High Concentration of Anti-SARS-CoV-2 Antibodies 2 Years after COVID-19 Vaccination Stems Not Only from Boosters but Also from Widespread, Often Unrecognized, Contact with the Virus.

This study follows 99 subjects vaccinated with Pfizer/BioNTech COVID-19 vaccines over two years, with particular focus on the last year of observation (between days 360 and 720). The response to the vaccination was assessed with Diasorin's SARS-CoV-2 TrimericSpike IgG. Screening for SARS-CoV-2 infection was performed with Abbott's SARS-CoV-2 Nucleocapsid IgG immunoassay. Data from questionnaires were also analyzed. Two years after the first vaccine dose administration, 100% of the subjects were positive for anti-spike SARS-CoV-2 IgG and the median antibody level was still high (3600 BAU/mL), dropping insignificantly over the last year. Simultaneously, a substantial increase in seropositivity in anti-nucleocapsid SARS-CoV-2 IgG was noted, reaching 33%. There was no statistically significant agreement between anti-N seropositivity and reported COVID-19. Higher anti-spike concentrations and lower COVID-19 incidence was seen in the older vaccinees. It was noted that only subjects boosted between days 360 and 720 showed an increase in anti-spike IgG concentrations. The higher antibody concentrations (median 7440 BAU/mL) on day 360 were noted in participants not infected over the following year. Vaccination, including booster administrations, and natural, even unrecognized, contact with SARS-CoV-2 entwined two years after the primary vaccination, leading to high anti-spike antibody concentrations.

A comparison of 7 commercial anti-SARS-CoV-2 antibody immunoassays.

Introduction: Serological testing in SARS-CoV-2 infection is gaining both patients' and clinicians' attention. Antibody assessment has potential multidirectional utility, hampered by the scarcity of clinical validation studies of the tests available on the market. Therefore, this study aimed to provide some evidence on the clinical utility of anti-SARS-CoV-2 commercial assays, based on the comparison of the results obtained with different methods. Material and methods: The study included 52 samples from patients and healthy volunteers. The control samples (n = 20) were obtained during the SARS-CoV-2 pandemic. The case cohort consisted of 32 consecutive patients referred to the Diagnostyka medical laboratory for anti-SARS-CoV-2 antibody testing. For the purpose of this study, the MAGLUMI chemiluminescent immunoassay (CLIA) was chosen as a comparative method. All samples were tested with this method, as well as with the Euroimmun enzyme-linked immunosorbent assay (ELISA) and five different lateral flow immunoassays (LFIAs). Results: The results obtained in this study provide evidence for high overall concordance between the comparative CLIA method and both ELISA and different LFIAs. The agreement between CLIA and LFIAs was 92.3-98.0% for IgG and 90.0-96.1% for IgM, depending on the kit. The concordance between CLIA and ELISA was 92.3% for IgG and 75.0% for IgA (compared to the MAGLUMI CLIA IgM). Conclusions: The results obtained in this study provide evidence for high overall concordance between the comparative CLIA method and different LFIAs. This could justify the use of LFIAs in some settings, where automated assays are not available, provided that some limitations are considered.

The Influence of Booster Shot and SARS-CoV-2 Infection on the Anti-Spike Antibody Concentration One Year after the First COVID-19 Vaccine Dose Administration.

This study pictures the humoral response of 100 vaccinees to Pfizer/BioNTech COVID-19 vaccine over a year, with particular focus on the influence of a booster shot administered around 10 months after the primary immunization. The response to the vaccination was assessed with Diasorin's SARS-CoV-2 TrimericSpike IgG. Abbott's SARS-CoV-2 Nucleocapsid IgG immunoassay was used to identify SARS-CoV-2 contact, even asymptomatic. In contrast to the gradual decline of the anti-spike IgG between 30 and 240 days after the first dose, an increase was noted between days 240 and 360 in the whole cohort. However, a statistically significant rise was seen only in boosted individuals, and this effect of the booster decreased over time. An increase was also observed in non-boosted but recently infected participants and a decrease was reported in non-boosted, non-infected subjects. These changes were not statistically significant. On day 360, a percentage of new SARS-CoV-2 infections was statistically lower in the boosted vs. non-boosted subgroups. The booster immunization is the most efficient way of stimulating production of anti-spike, potentially neutralizing antibodies. The response is additionally enhanced by the natural contact with the virus. Individuals with a low level of anti-spike antibodies may benefit the most from the booster dose administration.

Head-to-Head Comparison of 5 Anti-SARS-CoV-2 Assays Performance in One Hundred COVID-19 Vaccinees, over an 8-Month Course.

The immunoassays used to measure anti-spike SARS-CoV-2 antibodies are widely available on the market. However, their performance in COVID-19 vaccinees is not yet adequately assessed. Our study provides a head-to-head comparison of five methods: Abbott's S1-RBD IgG, Roche's S1-RBD total antibody, Euroimmun's S1 IgG, and DiaSorin's TrimericS IgG and S1/S2 IgG assays. Testing was performed in one hundred vaccinated subjects, at eight timepoints over eight months after vaccination. The results differed substantially between methods; however, they correlated strongly and demonstrated the individuals' responses to both doses of vaccination and the waning of humoral immunity after eight months. Importantly, we encountered a high percentage of results above the assay-specific upper quantitation limit (UQL) for undiluted samples. This was the most pronounced for the Roche's and Euroimmun's assays. The Abbott's assay showed the lowest percentage of results above the UQL. We also attempted to find a common way to establish antibody concentrations that might be classified as high. However, this resulted in between 10% and 100% of such results for different methods on day 240'. This highlights the need for an assay-specific approach for adjusting the cut-offs that may indicate COVID-19 immunity.

Anti-Spike SARS-CoV-2 IgG Assessment with a Commercial Assay during a 4-Month Course after COVID-19 Vaccination.

We intended to assess the humoral response induced by the Pfizer/BioNTech Comirnaty COVID-19 vaccine with commercially available immunoassays: anti-spike (S) IgG and IgM, and anti-nucleocapsid (N) IgG antibodies, over a 4-month course. One hundred subjects, including 15 COVID-19 convalescents, comprised the study cohort. The SARS-CoV-2 antibodies concentrations were measured on day 0' and 10', 20', 30', 60', 90', and 120' after the first dose administration. Over the course of the study, 100% of the participants developed and sustained anti-SARS-CoV-2 S IgG antibodies. The highest concentration, exceeding the quantification range of the test (2080 BAU/mL), was reached by 67% of the subjects on day 30'. The concentration of the antibodies remained stable between days 30' and 90' but was followed by a significant decrease between days 90' and 120'. The stronger and more persistent humoral response was noted for women. The COVID-19 convalescents developed higher antibody levels, particularly 10 days after the first Comirnaty dose. Twenty-three out of the eighty-five naïve vaccinees failed to develop a detectable IgM response. LIAISON® SARS-CoV-2 TrimericS IgG (DiaSorin S.p.A, Saluggia, Italy) may be useful in the assessment of the humoral response to the Comirnaty vaccine. In contrast, Abbott's anti-S SARS-CoV-2 IgM has a limited utility in this context.

The real life performance of 7 automated anti-SARS-CoV-2 IgG and IgM/IgA immunoassays.

OBJECTIVES: This study was aimed at providing some insights into the real-life performance of the commercial, clinically validated anti-SARS-CoV-2 antibody assays. METHODS: The residual, anonymized samples from 97 patients referred for anti-SARS-CoV-2 antibodies testing were included in the study. The initial assessment was performed with the Euroimmun ELISAs, followed by the assays provided by: NovaTec, Snibe, Vircell, Roche, Abbott and DiaSorin. The analyses of the results were performed separately for the antibodies of the early (IgM/IgA) and late (IgG) immune response. RESULTS: We observed a high variability of the results obtained with the investigated immunoassays. The fully concordant results were reported for only 57 out of 97 samples tested for IgG antibodies and for 34 out of 97 samples for IgM/IgA. The highest percentage of positive results was noted for the Euroimmun and Vircell ELISAs and the lowest for Novatec ELISAs.We proposed to distinguish true and false positive results based on the sum of positive results obtained with different methods. We arbitrarily considered reference positive samples reactive in at least half of the assays. The assay that proved to correlate the best with those reference results was the Roche electrochemiluminescence immunoassay. CONCLUSIONS: The differences observed between immunoassays targeting the early phase antibodies were much more pronounced than between IgG assays, suggesting their lower value for clinical use. Our study also showed a high percentage of plausibly false (positive or negative) results obtained with ELISAs, which suggests their inferiority to the automated immunoassays.

Osteosíntesis de múltiples fracturas costales desplazadas en un paciente con tórax batiente / Osteosynthesis of multiple displaced costal fractures in a patient with flail chest

El tratamiento de las fracturas costales debe ser individualizado de acuerdo con la severidad de las lesiones y a la magnitud del trauma. El objetivo de esta investigación es presentar un caso donde se utilizaron láminas de titanio, en un paciente con fracturas múltiples de las costillas. Se reporta el caso de un paciente con múltiples fracturas costales de forma lineal y paralelas de los arcos costales con un tórax batiente, que llega al cuerpo de guardia con dolor torácico moderado y disnea. Aunque aún no existe suficiente evidencia científica a favor de los métodos de fijación costal, se realizó la fijación con láminas de titanio logrando la estabilidad de la pared, aliviando el dolor, mejorando la mecánica ventilatoria y logrando su rápida reincorporación a la sociedad(AU)

The treatment of costal fractures should be individualized according to the severity of the injuries and the magnitude of trauma. The objective of this investigation is to present a case where titanium plates were used in a patient with multiple rib fractures. We report the case of a patient with multiple rib fractures of a linear and parallel shape of the costal arches with a swinging thorax, who arrives the emergency room with moderate chest pain and dyspnea. Although there is still not enough scientific evidence that favors the costal fixation methods, the fixation with titanium plates was performed, achieving the stability of the wall, relieving pain, improving the ventilatory mechanics, and achieving the patient's quick reincorporation to the society(AU)

Osteosíntesis de múltiples fracturas costales desplazadas en un paciente con tórax batiente / Osteosynthesis of multiple displaced costal fractures in a patient with flail chest

El tratamiento de las fracturas costales debe ser individualizado de acuerdo con la severidad de las lesiones y a la magnitud del trauma. El objetivo de esta investigación es presentar un caso donde se utilizaron láminas de titanio, en un paciente con fracturas múltiples de las costillas. Se reporta el caso de un paciente con múltiples fracturas costales de forma lineal y paralelas de los arcos costales con un tórax batiente, que llega al cuerpo de guardia con dolor torácico moderado y disnea. Aunque aún no existe suficiente evidencia científica a favor de los métodos de fijación costal, se realizó la fijación con láminas de titanio logrando la estabilidad de la pared, aliviando el dolor, mejorando la mecánica ventilatoria y logrando su rápida reincorporación a la sociedad(AU)

The treatment of costal fractures should be individualized according to the severity of the injuries and the magnitude of trauma. The objective of this investigation is to present a case where titanium plates were used in a patient with multiple rib fractures. We report the case of a patient with multiple rib fractures of a linear and parallel shape of the costal arches with a swinging thorax, who arrives the emergency room with moderate chest pain and dyspnea. Although there is still not enough scientific evidence that favors the costal fixation methods, the fixation with titanium plates was performed, achieving the stability of the wall, relieving pain, improving the ventilatory mechanics, and achieving the patient's quick reincorporation to the society(AU)

The -2518 A/G polymorphism in the monocyte chemoattractant protein 1 gene (MCP-1) is associated with an increased risk of rheumatoid arthritis in Argentine patients.

The aim of this study was to analyze the influence of nucleotide transition (G/A) in position -2518 of the MCP-1 gene related to the susceptibility of developing RA. Two hundred twenty-three consecutive RA patients according to 2010 ACR/EULAR criteria were included; 120 healthy subjects were used as controls. MCP-1 -2518 A/G polymorphism (AG + GG) was present in 162 (72.6 %) RA patients and in 63 (52.5 %) healthy subjects [OR 2.44 (IC95% 1.53-3.88, p = 0.0002)]; associations for heterozygotes and homozygotes were OR 1.92 (IC95% 1.19-3.15, p = 0.001) and OR 5.19 (IC95% 2.34-11.51, p = 0.001), respectively. In Argentine patients, MCP-1 gene polymorphism confers susceptibility for developing RA.

The -308 G/A polymorphism in the tumor necrosis factor-α gene is not associated with development and progression of rheumatoid arthritis in Argentinean patients.

AIM: A polymorphism in the tumor necrosis factor-alpha (TNF-α) promoter region has been associated with disease susceptibility and progression in rheumatoid arthritis (RA). The presence of an adenosine (TNF2 allele) instead of a guanine (TNF1 allele) at position -308 may be responsible for a general increase in the transcriptional activity of the TNF-α gene. Our aim was to evaluate the association of the TNF2 allele with the risk of disease development and/or progression of RA in an Argentine population cohort. METHODS: Two hundred and twenty-three consecutive patients with RA according to the 1987 criteria of the American College of Rheumatology were included in the study. Clinical variables, Disease Activity Score 28, Health Assessment Questionnaire and Rheumatoid Arthritis Quality of Life were recorded. The radiographic erosions were determined by the method of Sharp/van der Heijde. A group of 111 healthy subjects matched by sex and age was used as a control. All samples were genotyped for the -308 G/A TNF-α polymorphism. RESULTS: No significant differences were observed either in the frequency of the TNF2 allele or in the genotypic distributions of the -308 G/A TNF-α polymorphism (P > 0.05) between the control group and the RA patients. No association was found between the TNF2 allele and the variables related to the course and outcome of the disease (P > 0.05). CONCLUSION: In this cohort of Argentinean patients with RA, the TNF2 allele was neither associated with susceptibility to the disease nor was it associated with the variables related to the course and outcome of the disease.

Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.

Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

Efectividad del tratamiento con campos magnéticos oscilantes de ultrabaja frecuencia en el tratamiento de la inflamación pélvica

Desde la antigüedad, griegos, romanos y chinos utilizaron los campos magnéticos con fines terapéuticos, en Cuba se introduce y difunde en la década de los 80. Realizamos un ensayo clínico fase III aleatorizado, estratificado, con un diseño en paralelo que interesó a 468 pacientes con el diagnóstico de enfermedad inflamatoria pélvica, atendidas en el servicio de sepsis del Hospital Materno Norte Tamara Bunke Bider, desde agosto del 2004 hasta julio del 2006, con el fin de precisar la efectividad y seguridad del tratamiento con campos magnéticos oscilantes. Se definieron criterios para medir efectividad, utilizando parámetros clínicos y análisis complementarios. Se describieron las reacciones adversas ocurridas para ambas modalidades terapéuticas. Se demostró que la terapéutica con campos magnéticos oscilantes mediante el inductor local Nak-02 fue segura y efectiva en el tratamiento de la enfermedad inflamatoria pélvica tumoral, logrando la recuperación del estado de salud de las pacientes en menor tiempo y con una menor incidencia de reacciones adversas(AU)