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1.
Probiotics: A potential immunomodulator in COVID-19 infection management.
Singh, K, Rao, A
Nutrition research (New York, N.Y.). 2021;:1-12
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Abstract
COVID-19 caused by SARS-CoV-2 is an ongoing global pandemic. SARS-CoV-2 affects the human respiratory tract's epithelial cells, leading to a proinflammatory cytokine storm and chronic lung inflammation. With numerous patients dying daily, a vaccine and specific antiviral drug regimens are being explored. Probiotics are live microorganisms with proven beneficial effects on human health. While probiotics as nutritional supplements are long practiced in different cuisines across various countries, the emerging scientific evidence supports the antiviral and general immune-strengthening health effects of the probiotics. Here, we present an overview of the experimental studies published in the last 10 years that provide a scientific basis for unexplored probiotics as a preventive approach to respiratory viral infections. Based on collated insights from these experimental data, we identify promising microbial strains that may serve as lead prophylactic and immune-boosting probiotics in COVID-19 management.
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Probiotics-Derived Peptides and Their Immunomodulatory Molecules Can Play a Preventive Role Against Viral Diseases Including COVID-19.
Manna, S, Chowdhury, T, Chakraborty, R, Mandal, SM
Probiotics and antimicrobial proteins. 2021;(3):611-623
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Abstract
As of recent, the pandemic episode of COVID-19, a severe acute respiratory syndrome brought about by a novel coronavirus (SARS-CoV-2) expanding the pace of mortality, has affected the disease rate profoundly. Invulnerability is the fundamental choice to prevent the ruining event of COVID-19, as the drugs and antibodies are in the phase of preliminary clinical trials. Within this brief period, a few strains of SARS-CoV-2 have been recognized by the vaccine manufacturers, which could be an incorrect guess about the strain that will end up spreading. Since the circulating SARS-CoV-2 strains continue to mutate, immunizations, if at all works, might be for a restricted time. We have not put sufficient time in research to understand the immune responses that correlate with protection as this could help refine vaccines. Here, we have summed up the adequacy of the immunomodulatory component of probiotics for the prevention against viral infections. Furthermore, an in silico data have been provided in support of the "probiotics-derived lipopeptides" role in inactivating spike (S) glycoprotein of SARS-CoV-2 and its host receptor molecule, ACE2. Among well characterized lipopeptides derived from different probiotic strains, subtilisin (Bacillus amyloliquefaciens), curvacin A (Lactobacillus curvatus), sakacin P (Lactobacillus sakei), lactococcin Gb (Lactococcus lactis) was utilized in this study to demonstrate a higher binding proclivity to S-protein of SARS-CoV-2 and human ACE2. The outcome revealed noteworthy capabilities of the lipopeptides, due to their amphiphilic nature, to bind spike protein and receptor molecule, which may act to competitively inhibit the mandatory interaction of SARS-CoV-2 with the host epithelial cell expressing ACE2 for its entry into the cell for reproduction. In the current situation, probiotic treatment alongside chemotherapy may assist in bringing about substantial improvement of the health of COVID-19 patients. At the same time, probiotics may aid towards building up the immune defenses in people to evade COVID-19.
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The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities.
Fiorino, S, Zippi, M, Gallo, C, Sifo, D, Sabbatani, S, Manfredi, R, Rasciti, E, Rasciti, L, Giampieri, E, Corazza, I, et al
The British journal of nutrition. 2021;(3):275-293
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Abstract
In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.
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Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response.
Geindreau, M, Ghiringhelli, F, Bruchard, M
International journal of molecular sciences. 2021;(9)
Abstract
During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune response. In addition, we summarize therapeutic strategies based on its inhibition, and their clinical approval.
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Vitamin D Effects on the Immune System from Periconception through Pregnancy.
Schröder-Heurich, B, Springer, CJP, von Versen-Höynck, F
Nutrients. 2020;(5)
Abstract
Vitamin D is a well-known secosteroid and guardian of bone health and calcium homeostasis. Studies on its role in immunomodulatory functions have expanded its field in recent years. In addition to its impact on human physiology, vitamin D influences the differentiation and proliferation of immune system modulators, interleukin expression and antimicrobial responses. Furthermore, it has been shown that vitamin D is synthesized in female reproductive tissues and, by modulating the immune system, affects the periconception period and reproductive outcomes. B cells, T cells, macrophages and dendritic cells can all synthesize active vitamin D and are involved in processes which occur from fertilization, implantation and maintenance of pregnancy. Components of vitamin D synthesis are expressed in the ovary, decidua, endometrium and placenta. An inadequate vitamin D level has been associated with recurrent implantation failure and pregnancy loss and is associated with pregnancy-related disorders like preeclampsia. This paper reviews the most important data on immunomodulatory vitamin D effects in relation to the immune system from periconception to pregnancy and provides an insight into the possible consequences of vitamin D deficiency before and during pregnancy.
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Transfer of monoclonal antibodies into breastmilk in neurologic and non-neurologic diseases.
LaHue, SC, Anderson, A, Krysko, KM, Rutatangwa, A, Dorsey, MJ, Hale, T, Mahadevan, U, Rogers, EE, Rosenstein, MG, Bove, R
Neurology(R) neuroimmunology & neuroinflammation. 2020;(4)
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Abstract
OBJECTIVE To review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases. METHODS We systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowledge of an additional article. These 30 studies were reviewed. These assessed the presence of our selected mAbs in human breastmilk in samples collected from a total of 155 individual women. RESULTS Drug concentrations were typically low in breastmilk and tended to peak within 48 hours, although maximum levels could occur up to 14 days from infusion. Most studies did not evaluate the breastmilk to maternal serum drug concentration ratio, but in those evaluating this, the highest ratio was 1:20 for infliximab. Relative infant dose, a metric comparing the infant with maternal drug dose (<10% is generally considered safe), was evaluated for certolizumab (<1%), rituximab (<1%), and natalizumab (maximum of 5.3%; cumulative effects of monthly dosing are anticipated). Importantly, a total of 368 infants were followed for ≥6 months after exposure to breastmilk of mothers treated with mAbs; none experienced reported developmental delay or serious infections. CONCLUSIONS The current data are reassuring for low mAb drug transfer to breastmilk, but further studies are needed, including of longer-term effects on infant immunity and childhood development.
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Exploring the Evidence for an Immunomodulatory Role of Vitamin D in Juvenile and Adult Rheumatic Disease.
Zou, J, Thornton, C, Chambers, ES, Rosser, EC, Ciurtin, C
Frontiers in immunology. 2020;:616483
Abstract
Vitamin D is synthesized in the skin following exposure to UVB radiation or is directly absorbed from the diet. Following hydroxylation in the liver and kidneys, vitamin D becomes its bioactive form, 1,25(OH)2D, which has been described to have potent immunomodulatory capacity. This review will focus on the effect of vitamin D in modulating the dysregulated immune system of autoimmune rheumatic diseases (ARD) patients across age, in particular in arthritis (rheumatoid arthritis and juvenile idiopathic arthritis), and systemic lupus erythematosus (with adult and juvenile onset). As well as delineating the impact of vitamin D on the innate and adaptive immune functions associated with each disease pathology, this review will also summarize and evaluate studies that link vitamin D status with disease prevalence, and supplementation studies that examine the potential benefits of vitamin D on disease outcomes. Exploring this evidence reveals that better designed randomized controlled studies are required to clarify the impact of vitamin D supplementation on ARD outcomes and general health. Considering the accessibility and affordability of vitamin D as a therapeutic option, there is a major unmet need for evidence-based treatment recommendations for the use of vitamin D in this patient population.
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Lactoferrin as potential preventative and adjunct treatment for COVID-19.
Chang, R, Ng, TB, Sun, WZ
International journal of antimicrobial agents. 2020;(3):106118
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic is rapidly advancing across the globe despite drastic public and personal health measures. Antivirals and nutritional supplements have been proposed as potentially useful against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that causes COVID-19, but few have been clinically established. Lactoferrin (Lf) is a naturally occurring, non-toxic glycoprotein that is orally available as a nutritional supplement and has established in vitro antiviral efficacy against a wide range of viruses, including SARS-CoV, a closely related coronavirus to SARS-CoV-2. Furthermore, Lf possesses unique immunomodulatory and anti-inflammatory effects that may be especially relevant to the pathophysiology of severe COVID-19 cases. Here we review the underlying biological mechanisms of Lf as an antiviral and immune regulator, and propose its unique potential as a preventative and adjunct treatment for COVID-19. We hope that further research and development of Lf nutritional supplementation would establish its role for COVID-19.
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Can Vitamins, as Epigenetic Modifiers, Enhance Immunity in COVID-19 Patients with Non-communicable Disease?
Singh, V
Current nutrition reports. 2020;(3):202-209
Abstract
PURPOSE OF REVIEW The highly infectious transmissible disease, the novel SARS-CoV-2, causing the coronavirus disease (COVID-19), has a median incubation time of 5 to 15 days. The symptoms vary from person to person and many are "hidden carriers." Few people experience immediate reaction and even death within 48 h of infection. However, many show mild to chronic symptoms and recover. Nevertheless, the death rate due to COVID-19 transmission is high especially among patients with non-communicable diseases. The purpose of this review is to provide evidence to consider vitamins as epigenetic modifiers to enhance immunity and reduce inflammatory response in COVID-19 patients with non-communicable diseases. RECENT FINDINGS Clinical evidence has suggested the risk of getting infected is high among individuals with non-communicable diseases such as cardiovascular disease, type-2 diabetes, cancer, acute respiratory distress syndrome, and renal disease, as well as the elderly with high mortality rate among the cohort. The impact is due to an already compromised immune system of patients. Every patient has a different response to COVID-19, which shows that the ability to combat the deadly virus varies individually. Thus, treatment can be personalized and adjusted to help protect and combat COVID-19 infections, especially in individuals with non-communicable diseases. Based on current published scientific and medical evidence, the suggestions made in this article for combination of vitamin therapy as epigenetic modifiers to control the unregulated inflammatory and cytokine marker expressions, further needs to be clinically proven. Future research and clinical trials can apply the suggestions given in this article to support metabolic activities in patients and enhance the immune response.
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The exploration of Hashimoto's Thyroiditis related miscarriage for better treatment modalities.
Min, Y, Wang, X, Chen, H, Yin, G
International journal of medical sciences. 2020;(16):2402-2415
Abstract
Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disease (ATD) worldwide and is strongly associated with miscarriage and even recurrent miscarriage (RM). Moreover, with a deepening understanding, emerging evidence has shown that immune dysfunctions caused by HT conditions, including imbalanced subsets of CD4+ T-helper cells, B regulatory (Breg) cells, high expression levels of CD56dim natural killer (NK) cells, and cytokines, possibly play an important role in impairing maternal tolerance to the fetus. In recent years, unprecedented progress has been made in recognizing the specific changes in immune cells and molecules in patients with HT, which will be helpful in exploring the mechanism of HT-related miscarriage. Based on these findings, research investigating some potentially more effective treatments, such as selenium (Se), vitamin D3, and intravenous immunoglobulin (IVIG), has been well developed over the past few years. In this review, we highlight some of the latest advances in the possible immunological pathogenesis of HT-related miscarriage and focus on the efficacies of treatments that have been widely introduced to clinical trials or practice described in the most recent literature.