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Background and Objectives: New investigations have detected an enhanced probability for women to develop menstrual cycle alterations after anti-COVID-19 vaccination. Moreover, given that the protective immunity provided by anti-COVID-19 vaccination appears to wane quickly, booster vaccination has been recommended. Nonetheless, whether adverse events arise from such repeated immunization has not been studied. Materials and Methods: We studied the incidence of menstrual cycle alterations, the quantity of menstrual cycle alterations per subject, and of altered menstrual cycles in nonpregnant women of fertile age after anti-COVID-19 vaccination in a cohort of vaccinated female subjects by the means of a standardized questionary that was applied via telephone calls each month. Subjects that received up to four doses were studied for 6 months after each dose. We calculated the odds ratio for enhanced incidence, as well as quadratic functions for the tendencies. A sensitivity analysis excluding subjects taking hormonal birth control and those with polycystic ovary syndrome was performed. Results: Anti-COVID-19 vaccination enhanced the probability to develop menstrual cycle alterations (OR 1.52, CI at 95% 1.2-1.8, p < 0.0001) and, interestingly, such a tendency was enhanced when subjects received more doses (R2 = 0.91). Furthermore, the same trends repeated for the quantity of alterations per subject, and of altered cycles. Such an effect was further demonstrated to be independent upon the vaccine brand being applied, the birth control status, and the diagnosis of polycystic ovary syndrome. Conclusions: Vaccination is the most cost-effective measure for primary prevention and is considered to be safe. Nonetheless, in this article, we show data that suggest that repeated vaccination of adult female subjects may lead to an enhanced incidence of menstrual cycle-related adverse events, quantity of alterations per subject, and altered cycles. We therefore think that the development of new vaccine formulations that produce longer-lasting immunity is of paramount importance to reduce the potential for dose accumulation-dependent enhanced risk.
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Vacunas contra la COVID-19 , COVID-19 , Ciclo Menstrual , Humanos , Femenino , Adulto , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Ciclo Menstrual/efectos de los fármacos , COVID-19/prevención & control , SARS-CoV-2/inmunología , Vacunación/métodos , Vacunación/efectos adversos , Trastornos de la Menstruación/epidemiología , Estudios de Cohortes , Inmunización Secundaria/métodos , Incidencia , Adulto JovenRESUMEN
Prognostic scales may help to optimize the use of hospital resources, which may be of prime interest in the context of a fast spreading pandemics. Nonetheless, such tools are underdeveloped in the context of COVID-19. In the present article we asked whether accurate prognostic scales could be developed to optimize the use of hospital resources. We retrospectively studied 467 files of hospitalized patients after COVID-19. The odds ratios for 16 different biomarkers were calculated, those that were significantly associated were screened by a Pearson's correlation, and such index was used to establish the mathematical function for each marker. The scales to predict the need for hospitalization, intensive-care requirement and mortality had enhanced sensitivities (0.91 CI 0.87-0.94; 0.96 CI 0.94-0.98; 0.96 CI 0.94-0.98; all with p < 0.0001) and specificities (0.74 CI 0.62-0.83; 0.92 CI 0.87-0.96 and 0.91 CI 0.86-0.94; all with p < 0.0001). Interestingly, when a different population was assayed, these parameters did not change considerably. These results show a novel approach to establish the mathematical function of a marker in the development of highly sensitive prognostic tools, which in this case, may aid in the optimization of hospital resources. An online version of the three algorithms can be found at: http://benepachuca.no-ip.org/covid/index.php.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudios Retrospectivos , Unidades de Cuidados Intensivos , Hospitalización , Cuidados Críticos , Biomarcadores , ProbabilidadRESUMEN
Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Proteína C-Reactiva/análisis , COVID-19/mortalidad , COVID-19/patología , Relación Dosis-Respuesta a Droga , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Oportunidad Relativa , Estudios Retrospectivos , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
The off-label use of antiviral and antimalarial drugs has been considered by many researchers as a fast and relatively safe alternative to provide therapeutic options to treat COVID-19, but the assessment of such drug-specific effectiveness in this regard is far from complete. Especially, the current body of knowledge about COVID-19 therapeutics needs more data regarding drug effectiveness and safety in the severely ill patients with comorbidities. In the present article, we retrospectively analyze data from 61 patients that received treatment with chloroquine, lopinavir/ritonavir, both drugs administered together, or a standard treatment with no antiviral drugs, and the study was carried in severely ill patients. We found that either drug is ineffective at treating COVID-19, as they are not able to reduce hospitalization length, mortality, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-Dimer, or ferritin, or to enhance gasometric parameters, lymphocytes, total leukocytes, and neutrophil levels, whereas both drugs administered together decrease circulating lymphocytes, increase LDH and ferritin levels, and more importantly, enhance mortality. In this way, our results show that both drugs are ineffective and even potentially harmful alternatives against SARS-CoV-2.
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Tratamiento Farmacológico de COVID-19 , Cloroquina/efectos adversos , Cloroquina/uso terapéutico , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Antivirales/efectos adversos , Antivirales/uso terapéutico , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2/efectos de los fármacos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Antimicrobial resistance (AR) is one of the most important public health challenges worldwide as it represents a serious complication that is able to increase the mortality, morbidity, disability, hospital stay and economic burden related to infectious diseases. As such, the spread of AR-pathogens must be considered as an emergency, and interdisciplinary approaches must be undertaken in order to develop not only drugs, but holistic strategies to undermine the epidemic and pathogenic potentials of multi-drug resistant (MDR) pathogens. One of such approaches has focused on the use of antimicrobial nanoparticles (ANPs), as they have demonstrated to possess strong antimicrobial effects on MDR pathogens. On the other hand, the ability of bacteria to develop resistance to such agents is minimal. In this way, ANPs may seem a good choice for the development of new drugs, but there is no certainty about their safety, which may delay its translation to the clinical setting. As MDR pathogens are quickly becoming more prevalent and drug development is slow and expensive, there is an increasing need for the rapid development of new strategies to control such agents. We hereby explore the possibility of designing ANP-based devices such as surgical masks and fabrics, wound dressings, catheters, prostheses, dentifrices, water filters, and nanoparticle-coated metals to exploit the potential of such materials in the combat of MDR pathogens, with a good potential for translation into the clinical setting.
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Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. In such a setting, the establishment of an effective therapy to treat this condition has been elusive, perhaps because the experimental treatments have been conceived to block just one of the many pathogenic pathways of the disease, or because they thwart the tissue-repairing phase of the syndrome. Either way, we think that a discussion about the pathophysiology of the disease and the mechanisms of action of some drugs may shed some clarity on the topic.
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Isquemia Miocárdica/patología , Isquemia Miocárdica/terapia , Daño por Reperfusión/patología , Daño por Reperfusión/terapia , Animales , Humanos , Inmunidad Innata , Terapia de Inmunosupresión , Inflamación , Mediadores de Inflamación , Isquemia , Ratones , Infarto del Miocardio/terapia , Reperfusión Miocárdica , Daño por Reperfusión Miocárdica/prevención & control , Fenotipo , Células TH1/citología , Células Th2/citologíaRESUMEN
A negative correlation between the geographical distribution of autoimmune diseases and helminth infections has been largely associated in the last few years with a possible role for such type of parasites in the regulation of inflammatory diseases, suggesting new pathways for drug development. However, few helminth-derived immunomodulators have been tested in experimental autoimmune encephalomyelitis (EAE), an animal model of the human disease multiple sclerosis (MS). The immunomodulatory activities of Taenia crassiceps excreted/secreted products (TcES) that may suppress EAE development were sought for. Interestingly, it was discovered that TcES was able to suppress EAE development with more potency than dexamethasone; moreover, TcES treatment was still effective even when inoculated at later stages after the onset of EAE. Importantly, the TcES treatment was able to induce a range of Th2-type cytokines, while suppressing Th1 and Th17 responses. Both the polyclonal and the antigen-specific proliferative responses of lymphocytes were also inhibited in EAE-ill mice receiving TcES in association with a potent recruitment of suppressor cell populations. Peritoneal inoculation of TcES was able to direct the normal inflammatory cell traffic to the site of injection, thus modulating CNS infiltration, which may work along with Th2 immune polarization and lymphocyte activation impairment to downregulate EAE development.
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Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Helmintos/química , Factores Inmunológicos/uso terapéutico , Animales , Proliferación Celular/efectos de los fármacos , Sistema Nervioso Central/efectos de los fármacos , Sistema Nervioso Central/metabolismo , Encefalomielitis Autoinmune Experimental/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Factores Inmunológicos/química , Ratones , Ratones Endogámicos BALB C , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Taenia/química , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Células Th17/efectos de los fármacos , Células Th17/metabolismoRESUMEN
Taenia crassiceps is a cestode parasite of rodents (in its larval stage) and canids (in its adult stage) that can also parasitize immunocompromised humans. We have studied the immune response elicited by this helminth and its antigens in mice and human cells, and have discovered that they have a strong capacity to induce chronic Th2-type responses that are primarily characterized by high levels of Th2 cytokines, low proliferative responses in lymphocytes, an immature and LPS-tolerogenic profile in dendritic cells, the recruitment of myeloid-derived suppressor cells and, specially, alternatively activated macrophages. We also have utilized the immunoregulatory capabilities of this helminth to successfully modulate autoimmune responses and the outcome of other infectious diseases. In the present paper, we review the work of others and ourselves with regard to the immune response induced by T. crassiceps and its antigens, and we compare the advances in our understanding of this parasitic infection model with the knowledge that has been obtained from other selected models.
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Antígenos Helmínticos/inmunología , Autoinmunidad , Activación de Macrófagos , Macrófagos/inmunología , Taenia/inmunología , Teniasis/inmunología , Células Th2/inmunología , Adulto , Animales , Citocinas/inmunología , Células Dendríticas/inmunología , Humanos , RatonesRESUMEN
Macrophages are innate immune cells derived from monocytes, which, in turn, arise from myeloid precursor cells in the bone marrow. Macrophages have many important roles in the innate and adaptive immune response, as well as in tissue homeostasis. Two major populations have been defined: The classically activated macrophages that respond to intracellular pathogens by secreting proinflammatory cytokines and reactive oxygen species and alternatively activated macrophages which are induced during Th2 responses displaying anti-inflammatory activities. Both macrophage populations are central players in diabetes, the first one triggering inflammatory responses which initiates insulitis and pancreatic ß cell death during type 1 diabetes, whereas the second population decreases hyperglycemia, insulitis, and inflammation in the pancreas, thereby negatively regulate type 1 diabetes. Obesity is an important factor in the development of type 2 diabetes; classically activated macrophages are a dominant cell population involved in the establishment of the inflammatory profile, insulin resistance, and activation of inflammatory signals during the development and progression of this disease. In contrast, alternatively activated macrophages regulate the release of proinflammatory cytokines, attenuating adipose tissue inflammation. Here, we review the advantages and disadvantages of these two macrophage populations with regard to their roles in types 1 and 2 diabetes.