COVID-19-associated-mucormycosis: possible role of free iron uptake and immunosuppression.
Molecular biology reports. 2022;(1):747-754
COVID-19-associated-mucormycosis, commonly referred to as the "Black Fungus," is a rare secondary fungal infection in COVID-19 patients prompted by a group of mucor molds. Association of this rare fungal infection with SARS-CoV-2 infection has been declared as an endemic in India, with minor cases in several other countries around the globe. Although the fungal infection is not contagious like the viral infection, the causative fungal agent is omnipresent. Infection displays an overall mortality rate of around 50%, with many other secondary side effects posing a potential threat in exacerbating COVID-19 mortality rates. In this review, we have accessed the role of free iron availability in COVID-19 patients that might correlate to the pathogenesis of the causative fungal agent. Besides, we have analyzed the negative consequences of using immunosuppressive drugs in encouraging this opportunistic fungal infection.
The Impact of COVID-19-Related Living Restrictions on Eating Behaviours in Children and Adolescents: A Systematic Review.
The COVID-19 pandemic prompted the imposition of physical and social distancing measures worldwide. Emerging data suggest that younger age groups may be particularly vulnerable to the adverse mental health impacts of the pandemic. Since the start of the COVID-19 pandemic, there has been an unprecedented increase in demand for child and adolescent eating disorder services. The aim of this review was to systematically review and appraise the current literature on the impact of COVID-19-related living restrictions on the eating behaviours of children and adolescents. Searches of eight electronic databases were conducted in March 2021 and December 2021 for published and grey literature on eating behaviours of population samples of children and adolescents (aged 18 months to 18 years old) who were exposed to COVID-19-related living restrictions. Of 3165 retrieved references, sixteen studies were included in this review, comprising data from 125, 286 participants. There was a pattern towards healthier eating behaviours among children and adolescents during the COVID-19 lockdown. However, young people from lower socioeconomic groups showed a tendency towards more unhealthy eating behaviours, and there was an association between mood difficulties and greater changes in eating; this suggests that such groups may be more vulnerable to the adverse health consequences of lockdowns.
Prevention of Recurrent Childhood Caries with Probiotic Supplements: A Randomized Controlled Trial with a 12-Month Follow-Up.
Probiotics and antimicrobial proteins. 2022;(2):384-390
The aim of this study was to evaluate the effect of drops containing probiotic bacteria on the recurrence of dental caries in preschool children. The study employed a randomized, placebo-controlled, double-blinded design with two parallel arms. 38 preschool children were enrolled after comprehensive restorative treatment under general anesthesia or conscious sedation (baseline), and they were followed up after 6 and 12 months. Parents of children in the test group were instructed to give 5 daily drops containing two strains of Limosilactobacillus reuteri (DSM 17938 and ATCC PTA 5289) at bedtime. The placebo drops were identically composed but lacked bacteria. The duration of the intervention was 12 months. The primary endpoint was recurrence of new caries lesions on subject level (yes/no), and secondary endpoints were presence of dental plaque and gingivitis. We found high rate of recurrent moderate and extensive lesions after 12 months (67%) but there were no significant differences between the groups. We observed no beneficial effects on dental plaque or gingival inflammation. The findings were however uncertain and inconclusive due to lack of power, a consequence of the COVID-19 pandemic. ClinTrials.gov Identifier: (NCT04929340), June 18, 2021; retrospectively registered.
Thyroid Dysfunction and COVID-19: The Emerging Role of Selenium in This Intermingled Relationship.
International journal of environmental research and public health. 2022;(11)
COVID-19 represents a worldwide public health emergency, and, beyond the respiratory symptoms characterizing the classic viral disease, growing evidence has highlighted a possible reciprocal relationship between SARS-CoV-2 infection and thyroid dysfunction. The updated data discussed in this review suggests a role of SARS-CoV-2 infection on the thyroid gland, with multiple thyroid pictures described. Conversely, no conclusion can be drawn on the association between pre-existing thyroid disease and increased risk of SARS-CoV-2 infection. In this scenario, selenium (Se), an essential trace element critical for thyroid function and known as an effective agent against viral infections, is emerging as a potential novel therapeutic option for the treatment of COVID-19. Large multicentre cohort studies are required to elucidate the mechanisms underlying thyroid dysfunction during or following recovery from COVID-19, including Se status. Meanwhile, clinical trials should be performed to evaluate whether adequate intake of Se can help address COVID-19 in Se-deficient patients, also avoiding thyroid complications that can contribute to worsening outcomes during infection.
Immunoinflammatory role of apolipoprotein E4 in malnutrition and enteric infections and the increased risk for chronic diseases under adverse environments.
Nutrition reviews. 2022;(5):1001-1012
Apolipoprotein E plays a crucial role in cholesterol metabolism. The immunomodulatory functions of the human polymorphic APOE gene have gained particular interest because APOE4, a well-recognized risk factor for late-onset Alzheimer's disease, has also been recently linked to increased risk of COVID-19 infection severity in a large UK biobank study. Although much is known about apoE functions in the nervous system, much less is known about APOE polymorphism effects on malnutrition and enteric infections and the consequences for later development in underprivileged environments. In this review, recent findings are summarized of apoE's effects on intestinal function in health and disease and the role of APOE4 in protecting against infection and malnutrition in children living in unfavorable settings, where poor sanitation and hygiene prevail, is highlighted. The potential impact of APOE4 on later development also is discussed and gaps in knowledge are identified that need to be addressed to protect children's development under adverse environments.
Trained Immunity: An Overview and the Impact on COVID-19.
Frontiers in immunology. 2022;:837524
Effectively treating infectious diseases often requires a multi-step approach to target different components involved in disease pathogenesis. Similarly, the COVID-19 pandemic has become a global health crisis that requires a comprehensive understanding of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection to develop effective therapeutics. One potential strategy to instill greater immune protection against COVID-19 is boosting the innate immune system. This boosting, termed trained immunity, employs immune system modulators to train innate immune cells to produce an enhanced, non-specific immune response upon reactivation following exposure to pathogens, a process that has been studied in the context of in vitro and in vivo clinical studies prior to the COVID-19 pandemic. Evaluation of the underlying pathways that are essential to inducing protective trained immunity will provide insight into identifying potential therapeutic targets that may alleviate the COVID-19 crisis. Here we review multiple immune training agents, including Bacillus Calmette-Guérin (BCG), β-glucan, and lipopolysaccharide (LPS), and the two most popular cell types involved in trained immunity, monocytes and natural killer (NK) cells, and compare the signaling pathways involved in innate immunity. Additionally, we discuss COVID-19 trained immunity clinical trials, emphasizing the potential of trained immunity to fight SARS-CoV-2 infection. Understanding the mechanisms by which training agents activate innate immune cells to reprogram immune responses may prove beneficial in developing preventive and therapeutic targets against COVID-19.
A vaccine built from potential immunogenic pieces derived from the SARS-CoV-2 spike glycoprotein: A computational approximation.
Journal of immunological methods. 2022;:113216
Coronavirus Disease 2019 (COVID-19) represents a new global threat demanding a multidisciplinary effort to fight its etiological agent-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this regard, immunoinformatics may aid to predict prominent immunogenic regions from critical SARS-CoV-2 structural proteins, such as the spike (S) glycoprotein, for their use in prophylactic or therapeutic interventions against this highly pathogenic betacoronavirus. Accordingly, in this study, an integrated immunoinformatics approach was applied to identify cytotoxic T cell (CTC), T helper cell (THC), and Linear B cell (BC) epitopes from the S glycoprotein in an attempt to design a high-quality multi-epitope vaccine. The best CTC, THC, and BC epitopes showed high viral antigenicity and lack of allergenic or toxic residues, as well as CTC and THC epitopes showed suitable interactions with HLA class I (HLA-I) and HLA class II (HLA-II) molecules, respectively. Remarkably, SARS-CoV-2 receptor-binding domain (RBD) and its receptor-binding motif (RBM) harbour several potential epitopes. The structure prediction, refinement, and validation data indicate that the multi-epitope vaccine has an appropriate conformation and stability. Four conformational epitopes and an efficient binding between Toll-like receptor 4 (TLR4) and the vaccine model were observed. Importantly, the population coverage analysis showed that the multi-epitope vaccine could be used globally. Notably, computer-based simulations suggest that the vaccine model has a robust potential to evoke and maximize both immune effector responses and immunological memory to SARS-CoV-2. Further research is needed to accomplish with the mandatory international guidelines for human vaccine formulations.
Efficacy and Safety of Shenfu Injection for Severe Pneumonia in the Elderly: A Systematic Review and Meta-Analysis Based on Western and Eastern Medicine.
Frontiers in pharmacology. 2022;:779942
Background: Although increasing clinical trials studying Shenfu injection (SFI) comprising panaxoside 0.8 mg/ml extracted from Panax ginseng C.A. Mey. and aconitine 0.1 mg/ml extracted from Aconitum carmichaeli Debeaux for elderly patients with severe pneumonia on biomarkers associated with COVID-19 progression are emerging, there is no evidence-based evaluation for the effect of SFI on elderly severe pneumonia. Objectives: To evaluate the effect of SFI on elderly patients with severe pneumonia providing hints for treating critical COVID-19, we conducted a systematic review and meta-analysis. Methods: Nine databases, namely, PubMed, EMBASE, Web of Science, Science Direct, Google Scholar, Wanfang, Chongqing VIP Database, CNKI, and SinoMed were used to search clinical trials reporting the effect of SFI as an adjuvant for elderly severe pneumonia on outcomes of interest. Primary outcomes were total effective rate, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mortality, and safety. Secondary outcomes were predictors associated with COVID-19 progression. Duplicated or irrelevant articles with unavailable data were excluded. Cochrane Collaboration's tool was used to evaluate the risk of bias by two reviewers independently. All data were analyzed by Rev Man 5.4. Continuous variables were shown as weighted mean difference (WMD) or standard mean difference (SMD) with 95% confidence intervals (95% CI), whereas dichotomous data were calculated as the risk ratio (RR) with 95% CI. Results: We included 20 studies with 1, 909 participants, and the pooled data showed that compared with standard control, SFI could improve the total effective rate (RR = 1.25, 95% CI = 1.14-1.37, and n = 689), APACHE II score (WMD = -2.95, 95% CI = -3.35, -2.56, and n = 809), and predictors associated with COVID-19 progression (brain natriuretic peptide, creatine kinase, stroke volume, cardiac output, left ventricular ejection fraction, cardiac index, sE-selectin, von Willebrand factor, activated partial thromboplastin time, platelet counts, D-Dimer, procalcitonin, and WBC count). SFI may reduce mortality (RR = 0.52, 95% CI = 0.37-0.73, and n = 429) and safety concerns (RR = 0.29, 95% CI = 0.17-0.51, and n = 150) for elderly severe pneumonia. Conclusion: SFI as an adjuvant may improve the total effective rate, APACHE II score, gas exchange, and predictors associated with COVID-19 progression, reducing mortality and safety concerns for elderly patients with severe pneumonia.
Zinc and selenium supplementation in COVID-19 prevention and treatment: a systematic review of the experimental studies.
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2022;:126956
BACKGROUND AND AIM The COVID-19 pandemic has severely affected the world's population in the last two years. Along with non-pharmacological public health interventions, major efforts have also been made to identify effective drugs or active substances for COVID-19 prevention and treatment. These include, among many others, the trace elements zinc and selenium, based on laboratory studies and some observational human studies. However, both of these study designs are not adequate to identify and approve treatments in human medicine, and experimental studies in the form of randomized controlled trials are needed to demonstrate the effectiveness and the safety of any interventions. METHODS We undertook a systematic review in which we searched for published and unpublished clinical trials using zinc or selenium supplementation to treat or prevent COVID-19 in the Pubmed, Scopus and ClinicalTrials databases up to 10 January 2022. RESULTS Amongst the published studies, we did not find any trial with selenium, whereas we retrieved four eligible randomized clinical trials using zinc supplementation, only one of which was double-blind. One of these trials looked at the effect of the intervention on the rate of new SARS-CoV-2 infections, and three at the COVID-19 clinical outcome in already infected individuals. The study populations of the four trials were very heterogeneous, ranging from uninfected individuals to those hospitalized for COVID-19. Only two studies investigated zinc alone in the intervention arm with no differences in the endpoints. The other two studies examined zinc in association with one or more drugs and supplements in the intervention arm, therefore making it impossible to disentangle any specific effects of the element. In addition, we identified 22 unpublished ongoing clinical trials, 19 on zinc, one on selenium and two on both elements. CONCLUSION No trials investigated the effect of selenium supplementation on COVID-19, while the very few studies on the effects of zinc supplementation did not confirm efficacy. Therefore, preventive or therapeutic interventions against COVID-19 based on zinc or selenium supplementation are currently unjustified, although when the results of the on-going studies are published, this may change our conclusion.
A randomized pilot study using calcitriol in hospitalized COVID-19 patients.
The systemic illness associated with SARS-CoV-2 infection results in hospitalization rate of 380.3 hospitalizations per 100,000 population, overwhelming health care systems. Vitamin D regulates expression of approximately 11,000 genes spanning many physiologic functions that include regulation of both innate and adaptive immune function. We investigate potential benefit of calcitriol therapy given to patients hospitalized with COVID-19. This was an open label, randomized clinical trial of calcitriol or no treatment given to hospitalized adult patients with COVID-19. Subjects were randomly assigned treatment with calcitriol 0.5 μg daily for 14 days or hospital discharge; or no treatment (1:1) at time of enrollment. We enrolled 50 consecutive patients, 25 per trial arm. The change in peripheral arterial oxygen saturation to the inspired fraction of oxygen (SaO2/FIO2 ratio) was calculated on admission and discharge between the groups. The control group had an average increase of +13.2 (±127.7) on discharge and the calcitriol group had an increase of +91.04 (±119.08) (p = .0305), suggesting an improvement in oxygenation among subjects who received calcitriol. Additionally, 12 patients in the control group required oxygen supplementation on admission and 21 of them were discharged on room air. 14 subjects needed oxygen supplementation in the calcitriol group on admission while all 25 were discharged on room air. Other clinical markers showed the average length of stay was 9.24 (±9.4) in the control group compared to 5.5 (±3.9) days in the calcitriol group (p = .14). The need for ICU transfer was 8 in the control group and 5 in the calcitriol group. There were 3 deaths and 4 readmissions in the control group and 0 deaths and 2 readmissions in the calcitriol group. This pilot study illustrates improvement in oxygenation among hospitalized patients with COVID-19 treated with calcitriol and suggests the need for a larger randomized trial.