ABSTRACT
Objectives: To explore the appropriate controlled ovarian hyperstimulation (COH) protocols in infertility patients who received the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments during the COVID-19 pandemic. Materials and Methods: This retrospective cohort study evaluated the efficiency of the early follicular-phase long-acting GnRH-agonist long (EFLL) protocol (a new protocol developed by Chinese clinicians), prolonged pituitary down-regulation of EFLL protocol (Pro-EFLL), and the GnRH-ant protocol for couples meeting the study criteria between February 2020 and June 2020 who were treated by the First Affiliated Hospital of Zhengzhou University during the COVID-19 pandemic, and compared the pregnancy rates and miscarriage rates per fresh transfer cycle, number of retrieved oocytes, endometrial thickness on the day of hCG injection and the number of fertilized oocytes, mature oocytes, fertilized oocytes, and transferable embryos among the three protocols. Results: We found that the prolonged pituitary down-regulation during the COVID-19 pandemic by utilizing a full-dose of GnRH-a administrated in infertility patients were no differences in clinical outcomes than other protocols, The prolonged pituitary down-regulation protocol and EFLL protocol were associated with a higher Endometrial thickness on the day of hCG injection (12.67 ± 2.21 vs. 12.09 ± 2.35 vs. 10.79 ± 2.38, P < 0.001), retrieved oocytes (14.49 ± 6.30 vs. 15.02 ± 7.93 vs. 10.06 ± 7.63, P < 0.001), mature oocytes (11.60 ± 5.71 vs. 11.96 ± 6.00 vs. 7.63 ± 6.50, P < 0.001), fertilized oocytes (9.14 ± 5.43 vs. 8.44 ± 5.34 vs. 5.42 ± 5.20, P < 0.001), and transferable embryos (4.87 ± 2.96 vs. 6.47 ± 5.12 vs. 3.00 ± 3.28 vs. P < 0.001) in the GnRH-antagonist protocol. Conclusion: We recommend that patients start Gn injections 33-42 days after a pituitary downregulated full dose (3.75 mg) of gonadotropin-releasing hormone agonist during the COVID-19 pandemic, even a delay of 2-4 weeks does not affect the implantation rate. The study can provide a more detailed estimate and clinical management strategies for infertile couples during the COVID-19 pandemic.
ABSTRACT
Remdesivir (RDV) has generated much anticipation for its moderate effect in treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the unsatisfactory survival rates of hospitalized patients limit its application to the treatment of coronavirus disease 2019 (COVID-19). Therefore, improvement of antiviral efficacy of RDV is urgently needed. As a typical nucleotide analog, the activation of RDV to bioactive triphosphate will affect the biosynthesis of endogenous ribonucleotides (RNs) and deoxyribonucleotides (dRNs), which are essential to RNA and DNA replication in host cells. The imbalance of RN pools will inhibit virus replication as well. In order to investigate the effects of RDV on cellular nucleotide pools and on RNA transcription and DNA replication, cellular RNs and dRNs concentrations were measured by the liquid chromatography-mass spectrometry method, and the synthesis of RNA and DNA was monitored using click chemistry. The results showed that the IC50 values for BEAS-2B cells at exposure durations of 48 and 72 h were 25.3 ± 2.6 and 9.6 ± 0.7 µM, respectively. Ten (10) µM RDV caused BEAS-2B arrest at S-phase and significant suppression of RNA and DNA synthesis after treatment for 24 h. In addition, a general increase in the abundance of nucleotides and an increase of specific nucleotides more than 2 folds were observed. However, the variation of pyrimidine ribonucleotides was relatively slight or even absent, resulting in an obvious imbalance between purine and pyrimidine ribonucleotides. Interestingly, the very marked disequilibrium between cytidine triphosphate (CTP) and cytidine monophosphate might result from the inhibition of CTP synthase. Due to nucleotides which are also precursors for the synthesis of viral nucleic acids, the perturbation of nucleotide pools would block viral RNA replication. Considering the metabolic vulnerability of endogenous nucleotides, exacerbating the imbalance of nucleotide pools imparts great promise to enhance the efficacy of RDV, which possibly has special implications for treatment of COVID-19.
ABSTRACT
The pathogenesis similarity is leading to the introduction of drugs commonly used in rheumatoid arthritis (RA) into coronavirus disease (COVID-19) treatment. Traditional Chinese medicine (TCM) was widely used for the treatment of infectious diseases and rheumatic diseases. However, there is little knowledge of the relationship between COVID-19 and RA treatment employing TCM formulas. The present work was aimed to compare the similarity and specificity of TCM formulas for the management of COVID-19 and RA, as well as to deduce the potential mechanism of TCM for COVID-19 treatment. Two formulas including lianhuaqingwen (LHQW) and duhuojisheng (DHJS) were selected as the representatives of TCM for COVID-19 and RA treatment, respectively. An integrated network pharmacology was used to investigate their similarity and specificity. Although different herbs are present in the two formulas, they generated fairly similar ingredients, targets, interaction networks and enriched pathways, which were mainly involved in virus infection, inflammation, and immune dysregulation. Undoubtedly, they also exhibited their respective specificity. LHQW showed the cold property and lung channel tropism which dominated heat-clearing and lung-freeing, while DHJS showed the warm property and liver channel tropism. Herbal compatibility of LHQW was more in line with the rules of the TCM formula against coronavirus disease. Although both formulas suggested multifunctionality in virus infection and inflammation, LHQW was inclined to cope with virus infection, while DHJS was inclined to cope with inflammation. Therefore, LHQW was reliable for providing the desired efficacy in COVID-19 management because of its cold property, lung channel tropism, and multifunctionality for coping with virus infection and inflammation.