Project description:Objective: To study the potential effect of COVID-19 on the endometrium of affected symptomatic women. Design: Preliminary study of the endometrial transcriptomes in women with COVID-19 through RNA sequencing. Setting: Hospital and university laboratories. Subjects: Women with COVID-19 lacking SARS-CoV-2 infection in endometrial tissue. Intervention/Exposure: Endometrial biopsy collection. Main outcomes measures: Endometrial gene expression and functional analysis of patients with COVID-19 versus uninfected individuals. Results: COVID-19 systemic disease alters endometrial gene expression in 75% of women, with patients exhibiting a preponderance of 163 up-regulated (e.g., UTS2, IFI6, IFIH1, BNIP3) and 72 down-regulated genes (e.g., CPZ, CDH3, IRF4) (FDR<0.05). A total of 161 dysregulated functions (36 up-regulated and 125 down-regulated) were typically enriched in COVID-19 endometria, including upregulation in pathways involved in response to virus and cytokine inflammation, highlighting upregulation of a COVID-19 response pathway. Conclusion: COVID-19 affects endometrial gene expression despite the absence of SARS-CoV-2 particles in endometrial tissues.
Project description:The purpose of this study was to identify miRNAs that were dysregulated after the onset of COVID-19 and thus potentially be used for risk stratification (i.e., mortality). Therefore, we conducted a multi-center, retrospective longitudinal cohort study enrolling 142 patients with laboratory-confirmed SARS-CoV-2 infection who presented to two Canadian hospitals from May 2020 – December 2020 along with a cohort of 27 SARS-CoV-2 patients with mild upper respiratory tract symptoms and 69 SARS-CoV-2-negative patients from the ICU. Blood was biobanked from SARS-CoV-2 positive patients in the emergency department (mild), ward (moderate) or intensive care unit (severe). Assessment of miRNA expression and co-regulatory network generation revealed significant transcriptome dyregulation in pateints with severe COVID-19 that was largely different from SARS-CoV-2 negative patients in the ICU.
Project description:ObjectivesResearchers studying treatment of coronavirus disease 2019 (COVID-19) have reported findings of randomized trials comparing standard care with care augmented by experimental drugs. Many trials have small sample sizes, so estimates of treatment effects are imprecise. Hence, clinicians may find it difficult to decide when to treat patients with experimental drugs. A conventional practice when comparing standard care and an innovation is to choose the innovation only if the estimated treatment effect is positive and statistically significant. This practice defers to standard care as the status quo. We study treatment choice from the perspective of statistical decision theory, which considers treatment options symmetrically when assessing trial findings.MethodsWe use the concept of near-optimality to evaluate criteria for treatment choice. This concept jointly considers the probability and magnitude of decision errors. An appealing criterion from this perspective is the empirical success rule, which chooses the treatment with the highest observed average patient outcome in the trial.ResultsConsidering the design of some COVID-19 trials, we show that the empirical success rule yields treatment choices that are much closer to optimal than those generated by prevailing decision criteria based on hypothesis tests.ConclusionUsing trial findings to make near-optimal treatment choices rather than perform hypothesis tests should improve clinical decision making.
Project description:Estimation of the effective reproduction number, R(t), of coronavirus disease (COVID-19) in real-time is a continuing challenge. R(t) reflects the epidemic dynamics based on readily available illness onset data, and is useful for the planning and implementation of public health and social measures. In the present study, we proposed a method for computing the R(t) of COVID-19, and applied this method to the epidemic in Osaka prefecture from February to September 2020. We estimated R(t) as a function of the time of infection using the date of illness onset. The epidemic in Osaka came under control around 2 April during the first wave, and 26 July during the second wave. R(t) did not decline drastically following any single intervention. However, when multiple interventions were combined, the relative reductions in R(t) during the first and second waves were 70% and 51%, respectively. Although the second wave was brought under control without declaring a state of emergency, our model comparison indicated that relying on a single intervention would not be sufficient to reduce R(t) < 1. The outcome of the COVID-19 pandemic continues to rely on political leadership to swiftly design and implement combined interventions capable of broadly and appropriately reducing contacts.
Project description:Coronavirus disease 2019 (COVID-19) is a type of viral pneumonia with an uncommon outbreak in Wuhan, China, in December 2019, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). SARS-CoV-2 is extremely contagious and has resulted in a fast pandemic of COVID-19. Currently, COVID-19 is on the rise around the world, and it poses a severe threat to public health around the world. This review provides an overview about the COVID-19 virus to increase public awareness and understanding of the virus and its consequences in terms of history, epidemiology, structure, genome, clinical symptoms, diagnosis, prevention, and treatment.
Project description:Patients with the severe form of coronavirus disease 2019 (COVID-19) have been frequently found to suffer from both arterial and venous thrombotic events due to the perpetuation of a hypercoagulable state. This phenomenon, termed COVID-19-associated coagulopathy, is now considered a major component of the pathophysiology of this novel infectious disease, leading to widespread thrombosis. While at first, the vascular insults may be limited to the pulmonary microvasculature, as the disease progresses, systemic involvement occurs, culminating in distant organ thrombosis and multiorgan dysfunction syndrome. In this review article, we discuss recent insights into the pathophysiologic mechanisms of COVID-19-associated coagulopathy and review the clinical, histopathologic, and laboratory evidence, which leads us to conclude that COVID-19 is both a pulmonary and vascular disorder.
Project description:SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.
Project description:ObjectivesEstimating the isolated effect of coronavirus disease 2019 (COVID-19) on the risk of mortality is challenging. We aimed to determine whether COVID-19 was associated with high rates of mortality independently of age, sex and underlying disorders.MethodsA population-based, matched, case-control study of adults insured by Clalit Health Services was performed. Cases were defined as patients who died of all causes between July and December 2020. Each case was matched in a ratio of 1:1 with a living control based on age, sex and co-morbidities. An unconditional logistic regression analysis was performed to identify independent risk factors for mortality.ResultsA total of 2874 patients who died were successfully matched with 2874 living controls. The prevalence of COVID-19 was higher among the patients who died than among the controls (13.5% [387/2874] vs. 4% [115/2874], respectively; OR, 3.73; 95% CI, 3.01-4.63; p < 0.001). A significantly increased odds of mortality was also observed in patients with COVID-19 without underlying diseases (OR, 3.67; 95% CI, 2.58-5.23) and in patients with COVID-19 and underlying diseases (OR, 3.77; 95% CI, 2.87-4.94). A multi-variate logistic analysis showed that COVID-19 (OR, 2.01; 95% CI, 1.07-3.77), low socio-economic status (OR, 1.36; 95% CI, 1.02-1.82), dementia (OR, 2.50; 95% CI, 2.10-3.01), smoking (OR, 1.35; 95% CI, 1.13-1.63) and an interaction variable of age >80 years and COVID-19 (OR, 2.27; 95% CI, 1.14-4.54) were independent risk factors for mortality, whereas influenza vaccination and high body mass index were associated with lower rates of mortality.ConclusionTesting positive for COVID-19 increased the risk of death three folds, regardless of underlying disorders. These results emphasize the effect of COVID-19 on mortality during the early period of the COVID-19 outbreak, when no vaccines or effective therapeutics were available.
Project description:The clinical spectrum of coronavirus disease 2019 (COVID-19) infection ranges from asymptomatic infection to severe pneumonia with respiratory failure and even death. More severe cases with higher mortality have been reported in older patients and in those with chronic illness such as hypertension, diabetes or cardiovascular diseases. In this regard, patients with chronic kidney disease (CKD) have a higher rate of all-type infections and cardiovascular disease than the general population. A markedly altered immune system and immunosuppressed state may predispose CKD patients to infectious complications. Likewise, they have a state of chronic systemic inflammation that may increase their morbidity and mortality. In this review we discuss the chronic immunologic changes observed in CKD patients, the risk of COVID-19 infections and the clinical implications for and specific COVID-19 therapy in CKD patients. Indeed, the risk for severe COVID-19 is 3-fold higher in CKD than in non-CKD patients; CKD is 12-fold more frequent in intensive care unit than in non-hospitalized COVID-19 patients, and this ratio is higher than for diabetes or cardiovascular disease; and acute COVID-19 mortality is 15-25% for haemodialysis patients even when not developing pneumonia.