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El fortalecimiento técnico de la Superintendencia Nacional de Salud (SuperSalud), ente de inspección, vigilancia y control del Sistema General de Seguridad Social en Salud de Colombia, es necesario. Para tal fin, se propone el uso eficiente de los sistemas de información, que permita la toma de decisiones en política pública y que garantice el derecho fundamental de la salud.

ObjectiveTo determine the associated factors with mortality, in addition to age and sex, in a high-complexity hospital in Bogota, Colombia, during the first year of the pandemic.DesignA case-control study.SettingHigh-complexity center above 2,640 meters above sea level (masl) in Colombia.MethodsA case-control study was conducted on 564 patients admitted to the hospital with confirmed COVID-19. Deceased patients (n: 282) and a control group (n: 282), matched by age, sex, and month of admission, were included. Clinical and paraclinical variables were retrospectively obtained by systematic revision of clinical records. Multiple imputations by chained equation (MICE) were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalization.ResultsMost of the patients included were males in the seventh decade of life. Most of the admissions occurred between July and August 2021. Surprisingly, recovered patients reported heterogeneous symptomatology, whereas deceased patients were most likely to present respiratory distress, dyspnea, and seizures on admission. In addition, the latter group exhibited a higher burden of comorbidities and alterations in laboratory parameters. After the imputation of datasets, CART analysis estimated 14 clinical profiles based on respiratory distress, LDH, dyspnea, hemoglobin, D-dimer, ferritin, blood urea nitrogen, C-reactive protein, PaO2/FiO2, dysgeusia, total bilirubin, platelets, and gastroesophageal reflux disease. The accuracy model for prediction was 85.6% (P < 0.0001).ConclusionMultivariate analysis yielded a reliable model to predict mortality in COVID-19. This analysis revealed new interactions between clinical and paraclinical features in addition to age and sex. Furthermore, this predictive model could offer new clues for the personalized management of this condition in clinical settings.

A case report is presented of a 50-year-old woman who was seen in Accident and Emergency because of pain in the lumbar area. She was subsequently diagnosed with septic arthritis of the left hip due to being Neisseria gonorrhoeae positive for beta-lactamase. She responded to treatment with ceftriaxone, but later required a total hip replacement.

Post-COVID syndrome (PCS) is recognized as a new entity in the context of SARS-CoV-2 infection. Though its pathogenesis is not completely understood, persistent inflammation from acute illness and the development of autoimmunity play a critical role in its development.The mechanisms involved in the emergence of PCS, their similarities with post-viral and post-care syndromes, its inclusion in the spectrum of autoimmunity and possible targets for its treatment.An autoimmune phenomenon plays a major role in most causative theories explaining PCS. There is a need for both PCS definition and classification criteria (including severity scores). Longitudinal and controlled studies are necessary to better understand this new entity, and to find what additional factors participate into its development. With the high prevalence of COVID-19 cases worldwide, together with the current evidence on latent autoimmunity in PCS, we may observe an increase of autoimmune diseases (ADs) in the coming years. Vaccination's effect on the development of PCS and ADs will also receive attention in the future. Health and social care services need to develop a new framework to deal with PCS.

Fragmento. El ser humano busca irremediablemente un sentido a su vida. Esa búsqueda se acentúa con la edad o durante la enfermedad. Todo ser humano, en la lógica de la vida, enfermará. Unos antes que otros. Cada cual, entonces, hará lo mejor de sí hasta cuando descubra que lo pudo haber hecho mejor. O lo contrario. Este número de MEDICINA ofrece un espacio para estas reflexiones. Los artículos sobre la historia de la medicina tratan aspectos que merecen ser recordados como testimonio del inicio de las capacidades científicas del país. No en vano la modernidad es el resultado de la crítica constructiva del pasado. La medicina de precisión, un ejemplo evidente de esta modernidad, ha dejado de ser un concepto de investigación y se ha convertido en la mejor opción de atención médica, que aprovecha toda la información de un individuo para predecir el tránsito de la salud a la enfermedad (prevención primaria) o para conocer el riesgo de desenlaces en un paciente (prevención secundaria y terciaria), incluyendo la respuesta a los tratamientos.

Background The clinical presentation and severity of Multisystem Inflammatory Syndrome in Children associated with COVID-19 is widespread and presents a very low mortality rate in highincome countries. This research describes the clinical characteristics of MIS-C in critically ill children in middle-income countries compared to described series in high-income countries along with the factors associated with mortality and worse outcomes. Methods An observational cohort study was conducted in 14 PICUs in Colombia between April 01, 2020 and January 31, 2021. Patient´s age ranged between one month and 18 years and they met the requirements set forth by WHO for MIS-C. Results There were seventy-eight children in this study. The median age was seven years (IQR 1- 11), 18% (14/78) were under one year old, and 56% were male. Thirty-five percent (29/78) were obese or overweight. The PICU stay was six days (IQR 4-7), and 100% had a fever on admission lasting five days (IQR 3.7-6). Seventy percent (55/78) had diarrhea, and 87% (68/78) had shock or myocardial dysfunction (78%). Compared to the United Kingdom (UK) study, there were more children under the age of five (37% vs. 10%; p=0.004), and there was a higher frequency of obesity (29.5% vs. 10%; p=0.008). With regard to the US study, there was more lymphadenopathy (23% vs. 13%; p=0.02), diarrhea (70.5% vs. 53%; p=0.001), lymphopenia (64% vs. 35%; p=0.001), shock (87% vs. 35%; p=0.001), elevated troponin (51% vs. 31%; p=0.006) and elevated proBNP (82% vs 43%; p=0.001), as well as greater mortality (9% vs 1.8%; p=0.001). The group that did not survive had a longer duration of the disease until admission to the PICU (6 days vs. 5 days; p = 0.003), more frequency of ferritin above 500 ngr/mL (100% vs. 45%; p = 0.012) and more cardiovascular complications (100% vs. 54%; p = 0.019) compared to the group that survived. Conclusions Multisystem Inflammatory Syndrome in Children due to SARS-CoV-2 in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics similar to those described in high-income countries. It was observed inflammatory response, and cardiovascular involvement were conditions that, added to the difficulties in accessing healthcare systems in countries with limited resources, may explain the higher mortality seen in these children.

Background and ObjectivesRecent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurologic side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4,000 ZIKV cases. Whether the neurologic symptoms of ZIKV infection are immune mediated is unclear. We used rodent and human live cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in the sera of patients with ZIKV with and without GBS.MethodsIn this study, 52 patients with ZIKV-GBS were compared with 134 ZIKV-infected patients without GBS and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens were validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array.ResultsOverall, IgG antibody reactivities to rat Schwann cells (SCs) (6.5%) and myelinated cocultures (9.6%) were significantly higher, albeit infrequent, in the ZIKV-GBS group compared with all controls. IgM antibody immunoreactivity to dorsal root ganglia neurones (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared with other controls, whereas IgM reactivity to cocultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from 1 patient were confirmed to react with neurofascin 155 and 186. Serum from a ZIKV-infected patient without GBS displayed strong myelin-binding and putative antilipid antigen reaction characteristics. There was, however, no significant association of ZIKV-GBS with any known antiglycolipid antibodies.DiscussionAutoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.

Frente al panorama creciente de contagios y con restricciones tanto financieras como logísticas para el acceso oportuno a las vacunas disponibles para la COVID-19, ¿valdría la pena, desde el costo-beneficio como de la selección de candidatos, evaluar la inmunidad individual contra SARS-CoV-2 para la optimización y priorización de la vacunación en países con dichas restricciones? Basados en la respuesta inmune al SARSCoV-2, los antecedentes históricos y las condiciones del país, se presentan argumentos para la discusión de la evaluación individual de la inmunidad al SARS-CoV-2 en la estrategia de vacunación. Si tal fuese el escenario, la implementación de una prueba costo efectiva y reproducible debería ser discutida y un estudio piloto considerado, el cual podría ser también útil en la evaluación de la inmunogenicidad de las vacunas.

Autoimmunity linked to COVID-19 immunization has been recorded throughout the pandemic. Herein we present six new patients who experienced relapses of previous autoimmune disease (AD) or developed a new autoimmune or autoinflammatory condition following vaccination. In addition, we documented additional cases through a systematic review of the literature up to August 1st, 2022, in which 464 studies (928 cases) were included. The majority of patients (53.6%) were women, with a median age of 48 years (IQR: 34 to 66). The median period between immunization and the start of symptoms was eight days (IQR: 3 to 14). New-onset conditions were observed in 81.5% (n: 756) of the cases. The most common diseases associated with new-onset events following vaccination were immune thrombocytopenia, myocarditis, and Guillain-Barré syndrome. In contrast, immune thrombocytopenia, psoriasis, IgA nephropathy, and systemic lupus erythematosus were the most common illnesses associated with relapsing episodes (18.5%, n: 172). The first dosage was linked with new-onset events (69.8% vs. 59.3%, P = 0.0100), whereas the second dose was related to relapsing disease (29.5% vs. 59.3%, P = 0.0159). New-onset conditions and relapsing diseases were more common in women (51.5% and 62.9%, respectively; P = 0.0081). The groups were evenly balanced in age. No deaths were recorded after the disease relapsed, while 4.7% of patients with new-onset conditions died (P = 0.0013). In conclusion, there may be an association between COVID-19 vaccination and autoimmune and inflammatory diseases. Some ADs seem to be more common than others. Vaccines and SARS-CoV-2 may induce autoimmunity through similar mechanisms. Large, well-controlled studies are warranted to validate this relationship and assess additional variables such as genetic and other environmental factors.

Background. Stroke is one of the most common causes of physical disability worldwide. The majority of survivors experience impairment of movement, often with lasting deficits affecting hand dexterity. To date, conventional rehabilitation primarily focuses on training compensatory maneuvers emphasizing goal completion rather than targeting reduction of motor impairment. Objective. We aim to determine whether finger dexterity impairment can be reduced in chronic stroke when training on a task focused on moving fingers against abnormal synergies without allowing for compensatory maneuvers. Methods. We recruited 18 chronic stroke patients with significant hand motor impairment. First, participants underwent baseline assessments of hand function, impairment, and finger individuation. Then, participants trained for 5 consecutive days, 3 to 4 h/d, on a multifinger piano-chord-like task that cannot be performed by compensatory actions of other body parts (e.g., arm). Participants had to learn to simultaneously coordinate and synchronize multiple fingers to break unwanted flexor synergies. To test generalization, we assessed performance in trained and nontrained chords and clinical measures in both the paretic and the nonparetic hands. To evaluate retention, we repeated the assessments 1 day, 1 week, and 6 months post-training. Results. Our results showed that finger impairment assessed by the individuation task was reduced after training. The reduction of impairment was accompanied by improvements in clinical hand function, including precision pinch. Notably, the effects were maintained for 6 months following training. Conclusion. Our findings provide preliminary evidence that chronic stroke patient can reduce hand impairment when training against abnormal flexor synergies, a change that was associated with meaningful clinical benefits.

Persistent cognitive, affective, and motor symptoms have been associated with sports-related concussions including several neurophysiological changes in the primary motor cortex. In particular, previous research has provided some evidence of altered latencies of the corticomotor pathway and altered motor neuroplasticity. However, to date, no studies have assessed these neurophysiological metrics in a common group of athletes across different phases of injury and recovery. In this study corticomotor latencies and neuroplasticity were assessed in collegiate athletes with or without a history of prior concussion across two different phases of injury: either in an acute state of concussion (within 2 wk of injury) or in a chronic state of concussion (more than 1 yr after injury). Corticomotor latencies were determined by measuring the motor evoked potential (MEP) onset time, and motor neuroplasticity was assessed by measuring MEP amplitudes following application of anodal transcranial direct current stimulation (tDCS) over the primary motor cortex (M1). We found that concussed athletes had slower corticomotor latencies than nonconcussed athletes, and corticomotor latency was also positively correlated with the number of prior concussions. In contrast, there was no evidence of altered motor neuroplasticity in athletes regardless of concussion history. These findings suggest concussions may lead to permanent changes in the corticospinal tract that are exacerbated by repeated injury. NEW & NOTEWORTHY We are the first to assess corticomotor latencies and motor neuroplasticity in a common group of collegiate athletes across different phases of injury and recovery. We found that the number of concussions an individual sustains negatively impacts corticomotor latencies with a higher number of prior concussions correlating positively with longer latencies. Our findings indicate that concussions may lead to permanent changes in the corticospinal tract that are exacerbated by repeated injury.

Background Pronounced sex differences in the susceptibility and response to SARS-CoV-2 infection remain poorly understood. Emerging evidence has highlighted the potential importance of autoimmune activation in modulating the acute response and recovery trajectories following SARS-CoV-2 exposure. Given that immune-inflammatory activity can be sex-biased in the setting of severe COVID-19 illness, the aim of the study was to examine sex-specific autoimmune reactivity to SARS-CoV-2 in the absence of extreme clinical disease. Methods In this study, we assessed autoantibody (AAB) reactivity to 91 autoantigens previously linked to a range of classic autoimmune diseases in a cohort of 177 participants (65% women, 35% men, mean age of 35) with confirmed evidence of prior SARS-CoV-2 infection based on presence of antibody to the nucleocapsid protein of SARS-CoV-2. Data were compared to 53 pre-pandemic healthy controls (49% women, 51% men). For each participant, socio-demographic data, serological analyses, SARS-CoV-2 infection status and COVID-19 related symptoms were collected by an electronic survey of questions. The symptoms burden score was constructed based on the total number of reported symptoms (N = 21) experienced within 6 months prior to the blood draw, wherein a greater number of symptoms corresponded to a higher score and assigned as more severe burden. Results In multivariable analyses, we observed sex-specific patterns of autoreactivity associated with the presence or absence (as well as timing and clustering of symptoms) associated with prior COVID-19 illness. Whereas the overall AAB response was more prominent in women following asymptomatic infection, the breadth and extent of AAB reactivity was more prominent in men following at least mildly symptomatic infection. Notably, the observed reactivity included distinct antigens with molecular homology with SARS-CoV-2. Conclusion Our results reveal that prior SARS-CoV-2 infection, even in the absence of severe clinical disease, can lead to a broad AAB response that exhibits sex-specific patterns of prevalence and antigen selectivity. Further understanding of the nature of triggered AAB activation among men and women exposed to SARS-CoV-2 will be essential for developing effective interventions against immune-mediated sequelae of COVID-19. Supplementary Information The online version contains supplementary material available at 10.1186/s12967-021-03184-8.

This article provides an overview of various aspects related to post-COVID syndrome. Apart from its prevalence, symptoms and sequelae, risk determinants, and psychosocial implications, the pathogenesis of post-COVID condition is discussed in more detail. A focus on thrombo-inflammation in SARS-CoV-2 infection, the role of neutrophil extracellular traps, and the prevalence of venous thromboembolism is made. Moreover, COVID-19 and post-COVID syndrome in immunocompromising conditions, and the impact of vaccination on the prevention and treatment of post-COVID symptoms are reviewed. Autoimmunity is a hallmark of post-COVID syndrome, and, therefore, is another focus of this article. Thus, misdirected cellular and humoral immune responses can enhance the risk of latent autoimmunity in post-COVID syndrome. Facing the high prevalence of COVID-19 cases worldwide, it can be assumed that autoimmune disorders will increase globally over the next few years. Recent advances in identifying genetically determined variants may open the avenue for a better understanding of the susceptibility to and severity of SARS-CoV-2 infection and post-COVID syndrome.

En México existen 3.8 millones de viviendas sin acceso al agua entubada, habitadas por cerca de 15 millones de personas, situación que genera desabasto, además de algunas enfermedades gastrointestinales.

This collaborative meta-analysis was supported by the Swiss National Science Foundation and the Laura and John Arnold Foundation (grant supporting the post-doctoral fellowship at the Meta-Research Innovation Center at Stanford (METRICS), Stanford University). The funders had no role in the design of this collaborative meta-analysis; in the collection, analysis, and interpretation of data; or in the report writing., We would like to express our warm gratitude to all participating patients and convalescent plasma donors. We thank Katja Suter and Sina Ullrich, University of Basel, for their administrative assistance. For their helpful contribution to individual trials, we thank Erica Wood, Iain Gosbell, Richard Charlewood, Thomas Hills, Veronica Hoad, Kristina Kairaitis, Aikaj Jindal, John Gerrard, Hong Foo, Adam Stewart, and Nanette Trask (ASCOT trial); Amalia Bravo-Lindoro, Ral Carrillo-Esper, Karla Maldonado-Silva, Catalina Casillas-Suárez, Orlando Carrillo-Torres, Sandra Murrieta, Elizabeth Diaz-Padilla, Eli Omar Zavaleta, Yadira Bejar-Ramirez, and Evelyn Cortina-de la Rosa (CPC-SARS trial); Sheri Renaud, Roel Rolando-Almario, and Jacqueline Day (NCT04385199 trial); Sandra Tingsgrd, MD, Karen Brorup Heje Pedersen, MD, Michaela Tinggaard, MD, Louise Thorlacius-Ussing, MD, Clara Lundetoft Clausen, MD, Nichlas Hovmand, MD, Simone Bastrup Israelsen, MD, Cecilie Leding, MD, Katrine Iversen, MD, Maria Engel Miller, MD, Hkon Sandholdt, MSc biostatistician (CCAP-2 trial). On behalf of the IRCT20200310046736N1 trial, we thank the Khuzestan Blood Transfusion Organization for specialized assistance in the preparation and maintenance of plasma samples. On behalf of the NCT04332835 trial, we thank all the members of the "PC-COVID-19 Group" at the Clinica del Occidente and Hospital Universitario Mayor Mederi in Bogota, and Clinica CES in Medellin. On behalf of the NCT04403477 trial, we thank Miles Carroll for his support regarding the antibody testing in Bangladesh. The Co-CLARITY team would like to extend their gratitude to the Department of Science and Technology Philippine Council for Health Research and Development and the UP-Philippine General Hospital for all their support in the setting up and conduct of the trial. For helpfully communicating details of their trial, we thank members of the PlasmAr trial, NCT04359810 trial (Max O´Donnell), NCT04468009 trial, and CTRI/2020/05/025299 trial. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute (https://www.cancer.gov/)., During the conduct of the study, the following is reported: Dr. Berry reports being employee with ownership role at Berry Consultants (receives payments for statistical modeling and design of REMAP-CAP). Dr. Castillo reports grants from DOST PCHRD. Dr. Daly reports grants from Medical Research Future Fund (Australian Govt) and RBWH. Dr. Denkinger reports grants from German Ministry for Education and Research. Dr. Dumagay reports grants from Philippine Council for Health Research and Development. Dr. Dunachie reports grants from UK Department of Health and Social Care, grants from UK National Institute of Health Research. Dr. Gauiran reports grants from Department of Science and Technology—Philippine Council for Health Research and Development. Dr. Gordon reports grants from NIHR, grants from NIHR Research Professorship (RP-2015-06-18), and non-financial support from NIHR Clinical Research Network. Dr. Higgins reports grants from NHMRC and from the Minderoo Foundation. Dr. Hills reports grants from Health Research Council of New Zealand. Dr. Holm reports grants from Swedish Government Funds for Clinical Research (ALF). Dr. Janssen and Dr. Müller-Tidow report grants from the Federal Ministry of Education and Research in Germany (BMBF) to the RECOVER clinical trial. Dr. Krapp reports grants from Department of Foreign Affairs, Trade, and Development of Canada, grants from Fundación Telefónica del Perú. Dr. J. Lim reports grants from the Department of Science and Technology, Philippine Council for Health Research and Development. Dr. Lucero reports grants from Philippine Council for Health Research and Development. Dr Manrique reports economic support from Grupo ISA Intercolombia for the project development of trial NCT04332835. Drs. McQuilten and Wood report grants from Medical Research Future Fund. Dr. McVerry reports grants from The Pittsburgh Foundation, Translational Breast Cancer Research Consortium, and from UPMC Learning While Doing Program. Mr. Mouncey reports grants from National Institute for Health Research and from the European Union FP7: PREPARE. Dr. Najdovski reports payment from KUL Leuven to Belgian Red Cross for supply of convalescent plasma. Dr. Nichol reports grants from Health Research Board of Ireland. Dr. D. Roberts reports grants from the National Institute for Health (UKRIDHSC COVID-19 Rapid Response Rolling Call—Grant Reference Number COV19-RECPLAS) and the European Commission (SUPPORT-E #101015756). Dr. Rowan reports grants from the European Commission and from the UK National Institute for Health Research. Dr. Shankar-Hari reports grants from National Institute for Health Research UK, grants from UKRI-National Institute for Health Research UK. Dr. Turgeon reports grants from Canadian Institutes of Health Research. Dr. Venkatesh reports grants from Baxter. Dr. Webb reports grants from National Health and Medical Research Council, grants from Minderoo Foundation. Dr. Zacharowski reports grants from EU Horizon 2020. The ASCOT trial team (Drs Bowen, Daly, Davis, Denholm, Hammond, Jha, L. Lim, McQuilten, Molton, Morpeth, O’Sullivan, Paterson, Perry, Price, Rees, Roberts, Rogers, Sasadeusz, Snelling, Tong, Venkatesh, Wood) is funded by grants from from Royal Brisbane and Women’s Hospital Foundation, Pratt Foundation, Minderoo Foundation, BHP Foundation, Hospital Research Foundation, Macquarie Group Foundation, Health Research Council of New Zealand, Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), and the collection and supply of convalescent plasma was conducted within Lifeblood’s funding arrangements. The CONFIDENT trial is funded by the Belgian KCE (blood establishments received payment for the convalescent plasma supplied in the clinical trial). REMAP-CAP was supported in part by funding from UKRIDHSC COVID-19 Rapid Response Rolling Call (Grant Reference Number COV19-RECPLAS). Collection of convalescent plasma for REMAP-CAP was funded by the Department of Health and Social Care, UK. The IRCT20200310046736N1 trial was supported by the Ahvaz Jundishapur University of Medical Sciences (Grant No. R.AJUMS.REC.1399.003, Dr. Pouladzadeh). The PC-COVID-19 Group is supported by the Universidad del Rosario, IDCBIS, ISA Group and Suramericana (Colombia). Outside the submitted work, the following is reported: Dr. Axfors reports postdoctoral grants from the Knut and Alice Wallenberg Foundation, Uppsala University, the Swedish Society of Medicine, the Blanceflor Foundation, and the Sweden-America Foundation. Dr. Aomar reports personal fees from SOBI, GEDEON RICHTER, and GSK. Dr. Benfield reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, and Pentabase ApS. Dr. Estcourt reports being an investigator on the RECOVERY trial. Dr. Gordon reports personal fees from GlaxoSmithKline, Bristol Myers Squibb, and 30 Respiratory. Dr. Jha reports grants and personal fees from Baxter Healthcare, personal fees from Astra Zeneca, grants from NephroPlus. Dr. Laterre reports personal fees from Adrenomed. Dr. McVerry reports grants from NIH/NHLBI and Bayer Pharmaceuticals, Inc. Dr. Mondragon reports financial activities outside the submitted work (employment at Johnson & Johnson). Dr. Perry reports partner being employed at CSL and owning shares in CSL. Dr. Paterson reports involvement with ALLIANCE trial of COVID-19 treatments. Dr. J. Roberts reports other COVID-19 related trials (in different patient groups): tocilizumab in ICU patients; hydroxychloroquine dosing in ICU patients; planned study of remdesivir pharmacokinetics in patients during expanded access program; and in silico evaluation of ivermectin dosing. Dr Sasadeusz reports grants from various Pharma companies including Gilead Sciences, Abvvie, Merck, and Takeda. Dr. Zacharowski reports personal fees from Biotest AG, CSL Behring, GE Heathcare, and is President of the ESAIC., Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. Conclusions: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care., Amalia Bravo-Lindoro, BHP Foundation, Blanceflor Foundation, Department of Foreign Affairs, Trade, and Development of Canada, Eli Omar Zavaleta, Erik and Susanna Olesen’s Charitable Fund, Federal Ministry of Education and Research in Germany, Fundación Telefónica del Perú, IDCBIS, ISA Group and Suramericana, Kai Hansen Foundation, Katja Suter and Sina Ullrich, Khuzestan Blood Transfusion Organization, Macquarie Group Foundation, Medical Research Future Fund, NephroPlus, RBWH, Roel Rolando-Almario NCT04385199, Royal Brisbane, Sheri Renaud, Simonsen Foundation, UKRI-National Institute for Health Research UK, UKRIDHSC COV19-RECPLAS, UP-Philippine General Hospital CTRI/2020/05/025299, NCT04359810, NCT04468009, Women’s Hospital Foundation, National Institutes of Health, National Heart, Lung, and Blood Institute, Pittsburgh Foundation, Pfizer, Baxter International, Stanford University, Gilead Sciences, National Institute on Handicapped Research RP-2015-06-18, Meso Scale Diagnostics, Universität Basel, Laura and John Arnold Foundation, Health Research Board, Pratt Foundation, Canadian Institutes of Health Research, National Institute for Health Research, Department of Health and Social Care, European Commission 101015756, National Health and Medical Research Council, Department of Science and Technology, Ministry of Science and Technology, India, Health Research Council of New Zealand, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Sweden-America Foundation, Bundesministerium für Bildung und Forschung, Lundbeckfonden, Knut och Alice Wallenbergs Stiftelse, Seventh Framework Programme, Ahvaz Jundishapur University of Medical Sciences, Université Pierre et Marie Curie, Uppsala Universitet, Horizon 2020, Svenska Läkaresällskapet, Universidad del Rosario, Pharmaceuticals Bayer, Novo Nordisk Fonden, Department of Science and Technology, Philippines, Philippine Council for Health Research and Development, Minderoo Foundation

BackgroundThe immunopathological pathways enabling post-COVID syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition.MethodsThirty-three patients were included for longitudinal clinical and autoantibody analyses of whom 12 patients were assessed for cytokines and lymphocyte populations. Patients were followed during 7-11 months after acute COVID-19. Autoimmune profile and immunological status were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry.ResultsLatent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by upregulated IFN-α, TNF-α, G-CSF, IL-17A, IL-6, IL-1β, and IL-13, whereas IP-10 was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of IgG S1-SARS-CoV-2 antibodies remained elevated over time.DiscussionThe clinical manifestations of PCS are associated with the persistence of a proinflammatory, and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

Background The immunopathological pathways enabling post-coronavirus disease 2019 (COVID-19) syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition. Methods Thirty-three patients were included for longitudinal clinical and autoantibody analyses, 12 of whom were assessed for cytokines and lymphocyte populations. Patients were followed for 7–11 months after acute COVID-19. Autoimmune profile and immunological statuses were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry. Results Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by up-regulated interferon-α, tumor necrosis factor-α, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-17A, IL-6, IL-1β, and IL-13, whereas interferon-γ-induced protein 10 (IP-10) was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of immunoglobulin G S1-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies remained elevated over time. Conclusions The clinical manifestations of PCS are associated with the persistence of a proinflammatory and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed "overt polyautoimmunity" (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as "latent PolyA". We aimed to explore a new taxonomy of ADs based on PolyA.In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs.Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes.This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials.

Sjögren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjögren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands.

Neutrophils play an important role in immune defence against several pathogens. These cells actively participate in the innate immune response through different functions, such as chemotaxis, phagocytosis, oxidative burst and degranulation, which have been widely studied. However, in the last few years, a new function has been described; activated neutrophils are able to release web-like chromatin structures known as neutrophil extracellular traps (NETs). These structures formed by DNA, histones, and proteins, immobilize and kill microorganisms. Disruption in NET formation is associated with the pathophysiology of several disorders, including the autoimmune diseases. NETs are an important source of the autoantigens involved in the production of autoantibodies and maintenance of the inflammatory milieu. This review provides a summary of the contribution of NETs to the pathogenesis of anti-neutrophil cytoplasmic antibodies-associated vasculitis, systemic lupus erythematosus, and rheumatoid arthritis. The preliminary findings on NETs components in Sjögren.'s syndrome will also be described. RESUMEN Los neutrófilos juegan un papel muy importante en la defensa inmune contra diferentes patógenos. Estas células participan activamente en la respuesta inmune innata a través de diferentes funciones como quimiotaxis, fagocitosis, estallido oxidativo y degranulación, las cuales han sido estudiadas ampliamente. Sin embargo, en los últimos años se ha descrito una nueva función; los neutrófilos activados son capaces de liberar redes de cromatina llamadas trampas extracelulares de neutrófilos (NETs). Estas estructuras están formadas por ADN, histonas y proteínas capaces de inmovilizar y matar microorganismos. Alteraciones en la formación de estas NETs están asociadas con la fisiopatología de varios trastornos, incluyendo las enfermedades autoinmunes (EAI). Las NETs son consideradas una fuente de autoantígenos que ayudan a la producción de autoanticuerpos y al mantenimiento de un ambiente inflamatorio. Esta revisión resume la contribución de las NETs a la patogénesis de vasculitis asociada a anticuerpos contra el citoplasma de los neutrófilos, lupus eritematoso sistémico y artritis reumatoide. Adicionalmente, se describirán los resultados preliminares de la detección de componentes de las NETs en pacientes con síndrome de Sjögren.

Polyautoimmunity (PolyA) is an emerging concept that may help to develop a better classification of autoimmune diseases (ADs). Thus, we aimed to develop new taxonomy based on PolyA. Two-hundred and fifty-four consecutive patients were included with rheumatoid arthritis (RA, n:146), systemic lupus erythematosus (SLE, n:45), Sjögren’s syndrome (SS, n:29), autoimmune thyroid disease (AITD, n:17) and systemic sclerosis (SSc, n:17). Clinical features, autoantigen array chip, lymphocytes immunophenotype and cytokine profile were assessed simultaneously. The coexistence of two or more ADs with classification criteria was termed “Overt PolyA”, whereas the presence of autoantibodies unrelated to the index AD, without criteria fulfillment, was named “Latent PolyA”. Combination of IgG autoantibodies yielded high accuracy for classification of ADs. In SLE, Histone H2A, Sm/RNP, ssDNA, and dsDNA IgG autoantibodies were the most predictive autoantibodies for this condition. Laminin, Ro/SSA (52 kDa), and U1−snRNP B/B’ for SS; Thyroglobulin for AITD; Ribo Phosphoprotein P1, and CENP-A for SSc. Interestingly, Thyroglobulin and U1−snRNP B/B’ were mutual diagnostic biomarkers in SS and SSc. Latent PolyA showed in nearly 70% of patients, whereas overt PolyA was most common in AITD (82.4%) and SLE (40%). Cluster analysis based on autoantibodies yielded three clusters of which clusters 2 and 3 exhibited high frequency of latent and overt PolyA with distinctive clinical and immunological phenotypes. Combination of autoantibodies demonstrated high performance for classification of ADs. Patients with both latent and overt PolyA cluster together and exhibit differential clinical and immunological features. High prevalence of latent and overt PolyA advocates for routinary surveillance in clinical settings.One Sentence SummaryThis is a proof-of-concept study which allowed a new classification of autoimmune diseases. The results highlight that most patients with both latent and overt polyautoimmunity cluster together, with differential clinical and immunological characteristics.

Stroke affects more than ten million individuals in the world each year, with most victims experiencing motor deficits usually referred to collectively as hemiparesis. While hemiparesis is one of the most common and clinically recognizable abnormalities, it remains under-characterized in terms of its behavioral subcomponents and how they combine to produce the overall post-stroke motor deficit. Hemiparesis is comprised of both negative and positive motor signs. Negative signs consist of weakness and loss of motor control (dexterity), whereas positive signs consist of spasticity, abnormal resting posture, and intrusive movement synergies whereby multiple muscles or joints become co-activated during voluntary movement. How positive and negative signs interact, and whether a common mechanism generates them, remains poorly understood. Here we employed a planar reaching task to assess post-stroke arm dexterity loss, which we compared to the Fugl-Meyer stroke scale; a measure primarily reflecting abnormal synergies. We examined 53 patients with hemiparesis after a first-time ischemic stroke. Reaching kinematics were markedly more impaired in patients with subacute ( 6 months) stroke even when matched for Fugl-Meyer score. While our reaching dexterity task mitigated the effect of weakness on synergies through the use of arm-weight support, we found that the Fugl-Meyer scale was a poor predictor of arm dexterity. This suggests a dissociation between abnormal synergies (reflected in the Fugl-Meyer scale) and loss of dexterity, which in turns suggests that different mechanisms may generate these particular positive and negative signs. At the same time, dynamometry suggested that Fugl-Meyer scores may capture weakness as well as abnormal synergies, in line with these two deficits sharing a neural substrate. These findings have two important implications: First, clinical studies that test for efficacy of rehabilitation interventions should specify which component of hemiparesis they are targeting and how they propose to measure it. Second, there may be an opportunity to design specific rehabilitation interventions to address specific subcomponents of the hemiparesis syndrome.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4%80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals70 years, 2.3% between 70 and 80 years, and 6.3%80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.

In this issue of The Journal , Sharma, et al 1 report on the differences among 3 groups of patients with Sjogren syndrome (SS). The first had a focus score (FS) of < 1 in the minor salivary gland (MSG) biopsy, another had an FS ≥ 1, and the other had an FS of zero. Patients without focal lymphocytic infiltration (i.e., FS = 0) exhibited a low frequency of anti-La antibodies, corneal compromise, and hypergammaglobulinemia, and had no elevated expression of interferon-regulated genes, but did have systemic disease. However, all these patients showed positive anti-Ro antibodies. These results indicate that anti-Ro antibodies may be a key factor influencing the development of the disease, and that the MSG biopsy may be negative in patients with SS. SS is a chronic autoimmune disease characterized by a progressive lymphocytic and plasma cell infiltration that mainly affects the salivary and lachrymal glands and leads to xerostomia and keratoconjunctivitis sicca (sicca symptoms). The diagnosis of SS is based on the combination of symptoms (sicca symptoms) and the presence of autoimmune characteristics: activation of B cells (i.e., presence of auto-antibodies) and/or T cells (i.e., positive MSG biopsy)2. The classification of the disease is currently based on the American-European consensus group classification criteria [American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR)], which include serological tests, clinical findings, and histological examination3. The presence of autoantibodies or a positive MSG biopsy is mandatory3. MSG biopsy plays an essential role in the diagnosis, stratification, and prognosis of SS as well as in the differential diagnosis of the disease (i.e., sarcoidosis, amyloidosis, etc.)4,5. In our view, for diagnostic purposes the MSG biopsy is preferred to parotid and lacrimal gland biopsies because it is less invasive and safer while offering similar … Address correspondence to Dr. J.M. Anaya, CREA, School of Medicine and Health Sciences, Universidad del Rosario, Carrera 24 No. 63C-69, Bogota, Colombia. E-mail: juan.anaya{at}urosario.edu.co

Objective: To evaluate the geoepidemiology of Sjögren's syndrome (SS) in Latin America. Methods: This was a three phase study in which original data from a Colombian cohort of patients with SS is presented, followed by a systematic review of Colombian and Latin American studies. Lastly, the geoepidemiology of SS in Latin America was assessed by comparing the clinical characteristics of the region with those of the rest of the world by means of a meta-analysis approach. Results: Data from 2970 patients from Latin America and 18019 patients from Europe, North America and Asia were analyzed. Colombian patients have a lower age at disease onset than those from other Latin American countries and a higher rate of positivity of antinuclear antibodies and rheumatoid factor. A significant difference in the proportion of female patients in Latin America compared with Europe and North America was observed. The spectrum of disease in Latin American was similar to North American patients, while strong differences were noticed between Latin American and European and Asian patients. Noteworthy, a paucity of reports including African and African-descendent patients was observed. Conclusions: The clinical spectrum of SS differs between countries and continents. Genetic differences relying upon ancestry could explain these findings. However, environmental factors have proven to be important determinants in the development of autoimmune diseases (i.e., autoimmune ecology). Thus, ancestry and the autoimmune ecology should be considered in studies aimed to evaluate the geoepidemiology of SS and other autoimmune diseases. © 2019 Société française de rhumatologie