Immunological Biomarkers of Fatal COVID-19: A Study of 868 Patients

Information on the immunopathobiology of coronavirus disease 2019 (COVID-19) is rapidly increasing; however, there remains a need to identify immune features predictive of fatal outcome. This large-scale study characterized immune responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection using multidimensional flow cytometry, with the aim of identifying high-risk immune biomarkers. Holistic and unbiased analyses of 17 immune cell-types were conducted on 1,075 peripheral blood samples obtained from 868 COVID-19 patients and on samples from 24 patients presenting with non-SARS-CoV-2 infections and 36 healthy donors. Immune profiles of COVID-19 patients were significantly different from those of age-matched healthy donors but generally similar to those of patients with non-SARS-CoV-2 infections. Unsupervised clustering analysis revealed three immunotypes during SARS-CoV-2 infection; immunotype 1 (14% of patients) was characterized by significantly lower percentages of all immune cell-types except neutrophils and circulating plasma cells, and was significantly associated with severe disease. Reduced B-cell percentage was most strongly associated with risk of death. On multivariate analysis incorporating age and comorbidities, B-cell and non-classical monocyte percentages were independent prognostic factors for survival in training (n=513) and validation (n=355) cohorts. Therefore, reduced percentages of B-cells and non-classical monocytes are high-risk immune biomarkers for risk-stratification of COVID-19 patients

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Sustainable oxygen evolution electrocatalysis in aqueous 1 M H2SO4 with earth abundant nanostructured Co3O4

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Sustainable oxygen evolution electrocatalysis in aqueous 1 M H2SO4 with earth abundant nanostructured Co3O4

Earth-abundant electrocatalysts for the oxygen evolution reaction (OER) able to work in acidic working conditions are elusive. While many first-row transition metal oxides are competitive in alkaline media, most of them just dissolve or become inactive at high proton concentrations where hydrogen evolution is preferred. Only noble-metal catalysts, such as IrO2, are fast and stable enough in acidic media. Herein, we report the excellent activity and long-term stability of Co3O4-based anodes in 1 M H2SO4 (pH 0.1) when processed in a partially hydrophobic carbon-based protecting matrix. These Co3O4@C composites reliably drive O2 evolution a 10 mA cm–2 current density for >40 h without appearance of performance fatigue, successfully passing benchmarking protocols without incorporating noble metals. Our strategy opens an alternative venue towards fast, energy efficient acid-media water oxidation electrodes

An Autonomous Device for Solar Hydrogen Production from Sea Water

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Author Correction: Sustainable oxygen evolution electrocatalysis in aqueous 1 M H2SO4 with earth abundant nanostructured Co3O4 (Nature Communications, (2022), 13, 1, (4341), 10.1038/s41467-022-32024-6)

The original version of this Article contained an error in Fig. 5, in which x-axis beneath panel c was incorrectly labelled. The correct version of Fig. 5 is: (Figure presented.)

Factors influencing referrals for ultrasound-diagnosed complications during prenatal care in five low and middle income countries

Abstract Background Ultrasound during antenatal care (ANC) is proposed as a strategy for increasing hospital deliveries for complicated pregnancies and improving maternal, fetal, and neonatal outcomes. The First Look study was a cluster-randomized trial conducted in the Democratic Republic of Congo, Guatemala, Kenya, Pakistan and Zambia to evaluate the impact of ANC-ultrasound on these outcomes. An additional survey was conducted to identify factors influencing women with complicated pregnancies to attend referrals for additional care. Methods Women who received referral due to ANC ultrasound findings participated in structured interviews to characterize their experiences. Cochran-Mantel-Haenszel statistics were used to examine differences between women who attended the referral and women who did not. Sonographers’ exam findings were compared to referred women’s recall. Results Among 700 referred women, 510 (71%) attended the referral. Among referred women, 97% received a referral card to present at the hospital, 91% were told where to go in the hospital, and 64% were told that the hospital was expecting them. The referred women who were told who to see at the hospital (88% vs 66%), where to go (94% vs 82%), or what should happen, were more likely to attend their referral (68% vs 56%). Barriers to attending referrals were cost, transportation, and distance. Barriers after reaching the hospital were substantial. These included not connecting with an appropriate provider, not knowing where to go, and being told to return later. These barriers at the hospital often led to an unsuccessful referral. Conclusions Our study found that ultrasound screening at ANC alone does not adequately address barriers to referrals. Better communication between the sonographer and the patient increases the likelihood of a completed referral. These types of communication include describing the ultrasound findings, including the reason for the referral, to the mother and staff; providing a referral card; describing where to go in the hospital; and explaining the procedures at the hospital. Thus, there are three levels of communication that need to be addressed to increase completion of appropriate referrals-communication between the sonographer and the woman, the sonographer and the clinic staff, and the sonographer and the hospital. Trial registration NCT01990625

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial

Background Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. Methods In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. Findings The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47 394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50 743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48 219 women in the intervention group and 867 (2%) of 51 523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). Interpretation Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development.Fil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: McClure, Elizabeth M.. Rti International;Fil: Hemingway Foday, Jennifer. Rti International;Fil: Berrueta, Amanda Mabel. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Mazzoni, Agustina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Ciganda, Alvaro. Unicem; Uruguay. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Goudar, Shivaprasad S.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Kodkany, Bhalachandra S.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Mahantshetti, Niranjana S.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Dhaded, Sangappa M.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Katageri, Geetanjali M.. S. Nijalingappa Medical College; IndiaFil: Metgud, Mrityunjay C.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Joshi, Anjali M.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Bellad, Mrutyunjaya B.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Honnungar, Narayan V.. Jawaharlal Nehru Medical College Belgaum; IndiaFil: Derman, Richard J.. Christiana Health Care Services; Estados UnidosFil: Saleem, Sarah. The Aga Khan University; PakistánFil: Pasha, Omrana. The Aga Khan University; PakistánFil: Ali, Sumera. The Aga Khan University; PakistánFil: Hasnain, Farid. The Aga Khan University; PakistánFil: Goldenberg, Robert L. Columbia University; Estados UnidosFil: Esamai, Fabian. Moi University; KeniaFil: Nyongesa, Paul. Moi University; KeniaFil: Ayunga, Silas. University of Alabama at Birmingahm; Estados UnidosFil: Liechty, Edward A. Indiana University; Estados UnidosFil: Garces, Ana L. Francisco Marroquin University; Guatemala. Fundacion Para la Alimentacion y Nutricion de Centro America y Panama; GuatemalaFil: Figueroa, Lester. Fundacion Para la Alimentacion y Nutricion de Centro America y Panama; GuatemalaFil: Hambidge, K Michael. State University of Colorado - Fort Collins; Estados UnidosFil: Krebs, Nancy F. State University of Colorado - Fort Collins; Estados UnidosFil: Patel, Archana. Government Medical College Nagpur; India. Lata Medical Research Foundation; IndiaFil: Bhandarkar, Anjali. Lata Medical Research Foundation; IndiaFil: Waikar, Manjushri. Lata Medical Research Foundation; IndiaFil: Hibberd, Patricia L. Massachusetts General Hospital; Estados UnidosFil: Chomba, Elwyn. University Teaching Hospital Lusaka; ZambiaFil: Carlo, Waldemar A. University of Alabama at Birmingahm; Estados UnidosFil: Mwiche, Angel. University Teaching Hospital Lusaka; ZambiaFil: Chiwila, Melody. Centre For Infectious Disease Research; ZambiaFil: Manasyan, Albert. University of Alabama at Birmingahm; Estados UnidosFil: Pineda, Sayury. Fundacion Para la Alimentacion y Nutricion de Centro America y Panama; GuatemalaFil: Meleth, Sreelatha. Rti International; Estados UnidosFil: Thorsten, Vanessa. Rti International; Estados UnidosFil: Stolka, Kristen. Rti International; Estados UnidosFil: Wallace, Dennis D. Rti International; Estados UnidosFil: Koso-Thomas, Marion. National Instituto Of Child Health & Human Developm.; Estados UnidosFil: Jobe, Alan H. Cincinnati Children's Hospital Medical Center; Estados UnidosFil: Buekens, Pierre M. Tulane University School Of Public Health And Tropical Medicine; Estados Unido