Probiotics and COVID-19: is there any link?

Understanding mechanisms of the novel SARS-CoV2 infection and progression can provide potential novel targets for prevention and/or treatment. This could be achieved via the inhibition of viral entry and/or replication, or by suppression of the immunologic response that is provoked by the infection (known as the cytokine storm). Probiotics are defined as 'live microorganisms that, when administered in adequate amounts, confer a health benefit on the host'. There is scarcity of evidence about the relationship between COVID-19 and gut microbiota. So, whether or not these supplements can prevent or ameliorate COVID-19-associated symptoms is not fully understood. The aim of this study is to provide an indirect evidence about the utility of probiotics in combating COVID-19 or its associated symptoms, through the review of its antiviral and anti-inflammatory properties in vitro, animal models and human trials. SIGNIFICANCE AND IMPACT OF THE STUDY: The role of probiotics in alleviation of the novel COVID-19 has not been established. This review provides an insight about the anti-inflammatory, antiviral effects of probiotics in vitro, animal models and human. The latter can provide an indirect evidence and/or hypothesis-driven approach to investigate the use of probiotics as adjunctive therapy in the prophylaxis and/or alleviation of COVID-19 symptoms.

Implication of COVID-19 on Erythrocytes Functionality: Red Blood Cell Biochemical Implications and Morpho-Functional Aspects.

Several diseases (such as diabetes, cancer, and neurodegenerative disorders) affect the morpho-functional aspects of red blood cells, sometimes altering their normal metabolism. In this review, the hematological changes are evaluated, with particular focus on the morphology and metabolic aspects of erythrocytes. Changes in the functionality of such cells may, in fact, help provide important information about disease severity and progression. The viral infection causes significant damage to the blood cells that are altered in size, rigidity, and distribution width. Lower levels of hemoglobin and anemia have been reported in several studies, and an alteration in the concentration of antioxidant enzymes has been shown to promote a dangerous state of oxidative stress in red blood cells. Patients with severe COVID-19 showed an increase in hematological changes, indicating a progressive worsening as COVID-19 severity progressed. Therefore, monitored hematological alterations in patients with COVID-19 may play an important role in the management of the disease and prevent the risk of a severe course of the disease. Finally, monitored changes in erythrocytes and blood, in general, may be one of the causes of the condition known as Long COVID.

Early experience of nintedanib in COVID-19 ARDS-related pulmonary fibrosis: a case series.

The current COVID-19 pandemic has spread like wildfire worldwide and has affected millions of people. The novel corona virus mainly affects the lungs leading to life threatening disease like acute respiratory distress syndrome (ARDS). The aftermath of the disease in form of pulmonary fibrosis is upcoming cause of further increase in morbidity and mortality. Nintedanib is an oral antifibrotics with proven role in idiopathic pulmonary fibrosis, however its use in COVID-19 related pulmonary fibrosis has not been studied. We report our early experience of use of nintedanib in COVID-19 related pulmonary fibrosis.

Lipid-based therapies against SARS-CoV-2 infection.

Viruses have evolved to manipulate host lipid metabolism to benefit their replication cycle. Enveloped viruses, including coronaviruses, use host lipids in various stages of the viral life cycle, particularly in the formation of replication compartments and envelopes. Host lipids are utilised by the virus in receptor binding, viral fusion and entry, as well as viral replication. Association of dyslipidaemia with the pathological development of Covid-19 raises the possibility that exploitation of host lipid metabolism might have therapeutic benefit against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, promising host lipid targets are discussed along with potential inhibitors. In addition, specific host lipids are involved in the inflammatory responses due to viral infection, so lipid supplementation represents another potential strategy to counteract the severity of viral infection. Furthermore, switching the lipid metabolism through a ketogenic diet is another potential way of limiting the effects of viral infection. Taken together, restricting the access of host lipids to the virus, either by using lipid inhibitors or supplementation with exogenous lipids, might significantly limit SARS-CoV-2 infection and/or severity.

Proposal of a food supplement for the management of post-COVID syndrome.

A vast majority of COVID-19 patients experience fatigue, extreme tiredness and symptoms that persist beyond the active phase of the disease. This condition is called post-COVID syndrome. The mechanisms by which the virus causes prolonged illness are still unclear. The aim of this review is to gather information regarding post-COVID syndrome so as to highlight its etiological basis and the nutritional regimes and supplements that can mitigate, alleviate or relieve the associated chronic fatigue, gastrointestinal disorders and continuing inflammatory reactions. Naturally-occurring food supplements, such as acetyl L-carnitine, hydroxytyrosol and vitamins B, C and D hold significant promise in the management of post-COVID syndrome. In this pilot observational study, we evaluated the effect of a food supplement containing hydroxytyrosol, acetyl L-carnitine and vitamins B, C and D in improving perceived fatigue in patients who recovered from COVID-19 but had post-COVID syndrome characterized by chronic fatigue. The results suggest that the food supplement could proceed to clinical trials of its efficacy in aiding the recovery of patients with long COVID.

Comments on the Discussion Forum: Oromucosal immunomodulation as clinical spectrum mitigating factor in SARS-CoV-2 infection.

The mammalian lactoperoxidase system, consisting of lactoperoxidase and the H2 O2 -producing enzyme duox, is our first line of defence against airborne microbes. This system catalyses the production of hypoiodite and hypoiodous acid in the presence of sufficient iodine. These products are highly efficient at destroying the H1N1 virus and the respiratory syncytial virus (RSV). Japan has not been affected as much as other nations during the COVID-19 pandemic (death rate about 10% of the United States), and we think this is due to a diet high in iodine. With this in mind, we suggest four actions to prevent SARS-CoV-2 infections. First, health professionals should study the preventative effect of increasing iodine in the diets of the aged, institutionalized, diabetics andsmokers. Second, the recommended daily intake (RDI) for iodine should be significantly increased, to at least double, the current RDI. Governments should encourage the use and distribution of cheap iodized salts, kelp and seaweed. Third, more research should be done around the physiology and the protective effects of the lactoperoxidase system. Finally, the degradation products of the SARS-CoV-2 viral particle by hypoiodite and hypoiodous acid should be characterized; portions of the damaged particle are likely to elicit stronger immunity and better vaccines.

Role of ACE2-Ang (1-7)-Mas axis in post-COVID-19 complications and its dietary modulation.

Severe acute respiratory syndrome-coronavirus-2 (COVID-19) virus uses Angiotensin-Converting Enzyme 2 (ACE2) as a gateway for their entry into the human body. The ACE2 with cleaved products have emerged as major contributing factors to multiple physiological functions and pathogenic complications leading to the clinical consequences of the COVID-19 infection Decreased ACE2 expression restricts the viral entry into the human cells and reduces the viral load. COVID-19 infection reduces the ACE2 expression and induces post-COVID-19 complications like pneumonia and lung injury. The modulation of the ACE2-Ang (1-7)-Mas (AAM) axis is also being explored as a modality to treat post-COVID-19 complications. Evidence indicates that specific food components may modulate the AAM axis. The variations in the susceptibility to COVID-19 infection and the post-COVID its complications are being correlated with varied dietary habits. Some of the food substances have emerged to have supportive roles in treating post-COVID-19 complications and are being considered as adjuvants to the COVID-19 therapy. It is possible that some of their active ingredients may emerge as the direct treatment for the COVID-19.

Nutritional Immunity, Zinc Sufficiency, and COVID-19 Mortality in Socially Similar European Populations.

The impact of zinc (Zn) sufficiency/supplementation on COVID-19-associated mortality and incidence (SARS-CoV-2 infections) remains unknown. During an infection, the levels of free Zn are reduced as part of "nutritional immunity" to limit the growth and replication of pathogen and the ensuing inflammatory damage. Considering its key role in immune competency and frequently recorded deficiency in large sections of different populations, Zn has been prescribed for both prophylactic and therapeutic purposes in COVID-19 without any corroborating evidence for its protective role. Multiple trials are underway evaluating the effect of Zn supplementation on COVID-19 outcome in patients getting standard of care treatment. However, the trial designs presumably lack the power to identify negative effects of Zn supplementation, especially in the vulnerable groups of elderly and patients with comorbidities (contributing 9 out of 10 deaths; up to >8,000-fold higher mortality). In this study, we have analyzed COVID-19 mortality and incidence (case) data from 23 socially similar European populations with comparable confounders (population: 522.47 million; experiencing up to >150-fold difference in death rates) and at the matching stage of the pandemic (March 12 to June 26, 2020; first wave of COVID-19 incidence and mortality). Our results suggest a positive correlation between populations' Zn-sufficiency status and COVID-19 mortality [r (23): 0.7893-0.6849, p-value < 0.0003] as well as incidence [r (23):0.8084-0.5658; p-value < 0.005]. The observed association is contrary to what would be expected if Zn sufficiency was protective in COVID-19. Thus, controlled trials or retrospective analyses of the adverse event patients' data should be undertaken to correctly guide the practice of Zn supplementation in COVID-19.

Impact of vitamin D on the course of COVID-19 during pregnancy: A case control study.

OBJECTIVE: We aimed to evaluate the vitamin D status of pregnant women with COVID-19, and the association between vitamin D level and severity of COVID-19. METHODS: In this case control study, 159 women with a single pregnancy and tested positive for SARS-CoV-2, and randomly selected 332 healthy pregnant women with similar gestational ages were included. COVID-19 patients were classified as mild, moderate, and severe. Vitamin D deficiency was defined as 25-hydroxycholecalciferol <20 ng/mL (50 nmol/L), and 25-OH D vitamin <10 ng/mL was defined as severe vitamin D deficiency, also 25-OH D vitamin level between 20-29 ng/mL (525-725 nmol/L) was defined as vitamin D insufficiency. RESULTS: Vitamin D levels of the pregnant women in the COVID-19 group (12.46) were lower than the control group (18.76). 25-OH D vitamin levels of those in the mild COVID-19 category (13.69) were significantly higher than those in the moderate/severe category (9.06). In terms of taking vitamin D supplementation, there was no statistically significant difference between the groups. However, it was observed that all of those who had severe COVID-19 were the patients who did not take vitamin D supplementation. CONCLUSION: The vitamin D levels are low in pregnant women with COVID-19. Also, there is a significant difference regarding to vitamin D level and COVID-19 severity in pregnant women. Maintenance of adequate vitamin D level can be useful as an approach for the prevention of an aggressive course of the inflammation induced by this novel coronavirus in pregnant women.

Covid 19: Diet Composition and Health.

The virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the disease coronavirus disease 2019 (COVID-19). The cumulative number of cases reported globally is now nearly 197 million and the number of cumulative deaths is 4.2 million (26 July to 1 August 2021). Currently we are focusing primarily on keeping a safe distance from others, washing our hands, and wearing masks, and the question of the effects of diet and diet-dependent risk factors remains outside the center of attention. Nevertheless, numerous studies indicate that diet can play an important role in the course of COVID-19. In this paper, based on select scientific reports, we discuss the structure and replication cycle of SARS-CoV-2, risk factors, dietary standards for sick patients, and the roles of the microbiome and dietary components supporting the immune system in preventing COVID-19.

Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.

BACKGROUND: The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS: Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS: 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS: Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.

Glycophosphopeptical AM3 Food Supplement: A Potential Adjuvant in the Treatment and Vaccination of SARS-CoV-2.

The world is currently experiencing the coronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-2 (SARS-CoV-2). Its global spread has resulted in millions of confirmed infections and deaths. While the global pandemic continues to grow, the availability of drugs to treat COVID-19 infections remains limited to supportive treatments. Moreover, the current speed of vaccination campaigns in many countries has been slow. Natural substrates with biological immunomodulatory activity, such as glucans, may represent an adjuvant therapeutic agent to treat SARS-CoV-2. AM3, a natural glycophosphopeptical, has previously been shown to effectively slow, with no side effects, the progression of infectious respiratory diseases by regulating effects on innate and adaptive immunity in experimental models. No clinical studies, however, exist on the use of AM3 in SARS-CoV-2 infected patients. This review aims to summarize the beneficial effects of AM3 on respiratory diseases, the inflammatory response, modulation of immune response, and attenuation of muscle. It will also discuss its potential effects as an immune system adjuvant for the treatment of COVID-19 infections and adjuvant for SARS-CoV-2 vaccination.

Evolution of Nutritional Status after Early Nutritional Management in COVID-19 Hospitalized Patients.

Background & Aims: SARS-CoV2 infection is associated with an increased risk of malnutrition. Although there are numerous screening and nutritional management protocols for malnutrition, only few studies have reported nutritional evolution after COVID-19. The objectives of this study were to describe the evolution of nutritional parameters between admission and 30 days after hospital discharge, and to determine predictive factors of poor nutritional outcome after recovery in adult COVID-19 patients. Methods: In this observational longitudinal study, we report findings after discharge in 91 out of 114 patients initially admitted for COVID-19 who received early nutritional management. Nutritional status was defined using GLIM criteria and compared between admission and day 30 after discharge. Baseline predictors of nutritional status at day 30 were assessed using logistic regression. Results: Thirty days after discharge, 28.6% of patients hospitalized for COVID-19 were malnourished, compared to 42.3% at admission. Half of malnourished patients (53%) at admission recovered a normal nutritional status after discharge. Weight trajectories were heterogeneous and differed if patients had been transferred to an intensive care unit (ICU) during hospitalization (p = 0.025). High oxygen requirement during hospitalization (invasive ventilation p = 0.016 (OR 8.3 [1.6-61.2]) and/or oxygen therapy over 5 L/min p = 0.021 (OR 3.2 [1.2-8.9]) were strong predictors of malnutrition one month after discharge. Conclusions: With early nutritional management, most patients hospitalized for COVID-19 improved nutritional parameters after discharge. These findings emphasize the importance of nutritional care in COVID-19 patients hospitalized in medicine departments, especially in those transferred from ICU.

COVID-19 and obesity: fighting two pandemics with intermittent fasting.

Obesity is strongly and independently associated with an increased risk of severe illness and death from coronavirus disease 2019 (COVID-19). The pathophysiological changes that result from elevated body weight lead to metabolic dysfunction, chronic inflammation, impaired immunological responses, and multisystem disorders, which increase vulnerability to severe illness from COVID-19. While vaccination strategies are under way across the world, the second and third waves of the pandemic, along with the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, continue to threaten the stability of medical systems worldwide. Furthermore, evidence from previous pandemics suggests that vaccines are less effective in obese individuals than in their healthy-weight counterparts over the long term. Therefore, a consideration of lifestyle changes that can boost metabolic health and immunity is critical to reduce the risk of complications and severe illness from viral infection. In this review, we discuss the potential mechanisms linking excess body weight with COVID-19 morbidity. We also present evidence that intermittent fasting (IF), a dietary program that has gained popularity in recent years, may be an effective strategy to improve metabolic health and immunity and thus reduce the impact of obesity on COVID-19 morbidity and mortality.

Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice.

Increasing age is the strongest predictor of risk of COVID-19 severity and mortality. Immunometabolic switch from glycolysis to ketolysis protects against inflammatory damage and influenza infection in adults. To investigate how age compromises defense against coronavirus infection, and whether a pro-longevity ketogenic diet (KD) impacts immune surveillance, we developed an aging model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain-A59 (MHV-A59). When inoculated intranasally, mCoV is pneumotropic and recapitulates several clinical hallmarks of COVID-19 infection. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue, and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Activation of ketogenesis in aged mice expands tissue protective γδ T cells, deactivates the NLRP3 inflammasome, and decreases pathogenic monocytes in lungs of infected aged mice. These data establish harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against coronavirus infection in the aged.

Assessment of the role of zinc in the prevention of COVID-19 infections and mortality: A retrospective study in the Asian and European population.

Several studies have demonstrated an association between individual zinc status and viral respiratory infections; however, evidence regarding COVID-19 is still missing or insufficient. This study aimed to evaluate the correlation between the prevalence of zinc deficiency and COVID-19 cases and deaths per million population in the Asian and European countries. The COVID-19 data from two different time points, that is, May 30 and June 30, 2020 for the Asian population and May 15 and June 15, 2020 for the European population, were analyzed to determine the correlation with the estimated zinc deficiency for these two continents. The prevalence of zinc deficiency was about two times higher in the Asian population (mean 17.5%) than in the European population (mean 8.9%). A significant positive correlation (p < .05) was observed between the prevalence of zinc deficiency and COVID-19 cases at both time periods for the Asian population. However, the correlation between zinc deficiency prevalence and COVID-19 deaths was not significant in the Asian population. In contrast, a significant but negative correlation (p < .05 for all cases) was observed for zinc deficiency with both COVID-19 cases and deaths per million population at both time periods in the European countries. Considering the direct antiviral properties of zinc, it can be suggested that zinc supplementation may be beneficial for most of the population, especially older people and those who are at risk of COVID-19 infections. In conclusion, there is not enough evidence on the association between individual zinc status and COVID-19 infections and mortality. Therefore, cohort studies and randomized controlled trials are required to test this hypothesis.

Possible Beneficial Actions of Caffeine in SARS-CoV-2.

The COVID-19 pandemic has established an unparalleled necessity to rapidly find effective treatments for the illness; unfortunately, no specific treatment has been found yet. As this is a new emerging chaotic situation, already existing drugs have been suggested to ameliorate the infection of SARS-CoV-2. The consumption of caffeine has been suggested primarily because it improves exercise performance, reduces fatigue, and increases wakefulness and awareness. Caffeine has been proven to be an effective anti-inflammatory and immunomodulator. In airway smooth muscle, it has bronchodilator effects mainly due to its activity as a phosphodiesterase inhibitor and adenosine receptor antagonist. In addition, a recent published document has suggested the potential antiviral activity of this drug using in silico molecular dynamics and molecular docking; in this regard, caffeine might block the viral entrance into host cells by inhibiting the formation of a receptor-binding domain and the angiotensin-converting enzyme complex and, additionally, might reduce viral replication by the inhibition of the activity of 3-chymotrypsin-like proteases. Here, we discuss how caffeine through certain mechanisms of action could be beneficial in SARS-CoV-2. Nevertheless, further studies are required for validation through in vitro and in vivo models.

[Zinc status improving as a pathogenetically grounded platform for maintaining immunity during SARS-CoV-2 pandemic].

The problem of increasing immunity has become especially relevant in the conditions of the rapid spread of the new coronavirus infection SARS-CoV-2. Nowadays it has been proven that a deficiency of certain micronutrients in the diet can disrupt chemical, structural and regulatory processes in the organism, which negatively affects, first of all, the state of immune system. Zinc is one of the most significant essential trace elements affecting immunological resistance. The aim of the study was to substantiate the need of including zinc-containing products and diet supplements in the diet of the population during the SARS-CoV-2 pandemic on the basis of the study of pathogenetic mechanisms of various disorders of the immunological status under zinc deficit. Material and methods. This review analyzes the data from scientific electronic libraries CyberLeninka, eLIBRARY.RU, the Google Scholar databases and bibliographic medical databases MEDLINE and PubMed-NCBI. Results and discussion. During the SARS-CoV-2 pandemic, adequate zinc supply is especially important, due to its antiviral, immunomodulatory and antiapoptotic effects. This element also regulates the severity of the cytokine response, exhibits antibacterial properties and helps to compensate for chronic comorbid diseases, which plays a particularly significant role in preventing severe SARS-CoV-2 and recurrent respiratory diseases. Prevention and correction of zinc deficiency is considered as one of the important measures during the SARS-CoV-2 pandemic, aimed at increasing antiviral and general immunity, reducing the systemic inflammatory response and correcting hormonal and metabolic status. Conclusion. The pathogenetically substantiated inclusion of zinc-containing foods and supplements in the diet will enhance the immunity of the population during the SARSCoV- 2 pandemic.