Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease
The emergence of the COVID-19 pandemic made it critical to understand the immune and inflammatory responses to the SARS-CoV-2 virus. It became increasingly recognized that the immune response was a key mediator of illness severity and that its mechanisms needed to be better understood. Early infecti...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1376654/full |
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| author | Hiam Naiditch Michael R. Betts H. Benjamin Larman Moshe Levi Avi Z. Rosenberg |
| author_facet | Hiam Naiditch Michael R. Betts H. Benjamin Larman Moshe Levi Avi Z. Rosenberg |
| author_sort | Hiam Naiditch |
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| description | The emergence of the COVID-19 pandemic made it critical to understand the immune and inflammatory responses to the SARS-CoV-2 virus. It became increasingly recognized that the immune response was a key mediator of illness severity and that its mechanisms needed to be better understood. Early infection of both tissue and immune cells, such as macrophages, leading to pyroptosis-mediated inflammasome production in an organ system critical for systemic oxygenation likely plays a central role in the morbidity wrought by SARS-CoV-2. Delayed transcription of Type I and Type III interferons by SARS-CoV-2 may lead to early disinhibition of viral replication. Cytokines such as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor α (TNFα), some of which may be produced through mechanisms involving nuclear factor kappa B (NF-κB), likely contribute to the hyperinflammatory state in patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) cells, CD8+ T-cells, and B-cells, can contribute to disease severity and may reflect direct cytopathic effects of SARS-CoV-2 or end-organ sequestration. Direct infection and immune activation of endothelial cells by SARS-CoV-2 may be a critical mechanism through which end-organ systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation and microthrombi development can be seen in the lungs and other critical organs throughout the body, such as the heart, gut, and brain. The kidney may be among the most impacted extrapulmonary organ by SARS-CoV-2 infection owing to a high concentration of ACE2 and exposure to systemic SARS-CoV-2. In the kidney, acute tubular injury, early myofibroblast activation, and collapsing glomerulopathy in select populations likely account for COVID-19-related AKI and CKD development. The development of COVID-19-associated nephropathy (COVAN), in particular, may be mediated through IL-6 and signal transducer and activator of transcription 3 (STAT3) signaling, suggesting a direct connection between the COVID-19-related immune response and the development of chronic disease. Chronic manifestations of COVID-19 also include systemic conditions like Multisystem Inflammatory Syndrome in Children (MIS-C) and Adults (MIS-A) and post-acute sequelae of COVID-19 (PASC), which may reflect a spectrum of clinical presentations of persistent immune dysregulation. The lessons learned and those undergoing continued study likely have broad implications for understanding viral infections’ immunologic and inflammatory consequences beyond coronaviruses. |
| format | Article |
| id | doaj-art-68c2f120c4fa40a6972228e4bdf93858 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-68c2f120c4fa40a6972228e4bdf938582025-02-12T07:26:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011510.3389/fimmu.2024.13766541376654Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal diseaseHiam Naiditch0Michael R. Betts1H. Benjamin Larman2Moshe Levi3Avi Z. Rosenberg4Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Pittsburgh, Pittsburgh, PA, United StatesDepartment of Microbiology and Institute of Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesInstitute for Cell Engineering, Division of Immunology, Department of Pathology, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC, United StatesDepartment of Pathology, Johns Hopkins University, Baltimore, MD, United StatesThe emergence of the COVID-19 pandemic made it critical to understand the immune and inflammatory responses to the SARS-CoV-2 virus. It became increasingly recognized that the immune response was a key mediator of illness severity and that its mechanisms needed to be better understood. Early infection of both tissue and immune cells, such as macrophages, leading to pyroptosis-mediated inflammasome production in an organ system critical for systemic oxygenation likely plays a central role in the morbidity wrought by SARS-CoV-2. Delayed transcription of Type I and Type III interferons by SARS-CoV-2 may lead to early disinhibition of viral replication. Cytokines such as interleukin-1 (IL-1), IL-6, IL-12, and tumor necrosis factor α (TNFα), some of which may be produced through mechanisms involving nuclear factor kappa B (NF-κB), likely contribute to the hyperinflammatory state in patients with severe COVID-19. Lymphopenia, more apparent among natural killer (NK) cells, CD8+ T-cells, and B-cells, can contribute to disease severity and may reflect direct cytopathic effects of SARS-CoV-2 or end-organ sequestration. Direct infection and immune activation of endothelial cells by SARS-CoV-2 may be a critical mechanism through which end-organ systems are impacted. In this context, endovascular neutrophil extracellular trap (NET) formation and microthrombi development can be seen in the lungs and other critical organs throughout the body, such as the heart, gut, and brain. The kidney may be among the most impacted extrapulmonary organ by SARS-CoV-2 infection owing to a high concentration of ACE2 and exposure to systemic SARS-CoV-2. In the kidney, acute tubular injury, early myofibroblast activation, and collapsing glomerulopathy in select populations likely account for COVID-19-related AKI and CKD development. The development of COVID-19-associated nephropathy (COVAN), in particular, may be mediated through IL-6 and signal transducer and activator of transcription 3 (STAT3) signaling, suggesting a direct connection between the COVID-19-related immune response and the development of chronic disease. Chronic manifestations of COVID-19 also include systemic conditions like Multisystem Inflammatory Syndrome in Children (MIS-C) and Adults (MIS-A) and post-acute sequelae of COVID-19 (PASC), which may reflect a spectrum of clinical presentations of persistent immune dysregulation. The lessons learned and those undergoing continued study likely have broad implications for understanding viral infections’ immunologic and inflammatory consequences beyond coronaviruses.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1376654/fullSARS-CoV-2COVID-19PASClong COVIDinflammasomeinflammation |
| spellingShingle | Hiam Naiditch Michael R. Betts H. Benjamin Larman Moshe Levi Avi Z. Rosenberg Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease Frontiers in Immunology SARS-CoV-2 COVID-19 PASC long COVID inflammasome inflammation |
| title | Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease |
| title_full | Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease |
| title_fullStr | Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease |
| title_full_unstemmed | Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease |
| title_short | Immunologic and inflammatory consequences of SARS-CoV-2 infection and its implications in renal disease |
| title_sort | immunologic and inflammatory consequences of sars cov 2 infection and its implications in renal disease |
| topic | SARS-CoV-2 COVID-19 PASC long COVID inflammasome inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1376654/full |
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