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Background: Interferons (IFNs) represent a first-line defense against viruses and other pathogens. It has been shown that an impaired and uncontrolled release of these glycoproteins can result in tissue damage and explain severe progression of coronavirus disease 2019 (COVID-19). However, their potential role in Long-COVID syndrome (LC) remains debateable. Objectives: The objective of the present study is to shed further light on the possible role of IFNs (and related genes) gene expression patterns in the progression of COVID-19 and LC patients. Methods: We carried out a multi-cohort study by analyzing the IFN gene expression patterns (using different IFN gene signatures) in five cohorts of acute COVID-19 (n = 541 samples) and LC patients (n = 188), and compared them to patterns observed in three autoimmune diseases (systemic lupus erythematous [n = 242], systemic sclerosis [n = 91], and Sjögren's syndrome [n = 282]). Results: The data show that, while the interferon signatures are strongly upregulated in severe COVID-19 patients and autoimmune diseases, it decays with the time from symptoms onset and in LC patients. Differential pathway analysis of IFN-related terms indicates an over activation in autoimmune diseases (IFN-I/II) and severe COVID-19 (IFN-I/II/III), while these pathways are mostly inactivated or downregulated in LC (IFN-I/III). By analyzing six proteomic LC datasets, we did not find evidence of a role of IFNs in this condition. Conclusion: Our findings suggest a potential role of cytokine exhaustion mediated by IFN gene expression inactivation as a possible driver of LC. [ABSTRACT FROM AUTHOR]

Jose Gómez-Rial,1,2 Irene Rivero-Calle,1,3 Antonio Salas,1,4 Federico Martinón-Torres1,3 1Genetics, Vaccines, Infectious Diseases Research Group (GENVIP), Health Research Institute Santiago (IDIS), Hospital Clínico Universitario Santiago de Compostela (SERGAS), Galicia 15706, Spain; 2Immunology Laboratory, Clinical Laboratory, Hospital Clínico Universitario Santiago de Compostela (SERGAS), Galicia 15706, Spain; 3Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago De Compostela, Galicia 15706, Spain; 4Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela, and GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia, 15706, SpainCorrespondence: Jose Gómez-Rial Tel +34 981 950 379Email jose.gomez.rial@sergas.escov-Abstract: Emerging studies from SARS-CoV-2-infected patients indicate a preponderant role of monocytes/macrophages in the pathogenesis of this viral infection, in a similar way to that previously observed in other coronavirus outbreaks (SARS and MERS). The clinical presentation of severe patients resembles viral-associated hemophagocytic syndrome, a rare condition previously seen during lethal influenza pandemics and during previous SARS and MERS coronavirus outbreaks. SARS-CoV-2 infection triggers an over-exuberant inflammatory response due to the development of a cytokine storm and the depletion of the adaptative immune compartment, which may prelude sepsis in many cases. The present review summarizes past evidence on the role of monocytes/macrophages in previous coronavirus outbreaks and the emerging knowledge on their role in COVID-19 pathogenesis. Treatment strategies incorporating the blockade of migration and differentiation of monocyte-macrophage, such as granulocyte macrophage-colony stimulating factor inhibitors, might enhance the promising results seen so far with selective cytokine blockade.Keywords: monocyte/macrophage, COVID-19 infection, anti-GM-CSF, coronavirus

Irene Rivero-Calle,1,2 Peter Francis Raguindin,2 Jose Gómez-Rial,2 Carmen Rodriguez-Tenreiro,2 Federico Martinón-Torres1,2 1Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, Galicia, Spain; 2Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Hospital Clínico Universitario and Universidad de Santiago de Compostela (USC), Galicia, SpainCorrespondence: Federico Martinón-TorresTranslational Pediatrics and Infectious Diseases Section, Pediatrics Department, Hospital Clínico Universitario de Santiago de Compostela, Travesía da Choupana, s/n, Santiago de Compostela 15706, SpainEmail Federico.Martinon.Torres@sergas.esAbstract: Invasive meningococcal disease (IMD) is a major public health concern because of its high case fatality, long-term morbidity, and potential to course with outbreaks. IMD caused by Nesseira meningitidis serogroup B has been predominant in different regions of the world like Europe and only recently broadly protective vaccines against B serogroup have become available. Two protein-based vaccines, namely 4CMenB (Bexsero®) and rLP2086 (Trumenba®) are currently licensed for use in different countries against MenB disease. These vaccines came from a novel technology on vaccine design (or antigen selection) using highly specific antigen targets identified through whole-genome sequence analysis. Moreover, it has the potential to confer protection against non-B meningococcus and against other Neisserial species such as gonococcus. Real-world data on the vaccine-use are rapidly accumulating from the UK and other countries which used the vaccine for control of outbreak or as part of routine immunization program, reiterating its safety and efficacy. Additional data on real-life effectiveness, long-term immunity, and eventual herd effects, including estimates on vaccine impact for cost-effectiveness assessment are further needed. Given the predominance of MenB in Europe and other parts of the world, these new vaccines are crucial for the prevention and public health control of the disease, and should be considered.Keywords: meningococcal disease, invasive meningococcal disease, meningococcal B, vaccine development, vaccine effectiveness, epidemiology

José Gómez-Rial,1,2 Sonia Sánchez-Batán,2 Irene Rivero-Calle,1,3 Jacobo Pardo-Seco,1 José María Martinón-Martínez,1 Antonio Salas,1,4,5 Federico Martinón-Torres1,3 1Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría (GENVIP), Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago de Compostela (SERGAS), Galicia, Spain; 2Laboratorio de Inmunología, Servicio de Análisis Clínicos, Hospital Clínico Universitario de Santiago de Compostela (SERGAS), Galicia, Spain; 3Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela (SERGAS), Galicia, Spain; 4Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forense, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain; 5GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago de Compostela (SERGAS), Galicia, Spain Abstract: The landscape of rotavirus (RV) infection has changed substantially in recent years. Autoimmune triggering has been added to clinical spectrum of this pathology, which is now known to be much broader than diarrhea. The impact of RV vaccines in these other conditions is becoming a growing field of research. The importance of host genetic background in RV susceptibility has been revealed, therefore increasing our understanding of vaccine effectiveness and giving some clues about the limited efficacy of RV vaccines in low-income settings. Also, interaction of RV with intestinal microbiota seems to play a key role in the process of infection vaccine effect. This article reviews current findings on the extraintestinal impact of RV infection and their widening clinical picture, and the recently described mechanisms of host susceptibility to infection and vaccine effectiveness. RV infection is a systemic disease with clinical and pathophysiological implications beyond the gut. We propose an “iceberg” model for this pathology with almost hidden clinical implications away from the gastrointestinal tract and eventually triggering the development of autoimmune diseases. Impact of current vaccines is being influenced by host genetics and gut microbiota interactions and these factors must be taken into account in the development of public health programs. Keywords: rotavolution, extraintestinal, seizures, vaccines, autoimmunity

Jose Gómez-Rial,1,2 Sonia Sánchez-Batán,2 Irene Rivero-Calle,1,3 Jacobo Pardo-Seco,1 José María Martinón-Martínez,1 Antonio Salas,1,4–5 Federico Martinón-Torres1,31Grupo de Investigación en Genética, Vacunas, Infecciones y Pediatría (GENVIP), Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago de Compostela (SERGAS); 2Laboratorio de Inmunología, Servicio de Análisis Clínicos, Hospital Clínico Universitario de Santiago de Compostela (SERGAS); 3Pediatría Trasnlacional y Enfermedades Infecciossas, Departamento de Pediatría, Hospital Clínico Universitario de Santiago de Compostela (SERGAS); 4Unidade de Xenética, Instituto de Ciencias Forenses (INCIFOR), Facultade de Medicina, Universidade de Santiago de Compostela; 5GenPoB Research Group, Instituto de Investigación Sanitaria de Santiago (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), Galicia, SpainWe have read with interest the comments from Orrico-Sánchez et al1 regarding our recent paper on extraintestinal features of rotavirus (RV) infection.2 Their main concerns relate to the section dealing with the potential of RV vaccines to decrease hospitalizations due to seizures, and more specifically, the issues we raised in regards to their non-significant findings that might have been caused by the use of an overfitted statistical model.3 As our article was a general review beyond the relationship between RV and seizures, we did not have room for detailed explanations. We now take the opportunity to address Orrico-Sánchez et al's concerns.3This is in response to the Letter to the EditorView the original paper by Gómez-Rial and colleagues