Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2.

Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading.

Lonicerae Japonicae Flos Attenuates Neutrophilic Inflammation by Inhibiting Oxidative Stress.

Lonicerae japonicae flos (LJ) is an Asian traditional herb that is used as a dietary supplement, tea, and beverage to clear heat and quench thirst. However, no studies investigated its effect on activated human neutrophils, which played a crucial role in the bad prognosis of coronavirus disease of 2019 (COVID-19) patients by aggravating lung inflammation and respiratory failure. Herein, we evaluated the anti-inflammatory effect of LJ ethanol extract (LJEE) on human neutrophils activated by N-formyl-methionyl-leucyl-phenylalanine (fMLF). Our experimental results indicated that LJEE suppressed fMLF-activated superoxide anion (O2•-) generation, the expression of CD11b, and cell adhesion and migration, as well as the formation of neutrophil extracellular traps in human neutrophils. Further in-depth mechanical investigation revealed that pretreatment with LJEE accelerated the Ca2+ clearance, but did not affect the phosphorylation of mitogen-activated protein kinases (MAPKs) and protein kinase B (Akt) in activated human neutrophils. In addition, LJEE displayed a dose-dependent reactive oxygen species (ROS) scavenger activity, which assisted its anti-inflammatory activity. From the bioassay-coupled chromatographic profile, chlorogenic acids were found to dominate the anti-inflammatory effects of LJEE. Moreover, LJ water extract (LJWE) demonstrated an interrupting effect on the severe acute respiratory syndrome coronavirus-2 spike protein (SARS-CoV-2-Spike)/angiotensin-converting enzyme 2 (ACE2) binding. In conclusion, the obtained results not only supported the traditional use of LJ for heat-clearance, but also suggested its potential application in daily health care during the COVID-19 pandemic.

Clinical application and development of anti-complement active substances

The complement system is an important component of the innate immune system, and the occurrence of rheumatoid arthritis, autoimmune hemolytic anemia, COVID-19 and other diseases is closely related to abnormalities of the complement system. At present, most of the complement inhibitors commonly used in clinical practice are chemical synthetic drugs, which are poorly selective, and long-term use can easily lead to a decrease in the body's immune ability. The anti-complement active ingredients from natural products are less toxic and easy to be digested and absorbed by the body, among which the anti-complement active substances of microbial sources have unique advantages and application potential, which can be quickly discovered and identified by genome mining, and use metabolic engineering to modify and optimize mass production, but the relevant research is still in the preliminary research and development stage. This review summarizes the clinical application of the more common complement inhibitors at home and abroad in recent years, and discusses the research and development progress of anti-complement active substances of microbial origin, in order to provide a reference for the clinical research of complement inhibitors and the development of new anti-complement active substances of natural sources.

Cuffless and Touchless Measurement of Blood Pressure from Ballistocardiogram Based on a Body Weight Scale.

Currently, in terms of reducing the infection risk of the COVID-19 virus spreading all over the world, the development of touchless blood pressure (BP) measurement has potential benefits. The pulse transit time (PTT) has a high relation with BP, which can be measured by electrocardiogram (ECG) and photoplethysmogram (PPG). The ballistocardiogram (BCG) reflects the mechanical vibration (or displacement) caused by the heart contraction/relaxation (or heart beating), which can be measured from multiple degrees of the body. The goal of this study is to develop a cuffless and touchless BP-measurement method based on a commercial weight scale combined with a PPG sensor when measuring body weight. The proposed method was that the PTTBCG-PPGT was extracted from the BCG signal measured by a weight scale, and the PPG signal was measured from the PPG probe placed at the toe. Four PTT models were used to estimate BP. The reference method was the PTTECG-PPGF extracted from the ECG signal and PPG signal measured from the PPG probe placed at the finger. The standard BP was measured by an electronic blood pressure monitor. Twenty subjects were recruited in this study. By the proposed method, the root-mean-square error (ERMS) of estimated systolic blood pressure (SBP) and diastolic blood pressure (DBP) are 6.7 ± 1.60 mmHg and 4.8 ± 1.47 mmHg, respectively. The correlation coefficients, r2, of the proposed model for the SBP and DBP are 0.606 ± 0.142 and 0.284 ± 0.166, respectively. The results show that the proposed method can serve for cuffless and touchless BP measurement.

Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types.

BACKGROUND: SARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. COVID-19 disease severity has been associated with some pre-existing conditions and the magnitude of the adaptive immune response to SARS-CoV-2, and a recent genome-wide association study (GWAS) of the risk of critical illness revealed a significant genetic component. To gain insight into how human genetic variation attenuates or exacerbates disease following SARS-CoV-2 infection, we implicated putatively functional COVID risk variants in the cis-regulatory landscapes of human immune cell types with established roles in disease severity and used high-resolution chromatin conformation capture to map these disease-associated elements to their effector genes. RESULTS: This functional genomic approach implicates 16 genes involved in viral replication, the interferon response, and inflammation. Several of these genes (PAXBP1, IFNAR2, OAS1, OAS3, TNFAIP8L1, GART) were differentially expressed in immune cells from patients with severe versus moderate COVID-19 disease, and we demonstrate a previously unappreciated role for GART in T cell-dependent antibody-producing B cell differentiation in a human tonsillar organoid model. CONCLUSIONS: This study offers immunogenetic insight into the basis of COVID-19 disease severity and implicates new targets for therapeutics that limit SARS-CoV-2 infection and its resultant life-threatening inflammation.

Virofree, an Herbal Medicine-Based Formula, Interrupts the Viral Infection of Delta and Omicron Variants of SARS-CoV-2

Coronavirus disease 2019 (COVID-19) remains a threat with the emergence of new variants, especially Delta and Omicron, without specific effective therapeutic drugs. The infection causes dysregulation of the immune system with a cytokine storm that eventually leads to fatal acute respiratory distress syndrome (ARDS) and further irreversible pulmonary fibrosis. Therefore, the promising way to inhibit infection is to disrupt the binding and fusion between the viral spike and the host ACE2 receptor. A transcriptome-based drug screening platform has been developed for COVID-19 to explore the possibility and potential of the long-established drugs or herbal medicines to reverse the unique genetic signature of COVID-19. In silico analysis showed that Virofree, an herbal medicine, reversed the genetic signature of COVID-19 and ARDS. Biochemical validations showed that Virofree could disrupt the binding of wild-type and Delta-variant spike proteins to ACE2 and its syncytial formation via cell-based pseudo-typed viral assays, as well as suppress binding between several variant recombinant spikes to ACE2, especially Delta and Omicron. Additionally, Virofree elevated miR-148b-5p levels, inhibited the main protease of SARS-CoV-2 (Mpro), and reduced LPS-induced TNF-α release. Virofree also prevented cellular iron accumulation leading to ferroptosis which occurs in SARS-CoV-2 patients. Furthermore, Virofree was able to reduce pulmonary fibrosis-related protein expression levels in vitro. In conclusion, Virofree was repurposed as a potential herbal medicine to combat COVID-19. This study highlights the inhibitory effect of Virofree on the entry of Delta and Omicron variants of SARS-CoV-2, which have not had any effective treatments during the emergence of the new variants spreading.

Cuffless and Touchless Measurement of Blood Pressure from Ballistocardiogram Based on a Body Weight Scale

Currently, in terms of reducing the infection risk of the COVID-19 virus spreading all over the world, the development of touchless blood pressure (BP) measurement has potential benefits. The pulse transit time (PTT) has a high relation with BP, which can be measured by electrocardiogram (ECG) and photoplethysmogram (PPG). The ballistocardiogram (BCG) reflects the mechanical vibration (or displacement) caused by the heart contraction/relaxation (or heart beating), which can be measured from multiple degrees of the body. The goal of this study is to develop a cuffless and touchless BP-measurement method based on a commercial weight scale combined with a PPG sensor when measuring body weight. The proposed method was that the PTTBCG-PPGT was extracted from the BCG signal measured by a weight scale, and the PPG signal was measured from the PPG probe placed at the toe. Four PTT models were used to estimate BP. The reference method was the PTTECG-PPGF extracted from the ECG signal and PPG signal measured from the PPG probe placed at the finger. The standard BP was measured by an electronic blood pressure monitor. Twenty subjects were recruited in this study. By the proposed method, the root-mean-square error (ERMS) of estimated systolic blood pressure (SBP) and diastolic blood pressure (DBP) are 6.7 ±1.60 mmHg and 4.8 ±1.47 mmHg, respectively. The correlation coefficients, r2, of the proposed model for the SBP and DBP are 0.606 ±0.142 and 0.284 ±0.166, respectively. The results show that the proposed method can serve for cuffless and touchless BP measurement.

Association of hydroxychloroquine and cardiac arrhythmia in patients with systemic lupus erythematosus: A population-based case control study.

OBJECTIVES: Hydroxychloroquine is widely used to treat certain viral and rheumatic diseases including systemic lupus erythematosus. Cardiac arrhythmia is an important safety issue with hydroxychloroquine. The aim of this study was to investigate whether hydroxychloroquine increases new-onset arrhythmia among patients with systemic lupus erythematosus. METHODS: This was a nested case-control study using data from the Longitudinal Health Insurance Database of Taiwan. A conditional logistic regression model was used to analyse differences in the risk of arrhythmia between systemic lupus erythematosus patients with and without hydroxychloroquine treatment after controlling for related variables. RESULTS: A total of 2499 patients with newly diagnosed systemic lupus erythematosus were identified (81% females), of whom 251 were enrolled in the new-onset arrhythmia group (mean age 50.4 years) and 251 in the non-arrhythmia group (mean age 49.1 years). There was no significantly increased risk of cardiac arrhythmia (adjusted odds ratio = 1.49, 95% confidence interval: 0.98-2.25) or ventricular arrhythmia (adjusted odds ratio = 1.02, 95% confidence interval: 0.19-5.41) between the patients with and without hydroxychloroquine treatment. In addition, there were no significant differences in the risk of arrhythmia between those receiving hydroxychloroquine treatment for <180 days or ≥180 days, with a drug adherence rate of <50% or ≥50%, and receiving a daily dose of <400 mg or ≥400 mg. CONCLUSION: In patients with systemic lupus erythematosus, hydroxychloroquine treatment did not significantly increase the risk of cardiac arrhythmia or life-threatening ventricular arrhythmia regardless of the different hydroxychloroquine treatment duration, drug adherence rate, or daily dose.

Statin Use Is Associated with a Decreased Risk of Mortality among Patients with COVID-19.

BACKGROUND: Recent epidemiological studies remain controversial regarding the association between statin use and reducing the risk of mortality among individuals with COVID-19. OBJECTIVE: The objective of this study was to clarify the association between statin use and the risk of mortality among patients with COVID-19. METHODS: We conducted a systematic articles search of online databases (PubMed, EMBASE, Scopus, and Web of Science) between 1 February 2020 and 20 February 2021, with no restriction on language. The following search terms were used: "Statins" and "COVID-19 mortality or COVID19 mortality or SARS-CoV-2 related mortality". Two authors individually examined all articles and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for study inclusion and exclusion. The overall risk ratio (RRs) with 95% confidence interval (CI) was calculated to show the strength of the association and the heterogeneity among the studies was presented Q and I2 statistic. RESULTS: Twenty-eight studies were assessed for eligibility and 22 studies met the inclusion criteria. Statin use was associated with a significantly decreased risk of mortality among patients with COVID-19 (RR adjusted = 0.64; 95% CI: 0.57-0.72, p < 0.001). Moreover, statin use both before and after the admission was associated with lowering the risk of mortality among the COVID-19 patients (RR adjusted;before = 0.69; 95% CI: 0.56-0.84, p < 0.001 and RR adjusted;after = 0.57; 95% CI: 0.54-0.60, p < 0.001). CONCLUSION: This comprehensive study showed that statin use is associated with a decreased risk of mortality among individuals with COVID-19. A randomized control trial is needed to confirm and refute the association between them.