A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection

The study titled “A Comprehensive SARS-CoV-2 and COVID-19 Review” provides an extensive analysis of the various impacts of SARS-CoV-2 and its resulting diseases, COVID-19 and Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as Long COVID-19. As of January 13, 2023, COVID-19 has led to over 671 million cases and more than 6.71 million deaths worldwide. The pandemic’s impact has been far-reaching, affecting multiple organ systems and leading to a variety of long-term health issues​​.

Key Insights from the Study:

  1. Metabolic Adaptations: SARS-CoV-2 infection induces significant shifts in metabolic and biochemical pathways, affecting oxidative phosphorylation and the tricarboxylic acid (TCA) cycle. These changes result in decreased mitochondrial function and increased glycolysis, leading to systemic effects, including tissue remodeling and shifts in whole-body metabolism​​.
  2. Humoral Adaptations: The study discusses the role of humoral factors like bradykinin, angiotensin, ACE, and ACE2 in the renin-angiotensin system (RAS), which are affected by SARS-CoV-2 infection. Changes in these factors can lead to cardiovascular symptoms seen in COVID-19 patients​​.
  3. Exosomes in SARS-CoV-2 Infection: Exosomes, extracellular vesicles that carry cellular components, are altered during SARS-CoV-2 infection. They may carry viral material and impact distant cells, contributing to inflammation and immune responses. Studies indicate that exosomes from COVID-19 patients show different profiles based on disease severity, potentially affecting endothelial cells and other cell types systemically​​.
  4. Roles of the Non-Coding Transcriptome: Non-coding RNAs like microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) play significant roles in regulating the viral replicative cycle and cellular antiviral responses. For instance, miRNAs can repress gene expression relevant to COVID-19 pathophysiology, and lncRNAs can regulate immune-related pathways. CircRNAs related to SARS-CoV-2 infection have been detected in the peripheral blood, suggesting their potential as biomarkers​​.
  5. Cardiovascular Adaptations: SARS-CoV-2 infection affects the cardiovascular system, with symptoms ranging from mild respiratory symptoms to severe respiratory and cardiac failure. The virus can directly infect cardiovascular cells and lead to myocardial injury, endothelial cell infection, thrombosis, and inflammation. These molecular-level changes can result in various cardiovascular complications and need further investigation​​.
  6. Immune System Adaptations: SARS-CoV-2 activates both the innate and adaptive immune systems. The virus can cause neutrophil infiltration and inflammation in the lungs, dysregulate type 1 interferon signaling, and lead to immune cell infiltration in various organs. These immune responses contribute to lung damage, inflammation, and other organ dysfunctions​​.
  7. Organ Alterations from SARS-CoV-2 Infection: The virus affects multiple organ systems, causing multi-organ dysfunction. Neurological, psychiatric, gastrointestinal, and other systemic symptoms have been reported, along with long-term impairments in various organs. The study highlights the need for further research to understand these organ alterations and their underlying biochemical pathways​​.
  8. Long COVID-19 (PASC): Long-term symptoms post-SARS-CoV-2 infection, known as PASC or Long COVID-19, include lung fibrosis, cardiovascular issues, chronic fatigue, and neurological symptoms. The study emphasizes the importance of understanding the systemic effects of PASC, its biological mechanisms, and developing treatments for functional recovery​​.

In conclusion, the study underscores the complexity and dynamics of COVID-19, highlighting the intricate interplay between various biochemical pathways and organ systems affected by SARS-CoV-2 infection. It also points out the gaps in current knowledge and the need for further research to develop effective treatments and interventions​​.

Read More: https://www.nature.com/articles/s41431-023-01462-1

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