Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have ...been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines' molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.
Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors ...and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.
A report published last year by the Centers for Medicare & Medicaid Services (CMS) highlighted that COVID-19 case counts are more likely to be high in lower quality nursing homes than in higher ...quality ones. Since then, multiple studies have examined this association with a handful also exploring the role of facility quality in explaining resident deaths from the virus. Despite this wide interest, no previous study has investigated how the relation between quality and COVID-19 mortality among nursing home residents may have changed, if at all, over the progression of the pandemic. This understanding is indeed lacking given that prior studies are either cross-sectional or are analyses limited to one specific state or region of the country. To address this gap, we analyzed changes in nursing home resident deaths across the US between June 1, 2020 and January 31, 2021 (n = 12,415 nursing homes X 8 months) using both descriptive and multivariable statistics. We merged publicly available data from multiple federal agencies with mortality rate (per 100,000 residents) as the outcome and CMS 5-star quality rating as the primary explanatory variable of interest. Covariates, based on the prior literature, consisted of both facility- and community-level characteristics. Findings from our secondary analysis provide robust evidence of the association between nursing home quality and resident deaths due to the virus diminishing over time. In connection, we discuss plausible reasons, especially duration of staff shortages, that over time might have played a critical role in driving the quality-mortality convergence across nursing homes in the US.
Patient-related risk factors for venous thromboembolism (VTE) are infrequently studied. We compared the role of patient-related risk factors for VTE in patients with solid organ cancers to their role ...in patients without cancer using National Inpatient Sample (NIS) data. Patients with cancer: risk of VTE hospitalization; Increased: chronic pulmonary disease (OR 1.172, 95% CI 1.102–1.247), obesity (OR 1.369, 95% CI 1.244–1.506). Decreased: liver disease (OR 0.654, 95% CI 0.562–0.762), chronic kidney disease (CKD) (OR 0.539, 95% CI 0.491–0.593), end-stage renal disease (ESRD) (OR 0.247, 95% CI 0.187–0.326). Patients without cancer: Risk of VTE hospitalization; Increased: age (OR 1.024, 95% CI 1.022–1.025), congestive heart failure (OR 1.221, 95% CI: 1.107–1.346), chronic pulmonary disease (OR 1.372, 95% CI 1.279–1.473), obesity (OR 2.627, 95% CI 2.431–2.838). Decreased: female gender (OR 0.772, 95% CI 0.730–0.816), diabetes (OR 0.756, 95% CI 0.701–0.815), ESRD (OR 0.315, 95% CI 0.252–0.395). In conclusion, chronic pulmonary disease and obesity increase VTE hospitalization risk in patients with and without cancer and the risk decreases in cancer patients with liver disease, CKD or ESRD.
Patients with COVID-19 infection are commonly reported to have an increased risk of venous thrombosis. The choice of anti-thrombotic agents and doses are currently being studied in randomized ...controlled trials and retrospective studies. There exists a need for individualized risk stratification of venous thromboembolism (VTE) to assist clinicians in decision-making on anticoagulation. We sought to identify the risk factors of VTE in COVID-19 patients, which could help physicians in the prevention, early identification, and management of VTE in hospitalized COVID-19 patients and improve clinical outcomes in these patients.
This is a multicenter, retrospective database of four main health systems in Southeast Michigan, United States. We compiled comprehensive data for adult COVID-19 patients who were admitted between 1st March 2020 and 31st December 2020. Four models, including the random forest, multiple logistic regression, multilinear regression, and decision trees, were built on the primary outcome of in-hospital acute deep vein thrombosis (DVT) and pulmonary embolism (PE) and tested for performance. The study also reported hospital length of stay (LOS) and intensive care unit (ICU) LOS in the VTE and the non-VTE patients. Four models were assessed using the area under the receiver operating characteristic curve and confusion matrix.
The cohort included 3531 admissions, 3526 had discharge diagnoses, and 6.68% of patients developed acute VTE (N = 236). VTE group had a longer hospital and ICU LOS than the non-VTE group (hospital LOS 12.2 days vs. 8.8 days, p < 0.001; ICU LOS 3.8 days vs. 1.9 days, p < 0.001). 9.8% of patients in the VTE group required more advanced oxygen support, compared to 2.7% of patients in the non-VTE group (p < 0.001). Among all four models, the random forest model had the best performance. The model suggested that blood pressure, electrolytes, renal function, hepatic enzymes, and inflammatory markers were predictors for in-hospital VTE in COVID-19 patients.
Patients with COVID-19 have a high risk for VTE, and patients who developed VTE had a prolonged hospital and ICU stay. This random forest prediction model for VTE in COVID-19 patients identifies predictors which could aid physicians in making a clinical judgment on empirical dosages of anticoagulation.
Abstract
Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an ...independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age 40–59 = 2, > 60 = 4, Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I > 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3, Electrolytes derangement magnesium/potassium = 1). RAM had a good discrimination (training AUC 0.777, 0.756–0.797; validation AUC 0.766, 0.741–0.790). The validation cohort was stratified as low-risk (score 0–8), intermediate-risk (score 9–13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.
Atrial arrhythmias (AAs) are common in hospitalized patients with COVID-19; however, it remains uncertain if AAs are a poor prognostic factor in SARS-CoV-2 infection. In this retrospective cohort ...study from 2014 to 2021, we report in-hospital mortality in patients with new-onset AA and history of AA. The incidence of new-onset congestive heart failure (CHF), hospital length of stay and readmission rate, intensive care unit admission, arterial and venous thromboembolism, and imaging outcomes were also analyzed. We further compared the clinical outcomes with a propensity-matched influenza cohort. Generalized linear regression was performed to identify the association of AA with mortality and other outcomes, relative to those without an AA diagnosis. Predictors of new-onset AA were also modeled. A total of 6,927 patients with COVID-19 were included (626 with new-onset AA, 779 with history of AA). We found that history of AA (adjusted relative risk aRR 1.38, confidence interval CI, 1.11 to 1.71, p = 0.003) and new-onset AA (aRR 2.02, 95% CI 1.68 to 2.43, p <0.001) were independent predictors of in-hospital mortality. The incidence of new-onset CHF was 6.3% in history of AA (odds ratio 1.91, 95% CI 1.30 to 2.79, p <0.001) and 11.3% in new-onset AA (odds ratio 4.01, 95% CI 3.00 to 5.35, p <0.001). New-onset AA was shown to be associated with worse clinical outcomes within the propensity-matched COVID-19 and influenza cohorts. The risk of new-onset AA was higher in patients with COVID-19 than influenza (aRR 2.02, 95% CI 1.76 to 2.32, p <0.0001), but mortality associated with new-onset AA was higher in influenza (aRR 12.58, 95% CI 4.27 to 37.06, p <0.0001) than COVID-19 (aRR 1.86, 95% CI 1.55 to 2.22, p <0.0001). In a subset of the patients with COVID-19 for which echocardiographic data were captured, abnormalities were common, including valvular abnormalities (40.9%), right ventricular dilation (29.6%), and elevated pulmonary artery systolic pressure (16.5%); although there was no evidence of a difference in incidence among the 3 groups. In conclusion, new-onset AAs are associated with poor clinical outcomes in patients with COVID-19.
•ACEi/ARB need not be discontinued in hospitalized COVID-19 patients•ACEi/ARB use need not be restricted due to COVID-19 pandemic•ACEi/ARB benefits for cardiovascular indications outweigh harm in ...COVID-19 patients.
Prior evidence indicates that predictors of older adult falls vary by indoor-outdoor location of the falls. While a subset of United States' studies reports this finding using primary data from a ...single geographic area, other secondary analyses of falls across the country do not distinguish between the two fall locations. Consequently, evidence at the national level on risk factors specific to indoor vs outdoor falls is lacking.
Using the 2017 Nationwide Emergency Department Sample (NEDS) data, we conducted a multivariable analysis of fall-related emergency department (ED) visits disaggregated by indoor vs outdoor fall locations of adults 65 years and older (N = 6,720,937) in the US.
Results are compatible with findings from previous primary studies. While women (relative risk RR = 1.43, 95% confidence interval CI, 1.42-1.44) were more likely to report indoor falls, men were more likely to present with an outdoor fall. Visits for indoor falls were highest among those 85 years and older (RR = 2.35, 95% CI, 2.33-2.37) with outdoor fall visits highest among those 84 years and younger. Additionally, the probabilities associated with an indoor fall in the presence of chronic conditions were consistently much higher when compared to an outdoor fall. We also found that residence in metropolitan areas increased the likelihood of an indoor elderly fall compared to higher outdoor fall visits from seniors in non-core rural areas, but both indoor and outdoor fall visits were higher among older adults in higher income ZIP codes.
Our findings highlight the contrasting risk profile for elderly ED patients who report indoor vs outdoor falls when compared to the elderly reporting no falls. In conjunction, we highlight implications from three perspectives: a population health standpoint for EDs working with their primary care and community care colleagues; an ED administrative vantage point; and from an individual emergency clinician's point of view.
The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment ...methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.
PDF
