Antiviral and antibacterial properties of phloroglucinols: a review on naturally occurring and (semi)synthetic derivatives with potential therapeutic interest.

Phloroglucinol and derived compounds comprise a huge class of secondary metabolites widely distributed in plants and brown algae. A vast array of biological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer has been associated to this class of compounds. In this review, the available data on the antiviral and antibacterial capacity of phloroglucinols have been analyzed. Some of these compounds and derivatives show important antimicrobial properties in vitro. Phloroglucinols have been shown to be effective against viruses, such as human immunodeficiency virus (HIV), herpes or enterovirus, and preliminary data through docking analysis suggest that they can be effective against SARS-CoV-19. Also, some phloroglucinols derivatives have shown antibacterial effects against diverse bacteria strains, including Bacillus subtilis and Staphylococcus aureus, and (semi)synthetic development of novel compounds have led to phloroglucinols with a significantly increased biological activity. However, therapeutic use of these compounds is hindered by the absence of in vivo studies and scarcity of information on their mechanisms of action, and hence further research efforts are required. On the basis of this consideration, our work aims to gather data regarding the efficacy of natural-occurring and synthetic phloroglucinol derivatives as antiviral and antibacterial agents against human pathogens, which have been published during the last three decades. The recollection of results reported in this review represents a valuable source of updated information that will potentially help researchers in the development of novel antimicrobial agents.

High SARS-CoV-2 infection rate in children unvaccinated with COVID-19 vaccine in Changzhou, China, shortly after lifting zero-COVID-19 policy in December 2022.

BACKGROUND: China experienced an overwhelming COVID-19 pandemic from middle December 2022 to middle January 2023 after lifting the zero-COVID-19 policy on December 7, 2022. However, the infection rate was less studied. We aimed to investigate the SARS-CoV-2 infection rate in children shortly after discontinuation of the zero-COVID-19 policy. METHODS: From February 20 to April 10, 2023, we included 393 children aged 8 months to less than 3 years who did not receive COVID-19 vaccination and 114 children aged 3 to 6 years who received inactivated COVID-19 vaccines based on the convenience sampling in this cross-sectional study. IgG and IgM antibodies against nucleocapsid (N) and subunit 1 of spike (S1) of SARS-CoV-2 (anti-N/S1) were measured with commercial kits (Shenzhen YHLO Biotech, China). RESULTS: Of the 393 unvaccinated children (1.5 ± 0.6 years; 52.2% boys), 369 (93.9%) were anti-N/S1 IgG positive. Of the 114 vaccinated children (5.3 ± 0.9 years; 48.2% boys), 112 (98.2%) were anti-N/S1 IgG positive. None of the unvaccinated or vaccinated children was anti-N/S1 IgM positive. The median IgG antibody titers in vaccinated children (344.91 AU/mL) were significantly higher than that in unvaccinated children (42.80 AU/mL) (P < 0.0001). The positive rates and titers of anti-N/S1 IgG had no significant difference between boys and girls respectively. CONCLUSION: Vast majority of children were infected with SARS-CoV-2 shortly after ending zero-COVID-19 policy in China. Whether these unvaccinated infected children should receive COVID-19 vaccine merits further investigation.

Comparison of the efficacy of equivalent doses of dexamethasone, methylprednisolone, and hydrocortisone for treatment of COVID-19-related acute respiratory distress syndrome: a prospective three-arm randomized clinical trial.

BACKGROUND: This prospective controlled clinical trial aimed to compare the efficacy of methylprednisolone, dexamethasone, and hydrocortisone at equivalent doses in patients with severe COVID-19. METHODS: In total, 106 patients with mild to moderate COVID-19-related acute respiratory distress syndrome (ARDS) were randomized to receive either dexamethasone (6 mg once a day), methylprednisolone (16 mg twice a day), or hydrocortisone (50 mg thrice a day) for up to 10 days. All participants received a standard of care for COVID-19. The primary and secondary efficacy outcomes included all-cause 28-day mortality, clinical status on day 28 assessed using the World Health Organization (WHO) eight-category ordinal clinical scale, number of patients requiring mechanical ventilation and intensive care unit (ICU) care, number of ventilator-free days, length of hospital and ICU stay, change in PaO2:FiO2 ratios during the first 5 days after treatment, and incidence of serious adverse events. P-values below 0.008 based on Bonferroni's multiple-testing correction method were considered statistically significant. RESULTS: According to the obtained results, there was a trend toward more favorable clinical outcomes in terms of needing mechanical ventilation and ICU care, number of ventilator-free days, change in PaO2:FiO2 ratios during the first 5 days after treatment, clinical status score at day 28, length of ICU and hospital stay, and overall 28-day mortality in patients receiving dexamethasone compared to those receiving methylprednisolone or hydrocortisone; however, likely due to the study's small sample size, the difference between groups reached a significant level only in the case of clinical status score on day 28 (p-value = 0.003). There was no significant difference in the incidence of serious adverse events between the study groups. CONCLUSION: Based on the results, severe cases of COVID-19 treated with dexamethasone might have a better clinical status at 28-day follow-up compared to methylprednisolone and hydrocortisone at an equivalent dose. Larger multicenter trials are required to confirm our findings.

Management of post-mortem examination in SARS-CoV-19 infections.

A brief overview on the management of autopsies during the SARS-CoV-19 epidemic is proposed. In particular, the point is made of the Italian laws on the subject, the characteristics required for the autopsy room and the sampling suggested for the histological examination.

Finally, an FDA Approval for an Immunization Against COVID-19: Hope on the Horizon.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a respiratory infection known as severe respiratory acute syndrome coronavirus 2 (SARS-CoV-2). The purpose of this manuscript is to review information leading to the Food and Drug Administration (FDA) approval of the Pfizer-BioNTech COVID-19 Vaccine. DATA SOURCES: A literature search was conducted of PubMed and clinicaltrials.gov (August 2018-October 2021) to identify trials related to the FDA approval of Pfizer-BioNTech COVID-19 Vaccine. STUDY SELECTION AND DATA EXTRACTION: Trials included are those the FDA deemed significant and accurate enough to be included in the FDA approval process. Information not recognized by the Centers of Disease Control and Prevention (CDC) nor FDA is omitted to not add to further confusion and misinformation. DATA SYNTHESIS: In persons 16 years or older without evidence of prior SARS-CoV-2 infection, a total of 77 COVID-19 cases (0.39%) in the vaccine group from 7 days onward after the second dose vs 833 (4.1%) in the placebo group (Vaccine efficacy 91.1%; 95% confidence interval [CI]: 88.8-93.1). According the CDC definition of severe infection, there were no severe infections in the vaccine group 7 days and onward after the second dose, compared to 31 (0.15%) in the placebo group (Vaccine efficacy 100%; 95% CI: 87.6-100.0). Relevance to Patient Care and Clinical Practice: Reduction of infection by SARS-COV-2 is a top priority in protecting the health of all people and the official approval of the Pfizer-BioNTech vaccination may improve this goal. CONCLUSIONS: Data available show a high efficacy rate of preventing SARS -CoV-2 with relatively low rates of ADE after full vaccination with Pfizer-BioNTech COVID-19 vaccine.

Early steroids and ventilator-associated pneumonia in COVID-19-related ARDS.

RATIONALE: Early corticosteroid treatment is used to treat COVID-19-related acute respiratory distress syndrome (ARDS). Infection is a well-documented adverse effect of corticosteroid therapy. OBJECTIVES: To determine whether early corticosteroid therapy to treat COVID-19 ARDS was associated with ventilator-associated pneumonia (VAP). METHODS: We retrospectively included adults with COVID-19-ARDS requiring invasive mechanical ventilation (MV) for ≥ 48 h at any of 15 intensive care units in 2020. We divided the patients into two groups based on whether they did or did not receive corticosteroids within 24 h. The primary outcome was VAP incidence, with death and extubation as competing events. Secondary outcomes were day 90-mortality, MV duration, other organ dysfunctions, and VAP characteristics. MEASUREMENTS AND MAIN RESULTS: Of 670 patients (mean age, 65 years), 369 did and 301 did not receive early corticosteroids. The cumulative VAP incidence was higher with early corticosteroids (adjusted hazard ratio [aHR] 1.29; 95% confidence interval [95% CI] 1.05-1.58; P = 0.016). Antibiotic resistance of VAP bacteria was not different between the two groups (odds ratio 0.94, 95% CI 0.58-1.53; P = 0.81). 90-day mortality was 30.9% with and 24.3% without early corticosteroids, a nonsignificant difference after adjustment on age, SOFA score, and VAP occurrence (aHR 1.15; 95% CI 0.83-1.60; P = 0.411). VAP was associated with higher 90-day mortality (aHR 1.86; 95% CI 1.33-2.61; P = 0.0003). CONCLUSIONS: Early corticosteroid treatment was associated with VAP in patients with COVID-19-ARDS. Although VAP was associated with higher 90-day mortality, early corticosteroid treatment was not. Longitudinal randomized controlled trials of early corticosteroids in COVID-19-ARDS requiring MV are warranted.

Therapeutic and prophylactic effect of flavonoids in post-COVID-19 therapy.

The high incidence of post-covid symptoms in humans confirms the need for effective treatment. Due to long-term complications across several disciplines, special treatment programs emerge for affected patients, emphasizing multidisciplinary care. For these reasons, we decided to look at current knowledge about possible long-term complications of COVID-19 disease and then present the effect of flavonoids, which could help alleviate or eliminate complications in humans after overcoming the COVID-19 infection. Based on articles published from 2003 to 2021, we summarize the flavonoids-based molecular mechanisms associated with the post-COVID-19 syndrome and simultaneously provide a complex view regarding their prophylactic and therapeutic potential. Review clearly sorts out the outcome of post-COVID-19 syndrome according particular body systems. The conclusion is that flavonoids play an important role in prevention of many diseases. We suggest that flavonoids as critical nutritional supplements, are suitable for the alleviation and shortening of the period associated with the post-COVID-19 syndrome. The most promising flavonoid with noteworthy therapeutic and prophylactic effect appears to be quercetin.

Preparation and Characterization of Disulfiram and Beta Cyclodextrin Inclusion Complexes for Potential Application in the Treatment of SARS-CoV-2 via Nebulization.

Disulfiram (DS), known as an anti-alcoholism drug, has shown a potent antiviral activity. Still, the potential clinical application of DS is limited by its low water solubility and rapid metabolism. Cyclodextrins (CDs) have been widely used to improve the solubility of drugs in water. In this study, five concentrations of hydroxypropyl ß-cyclodextrin (HP) and sulfobutyl ether ß-cyclodextrin (SBE) were used to form inclusion complexes of DS for enhanced solubility. Solutions were freeze-dried, and the interaction between DS and CD was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the nebulization properties of the DS-CD solutions were studied. The aqueous solubility of DS increased significantly when loaded to either of both CDs. The phase solubility of both complexes was a linear function of the CD concentration (AL type). Furthermore, physicochemical characterization studies showed a potent inclusion of the drug in the CD-DS complexes. Aerosolization studies demonstrated that these formulations are suitable for inhalation. Overall, the CD inclusion complexes have great potential for the enhancement of DS solubility. However, further studies are needed to assess the efficacy of DS-CD inclusion complexes against SARS-CoV-2 via nebulization.

Emergency General Surgery and COVID-19 Pandemic: Are There Any Changes? A Scoping Review.

Background and Objectives: The pandemic of SARS-CoV-19 has affected the overall spectrum of General Surgery, either in the case management part, or in the type of cases. The purpose of this review is to gather all the parameters affected and to compare these changes between the pandemic period and the corresponding time frame of the previous year. Materials and Methods: A review of literature in two electronic databases (PubMed and Scopus) was performed examining studies during the pre-pandemic (March to May 2019) and pandemic (March to May 2020) period about emergency surgeries. The differences in case presentation in emergency rooms, patient characteristics, length of hospitalization, type of surgery, complications and mortality rate were compared. Results: The comparison of the studies revealed significant results highlighting the differences between the two time periods for each parameter. There has been observed an overall decrease in the number of cases presented for emergency and urgent surgery. In terms of age, sex, and BMI, there were no significant variations amongst the patients. About the length of hospitalization, the patients hospitalized longer during the pandemic period. In terms of pathologies, the most common types of surgery were appendectomy, gastrointestinal, and colorectal resection. Mortality did not differ between the two study periods. Conclusions: COVID-19 affected a large part of Emergency General Surgery mainly concerns the type of operations performed. The hospitalization of patients, the complications that may have arisen and the recognition of emergencies were the most important issues faced by health care officials in hospitals during the period of COVID-19; however, there were parameters like mortality and patients' characteristics that did not appear to differ with pre-pandemic era.

Impact of the COVID-19 pandemic on treat-to-target strategies and physical consultations in >7000 patients with inflammatory arthritis.

OBJECTIVES: To explore the impact of the COVID-19 pandemic on treat-to-target strategies (disease activity, remission rates) and access to physical consultations in patients with inflammatory rheumatic disease, as well as to explore characteristics of patients with/without physical consultations in the clinic and the impact of early vs established disease. METHODS: Patients with RA, PsA or axial SpA (axSpA) prospectively followed in the nationwide DANBIO registry answered online questionnaires and reported patient-reported outcomes (PROs) in June and November 2020. Patient characteristics, disease activity and physical consultations in the clinic before and during the pandemic were identified in DANBIO [all patients and subgroups with early disease (disease duration ≤2 years)]. In individual patients, changes in PROs before and during the pandemic were calculated. Characteristics of patients with/without physical consultations were described (age, gender, education level, comorbidities, disease duration, treatment). RESULTS: We included 7836 patients (22% of eligible patients), 12% of which had early disease. PROs were stable before and during the pandemic, with median changes approximating zero, as well as in patients with early disease. Remission rates were stable. The relative decrease in the number of patients with physical consultations was 21-72%, which was highest in axSpA. Characteristics of patients with/without physical consultations were similar. Self-reported satisfaction with treatment options and access was >70%; the preferred contact form was physical consultation (66%). CONCLUSION: In this nationwide study performed during the first 8 months of the pandemic, patient satisfaction was high and the PROs and remission rates remained stable despite the remarkable reduction in physical consultations, as well as in patients with early disease. Characteristics of patients with/without physical consultations appeared similar.

Histopathological findings in COVID-19-induced cutaneous lesions. Clinicopathological correlation of SARS-CoV-19 dermatologic patterns: review of the literature.

An increasing number of publications have brought attention to COVID-19-associated cutaneous lesions. Histopathological descriptions and clinical correlation of the histopathological findings of COVID-19 skin lesions are lacking. In this manuscript, we reviewed and described the histopathological characteristics of COVID-19 infection cutaneous patterns reported in the literature.

Nonlinear science against the COVID-19 pandemic.

This special issue showcases recent uses of mathematical and nonlinear science methods in the study of different problems arising in the context of the COVID-19 pandemic. The sixteen original research papers included in this collection span a wide spectrum of studies including classical epidemiological models, new models accounting for COVID-19 specificities, non-pharmaceutical control measures, network models and other problems related to the pandemic.

[Assessing the impact of pandemic on the resilience of older adults in Tomsk region.]

The article presents pioneer results of assessing the impact of the pandemic on the resilience of the older adults of the Tomsk region. We assessed the resilience of older adults and its predictors basing upon the survey of 400 respondents aged 55-92 using the Connor-Davidson resilience scale (CD-RISC-25). The results reveal statistically significant relationship between the resilience, material well-being and emotional state of elderly respondents in the context of the coronavirus pandemic. The results of the study complement the existing approaches to assessing and measuring the parameters of the quality of life of the older adults, and can be used to design tools for strengthening the resilience in line with the concept of active ageing.

Congenital cardiac interventions during the peak phase of COVID-19 pandemics in the country in a pandemics hospital in Istanbul.

INTRODUCTION: In this report, we aim to present our algorithm and results of patients with congenital cardiac disorders who underwent surgical or interventional procedures during the peak phase of the pandemics in our country. PATIENTS AND METHODS: The first COVID-19 case was diagnosed in Turkey on 11 March, 2020, and the peak phase seemed to end by the end of April. All the patients whom were referred, treated, or previously operated but still at the hospital during the peak phase of COVID-19 pandemics in the country were included into this retrospective study. Patient's diagnosis, interventions, adverse events, and early post-procedural courses were studied. RESULTS: Thirty-one patients with various diagnoses of congenital cardiovascular disorders were retrospectively reviewed. Ages of the patients ranged between 2 days and 16 years. Seventeen cases were males and 14 cases were females. Elective cases were postponed. Priority was given to interventional procedures, and five cases were treated percutaneously. Palliative procedures were preferred in patients whom presumably would require long hospital stay. Corrective procedures were not hesitated in prioritised stable patients. Mortality occurred in one patient. Eight patients out of 151 ICU admissions were diagnosed with COVID-19, and they were transferred to COVID-19 ICU immediately. Three nurses whom also took care of the paediatric cases became infected with SARS-CoV-2; however, the children did not catch the disease. CONCLUSION: Mandatory and emergent congenital cardiac percutaneous and surgical procedures may be performed with similar postoperative risks as there are no pandemics with meticulous care and preventive measures.

NYU-EDA in modelling the effect of COVID-19 on patient volumes in a Finnish emergency department.

BACKGROUND: Emergency departments (EDs) worldwide have been in the epicentre of the novel coronavirus disease (COVID-19). However, the impact of the pandemic and national emergency measures on the number of non-COVID-19 presentations and the assessed acuity of those presentations remain uncertain. METHODS: We acquired a retrospective cohort containing all ED visits in a Finnish secondary care hospital during years 2018, 2019 and 2020. We compared the number of presentations in 2020 during the national state of emergency, i.e. from March 16 to June 11, with numbers from 2018 and 2019. Presentations were stratified using localized New York University Emergency Department Algorithm (NYU-EDA) to evaluate changes in presentations with different acuity levels. RESULTS: A total of 27,526 presentations were observed. Compared to previous two years, total daily presentations were reduced by 23% (from 113 to 87, p < .001). In NYU-EDA classes, Non-Emergent visits were reduced the most by 42% (from 18 to 10, p < .001). Emergent presentations were reduced by 19 to 28% depending on the subgroup (p < .001). Number of injuries were reduced by 25% (from 27 to 20, p < .001). The NYU-EDA distribution changed statistically significantly with 4% point reduction in Non-Emergent visits (from 16 to 12%, p < .001) and 0.9% point increase in Alcohol-related visits (from 1.6 to 2.5%, p < .001). CONCLUSIONS: We observed a significant reduction in total ED visits in the course of national state of emergency. Presentations were reduced in most of the NYU-EDA groups irrespective of the assessed acuity. A compensatory increase in presentations was not observed in the course of the 3 month lockdown. This implies either reduction in overall morbidity caused by decreased societal activity or widespread unwillingness to seek required medical advice.

Understanding the effects of COVID-19 on patients with diabetic nephropathy: a systematic review.

Background: Diabetic nephropathy is one of the consequences of diabetes mellitus that causes a continuous decline in the eGFR. After the COVID-19 pandemic, studies have shown that patients with diabetic nephropathy who had contracted COVID-19 have higher rates of morbidity and disease progression. The aim of this study was to systematically review the literature to determine and understand the effects and complications of SARS-CoV-2 on patients with diabetic nephropathy. Materials and methods: The authors' research protocol encompassed the study selection process, search strategy, inclusion/exclusion criteria, and a data extraction plan. A systematic review was conducted by a team of five reviewers, with an additional reviewer assigned to address any discrepancies. To ensure comprehensive coverage, the authors employed multiple search engines including PubMed, ResearchGate, ScienceDirect, SDL, Ovid, and Google Scholar. Results: A total of 14 articles meeting the inclusion criteria revealed that COVID-19 directly affects the kidneys by utilizing ACE2 receptors for cell entry, which is significant because ACE2 receptors are widely expressed in the kidney. Conclusion: COVID-19 affects kidney health, especially in individuals with diabetic nephropathy. The mechanisms include direct viral infection and immune-mediated injury. Early recognition and management are vital for improving the outcomes.

"Who Takes Care of Carers?": Experiences of Intensive Care Unit Nurses in the Acute Phase of the COVID-19 Pandemic.

Introduction: The COVID-19 pandemic caused an international health emergency situation where nursing took on a fundamental role. The high number of patients in hospital ICUs led to a shift in nurses' working conditions and workload. Objective: The objective of this study was to describe the experiences of nurses who worked in ICUs during the acute phase of the COVID-19 pandemic. Methodology: A qualitative, descriptive study was carried out, with the participation of 21 nurses who worked in the ICU during the pandemic. Data collection took place between May and July 2021 through 21 in-depth interviews. Results: Three main themes emerged: (1) COVID-19 in ICUs: nurses on the frontline. (2) United against adversity: teamwork. (3) New optics of critical care and the nursing profession. COVID-19 was perceived with harshness, and the lack of knowledge about the virus generated confusion, anxiety and fear due to the risk of transmission to family members and relatives. The pandemic marked a shift in the management of human, material and economic resources. Novice nurses learned critical care at an accelerated pace, with significant physical and psychological strain. Expert nurses carried the burden of training new nurses. Although there were tense situations, experiencing these adverse situations as a team led to feelings of increased belonging, togetherness and professional bonding for nurses. While the participants noted an increase in motivation to continue in their profession, they also had a feeling of not having been cared for as they deserve by healthcare institutions.

Tracheostomy before and during COVID-19 pandemic.

BACKGROUND: The aim of the study was to provide insight into the influence of the COVID-19 on the frequency and characteristics of urgent and emergent tracheostomies (TS), comparing data collected both before and during the pandemic. Our two hypotheses were that during COVID-19, more TS were performed in the emergent setting and that during COVID-19 more TS were performed under general anaesthesia. PATIENTS AND METHODS: The research was retrospective. The study period included the two years before and after the COVID-19 outbreak in Slovenia. Forty-one patients in each period met the inclusion criteria. Their medical charts were reviewed. The anamnestic, clinical, surgical and anaesthesiological data were collected. The two groups of patients from corresponding time periods were statistically compared. RESULTS: Predominantly men required the surgical resolution of acute upper airway obstruction (76% of patients). The causes for acute respiratory distress included head and neck cancer (62%), infections (20%), vocal cord paralysis (16%), and stenosis (2%). There were no statistically significant differences either in the (emergent/urgent) setting of TS or in the type of anaesthesia used. Both hypotheses were rejected. A statistically significant rise in use of the C-MAC laryngoscope during COVID-19 (from 3% to 15%) was reported. CONCLUSIONS: The outbreak of COVID-19 did not have a statistically significant effect on the frequency of performing emergent and urgent tracheostomies nor on the use of general or local anaesthesia. It did, however, require a change of intubation technique. Consequently, a significant rise in the use of the C-MAC laryngoscope was noted.

Covid-19 in Parkinson's Disease treated by drugs or brain stimulation.

PURPOSE: Covid-19 has affected all people, especially those with chronic diseases, including Parkinson's Disease (PD). Covid-19 may affect both motor and neuropsychiatric symptoms of PD patients. We intend to evaluate different aspects of Covid-19 impact on PD patients. METHODS: 647 PD patients were evaluated in terms of PD-related and Covid-19-related clinical presentations in addition to past medical history during the pandemic through an online questioner. They were compared with an age-matched control group consist of 673 individuals and a sample of the normal population consist of 1215 individuals. RESULTS: The prevalence of Covid-19 in PD patients was 11.28%. The mortality was 1.23% among PD patients. The prevalence of Covid-19 in PD patients who undergone Deep Brain Stimulation (DBS) was 18.18%. No significant association was found between the duration of disease and the prevalence of Covid-19. A statistically significant higher prevalence of Covid-19 in PD patients who had direct contact with SARS-CoV-19 infected individuals was found. No statistically significant association has been found between the worsening of motor symptoms and Covid-19. PD patients and the normal population may differ in the prevalence of some psychological disorders, including anxiety and sleeping disorders, and Covid-19 may affect the psychological status. CONCLUSION: PD patients possibly follow tighter preventive protocols, which lead to lower prevalence and severity of Covid-19 and its consequences in these patients. Although it seems Covid-19 does not affect motor and psychological aspects of PD as much as it was expected, more accurate evaluations are suggested in order to clarify such effects.