Chronological changes of viral shedding in adult inpatients with Omicron infection in Shanghai, China.

Background: Coronavirus disease 2019 (COVID-19) caused by the Omicron variant occurred in Shanghai, China, but its clinical characteristics and virology have not been comprehensively described. Methods: This retrospective cohort study included adult inpatients (≥18 years) diagnosed with COVID-19 at Changhai Hospital. Laboratory and clinical data were obtained from electronic medical records to investigate the clinical characteristics of COVID-19 and the variations in the patients' laboratory indexes were examined. Results: The symptoms of COVID-19 caused by the Omicron variant were relatively mild. Upper respiratory tract specimens yielded higher positive detection rates than lower respiratory tract and intestinal specimens. Peak COVID-19 viral load was reached at the time of admission; quantification cycle (Cq) values increased to approximately 35 after 8.54 days. In vivo viral shedding duration correlated with age and disease severity (p<0.05). The older the patient and the more severe the disease, the longer the duration of viral shedding was. Portion parameters of blood routine, coagulative function, clinical chemistry, and inflammatory factor showed a certain correlation with the SARS-CoV-2 viral load. Conclusions: Virus replication and shedding are rapid in Omicron-positive patients; COVID-19 in these patients is characterized by acute onset, mild symptoms, and fast recovery. Older patients and those with more severe disease demonstrate prolonged virus shedding. Routine hematological indexes can reveal disease severity and help clinically evaluate the patient's condition.

Antibiotic use in township hospitals during the COVID-19 pandemic in Shandong, China (preprint)

Background The overuse of antibiotics in primary healthcare settings (PHSs) has caused a serious public health problem in China. The Coronavirus Disease-19 (COVID-19) pandemic outbreak has brought about dramatic changes in the supply of and demand for medical services in PHSs, possibly resulting in unprecedented changes in antibiotic use.Objective This study aims to assess the immediate and long-term impacts of the COVID-19 pandemic on the changes in antibiotic consumption in PHSs.Method From January 2019 to December 2021, the data on antibiotic consumption were collected from selected township hospitals in Shandong, China. Antibiotic consumption was quantified by using the defined daily doses (DDDs) and the WHO Access, Watch, Reserve category. A Segmented regression model was established to analyze the immediate and long-term impacts of the COVID-19 pandemic on antibiotic use by using the interrupted time series analysis.Results The total antibiotic consumption on all PHSs decreased from 170.36 (DDDs in ten thousand) in 2019 to 128.86 (DDDs in ten thousand) in 2020/2021 with a 24.36% reduction under the COVID-19 pandemic. Over the entire study period, the use of penicillins (J01C) and cephalosporins (J01D) accounted for more than 50% of total antibiotic consumption. The average annual consumption of Watch category antibiotics in 2020/2021 down by 37.74% compared to that in 2019. According to the interrupted time series analysis, the total antibiotic consumption decreased significantly immediately after the COVID-19 pandemic outbreak (coef. =-2.712, p = 0.045) and then increased significantly month-over-month in the long-term (coef. =0.205, p = 0.005). Additionally, the consumption of Access category antibiotics increased significantly in PHSs in the log-term (coef. =0.136, p = 0.018), while the consumption of Watch category antibiotics declined sharply immediately (coef. =-1.222, p < 0.001) after the pandemic but increased slightly over the long-term (coef. =0.073, p = 0.001).Conclusion The extensive use of penicillin and cephalosporins should be of great concern. After the outbreak of COVID-19 pandemic, the total antibiotic consumption decreased generally and the use pattern was improved to some extent in the PHSs in Shandong, China. This provides an opportunity to improve the abuse of antibiotic in PHSs in China.

Molecular mechanism of antibiotic resistance induced by mono- and twin-chained quaternary ammonium compounds.

The usage of quaternary ammonium compounds (QACs) as disinfectants has increased dramatically since the outbreak of COVID-19 pandemic, leading to potentially accelerated emergence of antibiotic resistance. Long-term exposure to subinhibitory level QACs can lead to multidrug resistance, but the contribution of mutagenesis to resistance evolution is obscure. In this study, we subcultured E. coli K-12 under subinhibitory (0.25 × and 0.5 × Minimum Inhibitory Concentration, MIC) or inhibitory (1 × and 2 × MIC) concentrations of benzalkonium chloride (BAC, mono-chained) or didecyldimethylammonium chloride (DDAC, twin-chained) for 60 days. The sensitivity of QAC-adapted cells to five typical antibiotics decreased significantly, and in particular, the MIC of rifampicin increased by 85 times. E. coli adapted faster to BAC but developed 20-167% higher antibiotic resistance with 56% more mutations under DDAC exposure. The broader mutations induced by QACs, including negative regulators (acrR, marR, soxR, and crp), outer membrane proteins and transporters (mipA and sbmA), and RNA polymerase (rpoB and rpoC), potentially contributed to the high multi-drug resistance. After QACs stresses were removed, the phenotypic resistance induced by subinhibitory concentrations of QACs was reversible, whereas that induced by inhibitory concentrations of QACs was irreversible. The different patterns and molecular mechanism of antibiotic resistance induced by BAC and DDAC is informative to estimating the risks of broader QACs present at varied concentrations in the environment.

Incidence of adverse reaction of drugs used in COVID-19 management: a retrospective, observational study.

BACKGROUND: An urgent need for coronavirus infectious disease (COVID-19) treatment has resulted in off-label drug use. Although previous studies had investigated the adverse drug reaction (ADR) of the medications for COVID-19 in their respective local settings, the safety profile in a Malaysian setting remains unknown. Our study aims to establish the incidence of ADR for drugs used in COVID-19 management in a Malaysian tertiary hospital. METHODS: This retrospective observational study enrolled patients started on drugs for COVID-19 in Sungai Buloh Hospital from 1 March 2020 to 31 May 2020. The clinical staging of COVID-19 patients was decided by the treating physician in accordance with the Clinical Management of Confirmed COVID-19 Case in Adults (Annex 2E). Suspected ADRs were evaluated with a trigger tool of pre-defined laboratory values or the adverse events listed in the registered product insert. Causality assessment was conducted when an ADR was suspected using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system, and only cases classified as certain, probable and possible ADR were considered. Data analysis was completed with descriptive, univariate and multivariate analysis. RESULTS: The study (N = 1,080) identified 217 patients (20.1%) who experienced ADR, with 246 adverse events detected. Most events were related to the gastrointestinal (43.5%), hepatobiliary (36.2%) and cardiac (16.3%) systems. The most commonly suspected drugs were atazanavir (52.7%), chloroquine (36.8%) and lopinavir/ritonavir (34.6%). The independent risk factors of ADR were female (adjusted odds ratio (OR): 1.53; 95% CI 1.06-2.20; P = 0.024), diagnosis of COVID-19 stage 3 (adjusted OR: 2.58; 95% CI 1.20-5.55; P = 0.015) and stage 4 (adjusted OR: 4.17; 95% CI 1.79-9.73; P = 0.001), and the number of COVID-19 drugs (adjusted OR: 3.34; 95% CI 2.51-4.44; P < 0.001). Only 49 adverse events (19.9%) were manually reported by healthcare professionals, with hyperbilirubinaemia (65.3%) and QT prolongation (28.6%) most frequently reported. CONCLUSION: Medications used in COVID-19 management had resulted in one in five patients experiencing ADR. Our study has provided an overview on incidence of ADR for off-label use of medications used in COVID-19 management, which suggests a similar safety profile when used for FDA-approved indications.

Addressing Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) Following COVID-19 Vaccination: A Mini-Review of Practical Strategies.

In response to the COVID-19 pandemic, several vaccines were developed and rolled out at unprecedented speed, and notwithstanding this rapid pace of development, the results from initial clinical trials involving tens of thousands of adult subjects generally indicated that most vaccines were remarkably effective and safe, with no major safety warnings noted. However, with more than 2 billion vaccination doses administered to date, reports of rare adverse events following immunization (AEFI) are beginning to emerge. In late February 2021, atypical thrombotic events following immunization with the adenoviral vector-based ChAdOx1 nCov-19 vaccine were first reported, and similar events have also been observed in recipients of the adenoviral vector-based Ad26.COV2.S vaccine and the mRNA-based BNT162b2 and mRNA-1273 vaccines. These manifestations of atypical thrombosis and thrombocytopenia following COVID-19 vaccine immunization are now collectively referred to as vaccine-induced immune thrombotic thrombocytopenia (VITT). Although the reported incidence remains very low and does not affect the overall benefit of immunization, it is also true that if left untreated, VITT can be debilitating or even fatal. Therefore, this review seeks to provide a comprehensive overview regarding the incidence, pathogenesis, presentation, diagnosis, and treatment of VITT, as well as considerations for special populations, based on the currently available evidence in the literature. It is hoped that this will enhance awareness of this vaccine side effect, so that cases of VITT may be identified and treated in a timely and appropriate manner.