ABSTRACT
Vaccination against SARS-COV-2 has been the most important strategy for preventing infection and controlling pandemics of Coronavirus disease 2019 (COVID-19). But there is a lack of research on the pandemics in postoperative patients with breast cancer. We conducted a web-based questionnaire survey on SARS-CoV-2 vaccination in these populations. Univariate and multivariable logistic regression was used to estimate the associations. Among 947 valid online questionnaires, 341 (36.0%) accepted SARS-CoV-2 vaccination, while 606 (64.0%) were not. There were significant differences in age, current treatment, the time since surgery, and the symptoms of anxiety and depression between the two groups. We identified current treatment (odds ratio, OR = 0.51 for endocrine therapy; 95% CI: 0.29–0.89), the time since surgery (OR = 22.49 for 1–2 years; 95% CI: 12.31–41.10; OR = 8.49 for 2–5 years ; 95% CI: 4.98–14.46; OR = 1.79 for > 5 years ; 95% CI: 1.11–2.89), and the symptoms of depression (OR = 2.48; 95% CI: 1.19–5.15) as significant factors for unvaccination. The overall incidence of adverse reactions was 43.1%, and the most common local and systemic adverse reactions were pain at the injection site (28.4%) and fatigue (8.8%), respectively. Postoperative patients with breast cancer have a lower rate of vaccination for SARS-CoV-2. Receiving treatment, a shorter time since surgery and symptom of depression were associated with unvaccination. But, about 76.6% of the unvaccinated participants were willing to be vaccinated when their breast cancer was stable. More importantly, a favorable safety profile of the vaccines is indicated.
Subject(s)
COVID-19ABSTRACT
Due to the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), deepening the host genetic contribution to severe COVID-19 may further improve our understanding about underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes. We include detailed stratified analyses based on age, sex and disease severity. In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.31 and 19q13.33 associated with severe COVID-19 with respiratory failure. These associations implicate a highly pleiotropic ~0.9-Mb 17q21.31 inversion polymorphism, which affects lung function and immune and blood cell counts, and the NAPSA gene, involved in lung surfactant protein production, in COVID-19 pathogenesis.
Subject(s)
COVID-19 , Respiratory InsufficiencyABSTRACT
A key element to the prevention and management of the COVID-19 pandemic is the development of effective therapeutics. Drug combination strategies of repurposed drugs offer a number of advantages to monotherapies including the potential to achieve greater efficacy, the potential to increase the therapeutic index of drugs and the potential to reduce the emergence of drug resistance. Combination of agents with antiviral mechanisms of action with immune-modulatory or anti-inflammatory drug is also worthy of investigation. Here, we report on the in vitro synergistic interaction between two FDA approved drugs, remdesivir (RDV) and ivermectin (IVM) resulting in enhanced antiviral activity against SARS-CoV-2, the causative pathogen of COVID-19. These findings warrant further investigations into the clinical potential of this combination, together with studies to define the underlying mechanism.
Subject(s)
COVID-19ABSTRACT
Background Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, there has been increasing demand to identify predictors of severe clinical course in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human leukocyte antigen alleles (HLA) have been suggested as potential genetic host factors. We sought to evaluate this hypothesis by conducting an international multicenter study using HLA sequencing with subsequent independent validation. Methods We analyzed a total of 332 samples. First, we enrolled 233 patients in Germany, Spain, and Switzerland for HLA and whole exome sequencing. Furthermore, we validated our results in a public data set (United States, n=99). Patients older than 18 years presenting with COVID-19 were included, representing the full spectrum of the disease. HLA candidate alleles were identified in the derivation cohort (n=92) and tested in two independent validation cohorts (n=240). Results We identified HLA-C* 04:01 as a novel genetic predictor for severe clinical course in COVID-19. Carriers of HLA-C* 04:01 had twice the risk of intubation when infected with SARS-CoV-2 (hazard ratio 2.1, adjusted p-value=0.0036). Importantly, these findings were successfully replicated in an independent data set. Furthermore, our findings are biologically plausible, as HLA-C* 04:01 has fewer predicted bindings sites with relevant SARS-CoV-2 peptides as compared to other HLA alleles. Exome sequencing confirmed findings from HLA analysis. Conclusions HLA-C* 04:01 carriage is associated with a twofold increased risk of intubation in patients infected with SARS-CoV-2. Testing for HLA-C* 04:01 could have clinical implications to identify high-risk patients and individualize management.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
Background：COVID-19 poses a significant challenge to global public health. During the pandemic, COVID-19 patients and people in outbreak areas have suffered from stigma associated with the disease. This study aimed to evaluate the prevalence of COVID-19-related stigma toward COVID-19 patients and people from the city of Wuhan in China and assess the association of COVID-19-related stigma, health literacy, and sociodemographic characteristics.Methods：A cross-sectional survey covering 5,039 respondents was conducted in 31 provinces in China using a convenience sampling method. Binary logistic regressions were used to identify the factors associated with COVID-19-related stigma.Results：Among the participants, 122 (2.4%) reported themselves and 254 (5.0%) reported the communities they lived in held a stigmatizing attitude toward COVID-19 patients, respectively. Additionally, 114 (2.5%) and 475 (10.3%) reported that themselves and the communities they lived in, respectively, held a stigma against people from Wuhan, where was the most severely affected area in China. People aged over 40, lived in areas with severe epidemics (aOR=2.15, 95% CI [1.12-4.13]), and who felt it difficult to find and understand information about COVID-19 (aOR=1.91, 95% CI [1.08-3.27]; aOR=1.88, 95% CI [1.08-3.29]) were more likely to stigmatize COVID-19 patients. People who were male, aged 41 to 50, and had difficulty understanding information (aOR=2.08, 95% CI [1.17-3.69]) were more likely to stigmatize people from Wuhan.Conclusions：COVID-19 patients and Wuhan residents suffered stigma at both the individual and community levels, although proportion of those holding a stigma was not very high. Provinces close to Wuhan had relatively high stigma toward COVID-19 patients and people from Wuhan. There was a correlation between better health literacy and lower stigma during the COVID-19 outbreak. Tailored interventions were encouraged to improve health literacy and consequently to reduce stigma toward both COVID-19 patients and Wuhan people from individual and community levels, respectively.
Subject(s)
COVID-19ABSTRACT
BackgroundCOVID-19 is a novel and highly virulent virus, which caused a rapid and massive onset of clinical trials in a short period of time.With the aim to obtain suggestions in the guidance on performing public health emergency clinical trials, and control this virus in China and other countries and for the prevention of the onset of other infectious viruses in the future. Methods COVID-19, SARS, MERS and Ebola clinical trials registered in the Chinese clinical trial registry and clinical trials.gov were collected and analyzed and intervention protocols were descriptively analyzed, focusing on the analysis and comparison of the drug used. The search period ended on February 24, 2020.ResultsThe number of the registered COVID-19 clinical trials was 295. Among 203 intervention trials, 78.3% (159) were drug clinical trials. The 159 COVID-19 trials were designed and analyzed with the highest proportion of random, open control study [66.0% (105)], and blind randomized trials [13.8% (22)]. The drug mostly used was Lopinavir/Ritonavir (15.1%). The sample size median 100,IQR(interquartile range) 140. The number of the registered SARS was 6, MERS 15, and Ebola 97. Among 3 MERS and 19 Ebola drug intervention clinical trials, MERS and Ebola were randomized, blind, and placebo-controlled drug clinical trials accounting for 100% (3) and 31.6% (6), respectively, while SARS were vaccine trials, without drug intervention clinical trials registered.Conclusions Some of the COVID-19 clinical trials and drug selection performed are somewhat disordered, requiring greater attention to the needs, science assumptions, ethics and quality management of the clinical research. Thus, during the epidemic period, the country should deliver guidance on how to perform appropriate emergency clinical trials, design a scientifically based clinical trial program and focus on researching drugs or vaccines that have great potential.
Subject(s)
COVID-19 , Coronavirus InfectionsABSTRACT
BackgroundCOVID-19 is a novel and highly virulent virus, which caused a rapid and massive onset of clinical trials in a short period of time.With the aim to obtain suggestions in the guidance on performing emergency clinical trials, and control this virus in China and other countries and for the prevention of the onset of other infectious viruses in the future.MethodsCOVID-19, SARS, MERS and Ebola clinical trials registered in the Chinese clinical trial registry and clinical trials.gov were collected and analyzed and intervention protocols were compared, focusing on the analysis and comparison of the drug used. The search period ended on February 24, 2020.ResultsThe number of the registered COVID-19 clinical trials was 295. Among 203 intervention trials, 78.3% (159) were drug clinical trials, in which 46.3% (94) used chemical drugs and biological agents, 32.0% (65) were performed using Traditional Chinese Medicine (TCM) and integrated traditional Chinese and western medicine.The 159 COVID-19 trials were designed and analyzed with the highest proportion of blank randomized controls [45.9% (73)], and placebo randomized trials [14.5% (23)]. The drug mostly used was Lopinavir/Ritonavir (15.1%). The sample size ranged from 10 to 100 in 52.8% (84) trials. The number of the registered SARS was 6, MERS 15, and Ebola 97. Among 3 MERS and 19 Ebola drug intervention clinical trials, MERS and Ebola were randomized, blind, and placebo-controlled drug clinical trials accounting for 100% (3) and 31.6% (6), respectively, while SARS were vaccine trials, without drug intervention clinical trials registered.ConclusionsCompared with the SARS in 2003, the awareness and capability of clinical research in China greatly improved. However, some of the COVID-19 clinical trials and drug selection performed are somewhat disordered, requiring greater attention to the needs, science assumptions, ethics and quality management of the clinical research. Thus, during the epidemic period, the country should deliver guidance on how to perform appropriate emergency clinical trials, design a scientifically based clinical trial program and focus on researching drugs or vaccines that have great potential.