Efficacy and Safety of “Three Chinese Patent Medicines and Three TCM Prescriptions” for COVID-19: A Systematic Review and Network Meta-Analysis

Objective. To systematically evaluate the efficacy, safety, and precision of TMTP for COVID-19. Methods. Randomized controlled trials and retrospective studies were searched in 11 electronic databases. This network meta-analysis included trials using TMTP to treat patients with COVID-19. The traditional pairwise meta-analysis was done by using Stata 15, and Bayesian network meta-analysis was done with WinBUGS. Results. 18 trials were included with 2036 participants and 7 drugs. The results showed that LHQW had the most significant effects on improving expectoration, shortness of breath, sore throat, nausea, emesis, inappetence, muscle soreness, and headache, and it could produce the least adverse reactions. XBJ was the best drug for fever, fatigue, and diarrhea, which showed great advantages in lowering WBC levels. XFBD was the most effective drug for cough and chest distress, which had the least exacerbation rate. JHQG was the most effective for rhinobyon and rhinorrhea, while QFPD was the best drug in decreasing CRP levels. Conclusion. This study was the first most large-scale and comprehensive research of TMTP for COVID-19. The results showed that LHQW had good efficacy without obvious adverse reactions. Therefore, we believe that it should be firstly recommended for COVID-19 treatment. In addition, XBJ is recommended for patients with a severe fever, fatigue, and diarrhea, and JHQG is recommended for patients with obvious rhinobyon and rhinorrhea; then, XFBD is recommended for patients with cough and chest tightness as the main manifestation. Our findings will help experts develop new COVID-19 treatment guidelines to better guide clinical medication for protecting the health of COVID-19 patients.

Animal Model of Severe Fever With Thrombocytopenia Syndrome Virus Infection

Severe fever with thrombocytopenia syndrome (SFTS), an emerging life-threatening infectious disease caused by SFTS bunyavirus (SFTSV; genus Bandavirus, family Phenuiviridae, order Bunyavirales), has been a significant medical problem. Currently, there are no licensed vaccines or specific therapeutic agents available and the viral pathogenesis remains largely unclear. Developing appropriate animal models capable of recapitulating SFTSV infection in humans is crucial for both the study of the viral pathogenic processes and the development of treatment and prevention strategies. Here, we review the current progress in animal models for SFTSV infection by summarizing susceptibility of various potential animal models to SFTSV challenge and the clinical manifestations and histopathological changes in these models. Together with exemplification of studies on SFTSV molecular mechanisms, vaccine candidates, and antiviral drugs, in which animal infection models are utilized, the strengths and limitations of the existing SFTSV animal models and some important directions for future research are also discussed. Further exploration and optimization of SFTSV animal models and the corresponding experimental methods will be undoubtedly valuable for elucidating the viral infection and pathogenesis and evaluating vaccines and antiviral therapies.

The molecular evolution of Dabie bandavirus (Phenuiviridae: Bandavirus: Dabie bandavirus), the agent of severe fever with thrombocytopenia syndrome

Since the Dabie bandavirus (DBV; former SFTS virus, SFTSV) was identified, the epidemics of severe fever with thrombocytopenic syndrome (SFTS) caused by this virus have occurred in several countries in East Asia. The rapid increase in incidence indicates that this infectious agent has a pandemic potential and poses an imminent global public health threat.The analysis of molecular evolution of SFTS agent that includes its variants isolated in China, Japan and South Korea was performed in this review. The evolution rate of DBV and the estimated dates of existence of the common ancestor were ascertained, and the possibility of reassortation was demonstrated.The evolutionary rates of DBV genome segments were estimated to be 2.28 × 10-4 nucleotides/site/year for S-segment, 2.42 × 10-4 for M-segment, and 1.19 × 10-4 for L-segment. The positions of positive selection were detected in the viral genome.Phylogenetic analyses showed that virus may be divided into two clades, containing six different genotypes. The structures of phylogenetic trees for S-, M- and L-segments showed that all genotypes originate from the common ancestor.Data of sequence analysis suggest that DBV use several mechanisms to maintain the high level of its genetic diversity. Understanding the phylogenetic factors that determine the virus transmission is important for assessing the epidemiological characteristics of the disease and predicting its possible outbreaks.

Predictive Value of Triglyceride-Glucose Index for In-hospital Mortality in Patients With Severe Fever With Thrombocytopenia Syndrome: A Multi-Center Observational Study

Background: Triglyceride-glucose (TyG) index has been proposed as a reliable indicator for insulin resistance and proved to be closely associated with the severity and mortality risk of infectious diseases. It remains indistinct whether TyG index performs an important role in predicting in-hospital mortality in patients with severe fever with thrombocytopenia syndrome (SFTS).Methods: The current study retrospectively recruited patients who were admitted for SFTS from January to December 2019 at five medical centers. TyG index was calculated in accordance with the description of previous study: Ln [fasting triglyceride (TG) (mg/dl) × fasting blood glucose (FBG) (mg/dl)/2]. The observational endpoint of the present study was defined as the in-hospital death.Results: In total, 79 patients (64.9 ± 10.5 years, 39.2% female) who met the enrollment criteria were enrolled in the current study. During the hospitalization period, 17 (21.5%) patients died in the hospital. TyG index remained a significant and independent predictor for in-hospital death despite being fully adjusted for confounders, either being taken as a nominal [hazard ratio (HR) 5.923, 95% CI 1.208–29.036, P = 0.028] or continuous (HR 7.309, 95% CI 1.854–28.818, P = 0.004) variate. TyG index exhibited a moderate-to-high strength in predicting in-hospital death, with an area under the receiver operating characteristic curve (AUC) of 0.821 (95% CI 0.712–0.929, P < 0.001). The addition of TyG index displayed significant enhancement on the predictive value for in-hospital death beyond a baseline model, manifested as increased AUC (baseline model: 0.788, 95% CI 0.676–0.901 vs. + TyG index 0.866, 95% CI 0.783–0.950, P for comparison = 0.041), increased Harrell's C-index (baseline model: 0.762, 95% CI 0.645–0.880 vs. + TyG index 0.813, 95% CI 0.724–0.903, P for comparison = 0.035), significant continuous net reclassification improvement (NRI) (0.310, 95% CI 0.092–0.714, P = 0.013), and significant integrated discrimination improvement (0.111, 95% CI 0.008–0.254, P = 0.040).Conclusion: Triglyceride-glucose index, a novel indicator simply calculated from fasting TG and FBG, is strongly and independently associated with the risk of in-hospital death in patients with SFTS.

Development of Monoclonal Antibody Based IgG and IgM ELISA for Diagnosis of Severe Fever with Thrombocytopenia Syndrome Virus Infection

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly emerged virus that possesses a great threat to human health because of the high fatality rate. Method: To develop sensitive and specific sero-diagnosis systems for SFTSV infections, monoclonal antibodies (MAbs) against recombinant SFTSV nucleocapsid (rSFTSV-N) protein were developed by immunizing BALB/C mice with rSFTSV-N protein and fusing the spleen cells with SP2/0 myeloma cells. Three hybridoma cell lines secreting MAbs against rSFTSV-N were obtained. MAb based IgG sandwich enzyme linked immunosorbent assay (ELISA) and IgM capture ELISA systems were established by using the newly developed MAbs. One hundred fifteen clinical suspected SFTS patient serum samples were used to evaluate the newly established systems by comparing with the total antibody detecting sandwich ELISA system and indirect ELISA systems. Results: The MAb based sandwich IgG ELISA was perfectly matched with that of the total antibody sandwich ELISA and the indirect IgG ELISA with a sensitivity and specificity of 100%. IgM capture ELISA results perfectly matched with that of the total antibody sandwich ELISA while was more sensitive comparing with the indirect IgM ELISA. Conclusions: The MAbs against rSFTSV-N protein offer new tools for SFTSV studies and our newly developed MAb-based IgG and IgM capture ELISA systems would offer safe and useful tools for diagnosis of SFTS virus infections and epidemiological investigations.