Role of IgG against N-protein of SARS-CoV2 in COVID19 clinical outcomes.
ABSTRACT: The Nucleocapsid Protein (N Protein) of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) is located in the viral core. Immunoglobulin G (IgG) targeting N protein is detectable in the serum of infected patients. The effect of high titers of IgG against N-protein on clinical outcomes of SARS-CoV2 disease has not been described. We studied 400 RT-PCR confirmed SARS-CoV2 patients to determine independent factors associated with poor outcomes, including Medical Intensive Care Unit (MICU) admission, prolonged MICU stay and hospital admissions, and in-hospital mortality. We also measured serum IgG against the N protein and correlated its concentrations with clinical outcomes. We found that several factors, including Charlson comorbidity Index (CCI), high levels of IL6, and presentation with dyspnea were associated with poor clinical outcomes. It was shown that higher CCI and higher IL6 levels were independently associated with in-hospital mortality. Anti-N protein IgG was detected in the serum of 55 (55%) patients at the time of admission. A high concentration of antibodies, defined as signal to cut off ratio (S/Co)?>?1.5 (75 percentile of all measurements), was found in 25 (25%) patients. The multivariable logistic regression models showed that between being an African American, higher CCI, lymphocyte counts, and S/Co ratio?>?1.5, only S/Co ratio were independently associated with MICU admission and longer length of stay in hospital. This study recommends that titers of IgG targeting N-protein of SARS-CoV2 at admission is a prognostic factor for the clinical course of disease and should be measured in all patients with SARS-CoV2 infection.
Project description:<h4>Background</h4>Since the occurrence of the SARS-COV2 pandemic, there has been an increasing interest in investigating the epidemiology of delirium. Delirium is frequent in SARS-COV2 patients and it is associated with increased mortality; however, no information is available on the association between delirium duration in SARS-COV2 patients and related outcomes.<h4>Aims</h4>The aim of this study is to investigate the association between the duration of delirium symptoms and in-hospital mortality in older patients with SARS-COV2 infection.<h4>Methods</h4>Retrospective cohort study of patients 65 years of age and older with SARS-CoV 2 infection admitted to two acute geriatric wards and one rehabilitation ward. Delirium symptoms duration was assessed retrospectively with a chart-based validated method. In-hospital mortality was ascertained via medical records.<h4>Results</h4>A total of 241 patients were included. The prevalence of delirium on admission was 16%. The median number of days with delirium symptoms was 4 (IQR 2-6.5) vs. 0 (IQR 0-2) in patients with and without delirium on admission. In the multivariable Cox regression model, each day with a delirium symptom in a patient with the same length of stay was associated with a 10% increase in in-hospital mortality (Hazard ratio 1.1, 95% Confidence interval 1.01-1.2; p = 0.03). Other variables associated with increased risk of in-hospital death were age, comorbidity, CPAP, CRP levels and total number of drugs on admission.<h4>Conclusions</h4>The study supports the necessity to establish protocols for the monitoring and management of delirium during emergency conditions to allow an appropriate care for older patients.
Project description:<h4>Background</h4>Criteria for admitting patients with incurable diseases to the medical intensive care unit (MICU) remain unclear and have ethical implications.<h4>Methods</h4>We retrospectively evaluated MICU outcomes and identified risk factors for MICU mortality in consecutive patients with advanced lung cancer admitted to two university-hospital MICUs in France between 1996 and 2006.<h4>Results</h4>Of 76 included patients, 49 had non-small cell lung cancer (stage IIIB n = 20; stage IV n = 29). In 60 patients, MICU admission was directly related to the lung cancer (complication of cancer management, n = 30; cancer progression, n = 14; and lung-cancer-induced diseases, n = 17). Mechanical ventilation was required during the MICU stay in 57 patients. Thirty-six (47.4%) patients died in the MICU. Three factors were independently associated with MICU mortality: use of vasoactive agents (odds ratio [OR] 6.81 95% confidence interval [95%CI] [1.77-26.26], p = 0.005), mechanical ventilation (OR 6.61 95%CI [1.44-30.5], p = 0.015) and thrombocytopenia (OR 5.13; 95%CI [1.17-22.5], p = 0.030). In contrast, mortality was lower in patients admitted for a complication of cancer management (OR 0.206; 95%CI [0.058-0.738], p = 0.015). Of the 27 patients who returned home, four received specific lung cancer treatment after the MICU stay.<h4>Conclusions</h4>Patients with acute complications of treatment for advanced lung cancer may benefit from MCIU admission. Further studies are necessary to assess outcomes such as quality of life after MICU discharge.
Project description:<h4>Background</h4>Circulating androgens could have a relevant pathobiological role in clinical outcomes in men with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19).<h4>Objectives</h4>We aimed to assess: (a) circulating sex steroids levels in a cohort of 286 symptomatic men with laboratory-confirmed COVID-19 at hospital admission compared to a cohort of 281 healthy men; and (b) the association between serum testosterone levels (tT), COVID-19, and clinical outcomes.<h4>Materials and methods</h4>Demographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as tT ≤9.2 nmol/l. The Charlson Comorbidity Index (CCI) was used to score health-significant comorbidities. Severe clinical outcomes were defined as patients either transferred to intensive care unit (ICU) or death. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and tT levels. Univariable and multivariable logistic regression models tested the association between tT and severe clinical outcomes.<h4>Results</h4>Overall, a significantly lower levels of LH and tT were found in patients with COVID-19 compared to healthy controls (all p < 0.0001); conversely, healthy controls depicted lower values of circulating E<sub>2</sub> (p < 0.001). Testosterone levels suggestive for hypogonadism were observed in 257 (89.8%) patients at hospital admission. In as many as 243 (85%) cases, hypogonadism was secondary. SARS-CoV-2 infection status was independently associated with lower tT levels (p < 0.0001) and greater risk of hypogonadism (p < 0.0001), after accounting for age, BMI, CCI, and IL-6 values. Lower tT levels were associated with higher risk of ICU admission and death outcomes (all p ≤ 0.05), after accounting for clinical and laboratory parameters.<h4>Conclusions</h4>We unveil an independent association between SARS-CoV-2 infection status and secondary hypogonadism already at hospital admission, with lower testosterone levels predicting the most severe clinical outcomes.
Project description:<h4>Objective</h4>Vitamin D deficiency is prevalent in critically ill patients and may contribute to suboptimal clinical outcomes, but little is known about alterations of the calcium-parathyroid hormone (PTH)-vitamin D axis and prognosis in these individuals.<h4>Methods</h4>A prospective observational study was conducted on 216 patients admitted to a university-affiliated, tertiary-care medical intensive care unit(MICU) between June 2011 and December 2012. Serum levels of 25-hydroxyvitamin D, ionised calcium and intact PTH were determined within 24 h of MICU admission. The primary end point was all-cause hospital mortality within 90-days of admission.<h4>Results</h4>95 patients (44%) showed 25-hydroxyvitamin D deficiency. Patients deficient in vitamin D showed significantly higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score, rate of positive blood culture, incidence of multiple organ dysfunction syndrome, and 90-day mortality rate than did patients with vitamin D insufficiency or sufficiency (P<0.05), as well as lower levels of serum IgG. 25-Hydroxyvitamin D deficiency was identified as an independent risk factor for mortality (OR?=?3.018, 95%CI 1.329-6.854, P?=?0.008). Hypovitaminosis D in PTH-responders was associated with higher mortality than was the same condition in non-responders (P<0.05).<h4>Conclusions</h4>These results suggest that vitamin D deficiency is prevalent among MICU patients, suggesting a significant derangement of the calcium-PTH-vitamin D axis in critically ill patients. Vitamin D deficiency is an independent risk factor for 90-day mortality, and hypovitaminosis D in PTH-responders is associated with higher mortality than is the same condition in non-responders.
Project description:<h4>Background</h4>During the coronavirus disease 2019 (COVID-19) pandemic, concerns have been arisen on the use of renin-angiotensin system inhibitors (RASI) due to the potentially increased expression of Angiotensin-converting-enzyme (ACE)2 and patient's susceptibility to SARS-CoV2 infection. Diabetes mellitus have been recognized favoring the coronavirus infection with consequent increase mortality in COVID-19. No data have been so far reported in diabetic patients suffering from ST-elevation myocardial infarction (STEMI), a very high-risk population deserving of RASI treatment.<h4>Methods</h4>The ISACS-STEMI COVID-19 registry retrospectively assessed STEMI patients treated with primary percutaneous coronary intervention (PPCI) in March/June 2019 and 2020 in 109 European high-volume primary PCI centers. This subanalysis assessed the prognostic impact of chronic RASI therapy at admission on mortality and SARS-CoV2 infection among diabetic patients.<h4>Results</h4>Our population is represented by 3812 diabetic STEMI patients undergoing mechanical reperfusion, 2038 in 2019 and 1774 in 2020. Among 3761 patients with available data on chronic RASI therapy, between those ones with and without treatment there were several differences in baseline characteristics, (similar in both periods) but no difference in the prevalence of SARS-CoV2 infection (1.6% vs 1.3%, respectively, <i>p</i> = 0.786). Considering in-hospital medication, RASI therapy was overall associated with a significantly lower in-hospital mortality (3.3% vs 15.8%, <i>p</i> < 0.0001), consistently both in 2019 and in 2010.<h4>Conclusions</h4>This is first study to investigate the impact of RASI therapy on prognosis and SARS-CoV2 infection of diabetic patients experiencing STEMI and undergoing PPCI during the COVID-19 pandemic. Both pre-admission chronic RASI therapy and in-hospital RASI did not negatively affected patients' survival during the hospitalization, neither increased the risk of SARS-CoV2 infection.<h4>Trial registration number</h4>NCT04412655.
Project description:<h4>Introduction</h4>The endothelial protein C receptor (EPCR) is a protein that regulates the protein C anticoagulant and anti-inflammatory pathways. A soluble form of EPCR (sEPCR) circulates in plasma and inhibits activated protein C (APC) activities. The clinical impact of sEPCR and its involvement in COVID-19 has not been explored. In this study, we investigated whether sEPCR levels were related to COVID-19 patients' requirement for hospitalization.<h4>Methods</h4>Plasma sEPCR levels were measured on hospital admission in 84 COVID-19 patients, and in 11 non-hospitalized SARS-CoV2-positive patients approximately 6 days after reported manifestation of their symptoms. Multiple logistic regression analysis was performed to identify potential risk factors for hospitalization and receiver operating characteristic (ROC) curves were generated to assess their value.<h4>Results</h4>In our cohort, hospitalized patients had considerably higher sEPCR levels upon admission compared with outpatients [107.5 (76.7-156.3) vs. 44.6 (12.1-84.4) ng/mL; P < 0.0001)]. The ROC curve using hospitalization as the classification variable and sEPCR levels as the prognostic variable generated an area under the curve at 0.845 (95% CI = 0.710-0.981, P < 0.001). Additionally, we investigated the predictive value of sEPCR combined with BMI, age, or D-dimers.<h4>Conclusions</h4>In our cohort, sEPCR levels in COVID-19 patients upon hospital admission appear considerably elevated compared with outpatients; this could lead to impaired APC activities and might contribute to the pro-coagulant phenotype reported in such patients. sEPCR measurement might be useful as a point-of-care test in SARS-CoV2-positive patients.
Project description:<h4>Introduction</h4>Plasma harvested from convalescent COVID-19 patients (CCP) has been applied as first-line therapy in the early phase of the SARS-CoV2 pandemic through clinical studies using various protocols.<h4>Methods</h4>We present data from a cohort of 267 hospitalized severe COVID-19 patients who received CCP. No transfusion-related complications were reported, indicating the overall safety of CCP therapy.<h4>Results</h4>Patients who eventually died from COVID-19 received CCP significantly later (3.95 versus 5.22 days after hospital admission) and had higher interleukin 6 (IL-6) levels (28.9 pg/ml versus 102.5 pg/ml) than those who survived. In addition, CCP transfusion caused a significant reduction in the overall inflammatory status of the patients regardless of the severity of disease or outcome, as evidenced by decreasing C-reactive protein, IL6 and ferritin levels.<h4>Conclusion</h4>We conclude that CCP transfusion is a safe and effective supplementary treatment modality for hospitalized COVID-19 patients characterized by better expected outcome if applied as early as possible. We also observed that IL-6 may be a suitable laboratory parameter for patient selection and monitoring of CCP therapy effectiveness.
Project description:High-throughput sequencing of the miRNAs present in plasma of COVID-19 patients at an early stage of the disease including non-SARS-CoV2 infected patients. This study allowed us to identify and functionally characterize human miRNAs associated with a worse evolution of the disease and a greater mortality. Samples were collected at hospital entry or within the first days after hospitalization and before treatment with immunotherapy for IL6 (e.g. Tocilizumab), interferon beta, corticoids and ribavirin, among others. Plasma samples were obtained from peripheral blood extracted in EDTA tubes after centrifugation. Total RNA, including small RNAs, was isolated from 400μl of plasma with the miRNeasy Serum Plasma Advanced kit (Qiagen). RNA quality and quantity were evaluated by the Bioanalyzer 2100 with Agilent RNA 6000 Nano Kit.
Project description:<h4>Background</h4>In hospitalized patients with SARS-CoV-2 infection, outcomes markedly differ between locations, regions and countries. One possible cause for these variations in outcomes could be differences in patient treatment limitations (PTL) in different locations. We thus studied their role as predictor for mortality in a population of hospitalized patients with COVID-19.<h4>Methods</h4>In a region with high incidence of SARS-CoV-2 infection, adult hospitalized patients with PCR-confirmed SARS-CoV-2 infection were prospectively registered and characterized regarding sex, age, vital signs, symptoms, comorbidities (including Charlson comorbidity index (CCI)), transcutaneous pulse oximetry (SpO<sub>2</sub>) and laboratory values upon admission, as well as ICU-stay including respiratory support, discharge, transfer to another hospital and death. PTL assessed by routine clinical procedures comprised the acceptance of ICU-therapy, orotracheal intubation and/or cardiopulmonary resuscitation.<h4>Results</h4>Among 526 patients included (median [quartiles] age 73 [57; 82] years, 47% female), 226 (43%) had at least one treatment limitation. Each limitation was associated with age, dementia and eGFR (p < 0.05 each), that regarding resuscitation additionally with Charlson comorbidity index (CCI) and cardiac disease. Overall mortality was 27% and lower (p < 0.001) in patients without treatment limitation (12%) compared to those with any limitation (47%). In univariate analyses, age and comorbidities (diabetes, cardiac, cerebrovascular, renal, hepatic, malignant disease, dementia), SpO<sub>2</sub>, hemoglobin, leucocyte numbers, estimated glomerular filtration rate (eGFR), C-reactive protein (CRP), Interleukin-6 and LDH were predictive for death (p < 0.05 each). In multivariate analyses, the presence of any treatment limitation was an independent predictor of death (OR 4.34, 95%-CI 2.10-12.30; p = 0.001), in addition to CCI, eGFR < 55 ml/min, neutrophil number > 5 G/l, CRP > 7 mg/l and SpO<sub>2</sub> < 93% (p < 0.05 each).<h4>Conclusion</h4>In hospitalized patients with SARS-CoV-2, the percentage of patients with treatment limitations was high. PTL were linked to age, comorbidities and eGFR assessed upon admission and strong, independent risk factors for mortality. These findings might be useful for further understanding of COVID-19 mortality and its regional variations. Clinical trial registration ClinicalTrials.gov Identifier: NCT04344171.
Project description:This study aimed to determine if the risk of adverse outcomes (in-hospital and 60-day mortality, intensive care unit (ICU) and total hospital length of stay (LOS)) was greater for medical ICU (MICU) or high dependency unit (HDU) patients indirectly admitted from the emergency department (ED) than for directly admitted patients.This study was conducted at a large public acute care hospital in Singapore.In this retrospective cohort study, hospital records of patients who were admitted directly from the ED, or initially admitted to the general wards from the ED and subsequently transferred to the MICU/HDU within 24?h, were reviewed. Patients were included if they were: (A) discharged from the MICU/HDU in 2009 and were admitted from the ED and (B) transferred to the MICU/HDU within 24?h of presentation at the ED. Data from 706 patients were analysed; 58.4% were men with a median age of 61?years.The following outcomes were compared: in-hospital mortality, 60-day mortality, LOS at the MICU/HDU, as well as total hospital LOS.Of the 706 patients, 491 (69.5%) were directly admitted to the MICU/HDU. After adjusting for demographics, comorbidities, interventions at the ED and clinical parameters at the ED (heart rate, respiration, oxygen saturation, mean arterial pressure), as well as the Apache II score on arrival at the MICU/HDU, indirectly admitted patients had a higher risk of in-hospital mortality (OR=3.07, 95% CI 1.39 to 6.80), death within 60?days (OR=3.09, 95% CI 1.40 to 6.83) and risk of staying >1?day at the MICU/HDU (OR=2.54, 95% CI 1.48 to 4.36). There was no significant difference in total in-hospital LOS.Indirectly admitted MICU/HDU patients had generally poorer outcomes. As the magnitude of effect may vary across settings, context-specific studies may be useful for improving outcomes.