Project description:Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41-0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02-1.04; HR = 1.79, 95% CI:1.04-3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.
Project description:Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median Cumulative Illness Rating Scale score was 8 (range, 4-32). Thirty-nine percent were treatment naive ("watch and wait"), while 61% had received ≥1 CLL-directed therapy (median, 2; range, 1-8). Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly Bruton tyrosine kinase inhibitors (BTKi's; n = 68/90 [76%]). At a median follow-up of 16 days, the overall case fatality rate was 33%, though 25% remain admitted. Watch-and-wait and treated cohorts had similar rates of admission (89% vs 90%), intensive care unit admission (35% vs 36%), intubation (33% vs 25%), and mortality (37% vs 32%). CLL-directed treatment with BTKi's at COVID-19 diagnosis did not impact survival (case fatality rate, 34% vs 35%), though the BTKi was held during the COVID-19 course for most patients. These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess severe acute respiratory syndrome coronavirus 2 infection risk, these data should be validated independently, and randomized studies of BTKi's in COVID-19 are needed to provide definitive evidence of benefit.
Project description:Background The recent pandemic of coronavirus disease 19 (COVID-19) has been causing intense stress among the global population. In the case of hospitalized and ICU-admitted COVID-19 patients with comorbidities, it has been observed that a major portion of them are diabetic. Therefore, researchers had indicated a link between diabetes mellitus (DM) and COVID-19. Furthermore, DM is a potential risk factor for the severity of COVID-19 cases. Thus, in this study, the correlation existing between diabetic patients and COVID-19 was summarized. Main body of the abstract Diabetic patients have a weaker immune system, less viral clearance rate, malfunctions of metabolic activity due to their high blood glucose level, and other associated problems. This does not increase the susceptibility for the patients to be infected with COVID-19. However, the severity of COVID-19 can worsen due to the comorbidity of DM. Short conclusion Proper management, appropriate use of drugs that do not increase the ACE2 expression, lowering blood glucose level, decreasing the susceptibility of SARS-CoV-2, and maintaining a healthy lifestyle could be effective.
Project description:When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.
Project description:Single-cell RNA-sequencing reveals a shift from focused IFN alpha-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 – a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.
Project description:By December 2020, the COVID-19 pandemic had caused more than 74 million confirmed cases and 1.6 million related deaths around the world. However, only a few drugs have been approved in certain areas and for use in conditional patients, and the vaccine candidates were only recently approved or authorized for emergency use without being fully implemented worldwide, suggesting that we are yet to reach effective control of the current outbreak as its uninhibited transmission continues precariously. Over the past few months, several therapeutic candidates have been proven ineffective in large clinical trials, while some other agents exhibited promising preliminary results. Meanwhile, the investigation of SARS-CoV-2-specific antivirals is underway. Despite still being preclinical, these agents could be beneficial for the long-term control of COVID-19 and deserve more research focus. In this article, we update the current status of therapeutic candidates that have been examined for COVID-19 management, including the virus-targeting inhibitors and host-targeting agents, with their antiviral efficacy in vitro, in vivo, and in clinical studies. Finally, we highlight the current challenges and future prospect of developing potent therapeutic agents against COVID-19.
Project description:Since December 2019, SARS-CoV-2 (COVID-19), novel corona virus has caused pandemic globally, with rise in the number of cases and death of the patients. Vast majority of the countries that are dealing with rise in the active cases and death of patients suffering from novel corona viruses COVID-19 are trying to content the virus by isolating the patients and treating them with the approved antiviral that have been previously used in treating SARS, MERS, and drugs that are used to treat other viral infections. Some of these are under clinical trials. At present there are no therapeutically effective antiviral present and there are no vaccines or drugs available that are clinically approved for treating the corona virus. The current strategy is to re-purpose the available drugs or antiviral that can minimise or reduce the burden of the health care emergencies. In this article the reuse of antiviral, US-FDA approved drugs, plant based therapeutic, anti-malarial, anti-parasitic, anti-HIV drugs and the traditional medicines that are being currently used in treating the symptoms of COVID-19 patients is discussed emphasis is also given on the treatment using monoclonal antibodies. The present article provides the therapeutic strategies that will qualify as one of the best available treatment for the better management of the COVID-19 patients in order to achieve medical benefits.
Project description:Synopsis We review the current data on epidemiology, the clinical significance, the pathophysiologic mechanisms, and the treatment of VAs in the setting of COVID-19. VAs prevail in 0.15-8% of in hospitalized patients, but only sustained and rapid tachyarrhythmias are purportedly associated with a significant increase in mortality. Multiple factors can elicit VAs, which are ultimately deemed to be a marker of severe systemic disease rather than a distinct cardiac condition. Even though the electrophysiologist plays a determinant role in the secondary prevention of VAs, a multidisciplinary approach is indispensable for primary prophylaxis and acute management.
Project description:Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Comprehensively capturing the host physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index and APACHE II score were poor predictors of survival. Instead, using plasma proteomes quantifying 302 plasma protein groups at 387 timepoints in 57 critically ill patients on invasive mechanical ventilation, we found 14 proteins that showed trajectories different between survivors and non-survivors. A proteomic predictor trained on single samples obtained at the first time point at maximum treatment level (i.e. WHO grade 7) and weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81, n=49). We tested the established predictor on an independent validation cohort (AUROC of 1.0, n=24). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that predictors derived from plasma protein levels have the potential to substantially outperform current prognostic markers in intensive care.