Covid-19 en América Latina y México: brechas del bienestar

Este trabajo aborda empíricamente las brechas estructurales del bienestar reveladas por la epidemia de Covid-19 en cuatro países de América Latina: Argentina, Costa Rica, México y Panamá. Para ello, aborda diversos ámbitos: el sanitario, el económico, el del empleo y el de la protección social, particularmente en el ámbito de la afiliación a los sistemas de pensiones, la mayor o menor incidencia de la crisis en el ascenso de la pobreza y la pobreza extrema y la capacidad para responder a ese repunte, la agudización de las desigualdades de género y el surgimiento de brechas que magnifican las desigualdades educativas.Alternate abstract:This article empirically addresses structural welfare gaps revealed by the Covid-19 epidemic in four Latin American countries: Argentina, Costa Rica, Mexico, and Panama. To do this, it examines various areas: healthcare, the economy, employment, social protection, particularly in the field of affiliation to pension systems, the greater or lesser incidence of the crisis in the growth of poverty and extreme poverty and the ability of each state to respond to that rise, the worsening of gender inequalities, and the emergence of gaps that magnify educational inequalities.

SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination.

The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.

Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry.

Introduction: COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods: This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results: The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion: Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.

One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients.

The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3-6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7-391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16-20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p < 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.

SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders.

BACKGROUND: The clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established. PATIENTS AND METHODS: A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3-6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders. RESULTS: At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 days (range 7-195) after full vaccination. The incidence rate was 6.39 per 100 persons-year. Most patients were asymptomatic (19/37, 51.4%), whereas only 19% developed pneumonia. The mortality rate was 8%. Lack of detectable antibodies at 3-6 weeks after full vaccination was the only variable associated with breakthrough infection in multivariate logistic regression analysis (Odds Ratio 2.35, 95% confidence interval 1.2-4.6, p = 0.012). Median antibody titers were lower in cases than in non-cases [1.83 binding antibody units (BAU)/mL (range 0-4854.93) vs 730.81 BAU/mL (range 0-56,800), respectively (p = 0.007)]. We identified 250 BAU/mL as a cutoff above which incidence and severity of the infection were significantly lower. CONCLUSIONS: Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants.

Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients.

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.

Bacterial and Fungal Gut Dysbiosis and Clostridium difficile in COVID-19: A Review.

BACKGROUND: Gastrointestinal symptoms are common in Coronavirus Disease 2019 (COVID-19), related to infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) of intestinal cells through the angiotensin converting enzyme 2 (ACE2) receptor in the brush border. Also, patients are treated with multiple antibiotics. Therefore, an increase in gut dysbiosis and in the prevalence of Clostridium difficile infection (CDI) is expected in patients with COVID-19. METHODS: A PubMed search was conducted using the terms "gut microbiota," "gut mycobiota," "dysbiosis" AND "COVID-19"; "Clostridium difficile," "Clostridioides difficile" AND "COVID-19"; "probiotics," "bacteriotherapy AND COVID-19." Only case series, observational and experimental studies were included. RESULTS: A total of 384 papers were retrieved and 21 fulfilled selection criteria. Later, a new paper was identified, thus 22 papers were reviewed. Main findings: (1) gut bacterial dysbiosis has been found in fecal samples of COVID-19 patients, with enrichment of opportunistic organisms and decrease of beneficial commensals such as Faecalibacterium prausnitizii. Dysbiosis is related to inflammatory markers and illness severity. (2) There is evidence for abnormal gut barrier and bacterial translocation with a negative impact in the lungs. (3) Fungal dysbiosis correlating with pulmonary mycobiota, has also been found. (4) There is controversy in the CDI rates among COVID-19 patients versus controls and pandemic versus prepandemic era. (5) There is no available evidence yet to support bacteriotherapy in COVID-19. (6) Fecal microbiota transplantation (FMT) has been proposed for COVID-19, although there is no evidence to support it. Also, FMT can be safely used during the pandemic for CDI if strict screening protocols for donors and fecal product are implemented. CONCLUSIONS: In COVID-19 there is bacterial and fungal dysbiosis that correlates with systemic and pulmonary inflammation, and illness severity. Further investigations are warranted to determine the efficacy of bacteriotherapy and FMT for modulating gut dysbiosis in COVID-19.

Identifying SARS-CoV-2 'memory' NK cells from COVID-19 convalescent donors for adoptive cell therapy.

COVID-19 disease is the manifestation of syndrome coronavirus 2 (SARS-CoV-2) infection, which is causing a worldwide pandemic. This disease can lead to multiple and different symptoms, being lymphopenia associated with severity one of the most persistent. Natural killer cells (NK cells) are part of the innate immune system, being fighting against virus-infected cells one of their key roles. In this study, we determined the phenotype of NK cells after COVID-19 and the main characteristic of SARS-CoV-2-specific-like NK population in the blood of convalescent donors. CD57+ NKG2C+ phenotype in SARS-CoV-2 convalescent donors indicates the presence of 'memory'/activated NK cells as it has been shown for cytomegalovirus infections. Although the existence of this population is donor dependent, its expression may be crucial for the specific response against SARS-CoV-2, so that, it gives us a tool for selecting the best donors to produce off-the-shelf living drug for cell therapy to treat COVID-19 patients under the RELEASE clinical trial (NCT04578210).

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group.

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.

SARS-CoV-2-reactive interferon-γ-producing CD8+ T cells in patients hospitalized with coronavirus disease 2019.

There is limited information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell immune responses in patients with coronavirus disease 2019 (COVID-19). Both CD4+ and CD8+ T cells may be instrumental in resolution of and protection from SARS-CoV-2 infection. Here, we tested 25 hospitalized patients either with microbiologically documented COVID-19 (n = 19) or highly suspected of having the disease (n = 6) for presence of SARS-CoV-2-reactive CD69+ expressing interferon-γ (IFN-γ) producing CD8+ T cells using flow-cytometry for intracellular cytokine staining assay. Two sets of overlapping peptides encompassing the SARS-CoV-2 Spike glycoprotein N-terminal 1 to 643 amino acid sequence and the entire sequence of SARS-CoV-2 M protein were used simultaneously as antigenic stimulus. Ten patients (40%) had detectable responses, displaying frequencies ranging from 0.15 to 2.7% (median of 0.57 cells/µL; range, 0.43-9.98 cells/µL). The detection rate of SARS-CoV-2-reactive IFN-γ CD8+ T cells in patients admitted to intensive care was comparable (P = .28) to the rate in patients hospitalized in other medical wards. No correlation was found between SARS-CoV-2-reactive IFN-γ CD8+ T-cell counts and SARS-CoV-2 S-specific antibody levels. Likewise, no correlation was observed between either SARS-CoV-2-reactive IFN-γ CD8+ T cells or S-specific immunoglobulin G-antibody titers and blood cell count or levels of inflammatory biomarkers. In summary, in this descriptive, preliminary study we showed that SARS-CoV-2-reactive IFN-γ CD8+ T cells can be detected in a non-negligible percentage of patients with moderate to severe forms of COVID-19. Further studies are warranted to determine whether quantitation of these T-cell subsets may provide prognostic information on the clinical course of COVID-19.

Risk factors and outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. PATIENTS AND METHODS: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. RESULTS: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 109/L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). CONCLUSIONS: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.

Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (>16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G < 400 mg/dL, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (P = .03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS: Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.

The Postgraduate Studies Division in the Face of COVID-19: A Look Back at 2020.

The essay presents a review of the pandemic situation in the Division of Postgraduate Studies (DEP) at the Faculty of Medicine of UNAM during 2020. The intention is to reflect on the institutional response capacity, reconstructing the actions and events that show rhythms and orientations in three moments. In the first stage, concerns and efforts were aimed at protecting residents from the imminence of the risk of contagion and death. The DEP intensified relations with health institutions, and campaigns were carried out to give them the necessary tools for their protection. The second tram was for recomposition to reasume educational activities and pay attention to the training processes at each specialty. Finally, in the third period, that of the new normality, educational processes mediated by communication and information technologies were assumed, although clinical practice continued in face-to-face mode. As hospitals have returned to their pre-COVID dynamics, educational activities have also tended to re-establish. The COVID-19 contingency acted as an accelerator of change and the DEP was not indifferent to that process. Despite the mistakes and errors, some of the characteristics of academic institutionalization were transformed, promoting educational shifts. (English) [ABSTRACT FROM AUTHOR] El ensayo presenta una revisión de la coyuntura pandémica en la División de Estudios de Posgrado (DEP) de la Facultad de Medicina de la UNAM durante 2020. La intención es reflexionar en torno a la capacidad de respuesta institucional ante la contingencia, reconstruyendo las acciones y los hechos que muestran ritmos y orientaciones en tres momentos. En la primera etapa, la preocupación y los esfuerzos estuvieron encaminados a proteger a los residentes ante la inminencia del riesgo de contagio y muerte. La DEP intensificó las relaciones con las instituciones de salud y se llevaron a cabo campañas con el fin de darles las herramientas necesarias para su protección. El segundo tiempo fue de recomposición para retomar las actividades educativas y poner atención a los procesos formativos en cada especialidad. Finalmente, en el tercer período, el de la nueva normalidad, se asumieron los procesos educativos mediados por tecnologías de la comunicación y la información, aunque la práctica clínica siguió en modalidad presencial. A medida que los hospitales han vuelto a las dinámicas previas a la irrupción del COVID-19, las actividades educativas también han tendido a restablecerse. La contingencia por el COVID-19 actuó como un acelerador del cambio y la DEP no fue indiferente a ese proceso, las características de la institucionalización académica se transformaron promoviendo acciones educativas. (Spanish) [ABSTRACT FROM AUTHOR] Copyright of Revista de la Facultad de Medicina de la UNAM is the property of UNAM, Facultad de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)