scholarly journals Current Understanding of Cytomegalovirus Reactivation in Critical Illness

2020 ◽  
Vol 221 (Supplement_1) ◽  
pp. S94-S102
Author(s):  
Hannah Imlay ◽  
Ajit P Limaye
Keyword(s):  
Intensive Care Unit ◽  
Severe Sepsis ◽  
Critical Illness ◽  
Clinical Outcomes ◽  
Observational Studies ◽  
Underlying Mechanism ◽  
Causal Association ◽  
Efficacy Trial ◽  
Cytomegalovirus Reactivation ◽  
Cmv Reactivation

Abstract Cytomegalovirus (CMV) reactivation has been described in adults with critical illness caused by diverse etiologies, especially severe sepsis, and observational studies have linked CMV reactivation with worse clinical outcomes in this setting. In this study, we review observational clinical data linking development of CMV reactivation with worse outcomes in patients in the intensive care unit, discuss potential biologically plausible mechanisms for a causal association, and summarize results of initial interventional trials that examined the effects of CMV prevention. These data, taken together, highlight the need for a randomized, placebo-controlled efficacy trial (1) to definitively determine whether prevention of CMV reactivation improves clinical outcomes of patients with critical illness and (2) to define the underlying mechanism(s).

The Association between D-dimer Levels and Thromboembolism, Worsening Severity, and Mortality among Hospitalized Adults with COVID-19

2021 ◽  
Author(s):  
Patricia Pauline M. Remalante-Rayco ◽  
Evelyn O. Salido ◽  
Joey A. Tabula ◽  
Maria Teresa S. Tolosa
Keyword(s):  
Mechanical Ventilation ◽  
Critical Illness ◽  
Open Access ◽  
Clinical Outcomes ◽  
Observational Studies ◽  
Prognostic Indicator ◽  
Cochrane Library ◽  
Increased Risk ◽  
D Dimer

Objective. To assess the association between D-dimer and clinical outcomes in adults with COVID-19. Methods. We reviewed published articles and preprints from MEDLINE, Cochrane Library, Cornell Open Access Publication (COAP), MedRxiv, and BioRxiv databases. We included cohort studies on the association between D-dimer and the outcomes of thromboembolism, mortality, and worsening severity among hospitalized adults with COVID-19. Results. We found 25 observational studies on the association between D-dimer and the outcomes of thromboembolism, mortality, or worsening severity. There was an increased risk of thromboembolism (OR 5.61 [95% CI 3.97, 7.94]) with higher D-dimer levels across different COVID-19 severities. D-dimer levels are associated with higher in-hospital mortality (OR 5.57 [95% CI 2.74, 11.31]) and worsening severity manifesting as critical illness (OR 1.91 [95% CI 1.05, 3.48] to 2.58 [95% CI 1.57, 4.24]), disease progression (HR 2.846 [95% CI 2.10, 3.85]), or need for mechanical ventilation (HR 3.28 [95% CI 1.07, 10.10]). However, some methodological flaws, such as incomplete laboratory or follow-up data and concern on varied D-dimer cut-offs and definitions of worsening disease, raise some uncertainty in the widespread use of D-dimer as a prognostic marker. Conclusion. A higher D-dimer value is associated with worse clinical outcomes among hospitalized adults with COVID-19 and may be a useful prognostic indicator.

scholarly journals Risk Factors for Cytomegalovirus Reactivation and Association With Outcomes in Critically Ill Adults With Sepsis: A Pooled Analysis of Prospective Studies

2020 ◽  
Author(s):  
Hannah Imlay ◽  
Sayan Dasgupta ◽  
Michael Boeckh ◽  
Renee D Stapleton ◽  
Gordon D Rubenfeld ◽  
...  
Keyword(s):  
Risk Factors ◽  
Clinical Outcomes ◽  
Prospective Studies ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Potential Effect ◽  
Pooled Analysis ◽  
Cytomegalovirus Reactivation ◽  
Potential Risk Factors ◽  
Cmv Reactivation

Abstract We performed multivariable analysis of potential risk factors (including cytomegalovirus [CMV] reactivation) for clinical outcomes by day 28 (death or continued hospitalization, ventilator-free days, intensive care unit (ICU)-free days, hospital-free days) from pooled cohorts of 2 previous prospective studies of CMV-seropositive adults with sepsis. CMV reactivation at any level, >100 IU/mL, >1000 IU/mL, peak viral load, and area under the curve were independently associated with the clinical outcomes. We identified the potential effect size of CMV on outcomes that could be used as end points for future interventional trials of CMV prevention using antiviral prophylaxis in ICU patients with sepsis.

scholarly journals Statin use and clinical outcomes in patients with COVID-19: An updated systematic review and meta-analysis

2021 ◽  
pp. postgradmedj-2020-139172
Author(s):  
Rimesh Pal ◽  
Mainak Banerjee ◽  
Urmila Yadav ◽  
Sukrita Bhattacharjee
Keyword(s):  
Clinical Outcomes ◽  
Observational Studies ◽  
Fixed Effects ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Adverse Outcomes ◽  
Fixed Effects Model ◽  
Adjusted Risk ◽  
Risk Estimates ◽  
Statin Use

PurposeObservations studies have shown that prior use of statins is associated with a reduced risk of adverse clinical outcomes in patients with COVID-19. However, the available data are limited, inconsistent and conflicting. Besides, no randomised controlled trial exists in this regard. Hence, the present meta-analysis was conducted to provide an updated summary and collate the effect of statin use on clinical outcomes in COVID-19 using unadjusted and adjusted risk estimates.MethodsPubMed, Scopus and Web of Science databases were systematically searched using appropriate keywords till December 18 2020, to identify observational studies reporting clinical outcomes in COVID-19 patients using statins versus those not using statins. Prior and in-hospital use of statins were considered. Study quality was assessed using the Newcastle-Ottawa Scale. Unadjusted and adjusted pooled odds ratio (OR) with 95% CIs were calculated.ResultsWe included 14 observational studies pooling data retrieved from 19 988 patients with COVID-19. All the studies were of high/moderate quality. Pooled analysis of unadjusted data showed that statin use was not associated with improved clinical outcomes (OR 1.02; 95% CI 0.69 to 1.50, p=0.94, I2=94%, random-effects model). However, on pooling adjusted risk estimates, the use of statin was found to significantly reduce the risk of adverse outcomes (OR 0.51; 95% CI 0.41 to 0.63, p<0.0005, I2=0%, fixed-effects model).ConclusionsStatin use is associated with improved clinical outcomes in patients with COVID-19. Individuals with multiple comorbidities on statin therapy should be encouraged to continue the drug amid the ongoing pandemic.

scholarly journals Preemptive ganciclovir for mechanically ventilated patients with cytomegalovirus reactivation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laurent Papazian ◽  
◽  
Samir Jaber ◽  
Sami Hraiech ◽  
Karine Baumstarck ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Invasive Mechanical Ventilation ◽  
Double Blind ◽  
Intravenous Ganciclovir ◽  
Subdistribution Hazard ◽  
Mechanically Ventilated ◽  
Cytomegalovirus Reactivation ◽  
Secondary Outcomes ◽  
To Receive ◽  
Cmv Reactivation

Abstract Background The effect of cytomegalovirus (CMV) reactivation on the length of mechanical ventilation and mortality in immunocompetent ICU patients requiring invasive mechanical ventilation remains controversial. The main objective of this study was to determine whether preemptive intravenous ganciclovir increases the number of ventilator-free days in patients with CMV blood reactivation. Methods This double-blind, placebo-controlled, randomized clinical trial involved 19 ICUs in France. Seventy-six adults ≥ 18 years old who had been mechanically ventilated for at least 96 h, expected to remain on mechanical ventilation for ≥ 48 h, and exhibited reactivation of CMV in blood were enrolled between February 5th, 2014, and January 23rd, 2019. Participants were randomized to receive ganciclovir 5 mg/kg bid for 14 days (n = 39) or a matching placebo (n = 37). Results The primary endpoint was ventilator-free days from randomization to day 60. Prespecified secondary outcomes included day 60 mortality. The trial was stopped for futility based on the results of an interim analysis by the DSMB. The subdistribution hazard ratio for being alive and weaned from mechanical ventilation at day 60 for patients receiving ganciclovir (N = 39) compared with control patients (N = 37) was 1.14 (95% CI from 0.63 to 2.06; P = 0.66). The median [IQR] numbers of ventilator-free days for ganciclovir-treated patients and controls were 10 [0–51] and 0 [0–43] days, respectively (P = 0.46). Mortality at day 60 was 41% in patients in the ganciclovir group and 43% in the placebo group (P = .845). Creatinine levels and blood cells counts did not differ significantly between the two groups. Conclusions In patients mechanically ventilated for ≥ 96 h with CMV reactivation in blood, preemptive ganciclovir did not improve the outcome.

scholarly journals Incidence of thrombotic complications in COVID-19

2021 ◽  
Author(s):  
William J. Jenner ◽  
Diana A. Gorog
Keyword(s):  
Intensive Care Unit ◽  
Observational Studies ◽  
Severity Of Illness ◽  
Controlled Trials ◽  
Thrombotic Risk ◽  
Randomized Controlled ◽  
Hospitalised Patients ◽  
High Incidence ◽  
Thrombotic Complications ◽  
Asymptomatic Individuals

AbstractA high incidence of thrombosis in hospitalised patients with COVID-19 was identified early during the pandemic. Accurately quantifying thrombotic risk may assist prognosis and guide appropriate thromboprophylaxis. Observational studies have estimated the rate of thrombosis in both hospitalised and non-hospitalised patients with COVID-19, and how this corresponds to the severity of illness. In this review, we provide an overview of the incidence and prevalence of arterial and venous thrombotic events in patients with COVID-19 and highlight the limitations in the studies to date. Asymptomatic individuals with COVID-19 and those with mild symptoms are at very low risk of thrombotic complications. However, rates of thrombosis are substantially increased in hospitalised patients, and are strikingly high in those patients who are critically-ill requiring treatment on the intensive care unit and especially those requiring extracorporeal membrane oxygenation. Clinicians managing such patients need to be aware of these risks and take appropriate steps with respect to thromboprophylaxis and heightened clinical vigilance. Large prospective observational studies will more accurately quantify thrombotic rate, and randomized controlled trials are currently investigating optimal thromboprophylactic strategies.

scholarly journals Visualization of three-dimensional microcirculation of rodents’ retina and choroid for studies of critical illness using optical coherence tomography angiography

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jang Ryul Park ◽  
ByungKun Lee ◽  
Min Ji Lee ◽  
Kyuseok Kim ◽  
Wang-Yuhl Oh
Keyword(s):  
Blood Flow ◽  
Optical Coherence Tomography ◽  
Severe Sepsis ◽  
Critical Illness ◽  
Hemorrhagic Shock ◽  
Optical Coherence Tomography Angiography ◽  
Flow Index ◽  
Optical Coherence ◽  
Sepsis Model ◽  
Lactate Levels

AbstractWe developed a method to measure the relative blood flow speed using optical coherence tomography angiography (OCTA) in retina and choroid, and investigated the feasibility of this method for assessing microcirculatory function in rat models of sepsis and hemorrhagic shock. Two sepsis models, 6-h severe sepsis without treatment and 30-h moderate sepsis maintaining mean arterial pressure, and volume controlled hemorrhagic shock and fluid resuscitation model were used to see the change of microcirculation. The blood flow index (BFI), which was calculated from the OCTA images to represent the average relative blood flow, was decreasing during the 6-h severe sepsis model. Its change is in parallel with the mean arterial blood pressure (MAP) and blood lactate levels. In the 30-h moderate sepsis model, the BFI was decreased while maintaining MAP, and lactate was increased. In the hemorrhagic shock model, the change of BFI is in line with MAP and lactate levels. In all models, BFI change is more sensitive in choroid than in retina. This study presents the OCTA-based retinal and choroidal microcirculatory blood flow monitoring method and shows its utility for assessment of critical illness.

scholarly journals SARS-CoV-2 and Cytomegalovirus Co-Infections—A Case Series of Critically Ill Patients

2021 ◽  
Vol 10 (13) ◽  
pp. 2792
Author(s):  
Patrícia Moniz ◽  
Sérgio Brito ◽  
Pedro Póvoa
Keyword(s):  
Intensive Care Unit ◽  
Critically Ill ◽  
Immune Suppression ◽  
Clinical Course ◽  
Health Care Systems ◽  
Case Series ◽  
Confounding Factors ◽  
Care Systems ◽  
The Impact ◽  
Cmv Reactivation

The SARS-CoV-2 pandemic has placed great strain on the most developed of health care systems, especially in the context of critical care. Although co-infections with cytomegalovirus (CMV) are frequent in the critically ill due to underlying immune suppression of multiple causes, the impact on COVID-19 patients remains unclear. Furthermore, severe COVID-19 has recently been associated with significant immune suppression, and this may in turn impact CMV reactivation, possibly contributing to clinical course. Nevertheless, multiple confounding factors in these patients will certainly challenge upcoming research. The authors present a case series of five patients admitted to the intensive care unit (ICU) in the context of respiratory failure due to severe COVID-19. All patients evolved with CMV reactivation during ICU stay.

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