Background: The present study aimed to determine the global prevalence of anosmia and dysgeusia in coronavirus disease 2019 (COVID-19) patients and to assess their association with severity and mortality of COVID-19. Moreover, this study aimed to discuss the possible pathobiological mechanisms of anosmia and dysgeusia in COVID-19. Methods: Available articles from PubMed, Scopus, Web of Science, and preprint databases (MedRxiv, BioRxiv, and Researchsquare) were searched on November 10th, 2020. Data on the characteristics of the study (anosmia, dysgeusia, and COVID-19) were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Newcastle–Ottawa scale was used to assess research quality. Moreover, the pooled prevalence of anosmia and dysgeusia were calculated, and the association between anosmia and dysgeusia in presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed using the Z test. Results: Out of 32,142 COVID-19 patients from 107 studies, anosmia was reported in 12,038 patients with a prevalence of 38.2% (95% CI: 36.5%, 47.2%); whereas, dysgeusia was reported in 11,337 patients out of 30,901 COVID-19 patients from 101 studies, with prevalence of 36.6% (95% CI: 35.2%, 45.2%), worldwide. Furthermore, the prevalence of anosmia was 10.2-fold higher (OR: 10.21; 95% CI: 6.53, 15.96, p < 0.001) and that of dysgeusia was 8.6-fold higher (OR: 8.61; 95% CI: 5.26, 14.11, p < 0.001) in COVID-19 patients compared to those with other respiratory infections or COVID-19 like illness. To date, no study has assessed the association of anosmia and dysgeusia with severity and mortality of COVID-19. Conclusion: Anosmia and dysgeusia are prevalent in COVID-19 patients compared to those with the other non-COVID-19 respiratory infections. Several possible mechanisms have been hypothesized; however, future studies are warranted to elucidate the definitive mechanisms of anosmia and dysgeusia in COVID-19. Protocol registration: PROSPERO CRD42020223204.
The 2022 multi-country monkeypox outbreak in humans has brought new public health adversity on top of the ongoing coronavirus disease 2019 (COVID-19) pandemic. The disease has spread to 104 countries throughout six continents of the world, with the highest burden in North America and Europe. The etiologic agent, monkeypox virus (MPXV), has been known since 1959 after isolation from infected monkeys, and virulence among humans has been reported since the 1970s, mainly in endemic countries in West and Central Africa. However, the disease has re-emerged in 2022 at an unprecedented pace, with particular concern on its human-to-human transmissibility and community spread in non-endemic regions. As a mitigation effort, healthcare workers, public health policymakers, and the general public worldwide need to be well-informed on this relatively neglected viral disease. Here, we provide a comprehensive and up-to-date overview of monkeypox, including the following aspects: epidemiology, etiology, pathogenesis, clinical features, diagnosis, and management. In addition, the current review discusses the preventive and control measures, the latest vaccine developments, and the future research areas in this re-emerging viral disease that was declared as a public health emergency of international concern.
The CRISPR/Cas9 system provides a novel and promising tool for editing the HIV-1 proviral genome. We designed RNA-guided CRISPR/Cas9 targeting the HIV-1 regulatory genes tat and rev with guide RNAs (gRNA) selected from each gene based on CRISPR specificity and sequence conservation across six major HIV-1 subtypes. Each gRNA was cloned into lentiCRISPRv2 before co-transfection to create a lentiviral vector and transduction into target cells. CRISPR/Cas9 transduction into 293 T and HeLa cells stably expressing Tat and Rev proteins successfully abolished the expression of each protein relative to that in non-transduced and gRNA-absent vector-transduced cells. Tat functional assays showed significantly reduced HIV-1 promoter-driven luciferase expression after tat-CRISPR transduction, while Rev functional assays revealed abolished gp120 expression after rev-CRISPR transduction. The target gene was mutated at the Cas9 cleavage site with high frequency and various indel mutations. Conversely, no mutations were detected at off-target sites and Cas9 expression had no effect on cell viability. CRISPR/Cas9 was further tested in persistently and latently HIV-1-infected T-cell lines, in which p24 levels were significantly suppressed even after cytokine reactivation, and multiplexing all six gRNAs further increased efficiency. Thus, the CRISPR/Cas9 system targeting HIV-1 regulatory genes may serve as a favorable means to achieve functional cures.
Broad‐spectrum antiviral agents targeting viral RNA‐dependent RNA polymerase (RdRp) are expected to be a key therapeutic strategy in the ongoing coronavirus disease 2019 (COVID‐19) pandemic and its future variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus that causes COVID‐19. Molnupiravir is a nucleoside analog that in vivo experiments have been reported to inhibit the replication of SARS‐CoV‐2, the virus that causes COVID‐19. Clinical trials of molnupiravir as a therapy for patients with mild‐to‐moderate COVID‐19 also suggest its significant therapeutic efficacy in comparison to placebo. Molnupiravir is lethally mutagenic against viral RNA, but its effect on host cell DNA is being questioned. Herein, the safety concerns of molnupiravir are discussed with recent findings from published reports and clinical trials. The unchanged efficacy of molnupiravir against mutated SARS‐CoV‐2 variants is also highlighted. With its administration via the oral route, molnupiravir is expected to turn the tide of the COVID‐19 pandemic.
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