Biomarkers of sequela in adult patients convalescing from COVID-19.

Different biomarkers for SARS-CoV-2 have been linked to detection, diagnosis, treatment, disease progression, and development of new drugs and vaccines. The objective of this research was to evaluate various hematological, biochemicals, immunological, radiological and spirometric parameters in 20 adult patients convalescing from COVID-19 and their possible relationship with the clinical course of the disease. The frequencies of categorical variables were compared using the chi-square and Fisher's exact test. The levels of statistical significance were denoted in each figure legend. Two-dimensional clustering analysis was performed using MeV software from TIGR. The tests with P value of ≤ 0.05 were considered statistically significant. Most of the patients studied presented alterations in dissimilar laboratory, radiological and spirometric parameters, which were related to the clinical evolution of the disease. The results obtained show that certain hematological, biochemical, immunological and radiological parameters can be considered as biomarkers of sequela in adult COVID-19 patients, which allows their stratification, according to the degree of involvement or sequela, into three groups: I (mild degree of involvement or sequela), without lung lesions on computerized axial tomography (CT scan) and high values of IgG, C3 and hemoglobin, II (moderate degree of involvement or sequel), without lung lesions on CT scan, characterized by high levels of CD3+/CD4+ T lymphocytes and the rest of the variables with low values and III (severe degree of involvement or sequela), with lung lesions on CT scan and high values of erythrocyte sedimentation rate, monocytes and neutrophils, associated with lymphopenia and decreased concentrations of IgG and C3.

A single dose of SARS-CoV-2 FINLAY-FR-1A vaccine enhances neutralization response in COVID-19 convalescents, with a very good safety profile: An open-label phase 1 clinical trial.

BACKGROUND: As a first step towards a vaccine protecting COVID-19 convalescents from reinfection, we evaluated FINLAY-FR-1A vaccine in a clinical trial. METHODS: Thirty COVID-19 convalescents aged 22-57 years were studied: convalescents of mild COVID-19, asymptomatic convalescents, both with PCR-positive at the moment of diagnosis; and individuals with subclinical infection detected by viral-specific IgG. They received a single intramuscular injection of the FINLAY-FR-1A vaccine (50 µg of the recombinant dimeric receptor binding domain). The primary outcomes were safety and reactogenicity, assessed over 28 days after vaccination. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following vaccination was evaluated by ELISA and live-virus neutralization test. The effector T cellular response was also assessed. Cuban Public Registry of Clinical Trials, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. FINDINGS: No serious adverse events were reported. Minor adverse events were found, the most common, local pain: 3 (10%) and redness: 2 (6·7%). The vaccine elicited a >21 fold increase in IgG anti-RBD antibodies 28 days after vaccination. The median of inhibitory antibody titres (94·0%) was three times greater than that of the COVID-19 convalescent panel. Virus neutralization titres higher than 1:160 were found in 24 (80%) participants. There was also an increase in RBD-specific T cells producing IFN-γ and TNF-α. INTERPRETATION: A single dose of the FINLAY-FR-1A vaccine against SARS-CoV-2 was an efficient booster of pre-existing natural immunity, with excellent safety profile. FUNDING: Partial funding for this study was received from the Project-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministry of Science, Technology and the Environment, Cuba.   RESUMEN. ANTECEDENTES: Como un primer paso hacia una vacuna que proteja a los convalecientes de COVID-19 de la reinfección, evaluamos la vacuna FINLAY-FR-1A en un ensayo clínico. MÉTODOS: Se estudiaron treinta convalecientes de COVID-19 de 22 a 57 años: convalecientes de COVID-19 leve y convalecientes asintomáticos, ambos con prueba PCR positiva al momento del diagnóstico; e individuos con infección subclínica detectada por IgG específica viral. Los participantes recibieron una dosis única por vía intramuscular de la vacuna FINLAY-FR-1A (50 µg del dominio de unión al receptor recombinante dimérico del SARS CoV-2). Las variables de medida primarias fueron la seguridad y la reactogenicidad, evaluadas durante 28 días después de la vacunación. La variable secundaria, la inmunogenicidad. La respuesta humoral, al inicio del estudio y después de la vacunación, se evaluó por ELISA y mediante la prueba de neutralización del virus vivo. También se evaluó la respuesta de células T efectoras. Registro Público Cubano de Ensayos Clínicos, WHO-ICTRP: https://rpcec.sld.cu/en/trials/RPCEC00000349-En. RESULTADOS: No se reportaron eventos adversos graves. Se encontraron eventos adversos leves, los más comunes, dolor local: 3 (10%) y enrojecimiento: 2 (6·7%). La vacuna estimuló un incremento >21 veces de los anticuerpos IgG anti-RBD 28 días después de la vacunación. La mediana de los títulos de anticuerpos inhibidores (94·0%) fue aproximadamente tres veces mayor que la del panel de convalecientes de COVID-19. Se encontraron títulos de neutralización viral superiores a 1:160 en 24 (80%) de los participantes. También hubo un aumento en las células T específicas de RBD que producen IFN-γ y TNF-α. INTERPRETACIÓN: Una sola dosis de la vacuna FINLAY-FR-1A contra el SARS-CoV-2 reforzó eficazmente la inmunidad natural preexistente, con un excelente perfil de seguridad. FINANCIAMIENTO: Se recibió un financiamiento parcial del Proyecto-2020-20, Fondo de Ciencia e Innovación (FONCI), Ministerio de Ciencia, Tecnología y Medio Ambiente, Cuba.

Asociación entre hipoplasia del timo y disminución de inmunoglobulina A / Association between thymus hypoplasia and immunoglobulin A reduction

El sistema inmune madura gradualmente durante la infancia y el nacimiento es un momento crucial para este proceso. El paso por el canal del parto es el primer estímulo que el sistema inmunitario percibe para comenzar así su maduración progresiva. El timo como órgano linfoide primario, es el primero en aparecer entre todos los órganos linfoides; en este órgano ocurre la ontogenia, diferenciación y maduración de los linfocitos T que migran a los órganos linfoides secundarios como linfocitos T inmunocompetentes. La producción de IgA por los linfocitos B es uno de los mecanismos esenciales de respuesta inmune de las mucosas a las que protege en su forma de IgA secretoria. En el Instituto de Hematología e Inmunología, se atendieron en consulta 62 pacientes pediátricos entre uno y cinco años de edad, con antecedentes de infecciones respiratorias agudas frecuentes, con dos o más episodios en un mes, a los que se les diagnosticó por ultrasonografía una disminución del área tímica (hipoplasia). De ellos, 50 por ciento presentó además disminución de la concentración de IgA en suero. Estos resultados sugieren múltiples interrogantes. Consecuentemente, este trabajo tiene como objetivo presentar la asociación hallada entre la disminución del tamaño del timo y la disminución de la concentración en suero de IgA, en un grupo de niños de uno a cinco años, con antecedentes de infecciones respiratorias frecuentes, consultados en el Instituto de Hematología e Inmunología durante un año(AU)

The immune system gradually matures during childhood, and birth is a crucial moment in this process. Transit through the birth canal is the first stimulus perceived by the immune system to start its progressive maturation. The thymus, a primary lymphoid organ as it is, is the first lymphoid organ to appear. It is the site of the ontogeny, differentiation and maturation of the T-lymphocytes migrating to secondary lymphoid organs as immunocompetent T-lymphocytes. IgA production by B-lymphocytes is one of the essential immune response actions performed by mucosas, which they protect in the form of secretory IgA. A study was conducted of 62 pediatric patients aged 1-5 years attending consultation at the Institute of Hematology and Immunology who had a history of frequent acute respiratory infection, with two or more episodes in one month. These patients were ultrasonographically diagnosed with thymus size reduction (hypoplasia). Among them, 50 percent also presented a decrease in serum IgA concentration. These results pose many questions concerning the association between thymus hypoplasia and IgA reduction. The purpose of the study was therefore to present the association found between thymus size reduction and serum IgA concentration decrease in a group of children aged 1-5 years with a history of frequent respiratory infection attending the Institute of Hematology and Immunology during one year(AU)