retrospective study on incidence and outcome of pulmonary aspergillosis in COVID-19 ECMO patients by reviewing clinical, radiological, and mycological evidence. These patients were admitted to a tertiary cardiothoracic centre during the early COVID-19 surge between March 2020 and January 2021. Results and measurements: The study included 88 predominantly male COVID-19 ECMO patients with a median age and a BMI of 48 years and 32 kg/m2, respectively. Pulmonary aspergillosis incidence was 10% and was associated with very high mortality. Patients with an Aspergillus infection were almost eight times more likely to die compared with those without infection in multivariate analysis (OR 7.81, 95% CI: 1.20-50.68). BALF GM correlated well with culture results, with a Kappa value of 0.8 (95% CI: 0.6, 1.0). However, serum galactomannan (GM) and serum (1-3)-β-D-glucan (BDG) lacked sensitivity. Thoracic computed tomography (CT) diagnostic utility was also inconclusive, showing nonspecific ground glass opacities in almost all patients. In COVID-19 ECMO patients, pulmonary aspergillosis incidence was 10% and associated with very high mortality. Our results support the role of BALF in the diagnosis of pulmonary aspergillosis in COVID-19 ECMO patients. However, the diagnostic utility of BDG, serum GM, and CT scans is unclear.

The long-term impact of COVID-19 on nursing: An e-panel discussion from the International Network for Child and Family Centred Care.

To explore the International Network for Child and Family Centred Care (INCFCC) members' experiences and views on the long-term impact of COVID-19 on the nursing workforce. On the 11 March 2020, the World Health Organization declared COVID-19 a global pandemic. While some countries adopted a herd immunity approach, others imposed stricter measures to reduce the transmission of the virus. Hospitals in some countries faced an avalanche of extremely sick admissions, whereas others experienced an early surge in cases or were able to control the spread. Discursive paper. A web-based survey was e-mailed to 63 INCFCC members from 28 March to 30 April 2022, as an invitation to share their experience concerning the long-term impact of COVID-19 on their role as a nurse educator, clinician or researcher. Sixteen members responded, and the responses were grouped under the themes stress and anxiety, safe staffing and pay, doing things differently, impact on research, impact on teaching and learning, impact on clinical practice, nursing made visible and lessons for the future. The INCFCC members provided their views and highlighted the impact on their role in nursing education, administration, research and/or practice. This discussion of international perspectives on the similarities and differences imposed by COVID-19 found that the impact was wide-ranging and prolonged. The overarching theme revealed the resilience of the participating members in the face of COVID-19. This study highlights the importance of all areas of nursing, be it in academia or in clinical practice, to work together to learn from the present and to plan for the future. Future work should focus on supporting organizational and personal resiliency and effective interventions to support the nursing workforce both during a disaster and in the recovery phase. Nursing workforce resilience in the face of COVID-19.

The P323L substitution in the SARS-CoV-2 polymerase (NSP12) confers a selective advantage during infection

BackgroundThe mutational landscape of SARS-CoV-2 varies at the dominant viral genome sequence and minor genomic variant population. During the COVID-19 pandemic, an early substitution in the genome was the D614G change in the spike protein, associated with an increase in transmissibility. Genomes with D614G are accompanied by a P323L substitution in the viral polymerase (NSP12). However, P323L is not thought to be under strong selective pressure.ResultsInvestigation of P323L/D614G substitutions in the population shows rapid emergence during the containment phase and early surge phase during the first wave. These substitutions emerge from minor genomic variants which become dominant viral genome sequence. This is investigated in vivo and in vitro using SARS-CoV-2 with P323 and D614 in the dominant genome sequence and L323 and G614 in the minor variant population. During infection, there is rapid selection of L323 into the dominant viral genome sequence but not G614. Reverse genetics is used to create two viruses (either P323 or L323) with the same genetic background. L323 shows greater abundance of viral RNA and proteins and a smaller plaque morphology than P323.ConclusionsThese data suggest that P323L is an important contribution in the emergence of variants with transmission advantages. Sequence analysis of viral populations suggests it may be possible to predict the emergence of a new variant based on tracking the frequency of minor variant genomes. The ability to predict an emerging variant of SARS-CoV-2 in the global landscape may aid in the evaluation of medical countermeasures and non-pharmaceutical interventions.

How COVID-19 shifted the seasonal flu in Korea.

Prior to 2021, Republic of Korea had experienced typical seasonal epidemics of influenza, with some seasons showing higher rates of influenza-like illness. Typically, seasonal flu epidemics in the country are reported between December and March.1 In the 2019–2020 season, there was a relatively high number of ILI rates. Notably, during the 2020–2021 and 2021–2022 seasons, the ILI rates had remained below the epidemic threshold, as Figure 1 illustrates. There had been continuous concern for the possible “twindemic” since the emergence of COVID-19. In the 2021–2022 season, this concern had grown with the ease of non-pharmaceutical interventions, including social distancing measures. “Twindemic” is a term used to describe the simultaneous occurrence of two different epidemics: COVID-19 and the seasonal influenza. It is used to stress the possible subsequent burden on healthcare systems and on the overall society. The 2022–2023 flu season in the Republic of Korea has shown a similar pattern to seasons prior to the COVID-19 pandemic. Despite an increase in the ILI baseline since Week 40, no early increase was observed. ILI rates increased above the seasonal threshold (4.9 ILI cases per 1000 outpatients) in Week 40, gradually increasing until Week 49, and showing a typical exponential increase starting from Week 50, similar to the pattern before the COVID-19 pandemic. The peak was observed in Week 53 and has been decreasing since then. This reoccurrence of the typical flu epidemic in the Republic of Korea is not surprising, given the lifting of overall social distancing measures and reduced population immunity to seasonal influenza due to the absence of a flu epidemic in the 2020–2021 and 2021–2022 seasons.2 Influenza vaccination rates have been stable during the COVID-19 pandemic.3 Nevertheless, the indoor mask mandate has been maintained, which may have prevented an early surge of the seasonal flu epidemic, unlike in other countries, including Australia and the United States.4-6 The impact of the resurgence of the seasonal flu in the midst of the Omicron variant-driven COVID-19 pandemic has not been as catastrophic as feared in the country. There is a chance for a spring season second peak since the indoor mask mandate is set to be lifted by the end of January 2023. Therefore, close monitoring of seasonal flu and COVID-19 trends, as well as continuous encouragement of vaccination for both highly transmissible pathogens, is needed. At present, the worst-case scenario appears to have been averted. Nevertheless, it is imperative that we continue to exercise caution, as it is currently too early to lower our guard. Seunghyun Lewis Kwon: Conceptualization; formal analysis; methodology; writing – original draft; writing – review and editing. Bryan Inho Kim: Methodology; supervision; validation; writing – original draft; writing – review and editing. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The peer review history for this article is available at https://publons.com/publon/10.1111/irv.13113. These data were derived from the following resources available in the public domain: https://www.kdca.go.kr/board/board.es?mid=a30504000000&bid=0033.

"You're Socially Distant and Trying Not to Be Emotionally Distant." Physicians' Perspectives of Communication and Therapeutic Relationships in the ICU During the COVID-19 Pandemic: A Qualitative Study.

We conducted a qualitative study between September 2020 and February 2021 that explored facilitators and barriers to patient-clinician communication and the formation of therapeutic relationships. We used thematic analysis to develop findings describing patient-communication and therapeutic relationships within the ICU early in the COVID-19 pandemic. We purposively selected hospital dyads from regions in the United States that experienced early and/or large surges of patients hospitalized with COVID-19. We recruited a national sample of ICU physicians from Veteran Affairs (VA) Health Care Systems and their associated academic affiliate hospitals. None. Twenty-four intensivists from seven VA hospitals and six academic-affiliate hospitals participated. Intensivists noted the disproportionate impact of the pandemic on among people holding minoritized racial and ethnic identities, describing how language barriers and restrictive visitation policies exacerbated institutional mistrust and compromised physicians' ability to develop therapeutic relationships. We also identified several perceived influences on patient-clinician communication and the establishment of therapeutic relationships. Barriers included physicians' fear of becoming infected with COVID-19 and use of personal protective equipment, which created obstacles to effective physical and verbal interactions. Facilitators included the presence of on-site interpreters, use of web-based technology to interact with family members outside the ICU, and designation of a care team member or specialist service to provide routine updates to families. The COVID-19 pandemic has threatened patient-clinician communication and the development of therapeutic relationships in the ICU, particularly among people holding minoritized racial and ethnic identities and their families. We identified several facilitators to improve patient-clinician communication as perceived by intensivists that may help improve trust and foster therapeutic alliances.