scholarly journals Longitudinal Cytokine Profile in Patients With Mild to Critical COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Lowell Ling ◽  
Zigui Chen ◽  
Grace Lui ◽  
Chun Kwok Wong ◽  
Wai Tat Wong ◽  
...  

The cytokine release syndrome has been proposed as the driver of inflammation in coronavirus disease 2019 (COVID-19). However, studies on longitudinal cytokine profiles in patients across the whole severity spectrum of COVID-19 are lacking. In this prospective observational study on adult COVID-19 patients admitted to two Hong Kong public hospitals, cytokine profiling was performed on blood samples taken during early phase (within 7 days of symptom onset) and late phase (8 to 12 days of symptom onset). The primary objective was to evaluate the difference in early and late cytokine profiles among patient groups with different disease severity. The secondary objective was to assess the associations between cytokines and clinical endpoints in critically ill patients. A total of 40 adult patients (mild = 8, moderate = 15, severe/critical = 17) hospitalized with COVID-19 were included in this study. We found 22 cytokines which were correlated with disease severity, as proinflammatory Th1-related cytokines (interleukin (IL)-18, interferon-induced protein-10 (IP-10), monokine-induced by gamma interferon (MIG), and IL-10) and ARDS-associated cytokines (IL-6, monocyte chemoattractant protein-1 (MCP-1), interleukin-1 receptor antagonist (IL-1RA), and IL-8) were progressively elevated with increasing disease severity. Furthermore, 11 cytokines were consistently different in both early and late phases, including seven (growth-regulated oncogene-alpha (GRO-α), IL-1RA, IL-6, IL-8, IL-10, IP-10, and MIG) that increased and four (FGF-2, IL-5, macrophage-derived chemokine (MDC), and MIP-1α) that decreased from mild to severe/critical patients. IL-8, followed by IP-10 and MDC were the best performing early biomarkers to predict disease severity. Among critically ill patients, MCP-1 predicted the duration of mechanical ventilation, highest norepinephrine dose administered, and length of intensive care stay.

2016 ◽  
Vol 44 (6) ◽  
pp. 1034-1041 ◽  
Author(s):  
Jeremy Cohen ◽  
Carel J. Pretorius ◽  
Jacobus P. J. Ungerer ◽  
John Cardinal ◽  
Antje Blumenthal ◽  
...  

2021 ◽  
Vol 9 ◽  
Author(s):  
Feng-ming Ding ◽  
Yun Feng ◽  
Lei Han ◽  
Yan Zhou ◽  
Yong Ji ◽  
...  

Fever is one of the typical symptoms of coronavirus disease (COVID-19). We aimed to investigate the association between early fever (EF) and clinical outcomes in COVID-19 patients. A total of 1,014 COVID-19 patients at the Leishenshan Hospital were enrolled and classified into the EF and non-EF groups based on whether they had fever within 5 days of symptom onset. Risk factors for clinical outcomes in patients with different levels of disease severity were analyzed using multivariable analyses. Time from symptom onset to symptom alleviation, CT image improvement, and discharge were longer for patients with moderate and severe disease in the EF group than in the non-EF group. Multivariable analysis showed that sex, EF, eosinophil number, C-reactive protein, and IL-6 levels were positively correlated with the time from symptom onset to hospital discharge in moderate cases. The EF patients showed no significant differences in the development of acute respiratory distress syndrome, compared with the non-EF patients. The Kaplan–Meier curve showed no obvious differences in survival between the EF and non-EF patients. However, EF patients with increased temperature showed markedly lower survival than the non-EF patients with increased temperature. EF had no significant impact on the survival of critically ill patients, while an increase in temperature was identified as an independent risk factor. EF appears to be a predictor of longer recovery time in moderate/severe COVID-19 infections. However, its value in predicting mortality needs to be considered for critically ill patients with EF showing increasing temperature.


Author(s):  
Roberto de la Rica ◽  
Marcio Borges ◽  
María Aranda ◽  
Alberto del Castillo ◽  
Antonia Socias ◽  
...  

ABSTRACTOBJECTIVETo describe the clinical characteristics and epidemiological features of severe (non-ICU) and critically patients (ICU) with COVID-19 at triage, prior hospitalization, in one of the main hospitals in The Balearic Islands health care system.DESIGNRetrospective observational studySETTINGSon Llatzer University Hospital in Palma de Mallorca (Spain)PARTICIPANTSAmong a cohort of 52 hospitalized patients as of 31 March 2020, 48 with complete demographic information and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test, were analyzed. Data were collected between March 15th, 2020, and March 31th 2020, inclusive of these dates.MAIN OUTCOMESClinical, vital signs and routine laboratory outcomes at the time of hospitalization, including symptoms reported prior to hospitalization. Demographics and baseline comorbidities were also collected. Mortality was reported at the end of the study.RESULTS48 patients (27 non-ICU and 21 ICU) resident in Mallorca, Spain (mean age, 66 years, [range, 33-88 years]; 67% males) with positive SARS-CoV-2 infection were analyzed. There were no differences in age or sex among groups (p >.05). Initial symptoms included fever (100%), coughing (85%), dyspnea (76%), diarrhea (42%) and asthenia (21%). The majority of patients in this case series were hospitalized because of low SpO2 (SpO2 below 90%) and presentation of bilateral pneumonia (94%) at triage. ICU patients had a higher prevalence of dyspnea compared to non-ICU patients (95% vs 61%, p = .022). Acute respiratory syndrome (ARDS) was presented in 100% of the ICU-patients. All the patients included in the study required oxygen therapy. ICU-patients had lymphopenia as well as hypoalbuminemia. Inflammatory markers such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and procalcitonin were significantly higher in ICU patients compared to non-ICU (p < .001).Lower albumin levels were associated with poor prognosis measured as longer hospital length (r= −0.472, p <.001) and mortality (r= −0.424, p=.003). Interestingly we also found, that MCV was lower among of those patients who died (p=.0002). As of April 28, 2020, 10 patients (8 ICU and 2 non-ICU) had died (21% mortality) and while 100% of the non-ICU patients had been discharged, 33% of ICU patients still remained hospitalized (5 in ICU and 2 had been transferred to ward).CONCLUSIONCritically ill patients with COVID-19 present lymphopenia, hypoalbuminemia as well high levels of inflammation. Lower levels of albumin were associated with poorer outcomes in COVID-19 patients. Albumin might be of importance because of its association with disease severity in patients infected with SARS-CoV-2.WHAT IS ALREADY KNOWN IN THIS TOPICSpain has been hit particularly hard by the pandemic. By the time that this manuscript was written more than 25.000 deaths related to COVID-19 have been confirmed. There is limited information available describing the clinical and epidemiological features of Spanish patients requiring hospitalization for COVID-19. Also, it is important to know the characteristics of the hospitalized patients who become critically illWHAT THIS STUDY ADDSThis small case series provides the first steps towards a comprehensive clinical characterization of severe and critical COVID-19 adult patients in Spain. The overall mortality in our patients was 21%. To our knowledge this is the first report with reporting these features in Spain. At triage the majority of patients had lower SpO2 (<90%) and bilateral pneumonia. The most common comorbidities were hypertension (70%), dyslipidemia (62%) and cardiovascular disease (30%). Critically ill patients present hypoalbuminemia and lymphopenia, as well as higher levels of inflammation. Albumin might be of importance because of its association with disease severity and mortality in patients infected with SARS-CoV-2.


Author(s):  
Wandong Hong ◽  
Qin Chen ◽  
Songzan Qian ◽  
Zarrin Basharat ◽  
Vincent Zimmer ◽  
...  

ObjectivesThe objective of this study was to investigate the clinical features and laboratory findings of patients with and without critical COVID-19 pneumonia and identify predictors for the critical form of the disease.MethodsDemographic, clinical, and laboratory data of 63 COVID-19 pneumonia patients were retrospectively reviewed. Laboratory parameters were also collected within 3–5 days, 7–9 days, and 11–14 days of hospitalization. Outcomes were followed up until March 12, 2020.ResultsTwenty-two patients developed critically ill pneumonia; one of them died. Upon admission, older patients with critical illness were more likely to report cough and dyspnoea with higher respiration rates and had a greater possibility of abnormal laboratory parameters than patients without critical illness. When compared with the non-critically ill patients, patients with serious illness had a lower discharge rate and longer hospital stays, with a trend towards higher mortality. The interleukin-6 level in patients upon hospital admission was important in predicting disease severity and was associated with the length of hospitalization.ConclusionsMany differences in clinical features and laboratory findings were observed between patients exhibiting non-critically ill and critically ill COVID-19 pneumonia. Non-critically ill COVID-19 pneumonia also needs aggressive treatments. Interleukin-6 was a superior predictor of disease severity.


2007 ◽  
Vol 83 (3) ◽  
pp. 443-451 ◽  
Author(s):  
MYM Peeters ◽  
LJ Bras ◽  
J DeJongh ◽  
RMJ Wesselink ◽  
LPHJ Aarts ◽  
...  

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Kim C. M. van der Elst ◽  
Anette Veringa ◽  
Jan G. Zijlstra ◽  
Albertus Beishuizen ◽  
Rob Klont ◽  
...  

ABSTRACT In critically ill patients, drug exposure may be influenced by altered drug distribution and clearance. Earlier studies showed that the variability in caspofungin exposure was high in intensive care unit (ICU) patients. The primary objective of this study was to determine if the standard dose of caspofungin resulted in adequate exposure in critically ill patients. A multicenter prospective study in ICU patients with (suspected) invasive candidiasis was conducted in the Netherlands from November 2013 to October 2015. Patients received standard caspofungin treatment, and the exposure was determined on day 3 of treatment. An area under the concentration-time curve from 0 to 24 h (AUC0–24) of 98 mg · h/liter was considered adequate exposure. In case of low exposure (i.e., <79 mg · h/liter, a ≥20% lower AUC0–24), the caspofungin dose was increased and the exposure reevaluated. Twenty patients were included in the study, of whom 5 had a positive blood culture. The median caspofungin AUC0–24 at day 3 was 78 mg · h/liter (interquartile range [IQR], 69 to 97 mg · h/liter). A low AUC0–24 (<79 mg · h/liter) was seen in 10 patients. The AUC0–24 was significantly and positively correlated with the caspofungin dose in mg/kg/day (P = 0.011). The median AUC0–24 with a caspofungin dose of 1 mg/kg was estimated using a pharmacokinetic model and was 114.9 mg · h/liter (IQR, 103.2 to 143.5 mg · h/liter). In conclusion, the caspofungin exposure in ICU patients in this study was low compared with that in healthy volunteers and other (non)critically ill patients, most likely due to a larger volume of distribution. A weight-based dose regimen is probably more suitable for patients with substantially altered drug distribution. (This study has been registered at ClinicalTrials.gov under registration no. NCT01994096.)


2015 ◽  
Author(s):  
Neslihan Cuhaci ◽  
Berna Ogmen ◽  
Cihan Doger ◽  
Burcak Polat ◽  
Seval Izdes ◽  
...  

2020 ◽  
Author(s):  
Kelsey E. Huntington ◽  
Anna D. Louie ◽  
Chun Geun Lee ◽  
Jack A. Elias ◽  
Eric A. Ross ◽  
...  

ABSTRACTAlthough the range of immune responses to COVID-19 infection is variable, cytokine storm is observed in many affected individuals. To further understand the disease pathogenesis and, consequently, to develop an additional tool for clinicians to evaluate patients for presumptive intervention we sought to compare plasma cytokine levels between a range of donor and patient samples grouped by a COVID-19 Severity Score (CSS) based on need for hospitalization and oxygen requirement. Here we utilize a mutual information algorithm that classifies the information gain for CSS prediction provided by cytokine expression levels and clinical variables. Using this methodology, we found that a small number of clinical and cytokine expression variables are predictive of presenting COVID-19 disease severity, raising questions about the mechanism by which COVID-19 creates severe illness. The variables that were the most predictive of CSS included clinical variables such as age and abnormal chest x-ray as well as cytokines such as macrophage colony-stimulating factor (M-CSF), interferon-inducible protein 10 (IP-10) and Interleukin-1 Receptor Antagonist (IL-1RA). Our results suggest that SARS-CoV-2 infection causes a plethora of changes in cytokine profiles and that particularly in severely ill patients, these changes are consistent with the presence of Macrophage Activation Syndrome and could furthermore be used as a biomarker to predict disease severity.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S342-S342
Author(s):  
Michael Leonard ◽  
anthony Asher ◽  
Banks Kooken ◽  
Erin Donahue ◽  
james Symanowski ◽  
...  

Abstract Background Background:: Immune modulation in patients with clinical features suggestive of a cytokine release syndrome (CRS) has become a pharmacologic target for potential treatment of COVID-19 and prevention of ARDS. Tocilizumab is an IL-6 receptor blocker FDA-approved for chimeric antigen receptor (CAR) T cell-induced severe or life-threatening CRS. The objective of this study was to describe clinical outcomes associated with tocilizumab compared with those not receiving tocilizumab in critically ill patients with severe COVID-19. Methods Methods: Retrospective case series of 49 adult patients admitted to an intensive care unit with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients receiving tocilizumab were compared with those not receiving tocilizumab. The primary outcome was clinical improvement (decrease in supplemental oxygen requirement, discharge from ICU, or live discharge from hospital). Secondary endpoints included mortality and frequency of extubation. All comparative endpoints were assessed at 2 weeks after ICU admission. Results Results: 49 patients were identified with SARS-CoV-2 who were admitted to an ICU, 16 received tocilizumab. Baseline characteristics were similar; most were African American males with comorbidities such as obesity, cardiovascular disease, and diabetes. The time from symptom onset to positive test and subsequent intubation were similar (4 and 7 days, respectively). 75% received one dose (all received 8 mg/kg). The median time from symptom onset to tocilizumab administration was 11 days. In patients receiving tocilizumab compared with those not receiving tocilizumab, there were similar rates of clinical improvement (44% versus 61%, p=0.27), extubation (31% versus 45%, p=0.60), and mortality (18% versus 19%, p &gt;0.99, respectively). 81% of the tocilizumab group had resolution of fever and 75% had improvement in C-reactive protein levels. Conclusion Conclusion: In this study of patients with progressed disease, outcomes were similar regardless of receipt of tocilizumab. Randomized controlled trials are needed to assess the impact of earlier administration and identify clinical characteristics to assist with selection of appropriate patients who may benefit from tocilizumab. Disclosures All Authors: No reported disclosures


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