Aumento de mortalidad materna y de prematuridad durante pandemia de COVID-19 en Chile Increase in maternal mortality and prematurity during the COVID-19 pandemic in Chile

Introducción En Chile los casos reportados de COVID-19 a nivel nacional al tercer año de pandemia (3 de noviembre del 2022) son de 4.769.638 y 61.725 fallecidos (1,3%), con el 93% de la población con esquema completo de vacunación (17.686.528). Objetivo El objetivo de este estudio es una comunicación breve sobre el impacto de la pandemia de SARS-CoV-2 en la mortalidad materna, perinatal y prematuridad en Chile. Método Se utilizó la base de datos nacional del Departamento de Informática del Ministerio de Salud de Chile (DEIS), y la información reportada desde sitio web oficial de OMS. Se incluyeron todos los nacidos, muertes generales y fetales desde enero 1990 a septiembre del 2022. Se realiza una comparación entre los indicadores básicos maternos y perinatales de los últimos 30 años y los de los años de la pandemia. Resultados Desde marzo 2020 a septiembre 2022, fallecieron más de 61.000 personas en Chile con diagnóstico asociado al COVID-19, el 17% de la mortalidad general para el período (364.000 fallecidos). Se observó una aceleración en la tendencia histórica hacia la disminución de la razón nacimientos/defunciones generales de 1,9 pre-pandemia a 1,4 al tercer año de pandemia. La razón de mortalidad materna en el año 2020 fue de 28,1 × 100.000 nacidos vivos y aumentó en comparación al año 2019 pre-pandemia (19,1) o a la línea simple de tendencia histórica proyectada para el 2020 (18) en un 56%. La prematuridad bajo 37 semanas de gestación, se incrementó de 8,5% (2019) a 9,5% para los años 2021 y 2022. La mortalidad neonatal de los primeros 28 días se mantuvo estable en 9 × 1.000 nacidos vivos durante los 3 años de pandemia y la mortalidad fetal (>21 semanas) tuvo un leve incremento a 4,7 × 1.000 nacidos vivos (año 2020) en relación a 3,4 del año 2019. Conclusiones En Chile ocurrió un aumento de aproximadamente un 56% de la mortalidad materna el primer año de pandemia de SARS-CoV-2, el segundo año se observa un aumento significativo de la prematuridad tardía y un leve incremento de la mortalidad fetal. Estos hallazgos han sido reportados en las revisiones y últimas actualizaciones del año 2022.

Modeling shield immunity to reduce COVID-19 transmission in long-term care facilities.

PURPOSE: Nursing homes and long-term care facilities have experienced severe outbreaks and elevated mortality rates of COVID-19. When available, vaccination at-scale has helped drive a rapid reduction in severe cases. However, vaccination coverage remains incomplete among residents and staff, such that additional mitigation and prevention strategies are needed to reduce the ongoing risk of transmission. One such strategy is that of "shield immunity", in which immune individuals modulate their contact rates and shield uninfected individuals from potentially risky interactions. METHODS: Here, we adapt shield immunity principles to a network context, by using computational models to evaluate how restructured interactions between staff and residents affect SARS-CoV-2 epidemic dynamics. RESULTS: First, we identify a mitigation rewiring strategy that reassigns immune healthcare workers to infected residents, significantly reducing outbreak sizes given weekly testing and rewiring (48% reduction in the outbreak size). Second, we identify a preventative prewiring strategy in which susceptible healthcare workers are assigned to immunized residents. This preventative strategy reduces the risk and size of an outbreak via the inadvertent introduction of an infectious healthcare worker in a partially immunized population (44% reduction in the epidemic size). These mitigation levels derived from network-based interventions are similar to those derived from isolating infectious healthcare workers. CONCLUSIONS: This modeling-based assessment of shield immunity provides further support for leveraging infection and immune status in network-based interventions to control and prevent the spread of COVID-19.

Starting from scratch: Step-by-step development of diagnostic tests for SARS-CoV-2 detection by RT-LAMP.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Public health strategies to reduce viral transmission are based on widespread diagnostic testing to detect and isolate contagious patients. Several reverse transcription (RT)-PCR tests, along with other SARS-CoV-2 diagnostic assays, are available to attempt to cover the global demand. Loop-mediated isothermal amplification (LAMP) based methods have been established as rapid, accurate, point of care diagnostic tests for viral infections; hence, they represent an excellent alternative for SARS-CoV-2 detection. The aim of this study was to develop and describe molecular detection systems for SARS-CoV-2 based on RT-LAMP. Recombinant DNA polymerase from Bacillus stearothermophilus and thermostable engineered reverse transcriptase from Moloney Murine Leukemia Virus were expressed using a prokaryotic system and purified by fast protein liquid chromatography. These enzymes were used to set up fluorometric real time and colorimetric end-point RT-LAMP assays. Several reaction conditions were optimized such as reaction temperature, Tris-HCl concentration, and pH of the diagnostic tests. The key enzymes for RT-LAMP were purified and their enzymatic activity was determined. Standardized reaction conditions for both RT-LAMP assays were 65°C and a Tris-HCl-free buffer at pH 8.8. Colorimetric end-point RT-LAMP assay was successfully used for viral detection from clinical saliva samples with 100% sensitivity and 100% specificity compared to the results obtained by RT-qPCR based diagnostic protocols with Ct values until 30. The developed RT-LAMP diagnostic tests based on purified recombinant enzymes allowed a sensitive and specific detection of the nucleocapsid gene of SARS-CoV-2.

Self-Reported Periodontal Disease and Its Association with SARS-CoV-2 Infection.

Introduction: Knowledge of the oral manifestations associated with SARS-CoV-2 infection, the new coronavirus causing the COVID-19 pandemic, was hindered due to the restrictions issued to avoid proximity between people and to stop the rapid spread of the disease, which ultimately results in a hyperinflammatory cytokine storm that can cause death. Because periodontal disease is one of the most frequent inflammatory diseases of the oral cavity, various theories have emerged postulating periodontal disease as a risk factor for developing severe complications associated with COVID-19. This motivated various studies to integrate questions related to periodontal status. For the present work, we used a previously validated self-report, which is a useful tool for facilitating epidemiological studies of periodontal disease on a large scale. Methodology: A blinded case-control study with participants matched 1:1 by mean age (37.7 years), sex, tobacco habits and diseases was conducted. After the diagnostic samples for SARS-CoV-2 detection were taken in an ad hoc location at Guadalajara University, the subjects were interviewed using structured questionnaires to gather demographic, epidemiological and COVID-19 symptom information. The self-reported periodontal disease (Self-RPD) questionnaire included six questions, and subjects who met the criteria with a score ≥ 2 were considered to have periodontal disease. Results: In total, 369 participants were recruited, with 117 participants included in each group. After indicating the subjects who had self-reported periodontal disease, a statistically significant difference (p value ≤ 0.001) was observed, showing that self-reported periodontal disease (n = 95, 85.1%) was higher in SARS-CoV-2-positive individuals than in controls (n = 66, 56.4%), with an OR of 3.3 (1.8-6.0) for SARS-CoV-2 infection in people with self-reported periodontal disease. Cases reported a statistically higher median of symptoms (median = 7.0, Q1= 5.5, Q3 = 10.0) than controls (p value ≤ 0.01), and cases with positive self-RPD had a significantly (p value ≤ 0.05) higher number of symptoms (median = 8.0, Q1 = 6.0, Q3 = 10.0) in comparison with those who did negative self-RPD (median = 6.0, Q1 = 5.0, Q3 = 8.0). Conclusions: According to this study, self-reported periodontal disease could be considered a risk factor for SARS-CoV-2 infection, and these individuals present more symptoms.

Validation of the Mental Health Checklist (MHCL) during COVID-19 lockdown.

The COVID-19 pandemic resulted in unprecedented disruption to everyday life, including widespread social distancing and self-quarantining aimed at reducing the virus spread. The Mental Health Checklist (MHCL) is a measure developed to assess psychological health during extended periods of isolation and confinement, and has shown strong psychometric properties in community samples and during Antarctic missions. This study validated the MHCL in a sample of 359 U.S. and U.K adults during the peak of the COVID-19 lockdown. Confirmatory factor analysis (CFA) tested model fit, and convergent validity analyses were conducted to compare the MHCL with validated measures of depression, anxiety and stress, as well as insomnia. The MHCL exhibited good model fit for most CFA indices, and showed strong convergent validity with other measures of psychological well-being. Findings suggest that the MHCL is useful for assessing mental health in a variety of environments and conditions.

Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2.

New vaccine design approaches, platforms, and immunization strategies might foster antiviral mucosal effector and memory responses to reduce asymptomatic infection and transmission in vaccinated individuals. Here, we investigated a combined parenteral and mucosal immunization scheme to induce local and serum antibody responses, employing the epitope-based antigens 3BT and NG19m. These antigens target the important emerging and re-emerging viruses PRRSV-2 and SARS-CoV-2, respectively. We assessed two versions of the 3BT protein, which contains conserved epitopes from the GP5 envelope protein of PRRSV-2: soluble and expressed by the recombinant baculovirus BacDual-3BT. On the other hand, NG19m, comprising the receptor-binding motif of the S protein of SARS-CoV-2, was evaluated as a soluble recombinant protein only. Vietnamese mini-pigs were immunized employing different inoculation routes: subcutaneous, intranasal, or a combination of both (s.c.-i.n.). Animals produced antigen-binding and neut1ralizing antibodies in serum and mucosal fluids, with varying patterns of concentration and activity, depending on the antigen and the immunization schedule. Soluble 3BT was a potent immunogen to elicit binding and neutralizing antibodies in serum, nasal mucus, and vaginal swabs. The vectored immunogen BacDual-3BT induced binding antibodies in serum and mucosae, but PRRSV-2 neutralizing activity was found in nasal mucus exclusively when administered intranasally. NG19m promoted serum and mucosal binding antibodies, which showed differing neutralizing activity. Only serum samples from subcutaneously immunized animals inhibited RBD-ACE2 interaction, while mini-pigs inoculated intranasally or via the combined s.c.-i.n. scheme produced subtle neutralizing humoral responses in the upper and lower respiratory mucosae. Our results show that intranasal immunization, alone or combined with subcutaneous delivery of epitope-based antigens, generates local and systemic binding and neutralizing antibodies. Further investigation is needed to evaluate the capability of the induced responses to prevent infection and reduce transmission.

COVID-19 and pregnancy: clinical case of critical presentation, placental inflammation and demonstrated fetal vertical transmission / COVID-19 y embarazo: caso clínico de presentación crítica, inflamación placentaria y transmisión vertical fetal demostrada

ANTECEDENTES: La pandemia global de COVID-19 llega al continente americano en marzo del año 2020 y en menos de dos meses reúne a más de la mitad de los casos a nivel global. OBJETIVO: Caso clínico de una mujer embarazada con una presentación crítica de COVID-19 y embarazo a las 25 semanas de gestación, en el contexto del peak de la pandemia en Chile en el otoño del año 2020. CASO CLÍNICO: El 20 de junio de 2020, una mujer de 34 años, con 25 semanas de embarazo, es trasladada desde Hospital de San Bernardo a Clínica Las Condes en Santiago, Chile, con un cuadro de 10 días de evolución de COVID-19, que evoluciona a una situación crítica con insuficiencia respiratoria severa. Ingresa a unidad de cuidados intensivos para ventilación mecánica. Las imágenes de radiología simple y de tomografía axial computarizada de tórax demuestran una neumopatía bilateral con imágenes características opacidades en vidrio esmerilado, asociado a engrosamiento intersticial, imágenes descritas previamente como características para COVID-19. La paciente permanece en unidad de cuidados intensivos en ventilación mecánica por siete días, con evolución favorable posterior, mejoría del cuadro séptico y alta después de 22 días de hospitalización. El parto ocurre en forma espontánea a las 38 semanas, la madre y el recién nacido evolucionan en buen estado general. El examen histopatológico placentario demuestra compromiso inflamatorio vellositario y los exámenes de anticuerpos en sangre del recién nacido demuestran la presencia de anticuerpos del tipo IgG e IgM. Se trata de uno de los pocos casos demostrados reportados de transmisión transplacentaria vía sanguínea de SARS-CoV-2 de la madre al recién nacido.

BACKGROUND: The global COVID-19 pandemic reaches the American continent in March 2020 and in less than two months it brings together more than half of the cases globally.OBJECTIVE: The clinical case of a 25-week pregnant woman with a critical presentation of COVID-19 and pregnancy at 25 weeks of gestation, is presented in the context of the peak of the pandemic in Chile in the fall of 2020. CLINICAL CASE: On June 20, 2020, a 34-year-old woman, 25 weeks pregnant, is transferred from Hospital de San Bernardo to Clinica Las Condes in Santiago, Chile, with a ten-day evolution of a COVID-19 that evolves to critical with severe respiratory failure. She is admitted to the intensive care unit for mechanical ventilation. Chest computerized axial tomography images demonstrate bilateral pneumopathy with characteristic images of ground-glass opacities, associated with interstitial thickening, images previously described as characteristics for COVID-19. The patient remains in the intensive care unit on mechanical ventilation for seven days, with subsequent favorable evolution, improvement of the septic condition, and discharge after 22 days of hospitalization. Delivery occurs at 38 weeks, the mother and the newborn evolve in good general condition. The placental histopathological examination demonstrates villous inflammatory involvement, and the newborn's blood tests show the presence of IgG and IgM antibodies. It is one of the few reported cases of transplacental transmission of SARS-CoV-2 from the mother to the newborn.

Maternal and perinatal outcomes in pregnant women with confirmed severe and mild COVID-19 at one large maternity hospital in Chile.

OBJECTIVE AND METHODS: We conducted a prospective observational cohort study in 458 pregnant and puerperal women, with confirmed COVID-19 at Hospital San Jose, Santiago, Chile, to determine the impact of COVID-19 on pregnancy and confirm safety and feasibility of a management protocol based on clinical presentation of the disease. RESULTS: 25.5% (117/458) of women were severe and 74.4% (341/458) mild presentation. Three percent (9/341) of mild presentations required a subsequent hospitalization. Overall, 26/458 women (5.6%) were admitted to ICU, and 13/458 (2.8%) required mechanical ventilation. One maternal death occurred at 49-days postpartum. Severe presentation, infection above 24 weeks, and comorbidities were associated with an adverse maternal outcome. Of total deliveries, 16.5% (36/217) were <37 weeks. Perinatal mortality was 6/226 (2.7%), mostly due to the fetal component. CONCLUSIONS: A quarter of the women had severe COVID-19 that, combined with occurrence of disease in the second half of pregnancy, resulted in substantial maternal compromise. Perinatal morbidity and mortality in women with severe disease were high and warrant consideration. Outpatient management was safe for mild cases.

Modeling shield immunity to reduce COVID-19 epidemic spread.

The COVID-19 pandemic has precipitated a global crisis, with more than 1,430,000 confirmed cases and more than 85,000 confirmed deaths globally as of 9 April 20201-4. Mitigation and suppression of new infections have emerged as the two predominant public health control strategies5. Both strategies focus on reducing new infections by limiting human-to-human interactions, which could be both socially and economically unsustainable in the long term. We have developed and analyzed an epidemiological intervention model that leverages serological tests6,7 to identify and deploy recovered individuals8 as focal points for sustaining safer interactions via interaction substitution, developing what we term 'shield immunity' at the population scale. The objective of a shield immunity strategy is to help to sustain the interactions necessary for the functioning of essential goods and services9 while reducing the probability of transmission. Our shield immunity approach could substantively reduce the length and reduce the overall burden of the current outbreak, and can work synergistically with social distancing. The present model highlights the value of serological testing as part of intervention strategies, in addition to its well-recognized roles in estimating prevalence10,11 and in the potential development of plasma-based therapies12-15.