Limited Humoral and Specific T-Cell Responses After SARS-CoV-2 Vaccination in PWH With Poor Immune Reconstitution.

BACKGROUND: We analyzed humoral and cellular immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in people with human immunodeficiency virus (HIV; PWH) who had CD4+ T-cell counts <200/µL (HIV<200 group). METHODS: This prospective cohort study included 58 PWH in the HIV<200 group, 36 with CD4+ T-cell counts >500/µL (HIV>500 group), and 33 HIV-1-negative controls (control group). Antibodies against the SARS-CoV-2 spike protein (anti-S immunoglobulin [Ig] G) and the receptor-binding domain (anti-RBD IgG) were quantified before and 4 weeks after the first and the second doses of BNT162b2 or mRNA-1273 (at week 8). Viral neutralization activity and T-cell responses were also determined. RESULTS: At week 8, anti-S/anti-RBD IgG responses increased in all groups (P < .001). Median (interquartile range) anti-S and anti-RBD IgG levels at week 8 were 153.6 (26.4-654.9) and 171.9 (61.8-425.8) binding antibody units (BAU)/mL, respectively, in the HIV<200 group, compared with 245.6 (145-824) and 555.8 (166.4-1751) BAU/mL in the HIV>500 group and 274.7 (193.7-680.4) and 281.6 (181-831.8) BAU/mL in controls (P < .05). Neutralizing capacity and specific T-cell immune responses were absent or reduced in 33% of those in the HIV<200 group, compared with 3.7% in the HIV>500 group (P < .01). CONCLUSIONS: One-third of PWH with CD4+ T-cell counts <200/µL show low anti-S/anti-RBD IgG levels, reduced in vitro neutralization activity against SARS-CoV-2, and no vaccine-induced T cells after receiving coronavirus disease 2019 mRNA vaccines.

The prognostic importance of the angiotensin II/angiotensin-(1-7) ratio in patients with SARS-CoV-2 infection.

BACKGROUND: Information about angiotensin II (Ang II), angiotensin-converting enzyme 2 (ACE2), and Ang-(1-7) levels in patients with COVID-19 is scarce. OBJECTIVE: To characterize the Ang II-ACE2-Ang-(1-7) axis in patients with SARS-CoV-2 infection to understand its role in pathogenesis and prognosis. METHODS: Patients greater than 18 years diagnosed with COVID-19, based on clinical findings and positive RT-PCR test, who required hospitalization and treatment were included. We compared Ang II, aldosterone, Ang-(1-7), and Ang-(1-9) concentrations and ACE2 concentration and activity between COVID-19 patients and historic controls. We compared baseline demographics, laboratory results (enzyme, peptide, and inflammatory marker levels), and outcome (patients who survived versus those who died). RESULTS: Serum from 74 patients [age: 58 (48-67.2) years; 68% men] with moderate (20%) or severe (80%) COVID-19 were analyzed. During 13 (10-21) days of hospitalization, 25 patients died from COVID-19 and 49 patients survived. Compared with controls, Ang II concentration was higher and Ang-(1-7) concentration was lower, despite significantly higher ACE2 activity in patients. Ang II concentration was higher and Ang-(1-7) concentration was lower in patients who died. The Ang II/Ang-(1-7) ratio was significantly higher in patients who died. In multivariate analysis, Ang II/Ang-(1-7) ratio greater than 3.45 (OR = 5.87) and lymphocyte count ⩽0.65 × 103/µl (OR = 8.43) were independent predictors of mortality from COVID-19. CONCLUSION: In patients with severe SARS-CoV-2 infection, imbalance in the Ang II-ACE2-Ang-(1-7) axis may reflect deleterious effects of Ang II and may indicate a worse outcome.

Elevated Levels of Soluble CD147 are Associated with Hyperinflammation and Disease Severity in COVID-19: A Proof-of-Concept Clinical Study.

To evaluate soluble CD147 levels in COVID-19 and identify whether these are associated with hyperinflammation and disease severity. One-hundred and nine COVID-19 patients and 72 healthy blood donors were studied. Levels of CD147, matrix metalloproteases (MMP) and inflammatory markers were measured on hospital arrival, while the need for mechanical ventilation and the occurrence of death during hospitalization were recorded. CD147 levels were higher in COVID-19 (1.6, 1.0-2.3 vs 1.3, 1.0-1.6 ng/ml; P = 0.003) than controls. MMP-2 (9.2, 4.5-12.9 vs 4.2, 3.7-4.6 ng/ml; P < 0.001), MMP-3 (1.1, 0.9-1.3 vs 0.9, 0.7-1.0 ng/ml; P < 0.001) and MMP-9 (0.9, 0.5-1.2 vs 0.4, 0.2-0.6 ng/ml; P < 0.001) were also higher in COVID-19, while MMP-1 (0.6, 0-1.4 vs 0.6, 0.3-0.7 ng/ml; P = 0.711) was not different. Significant correlations were found between CD147 and MMP-2 (ρ = 0.34), MMP-3 (ρ = 0.21), interleukin 6 (ρ = 0.21), and the neutrophil/lymphocyte ratio (ρ = 0.26). Furthermore, CD147 levels were higher in patients who required mechanical ventilation (1.8, 1.4-2.4 vs 1.2, 0.8-1.9 ng/ml; P < 0.001) and in those who ultimately died (1.9, 1.4-2.7 vs 1.4, 0.9-1.9 ng/ml; P = 0.009). CD147 is elevated in COVID-19 and appears to contribute to hyperinflammation and disease severity.

Seroprevalence and estimation of the impact of SARS-CoV-2 infection in older adults residing in Long-term Care Facilities in Chile. / Seroprevalencia y estimación del impacto de la infección por SARS-CoV-2 en personas mayores residentes en centros de larga estadía en Chile.

Introduction: Older adults are at a higher risk of severe illness and death from COVID-19. This vulnerability increases in those who live in long-term care facilities due to overcrowding, greater physical dependence, and contact with health workers. Evidence on the impact of the pandemic on these establishments in lowand middle-income countries has been scant. This study aims to determine the seroprevalence of SARS-CoV-2 in older people residing in long-term care facilities and estimate the impact of infection after the first wave of the pandemic. Methods: A cross-sectional design with 2099 residents in three regions of Chile was carried out between September and November 2020. Measurement of antibodies was performed with a rapid test. The impact of SARS-CoV-2 infection was estimated with seropositive residents, those who had a history of positive polymerase chain reaction tests, and those who died from COVID-19. Bivariate analysis with the region, sex, age, history of COVID-19, physical dependence, and serological results were performed. In addition, we performed a correlation analysis between the seroprevalence of the centers by the municipality and the rate of confirmed cases. Results: The seroprevalence of SARS-CoV-2 antibodies in the three regions was 14.7% (95% confidence interval: 13.2 to 16.3%), the infection impact was 46.4%, and the fatality rate was 19.6%. A significant correlation was found between the seroprevalence of older adults residing in long-term care facilities and the cumulative incidence by municipalities. Conclusions: The seroprevalence of older adults residing in long-term care facilities was higher than the general population. The high impact of infection among this population at the end of the first wave of the COVID-19 pandemic is similar to other countries. The centers' environment is directly related to COVID-19 infection. Morbidity and mortality monitoring systems should be implemented promptly to establish prevention and control measures.

Introducción: Las personas mayores tienen más riesgo de enfermar gravemente y fallecer por COVID-19. Esta vulnerabilidad aumenta en quienes viven en establecimientos de larga estadía, debido a hacinamiento, mayor dependencia física y contacto con los trabajadores. La evidencia sobre el impacto de la pandemia de estos establecimientos en países de medianos y bajos ingresos ha sido escasa. El objetivo es determinar la seroprevalencia de la infección por SARS-CoV-2 en personas mayores que residen en establecimientos de larga estadía. Así como estimar el impacto global de la infección después de la primera ola de la pandemia. Métodos: Diseño transversal con 2099 residentes en tres regiones de Chile, realizado entre septiembre y noviembre 2020. Anticuerpos fueron medidos con test rápido contra SARS-CoV-2. Se estimó el impacto de la infección con los residentes seropositivos, los residentes con antecedentes de reacción en cadena de la polimerasa de transcripción inversa positiva, y residentes que murieron por COVID-19. Análisis bivariado entre el resultado serológico y región, sexo, edad, antecedentes de COVID-19 y dependencia física fueron realizados. Además, realizamos un análisis de correlación entre la seroprevalencia de los centros por municipio y la tasa acumulada de casos confirmados. Resultados: La seroprevalencia de anticuerpos en las tres regiones fue 14,7% (intervalo de confianza del 95%: 13,2 a 16,3%). El impacto real de la infección se estimó en 46,4% y la tasa de letalidad en 19,6%. La seroprevalencia de los residentes de los centros por comuna se correlacionó positiva y significativamente con la frecuencia de la enfermedad a nivel comunal. Conclusiones: Seroprevalencia superior a la de la población general, observándose un alto impacto de la infección por COVID-19 al final de la primera ola de la pandemia. El lugar en el que se encuentran los establecimientos está directamente relacionado con la tasa de seroprevalencia en ellos. Sistemas de vigilancia epidemiológica deben aplicarse con prontitud para establecer medidas de prevención y control.

Usefulness of Easy-to-Use Risk Scoring Systems Rated in the Emergency Department to Predict Major Adverse Outcomes in Hospitalized COVID-19 Patients.

BACKGROUND: Several easy-to-use risk scoring systems have been built to identify patients at risk of developing complications associated with COVID-19. However, information about the ability of each score to early predict major adverse outcomes during hospitalization of severe COVID-19 patients is still scarce. METHODS: Eight risk scoring systems were rated upon arrival at the Emergency Department, and the occurrence of thrombosis, need for mechanical ventilation, death, and a composite that included all major adverse outcomes were assessed during the hospital stay. The clinical performance of each risk scoring system was evaluated to predict each major outcome. Finally, the diagnostic characteristics of the risk scoring system that showed the best performance for each major outcome were obtained. RESULTS: One hundred and fifty-seven adult patients (55 ± 12 years, 66% men) were assessed at admission to the Emergency Department and included in the study. A total of 96 patients (61%) had at least one major outcome during hospitalization; 32 had thrombosis (20%), 80 required mechanical ventilation (50%), and 52 eventually died (33%). Of all the scores, Obesity and Diabetes (based on a history of comorbid conditions) showed the best performance for predicting mechanical ventilation (area under the ROC curve (AUC), 0.96; positive likelihood ratio (LR+), 23.7), death (AUC, 0.86; LR+, 4.6), and the composite outcome (AUC, 0.89; LR+, 15.6). Meanwhile, the inflammation-based risk scoring system (including leukocyte count, albumin, and C-reactive protein levels) was the best at predicting thrombosis (AUC, 0.63; LR+, 2.0). CONCLUSIONS: Both the Obesity and Diabetes score and the inflammation-based risk scoring system appeared to be efficient enough to be integrated into the evaluation of COVID-19 patients upon arrival at the Emergency Department.

Immunothrombosis in COVID-19: Implications of Neutrophil Extracellular Traps.

SARS-CoV-2 is a member of the family of coronaviruses associated with severe outbreaks of respiratory diseases in recent decades and is the causative agent of the COVID-19 pandemic. The recognition by and activation of the innate immune response recruits neutrophils, which, through their different mechanisms of action, form extracellular neutrophil traps, playing a role in infection control and trapping viral, bacterial, and fungal etiological agents. However, in patients with COVID-19, activation at the vascular level, combined with other cells and inflammatory mediators, leads to thrombotic events and disseminated intravascular coagulation, thus leading to a series of clinical manifestations in cerebrovascular, cardiac, pulmonary, and kidney disease while promoting severe disease and mortality. Previous studies of hospitalized patients with COVID-19 have shown that elevated levels of markers specific for NETs, such as free DNA, MPO, and H3Cit, are strongly associated with the total neutrophil count; with acute phase reactants that include CRP, D-dimer, lactate dehydrogenase, and interleukin secretion; and with an increased risk of severe COVID-19. This study analyzed the interactions between NETs and the activation pathways involved in immunothrombotic processes in patients with COVID-19.

A simple and readily available inflammation-based risk scoring system on admission predicts the need for mechanical ventilation in patients with COVID-19.

OBJECTIVE: To investigate whether a simplified inflammation-based risk scoring system comprising three readily available biomarkers (albumin, C-reactive protein, and leukocytes) may predict major adverse outcomes in patients with COVID-19. METHODS: Upon admission to the emergency room, the inflammation-based risk scoring system was applied and patients were classified as having mild, moderate, or severe inflammation. In-hospital occurrence of thrombosis, need for mechanical ventilation, and death were recorded. RESULTS: One-hundred patients (55 ± 13 years; 71% men) were included and classified as having mild (29%), moderate (12%), or severe (59%) inflammation. The need for mechanical ventilation differed among patients in each group (16%, 50%, and 71%, respectively; P < 0.0001), yielding a 4.1-fold increased risk of requiring mechanical ventilation in patients with moderate inflammation and 5.4 for those with severe inflammation. On the contrary, there were no differences for the occurrence of thrombosis (10%, 8%, and 22%, respectively; P = 0.142) or death (21%, 42%, and 39%, respectively; P = 0.106). In the multivariate analysis, only severe inflammation (hazard ratio [HR] = 4.1), D-dimer > 574 ng/mL (HR = 3.0), and troponin I ≥ 6.7 ng/mL (HR = 2.4) at hospital admission were independent predictors of the need for mechanical ventilation. CONCLUSION: The inflammation-based risk scoring system predicts the need for mechanical ventilation in patients with severe COVID-19.

First six sequences of the complete SARS-CoV-2 genome by NGS in El Salvador

En este trabajo se describen las primeras secuencias completas del genoma de SARS-CoV-2 a partir de muestras de pacientes salvadoreños. Objetivo. Reportar las primeras secuencias completas del genoma del SARS-CoV-2 de casos procedentes de El Salvador. Metodología. Se realizó una secuenciación masiva en la plataforma MiniSeq Illumina a partir de muestras de secreción nasofaríngea. Resultados. El análisis filogenético determinó que estas muestras pertenecen al clado 20C secundario de 20A que tiene en común la variante de la mutación D614G de la glicoproteína espícula. La mutación S: D614G fue encontrada en las seis secuencias de SARS-CoV-2. En la plataforma GISAID, las secuencias mostraron pertenecer al clado GH linaje pangolín B.1.2 y B.1.370;ambos linajes están presentes en Estados Unidos. Conclusión. El análisis filogenético evidenció que estas seis muestras pertenecen al clado 20C, clado secundario de 20A, que tiene en común la variante de la mutación D614G de la glicoproteína espícula This work describes the first complete sequences of the SARS-CoV-2 genome from samples of Salvadoran patients. Objective. Report the first complete sequences of the SARS-CoV-2 genome from cases from El Salvador. Methodology. Massive sequencing was performed on the MiniSeq Illumina platform from samples of nasopharyngeal secretion. Results. Phylogenetic analysis determined that these samples belong to the secondary 20C clade of 20A which has in common the variant of the spike glycoprotein D614G mutation. The S: D614G mutation was found in all six SARS-CoV-2 sequences. In the GISAID platform, the sequences were shown to belong to the clade GH pangolin lineage B.1.2 and B.1.370;both lineages are present in the United States. Conclusion. Phylogenetic analysis showed that these six samples belong to clade 20C, a secondary clade of 20A, which has in common the variant of the spike glycoprotein D614G mutation

Analysis of the D614G mutation in the sequence of the complete SARS-CoV-2 genome in El Salvador

El 18 de marzo se reporta el primer caso de infección por SARS- CoV-2 confirmado en El Salvador y durante el mes de octubre de 2020 se logra secuenciar el genoma de SARS-CoV-2 a partir de muestras obtenidas en el país. Objetivo. Analizar in silico las mutaciones detectadas en las secuencias aisladas en El Salvador. Metodología. Se utilizó la plataforma SOPHiA-DDM-V5.7.10., para la determinación de las variantes por mutaciones con sentido erróneo. Se utilizó la plataforma Nexclade beta v0.8.1.;se visualizó y comparó la proteína S silvestre (D614: PDB ID: 6VXX) y de la variante mutada (D614G: PDB ID: 6XS6). Para el modelamiento y generación de imágenes de los detalles moleculares de las proteínas se utilizó Pymol-v1.7.2.3. Resultados. Los cristales de la proteína S silvestre y mutada muestra diferencias a nivel molecular, incluyendo la pérdida de interacciones entre el residuo G614 del dominio S1 y la treonina 859 de dominio S2, favoreciendo de esta manera la conformación abierta de la proteína S, la cual es necesaria para la interacción de S con el receptor ACE2. Conclusión. Los hallazgos confirman el predominio de la variante D614G en este grupo de secuencias, lo cual probablemente favorece su transmisibilidad, que puede explicarse por la configuración de los sitios de unión con receptor ACE2. El predominio mundial de la D614G y las evidencias de laboratorio y bioinformáticas publicadas hasta la fecha, apuntan hacia una posible mayor infectividad y transmisibilidad On March 18, the first confirmed case of SARS-CoV-2 infection was reported in El Salvador and during the month of October 2020, the SARS-CoV-2 genome was sequenced from samples obtained in the country. Objective. To analyze in silico the mutations detected in the sequences isolated in El Salvador. Methodology. The SOPHiA-DDM-V5.7.10. Platform was used for the determination of variants due to missense mutations. The Nexclade beta v0.8.1 platform was used;The wild-type protein S (D614: PDB ID: 6VXX) and the mutated variant (D614G: PDB ID: 6XS6) were visualized and compared. For the modeling and generation of images of the molecular details of the proteins, Pymol-v1.7.2.3 was used. Results. The crystals of wild and mutated protein S show differences at the molecular level, including the loss of interactions between residue G614 of domain S1 and threonine 859 of domain S2, thus favoring the open conformation of protein S, which is necessary for the interaction of S with the ACE2 receptor. Conclusion. The findings confirm the predominance of the D614G variant in this group of sequences, which probably favors its transmissibility, which can be explained by the configuration of the ACE2 receptor binding sites. The worldwide prevalence