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Background COVID-19 became a pandemic disease in 2020, with multisystem involvement and high renal morbidity during the acute phase. Some affected patients began to present new or persistent symptoms in a condition known as Long COVID. The study aimed to evaluate renal function using clinical and laboratory findings, and to establish the frequency and staging of renal function decline in Long COVID patients, as well as the associated factors. Methods This is a cross-sectional observational study that selected participants from a Long COVID clinical care program between 2020 and 2022. Results A total of 246 patients were selected for this study, and renal function decline was found in 83 (33.7%). Patients over 60 years (29.6%) and those who developed glycaemic alterations (41.8%) exhibited a higher prevalence of renal outcomes in long COVID. Some laboratory test as LDH levels and glycated hemoglobin seems to have a statistic relation with a decrease in renal function ( p  < 0.05). Conclusion A decline in renal function was common in patients with Long COVID in this study, and older age and glycaemic alterations were relevant to this condition. Some laboratory markers can be used to predict this outcome.

Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host-pathogen association in organ-specific immune responses.

In the history of yellow fever (YF) outbreaks in Brazil, howler monkeys (Alouatta sp.) and marmosets (Callithrix sp.) have been among the most affected genera, exhibiting significant hepatic injuries similar to those seen in humans. However, limited information exists regarding yellow fever virus (YFV) infection in their central nervous system (CNS). To address this gap, an epidemiological study was conducted to assess tissue changes, viral detection, and cytokine profiles in the brains of both neotropical primate species when they are naturally infected with YFV. A total of 22 brain samples from these species (8 from Alouatta sp. and 14 from Callithrix sp.) showing infection with YFV in the liver via immunohistochemistry (IHC) were selected. From them, YFV antigen detection occurred in 35.7% (5/14) of Callithrix sp. brain samples and 87.5% (7/8) of Alouatta sp. samples, with a higher frequency of viral antigen quantification in Callithrix sp. Both species exhibited similar CNS lesions, characterized by congestion, low hemorrhage, limited inflammatory infiltration interstitial and perivascular edema associated with neuronal degeneration, neurophagy, and higher cell death (necrosis and apoptosis) quantification. Pro- and anti-inflammatory cytokine profiles were balanced, with TNF-α and IL-1β playing a key role in inflammation, while IL-10 and IL-13 exhibited a prominent role in immunomodulation, suggesting an anti-inflammatory modulation typical of flaviviruses occurs. This study demonstrates that YFV can induce CNS lesions in neotropical primates, establishing it as a secondary target of viral tropism. These findings highlight the importance of collecting nervous tissue during epizootics, particularly in Callithrix sp., as such tissue is often overlooked despite its critical role in disease monitoring.

Necroptosis is a regulated form of cell death implicated in several pathological conditions, including viral infections. In this study, we investigated the expression and correlation of necroptosis markers MLKL, RIP1 and RIP3 in human liver tissue from fatal cases of yellow fever (YF) using immunohistochemistry (IHC). The liver samples were obtained from 21 YF-positive individuals and five flavivirus-negative controls with preserved liver parenchymal architecture. The cases underwent histopathological analysis, followed by tissue immunostaining with the immunohistochemical method of streptavidin–biotin peroxidase. Using the in situ method, we evaluated the centrilobular zone (Z3), midzonal zone (Z2), periportal zone and portal tract (PT) of human liver parenchyma with markers for necroptosis, RIPK1, RIPK3 and MLKL. A quantitative analysis revealed a significantly higher expression of MLKL, RIP1 and RIP3 in the liver parenchyma of YF cases compared to controls in different zones (Z3, Z2, Z1) and portal tracts (PTs) of the liver, especially in zone 2. Immunostaining confirmed the localization of MLKL, RIP1 and RIP3 in hepatocytes and inflammatory infiltrates, highlighting their involvement in the pathogenesis of YF. A Pearson correlation analysis demonstrated significant correlations among necroptosis markers, which indicates their coordinated regulation during YF-induced liver injury.

Macrophages in the kidney play a pathogenic role in inflammation and fibrosis. Our study aimed to understand the polarisation of the M1 and M2 phenotypic profiles of macrophages in injured kidney tissue retrieved from fatal cases of yellow fever virus (YFV). A total of 11 renal tissue biopsies obtained from patients who died of yellow fever (YF) were analysed. To detect antibodies that promote the classical and alternative pathways of macrophage activation, immunohistochemical analysis was performed to detect CD163, CD68, inducible nitric oxide synthase (iNOS), arginase 1, interleukin (IL)-4, IL-10, interferon (IFN)-γ, IFN-β, tumour necrosis factor (TNF)-α, IL-13, and transforming growth factor (TGF)-β. There was a difference in the marker expression between fatal cases of YFV and control samples, with increased expression in the cortical region of the renal parenchyma. The immunoexpression of CD68 and CD163 receptors suggests the presence of activated macrophages migrating to infectious foci. The rise in IL-10, IL-4, and IL-13 indicated their potential role in the inactivation of the inflammatory macrophage response and phenotypic modulation of M2 macrophages. The altered expression of IFN-γ and IFN-β demonstrates the importance of the innate immune response in combating microorganisms. Our findings indicate that the polarisation of M1 and M2 macrophages plays a vital role in the renal immune response to YFV.

Yellow fever (YF) may cause lesions in different organs. There are no studies regarding the in situ immune response in the human lung and investigating immunopathological aspects in fatal cases can help to better understand the evolution of the infection. Lung tissue samples were collected from 10 fatal cases of human yellow fever and three flavivirus-negative controls who died of other causes and whose lung parenchymal architecture was preserved. In YFV-positive fatal cases, the main histopathological changes included the massive presence of diffuse alveolar inflammatory infiltrate, in addition to congestion and severe hemorrhage. The immunohistochemical analysis of tissues in the lung parenchyma showed significantly higher expression of E-selectin, P-selectin, ICAM-1, VCAM-1 in addition to cytokines such as IL-4, IL-10, IL-13, TNF- α, IFN-γ and TGF-β compared to the negative control. The increase in immunoglobulins ICAM-1 and VCAM-1 results in strengthening of tissue transmigration signaling. E-selectin and P-selectin actively participate in this process of cell migration and formation of the inflammatory infiltrate. IFN-γ and TNF-α participate in the process of cell injury and viral clearance. The cytokines IL-4 and TGF-β, acting in synergism, participate in the process of tissue regeneration and breakdown. The anti-inflammatory cytokines IL-4, IL-10 and IL-13 also act in the reduction of inflammation and tissue repair. Our study indicates that the activation of the endothelium aggravates the inflammatory response by inducing the expression of adhesion molecules and cytokines that contribute to the rolling, recruitment, migration and eliciting of the inflammatory process in the lung parenchyma, contributing to the fatal outcome of the disease.

Leprosy is a chronic infectious disease whose evolution involves complex immune mechanisms of the host that influence the clinical presentation of the disease. For many years, the main interpretation of the host defense response was based on characterization of the established immune paradigm between T helper (Th) 1 and Th2 lymphocytes. However, with advances in the knowledge of immunology, new approaches have emerged along with the development of new immunological pathways that have changed the interpretation of the long-established paradigm of the polar forms of the disease, especially with the identification of new subtypes of T lymphocytes such as Th9, Th17, Th22, and Tregs. Thus, this review discusses the role of these new subtypes of T helper lymphocytes and how the development of the immune response of these cells modifies the pattern of the Th1/Th2 response in the immunopathogenesis of leprosy.

Zika virus (ZIKV) is an arbovirus that is transmitted by Aedes mosquitos. Its prototype was isolated in 1947 from serum of a sentinel Rhesus monkey (Macaca mulatta) in the Zika forest of Uganda. As a member of the genus Flavivirus, family Flaviviridae, ZIKV is enveloped and icosahedral and possesses a single-stranded, positive-sense RNA genome of approximately 10.7 kb. Epidemiologically, infection by ZIKV has become a global health concern in recent years because of the occurrence of epidemics, its speed of dissemination, routes of transmission, and the sequelae it can cause especially in newborns. At the neural level, there are still many gaps in our understanding of the mechanisms that induce ZIKV infection-associated microcephaly. However, some studies already demonstrated that underlying cell death is determinant to induce the congenital malformation. In this report, we reviewed the various mechanisms of cell injury involved in the immunopathogenesis of ZIKV infection and discussed its relationship with the death of neuronal and glial cells development and microcephaly. Keywords: ZIKV, microcephaly, neuroinflammatory response, cell death

Neurotrophins are a family of proteins that regulate different aspects of biological development and neural function and are of great importance in neuroplasticity. This group of proteins has multiple functions in neuronal cells, as well as in other cellular populations. Nerve growth factor (NGF) is a neurotrophin that is endogenously produced during development and maturation by multiple cell types, including neurons, Schwann cells, oligodendrocytes, lymphocytes, mast cells, macrophages, keratinocytes, and fibroblasts. These cells produce proNGF, which is transformed by proteolytic cleavage into the biologically active NGF in the endoplasmic reticulum. The present review describes the role of NGF in the pathogenesis of leprosy and its correlations with different clinical forms of the disease and with the phenomena of regeneration and neural injury observed during infection. We discuss the involvement of NGF in the induction of neural damage and the pathophysiology of pain associated with peripheral neuropathy in leprosy. We also discuss the roles of immune factors in the evolution of this pathological process. Finally, we highlight avenues of investigation for future research to broaden our understanding of the role of NGF in the pathogenesis of leprosy. Our analysis of the literature indicates that NGF plays an important role in the evolution and outcome of infection. The findings described here highlight an important area of investigation, as leprosy is one of the main causes of infection in the peripheral nervous system.

Background Since macrophages are one of the major cell types involved in the Mycobacterium leprae immune response, roles of the M1 and M2 macrophage subpopulations have been well defined. However, the role of M4 macrophages in leprosy or other infectious diseases caused by mycobacteria has not yet been clearly characterized. This study aimed to investigate the presence and potential role of M4 macrophages in the immunopathology of leprosy. Methods We analyzed the presence of M4 macrophage markers (CD68, MRP8, MMP7, IL-6, and TNF-α) in 33 leprosy skin lesion samples from 18 patients with tuberculoid leprosy and 15 with lepromatous leprosy by immunohistochemistry. Results The M4 phenotype was more strongly expressed in patients with the lepromatous form of the disease, indicating that this subpopulation is less effective in the elimination of the bacillus and consequently is associated with the evolution to one of the multibacillary clinical forms of infection. Conclusion M4 macrophages are one of the cell types involved in the microbial response to M. leprae and probably are less effective in controlling bacillus replication, contributing to the evolution to the lepromatous form of the disease.