Predicted COVID-19 molecular effects on endometrium reveal key dysregulated genes and functions.

COVID-19 exerts systemic effects that can compromise various organs and systems. Although retrospective and in silico studies and prospective preliminary analysis have assessed the possibility of direct infection of the endometrium, there is a lack of in-depth and prospective studies on the impact of systemic disease on key endometrial genes and functions across the menstrual cycle and window of implantation. Gene expression data have been obtained from (i) healthy secretory endometrium collected from 42 women without endometrial pathologies and (ii) nasopharyngeal swabs from 231 women with COVID-19 and 30 negative controls. To predict how COVID-19-related gene expression changes impact key endometrial genes and functions, an in silico model was developed by integrating the endometrial and COVID-19 datasets in an affected mid-secretory endometrium gene co-expression network. An endometrial validation set comprising 16 women (8 confirmed to have COVID-19 and 8 negative test controls) was prospectively collected to validate the expression of key genes. We predicted that five genes important for embryo implantation were affected by COVID-19 (downregulation of COBL, GPX3 and SOCS3, and upregulation of DOCK2 and SLC2A3). We experimentally validated these genes in COVID-19 patients using endometrial biopsies during the secretory phase of the menstrual cycle. The results generally support the in silico model predictions, suggesting that the transcriptomic landscape changes mediated by COVID-19 affect endometrial receptivity genes and key processes necessary for fertility, such as immune system function, protection against oxidative damage and development vital for embryo implantation and early development.

First report and genome sequencing of SARS-CoV-2 in a cat (Felis catus) in Colombia

Introduction. SARS-CoV-2 is a virus of zoonotic origin that can bind to ACE2 receptors on the cells of various mammals, including animals such as cats, dogs, ferrets, hyenas, coatis, otters, big cats, non-human primates, white-tailed deer, manatees, hippopotamuses, hamsters, and minks. Studies have shown that the virus can circulate among minks and Syrian hamsters, mutate, lead to animal-to-human zoonotic jump, and further onward spread between humans. The transmission of the virus from humans to cats is evident, but the virus's return to humans has not yet been demonstrated. Infection in pets is unusual, and there are few human-to-pet transmission reports worldwide. Objective. To describe the SARS-CoV-2 infection in Cordoba, Colombian Caribbean, a domestic animal. Methods. A cross-sectional molecular surveillance study was carried out, oral and rectal swabs were taken from cats and dogs living with people diagnosed with COVID-19. Results. SARS-CoV-2 was found in a cat living with a person with COVID-19. Genome sequencing showed that the B.1.111 lineage caused the infection in the cat. The owner's sample could not be sequenced. The lineage is predominant in Colombia, and this variant is characterized by the presence of the D614D and Q57H mutation. Conclusion.This is the first report on sequencing the SARS-CoV-2 genome in a cat in Colombia shows the importance of some interesting SARS-CoV-2 mutations in promoting the transmissibility of this new coronavirus in companion animals. Lack of information Human-to-cat or cat-to-human infection. © 2022, Fundacao Oswaldo Cruz. All rights reserved.

#LaHoraSTEAM (The STEAM Hour) - An Initiative to Promote STEM-STEAM Learning in Quarantine Times (Work in Progress)

The pandemic produced by COVID-19 has forced a radical change in the strategies and methodologies used to share and transmit knowledge. With the schools/Universities' closure, the educational process changed radically from one day to the next. In particular, in several Latin-American countries, the quarantine conditions are extremely severe, limiting regular citizens' movement and confining them to remain at home, only allowing them to get out for "essential " activities. STEM-STEAM education, based on collaborative work, inquiry, experimentation, problem-solving, and project generation, encounters many obstacles. In the present situation, students and teachers' isolation does not have access to laboratories, materials, and other essential supplies to facilitate a quality educational process. Aware of these limitations, a group of professionals from several countries across the Americas have worked together and developed the ManifiestoSTEAM. The ManifiestoSTEAM is a voluntary team working without any monetary support. The ManifiestoSTEAM goal is to develop alternative ways to promote quality STEM-STEAM education reaching students, parents, and teachers directly at their homes. One of the initiatives developed by the ManifiestoSTEAM, #LaHoraSTEAM will be presented in this paper. #LaHora STEAM is a public broadcast (Facebook, YouTube) of one hour once a week - Saturdays to facilitate parents and children interaction. In each broadcast, one of the ManifiestoSTEAM members presents a "live" activity generating interactivity with the audience. Then, the other group members monitor the chats to share the audience's participation and show their questions to the presenter and the rest of the team to model a live learning experience based on STEM-STEAM activities. All the activities presented in the live broadcast are implemented using materials accessible at home! To ensure that the prospective participants receive the information (time, access link, list of materials), the ManifiestoSTEAM, allied with the Municipality of Lima - Perú manages the logistics of distributing the information live broadcasting. Following Lima's success, ManifiestoSTEAM implemented a similar series of seven activities in Medellin, Colombia. The name of Medellin's series is "Viernes de Ser + STEM." After discussing the methodology implemented to produce #LaHora STEAM, data collected in the first 15 broadcasts in Lima and seven in Medellin will be presented, showing the impact of the initiative. © American Society for Engineering Education, 2021

Suboptimal Humoral and Cellular Immune Response to SARS-CoV-2 RNA Vaccination in Myeloma Patients Is Associated with Anti-CD38 and BCMA-Targeted Treatment

Background: Multiple myeloma (MM) patients are immunocompromised due to defects in humoral/cellular immunity and immunosuppressive therapy. Reports indicate that the antibody (Ab) response in MM after 1 dose of SARS-CoV-2 RNA vaccine is attenuated. The impact of treatment on cellular immunity after vaccination remains unknown. Methods: We analyzed SARS-CoV-2 spike-binding (anti-S) IgG level in 320 MM patients receiving SARS-CoV-2 RNA vaccination. Blood and saliva were taken at multiple time points and compared with serology data of 69 age-matched vaccinated healthcare workers. We profiled SARS-CoV-2-specific T cell responses in a subset of 45 MM patients and 12 age-matched healthy controls by flow cytometry and ELIspot. All subjects were enrolled in studies approved by the Institutional Review Board at the Icahn School of Medicine at Mount Sinai. Results: The 320 patients (median age 68 year) received two-dose RNA vaccines (69.1% BNT162b2, 27.2% mRNA-1273). Median time to diagnosis was 60 months with a median of 2 prior treatment lines (range 0-16). We included 23 patients with smoldering MM. Patients received various treatments at vaccination with 148 (43.8%) on anti-CD38-containing treatment, 36 (11.3%) on BCMA-targeted therapy and 59 (18.4%) not on active treatment (incl. SMM patients). At the last available evaluation prior to vaccination, 131 (40.9%) exhibited a complete response. At data cutoff, a total of 260 patients (81.3%) had anti-S IgG measured >10 days after the second vaccine (median 51 days). Of these, 84.2% mounted measurable anti-S IgG levels (median 149 AU/mL). In the control group, Ab levels were significantly higher (median 300 AU/mL). Ab levels in the vaccinated MM patients with prior COVID-19 were 10-fold higher than those of patients without prior COVID-19 (p<0.001). Repeat Ab measurements up to 60 days after second vaccination confirm delayed and suboptimal IgG kinetics, particularly in patients receiving anti-MM treatment compared to controls (Figure 1). MM patients on active treatment had lower anti-S IgG levels (p=0.004) compared to patients not on therapy (median 70 vs 183 AU/mL). Notably, 41 patients (15.8%) failed to develop detectable anti-S IgG: 24/41 (58.5%) were on anti-CD38, 13/41 (31.7%) on anti-BCMA bispecific Ab therapy and 4/41 (9.8%) >3 months after CAR T. Univariate analysis showed an association of disease-related factors with absence of anti-S IgG: more previous lines of treatment (>3 lines, p=0.035;>5 lines, p=0.009), receiving active MM treatment (p=0.005), grade 3 lymphopenia (p=0.018), receiving anti-CD38 therapy (p=0.042) and receiving BCMA-targeted therapy (p<0.001). Multivariate analysis (corrected for age, vaccine type, lines of treatment, time since diagnosis, response status and lymphopenia) confirmed that anti-CD38 (p=0.005) and BCMA-targeted treatment (p<0.001) are associated with not developing detectable anti-S IgG. Clinical relevance is emphasized by 10 cases of COVID-19 after 1 (n=7) or 2 vaccine doses (n=3, all without anti-S IgG) with 1 patient passing due to respiratory failure. We studied SARS-CoV-2-specific T cell responses >2 weeks after the second vaccine in 18 MM patients with undetectable anti-S IgG (seronegative), 27 with detectable anti-S IgG (seropositive) and 12 healthy seropositive controls. We found that seropositive MM patients had CD4+CD154+ T cells producing IFNg, TNFa and IL-2 at similar levels as controls, whereas in the seronegative MM cohort CD4 T cell responses were significantly reduced (p<0.005). SARS-CoV-2-specific CD8 T cell responses were overall weaker and not different across cohorts. This data suggests that absence of detectable IgG is associated with suboptimal response of humoral and cellular immunity. Conclusion: MM patients mount a suboptimal IgG response after SARS-CoV-2 vaccination, with 15.8% of patients without detectable anti-S IgG. Ongoing analyses will highlight durability of serological protection against COVID-19. Additional data on T cell responses and immunophenotyping in the context of vaccination will be upda ed at the meeting. Implications are continuation of non-pharmacological interventions, e.g. masking/social distancing, for vulnerable patients. The findings underscore a need for serological monitoring of MM patients after vaccination and for trials assessing use of prophylactic strategies or studies exploring additional immunization strategies. [Formula presented] Disclosures: Wang: Sanofi Genzyme: Consultancy. Chari: Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees;Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Millenium/Takeda: Consultancy, Research Funding;Sanofi Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Pharmacyclics: Research Funding;GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees;Secura Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees;Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Research Funding;Janssen Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Shattuck Labs: Consultancy, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Takeda: Consultancy, Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cordon-Cardo: Kantaro: Patents & Royalties. Krammer: Kantaro: Patents & Royalties;Merck: Consultancy;Pfizer: Consultancy;Avimex: Consultancy;Seqirus: Consultancy. Jagannath: Legend Biotech: Consultancy;Karyopharm Therapeutics: Consultancy;Janssen Pharmaceuticals: Consultancy;Bristol Myers Squibb: Consultancy;Sanofi: Consultancy;Takeda: Consultancy. Simon: Kantaro: Patents & Royalties. Parekh: Foundation Medicine Inc: Consultancy;Amgen: Research Funding;PFIZER: Research Funding;CELGENE: Research Funding;Karyopharm Inv: Research Funding.

COVID-19 pandemic in Uruguay: evolution, lessons learned and challenges

America has become a new epicenter of the COVID-19 pandemic but the epidemic in Uruguay has had an atypical behavior compared to the region, with positive results in the management and control of the health crisis. This article describes the socio-sanitary characteristics of the country, the evolution of the pandemic, and the sanitary policies implemented, as well as the challenges to face the next stages. Since the beginning of the pandemic, the national health emergency was declared, the national emergency system was launched and a Coronavirus Fund was created to finance the required interventions. An outbreak mitigation strategy was implemented by recommending non-mandatory physical distancing. Likewise, the increase in diagnostic testing capacity through national developments, the management of suspected cases at the household level, and the implementation of telemedicine stand out. There is currently little community circulation of the virus. The largest increases in the number of cases have occurred mainly in clusters, institutional agglomerations, and small cities. In all these situations, index cases and contacts were quickly identified. An important role is attributed to the participation of the academic scientific community and the epidemiological surveillance system of the Ministry of Health, which has made it possible to effectively manage the outbreaks through surveillance and active search for cases. © 2020 Academia Nacional de Medicina. All rights reserved.

Social and professional consequences of COVID-19 lockdown in patients with multiple sclerosis from two very different populations. / Consecuencias sociolaborales del confinamiento por la COVID-19 en pacientes con esclerosis múltiple en dos poblaciones muy diferentes.

The global lockdown measures implemented due to the COVID-19 pandemic have nearly always had negative consequences for patients with multiple sclerosis (MS). OBJECTIVE: We compared the social and professional effects of confinement on patients with MS in 2 very different populations, from Spain and China. METHODS: Questionnaires were administered to a group of patients with MS who consulted at the MS unit of Vithas hospital (DINAC Foundation) in Seville, and patients with MS attended in several provinces of China in April 2020, with the aim of analysing the differences and similarities between populations in the social and professional effects of confinement. To this end, a database was created and subsequently analysed. RESULTS: The Chinese population includes a higher proportion of younger patients and no differences were identified regarding sex. Most of the variables studied behaved in the same way in both patient populations. Spanish patients presented a lesser impact (30.7%) on their socio-economic situation than Chinese patients (44%) (P < .05). There were no significant differences between populations in the remaining variables. Social networks were widely used in the majority of patients from both populations. CONCLUSIONS: The social and professional consequences of the pandemic were very similar in both groups; the use of social networks and family support was also similar. Spanish patients seem to present greater economic stability, perhaps due to the social support they receive.

Social and professional consequences of COVID-19 lockdown in patients with multiple sclerosis from 2 very different populations

The confinement due to the global COVID-19 pandemic has almost had negative consequences in patients with Multiple Sclerosis (MS). Objective We wanted to compare the socio-labor effect of confinement in two populations as different as Spain and China, in patients with MS. Method Questionnaires were applied to a group of MS patients who have been reviewed in the MS unit of the Vithas hospital (DINAC Foundation) in Seville, and MS patients attended in various provinces of China during the month of April 2020, with the aim of analyzing the differences and similarities of the socio-labor effect between both populations. To carry out this analysis, a database was created and subsequently analyzed. Results The Chinese population has a higher proportion of younger patients and there is no difference regarding gender. Most of the variables studied behaved the same way in both Spanish and Chinese MS patients. Spanish patients had less impact (30.7%) on their socio-economic situation than Chinese (44%), p < 0.05. There were no important differences in the rest of the variables between the two populations. Social networks were widely used in the majority of patients in both populations. Conclusions