No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study.

BACKGROUND: The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. METHODS: We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. RESULTS: We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. CONCLUSIONS: Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.

Computational study on the affinity of potential drugs to SARS-CoV-2 main protease.

Herein, we report a computational investigation of the binding affinity of dexamethasone, betamethasone, chloroquine and hydroxychloroquine to SARS-CoV-2 main protease using molecular and quantum mechanics as well as molecular docking methodologies. We aim to provide information on the anti-COVID-19 mechanism of the abovementioned potential drugs against SARS-CoV-2 coronavirus. Hence, the 6w63 structure of the SARS-CoV-2 main protease was selected as potential target site for the docking analysis. The study includes an initial conformational analysis of dexamethasone, betamethasone, chloroquine and hydroxychloroquine. For the most stable conformers, a spectroscopic analysis has been carried out. In addition, global and local reactivity indexes have been calculated to predict the chemical reactivity of these molecules. The molecular docking results indicate that dexamethasone and betamethasone have a higher affinity than chloroquine and hydroxychloroquine for their theoretical 6w63 target. Additionally, dexamethasone and betamethasone show a hydrogen bond with the His41 residue of the 6w63 protein, while the interaction between chloroquine and hydroxychloroquine with this amino acid is weak. Thus, we confirm the importance of His41 amino acid as a target to inhibit the SARS-CoV-2 Mpro activity.

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis of Early COVID-19 and Treated at Home Within 3 Days or After 3 Days of Symptom Onset with Prescribed and Non-Prescribed Treatments Between November 2020 and August 2021.

BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. RESULTS Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (<72 h from onset of symptoms), and group 2 (n=73) was treated >72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P<0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P<0.001). CONCLUSIONS This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization.

Scleredema adultorum of Buschke associated with hypothyroidism and liver cirrhosis.

Scleredema adultorum of Buschke is a rare disorder of the connective tissue, involving the skin. Here, we present a 61-year-old male, who is a known case of compensated liver cirrhosis with a past history of being treated for autoimmune thyrotoxicosis, who presented with complaints of alopecia, skin tightening, dry skin, pruritus, and woody indurated plaques on the skin of the upper back, shoulder, and arms. Skin biopsy of the arm revealed the characteristic features of scleredema. He was extensively evaluated for known literature-cited causes of scleredema, and the work up revealed a negative result. He was also found to be hypothyroid on presentation. Hence, we present a case of scleredema occurring in a patient with hypothyroidism and chronic liver disease, which to our knowledge is being described for the first time in literature.

Dexamethasone versus betamethasone for preterm birth: a systematic review and network meta-analysis.

OBJECTIVE: This study aimed to evaluate the comparative clinical effectiveness and safety of dexamethasone vs betamethasone for preterm birth. DATA SOURCES: The sources searched were MEDLINE, EMBASE, Cochrane Library, LILACS, ClinicalTrials.gov, and International Clinical Trials Registry Platform without language restrictions until October 2019 in addition to the reference lists of included studies. Field experts were also contacted. STUDY ELIGIBILITY CRITERIA: Randomized or quasi-randomized controlled trials comparing any corticosteroids against each other or against placebo at any dose for preterm birth were included in the study. METHODS: Three researchers independently selected and extracted data and assessed the risk of bias of the included studies by using Early Review Organizing Software and Covidence software. Random-effects pairwise meta-analysis and Bayesian network meta-analysis were performed. The primary outcomes were chorioamnionitis, endometritis or puerperal sepsis, neonatal death, respiratory distress syndrome, and neurodevelopmental disability. RESULTS: A total of 45 trials (11,227 women and 11,878 infants) were included in the study. No clinical or statistical difference was found between dexamethasone and betamethasone in neonatal death (odds ratio, 1.05; 95% confidence interval, 0.62-1.84; moderate-certainty evidence), neurodevelopmental disability (odds ratio, 1.03; 95% confidence interval, 0.80-1.33; moderate-certainty evidence), intraventricular hemorrhage (odds ratio, 1.04; 95% confidence interval, 0.56-1.78); low-certainty evidence), or birthweight (+5.29 g; 95% confidence interval, -49.79 to 58.97; high-certainty evidence). There was no statistically significant difference, but a potentially clinically important effect was found between dexamethasone and betamethasone in chorioamnionitis (odds ratio, 0.70; 95% confidence interval, 0.45-1.06; moderate-certainty evidence), fetal death (odds ratio, 0.81; 95% confidence interval, 0.24-2.41; low-certainty evidence), puerperal sepsis (odds ratio, 2.04; 95% confidence interval, 0.72-6.06; low-certainty evidence), and respiratory distress syndrome (odds ratio, 1.34; 95% confidence interval, 0.96-2.11; moderate-certainty evidence). Meta-regression, subgroup, and sensitivity analyses did not reveal important changes regarding the main analysis. CONCLUSION: Corticosteroids have proven effective for most neonatal and child-relevant outcomes compared with placebo or no treatment for women at risk of preterm birth. No important difference was found on neonatal death, neurodevelopmental disability, intraventricular hemorrhage, and birthweight between corticosteroids, and there was no statistically significant difference, but a potentially important difference was found in chorioamnionitis, fetal death, endometritis or puerperal sepsis, and respiratory distress syndrome. Further research is warranted to improve the certainty of evidence and inform health policies.

Randomised placebo-controlled multicentre effectiveness trial of adjunct betamethasone therapy in hospitalised children with community-acquired pneumonia: a trial protocol for the KIDS-STEP trial.

INTRODUCTION: Community-acquired pneumonia (CAP) causes around 10 hospitalisations per 1000 child-years, each associated with an average 13 non-routine days experienced and more than 4 parent workdays lost. In adults, steroid treatment shortens time to clinical stabilisation without an increase in complications in patients with CAP. However, despite promising data from observational studies, there is a lack of high-quality evidence for the use of steroids. METHODS AND ANALYSIS: The KIDS-STEP trial is a multicentre, randomised, double-blind, placebo-controlled superiority trial of betamethasone treatment on outcome of hospitalised children with CAP. Children are enrolled in paediatric emergency departments of hospitals across Switzerland and randomised to adjunct oral betamethasone for 2 days or matching placebo in addition to standard of care treatment. The co-primary outcomes are the proportion of children clinically stable 48 hours after randomisation and the proportion of children with CAP-related readmission within 28 days after randomisation. Secondary outcomes include length of hospital stay, time away from routine childcare and healthcare utilisation and total antibiotic prescriptions within 28 days from randomisation.Each of the co-primary outcomes will be analysed separately. We will test clinical stability rates using a proportion test; to test non-inferiority in readmission rates, we will construct 1-α % CI of the estimated difference and test if it contains the pre-defined margin of 7%. Success is conditional on both tests. A simulation-based sample size estimation determined that recruiting 700 patients will ensure a power of 80% for the study. ETHICS AND DISSEMINATION: The trial protocol and materials were approved by ethics committees in Switzerland (lead: Ethikkommission Nordwest und Zentralschweiz) and the regulatory authority Swissmedic. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate. TRIAL REGISTRATION NUMBER: NCT03474991 and SNCTP000002864.

Interventions for the treatment of persistent post-COVID-19 olfactory dysfunction.

BACKGROUND: Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training). OBJECTIVES: To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach.  SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA: Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Only individuals who had symptoms for at least four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included one study with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days. Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence). Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence). Serious adverse events andother adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available. For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.

Effect of nasal corticosteroid in the treatment of anosmia due to COVID-19: A randomised double-blind placebo-controlled study.

OBJECTIVES: Anosmia is a common debilitating symptom of the novel coronavirus disease 2019 (COVID-19). Currently, there is no satisfactory treatment of anosmia. Therefore, this study was conducted to evaluate the therapeutic effect of nasal betamethasone drops in the recovery of olfaction in COVID-19-associated anosmia. METHODS: The study was designed as a randomised, double-blind, placebo-controlled clinical trial. In total, 276 PCR-confirmed COVID-19 patients who were presented to the outpatient clinic with anosmia were enrolled in the study. In the betamethasone group, 138 participants received nasal drops of betamethasone 3 times daily until recovery for a maximum of one month. Similar dose of 9% NaCl drops was administered to 138 participants in the placebo group. RESULTS: The median age of participants was 29 years (IQR 23-37). Among them, 198 (71.7%) were females. Ageusia was co-presented with anosmia in 234 (84.8%) of participants. In this study, 83% of participants had recovered from anosmia within 30 days, with a median recovery time of 13 days (IQR 8-18). Compared to placebo, nasal application of betamethasone drops has no significant effect on the recovery time of anosmia (hazard ratio 0.88; 95% CI 0.68-1.14; P = 0.31). CONCLUSION: The use of nasal betamethasone to facilitate the recovery time of acute anosmia is not advised. In addition, age, smoking status, the duration of anosmia at presentation, and the co-presentation of ageusia with anosmia are important determinant covariates for the recovery time of anosmia. Further clinical trials, which take these covariates into account, will need to be undertaken. The trail has been registered at ClinicalTrails.gov, NCT04569825.

Understanding the clinical and demographic characteristics of second coronavirus spike in 192 patients in Tehran, Iran: A retrospective study.

During the last months of the coronavirus pandemic, with all those public restrictions and health interventions, the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears now to have been raised in some countries around the world. Iran was one of those first countries facing the second wave of coronavirus, due to the lack of appropriate public restrictions because of economic problems the country is facing. The clinical and demographic characteristics of severe cases and non-severe cases of Coronavirus Disease (COVID-19) in 192 patients in Tehran, Iran, between June 16 and July 11, 2020, were investigated. The patients were divided into severe cases (n = 82) and non-severe cases (n = 110). Demographic and clinical characteristics were compared between the two study clusters. The mean age was 54.6 ± 17.2 years, and the most common presenting symptom was persistent cough (81.8%) and fever (79.7%). The logistic regression model revealed that age, BMI, and affected family members were statistically associated with severity. Patients with complicated conditions of disorders faced more hospitalization days and medical care than the average statistical data. As the coronavirus spike in the case and death reports from June 2020, we observed the rise in the incidence of severe cases, where 42.7% (82/192) of cases have resulted in severe conditions. Our findings also suggested that the effect of IFB (Betamethasone) was more valid than the other alternative drugs such as LPV/r and IVIg.

Corticosteroid Guidance for Pregnancy during COVID-19 Pandemic.

The novel coronavirus disease 2019 (COVID-19) pandemic is causing a necessary, rapid adjustment within the field of obstetrics. Corticosteroid use is a mainstay of therapy for those women delivering prematurely. Unfortunately, corticosteroid use has been associated with worse outcomes in COVID-19 positive patients. Given this information, it is necessary that obstetricians adjust practice to carefully weigh the fetal benefits with maternal risks. Therefore, our institution has examined the risks and benefits and altered our corticosteroid recommendations. KEY POINTS: · Corticosteroid use is an important part of prematurity treatment because it provides benefit to the fetus.. · Corticosteroid use may be related with increased morbidity and mortality in novel coronavirus disease 2019 (COVID-19).. · Therefore, during the COVID-19 pandemic, an alteration in current corticosteroid practices is necessary to uniquely weigh the maternal risks and fetal benefits..