Atrial of arbidol hydrochloride in adults with COVID-19

Background: To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods: This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results: A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled;66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64]vs. 42.4% [14/33];difference of conversion rate 27.9%;95% confidence interval [CI], 7.7%-48.1%;P=0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 daysvs. 12.0 days;hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060,P=0.006), symptom of fever (median 3.0 daysvs. 12.0 days;HR: 18.990, 95% CI: 5.350-67.410,P<0.001), as well as hospitalization (median 12.5 daysvs. 20.0 days;P<0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 daysvs. 14.5 days;P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression.Conclusions: SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.

Investigation of the genetic etiology in male infertility with apparently balanced chromosomal structural rearrangements by genome sequencing

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1%of azoospermia or severe oligospermia.However,the underlying mechanisms of pathogenesis and etiologies are still largely unknown.Herein,we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants.In addition,high read-depth genome sequencing(GS)(30-fold)was performed to investigate point mutations causative of male infertility.Mate-pair GS(4-fold)revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements.Overall,the breakpoints caused truncations of 30 RefSeq genes,five of which were associated with spermatogenesis.Furthermore,the breakpoints disrupted 43 topological-associated domains.Direct disruptions or potential dysregulations of genes,which play potential roles in male germ cell development,apoptosis,and spermatogenesis,were found in all cases(n=6).In addition,high read-depth GS detected dual molecular findings in case MI6,involving a complex rearrangement and two point mutations in the gene DNAH1.Overall,our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility.We demonstrated the complexity of chromosomal structural rearrangements,potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.

Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease

Objectives The predisposition of intracranial atherosclerotic disease(ICAD)to East Asians over Caucasians infers a genetic basis which,however,remains largely unknown.Higher prevalence of vascular risk factors(VRFs)in Chinese over Caucasian patients who had a stroke,and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD.Methods Unrelated symptomatic patients with ICAD were recruited for genome sequencing(GS,60-fold).Rare and potentially deleterious single-nucleotide variants(SNVs)and small insertions/deletions(InDels)were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes.Rare aneuploidies,copy number variants(CNVs)and chromosomal structural rearrangements were also investigated.Lastly,candidate genes were used for pathway and gene ontology enrichment analysis.Results Among 92 patients(mean age at stroke onset 61.0±9.3 years),GS identified likely ICAD-associated rare genomic variants in 54.3%(50/92)of patients.Forty-eight patients(52.2%,48/92)had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes.None of the 59 rare variants were identified in local subjects without ICAD(n=126).31 SNVs/InDels were related to conventional VRFs,and 28 were discovered in genes related to other stroke subtypes.Our study also showed that rare CNVs(n=7)and structural rearrangement(a balanced translocation)were potentially related to ICAD in 8.7%(8/92)of patients.Lastly,candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process.Conclusions Our GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.