Molecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1ß, INF-α and INF-ß, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction.

Molecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2

Coronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1β, INF-α and INF-β, increasing the systemic and tissue inflammatory state;(b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species;and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction.

Leukocyte metabolism in obese type 2 diabetic individuals associated with COVID-19 severity.

Recent studies show that the metabolic characteristics of different leukocytes, such as, lymphocytes, neutrophils, and macrophages, undergo changes both in the face of infection with SARS-CoV-2 and in obesity and type 2 diabetes mellitus (DM2) condition. Thus, the objective of this review is to establish a correlation between the metabolic changes caused in leukocytes in DM2 and obesity that may favor a worse prognosis during SARS-Cov-2 infection. Chronic inflammation and hyperglycemia, specific and usual characteristics of obesity and DM2, contributes for the SARS-CoV-2 replication and metabolic disturbances in different leukocytes, favoring the proinflammatory response of these cells. Thus, obesity and DM2 are important risk factors for pro-inflammatory response and metabolic dysregulation that can favor the occurrence of the cytokine storm, implicated in the severity and high mortality risk of the COVID-19 in these patients.

SARS-COV-2 Variants: Differences and Potential of Immune Evasion.

The structural spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) plays an essential role in infection and is an important target for neutralizing antibody recognition. Mutations in the S gene can generate variants of concern (VOCs), which improve "viral fitness" through selective or survival advantages, such as increased ACE-2 receptor affinity, infectivity, viral replication, higher transmissibility, resistance to neutralizing antibodies and immune escape, increasing disease severity and reinfection risk. Five VOCs have been recognized and include B.1.1.7 (U.K.), B.1.351 (South Africa), P.1 (Brazil), B.1.617.2 (India), and B.1.1.529 (multiple countries). In this review, we addressed the following critical points concerning VOCs: a) characteristics of the SARS-CoV-2 VOCs with mutations in the S gene; b) possible evasion of variants from neutralizing antibodies generated through vaccination, previous infection, or immune therapies; c) potential risk of new pandemic waves induced by the variants worldwide; and d) perspectives for further studies and actions aimed at preventing or reducing the impact of new variants during the current COVID-19 pandemic.

A simple mathematical model for the evaluation of the long first wave of the COVID-19 pandemic in Brazil.

We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.

COVID-19 Pandemic in Brazil: History, Characteristics, and Evolution.

This chapter describes the eruption and spread of the SARS-COV-2 virus throughout Brazil. We also describe the governmental measures used to combat the virus, the regional influences impacting viral spreading, and the prevalence of the disease in different Brazilian subpopulations. It is hoped that such information will contribute to the control of the virus and help to prepare the region for future pandemics.

4-Aminoquinoline compounds from the Spanish flu to COVID-19.

In 1918, quinine was used as one of the unscientifically based treatments against the H1N1 virus during the Spanish flu pandemic. Originally, quinine was extracted from the bark of Chinchona trees by South American natives of the Amazon forest, and it has been used to treat fever since the seventeenth century. The recent COVID-19 pandemic caused by Sars-Cov-2 infection has forced researchers to search for ways to prevent and treat this disease. Based on the antiviral potential of two 4-aminoquinoline compounds derived from quinine, known as chloroquine (CQ) and hydroxychloroquine (HCQ), clinical investigations for treating COVID-19 are being conducted worldwide. However, there are some discrepancies among the clinical trial outcomes.Thus, even after one hundred years of quinine use during the Spanish flu pandemic, the antiviral properties promoted by 4-aminoquinoline compounds remain unclear. The underlying molecular mechanisms by which CQ and HCQ inhibit viral replication open up the possibility of developing novel analogs of these drugs to combat COVID-19 and other viruses.

Relationship between children physical activity, inflammatory mediators and lymphocyte activation: possible impact of social isolation (COVID-19).

OBJECTIVE: Lifestyle and body composition may be simultaneously responsible for immune response modulation. This study aimed to compare plasmatic adipokines concentration and lymphocyte cytokine production in children with different daily steps (DS) range, as well as to discuss the potential negative impact of the social isolation during COVID-19 pandemic in this context. DS can be a useful and low-cost way of monitoring children's health status. STUDY DESIGN: Fifty children were classified into clusters based in DS measured by pedometer: Sedentary Group (DS = 9338 ± 902 steps) and Active Group (DS = 13,614 ± 1003 steps). Plasma and lymphocytes were isolated and cultured to evaluate cytokine production. RESULTS: Sedentary group presented lower adiponectin (7573 ± 232 pg/mL), higher leptin (16,250 ± 1825 pg/mL) plasma concentration, and higher lymphocyte production of IL-17, IFN-gamma, TNF-, IL-2 in relation to active group, suggesting predominance of Th1 response. Otherwise, the active group presented higher lymphocyte supernatant concentration of IL-10 and higher regulatory T cell (Treg) percentage. CONCLUSION: These results indicate that lymphocytes of children performing higher DS have an anti-inflammatory profile, especially of Treg. Besides, the prolonged social isolation in children during the COVID-19 pandemic, limiting physical mobility and exercise, reduces DS and increases adiposity, which could impair the immune system function and raise the susceptibility to inflammatory diseases.