COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy?

Background: Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. Aims: To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for “respiratory diseases” within the current frame of the COVID-19 pandemic as an adjuvant treatment. Method: The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. Results: A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. Conclusions: Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches

The Importance of Macrophages, Lipid Membranes and Seeding in Experimental AA Amyloidosis

Amyloidosis is a group of protein misfolding diseases caused by tissue deposition of fibrillary protein aggregates termed amyloid. Amyloid A (AA) amyloidosis is a systemic form of amyloidosis that occurs as a complication of chronic inflammatory diseases, such as rheumatoid arthritis, familial Mediterranean fever and chronic infections, such as tuberculosis. AA amyloid is derived from the precursor protein serum amyloid A and is deposited in several organs preferably kidneys, liver and spleen. AA amyloidosis can be induced in mice by long standing inflammatory stimulation and concurrent administration of tissue extracts of AA amyloid, referred to as amyloid enhancing factor (AEF), reduces the time for amyloid deposition in the marginal zone of the spleen from 5 weeks to 2 days. The general aim of this thesis was to investigate the mechanisms involved in the development of AA amyloid in the mouse model of AA amyloidosis. Amyloid was induced in inflamed mice by injection of AEF and amyloid toxicity to splenic macrophages was investigated. We found that the marginal zone macrophages were very sensitive to amyloid formation and increasing amyloid load caused progressive depletion of these cells, whereas red pulp macrophages and metallophilic marginal zone macrophages appeared unaffected. To clarify the role of splenic macrophages in amyloidogenesis, macrophages were depleted by clodronate containing liposomes. We displayed that in the absence of splenic macrophages, especially marginal zone macrophages, amyloid formation was delayed implying a crucial role of macrophages in amyloid formation. The effect of lipid membranes on amyloid formation was studied and we showed that liposomes exhibited an amyloidogenic effect in inflamed mice although not as powerful as AEF. Following the fate of the liposomes, we showed that liposomes were rapidly cleared by uptake in the spleen and liver and colocalized with lysosomes. A tentative mechanism might be that accumulation of liposomes in lysosomes interfere with the SAA degradation process facilitating amyloid formation. Finally the conformational properties of two AEF (AEF1 and AEF2) preparations were studied using conformation sensitive luminescent-conjugated oligothiophenes (LCOs). We found that AEF1 and AEF2 displayed significantly different ultrastructure as well as conformation and consequently induced different cytotoxicity in vitro. Inducing amyloid formation in inflamed mice by AEF1 and AEF2 revealed that the polymorph of the amyloid aggregates was replicated in vivo. In summary, the results obtained in this thesis indicate an important role for macrophages for the formation of amyloid. The existence of amyloid strains has long been an in vitro finding, but the finding that AEF ultrastructure drives the morphology of newly formed amyloid in vivo opens up for new studies that can help us to understand the formation of homologous and heterologous fibrils. Thus, the fundamental mechanisms of various amyloid diseases are similar and the results presented in the thesis can increase the understanding of other amyloid diseases.Incorrect affiliation to Division of Experimental Pathology in publication. Correct affiliation is Division of Cell Biology.</p

The relationship between serum cobalamin, folic acid, and homocysteine and the risk of post-cardiac surgery delirium

Maryam Vahdat Shariatpanahi,1 Aynaz Velayati,2 Seyed Ali Jamalian,3 Mehdi Babevaynejad,4 Zahra Vahdat Shariatpanahi21Department of Psychiatry, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 2National Nutrition and Food Technology Research Institute, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3Department of Cardiology, Shahid Lavasani Hospital, Islamic Azad University, Tehran, Iran; 4Department of Cardiac Surgery, Shahid Lavasani Hospital, Islamic Azad University, Tehran, IranPurpose: It has been reported that cobalamin and folate deficiency is related to delirium in persons with dementia. We evaluated the association of admission serum levels of cobalamin, folic acid, and homocysteine with the occurrence of acute delirium after coronary artery bypass surgery.Methods: In this prospective cohort study, serum levels of cobalamin, folic acid, and homocysteine were measured for 296 patients upon admission. Delirium was defined by the confusion assessment method for the intensive care unit.Results: Postoperative delirium was detected in 23% (n=68) of patients. Cobalamin deficiency, folate deficiency, and hyperhomocysteinemia were observed in 29% (n=86), 6% (n=18), and 68% (n=200) of patients, respectively. The mean &plusmn; SD serum levels of folic acid were 10.77&plusmn;5.39 ng/mL and 12.86&plusmn;6.51 ng/mL in delirium and non-delirium patients, respectively&nbsp;(P=0.008). The median (interquartile range&nbsp;[IQR]) serum levels of cobalamin were 280 (216&ndash;351) and 247 (195.5&ndash;336) in delirium and non-delirium patients, respectively (P=0.09). The median (IQR) serum levels of homocysteine were 18.5 (14.5&ndash;22.1) &mu;mol/L&nbsp;and 17.33 (14.2&ndash;23.2) &mu;mol/L in delirium and non-delirium patients, respectively (P=0.94). Multivariate regression analysis adjusted by other risk factors indicated that serum homocysteine, folate, and cobalamin levels had no association with the occurrence of delirium.Conclusion: There was no relationship between the preoperative levels of cobalamin, folate, and homocysteine, and acute occurrence of delirium observed after cardiac surgery.Keywords: vitamin B12, CAM-ICU, cardiopulmonary bypass, intensive care uni

Evaluation of anorexia and analysis of related factors in patients with COVID-19

Objective: COVID-19 may cause an anorexic situation. This in turn leads to underfeeding, puts the patient in an energy protein malnutrition state, develops the hyperinflammation, weakens the immunity, and makes COVID-19 conditions more dangerous. Meanwhile, the more severe inflammation conditions in the body, the more severe the anorexia, which in turn affect the disease severity. Studies evaluating appetite in COVID-19 patients are very rare; therefore, we evaluated anorexia and analyzed the related factors in patients with COVID-19. Material and methods: In this cross sectional study, adult patients’ ≥18 years old with the positive real-time fluorescence polymerase chain reaction for COVID-19 were included. The patients were classified as mild, moderate, and severe based on the WHO classification. We measured the appetite score, weight, height, body mass index (BMI), depression and anxiety score, at admission for every patient. Results: A total of 301 patients participated in the study. The prevalence of admission anorexia was 58, and this rate was significantly more in the severe group compared to the mild and moderate groups (P < 0.001). Comorbidities, depression and anxiety were independently correlated with anorexia risk (OR = 3.6, 95% CI 1.68–7.70, P = 0.001), (OR = 1.23, 95% CI 1.16–1.30, P < 0001), and (OR = 1.24, 95% CI 1.17–1.31, P < 0001), respectively. This correlation was adherence to a U-shape association for BMI, which means BMI < 18.5 (OR = 3.35, 95% CI 1.8–10.42, P < 0001) and BMI ≥30 (OR = 2.45, 95% CI 1.02–6.53, P = 0.048) were related to higher risk of anorexia. Conclusion: We reported a high prevalence of anorexia (58%) in COVID-19 patients, which was positively correlated with disease severity. Furthermore, any factor worsening inflammatory state, including underweight, obesity, comorbidities, depression and anxiety can exacerbate anorexia in these patients. © 2021 Société francophone nutrition clinique et métabolisme (SFNCM

Ascorbic Acid to Prevent Postpolypectomy Bleeding in the Colon: A Randomized Controlled Trial

INTRODUCTION: It has been reported that vitamin C replacement can quickly reverse nonspecific bleeding in surgical patients with normal coagulation parameters. We evaluated the effect of intravenous ascorbic acid administration for prevention of postpolypectomy bleeding in large polyps of the colon. MATERIALS AND METHODS: Patients with large polyps with heads larger than 10 mm, stalk diameter larger than 5 mm, and a length larger than 10 mm were included in this randomized controlled clinical trial. In the study group, the first 500 mg intravenous dose of vitamin C diluted in normal saline was administered 2 h before colonoscopic resection of polyps and the second and third similar doses were administered on days 2 and 3 of polypectomy, respectively. The control group received normal saline in a similar fashion. The resection of polyps was performed in snare and cut-blend mode. Early and late postoperative bleeding were compared between the two groups. RESULTS: A total of 153 polyps were resected by endoscopic polypectomy. Early bleeding was observed in 7.2 of the patients, which was significantly lower in the vitamin C group (2.6 vs 11.8, P = 0.03). Late bleeding was observed in 6.5 of the patients with a trend lower in the vitamin C group (2.6 vs 10.5, P = 0.057). The proportion of postprocedural bleeding was significantly higher in the vitamin C group (5 vs 20, P = 0.007). Hazard ratios of early and postprocedural bleeding were 78 and 76 lower in the vitamin C group compared to the control group (P < 0.05). CONCLUSION: Intravenous ascorbic acid infusion could reduce postpolypectomy bleeding

Bosentan for high-risk outpatients with COVID-19 infection: a randomized, double blind, placebo-controlled trialResearch in context

Summary: Background: The endothelium is supposedly activated and damaged in COVID-19 because of endothelin-1 over-secretion. This study evaluates the effect of bosentan as an endothelin receptor blocker on the progression of disease in high-risk outpatients with COVID-19 infection. Methods: From 15 December 2021 to 15 May 2022, high-risk outpatients were randomly assigned to receive bosentan, 62.5 mg or placebo twice daily from enrollment for 30 days. Both groups received standard medical treatment too. On day 30 of the trial, the patients underwent complete doppler ultrasound of the lower extremities to detect asymptomatic thromboembolic events. The primary outcome in this study was hospitalization or death from any cause within the first 15 days. Secondary outcomes included thromboembolic events, hospital-free days and death from any cause within 30 days after randomization (IRCT.ir, IRCT20211203053263N1). Findings: Basal characteristics of the two groups were similar. Primary outcomes occurred in 3 (2.3%) of the 129 patients in the bosentan group versus 15 (11.5%) of the 130 patients in the placebo group [risk difference: −9.2% (95% CI: −15.3 to −3.1), P = 0.006]. Median hospital-free days was significantly higher in the bosentan group (P = 0.004). A total of three deaths occurred and all were in the control group. Bosentan was associated with a nonsignificant reduction in mortality compared with placebo (P = 0.24). Thromboembolic events occurred in one (1%) of 97 patients in the bosentan group versus nine (8.7%) of 104 patients in the placebo group within 30 days after randomization [risk difference: −8.3% (95% CI: −14.4 to −2.2), P = 0.008]. Interpretation: Early administration of bosentan may prevent disease progression and thromboembolic events in high-risk outpatients with COVID-19. Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Depletion of Spleen Macrophages Delays AA Amyloid Development: A Study Performed in the Rapid Mouse Model of AA Amyloidosis

AA amyloidosis is a systemic disease that develops secondary to chronic inflammatory diseases Macrophages are often found in the vicinity of amyloid deposits and considered to play a role in both formation and degradation of amyloid fibrils. In spleen reside at least three types of macrophages, red pulp macrophages (RPM), marginal zone macrophages (MZM), metallophilic marginal zone macrophages (MMZM). MMZM and MZM are located in the marginal zone and express a unique collection of scavenger receptors that are involved in the uptake of blood-born particles. The murine AA amyloid model that resembles the human form of the disease has been used to study amyloid effects on different macrophage populations. Amyloid was induced by intravenous injection of amyloid enhancing factor and subcutaneous injections of silver nitrate and macrophages were identified with specific antibodies. We show that MZMs are highly sensitive to amyloid and decrease in number progressively with increasing amyloid load. Total area of MMZMs is unaffected by amyloid but cells are activated and migrate into the white pulp. In a group of mice spleen macrophages were depleted by an intravenous injection of clodronate filled liposomes. Subsequent injections of AEF and silver nitrate showed a sustained amyloid development. RPMs that constitute the majority of macrophages in spleen, appear insensitive to amyloid and do not participate in amyloid formation.Funding Agencies|Swedish Research Council|GTW5343|County Council of Ostergotland Magnus Bergvalls research foundation||Ingrid Svenssons research foundation||Broderna Karlssons research foundation||Hildur Pettersons research foundation||</p

Depletion of Spleen Macrophages Delays AA Amyloid Development: A Study Performed in the Rapid Mouse Model of AA Amyloidosis

AA amyloidosis is a systemic disease that develops secondary to chronic inflammatory diseases Macrophages are often found in the vicinity of amyloid deposits and considered to play a role in both formation and degradation of amyloid fibrils. In spleen reside at least three types of macrophages, red pulp macrophages (RPM), marginal zone macrophages (MZM), metallophilic marginal zone macrophages (MMZM). MMZM and MZM are located in the marginal zone and express a unique collection of scavenger receptors that are involved in the uptake of blood-born particles. The murine AA amyloid model that resembles the human form of the disease has been used to study amyloid effects on different macrophage populations. Amyloid was induced by intravenous injection of amyloid enhancing factor and subcutaneous injections of silver nitrate and macrophages were identified with specific antibodies. We show that MZMs are highly sensitive to amyloid and decrease in number progressively with increasing amyloid load. Total area of MMZMs is unaffected by amyloid but cells are activated and migrate into the white pulp. In a group of mice spleen macrophages were depleted by an intravenous injection of clodronate filled liposomes. Subsequent injections of AEF and silver nitrate showed a sustained amyloid development. RPMs that constitute the majority of macrophages in spleen, appear insensitive to amyloid and do not participate in amyloid formation.Funding Agencies|Swedish Research Council|GTW5343|County Council of Ostergotland Magnus Bergvalls research foundation||Ingrid Svenssons research foundation||Broderna Karlssons research foundation||Hildur Pettersons research foundation||</p