Monocytes and Macrophages, Targets of Severe Acute Respiratory Syndrome Coronavirus 2: The Clue for Coronavirus Disease 2019 Immunoparalysis.
TL;DR: SARS-CoV-2 infection of macrophages induces a specific M2 transcriptional program characterized by the upregulation of M2-type molecules as mentioned in this paper. But their infection is abortive.
Abstract: Background Coronavirus disease 2019 (COVID-19) clinical expression is pleiomorphic, severity is related to age and comorbidities such as diabetes and hypertension, and pathophysiology involves aberrant immune activation and lymphopenia. We wondered if the myeloid compartment was affected during COVID-19 and if monocytes and macrophages could be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods Monocytes and monocyte-derived macrophages (MDMs) from COVID-19 patients and controls were infected with SARS-CoV-2 and extensively investigated with immunofluorescence, viral RNA extraction and quantification, and total RNA extraction followed by reverse-transcription quantitative polymerase chain reaction using specific primers, supernatant cytokines (interleukins 6, 10, and 1β; interferon-β; transforming growth factor-β1, and tumor necrosis factor-α), and flow cytometry. The effect of M1- vs M2-type or no polarization prior to infection was assessed. Results SARS-CoV-2 efficiently infected monocytes and MDMs, but their infection is abortive. Infection was associated with immunoregulatory cytokines secretion and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In vitro polarization did not account for permissivity to SARS-CoV-2, since M1- and M2-type MDMs were similarly infected. In COVID-19 patients, monocytes exhibited lower counts affecting all subsets, decreased expression of HLA-DR, and increased expression of CD163, irrespective of severity. Conclusions SARS-CoV-2 drives monocytes and macrophages to induce host immunoparalysis for the benefit of COVID-19 progression.SARS-CoV-2 infection of macrophages induces a specific M2 transcriptional program. In Covid-19 patients, monocyte subsets were decreased associated with up-expression of the immunoregulatory molecule CD163 suggesting that SARS-CoV-2 drives immune system for the benefit of Covid-19 disease progression.
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TL;DR: In this article , the authors reviewed the incidence of COVID-19-associated invasive fungal infections caused by these fungi in low-, middle- and high-income countries, evaluating the epidemiology, clinical risk factors, predisposing features of the host environment and immunological mechanisms that underlie the pathogenesis of these co-infections, set the scene for future research and development of clinical guidance.
Abstract: Coronavirus disease 2019 (COVID-19)-associated invasive fungal infections are an important complication in a substantial number of critically ill, hospitalized patients with COVID-19. Three groups of fungal pathogens cause co-infections in COVID-19: Aspergillus, Mucorales and Candida species, including Candida auris. Here we review the incidence of COVID-19-associated invasive fungal infections caused by these fungi in low-, middle- and high-income countries. By evaluating the epidemiology, clinical risk factors, predisposing features of the host environment and immunological mechanisms that underlie the pathogenesis of these co-infections, we set the scene for future research and development of clinical guidance.
91 citations
TL;DR: The pathogenesis of post-COVID syndrome is multi-factorial and more than one mechanism may be implicated in several clinical manifestations, including immune-mediated vascular dysfunction, thromboembolism, and nervous system dysfunction.
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TL;DR: In this article, SARS-CoV-2 antibodies bound to Fc receptors on macrophages and mast cells may represent two different mechanisms for antibody-dependent enhancement in patients.
Abstract: COVID-19 (SARS-CoV-2) disease severity and stages varies from asymptomatic, mild flu-like symptoms, moderate, severe, critical, and chronic disease. COVID-19 disease progression include lymphopenia, elevated proinflammatory cytokines and chemokines, accumulation of macrophages and neutrophils in lungs, immune dysregulation, cytokine storms, acute respiratory distress syndrome (ARDS), etc. Development of vaccines to severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome coronavirus (MERS-CoV), and other coronavirus has been difficult to create due to vaccine induced enhanced disease responses in animal models. Multiple betacoronaviruses including SARS-CoV-2 and SARS-CoV-1 expand cellular tropism by infecting some phagocytic cells (immature macrophages and dendritic cells) via antibody bound Fc receptor uptake of virus. Antibody-dependent enhancement (ADE) may be involved in the clinical observation of increased severity of symptoms associated with early high levels of SARS-CoV-2 antibodies in patients. Infants with multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 may also have ADE caused by maternally acquired SARS-CoV-2 antibodies bound to mast cells. ADE risks associated with SARS-CoV-2 has implications for COVID-19 and MIS-C treatments, B-cell vaccines, SARS-CoV-2 antibody therapy, and convalescent plasma therapy for patients. SARS-CoV-2 antibodies bound to mast cells may be involved in MIS-C and multisystem inflammatory syndrome in adults (MIS-A) following initial COVID-19 infection. SARS-CoV-2 antibodies bound to Fc receptors on macrophages and mast cells may represent two different mechanisms for ADE in patients. These two different ADE risks have possible implications for SARS-CoV-2 B-cell vaccines for subsets of populations based on age, cross-reactive antibodies, variabilities in antibody levels over time, and pregnancy. These models place increased emphasis on the importance of developing safe SARS-CoV-2 T cell vaccines that are not dependent upon antibodies.
83 citations
TL;DR: The role of macrophages in COVID-19 is focused on, as pathogenesis of the new coronavirus infection, especially in cases complicated by ARDS, largely depends on macrophage phenotypes and functionalities.
Abstract: Macrophages are cells that mediate both innate and adaptive immunity reactions, playing a major role in both physiological and pathological processes. Systemic SARS-CoV-2-associated complications include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome, edema, and pneumonia. These are predominantly effects of massive macrophage activation that collectively can be defined as macrophage activation syndrome. In this review we focus on the role of macrophages in COVID-19, as pathogenesis of the new coronavirus infection, especially in cases complicated by ARDS, largely depends on macrophage phenotypes and functionalities. We describe participation of monocytes, monocyte-derived and resident lung macrophages in SARS-CoV-2-associated ARDS and discuss possible utility of cell therapies for its treatment, notably the use of reprogrammed macrophages with stable pro- or anti-inflammatory phenotypes.
60 citations
TL;DR: In this article, the role of key metabolic pathways that can regulate severe acute respiratory syndrome coronavirus-2 reproduction and their association with disease severity was investigated using patient-derived multiomics data and in vitro infection assays.
54 citations
References
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TL;DR: O surto do novo coronavÃrus (COVID-19) em Wuhan, China, iniciado em dezembro de 2019, evoluiu para se tornar uma pandemia global A.
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TL;DR: A web tool called ClustVis that aims to have an intuitive user interface for the Principal Component Analysis and heatmap plots and is freely available at http://biit.cs.ut.ee/clustvis/.
Abstract: The Principal Component Analysis (PCA) is a widely used method of reducing the dimensionality of high-dimensional data, often followed by visualizing two of the components on the scatterplot. Although widely used, the method is lacking an easy-to-use web interface that scientists with little programming skills could use to make plots of their own data. The same applies to creating heatmaps: it is possible to add conditional formatting for Excel cells to show colored heatmaps, but for more advanced features such as clustering and experimental annotations, more sophisticated analysis tools have to be used. We present a web tool called ClustVis that aims to have an intuitive user interface. Users can upload data from a simple delimited text file that can be created in a spreadsheet program. It is possible to modify data processing methods and the final appearance of the PCA and heatmap plots by using drop-down menus, text boxes, sliders etc. Appropriate defaults are given to reduce the time needed by the user to specify input parameters. As an output, users can download PCA plot and heatmap in one of the preferred file formats. This web server is freely available at http://biit.cs.ut.ee/clustvis/.
2,293 citations
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1,984 citations
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