Application of Jiawei Maxing Shigan Tang in the treatment of COVID-19: An observational study.

Objective: To explore the clinical efficacy and adverse reactions of Jiawei Maxing Shigan Tang (JMST; a modified decoction of ephedra, apricot kernel, gypsum, and licorice) combined with western medicine in the symptomatic treatment of COVID-19. Methods: In this study, we retrospectively collected the basic data of 48 patients with COVID-19 who were discharged from our hospital between January 20 and February 28, 2020. Besides, the blood routines, biochemical indexes, nucleic acid detection results, clinical symptoms, lung imaging improvements, adverse reactions, and other clinical data of these patients before and after treatment were recorded. Finally, we drew comparisons between the outcomes and adverse reactions of patients in the combined treatment group (therapeutic regimen recommended by authoritative guidelines and supplemented by JMST) and the conventional treatment group (therapeutic regimen recommended by authoritative guidelines). Results: There were no significant differences in age, gender, clinical classification, and underlying medical conditions between the combined treatment group (28 cases) and the conventional treatment group (20 cases). However, the combined treatment group presented superior results to the conventional treatment group in several key areas. For instance, patients produced negative nasal/throat swab-based nucleic acid detection results in a shorter time, clinical symptoms were more effectively alleviated, and the absorption time of lung exudation was shorter (P < 0.05). Furthermore, the combined treatment group had a shorter length of stay (LOS) and faster lymphocyte recovery duration than the conventional treatment group, although the differences were not statistically significant. Moreover, there were no significant differences concerning gastrointestinal reaction, hepatic injury, renal impairment, myocardial injury, and other adverse reactions between the two groups. Conclusion: The results of this study indicate that JMST combined with the recommended therapeutic regimen enhances the recovery of COVID-19 patients without increasing the risk of adverse reactions. Therefore, this therapy promotes positive outcomes for COVID-19 patients.

Pathogenic microorganism monitoring and traceability exploration of medical waste disposal routes in children's hospital

OBJECTIVE: Due to the lack of effective monitoring of microbial spectrum of medical waste collection, transport, storage and transfer path, as well as the evaluation of disinfection effects in medical institutions, this study aimed to explore the microenvironment, prevention and control difficulties and management opinions of medical waste disposal path through the microbial analysis of the medical waste disposal path in model departments. METHODS According to the standard process, the environmental samples at different time periods before and after the disinfection of the medical waste disposal path in the model department were collected and analyzed. The drug resistance and molecular typing traceability of important pathogens were analyzed. And the dynamic effect of the whole path application of the disinfection scheme for medical waste disposal in the model department were evaluated. Efficient frequency and application effect of disinfection of and hygiene of relevant places and gloves were evaluated through environmental monitoring before and after disinfection. RESULTS Most of the isolated strains were environmental microorganisms, Acinetobacter baumannii, Pseudomonas aeruginosa, Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium were also isolated, and a multidrug-resistant A. baumannii strain was identified. Through typing and tracing the source, the multiple strains of A. Baumannii were found to be of different genetic origins and the two strains were from the same clonal line. Using original detection technology, no contamination of Salmonella and Shigella was found in the path. The new coronavirus and norovirus were not detected. However, the environmental pollution of rotavirus was obvious. CONCLUSION The risk of random transmission of rotavirus cannot completely solved by existing hand-sterilized regents. Timely or even frequent replacement of gloves is a simple solution in the workflow. The sterilized medical waste transfer vehicles are likely to become the pollution source of rotavirus after passing through a certain medical waste path. The medical waste disposal personnel should replace the rotating vehicle in time before entering other wards. In addition, due to the weak professional ability of cleaners, simple and easy process guidelines is the most effective solution at present.

N-3 polyunsaturated fatty acids block the trimethylamine-N-oxide- ACE2- TMPRSS2 cascade to inhibit the infection of human endothelial progenitor cells by SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is a novel coronavirus that infects many types of cells and causes cytokine storms, excessive inflammation, acute respiratory distress to induce failure of respiratory system and other critical organs. In this study, our results showed that trimethylamine-N-oxide (TMAO), a metabolite generated by gut microbiota, acts as a regulatory mediator to enhance the inerleukin-6 (IL-6) cytokine production and the infection of human endothelial progenitor cells (hEPCs) by SARS-CoV-2. Treatment of N-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) could effectively block the entry of SARS-CoV-2 in hEPCs. The anti-infection effects of N-3 PUFAs were associated with the inactivation of NF-κB signaling pathway, a decreased expression of the entry receptor angiotensin-converting enzyme 2 (ACE2) and downstream transmembrane serine protease 2 in hEPCs upon the stimulation of TMAO. Treatment of DHA and EPA further effectively inhibited TMAO-mediated expression of IL-6 protein, probably through an inactivation of MAPK/p38/JNK signaling cascades and a downregulation of microRNA (miR)-221 in hEPCs. In conclusion, N-3 PUFAs such as DHA and EPA could effectively act as preventive agents to block the infection of SARS-CoV-2 and IL-6 cytokine production in hEPCs upon the stimulation of TMAO.

Drivers and forecasts of multiple waves of the coronavirus disease 2019 pandemic: A systematic analysis based on an interpretable machine learning framework.

Coronavirus disease 2019 (COVID-19) has become a global pandemic and continues to prevail with multiple rebound waves in many countries. The driving factors for the spread of COVID-19 and their quantitative contributions, especially to rebound waves, are not well studied. Multidimensional time-series data, including policy, travel, medical, socioeconomic, environmental, mutant and vaccine-related data, were collected from 39 countries up to 30 June 2021, and an interpretable machine learning framework (XGBoost model with Shapley Additive explanation interpretation) was used to systematically analyze the effect of multiple factors on the spread of COVID-19, using the daily effective reproduction number as an indicator. Based on a model of the pre-vaccine era, policy-related factors were shown to be the main drivers of the spread of COVID-19, with a contribution of 60.81%. In the post-vaccine era, the contribution of policy-related factors decreased to 28.34%, accompanied by an increase in the contribution of travel-related factors, such as domestic flights, and contributions emerged for mutant-related (16.49%) and vaccine-related (7.06%) factors. For single-peak countries, the dominant ones were policy-related factors during both the rising and fading stages, with overall contributions of 33.7% and 37.7%, respectively. For double-peak countries, factors from the rebound stage contributed 45.8% and policy-related factors showed the greatest contribution in both the rebound (32.6%) and fading (25.0%) stages. For multiple-peak countries, the Delta variant, domestic flights (current month) and the daily vaccination population are the three greatest contributors (8.12%, 7.59% and 7.26%, respectively). Forecasting models to predict the rebound risk were built based on these findings, with accuracies of 0.78 and 0.81 for the pre- and post-vaccine eras, respectively. These findings quantitatively demonstrate the systematic drivers of the spread of COVID-19, and the framework proposed in this study will facilitate the targeted prevention and control of the ongoing COVID-19 pandemic.

CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity.

Safe, effective, and economical vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and end the pandemic. We constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains immunodominant peptides screened from the receptor-binding domain (RBD) and is fully chemically synthesized. It has been formulated in an optimized nanoemulsion formulation and is stable at 40 °C for 1 month. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of protective neutralizing antibodies against multiple RBD mutations, SARS-CoV-2 original strain, and variants (B.1.1.7 and B.1.617.2). Specific peptides booster immunization against the B.1.351 variant has also been shown to be effective in improving protection against B.1.351. Meanwhile, CoVac501 elicited the increase of memory T cells, antigen-specific CD8+ T-cell responses, and Th1-biased CD4+ T-cell immune responses in NHPs. Notably, at an extremely high SARS-CoV-2 challenge dose of 1 × 107 TCID50, CoVac501 provided near-complete protection for the upper and lower respiratory tracts of cynomolgus macaques.

Clinical features and follow-up of pediatric patients hospitalized for COVID-19.

OBJECTIVE: This report summarizes the clinical features and 1-month follow-up observations for pediatric patients who were hospitalized with coronavirus disease 2019 (COVID-19) in Wuhan Women and Children's Hospital. METHODS: The 1-month follow-up data included clinical manifestations and results from serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and IgM tests, reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2, lung computed tomography (CT) scans, and laboratory tests. RESULTS: Between January 20 and March 15, 2020, 127 patients aged 0-15 years were hospitalized for COVID-19 treatment, including 3 severe cases and 124 mild or moderate cases. The main therapies included inhalation of aerosolized interferon-α (122/127) and additional antiviral drugs (28/127). Among the 81 patients who had pneumonia at admission, 35 with right lobe pneumonia had the longest hospital stay (mean 14.5 ± 7 days); 17 with left lobe pneumonia had the highest creatine kinase (154 ± 106 U/L) and creatine kinase myocardial band  (CK-MB, 43 ± 48 U/L) levels; and 29 with bilateral pneumonia had the highest white blood cell counts (8.3 ± 4 × 109 /L). Among the 46 patients who were successfully followed up 1 month after discharge, two notable findings were right lobe pneumonia in 22% (95% confidence interval [CI]: 11%-37%) of patients and persistently elevated serum creatine kinase and CK-MB levels. The median duration of elevated CK-MB was 45 days. The mean concentrations of serum SARS-CoV-2 IgG and IgM in 41 patients were 8.0 ± 7.5 and 98 ± 40 ng/ml, respectively. At follow-up, four patients retested positive for SARS-CoV-2. CONCLUSIONS: The involvement of different lung lobes in patients with COVID-19 was associated with variations in the persistence of pneumonia and elevation of CK-MB levels and body temperature.

Impact of Systematic Factors on the Outbreak Outcomes of the Novel COVID-19 Disease in China: Factor Analysis Study.

BACKGROUND: The novel COVID-19 disease has spread worldwide, resulting in a new pandemic. The Chinese government implemented strong intervention measures in the early stage of the epidemic, including strict travel bans and social distancing policies. Prioritizing the analysis of different contributing factors to outbreak outcomes is important for the precise prevention and control of infectious diseases. We proposed a novel framework for resolving this issue and applied it to data from China. OBJECTIVE: This study aimed to systematically identify national-level and city-level contributing factors to the control of COVID-19 in China. METHODS: Daily COVID-19 case data and related multidimensional data, including travel-related, medical, socioeconomic, environmental, and influenza-like illness factors, from 343 cities in China were collected. A correlation analysis and interpretable machine learning algorithm were used to evaluate the quantitative contribution of factors to new cases and COVID-19 growth rates during the epidemic period (ie, January 17 to February 29, 2020). RESULTS: Many factors correlated with the spread of COVID-19 in China. Travel-related population movement was the main contributing factor for new cases and COVID-19 growth rates in China, and its contributions were as high as 77% and 41%, respectively. There was a clear lag effect for travel-related factors (previous vs current week: new cases, 45% vs 32%; COVID-19 growth rates, 21% vs 20%). Travel from non-Wuhan regions was the single factor with the most significant impact on COVID-19 growth rates (contribution: new cases, 12%; COVID-19 growth rate, 26%), and its contribution could not be ignored. City flow, a measure of outbreak control strength, contributed 16% and 7% to new cases and COVID-19 growth rates, respectively. Socioeconomic factors also played important roles in COVID-19 growth rates in China (contribution, 28%). Other factors, including medical, environmental, and influenza-like illness factors, also contributed to new cases and COVID-19 growth rates in China. Based on our analysis of individual cities, compared to Beijing, population flow from Wuhan and internal flow within Wenzhou were driving factors for increasing the number of new cases in Wenzhou. For Chongqing, the main contributing factor for new cases was population flow from Hubei, beyond Wuhan. The high COVID-19 growth rates in Wenzhou were driven by population-related factors. CONCLUSIONS: Many factors contributed to the COVID-19 outbreak outcomes in China. The differential effects of various factors, including specific city-level factors, emphasize the importance of precise, targeted strategies for controlling the COVID-19 outbreak and future infectious disease outbreaks.

Be aware of acute kidney injury in critically ill children with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a common complication of critically ill adult patients with COVID-19. However, currently, no studies investigate kidney impairment in children with COVID-19. We investigated incidence and treatment of AKI in pediatric patients with COVID-19 in Wuhan Children's Hospital during the early stages of the COVID-19 pandemic and discuss possible mechanisms of AKI related to SARS-CoV-2 infection. METHODS: By extracting data from electronic medical records, we conducted a retrospective observational study of kidney involvement in confirmed pediatric COVID-19 cases in Wuhan Children's Hospital during the coronavirus outbreak, from January 24 to March 20, 2020. Clinical presentations, clinical courses, laboratory findings, and medical interventions are described below. RESULTS: Among 238 confirmed COVID-19 cases, only three were critically ill and needed intensive care unit (ICU) admission. All three developed AKI, but AKI was not detected in any non-critically ill patients outside the ICU. Two of the three patients with AKI had prodromal gastrointestinal symptoms. Significantly elevated interleukin-6 (IL-6) levels and complement activation were observed in these patients with AKI. The three patients with AKI were treated with plasma exchange (PE) and continuous kidney replacement therapy (CKRT), resulting in one complete recovery, one partial recovery, and one mortality due to critical illness. CONCLUSIONS: Critically ill children with COVID-19 may develop AKI, especially following prodromal gastrointestinal symptoms. An inflammatory storm and complement-mediated injury may underlie AKI development in children with COVID-19. Our study supports implantation of PE and CKRT in management of critically ill patients with AKI.

Impact of population movement on the spread of 2019-nCoV in China.

Since Dec 2019, China has experienced an outbreak caused by a novel coronavirus, 2019-nCoV. A travel ban was implemented for Wuhan, Hubei on Jan 23 to slow down the outbreak. We found a significant positive correlation between population influx from Wuhan and confirmed cases in other cities across China (R2 = 0.85, P < 0.001), especially cities in Hubei (R2 = 0.88, P < 0.001). Removing the travel restriction would have increased 118% (91%-172%) of the overall cases for the coming week, and a travel ban taken three days or a week earlier would have reduced 47% (26%-58%) and 83% (78%-89%) of the early cases. We would expect a 61% (48%-92%) increase of overall cumulative cases without any restrictions on returning residents, and 11% (8%-16%) increase if the travel ban stays in place for Hubei. Cities from Yangtze River Delta, Pearl River Delta, and Capital Economic Circle regions are at higher risk.