This Research Topic is the second volume of the 'Community Series in Immunometabolic Mechanisms Underlying the Severity of COVID-19'. Please see the first volume
here.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of the global outbreak of coronavirus disease 2019 (COVID-19). An important number of patients with COVID-19 are at higher risk of developing the most severe form of the disease that includes pneumonia, acute respiratory distress syndrome (ARDS), multiorgan failure, and death. Fatal cases of COVID-19 are more prevalent in patients with preexisting comorbidities such as obesity, hypertension, and type 2 diabetes (T2D). These patients also experience a cytokine storm characterized by increased levels of proinflammatory cytokines such as interleukin (IL-) 1 beta, IL-6, and tumor necrosis factor alpha (TNF-alpha), among others. However, the mechanisms by which comorbidities contribute to the cytokine storm, increasing the progression, severity, and mortality of COVID-19 are not yet fully understood. Metabolic and cardiovascular comorbidities are characterized by the presence of immunometabolic agents such as excess glucose, free-fatty acids (FFA), low-density lipoproteins (LDL), and uric acid that appear to act in synergy with immune cells to promote the inflammatory response through mechanisms still unknown in COVID-19.
Metabolic alterations also modify epigenetic programming in monocyte and macrophages that can pre-dispose patients to more severe COVID-19. Accumulating evidence indicates a highly variable scenario of the long-COVID syndrome with large individual combinations of organ failure. Further, the role of metabolic pathologies in long-COVID needs urgent investigation. In parallel, the COVID-19 outbreak is entering the post-pandemic era, and assessing the efficacy of anti-SARS-CoV-2 vaccines in people with insulin resistance, dyslipidemia, T2D, or hypertension is imperative to reveal the number of vaccine booster shots able to increase long-term antibodies in these patients. Epidemiologic studies describing the contribution of comorbidities to persistent COVID-19 severity in vaccinated subjects will be crucial to develop novel therapeutic maneuvers to prevent disease worsening.
The main goal of this Research Topic is to congregate eminent contributors in the fields of metabolic and cardiovascular diseases, immune response, acute COVID-19, long-COVID syndrome, and vaccinology to help elucidate the mechanisms of the crosstalk between the metabolic and immunological pathways that have essential effects on the adaptive and innate immune responses. This includes T cell exhaustion, antibody deficiency, cytokine storm and long-term monocyte and macrophage pathological programming, complement activity and neutrophil trafficking in patients with preexisting comorbidities experiencing COVID-19. Furthermore, we invite submissions that characterize the cell signaling pathways mediating the effect of excess glucose, FFA, LDL, uric acid, and insulin, among others on T and B lymphocytes, monocytes and macrophages, neutrophils, and basophils in patients with SARS-CoV-2 infection. We also welcome clinical trials and epidemiologic studies focused on studying the efficacy of vaccines and the number of booster shots to avoid COVID-19 progression in patients with pre-existing comorbidities.
In this Research Topic we welcome the submission of Original Research (basic and clinical studies as well as Clinical Trial) and Review articles addressing in vitro and in vivo studies focused on, but not limited to, the following potential topics:
1. Role of excess glucose, FFA, LDL, uric acid, and insulin, among others in immune cell activation and cytokine release in patients with SARS-CoV-2 infection
2. Effect of immune-metabolic agents on chemokine production and neutrophil infiltration into airway epithelium, vascular endothelium, and pancreas of patients with COVID-19
3. Profiling of immune cell subpopulations in COVID-19 patients with cardio-metabolic disorders
4. Contribution of obesity, hypertension, T2D, insulin resistance, dyslipidemia, and metabolic syndrome to vascular inflammation in patients with SARS-CoV-2 infection
5. Characterization of cell signaling pathways mediating the effect of immune-metabolic agents on immune cell activity in SARS-CoV-2 infection
6. Therapeutic targets based on inhibiting the action of immune-metabolic agents in COVID-19
7. Identification of resident cells for the long-term persistence of SARS-CoV2, and analysis of detrimental immune programs and responses in patients with in long-COVID syndrome
8. Mechanisms of pre-disposition of patients with metabolic abnormalities for the risk, severity and duration of long-COVID-19 syndrome
9. Evaluation of the efficacy of anti-SARS-CoV-2 vaccines to avoid COVID-19 progression in patients with comorbidities
10. Estimation of the accurate number of vaccine booster shots to prevent COVID-19 worsening in patients with metabolic disease
