Anticuerpos contra el SARS-CoV-2 tras la dosis de vacuna de recuerdo. Identificación de subgrupos con respuesta insuficiente / SARS-CoV-2 antibodies after booster vaccination. Identification of subgroups with poor response

Objetivo Identificar dentro del grupo de pacientes de alto riesgo a aquellos que presentan más posibilidad de presentar inmunidad postvacunal insuficiente. Método Determinación de títulos de IgG frente a SARS-CoV-2 después de la dosis de recuerdo. Se clasificó la respuesta vacunal como negativa (títulos IgG <34 BAU/ml), indeterminada (títulos 34 - 259 BAU/ml) o positiva (≥260 BAU/ml). Resultados Se incluyeron 765 pacientes (31,25% de los vacunados): 54 (7,1%) en tratamiento con fármacos biológicos, 90 (11,8%) con enfermedad hematológica, 299 (39,1%) con patología oncológica, 304 (39,7%) con trasplante de órgano sólido y 18 (2,4%) con inmunosupresión por otros motivos. Un total de 74 pacientes (9,7%) tuvieron una serología negativa y 45 (5,9%) obtuvieron títulos indeterminados. Por grupo diagnóstico, los pacientes con mayor porcentaje de serología negativa o indeterminada fueron pacientes bajo tratamiento con fármacos biológicos (55,6%, fundamentalmente a expensas de antiCD20), hematológicos (35,4%) y los trasplantados (17,8%, principalmente pulmón y riñón). Los pacientes oncológicos y otros pacientes inmunosuprimidos tuvieron buena respuesta vacunal. Conclusión Los pacientes tratados con fármacos antiCD20, los hematológicos y los trasplantados (fundamentalmente de pulmón y riñón) presentaron mayor riesgo de no desarrollar inmunidad postvacunal. Es fundamental su identificación de cara a individualizar y mejorar su manejo (AU)

Objective To determine which patients within the high-risk group are most likely to have insufficient post-vaccination immunity. Methods Determination of IgG titers against SARS-CoV-2 after the booster dose. Vaccine response was categorized as negative (IgG titers <34 BAU/ml), indeterminate (titers 34 - 259 BAU/ml) or positive (≥ 260 BAU/ml). Results 765 patients were included (31.25% of those vaccinated). 54 (7.1%) on treatment with biologics, 90 (11.8%) with hematologic disease, 299 (39.1%) with oncologic pathology, 304 (39.7%) with solid organ transplant and 18 (2.4%) with immunosuppression for other reasons. 74 patients (9.7%) had negative serology and 45 (5.9%) had indeterminate titers. By diagnostic group, the patients with the highest proportion of negative or indeterminate serology were patients with biologic treatment (55.6%, mainly at expense of antiCD20), hematologic (35.4%) and transplant patients (17.8%, mainly lung and kidney). Oncology and other immunosuppressed patients had a favorable response to vaccination. Conclusion Patients treated with antiCD20 drugs, hematologic patients and transplanted patients (mainly lung and kidney) have a higher risk of not achieving post-vaccination immunity. It is essential to identify them in order to individualize and optimize their management (AU)

Role of vaccination and anti-SARS-CoV-2 antibodies in the clinical outcome of hospitalized COVID-19 patients / Papel de la vacunación y los anticuerpos anti-SARS-CoV-2 en el desenlace clínico de pacientes hospitalizados por COVID-19

Background Although vaccination has considerably reduced the risk of hospitalization and death from COVID19, the impact of vaccination and anti-SARS-CoV-2 antibody status on the outcome of patients who required hospitalization has been poorly investigated. Material and methods A prospective observational study in 232 patients hospitalized for COVID19 was carried out from October 2021 to January 2022 to evaluate the role on patient outcome of their vaccination and anti-SARS-CoV-2 antibody status and titer, comorbidities, analytical determinations, clinical presentation at admission, treatments and requirements for respiratory support. Cox regression and survival analyzes were performed. The SPSS and “R” programs were used. Results Patients with complete vaccination schedule had higher S-protein antibody titers (log10 3.73 [2.83–4.6]UI/ml vs 1.6 [2.99–2.61]UI/ml; p<0.001), lower probability of radiographic worsening (21.6% vs. 35.4%; p=0.005), less likely required high doses of dexamethasone (28.4% vs. 45.4%; p=0.012), high-flow oxygen (20.6% vs. 35.4%; p=0.02), ventilation (13.7% vs, 33.8%; p=0.001) and intensive care admissions (10.8% vs. 32.6%; p<0.001). Remdesivir (HR=0.38; p<0.001) and complete vaccination schedule (HR=0.34; p=0.008) were protective factors. No differences in antibody status were detected between groups (HR=0.58; p=0.219). Conclusions SARS-CoV-2 vaccination was associated with higher S-protein antibody titers and lower probability of radiological progression, immunomodulators requirement and respiratory support or death. However, vaccination but not antibody titters protected from adverse events pointing a role of immune-protective mechanisms in addition to humoral response (AU)

Antecedentes Aunque la vacunación ha reducido considerablemente el riesgo de hospitalización y muerte por COVID-19, se ha investigado poco el impacto de la vacunación y el estado de los anticuerpos anti-SARS-CoV-2 en la evolución de los pacientes que requieren hospitalización. Material y métodos Se realizó un estudio observacional prospectivo en 232 pacientes hospitalizados por COVID-19 desde octubre del 2021 hasta enero del 2022 para evaluar el impacto en la evolución clínica del estado vacunal, el título de anticuerpos anti-SARS-CoV-2, la presencia de comorbilidades, analítica, la clínica al ingreso, tratamientos y soporte respiratorio. Se realizaron análisis de supervivencia y regresión de Cox. Se utilizaron los programas SPSS y «R». Resultados Los pacientes con esquema de vacunación completo presentaron títulos de anticuerpos contra la proteína S más elevados (log10 3,73 [2,83-4,6] UI/mL vs. 1,6 [2,99-2,61] UI/mL; p < 0,001), menor probabilidad de empeoramiento radiográfico (21,6 vs. 35,4%; p = 0,005), requirieron con menor probabilidad dosis elevadas de dexametasona (28,4 vs. 45,4%; p = 0,012), oxígeno de alto flujo (20,6 vs. 35,4%; p = 0,02), ventilación (13,7 vs. 33,8%; p = 0,001) e ingresos en cuidados intensivos (10,8 vs. 32,6%; p < 0,001). El remdesivir (HR = 0,38; p < 0,001) y el esquema completo de vacunación (HR = 0,34; p = 0,008) fueron factores protectores de mala evolución. No se detectaron diferencias en el estado de los anticuerpos entre los grupos (HR = 0,58; p = 0,219). Conclusiones La vacunación contra el SARS-CoV-2 se asoció con mayores títulos de anticuerpos contra la proteína S y menor probabilidad de progresión radiológica, requerimiento de inmunomoduladores y soporte respiratorio o muerte. Sin embargo, la vacunación, pero no los títulos de anticuerpos, protegió de los eventos adversos, lo que indica un papel de los mecanismos de protección inmunológica además de la respuesta humoral (AU)

Searching for common ground.

The conserved coronavirus fusion peptide is a target of broadly neutralizing antibodies.

Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models.

To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.

Reactogenicidad de la vacuna de ARNm BNT162b2 (Pfizer-BioNTech) frente a COVID-19 en trabajadores de un hospital de tercer nivel / Reactogenicity of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) against COVID-19 in workers of a tertiary hospital

Objetivo: Analizar las reacciones locales y sistémicas aparecidas trasla primera y segunda dosis de la vacuna BNT162b2 (Pfizer-BioNTech)frente a COVID-19 en una muestra de trabajadores de un hospital detercer nivel, e identificar los factores relacionados con una mayor reactogenicidada la vacuna.Método: Se empleó un cuestionario autoadministrado para entrevistar a291 trabajadores de un hospital de tercer nivel que recibieron la vacunaBNT162b2 frente a COVID-19 entre enero y marzo de 2021. El cuestionarioincluyó preguntas acerca de las variables sociodemográficas de losparticipantes, infección previa de COVID-19 y las reacciones locales ysistémicas tras la primera y segunda dosis de la vacuna.Resultados: La reacción más comúnmente informada fue el dolor enel lugar de la inyección, siendo más frecuente tras la primera dosis de lavacuna. Las reacciones sistémicas evaluadas se informaron con mayor frecuenciatras la segunda dosis de la vacuna. Las mujeres, los adultos másjóvenes y las personas con una infección previa por COVID-19 notificaronuna mayor reactogenicidad. Además, una alta reactogenicidad tras laprimera dosis estuvo relacionada con un mayor número de reaccionesadversas tras la segunda dosis de la vacuna.Conclusiones:La distribución de la reactogenicidad en el presenteestudio es consistente con los datos reportados en los estudios realizados con la vacuna BNT162b2, especialmente en términos de asociación conlas características de los participantes. Estos hallazgos pueden facilitarla identificación de personas con mayor probabilidad de presentar unaalta reactogenicidad a la vacuna, permitiéndonos anticipar su aparicióny tratamiento.

Objective: To analyze the local and systemic reactions that appearedafter the first and second dose of the BNT162b2 vaccine againstCOVID‑19 (Pfizer-BioNTech) in a sample of workers from a tertiary hospital,and to identify the factors related to greater vaccine reactogenicity.Method: A self-administered questionnaire was used to interview291 workers from a tertiary hospital who received the BNT162b2 vaccineagainst COVID-19 between January and March 2021. The questionnaireincluded questions about the sociodemographic variables of the participants,previous COVID-19 infection, and local and systemic reactions afterthe first and second dose of the vaccine.Results: The most common adverse reaction was soreness at the injectionsite, which was reported more frequently after the first dose of thevaccine. The systemic reactions evaluated were reported more frequentlyafter the second dose of the vaccine. Women, younger adults, and subjectswith a prior COVID-19 infection reported increased reactogenicity.Furthermore, high reactogenicity after the first dose was found to be relatedto a higher number of adverse reactions after the second dose of thevaccine.Conclusions: The distribution of reactogenicity in the present study isconsistent with the data reported in previous studies on the BNT162b2vaccine, especially in terms of its association with the participants’ characteristics. These findings could facilitate the identification of people ata higher risk of developing high reactogenicity to the vaccine, therebymaking it possible to anticipate the appearance of adverse reactions andplan for their treatment.

Management of patients with Intestinal Bowel Disease and COVID-19: A review of current evidence and future perspectives / Manejo de pacientes con enfermedad inflamatoria intestinal y COVID-19: revisión de la evidencia actual y perspectivas futuras

The COVID-19 pandemic has been a challenge for countries and health professionals worldwide. Viral entry by ACE-2 receptor and an excessive activation of the immune system are key to understand both incidence and severity of disease. Inflammatory Bowel Disease (IBD) represents a special condition associated with an inordinate response of the immune system to external agents. IBD treatments have been associated to an increased risk of bacterial and viral infections. This has raised the question of possible higher incidence and severity of COVID-19 infection in IBD patients. Several papers have been published during this year of pandemic to answer that question. Moreover, COVID-19 vaccination offers great promise in controlling infection in patients with IBD. Based on current evidence, patients with IBD do not have a higher incidence of COVID-19 than the general population, and they do not have worse disease evolution. Advanced age and presence of a greater number of comorbidities have been associated with worse outcomes, similar to the general population. Corticosteroids are associated to an increased risk of COVID-19 infection, higher hospitalization rate and higher risk of severe COVID-19. 5-ASA/Sulfasalazine and Thiopurines have a possible increased risk of severe COVID-19, although studies are lacking. On the other hand, Anti-TNF may have a possible protective effect. It is recommended to maintain the treatment. Anti-IL-12/23, anti-integrins and tofacitinib have results comparable to anti-TNF. Based on the efficacy, expert recommendations, and the absence of other evidence, it is recommended that patients with IBD be vaccinated.(AU)

La pandemia por COVID-19ha supuesto un reto para los países y sus profesionales sanitarios. La entrada viral en el hospedador a través del receptor ACE-2 y una activación excesiva del sistema inmunológico son claves para comprender tanto la incidencia como la gravedad de la enfermedad. La enfermedad inflamatoria intestinal (EII) representa una condición especial asociada con una respuesta descontrolada del sistema inmunológico a agentes externos. Los tratamientos para la EII se han asociado con un mayor riesgo de infecciones bacterianas y virales, lo que ha planteado la cuestión de una posible mayor incidencia y gravedad de la infección por COVID-19 en pacientes con EII. A lo largo del año 2021 se han publicado varios artículos que tratan de responder esta cuestión. La vacunación contra la COVID-19 ofrece una gran promesa para controlar la infección en pacientes con EII. Según la evidencia actual, los pacientes con EII no tienen mayor incidencia de COVID-19 ni peor evolución de la enfermedad en comparación con la población general. La edad avanzada y la presencia de un mayor número de comorbilidades se han asociado con peores resultados. Los corticosteroides están asociados con un mayor riesgo de infección por COVID-19, una mayor tasa de hospitalizaciones y un mayor riesgo de enfermedad grave. La mesalazina/sulfasalazina y las tiopurinas presentan un posible aumento del riesgo de COVID-19 grave, aunque se requieren más estudios para demostrar esta asociación. Dentro de los fármacos biológicos, los anti-TNF pueden tener un posible efecto protector. Los anti-IL-12/23, anti-integrinas y tofacitinib presentan resultados comparables con anti-TNF. Se recomienda mantener el tratamiento con agentes biológicos. Con base en la eficacia, las recomendaciones de los expertos y la ausencia de otra evidencia, se recomienda la vacunación de pacientes con EII.(AU)

Seguimiento de resultados de Test de Antígenos en trabajadores del ámbito sanitario con infección activa por SARS-CoV-2 / Monitoring of Antigen Test results in healthcare workers with active SARS-CoV-2 infection

Introducción: La introducción del Test de Antígenos como prueba válida para valorar el alta de un trabajador del ámbito sanitario afectado por SARS-CoV-2, supone un cambio importante para los Servicios de Prevención de centros sanitarios, por lo que se decide el estudio de los resultados obtenidos de dichas pruebas, en un hospital de la Comunidad de Madrid durante un tiempo determinado en un periodo de alta transmisibilidad, valorando el tiempo que tarda un trabajador con infección activa por SARS-CoV-2 en negativizar un Test de Antígenos. Método: Estudio observacional, descriptivo, retrospectivo realizado en el Hospital Universitario Infanta Cristina en Parla (Madrid) desde el 11 de enero del 2.022 hasta el 21 de febrero 2.022, en el que se estudian variables como sexo, edad, vacunación, categoría profesional e infección previa por SARS-CoV-2 y su influencia en el tiempo de negativización de un Test de Antígenos. Resultados: Un total de 164 trabajadores del ámbito sanitario se vieron afectados por Covid-19 durante el periodo estudiado, de los cuales 74 (45,1%) dieron positivo en Test de Antígenos a los 7 días del inicio de la infección, llegando hasta el 13º día 4 trabajadores (2,4 %). Conclusiones: Se pone de manifiesto que el haber tenido una infección previa por Covid-19, influye en el tiempo que tarda en negativizar un Test de Antígenos; disminuyéndolo, en trabajadores con infección activa por SARS-CoV-2 (AU)

Introduction: The introduction of the Antigen Test as a valid test to assess the discharge of a healthcare worker affected by SARS-CoV-2, represents an important change for the Prevention Services of health centers, for which it is decided to study the results obtained from these tests, in a hospital in the Community of Madrid for a certain time in a period of high transmissibility, assessing the time it takes for a worker with active SARS-CoV-2 infection to make an Antigen Test negative. Method: Observational, descriptive, retrospective study carried out at the Infanta Cristina University Hospital in Parla (Madrid) from January 11, 2022 to February 21, 2022, in which variables such as sex, age, vaccination, category professional and previous SARS-CoV-2 infection and its influence on the negative time of an Antigen Test. Results: A total of 164 healthcare workers were affected by Covid-19 during the period studied, of which 74 (45,1%) tested positive for Antigen Test 7 days after the start of the infection, reaching up to the 13th day 4 workers (2.4%). Conclusions: It is shown that having had a previous Covid-19 infection influences the time it takes for an Antigen Test to become negative; decreasing it, in health workers with active SARS-CoV-2 infection (AU)

Antibody-mediated broad sarbecovirus neutralization through ACE2 molecular mimicry.

Understanding broadly neutralizing sarbecovirus antibody responses is key to developing countermeasures against SARS-CoV-2 variants and future zoonotic sarbecoviruses. We describe the isolation and characterization of a human monoclonal antibody, designated S2K146, that broadly neutralizes viruses belonging to SARS-CoV- and SARS-CoV-2-related sarbecovirus clades which use ACE2 as an entry receptor. Structural and functional studies show that most of the virus residues that directly bind S2K146 are also involved in binding to ACE2. This allows the antibody to potently inhibit receptor attachment. S2K146 protects against SARS-CoV-2 Beta challenge in hamsters and viral passaging experiments reveal a high barrier for emergence of escape mutants, making it a good candidate for clinical development. The conserved ACE2-binding residues present a site of vulnerability that might be leveraged for developing vaccines eliciting broad sarbecovirus immunity.

Structural basis for continued antibody evasion by the SARS-CoV-2 receptor binding domain.

Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.

Incomplete IgG avidity maturation after seasonal coronavirus infections.

In classical viral infections, the avidity of immunoglobulin G (IgG) is low during acute infection and high a few months later. As recently reported, SARS-CoV-2 infections are not following this scheme, but they are rather characterized by incomplete avidity maturation. This study was performed to clarify whether infection with seasonal coronaviruses also leads to incomplete avidity maturation. The avidity of IgG toward the nucleoprotein (NP) of the seasonal coronaviruses 229E, NL63, OC43, HKU1 and of SARS-CoV-2 was determined in the sera from 88 healthy, SARS-CoV-2-negative subjects and in the sera from 70 COVID-19 outpatients, using the recomLine SARS-CoV-2 assay with recombinant antigens. In the sera from SARS-CoV-2-negative subjects, incomplete avidity maturation (persistent low and intermediate avidity indices) was the lowest for infections with the alpha-coronaviruses 229E (33.3%) and NL63 (61.3%), and the highest for the beta-coronaviruses OC43 (77.5%) and HKU1 (71.4%). In the sera from COVID-19 patients, the degree of incomplete avidity maturation of IgG toward NP of 223E, OC43, and HKU1 was not significantly different from that found in SARS-CoV-2-negative subjects, but a significant increase in avidity was observed for IgG toward NP of NL63. Though there was no cross-reaction between SARS-CoV-2 and seasonal coronaviruses, higher concentrations of IgG directed toward seasonal coronaviruses seemed to indirectly increase avidity maturation of IgG directed toward SARS-CoV-2. Our data show that incomplete IgG avidity maturation represents a characteristic consequence of coronavirus infections. This raises problems for the serological differentiation between acute and past infections and may be important for the biology of coronaviruses.

Cross-Reactive Antibodies to SARS-CoV-2 and MERS-CoV in Pre-COVID-19 Blood Samples from Sierra Leoneans.

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.

Monoclonal Antibodies to S and N SARS-CoV-2 Proteins as Probes to Assess Structural and Antigenic Properties of Coronaviruses.

Antibodies targeting the spike (S) and nucleocapsid (N) proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are essential tools. In addition to important roles in the treatment and diagnosis of infection, the availability of high-quality specific antibodies for the S and N proteins is essential to facilitate basic research of virus replication and in the characterization of mutations responsible for variants of concern. We have developed panels of mouse and rabbit monoclonal antibodies (mAbs) to the SARS-CoV-2 spike receptor-binding domain (S-RBD) and N protein for functional and antigenic analyses. The mAbs to the S-RBD were tested for neutralization of native SARS-CoV-2, with several exhibiting neutralizing activity. The panels of mAbs to the N protein were assessed for cross-reactivity with the SARS-CoV and Middle East respiratory syndrome (MERS)-CoV N proteins and could be subdivided into sets that showed unique specificity for SARS-CoV-2 N protein, cross-reactivity between SARS-CoV-2 and SARS-CoV N proteins only, or cross-reactivity to all three coronavirus N proteins tested. Partial mapping of N-reactive mAbs were conducted using truncated fragments of the SARS-CoV-2 N protein and revealed near complete coverage of the N protein. Collectively, these sets of mouse and rabbit monoclonal antibodies can be used to examine structure/function studies for N proteins and to define the surface location of virus neutralizing epitopes on the RBD of the S protein.