Humoral and T Cell Response to SARS-CoV-2 Vaccination in Patients With Rheumatoid Arthritis.

OBJECTIVE: The objective of this study was to assess the SARS-CoV-2-specific humoral and T cell response after a two-dose regimen of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). METHODS: In this observational study, patients with RA who are ≥18 years of age and vaccinated for SARS-CoV-2 according to the Argentine National Health Ministry's vaccination strategy were included. Anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies (ELISA-COVIDAR test), neutralizing activity (cytotoxicity in VERO cells), and specific T cell response (IFN-γ ELISpot Assay) were assessed after the first and second dose. RESULTS: A total of 120 patients with RA were included. Mostly, homologous regimens were used, including Gam-COVID-Vac (27.5%), ChAdOx1 (24.2%), and BBIBP-CorV (22.5%). The most frequent combination was Gam-COVID-Vac/mRNA-1273 (21.7%). After the second dose, 81.7% presented with anti-SARS-CoV-2 antibodies, 70.0% presented with neutralizing activity, and 65.3% presented with specific T cell response. The use of BBIBP-CorV and treatment with abatacept (ABA) and rituximab (RTX) were associated with undetectable antibodies and no neutralizing activity after two doses. BBIBP-CorV was also associated with the absence of T cell response. The total incidence of adverse events was 357.1 events per 1,000 doses, significantly lower with BBIBP-CorV (166.7 events per 1,000 doses, P < 0.02). CONCLUSION: In this RA cohort vaccinated with homologous and heterologous regimens against COVID-19, 2 out of 10 patients did not develop anti-SARS-CoV-2 IgG, 70% presented with neutralizing activity, and 65% presented with specific T cell response. The use of BBIBP-CorV was associated with deficient humoral and cellular response, whereas treatment with ABA and RTX resulted in an impaired anti-SARS-CoV-2 IgG formation and neutralizing activity.

Serological response to SARS-COV-2 vaccines in patients with multiple sclerosis in Argentina / Respuesta serológica a vacunas contra SARS-CoV-2 en pacientes con esclerosis múltiple en Argentina

Abstract Introduction : The objective was to assess the im munogenicity and effectiveness of vaccines against SARSCoV-2 in multiple sclerosis (MS) patients included in the Argentinean MS registry. Methods : A prospective cohort study between May and December 2021. The primary outcome was im munogenicity and effectiveness of vaccines during a three-month follow-up. Immunogenicity was evalua ted based on detection of total antibodies (Ab) against spike protein and neutralizing Ab in serum 4 weeks after the second vaccine dose. A positive COVID-19 case was defined according to Argentinean Ministry of Health. Results : 94 patients were included, mean age: 41.7 ± 12.1 years. Eighty (85.1%) had relapsing remitting mul tiple sclerosis (RRMS); 30 (31.9%) were under fingolimod treatment. The Sputnik V vaccine was the first dose in 33 (35.1%), and AstraZeneca in 61 (64.9%). In 60 (63.8%), the vaccine elicited a specific humoral response. Immu nological response according to the vaccination schemes showed no qualitative differences (p = 0.45). Stratified analysis according to the MS treatment showed that a significantly smaller number of subjects developed anti bodies against spike antigen among those that were on ocrelizumab compared to other groups (p ≤ 0.001), while a reduced number of patients under ocrelizumab where evaluated (n = 7). This was also observed for neutralizing antibodies in the ocrelizumab group (p < 0.001). During the three-month follow-up, two individuals were diag nosed with COVID-19. Conclusion: We found that MS patients that recei ved Sputnik V or AstraZeneca vaccines for SARS-CoV-2 developed a serological response with no differences between the vaccines used.

Resumen Introducción : El objetivo fue evaluar la inmunogeni cidad y efectividad de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple (EM) incluidos en el registro argentino de EM (RelevarEM, NCT 03375177). Métodos : Estudio de cohorte prospectivo entre mayo y diciembre 2021. Se evaluó la inmunogenicidad (detec ción de anticuerpos totales (Ab) contra proteína espiga y anticuerpos neutralizantes en suero) y eficacia (nueva infección por COVID-19) durante seguimiento de tres meses. El momento de detección de anticuerpos fue 4 semanas después de segunda dosis de vacuna. Un caso positivo de COVID-19 se definió de acuerdo con la defi nición del Ministerio de Salud. Resultados : Se incluyeron 94 pacientes, edad media de 41.7 ± 12.1 años. Ochenta (85.1%) tenían EM remiten te-recurrente; 30 (31.9%) en tratamiento con fingolimod. La vacuna Sputnik V fue usada en 33 (35.1%), mientras que AstraZeneca se administró en 61 (64.9%). En 60 pa cientes (63.8 %), la vacuna provocó respuesta humoral específica. La respuesta inmunológica según esquemas de vacunación (Sputnik V, Astra Zeneca o esquemas he terólogos) no mostró diferencias cualitativas (p = 0.45). El análisis estratificado según tratamiento recibido para la EM mostró que número significativamente menor de sujetos desarrolló anticuerpos contra el antígeno espiga en los pacientes que recibieron ocrelizumab (p ≤ 0.001), aunque con un número reducido de pacientes evaluados bajo este tratamiento (n = 7). Esto también se observó para anticuerpos neutralizantes en el grupo bajo ocrelizumab (p < 0.001). Durante el seguimiento de tres meses, dos personas fueron diagnosticadas con COVID-19. Conclusión : Encontramos que los pacientes con EM que recibieron vacunas Sputnik V o AstraZeneca para el SARS-CoV-2 desarrollaron respuesta serológica sin diferencias entre las vacunas utilizadas.

Serological response to SARS-CoV-2 vaccines in patients with multiple sclerosis in Argentina.

INTRODUCTION: The objective was to assess the immunogenicity and effectiveness of vaccines against SARSCoV-2 in multiple sclerosis (MS) patients included in the Argentinean MS registry. METHODS: A prospective cohort study between May and December 2021. The primary outcome was immunogenicity and effectiveness of vaccines during a three-month follow-up. Immunogenicity was evaluated based on detection of total antibodies (Ab) against spike protein and neutralizing Ab in serum 4 weeks after the second vaccine dose. A positive COVID-19 case was defined according to Argentinean Ministry of Health. RESULTS: 94 patients were included, mean age: 41.7 ± 12.1 years. Eighty (85.1%) had relapsing remitting multiple sclerosis (RRMS); 30 (31.9%) were under fingolimod treatment. The Sputnik V vaccine was the first dose in 33 (35.1%), and AstraZeneca in 61 (64.9%). In 60 (63.8%), the vaccine elicited a specific humoral response. Immunological response according to the vaccination schemes showed no qualitative differences (p = 0.45). Stratified analysis according to the MS treatment showed that a significantly smaller number of subjects developed antibodies against spike antigen among those that were on ocrelizumab compared to other groups (p = 0.001), while a reduced number of patients under ocrelizumab where evaluated (n = 7). This was also observed for neutralizing antibodies in the ocrelizumab group (p < 0.001). During the three-month follow-up, two individuals were diagnosed with COVID-19. CONCLUSION: We found that MS patients that received Sputnik V or AstraZeneca vaccines for SARS-CoV-2 developed a serological response with no differences between the vaccines used.

Introducción: El objetivo fue evaluar la inmunogenicidad y efectividad de las vacunas contra el SARS-CoV-2 en pacientes con esclerosis múltiple (EM) incluidos en el registro argentino de EM (RelevarEM, NCT03375177). Métodos: Estudio de cohorte prospectivo entre mayo y diciembre 2021. Se evaluó la inmunogenicidad (detección de anticuerpos totales (Ab) contra proteína espiga y anticuerpos neutralizantes en suero) y eficacia (nueva infección por COVID-19) durante seguimiento de tres meses. El momento de detección de anticuerpos fue 4 semanas después de segunda dosis de vacuna. Un caso positivo de COVID-19 se definió de acuerdo con la definición del Ministerio de Salud. Resultados: Se incluyeron 94 pacientes, edad media de 41.7 ± 12.1 años. Ochenta (85.1%) tenían EM remitente-recurrente; 30 (31.9%) en tratamiento con fingolimod. La vacuna Sputnik V fue usada en 33 (35.1%), mientras que AstraZeneca se administró en 61 (64.9%). En 60 pacientes (63.8 %), la vacuna provocó respuesta humoral específica. La respuesta inmunológica según esquemas de vacunación (Sputnik V, Astra Zeneca o esquemas heterólogos) no mostró diferencias cualitativas (p = 0.45). El análisis estratificado según tratamiento recibido para la EM mostró que número significativamente menor de sujetos desarrolló anticuerpos contra el antígeno espiga en los pacientes que recibieron ocrelizumab (p = 0.001), aunque con un número reducido de pacientes evaluados bajo este tratamiento (n = 7). Esto también se observó para anticuerpos neutralizantes en el grupo bajo ocrelizumab (p < 0.001). Durante el seguimiento de tres meses, dos personas fueron diagnosticadas con COVID-19. Conclusión: Encontramos que los pacientes con EM que recibieron vacunas Sputnik V o AstraZeneca para el SARS-CoV-2 desarrollaron respuesta serológica sin diferencias entre las vacunas utilizadas.

Increased risk of false-positive HIV ELISA results after COVID-19.

OBJECTIVE: From the first-generation options available in 1985, tests to detect HIV-1 specific antibodies have increased its sensitivity and specificity. HIV-1 and SARS-CoV-2 surface glycoproteins present a certain degree of homology and shared epitope motifs, which results of relevance as both pandemics coexist. Here, we aimed to evaluate the rate of false-positive HIV serology results among individuals with COVID-19 diagnosis and in vaccinated individuals. DESIGN: A retrospective analysis of the samples stored at the Infectious Disease Biobank in Argentina from donors with previous COVID-19 diagnosis or anti-SARS-CoV-2 vaccination. METHODS: Plasma samples were analyzed using Genscreen Ultra HIV Ag-Ab. In those with a positive result, the following assays were also performed: ELISA lateral flow Determine Early Detect; RecomLine HIV-1 & HIV-2 IgG and Abbott m2000 RealTime PCR for HIV-1 viral load quantification. In all samples, the presence of anti-SARS-CoV-2 IgG antibodies was evaluated by ELISA using the COVIDAR kit. Statistical analysis was done using Pearson's and Fisher's exact chi-squared test; Mann-Whitney and Kruskal-Wallis tests. RESULTS: Globally, the false-positive HIV ELISA rate was 1.3% [95% confidence interval (95% CI) 0.66-2.22; χ2  = 4.68, P  = 0.03, when compared with the expected 0.4% false-positive rate]. It increased to 1.4% (95% CI 0.70-2.24, χ2  = 5.16, P  = 0.02) when only samples from individuals with previous COVID-19 diagnosis, and to 1.8% (95% CI 0.91-3.06, χ2  = 7.99, P  = 0.005) when only individuals with detectable IgG SARS-CoV-2 antibodies were considered. CONCLUSION: This higher occurrence of HIV false-positive results among individuals with detectable antibodies against Spike SARS-CoV-2 protein should be dispersed among virology testing settings, health providers, and authorities.

Respuesta inmune contra SARS-CoV-2 en personas con VIH convalecientes de COVID-19 / SARS-CoV-2 immunity in PWH

Desde principios de la pandemia de SARS-CoV-2 se ha debatido el curso de la enfermedad COVID-19 en personas con VIH. Por un lado, la inmunodeficiencia derivada de la infección por VIH y la mayor prevalencia de comorbilidades estarían asociadas al desarrollo de enfermedad grave. Por otro lado, la disfunción inmunológica podría evitar una respuesta inflamatoria exacerbada. En este trabajo de revisión analizamos la evidencia disponible en cuanto a la relación entre la manifestación clínica de COVID-19 y la respuesta inmune humoral y celular contra SARS-CoV-2 en el contexto de la coinfección con VIH. La bibliografía sugiere que las personas con VIH que reciben tratamiento antirretroviral logran respuestas eficaces contra SARS-CoV-2, a pesar de presentar algunas de las funciones celulares alteradas. Esto sugiere un impacto significativo de la terapia antirretroviral, no solo en el control del VIH sino en potenciar la inmunidad para restringir otras infecciones.

Since the beginning of SARS-CoV-2 pandemic, the course of COVID-19 in people with HIV has been debated. On the one hand, the immunodeficiency derived from HIV infec-tion and the higher prevalence of comorbidities would be associated with severe disease. On the other hand, due to its immunological dysfunction, an exacerbated inflam-matory response might be avoided.In this review, we analyzed the evidence regarding the clinical manifestation of COVID-19 and the humoral and cellular immune response against SARS-CoV-2 during HIV coinfection. The literature suggests that people with HIV on antiretroviral treatment achieved effective responses against SARS-CoV-2, despite having altered cell func-tions. This indicates a remarkable impact of antiretroviral therapy, not only in controlling HIV but also in boosting immunity to restrict other infections

Immune Response to SARS-CoV-2 Third Vaccine in Patients With Rheumatoid Arthritis Who Had No Seroconversion After Primary 2-Dose Regimen With Inactivated or Vector-Based Vaccines.

OBJECTIVE: The aim of this study was to assess the immune response after a third dose of SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA) with undetectable antibody titers after the primary regimen of 2 doses. METHODS: Patients with RA with no seroconversion after 2 doses of SARS-CoV-2 vaccine and who received a third dose of either an mRNA or vector-based vaccine were included. Anti-SARS-CoV-2 IgG antibodies, neutralizing activity, and T cell responses were assessed after the third dose. RESULTS: A total of 21 nonresponder patients were included. At the time of vaccination, 29% were receiving glucocorticoids and 85% biologic disease-modifying antirheumatic drugs (including 6 taking abatacept [ABA] and 4 taking rituximab [RTX]). The majority (95%) received the BNT162b2 vaccine and only one of them received the ChAdOx1 nCoV-19 vaccine. After the third dose, 91% of the patients presented detectable anti-SARS-CoV-2 IgG and 76% showed neutralizing activity. Compared to other treatments, ABA and RTX were associated with the absence of neutralizing activity in 4 out of 5 (80%) patients and lower titers of neutralizing antibodies (median 3, IQR 0-20 vs 8, IQR 4-128; P = 0.20). Specific T cell response was detected in 41% of all patients after the second dose, increasing to 71% after the third dose. The use of ABA was associated with a lower frequency of T cell response (33% vs 87%, P = 0.03). CONCLUSION: In this RA cohort, 91% of patients who failed to seroconvert after 2 doses of SARS-CoV-2 vaccine presented detectable anti-SARS-CoV-2 IgG after a third dose. The use of ABA was associated with a lower frequency of specific T cell response.

SARS-CoV-2-Specific IgG and IgA response in maternal blood and breastmilk of vaccinated naïve and convalescent lactating participants.

Background: Recent studies have shown the presence of SARS-CoV-2-specific antibodies in the milk of breastfeeding mothers vaccinated with mRNA and convalescent. However, limited information is available in lactating women receiving other vaccine platforms used in developing countries, such as the inactivated SARS-CoV-2 vaccine BBIBP-CorV (Sinopharm) and the non-replicating adenovirus vaccines Sputnik V (Gamaleya Institute) and ChAdOx1-S (Oxford AstraZeneca). Methods: Here, we evaluated anti-SARS-CoV-2 IgG and IgA levels in both serum and milk samples using a longitudinal and a cross-sectional cohort of 208 breastfeeding vaccinated women from Argentina with or without previous SARS-CoV-2 infection. Results: The analysis showed that IgA levels remain constant in serum and milk of breastfeeding mothers between the first and second doses of vector-based vaccines (Sputnik V and ChAdOx1-S). After the second dose, anti-spike IgA was found positive in 100% of the serum samples and in 66% of breastmilk samples. In addition, no significant differences in milk IgA levels were observed in participants receiving BBIBP-CorV, Sputnik V or ChAdOx1-S. IgG levels in milk increased after the second dose of vector-based vaccines. Paired longitudinal samples taken at 45 and 120 days after the second dose showed a decrease in milk IgG levels over time. Study of IgA levels in serum and milk of vaccinated naïve of infection and vaccinated-convalescent breastfeeding participants showed significantly higher levels in vaccinated-convalescent than in participants without previous infection. Conclusion: This study is relevant to understand the protection against SARS-CoV-2 by passive immunity in newborns and children who are not yet eligible to receive vaccination.

Antibody response against SARS-CoV-2 variants of concern in children infected with pre-Omicron variants: An observational cohort study.

BACKGROUND: Despite that pediatric COVID-19 is usually asymptomatic or mild, SARS-CoV-2 infection typically results in the development of an antibody response. Contradictory observations have been reported when the antibody response of children and adults were compared in terms of strength, specificity and perdurability. METHODS: This observational study includes three cohorts infected with SARS-CoV-2 between March 2020-July 2021: unvaccinated infected children (n=115), unvaccinated infected adults (n=62), and vaccinated infected children (n=76). Plasma anti-spike IgG antibodies and neutralising activity against Wuhan, Delta and Omicron variants after 7-17 months post-infection were analysed. FINDINGS: More than 95% of unvaccinated infected children and adults remained seropositive when evaluated at 382-491 and 386-420 days after infection, respectively. Anti-spike IgG titers and plasma neutralising activity against Wuhan, Delta and Omicron variants were higher in children compared to adults. No differences were found when unvaccinated infected children were stratified by age, gender or presence/absence of symptoms in the acute phase of SARS-CoV-2 infection, but a slight decrease in the antibody response was observed in those with comorbidities. Vaccination of previously infected children with two doses of the inactivated BBIBP-CorV or the mRNA vaccines, BNT162b2 and/or mRNA-1273, further increased anti-spike IgG titers and neutralising activity against Wuhan, Delta and Omicron variants. INTERPRETATION: Unvaccinated infected children mount a more potent and sustained antibody response compared with adults, which is significantly increased after vaccination. Further studies including not only the analysis of the immune response but also the effectiveness to prevent reinfections by the different Omicron lineages are required to optimise vaccination strategy in children. FUNDING: National Agency for Scientific and Technological Promotion from Argentina (PICTO-COVID-SECUELAS-00007 and PMO-BID-PICT2018-2548).

Impacto de la edad gestacional en la gravedad de la infección por Sars-CoV-2 en personas gestantes, en un hospital del conurbano bonaerense / Impact of gestational age on the severity of Sars-CoV-2 infection in pregnant people, in a hospital in the Buenos Aires surroundings

ntroducción: La información sobre la evolución de la infección por COVID-19 en personas gestantes (PG) continúa en desarrollo.Objetivos: Describir la presentación de la infección por Sars-CoV-2 en PG y determinar variables asociadas a mayor gravedad.Materiales y métodos: Estudio observacional retrospectivo. Periodo: 01/03/2020-31/07/2021. Se incluyeron PG con diagnóstico de COVID-19 asistidas en una maternidad de gestión pública: se clasificaron según gravedad y se dividieron en dos grupos: Grup o1 leve y de manejo ambulatorio; Grupo 2 moderado, severo y crítico, con internación. Se analizó la relación entre gravedad y obesidad, DBT, hipertensión inducida por el embarazo (HIE), edad gestacional, edad materna, vacunación antigripal. Recién nacidos (RN) de madres infectadas se estudiaron con PCR para Sars-CoV-2 24-48 hs postnacimiento. Análisis estadístico: Chi-cuadrado o test exacto de Fisher. Significancia= p<0,05. Aprobado porComité Ética Institucional.Resultados: 52 PG con diagnóstico de COVID-19. Edadmediana 29,6 años. Grupo 1: 29 PG (55,5%). Grupo 2: 23 PG(44%), 19 (36,5%) moderados, 2 (4%) severos y 2 (4%) críticos. No hubo fallecimientos maternos ni fetales. Edad gestacional ≥ 28 semanas fue la única variable asociada a mayor gravedad,p=0,00004. 48% de los embarazos finalizaron por cesárea.48/52 RN fueron estudiados con PCR para Sars-CoV-2, siendo 1 (2%) positivo (fue el único RN sintomático).Conclusiones: La infección por COVID-19 en PG se asoció a presentaciones clínicas más graves cuando la infecciónse cursó en el tercer trimestre de gestación y se asociócon mayor incidencia de cesáreas

ntroduction: The information concerning the impact of COVID-19 infection in pregnant people (PP) continues to be established.Aim: to describe the evolution of the Sars-CoV-2 infection in pregnant people and to determine variables associated with clinical severity.Materials and Methods: Retrospective observational study. Period: 01-03-2020 to 31-07-2021. We included PP with diagnosis of COVID-19, assisted in a public maternity hospital. The cases were classified according to clinical severity based on the NIH guidelines. The patients were divided into 2 groups: Group 1: mild (ambulatory manage-ment). Group 2: moderate, severe and critical (requiring hospitalization). The relationship between variables and clinical severity was analyzed. Variables studied: obesity, DBT, gestational hypertension, gestational age, maternal age, influenza vaccination. Newborns of infected mothers were studied with PCR for Sars-CoV-2 24 to 48 hours af-ter birth. Statistical analysis: Chi-square or Fisher's exact test, significance = p <0.05. Study approved by the Institu-tional Ethics Committee.Results: 52 PP with diagnosis of COVID-19 were includ-ed. Median age 29.6 years. 23 patients (44%) required hospitalization and 2 (4%) MRA (mechanical respiratory assistance). 29 (55.5%) were mild, 19 (36.5%) moderate, 2 (4%) severe, and 2 (4%) critical. There were no mater-nal or fetal deaths. Gestational age ≥ 28 weeks was the only variable associated with more severe clinical forms, p = 0.0001. 48% of the pregnancies ended by cesarean section. 48/52 newborns were studied with PCR for Sars-CoV-2, with only 1 (2%) being positive. This was the only symptomatic newborn.Conclusions: In our study, Sars-CoV-2 infection during pregnancy was associated with more severe clinical pre-sentations when the infection occurred in the 3rd trimes-ter of pregnancy. COVID-19 was also associated with a higher incidence of ter

Longitudinal Study after Sputnik V Vaccination Shows Durable SARS-CoV-2 Neutralizing Antibodies and Reduced Viral Variant Escape to Neutralization over Time.

Recent studies have shown a temporal increase in the neutralizing antibody potency and breadth to SARS-CoV-2 variants in coronavirus disease 2019 (COVID-19) convalescent individuals. Here, we examined longitudinal antibody responses and viral neutralizing capacity to the B.1 lineage virus (Wuhan related), to variants of concern (VOC; Alpha, Beta, Gamma, and Delta), and to a local variant of interest (VOI; Lambda) in volunteers receiving the Sputnik V vaccine in Argentina. Longitudinal serum samples (N = 536) collected from 118 volunteers obtained between January and October 2021 were used. The analysis indicates that while anti-spike IgG levels significantly wane over time, the neutralizing capacity for the Wuhan-related lineages of SARS-CoV-2 and VOC is maintained within 6 months of vaccination. In addition, an improved antibody cross-neutralizing ability for circulating variants of concern (Beta and Gamma) was observed over time postvaccination. The viral variants that displayed higher escape to neutralizing antibodies with respect to the original virus (Beta and Gamma variants) were the ones showing the largest increase in susceptibility to neutralization over time after vaccination. Our observations indicate that serum neutralizing antibodies are maintained for at least 6 months and show a reduction of VOC escape to neutralizing antibodies over time after vaccination. IMPORTANCE Vaccines have been produced in record time for SARS-CoV-2, offering the possibility of halting the global pandemic. However, inequalities in vaccine accessibility in different regions of the world create a need to increase international cooperation. Sputnik V is a recombinant adenovirus-based vaccine that has been widely used in Argentina and other developing countries, but limited information is available about its elicited immune responses. Here, we examined longitudinal antibody levels and viral neutralizing capacity elicited by Sputnik V vaccination. Using a cohort of 118 volunteers, we found that while anti-spike antibodies wane over time, the neutralizing capacity to viral variants of concern and local variants of interest is maintained within 4 months of vaccination. In addition, we observed an increased cross-neutralization activity over time for the Beta and Gamma variants. This study provides valuable information about the immune response generated by a vaccine platform used in many parts of the world.

Platelets modulate CD4+ T-cell function in COVID-19 through a PD-L1 dependent mechanism.

Severe COVID-19 is associated with a systemic inflammatory response and progressive CD4+ T-cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4+ T-cell dysfunction in COVID-19. We observed a high frequency of CD4+ T cell-platelet aggregates in COVID-19 inpatients that inversely correlated with lymphocyte counts. Platelets from COVID-19 inpatients but not from healthy donors (HD) inhibited the upregulation of CD25 expression and tumour necrosis factor (TNF)-α production by CD4+ T cells. In addition, interferon (IFN)-γ production was increased by platelets from HD but not from COVID-19 inpatients. A high expression of PD-L1 was found in platelets from COVID-19 patients to be inversely correlated with IFN-γ production by activated CD4+ T cells cocultured with platelets. We also found that a PD-L1-blocking antibody significantly restored platelets' ability to stimulate IFN-γ production by CD4+ T cells. Our study suggests that platelets might contribute to disease progression in COVID-19 not only by promoting thrombotic and inflammatory events, but also by affecting CD4+ T cells functionality.

Respuesta immune humoral asociada a las vacunas contra SARS-CoV-2 en pacientes con artritis reumatoidea: datos del registro SAR-CoVAC / Humoral immune response associated to the vaccines against SARS-CoV-2 in patients with rheumatic arthritis: data from the SAR-CoVAC registry

Introducción: la artritis reumatoidea (AR) y los tratamientos indicados para su manejo pueden afectar la respuesta a la vacuna para SARS-CoV-2. Sin embargo, aún no se cuenta con datos locales. Objetivos: evaluar la respuesta humoral de la vacuna para SARS-CoV-2 y su seguridad en esta población. Materiales y métodos: estudio observacional. Se incluyeron pacientes ≥18 años, con AR ACR/EULAR 2010 que recibieron la vacunación para SARS-CoV-2. Detección de IgG anti-proteína S (kit COVIDAR). Resultados: se incluyeron 120 pacientes con AR. El 24,4% recibió tratamiento con glucocorticoides, 50,9% drogas biológicas y 13,3% inhibidores de JAK (janus kinases). El 6% había tenido infección por SARS-CoV-2 previamente. La vacuna más utilizada en la primera dosis fue Sputnik V (52,9%). El 25% recibió esquemas heterólogos. Luego de la primera dosis, el 59% presentó una prueba no reactiva o indeterminada, y un 18% luego de la segunda dosis. La aplicación de esquemas homólogos de vacuna Sinopharm (63,6% vs 13,3%, p<0,0001), y el uso de abatacept (27,3% vs 5,1%, p=0,005) y rituximab (18,2% vs 0%, p=0,001) al momento de la vacunación se asociaron a un resultado no reactivo o indeterminado. Conclusiones: similar a lo reportado en otras poblaciones internacionales, en esta cohorte, dos de cada 10 pacientes no desarrollaron anticuerpos. Una menor respuesta se asoció con la vacuna Sinopharm y al tratamiento con abatacept y rituximab.

Introduction: rheumatoid arthritis (RA) and its treatments can affect the response to the SARS-CoV-2 vaccine. However, we still do not have local data. Objectives: to evaluate the humoral response of the SARS-CoV-2 vaccine and its safety in this population. Materials and methods: observational study. Patients ≥18 years of age, with RA ACR/EULAR 2010 who had received vaccination for SARS-CoV-2 were included. Detection of anti-protein S IgG (COVIDAR Kit). Results: a total of 120 patients with RA were included. A quarter was receiving glucocorticoids, 50.9% biological drugs and 13.3% JAK inhibitors (janus kinases). Only 6% had a history SARS-CoV-2 infection. The most used vaccine was Sputnik V (52.9%) and 25% received mixed regimenes. After the first dose, 59% had a non-reactive or indeterminate test, and after the second, 18% were still having this result. The application of homologous Sinopharm vaccine regimen (63.6% vs 13.3%, p<0.0001) and the use of abatacept (27.3% vs 5.1%, p=0.005) and rituximab (18.2% vs 0%, p=0.001) at vaccination was associated with a non-reactive or indeterminate result. Conclusions: similar to other international populations, in this cohort, two out of 10 patients did not develop antibodies. A lower response was associated with the Sinopharm vaccine and treatment with abatacept and rituximab.

Dynamics of SARS-CoV-2-specific antibodies among COVID19 biobank donors in Argentina.

Biobanks are instrumental for accelerating research. Early in SARS-CoV-2 pandemic, the Argentinean Biobank of Infectious Diseases (BBEI) initiated the COVID19 collection and started its characterization. Blood samples from subjects with confirmed SARS-CoV-2 infection either admitted to health institutions or outpatients, were enrolled. Highly exposed seronegative individuals, were also enrolled. Longitudinal samples were obtained in a subset of donors, including persons who donated plasma for therapeutic purposes (plasma donors). SARS-CoV-2-specific IgM and IgG levels, IgG titers and IgG viral neutralization capacity were determined. Out of 825 donors, 57.1% were females and median age was 41 years (IQR 32-53 years). Donors were segregated as acute or convalescent donors, and mild versus moderate/severe disease donors. Seventy-eight percent showed seroconversion to SARS-CoV-2 specific antibodies. Specific IgM and IgG showed comparable positivity rates in acute donors. IgM detectability rate declined in convalescent donors while IgG detectability remained elevated in early (74,8%) and late (83%) convalescent donors. Among donors with follow-up samples, IgG levels seemed to decline more rapidly in plasma donors. IgG levels were higher with age, disease severity, number of symptoms, and more durable in moderate/severe disease donors. Levels and titers of anti-spike/RBD IgG strongly correlated with neutralization activity against WT virus. The BBEI-COVID19 collection serves a dual role in this SARS-CoV-2 global crisis. First, it feeds researchers and developers transferring samples and data to fuel research projects. Second, it generates highly needed local data to understand and frame the regional dynamics of the infection.

Sputnik V vaccine elicits seroconversion and neutralizing capacity to SARS-CoV-2 after a single dose.

Massive vaccination offers great promise for halting the global COVID-19 pandemic. However, the limited supply and uneven vaccine distribution create an urgent need to optimize vaccination strategies. We evaluate SARS-CoV-2-specific antibody responses after Sputnik V vaccination of healthcare workers in Argentina, measuring IgG anti-spike titers and neutralizing capacity after one and two doses in a cohort of naive or previously infected volunteers. By 21 days after receiving the first dose of the vaccine, 94% of naive participants develop spike-specific IgG antibodies. A single Sputnik V dose elicits higher antibody levels and virus-neutralizing capacity in previously infected individuals than in naive ones receiving the full two-dose schedule. The high seroconversion rate after a single dose in naive participants suggests a benefit of delaying administration of the second dose to increase the number of people vaccinated. The data presented provide information for guiding public health decisions in light of the current global health emergency.

Creación de la colección COVID-19 del Biobanco de Enfermedades Infecciosas en Argentina / Establishment of a COVID-19 collection within the Biobank of Infectious Diseases in ArgentinaEsta obra está bajo una licencia de CreativeCommons Reconocimiento-NoComercial 4.0Internacionalhttps://creativecommons.org/licenses/by-nc/4.0/i

La pandemia de COVID-19 ha puesto en jaque a los sistemas de salud en el mundo; la vinculación entre la investigación biomédica y la práctica asistencial ha probado ser un requisito fundamental para dar respuesta a la misma de manera eficiente y rápida. En este sentido, los biobancos se constituyen como un componente clave ya que favorecen el almacenamiento de grandes volúmenes de muestras biológicas gestionadas en base a criterios que garanticen su óptima calidad, armonización y seguridad, respetando requisitos éticos y legales que aseguran los derechos de los ciudadanos. La cesión de estas muestras a distintos grupos de investigación promueve el desarrollo de nuevas herramientas diagnósticas y terapéuticas y vacunas. Frente a la llegada del SARS-CoV-2 a la Argentina, el Biobanco de Enfermedades Infecciosas estableció rápidamente la colección COVID-19 constituida por muestras de plasma, suero y células mononucleares de sangre periférica de personas cursando la enfermedad o recuperadas. En solo seis meses se enrolaron 825 donantes, lo que significa alrededor de 14.000 viales de material biológico almacenados y a disposición de los investigadores que lo soliciten. A tal efecto, se realizaron seis actos de cesión a diversos grupos pertenecientes a instituciones de investigación, mientras que tres se encuentran en evaluación. Las muestras cedidas han permitido, por ejemplo, el desarrollo de kits serológicos de producción nacional; lo que pone de manifiesto que el rápido establecimiento de esta colección, bajo un sistema de gestión eficiente, constituye una herramienta muy valiosa en la respuesta a esta nueva enfermedad

The COVID-19 pandemic has driven an unprecedented health crisis. Cooperation between biomedical research and healthcare practice has been shown to be a fundamental requirement to provide an efficient and timely response. In this regard, biobanks are key components since they allow the storage of large volumes of biological samples with guaranteed optimum quality, harmonization and safety, ensuring ethical and legal requirements which protect citizen rights. The transfer of these samples to different research groups fosters the development of new diagnostic and therapeutic tools as well as vaccines. Upon SARS-CoV-2 arrival to Argentina, the Biobank of Infectious Diseases rapidly established the COVID-19 collection comprised by plasma, serum and peripheral blood mononuclear cells samples obtained from people within the acute phase of the infection or who have already recovered. In only 6 months, 825 donors were enrolled, representing around 14,000 vials of biological material stored and available to researchers who might require it. In this line, 6 transfer agreements have been already performed to different groups belonging to national research institutions, while 3 are under evaluation. The transferred samples have allowed, for instance, the development of nationally produced serologic kits, which shows that the rapid establishment of this collection, under an efficient management system, represents a highly valuable tool in the response to this new disease.

Seroprevalencia de COVID 19 en personas viviendo con VIH en el Area Metropolitana / COVID-19 Seroprevalence and PLHIV

Se desconoce si las personas que viven con el VIH (PVV) tienen un mayor riesgo de contraer la infección por SARS-CoV-2. Los estudios serológicos prospectivos pueden permitir análisis de seroincidencia. Este estudio prospectivo incluyó a PVV sin antecedentes de vacunación contra SARS-CoV-2 de la Ciudad Autónoma de Buenos Aires (CABA) y Gran Buenos Aires (GBA) que concurrieron entre marzo y junio de 2021 a realizar sus controles al instituto INBIRS. La tasa de seroprevalencia de anticuerpos contra la proteína espiga del SARS-CoV-2 fue del 33,3% (IC 24,9-42,5%) para la población estudiada. Esta prevalencia fue significativamente mayor a la reportada previamente para la población general de la misma región geográfica. No se observó una asociación entre el recuento de linfocitos T CD4+ con los niveles de IgG específica. En conclusión, el hallazgo de una alta seroprevalencia de anticuerpos contra SARS-CoV-2 entre las PVV en CABA y GBA puede sugerir una mayor susceptibilidad a la infección por este virus; sin embargo, puede ser también un marcador subrogante que indica la tasa de seroprevalencia en población general se encuentra subestimada

It is not known whether people living with HIV (PLHIV) are at increased risk of acquiring SARS-CoV-2 infection. Prospective serological studies can allow seroincidence analysis. This prospective study included PLHIV, without a history of vaccination against SARS-CoV-2, from the Autonomous City of Buenos Aires (CABA) and Buenos Aires surroundings (GBA), who attended INBIRS Institute between March and June 2021 to carry out their controls. The seroprevalence rate of antibodies against the SARS-CoV-2 spike protein was 33.3% (CI 24.9-42.5%) for the study population. This prevalence was significantly higher than that previously reported for the general population of the same geographic region. No association was found between CD4+ T-cell counts with levels of SARS-CoV-2 specific IgG. In conclusion, the finding of a high seroprevalence of antibodies against SARS-CoV-2 among PLHIV in CABA and GBA may suggest a greater susceptibility to infection; however, it can also be a surrogate marker that the seroprevalence rate in the general population is underestimated.

Two novel mutations of the TSH-beta subunit gene underlying congenital central hypothyroidism undetectable in neonatal TSH screening.

CONTEXT: Patients with TSH-beta subunit defects and congenital hypothyroidism are missed by TSH-based neonatal screening. OBJECTIVE: Our objective was to report the molecular consequences of a novel splice-junction mutation and a novel missense mutation in the TSH-beta subunit gene found in two patients with congenital central hypothyroidism and conventional treatment-resistant anemia. RESULTS: Patient 1 had a homozygous G to A nucleotide change at the 5' donor splice site of exon/intron 2. This resulted in a silent change at codon 34 of the mature protein. In vitro splicing assays showed that the mutant minigene dramatically affected pre-mRNA processing, causing exon 2 to be completely skipped. The putative product from a new out-of-frame translational start point in exon 3 is expected to yield a nonsense 25-amino-acid peptide. In patient 2, sequence analysis revealed a compound heterozygosis for the already reported 313delT (C105Vfs114X) mutation and for a second novel mutation in exon 3, substituting G for A at cDNA nucleotide position 323, resulting in a C88Y change. This cysteine residue is conserved among all dimeric pituitary and placental glycoprotein hormone-beta subunits. Data from in silico analysis confirmed that the C88Y mutation would affect subunit conformation. Indeed, two different bioinformatics approaches, PolyPhen and SIFT analysis, predicted C88Y to be a damaging substitution. CONCLUSIONS: In isolated TSH deficiency, the exact molecular diagnosis is mandatory for diagnosis of isolated pituitary deficiency, delineation of prognosis, and genetic counseling. Moreover, diagnosis of central hypothyroidism should be considered in the face of severe infant anemia of uncertain etiology.