The Use of the Anticoagulant Heparin and Corticosteroid Dexamethasone as Prominent Treatments for COVID-19.

COVID-19 is spreading worldwide at disturbing rates, overwhelming global healthcare. Mounting death cases due to disease complications highlight the necessity of describing efficient drug therapy strategies for severe patients. COVID-19 severity associates with hypercoagulation and exacerbated inflammation, both influenced by ACE2 downregulation and cytokine storm occurrence. In this review, we discuss the applicability of the anticoagulant heparin and the anti-inflammatory corticosteroid dexamethasone for managing severe COVID-19 patients. The upregulated inflammation and blood clotting may be mitigated by administrating heparin and its derivatives. Heparin enhances the anticoagulant property of anti-thrombin (AT) and may be useful in conjunction with fibrinolytic drugs for severe COVID-19 patients. Besides, heparin can also modulate immune responses, alleviating TNF-α-mediated inflammation, impairing IL-6 production and secretion, and binding to complement proteins and leukotriene B4 (LTB4). Moreover, heparin may present anti-SARS-CoV-2 potential once it can impact viral infectivity and alter SARS-CoV-2 Spike protein architecture. Another feasible approach is the administration of the glucocorticoid dexamethasone. Although glucocorticoid's administration for viral infection managing is controversial, there is increasing evidence demonstrating that dexamethasone treatment is capable of drastically diminishing the death rate of patients presenting with Acute Respiratory Distress Syndrome (ARDS) that required invasive mechanical ventilation. Importantly, dexamethasone may be detrimental by impairing viral clearance and inducing hyperglycemia and sodium retention, hence possibly being deleterious for diabetics and hypertensive patients, two major COVID-19 risk groups. Therefore, while heparin's multitarget capacity shows to be strongly beneficial for severe COVID-19 patients, dexamethasone should be carefully administered taking into consideration underlying medical conditions and COVID-19 disease severity. Therefore, we suggest that the multitarget impact of heparin as an anti-viral, antithrombotic and anti-inflammatory drug in the early stage of the COVID-19 could significantly reduce the need for dexamethasone treatment in the initial phase of this disease. If the standard treatment of heparins fails on protecting against severe illness, dexamethasone must be applied as a potent anti-inflammatory shutting-down the uncontrolled and exacerbated inflammation.

Gut microbiota modulation induced by Zika virus infection in immunocompetent mice.

Gut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.

Hypercoagulopathy and Adipose Tissue Exacerbated Inflammation May Explain Higher Mortality in COVID-19 Patients With Obesity.

COVID-19, caused by SARS-CoV-2, is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Several reports from around the world have identified obesity and severe obesity as one of the strongest risk factors for COVID-19 hospitalization and mechanical ventilation. Moreover, countries with greater obesity prevalence have a higher morbidity and mortality risk of developing serious outcomes from COVID-19. The understanding of how this increased susceptibility of the people with obesity to develop severe forms of the SARS-CoV-2 infection occurs is crucial for implementing appropriate public health and therapeutic strategies to avoid COVID-19 severe symptoms and complications in people living with obesity. We hypothesize here that increased ACE2 expression in adipose tissue displayed by people with obesity may increase SARS-CoV-2 infection and accessibility to this tissue. Individuals with obesity have increased white adipose tissue, which may act as a reservoir for a more extensive viral spread with increased shedding, immune activation and pro-inflammatory cytokine amplification. Here we discuss how obesity is related to a pro-inflammatory and metabolic dysregulation, increased SARS-CoV-2 host cell entry in adipose tissue and induction of hypercoagulopathy, leading people with obesity to develop severe forms of COVID-19 and also death. Taken together, it may be crucial to better explore the role of visceral adipose tissue in the inflammatory response to SARS-CoV-2 infection and investigate the potential therapeutic effect of using specific target anti-inflammatories (canakinumab or anakinra for IL-1ß inhibition; anti-IL-6 antibodies for IL-6 inhibition), anticoagulant or anti-diabetic drugs in COVID-19 treatment of people with obesity. Defining the immunopathological changes in COVID-19 patients with obesity can provide prominent targets for drug discovery and clinical management improvement.

Enzyme-Linked Immunosorbent Assay and Quantitative Reverse Transcription PCR as a Technique to Analyze Inflammation.

Inflammation is part of a defense reaction of live tissues that is triggered by pathogens, chemical reagents, trauma, and radiation. Understanding the inflammatory process triggered by Zika virus (ZIKV) is important to better understand the pathogen-host interaction. The evaluation of this process can be done using tools such as enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription PCR (RT-qPCR). Both techniques have been an indispensable tool not just for immunologists but for all interested in understanding the inflammatory process.

The Cellular Impact of the ZIKA Virus on Male Reproductive Tract Immunology and Physiology.

Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.

Potential neuroprotective and anti-inflammatory effects provided by omega-3 (DHA) against Zika virus infection in human SH-SY5Y cells.

Zika virus (ZIKV) has a strong tropism for the nervous system and has been related to post-infection neurological syndromes. Once neuronal cells are infected, the virus is capable of modulating cell metabolism, leading to neurotoxicity and cellular death. The negative effect of ZIKV in neuron cells has been characterized. However, the description of molecules capable of reversing these cytotoxic effects is still under investigation. In this context, it has been largely demonstrated that docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, is highly neuroprotective. Here, we hypothesized that DHA's neuroprotective proprieties could have an influence on ZIKV-induced neurotoxicity in SH-SY5Y cells. Our data showed that pre-treatment of SH-SY5Y cells with DHA increased the cell viability and proliferation in ZIKV-infected cells. Moreover, DHA triggered an anti-inflammatory response in those infected cells. Besides, DHA was capable of restoring mitochondria function and number in ZIKV-infected SH-SY5Y cells. In addition, cells pre-treated with DHA prior to ZIKV infection presented a lower viral load at different times of infection. Taking together, these results demonstrated that DHA has a potential anti-inflammatory and neuroprotective effect against ZIKV infection in these neuron-like cells and could be a useful tool in the treatment against this virus.