Factors Associated with the Antibiotic Treatment of Children Hospitalized for COVID-19 during the Lockdown in Serbia.

Unselective use of antibiotics to treat children with COVID-19 is one of the major issues during the pandemic in Serbia. Thus far, there has been no evidence about the predictors of multiple antibiotic use in the treatment of children with COVID-19. The purpose of this study was to assess the prevalence of antibiotic use, as well as to examine demographic and clinical factors associated with a greater number of antibiotics and with a longer antibiotic treatment administered to hospitalized children with COVID-19 during the lockdown in Serbia. This study included all children who were hospitalized from 6 March to 31 May 2020 at the only pediatric COVID-19 hospital, and who were confirmed to have SARS-CoV-2 infection. Demographic, clinical, and laboratory data were collected from medical records. The antibiotic treatment included the use of azithromycin, cephalosporin (ceftriaxone), ampicillin-amikacin, and hydroxychloroquine. The overall prevalence of antibiotics use in children hospitalized with COVID-19 regardless of age was 47.2% (43.3% in children aged 1-5 years and 44.4% in those aged 5-17 years). In children aged 1-5 years, not having a family member affected by COVID-19 (B = -1.38, 95% confidence interval [CI] -2.43, -0.34, p = 0.011), having pneumonia on chest X-ray (B = 0.81, 95%CI 0.34, 1.29, p = 0.002), being a boy (B = -0.65, 95%CI -1.17, -0.13, p = 0.018), and having higher C-reactive protein (CRP) values on admission (B = 0.12, 95%CI 0.07, 0.17, p = 0.001) were associated with the administration of a higher number of antibiotics. These factors, along with having fever (B = 3.20, 95%CI 1.03, 5.37, p = 0.006), were associated with a longer duration of antibiotic treatment in children aged 1-5 years. In children aged 5-17 years, having pharyngeal erythema (B = 1.37, 95%CI 0.61, 2.13, p = 0.001), fever (B = 0.43, 95%CI 0.07, 0.79, p = 0.018), and pneumonia on chest X-ray (B = 0.91, 95%CI 0.53, 1.29, p = 0.001), not having rhinorrhea (B = -1.27, 95%CI -2.47, -0.08, p = 0.037), being a girl (B = 0.52, 95%CI 0.08, 0.97, p = 0.021), and having higher CRP values on admission (B = 0.04, 95%CI 0.01, 0.06, p = 0.006) were associated with the administration of a higher number of antibiotics. These factors, not including the absence of rhinorrhea, were associated with a longer duration of antibiotics treatment in children aged 5-17 years. Demographic, epidemiological, clinical, and laboratory parameters were associated with the use of multiple antibiotics and a longer duration of antibiotic treatment both among children aged 1-5 years and those aged 5-17 years.

How Covid-19 changed the epidemiology of febrile urinary tract infections in children in the emergency department during the first outbreak.

BACKGROUND: The first Covid-19 pandemic affected the epidemiology of several diseases. A general reduction in the emergency department (ED) accesses was observed during this period, both in adult and pediatric contexts. METHODS: This retrospective study was conducted on the behalf of the Italian Society of Pediatric Nephrology (SINePe) in 17 Italian pediatric EDs in March and April 2020, comparing them with data from the same periods in 2018 and 2019. The total number of pediatric (age 0-18 years) ED visits, the number of febrile urinary tract infection (UTI) diagnoses, and clinical and laboratory parameters were retrospectively collected. RESULTS: The total number of febrile UTI diagnoses was 339 (73 in 2020, 140 in 2019, and 126 in 2018). During the first Covid-19 pandemic, the total number of ED visits decreased by 75.1%, the total number of febrile UTI diagnoses by 45.1%, with an increase in the UTI diagnosis rate (+ 121.7%). The data collected revealed an increased rate of patients with two or more days of fever before admission (p = 0.02), a significant increase in hospitalization rate (+ 17.5%, p = 0.008) and also in values of C reactive protein (CRP) (p = 0.006). In 2020, intravenous antibiotics use was significantly higher than in 2018 and 2019 (+ 15%, p = 0.025). Urine cultures showed higher Pseudomonas aeruginosa and Enterococcus faecalis percentages and lower rates of Escherichia coli (p = 0.02). CONCLUSIONS: The first wave of the Covid-19 pandemic had an essential impact on managing febrile UTIs in the ED, causing an absolute reduction of cases referring to the ED but with higher clinical severity. Children with febrile UTI were more severely ill than the previous two years, probably due to delayed access caused by the fear of potential hospital-acquired Sars-Cov-2 infection. The possible increase in consequent kidney scarring in this population should be considered.

A retrospective comparative analysis of factors affecting the decision and outcome of initial intravenous immunoglobulin alone or intravenous immunoglobulin plus methylprednisolone use in children with the multisystem inflammatory syndrome.

BACKGROUND: For children with the multisystem inflammatory syndrome(MIS-C), intravenous immunoglobulins (IVIG) with or without methylprednisolone are the most effective treatment. In this study, IVIG combined with methylprednisolone was compared to IVIG used alone in children with MIS-C. METHODS: This retrospective cohort study was carried out between April 1, 2020, and November 1, 2021. This study covered all children with MIS-C. According to whether they received IVIG alone or IVIG with methylprednisolone as an initial treatment for MIS-C, the patients were split into two groups. The IVIG dosage for the patients in group I was 2 gr/kg, whereas the IVIG dosage for the patients in group II was 2 gr/kg + 2 mg/kg/day of methylprednisolone. These two groups were contrasted in terms of the frequency of fever, length of hospital stay, and admission to the pediatric intensive care unit. RESULTS: The study comprised 91 patients who were diagnosed with MIS-C and were under the age of 18. 42 (46.2%) of these patients were in the IVIG alone group (group I), and 49 (53.8%) were in the IVIG + methylprednisolone group (group II). Patients in group II had a severe MIS-C ratio of 36.7%, which was substantially greater than the rate of severe MIS-C patients in group I (9.5%) (p 0.01). When compared to group I (9.5%), the rate of hypotension was considerably higher in group II (30.6%) (p = 0.014). Additionally, patients in group II had considerably higher mean serum levels of C-reactive protein. The incidence of fever recurrence was 26.5% in group II and 33.3% in group I, however the difference was not statistically significant (p > 0.05). CONCLUSIONS: The choice of treatment for patients with MIS-C should be based on an individual evaluation. In MIS-C children with hypotension and/or with an indication for a pediatric intensive care unit, a combination of IVIG and methylprednisolone may be administered. For the treatment modalities of children with MIS-C, however, randomized double-blind studies are necessary.

[Overview of Meta-analysis of Lianhua Qingwen preparations in treatment of viral diseases].

This study aims to obtain higher-level evidence by overviewing the Meta-analysis of Lianhua Qingwen preparations in the treatment of viral diseases including influenza, coronavirus disease 2019(COVID-19), and hand, foot and mouth disease(HFMD). CNKI, Wanfang, VIP, China Clinical Trial Registry(ChiCTR), PubMed, EMbase, Web of Science, and Cochrane Library were searched for the Meta-analysis about the treatment of viral diseases with Lianhua Qingwen preparations from the database establishment to April 1, 2022. After literature screening and data extraction, AMSTAR2 and the grading of recommendations assessment, development and evaluations(GRADE) system were used to assess the methodological quality and evidence quality, respectively, and then the efficacy and safety outcomes of Lianhua Qingwen preparations in the treatment of viral diseases were summarized. Thirteen Meta-analysis were finally included, three of which were rated as low grade by AMSTAR2 and ten as very low grade. A total of 75 outcome indicators were obtained, involving influenza, COVID-19, and HFMD. According to the GRADE scoring results, the 75 outcome indicators included 5(6.7%) high-level indicators, 18(24.0%) mediate-level indicators, 25(33.3%) low-level evidence indicators, and 27(36.0%) very low-level indicators.(1)In the treatment of influenza, Lianhua Qingwen preparations exhibited better clinical efficacy than other Chinese patent medicines and Ribavirin and had similar clinical efficacy compared with Oseltamivir. Lianhua Qingwen preparations were superior to other Chinese patent medicines, Oseltamivir, and Ribavirin in alleviating clinical symptoms. They showed no significant differences from Oseltamivir or conventional anti-influenza treatment in terms of the time to and rate of negative result of viral nucleic acid test.(2)In the treatment of COVID-19, Lianhua Qingwen preparation alone or combined with conventional treatment was superior to conventional treatment in terms of total effective rate, main symptom subsidence rate and time, fever clearance rate, duration of fever, time to fever clearance, cough subsidence rate, time to cough subsidence, fatigue subsidence rate, time to fatigue subsidence, myalgia subsidence rate, expectoration subsidence rate, chest tightness subsidence rate, etc. Lianhua Qingwen preparations no difference from conventional treatment in terms of subsiding sore throat, nausea, diarrhea, loss of appetite, headache, and dyspnea. In terms of chest CT improvement rate, rate of progression to severe case, cure time, and hospitalization time, Lianhua Qingwen alone or in combination with conventional treatment was superior to conventional treatment.(3)In the treatment of HFMD, Lianhua Qingwen Granules was superior to conventional treatment in terms of total effective rate, average fever clearance time, time to herpes subsidence, and time to negative result of viral nucleic acid test.(4)In terms of safety, Lianhua Qingwen preparations led to low incidence of adverse reactions, all of which were mild and disappeared after drug withdrawal. The available evidence suggests that in the treatment of influenza, COVID-19, and HFMD, Lianhua Qingwen preparations can relieve the clinical symptoms, shorten the hospitalization time, and improve the chest CT. They have therapeutic effect and good safety in the treatment of viral diseases. However, due to the low quality of available studies, more high-quality clinical trials are needed to support the above conclusions.

COVID-19 Infection in Well-Appearing 30- to 90-Day-Old Infants with Fever without a Source.

Fever without a source (FWS) is common clinical status in the young infants. The aim of this study was to evaluate the clinical and laboratory findings of coronavirus disease (COVID-19) infection in well-appearing infants with FWS. Well-appearing febrile infants between 30 and 90 days who were evaluated as FWS in the pediatric emergency department and tested for COVID-19 were divided into two groups: COVID-19 (+) and (-). The clinical and laboratory findings of the patients were compared. The study included 95 febrile infants with FWS, and the mean age was 59.62 ± 16.82 days. The nasopharyngeal COVID-19 polymerase chain reaction test results of 29/95 (30.5%) patients were positive, while 66/95 (69.5%) were negative. The complaints of irritability and nasal congestion were found to be significantly more common in COVID-19-positive patients (p = 0.04 and p = 0.041, respectively). The hospitalization rate (p = 0.009), length of hospital stay (p = 0.026), initiation of antibiotic treatment (p < 0.001) and duration of antibiotic treatment (p = 0.036) were significantly lower in the COVID-19 (+) patients. The C-reactive protein (CRP, p < 0.001), absolute neutrophil count (ANC, p < 0.001), absolute lymphocyte count (ALC, p = 0.015), white blood cell (WBC, p < 0.001) and systemic immune-inflammation index (SII, p < 0.001) were found to be significantly lower in the COVID-19 (+) patient group. There was no significant difference between the groups in terms of neutropenia, lymphopenia or leukopenia.COVID-19 infection may present as an FWS. During the pandemic period, testing for COVID-19 among infants who were evaluated as FWS may reduce unnecessary hospitalizations and antibiotic treatments, and shorten hospital stays and duration of antibiotics.

Fosfomycin Vs Ciprofloxacin as Oral Step-Down Treatment for Escherichia coli Febrile Urinary Tract Infections in Women: A Randomized, Placebo-Controlled, Double-Blind, Multicenter Trial.

BACKGROUND: We aimed to determine the noninferiority of fosfomycin compared to ciprofloxacin as an oral step-down treatment for Escherichia coli febrile urinary tract infections (fUTIs) in women. METHODS: This was a double-blind, randomized, controlled trial in 15 Dutch hospitals. Adult women who were receiving 2-5 days of empirical intravenous antimicrobials for E. coli fUTI were assigned to step-down treatment with once-daily 3g fosfomycin or twice-daily 0.5g ciprofloxacin for 10 days of total antibiotic treatment. For the primary end point, clinical cure at days 6-10 post-end of treatment (PET), a noninferiority margin of 10% was chosen. The trial was registered on Trialregister.nl (NTR6449). RESULTS: After enrollment of 97 patients between 2017 and 2020, the trial ended prematurely because of the coronavirus disease 2019 pandemic. The primary end point was met in 36 of 48 patients (75.0%) assigned to fosfomycin and 30 of 46 patients (65.2%) assigned to ciprofloxacin (risk difference [RD], 9.6%; 95% confidence interval [CI]: -8.8% to 28.0%). In patients assigned to fosfomycin and ciprofloxacin, microbiological cure at days 6-10 PET occurred in 29 of 37 (78.4%) and 33 of 35 (94.3%; RD, -16.2%; 95% CI: -32.7 to -0.0%). Any gastrointestinal adverse event was reported in 25 of 48 (52.1%) and 14 of 46 (30.4%) patients (RD, 20.8%; 95% CI: 1.6% to 40.0%), respectively. CONCLUSIONS: Fosfomycin is noninferior to ciprofloxacin as oral step-down treatment for fUTI caused by E. coli in women. Fosfomycin use is associated with more gastrointestinal events. CLINICAL TRIAL REGISTRATION: Trial NL6275 (NTR6449).

TAFRO syndrome with a fatal clinical course following BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccination: A case report.

TAFRO syndrome is a rare disorder that manifests as thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. Although this disease often follows a severe clinical course, the cause remains unknown. The coronavirus disease 2019 (COVID-19) pandemic is a major global problem. Vaccination against COVID-19 has been successful; however, there are concerns about severe adverse events. Herein, we report a rare presentation of TAFRO syndrome triggered by the COVID-19 vaccine with a fatal clinical course. A 42-year-old Japanese man presented to our hospital complaining of fever lasting for 2 weeks that occurred a day after receiving the BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccine. The patient had a low platelet count, ascites, reticulin myelofibrosis, renal failure, and lymphadenopathy and was diagnosed with TAFRO syndrome. Despite administering several immunosuppressive drugs, the condition did not improve. The patient repetitively developed and eventually died of bacteremia caused by multidrug-resistant Klebsiella pneumoniae. We highlight the first reported case of TAFRO syndrome after COVID-19 vaccination.

Panic or peace - prioritising infant welfare when medicating feverish infants: a grounded theory study of adherence in a paediatric clinical trial.

BACKGROUND: Literature on factors influencing medication adherence within paediatric clinical trials is sparse. The Paracetamol and Ibuprofen in the Primary Prevention of Asthma in Tamariki (PIPPA Tamariki) trial is an open-label, randomised controlled trial aiming to determine whether paracetamol treatment, compared with ibuprofen treatment, as required for fever and pain in the first year of life, increases the risk of asthma at age six years. To inform strategies for reducing trial medication crossovers, understanding factors influencing the observed ibuprofen-to-paracetamol crossovers (non-protocol adherence) is vital. The aim of this study was to investigate the factors influencing the decision-making process when administering or prescribing ibuprofen to infants that may contribute to the crossover events in the PIPPA Tamariki trial. METHODS: Constructivist grounded theory methods were employed. We conducted semi-structured interviews of caregivers of enrolled PIPPA Tamariki infants and healthcare professionals in various healthcare settings. Increasing theoretical sensitivity of the interviewers led to theoretical sampling of participants who could expand on the teams' early constructed codes. Transcribed interviews were coded and analysed using the constant comparative method of concurrent data collection and analysis. RESULTS: Between September and December 2020, 20 participants (12 caregivers; 8 healthcare professionals) were interviewed. We constructed a grounded theory of prioritising infant welfare that represents a basic social process when caregivers and healthcare professionals medicate feverish infants. This process comprises three categories: historical, trusting relationships and being discerning; and is modified by one condition: being conflicted. Participants bring with them historical ideas. Trusting relationships with researchers, treating clinicians and family play a central role in enabling participants to challenge historical ideas and be discerning. Trial medication crossovers occur when participants become conflicted, and they revert to historical practices that feel familiar and safer. CONCLUSIONS: We identified factors and a basic social process influencing ibuprofen use in infants and trial medication crossover events, which can inform strategies for promoting adherence in the PIPPA Tamariki trial. Future studies should explore the role of trusting relationships between researchers and treating clinicians when conducting research.

Does immunosuppressive property of non-steroidal anti-inflammatory drugs (NSAIDs) reduce COVID-19 vaccine-induced systemic side effects?

To help stop the coronavirus disease 2019 (COVID-19) pandemic, vaccines are currently the most critical tool. However, the COVID-19 mRNA vaccines frequently cause systemic side effects shortly after the injection, such as fever, headache and generalized fatigue. In our survey, after receiving the second dose of the COVID-19 vaccine, 80% developed fever, 62% headache and 69% generalized fatigue. Among people who required antipyretics, the average durations of fever and headache were significantly shorter in those who took non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, loxoprofen and ibuprofen, than those who took acetaminophen. In our patch-clamp studies, NSAIDs effectively suppressed the delayed rectifier K+-channel (Kv1.3) currents in T-lymphocytes and thus exerted immunosuppressive effects. Because of this pharmacological property, the use of NSAIDs should be more effective in reducing the vaccine-induced systemic side effects that are caused primarily by the enhanced cellular immunity.

Self-medication practices to prevent or manage COVID-19: A systematic review.

BACKGROUND: Previous studies have assessed the prevalence and characteristics of self-medication in COVID-19. However, no systematic review has summarized their findings. OBJECTIVE: We conducted a systematic review to assess the prevalence of self-medication to prevent or manage COVID-19. METHODS: We used different keywords and searched studies published in PubMed, Scopus, Web of Science, Embase, two preprint repositories, Google, and Google Scholar. We included studies that reported original data and assessed self-medication to prevent or manage COVID-19. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) modified for cross-sectional studies. RESULTS: We identified eight studies, all studies were cross-sectional, and only one detailed the question used to assess self-medication. The recall period was heterogeneous across studies. Of the eight studies, seven assessed self-medication without focusing on a specific symptom: four performed in the general population (self-medication prevalence ranged between <4% to 88.3%) and three in specific populations (range: 33.9% to 51.3%). In these seven studies, the most used medications varied widely, including antibiotics, chloroquine or hydroxychloroquine, acetaminophen, vitamins or supplements, ivermectin, and ibuprofen. The last study only assessed self-medication for fever due to COVID-19. Most studies had a risk of bias in the "representativeness of the sample" and "assessment of outcome" items of the NOS. CONCLUSIONS: Studies that assessed self-medication for COVID-19 found heterogeneous results regarding self-medication prevalence and medications used. More well-designed and adequately reported studies are warranted to assess this topic.

Evaluation of early antibiotic use in patients with non-severe COVID-19 without bacterial infection.

OBJECTIVES: The use of antibiotics was common in some countries during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, but adequate evaluation remains lacking. This study aimed to evaluate the effect of early antibiotic use in patients with non-severe COVID-19 admitted without bacterial infection. METHODS: This multi-centre retrospective cohort study included 1,373 inpatients with non-severe COVID-19 admitted without bacterial infection. Patients were divided into two groups according to their exposure to antibiotics within 48 h of admission. The outcomes were progression to severe COVID-19, length of stay >15 days and mortality rate. A mixed-effect Cox model and random effect logistic regression were used to explore the association between early antibiotic use and outcomes. RESULTS: During the 30-day follow-up period, the proportion of patients who progressed to severe COVID-19 in the early antibiotic use group was almost 1.4 times that of the comparison group. In the mixed-effect model, the early use of antibiotics was associated with higher probability of developing severe COVID-19 and staying in hospital for >15 days. However, there was no significant association between early use of antibiotics and mortality. Analysis with propensity-score-matched cohorts displayed similar results. In subgroup analysis, patients receiving any class of antibiotic were at increased risk of adverse health outcomes. Azithromycin did not improve disease progression and length of stay in patients with COVID-19. CONCLUSIONS: It is suggested that antibiotic use should be avoided unless absolutely necessary in patients with non-severe COVID-19, particularly in the early stages.

Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): A systematic review and meta-analysis.

SARS Coronavirus-2 is one of the most widespread viruses globally during the 21st century, whose severity and ability to cause severe pneumonia and death vary. We performed a comprehensive systematic review of all studies that met our standardised criteria and then extracted data on the age, symptoms, and different treatments of Covid-19 patients and the prognosis of this disease during follow-up. Cases in this study were divided according to severity and death status and meta-analysed separately using raw mean and single proportion methods. We included 171 complete studies including 62,909 confirmed cases of Covid-19, of which 148 studies were meta-analysed. Symptoms clearly emerged in an escalating manner from mild-moderate symptoms, pneumonia, severe-critical to the group of non-survivors. Hypertension (Pooled proportion (PP): 0.48 [95% Confident interval (CI): 0.35-0.61]), diabetes (PP: 0.23 [95% CI: 0.16-0.33]) and smoking (PP: 0.12 [95% CI: 0.03-0.38]) were highest regarding pre-infection comorbidities in the non-survivor group. While acute respiratory distress syndrome (PP: 0.49 [95% CI: 0.29-0.78]), (PP: 0.63 [95% CI: 0.34-0.97]) remained one of the most common complications in the severe and death group respectively. Bilateral ground-glass opacification (PP: 0.68 [95% CI: 0.59-0.75]) was the most visible radiological image. The mortality rates estimated (PP: 0.11 [95% CI: 0.06-0.19]), (PP: 0.03 [95% CI: 0.01-0.05]), and (PP: 0.01 [95% CI: 0-0.3]) in severe-critical, pneumonia and mild-moderate groups respectively. This study can serve as a high evidence guideline for different clinical presentations of Covid-19, graded from mild to severe, and for special forms like pneumonia and death groups.

Application of Humanized Zebrafish Model in the Suppression of SARS-CoV-2 Spike Protein Induced Pathology by Tri-Herbal Medicine Coronil via Cytokine Modulation.

Zebrafish has been a reliable model system for studying human viral pathologies. SARS-CoV-2 viral infection has become a global chaos, affecting millions of people. There is an urgent need to contain the pandemic and develop reliable therapies. We report the use of a humanized zebrafish model, xeno-transplanted with human lung epithelial cells, A549, for studying the protective effects of a tri-herbal medicine Coronil. At human relevant doses of 12 and 58 µg/kg, Coronil inhibited SARS-CoV-2 spike protein, induced humanized zebrafish mortality, and rescued from behavioral fever. Morphological and cellular abnormalities along with granulocyte and macrophage accumulation in the swim bladder were restored to normal. Skin hemorrhage, renal cell degeneration, and necrosis were also significantly attenuated by Coronil treatment. Ultra-high-performance liquid chromatography (UHPLC) analysis identified ursolic acid, betulinic acid, withanone, withaferine A, withanoside IV-V, cordifolioside A, magnoflorine, rosmarinic acid, and palmatine as phyto-metabolites present in Coronil. In A549 cells, Coronil attenuated the IL-1ß induced IL-6 and TNF-α cytokine secretions, and decreased TNF-α induced NF-κB/AP-1 transcriptional activity. Taken together, we show the disease modifying immunomodulatory properties of Coronil, at human equivalent doses, in rescuing the pathological features induced by the SARS-CoV-2 spike protein, suggesting its potential use in SARS-CoV-2 infectivity.

Add-on effect of Chinese herbal medicine in the treatment of mild to moderate COVID-19: A systematic review and meta-analysis.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic since its outbreak in Wuhan, China. It is an urgent task to prevent and treat COVID-19 effectively early. In China's experience combating the COVID-19 pandemic, Chinese herbal medicine (CHM) has played an indispensable role. A large number of epidemiological investigations have shown that mild to moderate COVID-19 accounts for the largest proportion of cases. It is of great importance to treat such COVID-19 cases, which can help control epidemic progression. Many trials have shown that CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 was superior to conventional therapy alone. This review was designed to evaluate the add-on effect of CHM in the treatment of mild to moderate COVID-19. METHODS: Eight electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Clinical Trials.gov website, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database and China Biology Medicine (CBM) were searched from December 2019 to March 2021 without language restrictions. Two reviewers searched and selected studies, and extracted data according to inclusion and exclusion criteria independently. Cochrane Risk of Bias (ROB) tool was used to assess the methodological quality of the included RCTs. Review Manager 5.3.0 software was used for statistical analysis. RESULTS: Twelve eligible RCTs including 1393 participants were included in this meta-analysis. Our meta-analyses found that lung CT parameters [RR = 1.26, 95% CI (1.15, 1.38), P<0.00001] and the clinical cure rate [RR = 1.26, 95%CI (1.16, 1.38), P<0.00001] of CHM combined with conventional therapy in the treatment of mild to moderate COVID-19 were better than those of conventional therapy. The rate of conversion to severe cases [RR = 0.48, 95%CI (0.32, 0.73), P = 0.0005], TCM symptom score of fever [MD = -0.62, 95%CI (-0.79, -0.45), P<0.00001], cough cases [RR = 1.43, 95%CI (1.16, 1.75), P = 0.0006], TCM symptom score of cough[MD = -1.07, 95%CI (-1.29, -0.85), P<0.00001], TCM symptom score of fatigue[MD = -0.66, 95%CI (-1.05, -0.28), P = 0.0007], and CRP[MD = -5.46, 95%CI (-8.19, -2.72), P<0.0001] of combination therapy was significantly lower than that of conventional therapy. The WBC count was significantly higher than that of conventional therapy[MD = 0.38, 95%CI (0.31, 0.44), P<0.00001]. Our meta-analysis results were robust through sensitivity analysis. CONCLUSION: Chinese herbal medicine combined with conventional therapy may be effective and safe in the treatment of mild to moderate COVID-19. More high-quality RCTs are needed in the future.

Therapeutic efficacy of macrolides in management of patients with mild COVID-19.

Evidence on the efficacy of adding macrolides (azithromycin or clarithromycin) to the treatment regimen for COVID-19 is limited. We testify whether adding azithromycin or clarithromycin to a standard of care regimen was superior to standard of supportive care alone in patients with mild COVID-19.This randomized trial included three groups of patients with COVID-19. The azithromycin group included, 107 patients who received azithromycin 500 mg/24 h for 7 days, the clarithromycin group included 99 patients who received clarithromycin 500 /12 h for 7 days, and the control group included 99 patients who received standard care only. All three groups received only symptomatic treatment for control of fever and cough .Clinical and biochemical evaluations of the study participants including assessment of the symptoms duration, real-time reverse transcription-polymerase chain reaction (rRT-PCR), C-reactive protein (CRP), serum ferritin, D-dimer, complete blood count (CBC), in addition to non-contrast chest computed tomography (CT), were performed. The overall results revealed significant early improvement of symptoms (fever, dyspnea and cough) in patients treated with either azithromycin or clarithromycin compared to control group, also there was significant early conversion of SARS-CoV-2 PCR to negative in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).There was no significant difference in time to improvement of fever, cough, dyspnea, anosmia, gastrointestinal tract "GIT" symptoms and time to PCR negative conversion between patients treated with azithromycin compared to patients treated with clarithromycin (p > 0.05 for all). Follow up chest CT done after 2 weeks of start of treatment showed significant improvement in patients treated with either azithromycin or clarithromycin compared to control group (p < 0.05 for all).Adding Clarithromycin or azithromycin to the therapeutic protocols for COVID-19 could be beneficial for early control of fever and early PCR negative conversion in Mild COVID-19.Trial registration: (NCT04622891) www.ClinicalTrials.gov retrospectively registered (November 10, 2020).

Emergency Department Utilization by In-hospital Healthcare Workers after COVID-19 Vaccination.

BACKGROUND: This is an observational study to analyze an emergency department (ED) utilization pattern of coronavirus disease 2019 (COVID-19) vaccinated in-hospital healthcare workers (HCWs). METHODS: We included 4,703 HCWs who were administered the first dose of the COVID-19 vaccine between March 4 and April 2, 2021, in a tertiary hospital in Korea where fast-track and post-vaccination cohort zone (PVCZ) were introduced in ED. We analyzed data of participants' age, sex, occupation, date and type of vaccination, and their clinical information using SPSS v25.0. RESULTS: The sample comprised HCWs, who received either the ChAdOx1 (n = 4,458) or the BNT162B2 (n = 245) vaccines; most participants were female (73.5%), and 81.1% were under 50 years old. Further, 153 (3.3%) visited the ED and reported experiencing fever (66.9%) and myalgia (56.1%). Additionally, 91 (59.5%) of them were in their 20s, and 106 (67.5%) were assigned to the PVCZ. Lastly, 107 (68.2%) of the patients received parenteral management. No patient required hospitalization. CONCLUSION: In conclusion, vaccinated HCWs who visited the ED with adverse events had a high incidence of fever and a low likelihood of developing serious illnesses. As the COVID-19 vaccination program for Korean citizens continues to expand, strategies to minimize unnecessary ED overcrowding should be put into effect.