Non-survivors Of COVID-19 Research Articles

Peak value of serum KL-6 may be useful for predicting poor prognosis of severe COVID-19 patients

BackgroundSerum Krebs von den Lungen 6 (KL-6), which reflects alveolar epithelial injury, was reported to be useful to predict the progression of pneumonitis induced by COVID-19 in the early phase. This study aimed to evaluate the peak value of serum KL-6 during hospitalization for COVID-19 to discover a more useful biomarker for predicting prognosis in COVID-19 patients.MethodsIn this retrospective, single-center, observational study, we analyzed the data of 147 hospitalized patients who required supplemental oxygen, high-flow oxygen therapy, or invasive mechanical ventilation for respiratory failure due to COVID-19 from March 2020 to February 2021. We extracted data on patient sex, age, comorbidities, treatment, and biomarkers including the initial and peak values of KL-6. Inclusion criteria were examination of the studied biomarkers at least once within 3 days of admission, then at least once a week, and at a minimum, at least twice during the entire hospitalization. Area under the receiver operating curve (AUC) was analyzed to determine the accuracy of several biomarkers including KL-6 and LDH for predicting poor prognosis defined as survivors requiring invasive mechanical ventilation for over 28 days or non-survivors of COVID-19. Univariable and multivariate logistic regression analyses were performed to investigate the prognostic value of the baseline characteristics and biomarkers.ResultsAmong the 147 patients, 108 (73.5%) had a good prognosis and 39 (26.5%) had a poor prognosis. The AUC analysis indicated that peak KL-6 showed precise accuracy in the discrimination of patients with poor prognosis (AUC 0.89, p < 0.001). The best cut-off value for KL-6 concentration was 966 U/mL (sensitivity 81.6%, specificity84.3%). After adjustment, increasing peak values of KL-6 or LDH were associated with a high risk of poor prognosis, with an adjusted odds ratio of 1.35 for peak value of KL-6, per 100 U/mL increase (95% CI 1.17–1.57, p < 0.001) and 2.16 for peak value of LDH, per 100 U/L increase (95% CI 1.46–3.20, p < 0.001).ConclusionsPeak values of KL-6 and LDH measured during hospitalization might help to identify COVID-19 patients with respiratory failure who are at higher risk for a poor prognosis.

Fibronectin as a Marker of Disease Severity in Critically Ill COVID-19 Patients.

The SARS-CoV-2 virus alters the expression of genes for extracellular matrix proteins, including fibronectin. The aim of the study was to establish the relationship between different forms of fibronectin, such as plasma (pFN), cellular (EDA-FN), and proteolytic FN-fragments, and disease severity and mortality of critically ill patients treated in the intensive care unit. The levels of pFN, EDA-FN, and FN-fragments were measured in patients with a viral (N = 43, COVID-19) or bacterial (N = 41, sepsis) infection, using immunoblotting and ELISA. The level of EDA-FN, but not pFN, was related to the treatment outcome and was significantly higher in COVID-19 Non-survivors than in Survivors. Furthermore, EDA-FN levels correlated with APACHE II and SOFA scores. FN-fragments were detected in 95% of COVID-19 samples and the amount was significantly higher in Non-survivors than in Survivors. Interestingly, FN-fragments were present in only 56% of samples from patients with bacterial sepsis, with no significant differences between Non-survivors and Survivors. The new knowledge gained from our research will help to understand the differences in immune response depending on the etiology of the infection. Fibronectin is a potential biomarker that can be used in clinical settings to monitor the condition of COVID-19 patients and predict treatment outcomes.

Time-Dependent Changes of Laboratory Parameters as Independent Predictors of All-Cause Mortality in COVID-19 Patients.

Simple SummarySeveral independent predictors of mortality for COVID-19 patients have been identified. However, those markers are usually parameters evaluated upon hospital admission, and clinical and biochemical parameters during the clinical course of the patients are usually neglected. To know the whole picture of COVID-19 patients it is important to evaluate the clinical course, as this will dictate how the patient progresses. We identify herein clinical and laboratory parameters from admission to discharge, or death, that distinguish between survivors and non-survivors of COVID-19, including those with independent ability to predict mortality.Independent predictors of mortality for COVID-19 patients have been identified upon hospital admission; however, how they behave after hospitalization remains unknown. The aim of this study is to identify clinical and laboratory parameters from admission to discharge or death that distinguish survivors and non-survivors of COVID-19, including those with independent ability to predict mortality. In a cohort of 266 adult patients, clinical and laboratory data were analyzed from admission and throughout hospital stay until discharge or death. Upon admission, non-survivors had significantly increased C reactive protein (CRP), neutrophil count, neutrophil to lymphocyte ratio (NLR) (p < 0.0001, each), ferritin (p < 0.001), and AST (aspartate transaminase) (p = 0.009) compared to survivors. During the hospital stay, deceased patients maintained elevated CRP (21.7 mg/dL [admission] vs. 19.3 [hospitalization], p = 0.060), ferritin, neutrophil count and NLR. Conversely, survivors showed significant reductions in CRP (15.8 mg/dL [admission] vs. 9.3 [hospitalization], p < 0.0001], ferritin, neutrophil count and NLR during hospital stay. Upon admission, elevated CRP, ferritin, and diabetes were independent predictors of mortality, as were persistently high CRP, neutrophilia, and the requirement of invasive mechanical ventilation during hospital stay. Inflammatory and clinical parameters distinguishing survivors from non-survivors upon admission changed significantly during hospital stay. These markers warrant close evaluation to monitor and predict patients’ outcome once hospitalized.

Clinical characteristics and risk factors for mortality in patients with COVID-19: A retrospective nationwide study in Malaysia

BackgroundAge and multiple comorbidities have been reported to influence the case fatality rate of COVID-19 worldwide, so also in Malaysia; however, to date, no scientific study among the local population has been published to confirm this. This study aimed to determine the overall demographics and clinical characteristics of COVID-19 non-survivors in Malaysia, stratified by age (< 65 vs. ≥ 65 years old). The mortality was also compared between two half-year periods: March–August 2020 and September 2020–March 2021.MethodDaily reports containing demographics and medical history of COVID-19 non-survivors from March 2020 to March 2021 were obtained from the Malaysian Ministry of Health website. All information was extracted retrospectively and analysed using descriptive and inferential statistics with SPSS.ResultsOf 1192 COVID-19 non-survivors, the overall mean (SD) age was 64.8 (15.7) years, with 64.7% male. Death was seen mostly among 50- to 64-year-olds (33.1%) and 65- to 74-year-olds (24.8%). The presence of underlying hypertension (61.8%) and diabetes mellitus (48.2%) were the most common comorbid diseases encountered in the COVID-19 non-survivors. Underlying hypertension, stroke, heart disease and dyslipidaemia were significantly higher among COVID-19 non-survivors who were ≥ 65 years old compared to those < 65 (p < 0.05). Mortality was a lot higher in September 2020–March 2021 compared to March 2020–August 2020 (91.3% vs. 8.3%).ConclusionOlder age, male gender and the presence of multimorbidity (hypertension, diabetes mellitus, stroke and heart disease) are risk factors that contribute to mortality due to COVID-19 in Malaysia, especially among those ≥ 65 years old.

Triglyceride/High-Density Lipoprotein Cholesterol Ratio is Associated with the Mortality of COVID-19: A Retrospective Study in China.

BackgroundTriglyceride to high density lipoprotein cholesterol ratio (TG/HDL-c) is crucial when researching metabolic and vascular diseases, and its involvement in COVID-19 was sparsely elaborated on. The purpose of the study was to explore the inflammatory associations between the TG/HDL-c ratio and COVID-19 prognosis.MethodsA total of 262 COVID-19 patients consisting of 244 survivors and 18 non-survivors were retrospectively investigated. The clinical features and baseline hematological parameters were recorded and analyzed. The receiver operating characteristic curve (ROC) was used to explore the role of TG/HDL-c in predicting the mortality of COVID-19, the Spearman’s rank correlation coefficients were used to measure the correlation between TG/HDL-c and inflammatory indicators, and the Kaplan–Meier (KM) curve was used to estimate the survival of COVID-19 patients with high and low TG/HDL-c ratio. Logistic regression analyses were performed to investigate the role of TG/HDL-c ratio on mortality of COVID-19 with no underlying diseases.ResultsCompared with the survivors, the non-survivors of COVID-19 had significantly higher levels of white blood cells (4.7 vs 13.0 × 109/L; P < 0.001), neutrophils (3.0 vs 11.6 × 109/L; P < 0.001), C-reactive proteins (15.7 vs 76.7 mg/L; P < 0.001) and TG/HDL-c ratio (1.4 vs 2.5; P = 0.001). The ROC curve [area under the curve (AUC), 0.731; 95% confidence interval (CI), 0.609–0.853; P = 0.001] suggested that the TG/HDL-c ratio could predict the mortality of COVID-19. The TG/HDL-c ratio was positively correlated with white blood cells (r = 0.255, P < 0.001), neutrophils (r = 0.243, P < 0.001) and C-reactive proteins (r = 0.170, P < 0.006). Patients with high TG/HDL-c ratio showed a worse survival compared with those with low TG/HDL-c ratio (Log rank P = 0.003). Moreover, TG/HDL-c ratio was an independent factor in predicting the mortality of COVID-19 patients with no underlying diseases.ConclusionOur study demonstrated that TG/HDL-c ratio might potentially be a predictive marker for mortality in COVID-19 patients.

Effect of combining anticoagulant and glucocorticoid therapy on mortality in patients with severe COVID-19

IntroductionCoronavirus disease (COVID-19) has spread rapidly to more than 200 countries and regions worldwide. Although several options have been implemented in attempts to control the rate of COVID-19 infection, the mortality rates remain high. The aim of this study is to evaluate whether patients with severe COVID-19 will benefit from the combination of anticoagulant and glucocorticoid therapy.MethodsA single-center retrospective cohort study of patients with COVID-19 was performed. Several factors influencing patients with COVID-19 have been analyzed retrospectively, including basic conditions, inflammatory factors, coagulation parameters, medications, and outcomes. Continuous and categorical variables have been evaluated via binary logistic regression analysis to predict mortality. The association between anticoagulant treatment and outcomes has also been evaluated, stratifying patients according to glucocorticoid treatment.Results61 patients with severe COVID-19, including 23 critically ill patients have been enrolled in the study. In those with severe and critical illness COVID-19, mortality rate was lower in those who received combined anticoagulant and glucocorticoid with odds ratio of 0.003 (p = 0.042) and 0.031 (p = 0.046), respectively. In cases of severe COVID-19, those who were treated with both anticoagulant and glucocorticoid had lower mortality (17.6%) than those treated with glucocorticoid alone (31.8%), although this did not reach statistical significance (p = 0.321). In the critically ill COVID-19 patients who received both anticoagulant and glucocorticoid, there was significantly lower mortality (30%) than those who received glucocorticoid alone (77.8%) (p = 0.047). Seventy-five percent of non-survivors of COVID-19 met the International Society on Thrombosis and Haemostasis criteria of disseminated intravascular coagulation (total points ≥5).ConclusionPatients with severe COVID-19 or critically ill patients with COVID-19 may benefit from the combination therapy of anticoagulant and glucocorticoid. As the disease getting severe, more benefits may be obtained from the combination therapy.

Contribution of the von Willebrand factor/ADAMTS13 imbalance to COVID-19 coagulopathy.

The 2019 coronavirus disease (COVID-19) is the disease caused by SARS-CoV-2 infection. Although this infection has been shown to affect the respiratory system, a high incidence of thrombotic events has been observed in severe cases of COVID-19 and in a significant portion of COVID-19 nonsurvivors. Although prior literature has reported on both the coagulopathy and hypercoagulability of COVID-19, the specifics of coagulation have not been fully investigated. Observations of microthrombosis in patients with COVID-19 have brought attention to potential inflammatory endothelial injury. Von Willebrand factor (VWF) and its protease, A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), play an important homeostatic role in responding to endothelial injury. This report provides an overview of the literature investigating the role the VWF/ADAMTS13 axis may have in COVID-19 thrombotic events and suggests potential therapeutic strategies to prevent the progression of coagulopathy in patients with COVID-19.

Abstract 11241: Longitudinal Myocardial Mechanics in Covid-19 Survivors with Normal Left Ventricular Ejection Fraction, a Single Center Study

Introduction: Subclinical cardiovascular involvement in COVID-19 patients has not been well described. 2D-Speckle Tracking Echocardiography derived global longitudinal strain (GLS) and systolic and early diastolic strain rate (SRs, SRe) measurements are more sensitive than standard echocardiographic parameters to diagnose subclinical mechanical dysfunction in patients with normal Left Ventricle Ejection Fraction (LVEF). Hypothesis: Evaluate subclinical myocardial mechanical function and reserve in active COVID-19 systemic disease patients with normal LVEF vs controls and between survivors and non survivors of COVID-19 in the longitudinal domain of contractility. Methods &amp; Results: 166 adult patients with active COVID 19 having normal LVEF were included and compared to 89 healthy volunteers. Baseline parameters were recorded. Peak GLS, SRs and SRe, were measured offline. Mean age was 62.53 ± 18.96 years and 87 (52%) were males and Mean LVEF was 62±5%. COVID-19 patients had higher GLS compared to controls (-20.93%±0.30 vs. -18.48%±0.40; p value &lt;0.0001), SRs was similar (-0.97 s -1 ±0.10 vs. -0.98 s -1 ±0.02, p value 0.2528) and SRe was lower (0.85 s -1 ±0.0 vs. 1.05 s -1 ±0.02; p value &lt;0.0001) respectively. After adjusting for age and sex, GLS, SRs and SRe was significant (p&lt;0.001). GLS, SRs and SRe were similar in survivors vs. non survivors (p NS), both groups had elevated biomarkers (cardiac troponin, NT-pro BNP, CRP), but non survivors had higher levels (3.22±0.18 vs 3.62±0.28, p = 0.2371, 5.86±0.19 vs 7.15±0.27, p = 0.0004, 3.75±0.14 vs 4.31±0.21, p = 0.0422, 7.64±0.17 vs 8.26±0.25, p=0.0487 respectively) (Table 1). Conclusions: In our cohort, COVID-19 patients had better systolic reserve and abnormal relaxation compared to controls. There was no significant difference in strain (GLS) and strain rate (SRs &amp; SRe) amongst survivors and non survivors in the longitudinal domain of contractility despite of higher inflammatory biomarkers in non-survivors.

Abstract 14159: Characteristics and Outcomes in COVID-19 Pediatric In-Hospital Cardiac Arrest Patients

Introduction: Survival of adult patients with COVID-19 who had an in-hospital cardiac arrest (IHCA) are poor. Characteristics and outcomes for pediatric IHCA patients with COVID-19 are unknown. Hypothesis: We hypothesized that pediatric COVID-19 patients would have worse survival outcomes when compared to non-COVID patients. Methods: A multicenter, multinational cohort of pediatric IHCA in the pediRES-Q collaborative were reviewed (March 1, 2020 - April 1, 2021). We characterized patients with COVID-19 compared to patients without COVID-19 and investigated whether COVID-19 was associated with survival outcomes using multivariate logistic regression with mixed effects. Results: We identified 362 pediatric IHCAs of which 14 were COVID-19 positive. For non-COVID-19 vs COVID-19 patients respectively, median [Q1; Q3] age was 1.0 [0.3; 7.1] vs. 7.1 [1.5; 14.0] years and 42% vs. 43% were female. Immediate cause of arrest was hypotension: 8% vs. 43%, respiratory decompensation: 19% vs. 21%, and hypoxia 22% vs. 36% for non-COVID-19 vs. COVID-19 patients. For non-COVID-19 vs COVID-19 patients, total CPR duration was 10 [4; 33] min vs 19 [5; 33] min (for non-return of spontaneous circulation (ROSC) cases only: 35 [20; 55] min vs 34 [24; 34] min). For non-COVID-19 vs COVID-19 patients, ROSC was 79% vs. 57%, aOR: 0.48 (95% CI: 0.24-0.98), survival to hospital discharge was 45% vs. 29%, aOR: 0.63 (95% CI: 0.25-1.57) and survival with favorable neurological outcome was 39% vs. 21%, aOR: 0.51 (95% CI: 0.16-1.65). Conclusions: In a pediatric resuscitation quality improvement collaborative, pediatric IHCA patients with COVID-19 were older when compared to non-COVID-19 patients. Median CPR duration was &gt;30 minutes for COVID-19 non-survivors, COVID-19 patients had lower chance of ROSC when compared to non-COVID-19 patients but considerably better survival outcomes than those reported for adults.

Analysis of transcriptomic data sets supports the role of IL-6 in NETosis and immunothrombosis in severe COVID-19

BackgroundThere is an urgent need to understand the key events driving pathogenesis of severe COVID-19 disease, so that precise treatment can be instituted. In this respect NETosis is gaining increased attention in the scientific community, as an important pathological process contributing to mortality. We sought to test if indeed there exists robust evidence of NETosis in multiple transcriptomic data sets from human subjects with severe COVID-19 disease. Gene set enrichment analysis was performed to test for up-regulation of gene set functional in NETosis in the blood of patients with COVID-19 illness.ResultsBlood gene expression functional in NETosis increased with severity of illness, showed negative correlation with blood oxygen saturation, and was validated in the lung of COVID-19 non-survivors. Temporal expression of IL-6 was compared between severe and moderate illness with COVID-19. Unsupervised clustering was performed to reveal co-expression of IL-6 with complement genes. In severe COVID-19 illness, there is transcriptional evidence of activation of NETosis, complement and coagulation cascade, and negative correlation between NETosis and respiratory function (oxygen saturation). An early spike in IL-6 is observed in severe COVID-19 illness that is correlated with complement activation.ConclusionsBased on the transcriptional dynamics of IL-6 expression and its downstream effect on complement activation, we constructed a model that links early spike in IL-6 level with persistent and self-perpetuating complement activation, NETosis, immunothrombosis and respiratory dysfunction. Our model supports the early initiation of anti-IL6 therapy in severe COVID-19 disease before the life-threatening complications of the disease can perpetuate themselves autonomously.

Lymphocyte Ratios Progressively Worsen in Non-Survivors of COVID-19

Background:Brazil became the South American epicenter for coronavirus disease (COVID-19) soon after the first case was diagnosed in February 2020 with the highest infection rate occurring in the state of Sao Paulo. COVID-19 is characterized by marked thrombo-inflammation mechanisms, and neutrophil-lymphocyte ratio (NLR) among many clinical and laboratory data, is becoming an inflammatory marker of severity and mortality of COVID-19. We evaluated the serial weekly lymphocyte ratios, which are easily derivable from the routine blood counts, in the survivors and non-survivors of COVID-19 at the Clinical Hospital of University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil, from time of diagnosis to the 3 rd week of care. This hospital is one of the referral centers for COVID-19 patients in this state.Methods: In this retrospective study, we reviewed the medical notes of 320 adults hospitalized patients with PCR-confirmed COVID-19 at the Clinical Hospital of UNICAMP, from March 2020 to March 2021. The serial weekly hematological parameters (analyzed using automated counter - XN 9000™, Sysmex, Japan) from the time of diagnosis were analyzed and lymphocytes ratios (neutrophil-lymphocyte, NLR, platelet-lymphocyte PLR, and monocyte-lymphocyte MLR) were calculated. The survivors (n=257) were those who recovered from the disease and were discharged from the hospital, while the non-survivors (n=63) were those who died in the course of treatment. Statistical analyses were performed using SPSS (version 22). Unpaired data of Survivors and Non-survivors with COVID-19 were compared using Mann-Whitney tests. Repeated measures were compared within and between groups using univariate and multivariate tests in general linear models. All results were considered significant if p<0.05.Results: Of the 320 patients, 257 (80.3%) were survivors and had lower mean age than the non-survivors (57.73 vs 64.65 years, p<0.001). At diagnosis, the non-survivors had a lower lymphocyte count (p=0.002), basophil count (p=0.049), and hematocrit (p=0.021) than the survivors, Table 1.We used general linear models for repeated measures and corrected for the patients who did not stay long enough to have a complete series of blood counts, Figure 1 A-G. Multivariate tests between the survivor and non-survivor groups showed significant variations with serial weekly lymphocyte count (p<0.001), neutrophil count (P=0.005), NLR (p=0.009), MLR (p=0.010), and PLR (p=0.035) but not with the weekly monocyte count (p=0.352) and platelet count (p=0.505). The NLR was higher and PLR was lower in the non-survivors at diagnosis (p<0.001 and p=0.047 respectively), both were higher in the 2 nd week post-diagnosis (p<0.001 and 0.043 respectively), and in the 3 rd week (p<0.001 and p=0.043 respectively) (Figure 1D and E). The MLR was not significantly different at diagnosis but became elevated in the following two weeks post-diagnosis (p=0.09, p=0.022, and p<0.001 respectively) (Figure 1F).Conclusions: The non-survivors were older and their NLR and MLR tend to increase from the time of diagnosis while their PLR tend to decrease after the 2 nd week post-COVID-19 diagnosis and treatment. On the other hand, all three ratios significantly decrease in the survivors. While neutrophilia and lymphopenia improved in the survivor, they worsen in non-survivors. These cells may have contributed towards the recovery by ameliorating the inflammatory response in survivors, and death by worsening the response in non-survivors of COVID-19. This study shows that serial lymphocyte count, neutrophil count, NLR, PLR, and MLR could serve as good and easily accessible markers of outcomes in patients with COVID-19 and could be used for monitoring of response to treatment. [Display omitted] DisclosuresCosta: Novartis: Consultancy.

Clinical and laboratory characteristics of 98 COVID-19 nonsurvivors in a tertiary care centre in Tamilnadu, India: a ret- rospective study

Clinical and laboratory characteristics of 98 COVID-19 nonsurvivors in a tertiary care centre in Tamilnadu, India: a ret- rospective study

Reader Response: Early Postmortem Brain MRI Findings in COVID-19 Non-survivors.

Coolen et al.1 published valuable research exploring the existence of structural brain abnormalities by MRI studies in nonsurvivors of COVID-19. They described cortico-subcortical edematous changes suggestive of posterior reversible encephalopathy syndrome (PRES) in 1 decedent. The most accepted theory of PRES is a loss of autoregulation in cerebral blood flow—usually associated with hypertension or arterial pressure fluctuations, with a subsequent increase in vascular permeability and leakage of blood plasma and erythrocytes—producing vasogenic edema. Other theories have been proposed in the pathogenesis of PRES, but they all lead to activation and injury of the endothelium, stimulation of the immune system, and release of cytokines.2,3 SARS-CoV-2 neurotropism has been recently supported.4,5 Its invasion of the CNS is usually responsible of cytokine storms, leading to endothelium dysfunction,1,2 which might trigger the necessary pathophysiology mechanisms for PRES appearance. The patient described by Coolen et al. did not show arterial pressure abnormalities, and then, the direct virus invasion to the brain seems to be the mechanism involved in this patient. PRES pathophysiology is directly related to the posterior circulation of the brain. The posterior cerebral artery also offers blood supply to a large portion of the thalamus and the upper brainstem.1-3 As this is a reversible syndrome, the possibility of the occurrence of endothelial dysfunction in the rest of the brainstem—affecting the respiratory centers—cannot be excluded. I discussed that SARS-CoV-2 infection might partially explain the acute respiratory distress syndrome refractory to treatments, commonly found in this pandemic.5

Prognostic value of pre-infection routine laboratory parameters for COVID-19 mortality in tumor patients: Results of the ADHOK Coronavirus Tumor Registry.

10571 Background: Tumor patients (pts.) are considered susceptible to severe COVID-19 after SARS-CoV-2 infection. However, they represent a heterogeneous group of individuals with variable risk. Identification of vulnerable subgroups is important for prioritization of vaccination strategies and possible early therapeutic intervention after infection. Methods: Tumor pts. with PCR-confirmed SARS-CoV-2 infection were included in the multicentric ADHOK registry by 22 institutions. Detailed information about tumor disease and treatment, as well as routine laboratory parameters determined at least 10 days prior to SARS-CoV-2 infection, was collected retrospectively. The primary endpoint was defined as the outcome of the SARS-CoV-2 infection, graded according to the WHO: asymptomatic, mild, moderate, severe, critical, and COVID-19-related death. Results: Until Feb. 5, 2021, 215 pts. (67% with solid tumors, 33% with hematological neoplasms) were included in the registry. 74% of the pts. had an active malignancy. The course of SARS-CoV-2 infection was rather variable: 66% of the pts. remained asymptomatic or showed a mild-to-moderate course, while the rest developed severe or critical disease. The COVID-19-related mortality rate was 24%. Pre-infection routine laboratory values were available for 104 pts., obtained at a median of 21 days before SARS-CoV-2 infection. Compared to COVID-19 survivors, COVID-19 non-survivors showed significantly higher median levels of absolute neutrophil count (ANC: 3.6 vs. 6.4 /nL; p = 0.006, n = 91), neutrophil-to-lymphocyte ratio (NLR: 2.2 vs. 7.2; p = 0.005, n = 75), C-reactive protein (CRP: 9.9 vs. 42.0 mg/L; p = 0.001, n = 104), and lactate dehydrogenase (LDH: 213.0 vs. 267.0 U/L; p = 0.016, n = 78). When categorized by a median split, COVID-19 mortality was significantly higher in pts. with ANC &gt; 4.4 /nL (4% vs. 55%, p &lt; 0.001), NLR &gt; 4.1 (5% vs. 58%, p &lt; 0.001), CRP &gt; 15.4 mg/L (18% vs. 46%, p = 0.003), LDH &gt; 236 U/L (15% vs. 49%, p = 0.003) and lymphocytes &lt; 1.3 /nL (41% vs. 11% p = 0.002). In multivariable analysis, ANC and CRP showed a strong and significant association with COVID-19-related death (OR 23.0 and 7.7, p = 0.007 and 0.029, respectively). To develop an easy-to-apply pre-infection score, we combined ANC and CRP and were able to separate three groups of pts. with significantly different COVID-19 outcomes (p &lt; 0.001) (Table). Conclusions: Our results unveil subgroups of tumor pts. who may be at increased risk of severe COVID-19 and point to pre-infection routine laboratory parameters with potential prognostic power: ANC and CRP may help identify pts. at risk for severe COVID-19 before SARS-CoV-2 infection.[Table: see text]

Association of endothelial activation assessed through endothelin-I precursor peptide measurement with mortality in COVID-19 patients: an observational analysis

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19.MethodsWe measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality.ResultsOverall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality.ConclusionsCompared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.

Hematological profile and biochemical markers of COVID-19 non-survivors: A retrospective analysis

BackgroundCoronavirus disease is primarily transmitted through the respiratory route and bodily contact. The fatality in COVID-19 cases was alarming in the initial days. This study analyzes hematological and biochemical markers of COVID-19 non-survivors. Material and methodsIn this single-center study, records of 249 patients hospitalized with COVID-19 were studied for hematological profile and biochemical markers. Records of patients with laboratory-confirmed COVID-19 disease hospitalized between April 14, 2020, to August 15, 2020, were included in the analysis. ResultsSignificantly, the disease mortality was associated with increased procalcitonin (P < 0.05), C-reactive protein (P < 0.05), aspartate transaminase (P < 0.05), serum potassium (P < 0.05), neutrophils count (P < 0.05), white blood cell count (P < 0.05), prothrombin time (P < 0.05) and activated prothrombin time (P < 0.05) in patients reported abnormal x-ray findings. Further, patients with abnormal radiological findings significantly showed a reduced level of lymphocyte counts (P < 0.05), oxygen saturation (P < 0.05), and partial oxygen pressure (P < 0.05). Reduced level of aspartate aminotransferase (P < 0.05), alanine aminotransferase (P < 0.05) and lactate dehydrogenase (P < 0.05) reported significant association with mortality among patients with COVID-19. ConclusionsThe clinicians may consider the hematological and biochemical parameters in the patients with COVID-19 in future decision-making. These indicators might support clinical decisions to identify high fatality cases and poor diagnosis in the initial admission phase. In COVID-19 patients, we recommend close monitoring on procalcitonin, C-reactive protein, neutrophils count, and white blood cell count as a clinical indicator for potential progression to critical illness.

Longitudinal multi-omics transition associated with fatality in critically ill COVID-19 patients

PurposeCritically ill COVID-19 patients have significantly increased risk of death. Although several circulating biomarkers are thought to be related to COVID-19 severity, few studies have focused on the characteristics of critically ill patients with different outcomes. The objective of this study was to perform a longitudinal investigation of the potential mechanisms affecting the prognosis of critically ill COVID-19 patients.MethodsIn addition to clinical data, 113 whole blood samples and 85 serum samples were collected from 33 severe and critical COVID-19 patients without selected comorbidities. Multi-omics analysis was then performed using longitudinal samples.ResultsObvious transcriptional transitions were more frequent in critical survivors than in critical non-survivors, indicating that phase transition may be related to survival. Based on analysis of differentially expressed genes during transition, the erythrocyte differentiation pathway was significantly enriched. Furthermore, clinical data indicated that red blood cell counts showed greater fluctuation in survivors than in non-survivors. Moreover, declining red blood cell counts and hemoglobin levels were validated as prognostic markers of poor outcome in an independent cohort of 114 critical COVID-19 patients. Protein–metabolite–lipid network analysis indicated that tryptophan metabolism and melatonin may contribute to molecular transitions in critical COVID-19 patients with different outcomes.ConclusionsThis study systematically and comprehensively depicted the longitudinal hallmarks of critical COVID-19 patients and indicated that multi-omics transition may impact the prognosis.Take home messageFrequent transcriptional phase transitions may contribute to outcome in critically ill COVID-19 patients. Furthermore, fluctuation in red blood cell and hemoglobin levels may relate to poor prognosis. The biological function of melatonin was suppressed in COVID-19 non-survivors, which may provide a potential theoretical basis for clinical administration.

Neutrophil-to-lymphocyte ratio on admission to predict the severity and mortality of COVID-19 patients: A meta-analysis.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, was suggested to be predictive of severity and mortality in COVID-19 patients. Here, we investigated whether NLR levels on admission could predict the severity and mortality of COVID-19 patients.MethodsA literature search was conducted on 23 July 2020 to retrieve all published articles, including grey literature and preprints, investigating the association between on-admission NLR values and severity or mortality in COVID-19 patients. A meta-analysis was performed to determine the overall standardized mean difference (SMD) in NLR values and the pooled risk ratio (RR) for severity and mortality with the 95% Confidence Interval (95%CI).ResultsA total of 38 articles, including 5699 patients with severity outcomes and 6033 patients with mortality outcomes, were included. The meta-analysis showed that severe and non-survivors of COVID-19 had higher on-admission NLR levels than non-severe and survivors (SMD 0.88; 95%CI 0.72–1.04; I2 = 75.52% and 1.87; 95%CI 1.25–2.49; I2 = 97.81%, respectively). Regardless of the different NLR cut-off values, the pooled mortality RR in patients with elevated vs. normal NLR levels was 2.74 (95%CI 0.98–7.66).ConclusionHigh NLR levels on admission were associated with severe COVID-19 and mortality. Further studies need to focus on determining the optimal cut-off value for NLR before clinical use.

Characteristics and outcomes of cancer patients with covid-19 at a safety-net hospital

Patients with cancer are a vulnerable population during the COVID-19 pandemic due to underlying immunosuppression, pre-existing comorbidities, and poor nutrition. There is a lack of data describing the disease course of cancer patients with COVID-19 disease. Therefore, we analyzed data from cancer patients with COVID-19 who were admitted to our hospital. Cancer patients were categorized into two groups as survivors and non-survivors of COVID-19. Among 68 cancer patients with COVID-19, 27% of patients were admitted to ICU, and 37% of the patients died. The median age was 72, and non-survivors were older than survivors (p = 0.001). Non-survivors had higher comorbidity scores, late-stage cancer, and worse ECOG performance status than survivors (all p values<0.005). Non-survivors also had significantly lower lymphocyte count and albumin level but higher lactate dehydrogenase, C-reactive protein, fibrinogen, troponin, and ferritin levels than survivors. On multivariable analysis, increased age and mechanical ventilation were associated with increased odds of death. We report no association between anti-cancer treatments and mortality from COVID-19 disease. In summary, cancer patients have higher mortality of COVID-19 infection than the general population. In addition to generally known risk factors, the high mortality rate in cancer patients with COVID-19 is associated with several cancer-specific factors.

Echocardiographic systolic pulmonary arterial pressure and mortality in coronavirus disease 2019 patients.

We perfromed a systematic review and meta-analysis to compare the echocardiographic systolic pulmonary arterial pressure (sPAP) difference between COVID-19 survivors (S) and nonsurvivors (NS). MEDLINE and Scopus databases were systematically searched for articles, published in English language, from inception through 15 May 2021 using the following Medical Subject Heading (MESH) terms: COVID-19 [Title/Abstract] AND pulmonary arterial pressure [Title/ Abstract] OR Echocardiography [Title/Abstract]. The difference of sPAP measurement obtained at transthoracic echocardiography between nonsurvivors and survivors was expressed as mean difference with the corresponding 95% confidence interval (CI) using a random-effect model. Nine studies, enrolling 788 patients (mean age 62.8 years old, 479,men) met the inclusion criteria and were included into the analysis. Using a randomeffect mode, sPAP was 11.8mmHg (95% CI, 6.60-16.97; P < 0.0001, I2 = 89.3%) higher in NS compared with S. Sensitivity analysis confirmed yielded results. COVID-19 NS had a higher sPAP compared with S, reinforcing previous observations demonstrating the critical role of RV function in determining the short-term outcome of COVID-19 patients.