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Understanding Viral Infection Mechanisms and Patient Symptoms for the Development of COVID-19 Therapeutics.
Choi, HM, Moon, SY, Yang, HI, Kim, KS
International journal of molecular sciences. 2021;22(4)
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The outbreak of a novel coronavirus was reported in Wuhan, in the Hubei province of China, in December 2019. This virus was officially designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of its phylogenetic and taxonomic similarities to other coronaviruses. The aim of this review was to understand the viral infection mechanisms of SARS-CoV-2, the clinical features of Covid-19 and the mechanisms through which Covid-19 can be effectively treated with existing drugs. Literature shows that: • SARS-CoV-2 is usually transmitted by inhalation or contact with infected droplets. Inhaled droplets or aerosol carrying the virus then infect and spread through the respiratory tracts. • Severe inflammatory response is a remarkable feature of Covid-19 symptoms. This is caused by delayed viral clearance, which induces chronic systemic inflammation and widespread tissue damage, even leading to cytokine storms. • The incubation period is generally 5-6 days, but it ranges from one day to as much as two weeks. • Interstitial pneumonia and subsequent acute respiratory distress syndrome are the leading causes of death in patients with Covid-19. • There is no licensed treatment for Covid-19, only a combination of antiviral and anti-inflammatory drug treatments are being used. Authors conclude that their finding may provide new insights into the development of therapeutics by understanding the various clinical and basic research studies currently underway.
Abstract
Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has become a worldwide pandemic. Symptoms range from mild fever to cough, fatigue, severe pneumonia, acute respiratory distress syndrome (ARDS), and organ failure, with a mortality rate of 2.2%. However, there are no licensed drugs or definitive treatment strategies for patients with severe COVID-19. Only antiviral or anti-inflammatory drugs are used as symptomatic treatments based on clinician experience. Basic medical researchers are also trying to develop COVID-19 therapeutics. However, there is limited systematic information about the pathogenesis of COVID-19 symptoms that cause tissue damage or death and the mechanisms by which the virus infects and replicates in cells. Here, we introduce recent knowledge of time course changes in viral titers, delayed virus clearance, and persistent systemic inflammation in patients with severe COVID-19. Based on the concept of drug reposition, we review which antiviral or anti-inflammatory drugs can effectively treat COVID-19 patients based on progressive symptoms and the mechanisms inhibiting virus infection and replication.
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Updated Review and Meta-Analysis of Probiotics for the Treatment of Clinical Depression: Adjunctive vs. Stand-Alone Treatment.
Nikolova, VL, Cleare, AJ, Young, AH, Stone, JM
Journal of clinical medicine. 2021;10(4)
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Major depressive disorder is a common, complex, and heterogeneous illness that is characterized by persistent low mood and anhedonia, and a combination of sleep disturbances, changes in appetite, feelings of worthlessness or guilt, poor concentration, and suicidal ideation. The aim of this study was to identify and evaluate all current evidence from randomised controlled trials on the efficacy of probiotics in reducing depressive symptoms among people with clinical depression. This study is a review and meta-analysis of randomised controlled trials which included seven studies for qualitative and quantitative analysis. Results demonstrate that probiotics significantly reduce depressive symptoms after eight weeks of use, but only when used in addition to an approved antidepressant. Authors conclude that their findings support the clinical use of probiotics in depressed populations and provides an insight into the mode of administration more likely to yield antidepressant effects.
Abstract
Recent years have seen a rapid increase in the use of gut microbiota-targeting interventions, such as probiotics, for the treatment of psychiatric disorders. The objective of this update review was to evaluate all randomised controlled clinical trial evidence on the efficacy of probiotics for clinical depression. Cochrane guidelines for updated reviews were followed. By searching PubMed and Web of Science databases, we identified 546 new records since our previous review. A total of seven studies met selection criteria, capturing 404 people with depression. A random effects meta-analysis using treatment type (stand-alone vs. adjunctive) as subgroup was performed. The results demonstrated that probiotics are effective in reducing depressive symptoms when administered in addition to antidepressants (SMD = 0.83, 95%CI 0.49-1.17), however, they do not seem to offer significant benefits when used as stand-alone treatment (SMD = -0.02, 95%CI -0.34-0.30). Potential mechanisms of action may be via increases in brain-derived neurotrophic factor (BDNF) and decreases in C-reactive protein (CRP), although limited evidence is available at present. This review offers stronger evidence to support the clinical use of probiotics in depressed populations and provides an insight into the mode of administration more likely to yield antidepressant effects.
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Meta-inflammaging at the crossroad of geroscience.
Chen, G, Yung, R
Aging medicine (Milton (N.S.W)). 2019;2(3):157-161
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The concept of “geroscience” represents a perspective in the understanding of the molecular underpinning of aging. Currently, seven biological processes are regarded as the underpinning of the aging process. This study is a review which focused on the link between chronic low‐grade sterile inflammation prevalent in old age and obesity‐associated metabolic inflammation. Old age, particularly in elderly adults with poor physical function or frailty, is linked to a state of chronic low‐grade sterile inflammation (inflammaging) with elevated pro‐inflammatory cytokines [a general term for the immunoregulatory cytokines that favour inflammation]. Another potential source of pro‐inflammatory cytokines in aging is adipose, or fat tissue, which can be the largest organ in obese individuals. Obesity has been linked to a low‐grade sterile chronic inflammatory state, with similarities to inflammaging, and is termed “metainflammation”. Adiposity has emerged as a major source of inflammation in both diet‐ and aging‐associated obesity, which in turn is linked to most common diseases in old age.
Abstract
Geroscience posits that selected fundamental biological processes are the foundation of age-related chronic diseases and are responsible for the decline in physical and mental function in old age. Late-life chronic low-grade inflammation ("inflammaging") and altered signal transduction pathways in metabolism have been identified as two of the key themes in the aging process. Age-related changes in the immune and metabolic responses are also recognized as playing a critical pathogenic role in most common chronic medical conditions that plague the elderly. Emerging investigations emphasize the interconnectedness of the immune and metabolic responses in aging, an area of gerontological research that can be termed "meta-inflammaging."
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Daily Intake of Fermented Milk Containing Lactobacillus casei Shirota (Lcs) Modulates Systemic and Upper Airways Immune/Inflammatory Responses in Marathon Runners.
Vaisberg, M, Paixão, V, Almeida, EB, Santos, JMB, Foster, R, Rossi, M, Pithon-Curi, TC, Gorjão, R, Momesso, CM, Andrade, MS, et al
Nutrients. 2019;11(7)
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Athletes undergoing high-intensity efforts show increased incidence of upper respiratory tract infections (URTI), both in the context of competitions and during strenuous training. The aim of this study was to evaluate the influence of the daily intake of fermented milk (containing Lactobacillus casei Shirota) on the systemic and upper airway immune/inflammatory responses before and after a race in marathon runners who previously reported upper respiratory symptoms (URS) after an exhaustive physical exercise session. The study is a double-blind randomised clinical study which recruited 42 male amateur marathon runners with an average age of 39 years. The participants were randomly separated into two groups: Lactobacillus casei Shirota group (n=20) or the placebo group (n=22). Results indicate that daily ingestion of fermented milk (containing Lactobacillus casei Shirota) was able to control both immunological and inflammatory responses in the blood and also in the upper airways mucosal of amateurs´ runners after a marathon. Authors conclude that Lactobacillus casei Shirota is able to modulate the systemic and airways immune responses post-marathon, presenting protective effects.
Abstract
BACKGROUND Although Lactobacillus casei Shirota (LcS) can benefit the immune status, the effects of LcS in the immune/inflammatory responses of marathon runners has never been evaluated. Therefore, here we evaluated the effect of daily ingestion of fermented milk containing or not LcS in the systemic and upper airway immune/inflammatory responses before and after a marathon. METHODS Forty-two male marathon runners ingested a fermented milk containing 40 billion of LcS/day (LcS group, n = 20) or placebo (unfermented milk, n = 22) during 30 days pre-marathon. Immune/inflammatory parameters in nasal mucosa and serum, as well as concentrations of secretory IgA (SIgA) and antimicrobial peptides in saliva, were evaluated before and after fermented milk ingestion, immediately, 72 h, and 14 d post-marathon. RESULTS Higher proinflammatory cytokine levels in serum and nasal mucosa, and also lower salivary levels of SIgA and antimicrobial peptides, were found immediately post-marathon in the placebo group compared to other time points and to LcS group. In opposite, higher anti-inflammatory levels and reduced neutrophil infiltration on nasal mucosa were found in the LcS group compared to other time points and to the placebo group. CONCLUSION For the first time, it is shown that LcS is able to modulate the systemic and airways immune responses post-marathon.
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Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial.
Tangpricha, V, Lukemire, J, Chen, Y, Binongo, JNG, Judd, SE, Michalski, ES, Lee, MJ, Walker, S, Ziegler, TR, Tirouvanziam, R, et al
The American journal of clinical nutrition. 2019;109(3):544-553
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Patients with cystic fibrosis (CF) have a mutation in a particular gene which results in derangements in chloride transport across epithelial surfaces, leading to abnormally thickened mucus on the surfaces of the lung, pancreas, intestines, and other organs. The aim of this study was to investigate the impact of high-dose vitamin D3 administered to adults with CF during and after an acute pulmonary exacerbation. The study is a double-blind, randomised, placebo-controlled clinical trial. Subjects were randomly assigned and stratified to one of the two groups: vitamin D (5 capsules of vitamin D3 containing 50,000 IU) or placebo (5 capsules that were identical in size, shape, and colour to the vitamin D3 capsule). Results demonstrated that high-dose vitamin D3 administration to adults with CF initiated at the time of a pulmonary exacerbation did not improve time to next pulmonary exacerbation or 1 year survival. Authors conclude that a high-dose vitamin D3 bolus, combined with maintenance therapy given to adults with CF during acute pulmonary exacerbation of CF did not improve 1 year survival or recovery of lung function.
Abstract
BACKGROUND Patients with cystic fibrosis (CF) have increased risk of vitamin D deficiency owing to fat malabsorption and other factors. Vitamin D deficiency has been associated with increased risk of pulmonary exacerbations of CF. OBJECTIVES The primary objective of this study was to examine the impact of a single high-dose bolus of vitamin D3 followed by maintenance treatment given to adults with CF during an acute pulmonary exacerbation on future recurrence of pulmonary exacerbations. METHODS This was a multicenter, double-blind, placebo-controlled, intent-to-treat clinical trial. Subjects with CF were randomly assigned to oral vitamin D3 given as a single dose of 250,000 International Units (IU) or to placebo within 72 h of hospital admission for an acute pulmonary exacerbation, followed by 50,000 IU of vitamin D3 or an identically matched placebo pill taken orally every other week starting at 3 mo after random assignment. The primary outcome was the composite endpoint of the time to next pulmonary exacerbation or death within 1 y. The secondary outcomes included circulating concentrations of the antimicrobial peptide cathelicidin and recovery of lung function as assessed by the percentage of predicted forced expiratory volume in 1 s (FEV1%). RESULTS A total of 91 subjects were enrolled in the study. There were no differences between the vitamin D3 and placebo groups in time to next pulmonary exacerbation or death at 1 y. In addition, there were no differences in serial recovery of lung function after pulmonary exacerbation by FEV1% or in serial concentrations of plasma cathelicidin. CONCLUSIONS Vitamin D3 initially given at the time of pulmonary exacerbation of CF did not alter the time to the next pulmonary exacerbation, 12-mo mortality, serial lung function, or serial plasma cathelicidin concentrations. This trial was registered at clinicaltrials.gov as NCT01426256.