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 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.
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.
Background: This study aimed to determine the cumulative prevalence of prolonged gastrointestinal (GI) symptoms, including nausea, vomiting, diarrhea, lack of appetite, abdominal pain, and dysgeusia, in survivors of both mild and severe COVID-19 worldwide and to discuss the potential pathogenesis. Methods: Three databases (PubMed, Scopus, and Web of Science) were searched for relevant articles up to January 30, 2021. Data on study characteristics, clinical characteristics during follow-up, the number of patients with prolonged GI symptoms, and total number of COVID-19 survivors were retrieved according to PRISMA guidelines. The quality of eligible studies was assessed using the Newcastle-Ottawa scale. The pooled prevalence of specific prolonged GI symptoms was calculated and the association between COVID-19 severity and the occurrence of prolonged GI symptoms was assessed if appropriate. Results: The global prevalence of prolonged nausea was 3.23% (95% CI: 0.54%–16.53%) among 527 COVID-19 survivors. Vomiting persisted in 93 of 2,238 COVID-19 survivors (3.19%, 95% CI: 1.62%–6.17%) and prolonged diarrhea was found in 34 of 1,073 survivors (4.12%, 95% CI: 1.07%–14.64%). A total of 156 patients among 2,238 COVID-19 survivors (4.41%, 95% CI: 1.91%–9.94%) complained of persistent decreased or loss of appetite. The cumulative prevalence of prolonged abdominal pain was 1.68% (95% CI: 0.84%–3.32%), whereas persistent dysgeusia was identified in 130 cases among 1,887 COVID-19 survivors (7.04%, 95% CI: 5.96%–8.30%). Data was insufficient to assess the relationship between COVID-19 severity and the occurrence of all prolonged GI symptoms. Conclusion: Persistent GI symptoms among COVID-19 survivors after discharge or recovery raises a concern regarding the long-term impact of the COVID-19 infection on the quality of life of the survivors. Despite several potential explanations proposed, studies that aim to follow patients after recovery from COVID-19 and determine the pathogenesis of the prolonged symptoms of COVID-19 survivors are warranted. PROSPERO registration: CRD42021239187.
The study sought to determine the prevalence of persistent long COVID symptoms such as anxiety, depression, dizziness, chest pain, sleep difficulty, palpitations, weight loss, and hair loss among coronavirus disease 2019 (COVID-19) survivors worldwide and to discuss the potential pathogeneses. Potential studies were searched in three databases (PubMed, Scopus, and Web of Science) as of January 30, 2021. Data on study characteristics, patient characteristics during the follow-up, the number of patients with persistent long COVID symptoms and total COVID-19 survivors were collected according to PRISMA guidelines. To assess the quality of studies, the Newcastle-Ottawa scale was used. The estimated prevalence of each long COVID symptom and the association between COVID-19 severity and the occurrence of prolonged symptoms was assessed, if appropriate. The global prevalence of prolonged anxiety was 15.76% (95%CI: 6.36%, 25.15%). Chest pain persisted in 10.36% (239/3,224) of COVID-19 patients (95%CI: 4.92%, 15.80%). Prolonged depression was found in 24 of 548 COVID-19 survivors with an estimated prevalence of 4.32% (95%CI: 2.62%, 6.03%) and dizziness was presented in 4.83% (118/2,219, 95%CI: 1.50%, 8.16%) after recovery. Hair loss was complained by 527 of 2,251 recovered patients (cumulative prevalence of 24.76%, 95%CI: 19.60%, 29.91%), while weight loss was identified in 37 cases among 452 COVID-19 survivors (8.19%, 95%CI: 5.66%, 10.71%). Prolonged palpitation was experienced by 19.38% (211/1,926) survivors with 95%CI: 2.40%, 41.16%. Sleep difficulty was found in 541 of 2,622 COVID-19 survivors (17.87%, 95%CI: 7.55%, 28.20%). The association between COVID-19 severity and the occurrence of persistent long COVID symptoms was not analyzed due to the lack of data. In conclusion, persistent psychological symptoms are frequently reported among COVID-19 survivors. Follow-up studies with a longer duration and larger population are warranted to assess the extent of prolonged symptoms and the quality of life of COVID-19 survivors. Despite various potential pathogeneses that have been hypothesized, a definitive mechanism is yet to be addressed.
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.
Background Suicidal behavior is a prevalent psychiatric emergency in HIV-infected adults. Detection of suicidal ideation is important in planning early psychiatric intervention and optimizing HIV/AIDS management. Characterization of suicidal ideation among HIV-infected adults is crucial; however, practically there is no data in Indonesia, the country with the second largest burden of HIV/AIDS epidemic in Asia. This study aims to identify suicidal ideation and analyze the associated psychopathology and determining factors among HIV-infected adults in Indonesia. Methods An observational cross-sectional study was conducted among HIV-infected adults aged 18–65 years old receiving antiretroviral therapy (ART). Measurement using Symptom Checklist-90 (SCL-90) was performed to assess the existing psychopathology. Firth’s penalized logistic regression analysis was performed to identify factors associated with suicidal ideation. Results A total of 86 subjects were recruited. Most subjects were male (65.1%), median age was 35 years, and median latest CD4 count was 463 cells/μl. Lifetime suicidal ideation was identified in 20 subjects (23.3%). Mean SCL-90 T-score for depressive and anxiety symptoms were both significantly higher among subjects with suicidal ideation (M = 60.75, SD = 12.0, p = 0.000 and M = 57.9, SD = 2.8, p = 0.001, respectively) compared to those without. Bivariate analyses showed that lifetime suicidal ideation was associated with depressive and anxiety symptoms, non-marital status, CD4 count < 500 cells/μl, and efavirenz use. Multivariate analysis identified that a single-point increase in SCL-90 depression symptoms score (AOR 1.16, 95% CI 4.5–123.6, p = 0.000) and efavirenz use (AOR 5.00, 95% CI 1.02–24.6, p = 0.048) were significant independent factors related to suicidal ideation. Conclusion Suicidal ideation is commonly found among Indonesian HIV-infected adults on ART. Depressive symptoms and efavirenz use are independent factors related to the presence of suicidal ideation. Thus, early screening of psychopathology as well as substitution of efavirenz with other ART regiment are recommended to prevent suicide and improve HIV/AIDS management outcome.
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