scholarly journals 499. Rapid and Sustained Decline in CXCL-10 (IP-10) Annotates Clinical Outcomes Following TNF-α Antagonist Therapy in Hospitalized Patients with Severe and Critical COVID-19 Respiratory Failure

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S351-S352
Author(s):  
Courtney Schroeder ◽  
Hilal Hachem ◽  
Amandeep Godara ◽  
Daniel Fein ◽  
Hashim Mann ◽  
...  

Abstract Background TNFα and IFN-γ may synergize to induce cytokine-driven lethal hyperinflammation and immune exhaustion in COVID-19 illness. Methods To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥ 50 compared to baseline and sustained for 48 hours. Secondary endpoints included 28-day mortality, dynamic cytokine profiles (Human Cytokine 48-Plex Discovery Assay), secondary infections, duration of supplemental oxygen support and hospitalization. Consort diagram Hospitalized patients with SARS-COV2 infection and pneumonia that were referred to the infliximab-abda study team for evaluation. Results Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 yrs, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days, 15/18 (83%) recovered from respiratory failure, and 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Deaths among three patients ≥ 65 years age with pre-existing lung disease or multiple comorbidities were attributed to secondary lung infections. Mean plasma IP-10 levels declined sharply from 9183 pg/ml to 483 pg/ml at Day 3 and 146 pg/ml at Day 14/discharge. Significant declines in IFN-γ, TNFα, IL-27, IL-6 (baseline above 10pg/ml), CRP and ferritin were specifically observed at Day 3 whereas other cytokines were unaffected. Among 13 lymphopenic patients, six (46%) had resolution of lymphopenia by day 3, and 11 by day 14. CXCR3-ligand (IP-10 and CXCL-9) declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, p-value: 0.0006). Demographics and clinical characteristics Demographics, comorbidities, clinical features, inflammatory markers, and outcomes of 18 patients with COVID-19 respiratory failure treated with infliximab-abda between April and December 2020. Changes in oxygen support status following infliximab-abda treatment Colored bars indicate the maximal level of oxygen support for each individual following treatment with infliximab-abda. The status of the patient at last follow-up (discharged, alive or dead) is indicated. ECMO: extracorporeal membrane oxygenation Control of inflammatory markers and cytokines following infliximab therapy Values from individuals are connected with solid lines, with deceased individuals indicated in red. Statistics: n=18, paired ratio t-test compared to baseline; *: P<0.05, **: P<0.01, ***: P<0.001, ****: P<0.0001, n.s.: not significant. Conclusion Consistent with a central role of TNFα, the clinical and cytokine data indicate that infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19. Randomized studies are formally evaluating infliximab therapy in this context. Funding: National Center for Advancing Translational Sciences Disclosures All Authors: No reported disclosures

2021 ◽  
Author(s):  
Hilal Hachem ◽  
Amandeep Godara ◽  
Courtney Schroeder ◽  
Daniel Fein ◽  
Hashim Mann ◽  
...  

Background: A feed-forward pathological signaling loop generated by TNFα and IFN-γ in inflamed lung tissue, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define, sustain and amplify the inflammatory biology of lethal COVID-19 respiratory failure. Methods: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by >50 compared to baseline and sustained for 48 hours. Secondary endpoints included 28-day mortality, dynamic cytokine profiles (Human Cytokine 48-Plex Discovery Assay, Eve Technologies), secondary infections, duration of supplemental oxygen support and hospitalization. Findings: Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 yrs, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days, 15/18 (83%) recovered from respiratory failure, and 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Deaths among three patients > 65yrs age with pre-existing lung disease or multiple comorbidities were attributed to secondary lung infection. Mean plasma IP-10 levels declined sharply from 9183 pg/ml to 483 pg/ml at Day 3 and further to 146 pg/ml at Day 14/discharge. Significant declines in IFN-γ, TNFα, IL-27, CRP and ferritin were specifically observed at Day 3 whereas other cytokines were unmodified. IL-6 levels declined sharply among patients with baseline levels >10 pg/ml. Among 13 lymphopenic patients, six (46%) had resolution of lymphopenia by day 3, and 11 by day 14. CXCR3-ligand (IP-10 and CXCL-9) declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, p-value: 0.0006). Interpretation: Consistent with a pathophysiological role of TNFα, the clinical and cytokine data indicate that infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19. Randomized studies are required to formally assess mortality outcomes. Funding: National Center for Advancing Translational Sciences


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Irles ◽  
F Salerno ◽  
R Cassagneau ◽  
R Eschallier ◽  
C Maupain ◽  
...  

Abstract Background The evolution of atrioventricular block (AVB) after Trans Aortic Valve Implantation (TAVI) is poorly understood, and indications of pacemaker (PM) implantation after TAVI not well defined. Modern PM algorithms can help studying the evolution of these AV conduction disorders after TAVI. SafeR® mode (Sorin® PM) allows to monitor precisely the AV conduction and to store AVB episodes in the PM memory as intracardiac electrograms, which can be re-read and validated afterwards. Methods From November 2015 and January 2017, all patients implanted in one of the 19 French enrolling centers with a Sorin® PM set in SafeR® mode after TAVI could be prospectively included in the study. All the PM interrogation files were centrally collected. The primary endpoint (PE) was the presence of at least one episode of high grade AVB (HG-AVB) beyond day 7 (D7) to one year after the TAVI. It could be validated either by the presence of a HG-AVB on EKG or telemetry, or by the confirmation of a HG-AVB in the PM memory files. Results 273 patients were included in the study, the PE was assessable in 197 patients. PE was validated in 74.6% patients. In univariate analysis, the use of an oversized prothesis or balloon, and all early episodes of HG-AVB (all those occurring up to D7) influence the validation of the PE. Other AV conduction disorders have no influence on the PE (Table). In multivariate analysis, only HG-AVB occurring between D2 and D7 has a significant influence on the PE. Factors influencing HG-AVB after TAVI Studied factor HG-AVB episode(s) during the one year follow up No HG-AVB episode during the one year follow up p value RBBB before TAVI (%) 41 34 0,346 Low implantation (>6mm) (%) 59 37 0,156 Use of Autoexpansive Valve (%) 62 62 0,990 Oversizing (%) 19 6 0,022 HG-AVB per TAVI (%) 56 30 0,001 HG-AVB D0-D1 (%) 53 24 0,001 HG-AVB D2-D7 (%) 68 34 0,001 New or wiser LBBB and improvement of PR interval after TAVI (%) 30 39 0,253 Influence of predefined factors on the Primary Endpoint. Conclusion The analysis of the SafeR® algorithm files in patients implanted with a PM after TAVI show a high incidence of HG-AVB during the one year follow up. In multivariate analysis, only HG-AVB occurring between D2 and D7 significantly influence the PE, confirming that AV conduction disorders occurring during the first 24 hours may spontaneously normalize. Acknowledgement/Funding Microport CRM


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.P De Sousa Bispo ◽  
P Azevedo ◽  
P Freitas ◽  
N Marques ◽  
C Reis ◽  
...  

Abstract Introduction Several studies have addressed the importance of transthoracic echocardiography (TTE) in risk prediction of subsequent adverse events after ST elevation myocardial infarction (STEMI). While several traditional echo parameters have a well-established prognostic value, data derived from 2D-Speckle Tracking Echocardiography (2DSTE) needs further investigation. Objectives To determine if 2DSTE parameters provide additional information beyond conventional echocardiography to predict long-term adverse outcomes in patients admitted with STEMI Methods Retrospective, single-center study, that included all patients without previous cardiovascular events admitted with STEMI (who underwent primary coronary angioplasty) between 2015 and 2017. Patients with poor acoustic windows, severe valvular disease, irregular heart rhythm, and those who died during hospital stay were excluded. We reviewed all pre-discharge TTE to assess conventional parameters of LV systolic and diastolic function and data obtained by 2DSTE: global longitudinal strain (GLS) and peak strain dispersion (PSD), an index that is the standard deviation from time to peak strain of all segments over the entire cardiac cycle. Demographic and clinical data was obtained through electronic hospital records. Minimum follow-up was 2 years. The primary endpoint was a composite of all-cause mortality and cardiovascular re-admission at follow-up. Survival analysis was used to determine independent predictors of the primary endpoint. Results 377 patients were included, mean age 62±13 years, 72% male. Mean LVEF was 50±10% with 19% of patients having LVEF <40%. Mean indexed left atrium volume (LAVi) was 33±10 ml/m2, mean GLS was −14±4%, and PSD was 60±22 msec. Average follow-up was 36±11 months, with a combined endpoint of mortality and hospitalization of 27% (n=102) Univariate analysis of echocardiographic variables revealed an association between heart rate, LVEF, indexed LV end-systolic volume, indexed stroke volume, LAVi, GLS and PSD with the endpoint. However, on multivariate analysis only LAVi [HR 1.030 (95% CI 1.009 - 1.051), p-value = 0.005] and PSD [HR 1.011 (95% CI 1.002 - 1.020), p-value = 0.012] remained independent predictors of the primary endpoint. We determined that a PSD value higher than 52 msec has a sensitivity of 76% and a negative predictive value of 83% for mortality and hospitalization, and that this cut-off point discriminates patients at a higher risk of events in Kaplan-Meier Survival analysis with a Log-Rank p-value=0.001. Conclusion PSD derived by longitudinal strain analysis is a promising prognostic predictor after STEMI. PSD outperformed conventional echocardiographic parameters in the risk stratification of STEMI patients at discharge. Kaplan-Meier Survival Curves Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Alkhalil ◽  
A K Kearney ◽  
M H Hegarty ◽  
C S Stewart ◽  
P D Devlin ◽  
...  

Abstract Background Inflammation is an indicator of worse clinical outcomes following acute myocardial infarction. Eosinopenia was identified as a surrogate of inflammation in sepsis and obstructive airway disease. Whether this readily-available marker has any impact on long term outcomes following ST-segment elevation myocardial infarction (STEMI) is yet to be determined. Purpose We sought to study the incidence and relationship between eosinopenia and infarct severity and whether low eosinophil had impact on clinical outcomes following STEMI. Methods 606 consecutive STEMI patients undergoing primary PCI from a large volume single centre were enrolled. Low eosinophil count was defined as <40 cells/ml from samples within 2 -hours post reperfusion. Primary endpoint was defined as composite of death, MI, stroke, unplanned revascularisation, re-admission for heart failure over 3.5 years follow up. Results 65% of patients had eosinopenia. Patients in the low eosinophil group had larger infarct size as measured by troponin value [2934 vs. 1177ng/L, P<0.001] and left ventricle (LV) systolic function on echocardiography [48% vs. 50%, P=0.029]. Thehre was a modest correlation between eosinophil count and both troponin (r=−0.25, P<0.001) and ejection fraction (r=0.10, P=0.017). The primary endpoint was higher in eosinopenic patients (28.8% vs. 20.4%, HR 1.49, 95% CI 1.05 to 2.13, P=0.023) (Figure). The difference was mainly driven from higher percentage of unplanned revascularisations (8.2% versus 2.9%, P=0.012) (Table). Low eosinophil count was an independent predictor of adverse cardiovascular events, beyond infarct severity, in elderly, non-diabetic patients (HR 2.04, 95% CI 1.04 to 4.01, P=0.038). Incidence rate of major clinical Clinical characteristics Low eosinophil Normal eosinophil P value Long term clinical events 28.8% (112) 20.4% (42) 0.026 Long term mortality 14.1% (55) 11.1% (23) 0.31 Long term MI 6.9% (27) 4.9% (10) 0.32 Long term unplanned revascularisation 8.2% (32) 2.9% (6) 0.012 Long term re-admission CCF 6.7% (26) 4.9% (10) 0.37 Long term stroke 2.6% (10) 1% (2) 0.19 Conclusions Eosinopenia is a readily-available marker which was associated with a larger infarcts and worse clinical outcomes over long term follow up.


2021 ◽  
Author(s):  
Fernando Cabanillas ◽  
Javier Morales ◽  
José G. Conde ◽  
Jorge Bertrán-Pasarell ◽  
Ricardo Fernández ◽  
...  

AbstractIntroductionCovid-19 is a triphasic disorder first typified by a viral phase that lasts from the first onset of symptoms until seven days later. This is followed by a second and third phase, initially characterized by the appearance of lung infiltrates, followed in 20% by respiratory failure. The second phase is usually heralded by an elevation of serologic inflammatory markers including CRP, ferritin, IL-6, LDH as well as D-dimers. Approximately 20% proceed to the second phase and are usually then treated with dexamethasone, provided they are oxygen-dependent since these are the only cases that benefit from dexamethasone. If we had objective criteria to predict this 20% that develop severe illness, they could preemptively be treated with steroids. In this exploratory study we investigated the early use of preemptive steroids in the setting of early disease, in high-risk non-oxygen dependent cases.MethodsEligible patients were those 21 years or older with a diagnosis of Covid-19 and oxygen saturation ≥91%. For patients to be classified as high-risk, they had to exhibit two or more of the following abnormalities 7-10 days after first symptom: IL-6 ≥ 10 pg/ml, ferritin > 500 ng/ml, D-dimer > 1 mg/L (1,000 ng/ml), CRP > 10 mg/dL (100 mg/L), LDH above normal range lymphopenia (absolute lymphocyte count <1,000 /µL), oxygen saturation between 91-94%, or CT chest with evidence of ground glass infiltrates. Primary endpoint was progression to respiratory failure. CALL score method was used to predict the expected number of cases of respiratory failure. High risk patients received methylprednisolone (MPS) 80 mg IV daily x 5 days starting no earlier than seven days from first onset of symptoms. The primary endpoint was progression to hypoxemic respiratory failure defined as PaO2 <60 mm Hg or oxygen saturation ≤90%. Secondary endpoints included survival at 28 days from registration, admission to intensive care and live discharge from the hospital. Change in levels of inflammatory markers and length of hospitalization were also assessed.ResultsIn 76 patients, the expected number with respiratory failure was 30 (39.5%), yet only 4 (5.3%) developed that complication (p=.00001). Survival at 28 days was 98.6%.Improvement in inflammatory markers correlated with favorable outcome.ConclusionsOur results are encouraging and suggest that this approach is both effective and safe.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Yun Viladomat ◽  
C Enjuanes Grau ◽  
E Calero Molina ◽  
E Hidalgo Quiros ◽  
N Jose Bazan ◽  
...  

Abstract Background/Introduction The potential impact of telemedicine (TM) in the monitoring of heart failure (HF) patients is still uncertain, largely due to the heterogeneity of the studies published to date. A subgroup of patients in which its key role is particularly uncertain is that of the frailest patients mainly due to TM-based strategies have been often discouraged on the basis of a foreseeable limited benefit in them. Purpose The aim of this study was to define the efficacy of a TM-based managed care solution across different HF patient frailty phenotypes in a cohort of HF patients recruited in a randomized clinical trial (The Insuficiència Cardíaca Optimitzaciό Remota [iCOR] study) evaluating the efficacy of a TM-based management compared to usual care (UC) in the early post-discharge period. Methods Five previously described frailty clusters were analysed. Cox proportional-hazards regression models were used to evaluate the effect of each cluster and group of treatment (and its interaction) on a series of endpoints (the incidence of non-fatal HF events as primary endpoint and all-cause hospitalization, all-cause death and the composite endpoint combining of all-cause death or non-fatal HF events as secondary endpoints). The incidence proportion of the first occurrence of each of the study endpoints was calculated for each study arm and for cluster, and these compared using χ2 tests. Additionally, a survival analysis was conducted using Cox regression to describe the event-free survival experience of the combination of the clusters with each of the 2 treatment groups for the study endpoints evaluated, and p-value was used to compare the different curves. Results The positive effect of TM compared to UC strategy was consistent across all frailty phenotypes (p-value for interaction 0.711). The risk of experiencing a primary event was significantly lower in patients that underwent allocation to the TM arm compared to UC (p-value=0.016). As shown for the primary endpoint, the positive effect of TM compared to UC strategy was consistent across all frailty phenotypes also for the secondary endpoints (all p-value for interaction &gt;0.05). Likewise, the risk of all-cause hospitalization or the composite end-point of all-cause death or non-fatal HF event was significantly lower in patients that underwent allocation to the TM arm compared to UC (p-value=0.030 and 0.016 respectively). However, the risk of all-cause death did not differ across subgroup strata (p-value&gt;0.05). Conclusion(s) This study showed that non-invasive TM-based follow-up tools are effective compared to UC in preventing fatal and non-fatal adverse events in the early post-discharge period, regardless of the 5 different frailty phenotypes. Importantly, when comparing TM-based follow-up with UC management in patients belonging to equal frailty cluster, those who were followed-up by eHealth had a considerably lower risk of non-fatal HF events, hospitalization or death. FUNDunding Acknowledgement Type of funding sources: None. Cox regression non-fatal HF events Cox regression all-cause hospitalization


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Alberto Michielon ◽  
Priscilla Tifi ◽  
Maddalena Piro ◽  
Massimo Volpe ◽  
Roberto Ricci ◽  
...  

Abstract Aims COVID-19 has a wide spectrum of clinical presentation, from severe forms that require hospitalization to less severe forms that can be managed at home. An acute myocardial involvement was demonstrated in a large proportion of patients admitted for COVID-19 and may persist in the long term. We evaluated the possible cardiac involvement using echocardiography, comprehensive of right and left ventricular strain, in patients who recovered from SARS-CoV-2 infection (hospitalized or home-treated) comparing them with a population of healthy volunteers. Methods and results Forty-one patients with COVID-19, of which fifteen hospitalized, with no prior heart disease, were compared with 13 healthy volunteers. COVID-19 diagnosis was made by a positive molecular swab. Patients with history of pre-existing heart disease were excluded. The median time from infection to outpatient follow-up was 5.9 months. Numerous echocardiographic parameters were compared by unpaired t-test including left ventricular EF, left ventricular GLS, RV free wall strain, FAC, TAPSE, PAPS, TAPSE/PAPS ratio, RA area, and RV thickness. There was a significant difference in RV free wall strain between hospitalized patients and control (−14.6 ± 2.8% vs. −22 ± 0.7%; P-value 0.03) and between hospitalized and home-treated patients (−14.6 ± 2.8% vs. −19.8 ± 0.9%; P-value 0.03), the difference was not significant between control and home-treated patients (−22 ± 0.7% vs. −19.8 ± 0.8%; P-value 0.09). Between hospitalized and not hospitalized group there was a significant reduction in FAC (38.5 ± 3.2% vs. 44.7 ± 1.3%; P-value 0.03) with an increase of RV end diastolic area (19.9 ± 1.3 cm2 vs. 16.8 ± 0.7 cm2; P-value 0.037) and also of end systolic right atrium area (18.2 ± 1.3 cm2 vs. 15.4 ± 0.5 cm2; P-value 0.01). No difference was observed between hospitalized and home-treated patients in TAPSE (22.38 ± 1.26 mm vs. 23.02 ± 0.68 mm; P-value 0.6) and PAPS (24.3 ± 1.6 mmHg vs. 20.2 ± 1.4 mmHg; P-value 0.07) but there was a borderline significant decrease in right ventricular coupling evaluated with TAPSE/PAPS ratio (0.97 ± 0.08 mm/mmHg vs. 1.29 ± 0.10 mm/mmHg; P-value 0.056) and a significant increase in RV thickness in hospitalized patients (5.32 ± 0.45 mm vs. 3.69 ± 0.24 mm; P-value 0.0014). No significant differences were found between hospitalized and not hospitalized group in left ventricular EF (57.8 ± 1.9% vs. 59.9 ± 1.0%; P-value 0.3) and left ventricular GLS (−15.2 ± 0.6% vs. −16.4 ± 0.4%; P-value 0.1). Conclusions Patients hospitalized for COVID-19 showed a dysfunction in RV parameters at 6 months follow-up compared to non-hospitalized patients. No difference in RV function was found between home treated patients and healthy volunteers. No significant differences in LV function were found among the three groups. These preliminary data confirm a decrease in RV function in more severe COVID-19 infection requiring hospital admission, possibly related to increased pulmonary afterload.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 25-25
Author(s):  
Amardeep Kalsi ◽  
Sana Irfan Khan ◽  
Asad Rehman ◽  
Neil Nimkar ◽  
Angelica Singh ◽  
...  

Introduction COVID-19 is an ongoing pandemic that has impacted millions of individuals throughout the world. The spectrum of clinical features of COVID-19 can vary from asymptomatic infection to severe multiorgan failure leading to death. There is no single biomarker available that can predict the trajectory of the infected patient. Few clinical reports suggest a correlation between the severity of COVID-19 and elevation of certain hematological and inflammatory markers. We used a novel COVID-19 Prognostic Score (CPS) which included lymphocyte count, elevated lactate dehydrogenase (LDH), C-reactive protein (CRP) and ferritin levels to predict the outcomes of COVID-19 patients. Methods We performed a retrospective chart review of COVID-19 patients admitted to New York Presbyterian Brooklyn Methodist Hospital between March and April of 2020. Clinical data was extracted manually from electronic medical records. Patients were divided into 2 cohorts. The first cohort included a combination of low lymphocyte count, elevated LDH, CRP and ferritin. The second cohort included normal lymphocyte count, low LDH, CRP and ferritin. Low lymphocyte count was defined as &lt; 20% of white blood cell count (WBC), high LDH as ≥ 300 U/L, high CRP as ≥50mg/L and high ferritin as ≥600 ng/mL. Statistical analysis was performed by computing odds ratio using a p-value of &lt; 0.05 as statistically significant. Results We analyzed 683 hospitalized patients who were diagnosed with COVID-19 confirmed via viral PCR resting. The median age was 66.5 years, males were 52.2% and blacks were 47.2%. 16.3% had coronary artery disease (CAD), 38.6% had Diabetes Mellitus (DM), 63.1% had hypertension and 21.6% had pulmonary disease. 181 patients (26.5%) were intubated and transferred to ICU. The median LDH was 438 U/L, the median CRP was 107 mg/L and the median ferritin was 687 ng/mL. 4.6% of patients developed a thromboembolic event. The overall inpatient mortality rate was 32.1%. There were 178 patients in the CPS-High cohort while there were 41 patients who qualified for the CPS-Low cohort. The median age of CPS-High was 65 years and the median age of CPS-Low was 58 years. The percentage of CAD, DM, hypertension, pulmonary disease in CPS-High and CPS-Low were 11.8%, 39.3%, 57.9%, 10.7% and 19.5%, 17.1%, 43.9%, 12.2% respectively. In the CPS-High cohort the overall inpatient mortality was 42% while the inpatient mortality rate for CPS-Low was 7.3%. In univariate analysis, patients who had CPS low had significantly reduced inpatient mortality (Odds ratio 0.108, 95% CI 0.03-0.36, p-value = 0.0003). Discussion Our study suggests that a combination of hematological characteristics and inflammatory markers can be used to assess the severity of illness with COVID-19. This study shows that there is a likelihood of 6-times higher mortality with COVID-19 if all the clinical characteristics are abnormal including lymphocyte count, LDH, CRP, and ferritin. This simple clinical prognostic score can be used at the time of hospital admission to efficiently triage patients, which may likely improve the outcomes of these patients. This prognostic tool needs to be validated in a larger dataset or prospective clinical study. Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Tatum Sevenoaks ◽  
Catherine J. Wedderburn ◽  
Kirsten A. Donald ◽  
Whitney Barnett ◽  
Heather J. Zar ◽  
...  

ABSTRACTHIV-exposed uninfected (HEU) children may have altered immune regulation and poorer neurodevelopment outcomes compared to their HIV-unexposed (HU) counterparts. However, studies investigating the association of maternal and infant inflammation with neurodevelopment in HEU children are limited and longitudinal data are lacking. This study investigated serum inflammatory markers in HIV-infected vs. uninfected women during pregnancy and in their children, as well as associations with neurodevelopmental outcomes at two years of age in an African birth cohort study. A sub-group of mother-child dyads from the Drakenstein Child Health Study had serum inflammatory markers measured at ≈26 week’s gestation (n=77 HIV-infected mothers; n=190 HIV-uninfected mothers), at 6-10 weeks (n=63 HEU infants and n=159 HU infants) and at 24-28 months (n=77 HEU children and n=190 HU children). Serum inflammatory markers [granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were analyzed with a multiplex bead array and ELISA assays. The Bayley Scales of Infant and Toddler Development, third edition, was used to assess neurodevelopment at 24-28 months. After correcting for multiple comparisons, HIV-infection during pregnancy was associated with lower serum levels of inflammatory markers in mothers at 26 weeks gestation (GM-CSF and MMP9, p<0.05) and HEU children at 6-10 weeks (IFN-γ and IL-1β, p<0.01), and at 24-28 months (IFN-γ, IL-1β, IL-2 and IL-4, p<0.05) compared to HIV-uninfected mothers and HU children. In HEU infants at 6-10 weeks, inflammatory markers (GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1P, IL-2, IL-4, IL-6 and NGAL, all p<0.05) were associated with poorer motor function at two years of age. This is the first study to evaluate the associations of follow-up immune markers in HEU children with neurodevelopment. These findings suggest that maternal HIV infection is associated with immune dysregulation in mothers and their children through two years of age. An altered immune system in HEU infants is associated with poorer follow-up motor neurodevelopment. These data highlight the important role of the immune system in early neurodevelopment and provide a foundation for future research.


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