[What do we know about the origin of COVID-19 three years later?] / ¿Qué sabemos del origen del COVID-19 tres años después?

More than three years have passed since the first case of a new coronavirus infection (SARS-CoV-2) in the city of Wuhan (Hubei, China). The Wuhan Institute of Virology was founded in that city in 1956 and the country's first biosafety level 4 laboratory opened within that center in 2015. The coincidence that the first cases of infection emerged in the city where the virology institute's headquarters is located, the failure to 100% identify the virus' RNA in any of the coronaviruses isolated in bats, and the lack of evidence on a possible intermediate animal host in the contagion's transmission make it so that at present, there are doubts about the real origin of SARS-CoV-2. This article will review two theories: SARS-CoV-2 as a virus of zoonotic origin or as a leak from the high-level biosafety laboratory in Wuhan.

Remdesivir Resistance Analyses from the Pinetree Study in Outpatients with Covid-19

Background: Remdesivir (RDV) is a broad-spectrum nucleotide analog antiviral approved for the treatment of COVID-19 in patients who are hospitalized or non-hospitalized and at risk of progressing to severe disease. Here we present SARS-CoV-2 resistance analyses from the Phase 3 PINETREE trial. Method(s): PINETREE was a double-blind, placebo-controlled trial of nonhospitalized participants (N=562) with COVID-19 and >=1 risk factor for disease progression, randomized to receive RDV or placebo once-daily for 3 days. The whole genome of SARS-CoV-2 was sequenced from nasopharyngeal swabs collected at days 1 (baseline), 2, 3, 7, and 14 using next-generation sequencing. Emergent amino acid substitutions in SARS-CoV-2 from participants treated with RDV were tested in a replicon system to determine if they alter sensitivity to RDV. Result(s): Resistance analysis criteria included all participants in the RDV group and 50% in the placebo group with viral load above the lower limit of detection for the viral load assay. Of 281 participants who met these criteria, baseline and postbaseline sequencing data were available for 115/130 (88.5%) participants in the RDV group and 129/151 (85.4%) participants in the placebo group (Table 1). Among these, emergent substitutions in Nsp12 were observed in 8/115 (7.0%) in the RDV group and 7/129 (5.4%) in the placebo group. A total of 7 emergent amino acid substitutions in Nsp12 were observed in the RDV group, but not in the placebo group. Among these, only one substitution from one participant (A376V;first detected at day 14), showed reduced in vitro susceptibility to RDV, with a half-maximal effective concentration (EC50) fold-change of 12.6 compared with a wildtype reference. The participant achieved clinical recovery by day 14. None of the other substitutions impacted RDV susceptibility (EC50 fold-change <=1.4). Emergent substitutions in Nsp8, Nsp10, Nsp13, or Nsp14 were detected in 10/115 (8.7%) of participants in the RDV group and 10/129 (7.8%) in the placebo group, with substitutions in the RDV group showing similar susceptibility to RDV as the wildtype reference (EC50 fold-change <=2.3). Conclusion(s): Overall, emergent substitutions in the SARS-CoV-2 replication complex including Nsp12 were observed with similar frequency in the RDV and placebo groups, with only one participant developing a substitution associated with reduced in vitro RDV susceptibility, indicating a high barrier to the development of RDV resistance in COVID-19 patients.

REMDESIVIR RETAINS POTENT ACTIVITY AGAINST SARS-CoV-2 VARIANTS OF CONCERN

Background: Recent SARS-CoV-2 variants of concern (VOCs) have shown a progressive loss of sensitivity to monoclonal antibody therapeutics. Remdesivir (RDV) is a nucleotide analog prodrug that targets the viral RNA-dependent RNA polymerase (RdRp) Nsp12 and is approved to treat COVID-19 in hospitalized and non-hospitalized patients. Nsp12 is highly conserved across VOCs to date and RDV antiviral activity against previous VOCs (Alpha to Omicron BA.1) has been maintained. Here, we conduct a structural analysis of Nsp12 substitutions observed in recent Omicron subvariants (BA.2, BA.2.12.1, BA.4, BA.5 and BA.2.75) and assess RDV antiviral activity against clinical isolates and sitedirected mutants (SDMs) in a replicon system. Method(s): The prevalence of Nsp12 substitutions in Omicron subvariants was evaluated by analysis of sequences from the Global Initiative on Sharing Avian Influenza Data (GISAID) EpiCoV database. Structural analysis of identified substitutions was conducted on a prior cryo-electron microscopy-based model of the replication-transcription complex. Antiviral activity against subvariant clinical isolates was assessed by nucleoprotein ELISA in A549-hACE2-TMPRSS2 cells and by SDMs in the replicon system. Result(s): Genomic analysis of >1.4 million Omicron subvariant sequences revealed unique substitutions in Nsp12 compared to the ancestral WA1 strain. Besides P323L, present in all subvariants, G671S was observed in 95.9% of BA.2.75 sequences, F694Y was observed in <=1.9% of BA.4, BA.5 and BA.2.75 sequences, and Y521C was observed in 1.7% of BA.5 sequences. As anticipated, structural analysis of these substitutions showed no direct interaction with the incoming RDV nucleotide triphosphate or the viral RNA. Phenotyping of clinical isolates of Omicron subvariants BA.2, BA.2.12.1, BA.4, BA.5, and BA.2.75 consistently resulted in mean RDV EC50 values of 24.5 nM (BA.2) to 106.0 nM (BA.5). This represented 0.15-to 0.66-fold changes compared to WA1, indicating no loss of in vitro RDV antiviral activity against these VOCs. P323L, G671S, and F694Y were shown previously to have no impact on RDV antiviral activity. Similarly, the individual substitution Y521C showed no change in RDV susceptibility in the SARS-CoV-2 replicon system. Conclusion(s): RDV retained potent in vitro antiviral activity against all tested Omicron VOCs with potencies comparable to the WA1 isolate. These data support the continued use of RDV in patients infected with Omicron subvariants.

SARS-CoV-2 REPLICON SYSTEM FOR THE PHENOTYPIC EVALUATION OF NSP GENE SUBSTITUTIONS

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the current global pandemic of the COVID-19, which has persisted partly through the emergence of new variants. A non-infectious, convenient, and reproducible in vitro system is needed to assess drug susceptibility of new variants of concern and potential drug resistance mutations. Method(s): The SARS-CoV-2 replicon protocol was adapted and optimized based on {Zhang 2021}. The replicon RNA was produced by in vitro transcription of full-length replicon DNA assembled by ligation of plasmid fragments encoding for the SARS-CoV-2 non-structural proteins (Nsps), nucleoprotein and gaussia luciferase reporter protein. Wild-type and mutant replicon RNAs were transfected into Huh7-1CN cells by electroporation and treated with remdesivir (RDV). To determine EC50 values, luciferase activity was determined at 48 hours post transfection. A recombinant SARS-CoV-2 virus rescue system {Xie 2020} was used to generate matching Nsp mutants for comparison with the replicon system. Result(s): The selected substitutions reflective of Omicron BA.5 sub-lineage BF.7 variant: the triple mutants (Nsp12 (P323L) +Nsp13 (R392C) + Nsp14 (I42V), and a single Nsp12 L247F mutant as well as several specific Nsp12 mutations identified by in vitro resistance selection with RDV or RDV parent nucleoside analog GS-441524 were cloned into the replicon and tested for susceptibility to RDV. RDV inhibited the SARS-CoV-2 wild-type replicon with a mean EC50 value of 14.7 +/- 3.5 nM (N=9). The Nsp12 P323L substitution, a common polymorphism in all major variants of concern including Omicron, was fully susceptible to RDV with a 0.6-fold change in EC50 from the wild-type. The Omicron BF.7 triple mutants and L247F were also fully susceptible to RDV with 0.5- and 0.4-fold changes, respectively. Nsp12 substitutions F480L, V557L, V792I, S759A+V792I, and C799F resulting from in vitro resistance selections with RDV showed minimal to moderate levels of reduced susceptibility to RDV (1.8 to 18.3-fold change) (Table 1). The RDV EC50 fold changes correlated between the noninfectious replicon and recombinant infection virus system (Table 1). Conclusion(s): The replicon system is a convenient and reproducible model to test the susceptibility of SARS-CoV-2 mutant variants to RDV and potentially other antivirals. The common Nsp12 polymorphisms in all variants including the highly transmissible Omicron variant were fully susceptible to RDV.

Multi-organ ultrasound for SARS-COV-2 disease

Aim: There is growing evidence regarding the imaging ultrasound findings of coronavirus disease 2019 COVID-19. Multi-organ ultrasound has played a significant role in the diagnosis and follow-up of these patients. The aim of this study was to describe the ultrasound findings at pulmonary, cardiac and deep venous system of the lower extremities in patients with SARS-COV-2 infection. Material and method: Prospective, cross-sectional, observational study was conducted in patients with confirmed COVID-19 who underwent a multi-organ point-of-care ultrasound (POCUS) examination during hospitalization. Results: A total of 107 patients were enrolled. Lung involvement was present in 100% of the patients, 93.4% bilaterally involvement. The most affected lung area was the posteroinferior (94.39%) followed by the lateral (89.72%). Subpleural consolidations were present in 71% of patients and consolidations larger than 1 cm in 25%. More echographic lung involvement is relational with the degree of respiratory insufficiency. Only two patients had proximal deep vein thrombosis in the lower extremities, 27 angiography tomography scan were performed and pulmonary thromboembolism was confirmed in 14 patients. The most frequent echocardiographic findings were impaired left ventricular relaxation and left ventricular hypertrophy. All patients with thromboembolic disease had severe or critical echocardiographic pulmonary involvement. Conclusions: Multi-organ POCUS ultrasound may be useful for the manifestations of COVID-19. The degree of lung ultrasound involvement was related to the degree of respiratory failure and to the presence of VTED. The relationship between DVT and PTE was lower than expected. Cardiac involvement has little relevance in our series.

[Analysis of infectious diseases care in Spanish hospitals from 2016-2020, including the first year of the SARS-CoV-2 pandemic]. / Análisis de la atención a patologías infecciosas en los hospitales españoles en el periodo 2016-2020, incluyendo el primer año de pandemia por SARS-CoV-2.

Aims: This work aimed to review patients discharged from Spanish hospitals with a principal diagnosis of infection during a 5-year period, including the first year of the SARS-CoV-2 pandemic. Materials and method: This work analyzed the Basic Minimum Data Set (CMBD) of patients discharged during the 2016-2020 period from hospitals in the Spanish National Health Service in order to identify cases with a principal diagnosis of an infectious disease according to the ICD-10-S code. All patients older than 14 years of age admitted to a conventional ward or intensive care unit, excluding labor and delivery, were included in the analysis and were evaluated based on the discharging department. Results: Patients discharged with infectious diseases as the principal diagnosis have increased from 10% to 19% in recent years. A large part of the growth is due to the SARS-CoV-2 pandemic. Internal medicine departments cared for more than 50% of these patients, followed by pulmonology (9%) and surgery (5%). In 2020, 57% of patients with a principal diagnosis of infection were discharged by internists, who cared for 67% of patients with SARS CoV-2. Conclusions: At present, more than half of patients admitted with a principal diagnosis of infection are discharged from internal medicine departments. Given the growing complexity of infections, the authors advocate for an approach in which training allows for specialization, but within a generalist context, for the better management of these patients.

Top-ten papers in pneumonia (2020-2021).

Despite the fact that the last year has been marked by the SARS-CoV-2 pandemic, there have been many articles published on non-COVID pneumonia. Making the selection has not been easy, having based on those articles that we think can bring us some novelty and help in clinical practice. We have divided the selection into seven sections: patient severity, diagnosis, treatment, ventilation, novelties in the guidelines, fungal infection and organ donation.

East of Eden: An existential view of the pandemic

In this chapter the author explores the challenges to individuals and communities. Drawing on the existential human givens, introduced earlier, he considers how the pandemic has drawn attention to these existential challenges. In particular, he considers changes in our relationship with our mortality, the importance of the relationship between freedom and responsibility, and how lockdowns and social distancing have changed our relationship with others. He then looks at how the pandemic has called for us to re-examine what is meaningful and how we position ourselves in relation to our pandemic experience. This includes the need to accept the responsibility for creating meaning, and to take on a creator rather than a victim role. © 2023 selection and editorial matter, Monica Hanaway;individual chapters, the contributors.

Rethinking spatial policy in an era of multiple crises

After more than thirty years of post-war relative regional convergence, since the 1980s geographical inequalities in economic prosperity and social conditions have widened again in most capitalist countries. In this paper we argue that this resumption of spatial inequality is in part explained by the significant changes observed in the role of the state and in public intervention in the shift from the post-war 'Keynesian' regime of state regulation to the 'Neoliberal' regime that has held sway over the past four decades. We argue that most public policies enacted in this latter period have actually exacerbated socioeconomic - and spatial - polarization, favouring a few metropolitan areas and regions at the expense of a substantial number of what are now commonly referred to as 'left behind places'. We contend that we are now at a new juncture in the evolution of capitalism: in the space of little more than decade the global system has been destabilized by a major financial crisis (2008) and the COVID-19 pandemic (2020), both with enduring socio-economic aftershocks, while the climate emergency is reaching existential proportions. In this Editorial Introduction we call for a bold 'rethinking' of public action - and especially spatial policy - to face these recurring crises, and we outline some pointers for more effective and inclusive policies. © 2022 The Author(s). Published by Oxford University Press on behalf of the Cambridge Political Economy Society. All rights reserved.

Plasma degradation of contaminated PPE: an energy-efficient method to treat contaminated plastic waste.

The use of PPE has drastically increased because of the SARS-CoV-2 (COVID-19) pandemic as disposable surgical face masks made from non-biodegradable polypropylene (PP) polymers have generated a significant amount of waste. In this work, a low-power plasma method has been used to degrade surgical masks. Several analytical techniques (gravimetric analysis, scanning electron microscopy (SEM), attenuated total reflection-infra-red spectroscopy (ATR-IR), x-ray photoelectron spectroscopy (XPS), thermogravimetric analysis/differential scanning calorimetry (TGA/DSC) and wide-angle x-ray scattering (WAXS)) were used to evaluate the effects of plasma irradiation on mask samples. After 4 h of irradiation, an overall mass loss of 63 ± 8%, through oxidation followed by fragmentation, was observed on the non-woven 3-ply surgical mask, which is 20 times faster than degrading a bulk PP sample. Individual components of the mask also showed different degradation rates. Air plasma clearly represents an energy-efficient tool for treating contaminated PPE in an environmentally friendly approach.

Low-dose intravenous and subcutaneous CIS43LS monoclonal antibody for protection against malaria (VRC 612 Part C): a phase 1, adaptive trial.

BACKGROUND: Human monoclonal antibodies might offer an important new approach to reduce malaria morbidity and mortality. In the first two parts of a three-part clinical trial, the antimalarial monoclonal antibody CIS43LS conferred high protection against parasitaemia at doses of 20 mg/kg or 40 mg/kg administered intravenously followed by controlled human malaria infection. The ability of CIS43LS to confer protection at lower doses or by the subcutaneous route is unknown. We aimed to provide data on the safety and optimisation of dose and route for the human antimalaria monoclonal antibody CIS43LS. METHODS: VRC 612 Part C was the third part of a three-part, first-in-human, phase 1, adaptive trial, conducted at the University of Maryland, Baltimore Center for Vaccine Development and Global Health, Baltimore, MD, USA. We enrolled adults aged 18-50 years with no previous malaria vaccinations or infections, in a sequential, dose-escalating manner. Eligible participants received the monoclonal antibody CIS43LS in a single, open-label dose of 1 mg/kg, 5 mg/kg, or 10 mg/kg intravenously, or 5 mg/kg or 10 mg/kg subcutaneously. Participants underwent controlled human malaria infection by the bites of five mosquitoes infected with Plasmodium falciparum 3D7 strain approximately 8 weeks after their monoclonal antibody inoculation. Six additional control participants who did not receive CIS43LS underwent controlled human malaria infection simultaneously. Participants were followed-up daily on days 7-18 and day 21, with qualitative PCR used for P falciparum detection. Participants who tested positive for P falciparum were treated with atovaquone-proguanil and those who remained negative were treated at day 21. Participants were followed-up until 24 weeks after dosing. The primary outcome was safety and tolerability of CIS43LS at each dose level, assessed in the as-treated population. Secondary outcomes included protective efficacy of CIS43LS after controlled human malaria infection. This trial is now complete and is registered with ClinicalTrials.gov, NCT04206332. FINDINGS: Between Sept 1, 2021, and Oct 29, 2021, 47 people were assessed for eligibility and 31 were enrolled (one subsequently withdrew and was replaced) and assigned to receive doses of 1 mg/kg (n=7), 5 mg/kg (n=4), and 10 mg/kg (n=3) intravenously and 5 mg/kg (n=4) and 10 mg/kg (n=4) subcutaneously, or to the control group (n=8). CIS43LS administration was safe and well tolerated; no serious adverse events occurred. CIS43LS protected 18 (82%) of 22 participants who received a dose. No participants developed parasitaemia following dosing at 5 mg/kg intravenously or subcutaneously, or at 10 mg/kg intravenously or subcutaneously. All six control participants and four of seven participants dosed at 1 mg/kg intravenously developed parasitaemia after controlled human malaria infection. INTERPRETATION: CIS43LS was safe and well tolerated, and conferred protection against P falciparum at low doses and by the subcutaneous route, providing evidence that this approach might be useful to prevent malaria across several clinical use cases. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health.

An influenza hemagglutinin stem nanoparticle vaccine induces cross-group 1 neutralizing antibodies in healthy adults.

Influenza vaccines could be improved by platforms inducing cross-reactive immunity. Immunodominance of the influenza hemagglutinin (HA) head in currently licensed vaccines impedes induction of cross-reactive neutralizing stem-directed antibodies. A vaccine without the variable HA head domain has the potential to focus the immune response on the conserved HA stem. This first-in-human dose-escalation open-label phase 1 clinical trial (NCT03814720) tested an HA stabilized stem ferritin nanoparticle vaccine (H1ssF) based on the H1 HA stem of A/New Caledonia/20/1999. Fifty-two healthy adults aged 18 to 70 years old enrolled to receive either 20 µg of H1ssF once (n = 5) or 60 µg of H1ssF twice (n = 47) with a prime-boost interval of 16 weeks. Thirty-five (74%) 60-µg dose participants received the boost, whereas 11 (23%) boost vaccinations were missed because of public health restrictions in the early stages of the COVID-19 pandemic. The primary objective of this trial was to evaluate the safety and tolerability of H1ssF, and the secondary objective was to evaluate antibody responses after vaccination. H1ssF was safe and well tolerated, with mild solicited local and systemic reactogenicity. The most common symptoms included pain or tenderness at the injection site (n = 10, 19%), headache (n = 10, 19%), and malaise (n = 6, 12%). We found that H1ssF elicited cross-reactive neutralizing antibodies against the conserved HA stem of group 1 influenza viruses, despite previous H1 subtype head-specific immunity. These responses were durable, with neutralizing antibodies observed more than 1 year after vaccination. Our results support this platform as a step forward in the development of a universal influenza vaccine.

Spanish secondary school teachers' digital competence in COVID-19 time

The main objective of this research was to analyse the ICT resources and teaching methodologies used by high school teachers before and during the state of alarm decreed by the Spanish state to combat COVID-19, as well as the teachers' opinion about their own training in digital competences. The information was collected through a questionnaire designed ad hoc addressed to all Biology and Geology teachers in the autonomous community of Castilla y León (Spain) who taught in ESO, Baccalaureate and/or Vocational Training centres during the 2020/2021 academic year (n=145). The results obtained show that the use of ICT increased considerably during the state of alarm, allowing for the adaptation of teaching programmes and methodology. The teachers surveyed considered that their use facilitated the teaching-learning process, however, a high percentage claimed not to have the necessary training and resources. Our study also suggests the existence of a digital divide in the Spanish education system, as a high percentage of teachers indicated that not all their students had the means and/or the necessary training to use virtual learning environments or virtual educational communication tools. © 2022 Universidade Federal do Rio Grande do Sul, Instituto de Fisica. All rights reserved.

Providing Comprehensive Services to Treat Patients and the Inpatient Psychiatric Bed Crisis

Objectives: A growing mental health crisis and a shortage of inpatient psychiatric beds have resulted in a surge of patients' boarded' in emergency departments awaiting acute inpatient psychiatric placement. This delays care and causes a further burden on already stressed emergency services. In June 2020, the Centers for Disease Control and Prevention (CDC) reported an increased incidence of anxiety and depressive disorders since March of 2020, in comparison to pre-pandemic data. This has further exacerbated the shortage of psychiatric beds nationwide. In addition, staff shortages at state psychiatric hospitals in the Commonwealth of Virginia led to temporary closures to admissions. State facilities in VA provide care for our most vulnerable population, including (involuntary) patients on a temporary detention order (TDO). Carilion Clinic implemented the Comprehensive Psychiatric Emergency Program (CPEP) in August 2020 with the goal of early identification and robust treatment of psychiatric patients while in the ED. Since implementation of the CPEP, providers have been able to redirect patients away from burdened state psychiatric facilities by rapid stabilization of patients in the ED. Patients were able to step down to a less restrictive environment, often no longer meeting criteria for TDO. This study aims to assess the rate of TDO releases pre- and postimplementation of the CPEP at Carilion Clinic. Method(s): A pilot program was launched in August 2020 at Carilion Roanoke Memorial Hospital through a collaboration of the Departments of Emergency Medicine and Psychiatry. The staff was comprised of a psychiatrist, a psychiatric nurse practitioner, and a social worker. Data was collected from May 2020 to June 2021 from the Epic electronic medical record and included all patients in the ED on a TDO, ages six and above. Patients who no longer met criteria for a TDO were released from involuntary status and either redirected as a voluntary patient to an inpatient psychiatric unit or discharged to the community. The rate of TDO releases three months prior to CPEP implementation was assessed and compared to the TDO release rate post-CPEP implementation. Result(s): Prior to CPEP implementation, the TDO release rate was 7%, amounting to four patients released from a TDO per month. After implementation of CPEP, the TDO release rate increased to 19%, equating to thirteen patients released from a TDO per month during the pilot period. This led to a decrease in the number of patients that would have previously been admitted to a state psychiatric facility. Patients who benefitted from implementation of the CPEP were those with conditions in the following categories: chronic mental illness (32%), individual/family crisis (24%), neurocognitive disorders (20%), substance use disorder (18%), autism spectrum disorders and intellectual/developmental disabilities (6%). Conclusion/Implications: Implementation of the Comprehensive Psychiatric Emergency Program (CPEP) in Carilion Clinic' Emergency Department was successful in reducing the number of state psychiatric admissions by redirecting 11% more involuntary patients to voluntary status. The results of this study highlight the benefits of having in-house psychiatry teams dedicated to early triage, rapid treatment, and comprehensive case management for psychiatric patients in the emergency department. References- CDC, National Center for Health Statistics. Indicators of anxiety or depression based on reported frequency of symptoms during the last 7 days. Household Pulse Survey. Atlanta, GA: US Department of Health and Human Services, CDC, National Center for Health Statistics;2020. https:// www.cdc.gov/nchs/covid19/pulse/mental-health.htm.

What do we know about the origin of COVID-19 three years later? ¿Qué sabemos del origen del COVID-19 tres años después?

More than three years have passed since the first case of a new coronavirus infection (SARS-CoV-2) in the city of Wuhan (Hubei, China). The Wuhan Institute of Virology was founded in that city in 1956 and the country's first biosafety level 4 laboratory opened within that center in 2015. The coincidence that the first cases of infection emerged in the city where the virology institute's headquarters is located, the failure to 100% identify the virus' RNA in any of the coronaviruses isolated in bats, and the lack of evidence on a possible intermediate animal host in the contagion's transmission make it so that at present, there are doubts about the real origin of SARS-CoV-2. This article will review two theories: SARS-CoV-2 as a virus of zoonotic origin or as a leak from the high-level biosafety laboratory in Wuhan.

What do we know about the origin of COVID-19 three years later?

More than three years have passed since the first case of a new coronavirus infection (SARS-CoV-2) in the city of Wuhan (Hubei, China). The Wuhan Institute of Virology was founded in that city in 1956 and the country's first biosafety level 4 laboratory opened within that center in 2015. The coincidence that the first cases of infection emerged in the city where the virology institute's headquarters is located, the failure to 100% identify the virus' RNA in any of the coronaviruses isolated in bats, and the lack of evidence on a possible intermediate animal host in the contagion's transmission make it so that at present, there are doubts about the real origin of SARS-CoV-2. This article will review two theories: SARS-CoV-2 as a virus of zoonotic origin or as a leak from the high-level biosafety laboratory in Wuhan.

Anemia in children aged 6-59 months was significantly associated with maternal anemia status in rural Zimbabwe.

Globally, anemia is a public health problem affecting mostly women of reproductive age (WRA, n = 452) and children aged 6-59 months (n = 452) from low- and lower-middle-income countries. This cross-sectional study assessed the prevalence and determinants of anemia in WRA and children aged 6-59 months in rural Zimbabwe. The venous blood sample was measured for hemoglobin utilizing a HemoCue machine. Anthropometric indices were assessed and classified based on World Health Organization standards. Socioeconomic characteristics were assessed. The median (±inter quartile range (IQR)) age of WRA was 29 ± 12 years and that for children was 29 ± 14 months. The prevalence of anemia was 29.6% and 17.9% in children and WRA, respectively, while the median (±IQR) hemoglobin levels were 13.4 ± 1.8 and 11.7 ± 1.5 g/dl among women and children, respectively. Multiple logistic regression analysis was used to assess determinants of anemia. Anemia in children was significantly associated with maternal anemia (odds ratio (OR) = 2.02; 95% CI 1.21-3.37; p = .007) and being a boy (OR = 0.63; 95% CI 0.41-0.95; p = .029), while anemia in WRA was significantly associated with the use of unimproved dug wells as a source of drinking water (OR = 0.36; 95% CI 0.20-0.66; p = .001) and lack of agricultural land ownership (OR = 0.51; 95% CI 0.31-0.85; p = .009). Anemia is a public health problem in the study setting. The positive association between maternal and child anemia reflects the possibility of cross-generational anemia. Therefore, interventions that focus on improving preconceptual and maternal nutritional status may help to reduce anemia in low-income settings.

Axillary Lymphadenopathy After a COVID-19 Vaccine Booster Dose: Time to Resolution on Ultrasound Follow-Up and Associated Factors.

BACKGROUND. Because administration of booster doses of COVID-19 vaccines is ongoing, radiologists are continuing to encounter COVID-19 vaccine-related axillary lymphadenopathy on imaging. OBJECTIVE. The purposes of this study were to assess time to resolution of COVID-19 vaccine-related axillary lymphadenopathy identified on breast ultrasound after administration of a booster dose and to assess factors potentially associated with time to resolution. METHODS. This retrospective single-institution study included 54 patients (mean age, 57 years) with unilateral axillary lymphadenopathy ipsilateral to the site of injection of a booster dose of mRNA COVID-19 vaccine visualized on ultrasound (whether an initial breast imaging examination or follow-up to prior screening or diagnostic breast imaging) performed between September 1, 2021, and December 31, 2022, and who underwent follow-up ultrasound examinations until resolution of lymphadenopathy. Patient information was extracted from the EMR. Univariable and multivariable linear regression analyses were used to identify predictors of time to resolution. Time to resolution was compared with that in a previously described sample of 64 patients from the study institution that was used to evaluate time to resolution of axillary lymphadenopathy after the initial vaccination series. RESULTS. Six of the 54 patients had a history of breast cancer, and two had symptoms related to axillary lymphadenopathy (axillary pain in both patients). Among the 54 initial ultrasound examinations showing lymphadenopathy, 33 were screening examinations and 21 were diagnostic examinations. Lymphadenopathy had resolved a mean of 102 ± 56 days after administration of the booster dose and 84 ± 49 days after the initial ultrasound showing lymphadenopathy. Age, vaccine booster type (Moderna vs Pfizer-BioNTech), and history of breast cancer were not significantly associated with time to resolution in univariable or multivariable analyses (all p > .05). Time to resolution after administration of a booster dose was significantly shorter than time to resolution after administration of the first dose in the initial series (mean, 129 ± 37 days) (p = .01). CONCLUSION. Axillary lymphadenopathy after administration of a COVID-19 vaccine booster dose has a mean time to resolution of 102 days, shorter than the time to resolution after the initial vaccination series. CLINICAL IMPACT. The time to resolution after administration of a booster dose supports the current recommendation for a follow-up interval of at least 12 weeks when vaccine-related lymphadenopathy is suspected.

Digitalization and entrepreneurial firms' resilience to pandemic crises: Evidence from COVID-19 and the German Mittelstand.

While stressing the relevance of context, the organizational resilience literature has so far not extensively examined resilience in times of healthcare crises such as the ongoing COVID-19 pandemic. The Parasite Stress Theory of Values suggests that such pandemic crises have detrimental impacts on entrepreneurial activity due to social distancing and its effects on interaction, collaboration, and innovation. However, alternatives to personal contact now available thanks to digitalization, have not yet been examined. We expect entrepreneurial firms with more digitalized business models to show higher resilience to pandemic crises, especially those highly affected by globalization and more for non-family businesses than for family businesses. Based on a survey of German Mittelstand firms in the midst of the crisis induced by COVID-19, our findings broadly support our expectations and thus help qualify the Parasite Stress Theory of Values and contribute to a better understanding of organizational resilience in times of pandemic crises.