Efficacy and safety of the combination of Liushen capsules and Arbidol in the treatment of COVID-19:protocol for a randomized,multi-center pilot study

Background:From early experience,some Traditional Chinese Medicine and Arbidol had effects of against COVID-19,infer that the combination of Liushen capsules and Arbidol may further increase the therapeutic.Methods/Design:We conducted a randomized,blank parallel-controlled,open-label,multi-center,basal therapy-loaded design clinical trial.A total of 40 patients are going to be recruited after satisfying the criteria.Participants will be allocated randomly into the treatment group with the combination of Arbidol and Liushen capsules and the control group with the basic therapy.Each group will receive treatment at least 7-days or until the virus becomes negative,and visits after drug administration at day 3(visit 1),the day when the virus becomes negative(visit 2),day 7(visit 3),the day before discharge(visit 4)and day 28(visit 5),to collect their survival status and disease prognosis so that the efficacy and safety of a combination of Arbidol and Liushen capsule will be evaluated.Discussion:We described the protocol of the first clinical trial for treatment COVID-19 by using a combination of Arbidol and Liushen capsules.The results of this study will provide a basis for the design and sample size estimate of subsequent large-scale clinical trials.Trial registration:This study has been registered at Chinese clinical trial Registry(chictr.org.cn):ChiCTR2000029993.

Longitudinal virological changes and underlying pathogenesis in hospitalized COVID-19 patients in Guangzhou,China

Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)in coronavirus disease 2019(COVID-19)patients have been reported.However,the clinical outcome and pathogenesis remain unclear.In this study,we recruited 43 laboratory-confirmed COVID-19 patients.We found that prolonged viral RNA shedding or recurrence mainly occurred in severe/critical patients(P<0.05).The average viral shedding time in severe/critical patients was more than 50 days,and up to 100 days in some patients,after symptom onset.However,chest computed tomography gradually improved and complete absorption occurred when SARS-CoV-2 RT-PCR was still positive,but specific antibodies appeared.Furthermore,the viral shedding time significantly decreased when the A1,430G or C12,473T mutation occurred(P<0.01 and FDR<0.01)and increased when G227A occurred(P<0.05 and FDR<0.05).High IL1R1,IL1R2,and TNFRSF21 expression in the host positively correlated with viral shedding time(P<0.05 and false discovery rate<0.05).Prolonged viral RNA shedding often occurs but may not increase disease damage.Prolonged viral RNA shedding is associated with viral mutations and host factors.

Prevalence of bacteria, fungi, and virus coinfections with SARS-CoV-2 Omicron variant among patients with severe COVID-19 in Guangzhou, China, winter 2022

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially to the overloaded severe cases,needs to be investigated.We analyzed the coinfection status of 385 severe patients infected with the Omicron variant in Guangzhou using metagenomic sequencing.We found that 317(82.3%)patients were coinfected with at least one additional pathogen(s),including bacteria(58.7%),fungi(27.1%)and viruses(73.5%).Pseudomonas aeruginosa(P.aeruginosa)(24.2%),Staphylococcus aureus(S.aureus)(14.0%),andKlebsiella pneumoniae(K.pneumonia)(13.4%)ranked as the top three coinfected bacteria.Aspergillus fumigatus(A.fumigatus)(39.5%),Pneumocystis jirovecii(P.jirovecii)(24.4%)andCanidia albicans(C.albicans)(22.1%)were the top three coinfected fungi.Epstein-Barr virus(EBV)(63.1%),Human herpesvirus 7(HHV-7)(34.8%),and Herpes simplex virus 1(HSV-1)(32.6%)were the top three coinfected viruses.Of note,the detection of multiple coinfections of potential pathogenic bacteria,fungi,and viruses,despite lacking consistent patterns,highlighted a complicated synergistic contribution to disease severity.Our study presents the most comprehensive spectrum of bacterial,fungal,and viral coinfections in Omicron-associated severe coronavirus disease 2019(COVID-19),implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.

Introduction to bioimaging-based spatial multi-omic novel methods

Background: Spatial multi-omics are demonstrated to be a powerful method to assist researchers on genetic studies. In this review, bioimaging-based spatial multi-omics techniques such as seqFISH+, merFISH, integrated DNA seqFISH+, DNA merFISH, and MINA are introduced along with each technique’s probe design, development, and imaging processes.Results: seqFISH employed 4–5 fluorophores to barcode and conducted multiple rounds of hybridization, in order that mRNA can be identified through color-coding. seqFISH+ added 60 pseudo-color and distributed them equally into three channels to enhance imaging power, in order that i.e., 24,000 genes can be imaged in total. merFISH utilized 4 out 16 Hamming distance to innovatively provide a robust error-detecting method. MINA, a methodology combining merFISH (multiplexed error-robust fluorescence in situ hybridization) and chromosomal tracing, enabled multiplexed genomic architecture imaged in mammalian single cells. Optical reconstruction of chromatin architecture (ORCA) a method that could conduct DNA path tracing in nanoscale manner with kilobase resolution, an FISH variation that improved genetic resolution, enable high-precision fiducial registration and sequential imaging, and utilized Oligopaint probe to hybridize the short genomic region ranging from 2 to 10 kilobase. ORCA then prescribes these short section primary probes with individual barcodes to attach fluorophore and to be imaged.Conclusion: This review concentrated on providing a comprehensive overview for these spatial-multi-omics techniques with the intention on helping researchers on selecting appropriate technique for their research.

Alteration of the respiratory microbiome in COVID-19 patients with different severities

Coronavirus disease 2019(COVID-19) is rampant worldwide and has affected more than 215 countries and regions. According to the World Health Organization's report, there were 226,018,919 COVID-19 cases and 4,654,898 deaths as of March 14, 2021, although300,002,228 vaccines have been administered globally. COVID-19patients have different clinical phenotypes and can be divided into asymptomatic, normal, mild, severe, and critical patients.