Antibody Avidity Maturation Following Recovery From Infection or the Booster Vaccination Grants Breadth of SARS-CoV-2 Neutralizing Capacity.

BACKGROUND: Cross-neutralizing capacity of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important in mitigating (re-)exposures. Role of antibody maturation, the process whereby selection of higher affinity antibodies augments host immunity, to determine SARS-CoV-2 neutralizing capacity was investigated. METHODS: Sera from SARS-CoV-2 convalescents at 2, 6, or 10 months postrecovery, and BNT162b2 vaccine recipients at 3 or 25 weeks postvaccination, were analyzed. Anti-spike IgG avidity was measured in urea-treated ELISAs. Neutralizing capacity was assessed by surrogate neutralization assays. Fold change between variant and wild-type neutralization inferred the breadth of neutralizing capacity. RESULTS: Compared with early-convalescent, avidity indices of late-convalescent sera were significantly higher (median, 37.7 [interquartile range 28.4-45.1] vs 64.9 [57.5-71.5], P < .0001). Urea-resistant, high-avidity IgG best predicted neutralizing capacity (Spearman r = 0.49 vs 0.67 [wild-type]; 0.18-0.52 vs 0.48-0.83 [variants]). Higher-avidity convalescent sera better cross-neutralized SARS-CoV-2 variants (P < .001 [Alpha]; P < .01 [Delta and Omicron]). Vaccinees only experienced meaningful avidity maturation following the booster dose, exhibiting rather limited cross-neutralizing capacity at week 25. CONCLUSIONS: Avidity maturation was progressive beyond acute recovery from infection, or became apparent after the booster vaccine dose, granting broader anti-SARS-CoV-2 neutralizing capacity. Understanding the maturation kinetics of the 2 building blocks of anti-SARS-CoV-2 humoral immunity is crucial.

Risk of stroke and other adverse outcomes in patients with perioperative atrial fibrillation 1 year after non-cardiac surgery.

AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery. METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P < 0.001. Patients with POAF also had an increased risk of death (incidence 31.37 vs. 9.34; aHR 2.51, 95% CI 2.01-3.14; P < 0.001) and MI (incidence 26.20 vs. 8.23; aHR 5.10, 95% CI 3.91-6.64; P < 0.001). CONCLUSION: Patients with POAF have a significantly increased risk of stroke, MI, and death at 1 year. Intervention studies are needed to evaluate risk reduction strategies in this high-risk population.

Maternal morbidity under an absolute abortion ban: insights from a 6-year case series of fatal fetal malformations in El Salvador.

BACKGROUND: A striking number of national and subnational governments that previously allowed legal abortion in cases of severe fetal anomaly have passed new legislation to explicitly remove these allowances. However, we know little about the maternal health implications of such restrictions. OBJECTIVE: This study aimed to examine the health outcomes of pregnant individuals in El Salvador whose fetuses were diagnosed with a fatal congenital malformation and who were legally required to carry these nonviable pregnancies to term under the nation's absolute abortion ban. STUDY DESIGN: We reviewed the charts of all 239 pregnancies with fetuses classified as having 1 of 18 congenital malformations typically considered to be incompatible with extrauterine life that were evaluated at the National Women's Hospital in El Salvador between January 1, 2013 and December 31, 2018. Because regional healthcare providers who identify pregnancy complications in El Salvador are instructed to refer those patients to the National Women's Hospital, our analysis captured the total population of lethal fetal malformations treated by the national public health system. We documented pregnant patients' socioeconomic characteristics, pregnancy-related complications, and the medical procedures used to mitigate complications. RESULTS: Individuals who were required to carry pregnancies with severe fetal malformations to term (or until preterm labor began naturally) experienced high rates of maternal morbidity. More than half (54.9%) of pregnancies experienced at least 1 serious pregnancy-related health complication, whereas 47.9% underwent a physically-invasive medical procedure to manage complications, including cesarean deliveries, decompression amniocenteses, fetal head decompressions, and, in 1 case, a full hysterectomy. A total of 9% of patients opted to discontinue care after receiving the diagnosis of fatal fetal malformation. We also found striking variation in how physicians managed pregnancies with fatal fetal malformations, suggesting that different interpretations of the law lead to inequities in individual-level patient care. CONCLUSION: Laws prohibiting abortions in cases of severe fetal malformation can increase risks to pregnant patients by requiring clinicians to subject healthy patients to a course of treatment that generates morbidity.

Effects of the WHO 8-step wheelchair-service-delivery process on wheelchair users in El Salvador: a cohort study.

PURPOSE: To test the hypotheses that, after the delivery of manual wheelchairs following the WHO 8-step service-delivery process, wheelchair-related health and quality of life, wheelchair skills, wheelchair use, and poverty probability would improve; and that the number of wheelchair repairs required, adverse events, caregiver burden, and the level of assistance provided would decrease. METHODS: This was a longitudinal, prospective within-subject study including 247 manual wheelchair users, and 119 caregivers, in El Salvador who received a wheelchair following the WHO 8-step process as well as maintenance reminders. Outcome measurements were performed via structured questionnaires and dataloggers at the initial assessment, at wheelchair delivery, and at 3- and 6-month follow-up. RESULTS: Significant improvements in wheelchair-related health indicators (all with p < 0.004) and quality of life (p = 0.001), and a significant reduction in national and "extreme" poverty probability (p = 0.004 and p = 0.012) were observed by six months. Wheelchair use significantly decreased (p = 0.011 and p = 0.035) and wheelchair skills increased (p = 0.009). Caregiver burden did not change (p = 0.226) but the number of activities of daily living (ADLs) that required no assistance significantly increased (p = 0.001) by three months and those who required complete assistance decreased (p = 0.001). No changes were observed in wheelchair repairs (p = 0.967) and breakdowns over time with new wheelchairs. CONCLUSIONS: Wheelchair service delivery using the WHO 8-step process on manual wheelchair users in El Salvador has positive effects on health and quality of life, wheelchair skills, caregiver assistance levels, and poverty. Further research is needed to determine the relative contributions of the intervention components.Implications for RehabilitationProviding manual wheelchairs using the 8-step process of the WHO has benefits on health and quality of life, wheelchair skills, caregiver assistance levels, and poverty.The WHO 8-steps service delivery process for manual wheelchairs can be used in less-resourced settings.

Hallazgos histopatológicos pulmonares asociados a COVID-19. Una revisión sistemática y meta-análisis / Histopathological findings in lungs of COVID-19 infected subjects. A systematic review and meta-analysis

El COVID-19 es una nueva enfermedad que requería resultados prontos provenientes de la investigación. Un abordaje para la comprensión de su fisiopatología es conocer el daño a nivel histopatológico que genera en los pulmones de los afectados. Objetivo. Proveer un resumen riguroso de la evidencia disponible sobre los hallazgos histopatológicos pulmonares en pacientes con COVID-19. Se desarrolló una revisión sistemática con metaanálisis de proporciones. Se incluyeron estudios primarios de cualquier diseño que tuvieran datos primarios de hallazgos histopatológicos de pulmones en pacientes COVID-19. Se excluyeron revisiones y guías. Las fuentes de información fueron el repositorio centralizado Living OVerview of Evidence, PubMed/Medline, LitCovid, la base de datos COVID-19 de la Organización Mundial de la Salud, y medRxiv hasta el 3 de abril 2021. La evaluación del riesgo de sesgos se realizó utilizando las herramientas del Instituto Joanna Briggs para series de casos y reportes de casos. Se extrajo cada dato de hallazgo pulmonar histopatológico. Se calcularon las frecuencias encontradas y los datos de los hallazgos más frecuentes fueron resumidas en metaanálisis usando el método de efectos aleatorios de Der Simmonian-Liard. Se midió la heterogeneidad. Los criterios de inclusión fueron cumplidos por 69 artículos sumando 594 sujetos. Presentaron bajo riesgo de sesgos 35 artículos. El metaanálisis de proporciones mostro daño alveolar difuso en 0,62 (IC 95 % 0,51-0,72), I2 59 % (p < 0,01), en su fase temprana (85,14 %). Conclusión. El daño alveolar difuso temprano fue el hallazgo histopatológico más frecuente en muestras pulmonares de pacientes con COVID-19

COVID-19 is a new disease that required prompt results from research. An approach to understanding its pathophysiology is to know the damage at the histopathological level that it generates in the lungs of those affected. Aim. To provide a rigorous summary of the available evidence on pulmonary histopathological findings in patients with COVID-19. A systematic review with meta-analysis of proportions was developed. Primary studies of any design that had primary data on lung histopathology findings in COVID-19 patients were included. Reviews and guidelines were excluded. The sources of information were the Living OVerview of Evidence centralized repository, PubMed/Medline, LitCovid, the World Health Organization COVID-19 database, and medRxiv up to April 3, 2021. The risk of bias assessment was performed using the Joanna Briggs Institute tools for case series and case reports. Each histopathological pulmonary finding data was extracted. The frequencies found were calculated and the data of the most frequent findings were summarized in meta-analyses using the Der Simmonian-Liard random effects method. Heterogeneity was measured. The inclusion criteria were met by 69 articles totaling 594 subjects. Thirty-five articles presented low risk of bias. The meta-analysis of proportions showed diffuse alveolar damage in 0.62 (95% CI 0.51-0.72), I2 59% (p < 0.01), in its early phase (85.14%). Conclution. Early diffuse alveolar damage was the most frequent histopathological finding in lung samples from patients with COVID-19