Differences in Inflammatory Marker Kinetics between the First and Second Wave of COVID-19 Patients Admitted to the ICU: A Retrospective, Single-Center Study.
26 Jul 2021-Journal of Clinical Medicine (Multidisciplinary Digital Publishing Institute)-Vol. 10, Iss: 15, pp 3290
TL;DR: In this paper, a single-center retrospective observational study was conducted to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels.
Abstract: Background: We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients. Methods: In a single-center retrospective observational study, ICU patients were enrolled during the first and second waves of the COVID-19 pandemic. Data were collected on patient demographics, comorbidities, laboratory results, management strategies, and complications during the ICU stay. The inflammatory response was evaluated using WBC count, CRP, PCT, and Ferritin levels on the day of admission until Day 28, respectively. Organ dysfunction was measured by the SOFA score. Results: 65 patients were admitted during the first and 113 patients during the second wave. WBC and ferritin levels were higher in the second wave. CRP and PCT showed markedly different longitudinal kinetics up until day 28 of ICU stay between the first and second wave, with significantly lower levels in the second wave. Steroid and immunomodulatory therapy use was significantly greater in the second wave. Mortality was similar in both waves. Conclusions: We found that there was a significantly reduced inflammatory response in the second wave, which is likely to be attributable to the more widespread use of immunomodulatory therapies.
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TL;DR: In this paper, a single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients.
Abstract: Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise (p = 0.167) or a WBC rise (p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.
14 citations
TL;DR: In this paper, a retrospective cohort study was conducted, evaluating all patients with critical COVID-19 admitted to the ICU of a hospital in Southern Peru from 28 March 2020 to 1 March 2021.
Abstract: Overuse of antibiotics during the Coronavirus Disease 2019 (COVID-19) pandemic could increase the selection of extensively resistant bacteria (XDR). However, it is unknown what impact they could have on the evolution of patients, particularly critically ill patients. This study aimed to evaluate the characteristics and impact of ICU-acquired infections in patients with COVID-19. A retrospective cohort study was conducted, evaluating all patients with critical COVID-19 admitted to the intensive care unit (ICU) of a hospital in Southern Peru from 28 March 2020 to 1 March 2021. Of the 124 patients evaluated, 50 (40.32%) developed a healthcare-associated infection (HAI), which occurred at a median of 8 days (IQR 6-17) after ICU admission. The proportion of patients with HAI that required ceftriaxone was significantly higher; the same was true for the use of dexamethasone. Forty bacteria isolations (80%) were classified as XDR to antibiotics, with the most common organisms being Acinetobacter baumannii (54%) and Pseudomonas aeruginosa (22%); 33% (41/124) died at the ICU during the follow-up. In the adjusted analysis, healthcare-associated infection was associated with an increased risk of mortality (aHR= 2.7; 95% CI: 1.33-5.60) and of developing acute renal failure (aRR = 3.1; 95% CI: 1.42-6.72). The incidence of healthcare infection mainly by XDR pathogens is high in critically ill patients with COVID-19 and is associated with an increased risk of complications or death.
10 citations
TL;DR: An LDRT effect is large enough in principle to provide a life-saving immunomodulatory effect, though patients treated with LDRt already near the peak of their inflammation trajectory are unlikely to see drastic reductions in that peak.
Abstract: Abstract Purpose Low dose radiation therapy (LDRT) using doses in the range of 30–150 cGy has been proposed as a means of mitigating the pneumonia associated with COVID-19. However, preliminary results from ongoing clinical trials have been mixed. The aim of this work is to develop a mathematical model of the viral infection and associated systemic inflammation in a patient based on the time evolution of the viral load. The model further proposes an immunomodulatory response to LDRT based on available data. Inflammation kinetics are then explored and compared to clinical results. Methods The time evolution of a viral infection, inflammatory signaling factors, and inflammatory response are modeled by a set of coupled differential equations. Adjustable parameters are taken from the literature where available and otherwise iteratively adjusted to fit relevant data. Simple functions modeling both the suppression of pro-inflammatory signal factors and the enhancement of anti-inflammatory factors in response to low doses of radiation are developed. The inflammation response is benchmarked against C-reactive protein (CRP) levels measured for cohorts of patients with severe COVID-19. Results The model fit the time-evolution of viral load data, cytokine data, and inflammation (CRP) data. When LDRT was applied early, the model predicted a reduction in peak inflammation consistent with the difference between the non-surviving and surviving cohorts. This reduction of peak inflammation diminished as the application of LDRT was delayed. Conclusion The model tracks the available data on viral load, cytokine levels, and inflammatory biomarkers well. An LDRT effect is large enough in principle to provide a life-saving immunomodulatory effect, though patients treated with LDRT already near the peak of their inflammation trajectory are unlikely to see drastic reductions in that peak. This result potentially explains some discrepancies in the preliminary clinical trial data.
2 citations
18 Apr 2022-Vestnik Rossiĭskoĭ akademii meditsinskikh nauk / Rossiĭskaia akademiia meditsinskikh nauk
TL;DR: In patients with COVID-19, the risk factors for transfer to IMV/NIVL in the period of 14 and 28 days from the beginning of hospitalization were identified, which enable patients mechanical ventilation stratification and to plan respiratory support resources.
Abstract: Background. The COVID-19 pandemic is associated with significant number of complications and mortality and a burden on the healthcare system. In 1015% of hospitalized patients, the invasive and non-invasive mechanical ventilation (IMV/NIMV) is required. At the same time, it is important to stratify the risk of mechanical ventilation upon admission to the hospital. Aims to identify clinical and laboratory risk factors for transfer to IMV and NIMV in hospitalized patients with COVID-19-associated pneumonia. Methods. A retrospective one-center nonrandomized study of 386 consecutive hospitalized patients with COVID-19-associated pneumonia was performed. The primary endpoints were IMV (n=22) and NIMV (n=28). Risk factors of artificial ventilation were considered for periods up to 14 and 28 days for both variants. To select a risk predictor, a univariate analysis based on Cox survival regression was performed, followed by multivariate analysis to determine risk factors at these time points. Results. After 28 days from admission the mortal exit was registered in 20 patients from 386 patients (5.2%). 22 patients (5.7%) were transferred to IMV, and 28 patients (7.3%) to NIV, and 9 of the latter were transferred later to IMV. As a result of univariate and multivariate analyzes, the risk factors for transfer to mechanical ventilation on 14th day were: age 65 years (OR=5.91), a history of stroke (OR=17.04), an increased serum level of urea (OR=6.36), LDH (OR=7.39), decreased sodium (OR=12.32), GFR 80 mL/min/1.73 m2 (OR=13.75) and platelets (OR=4.14); on the 28th day age 65 years (OR=4.58), J-wave on the ECG (OR=2.98), an increase of LDH (OR=9.99) and a decrease in albumin (OR=2.77) in serum. Predictors of the transfer of patients with COVID-19 to NIV within the period up to 14 days from the beginning of hospitalization were the age 65 years (OR=5.09), procalcitonin level in the blood 0.25 ng/ml (OR=0.19), leukocytes 11109 (OR=19.64) and increased LDH (OR=3.9). Conclusions. In patients with COVID-19, the risk factors for transfer to IMV/NIVL in the period of 14 and 28 days from the beginning of hospitalization were identified, which enable patients mechanical ventilation stratification and to plan respiratory support resources.
2 citations
TL;DR: TLC, ANC, NLR, and low platelet count were the worst hematological markers in COVID-19 in the first wave, while d-dimer and CRP were the primary prognostic inflammatory markers.
Abstract: OBJECTIVES:
To compare the values of the hematological and inflammatory markers in 1st and 4th waves to predict the outcome of COVID-19 in a hospital-based study.
METHODOLOGY:
This comparative study was conducted in the Department of Hematology, Hayatabad Medical Complex Peshawar, from April 2020 to 20 August 2021. Tests of significance (Independent t-test/Mann Whitney U test) and Chi-square test were used. Relevant information was recorded on a pre-designed proforma prepared following the study's objectives.
RESULTS:
A total of 178 patients, 71 from (the 1st wave) and 107 from (the 4th wave) with known outcomes, were studied. A statistically significant difference exists between the groups (1st vs 4th wave) regarding hematological markers; neutrophil to lymphocyte ratio (NLR) (p=0.02), Absolute Neutrophilic count (ANC) (p=0.01) and platelet count (p=0.001). Similarly, significantly higher inflammatory markers values were recorded in the 1st wave compared with the 4th wave regarding inflammatory markers; CRP (p=0.002) and D-dimer (p=0.001). During the 1st wave, Total Leukocyte Count (TLC), ANC and d-dimer were the leading prognostic indicators to predict mortality/worst outcome in COVID-19 with an Area Under Curve (AUC) of 0.74, 0.70 and 0.7 on receiver operating characteristics (ROC) respectively. In 4th, the Area under the curve (AUC) of d-dimer was 0.84 to predict mortality.
CONCLUSION:
TLC, ANC, NLR, and low platelet count were the worst hematological markers in COVID-19 in the first wave, while d-dimer and CRP were the primary prognostic inflammatory markers. Unlikely in the 4th wave, the prognostic values of hematological markers were merely significant. The d-dimer values in both the waves proved to be reliable for predicting the severity and mortality of COVID-19.
References
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TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
20,189 citations
TL;DR: In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
Abstract: BackgroundCoronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death.MethodsIn this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the final results of this assessment.ResultsA total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.92 to 1.55).ConclusionsIn patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936. opens in new tab; ISRCTN number, 50189673. opens in new tab.)
4,501 citations
TL;DR: Investigation of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19 and shows the novel coronavirus might mainly act on lymphocytes, especially T lymphocytes.
Abstract: BACKGROUND: In December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China. METHODS: Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from 10 January to 12 February 2020 were collected and analyzed. The data on laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between patients with severe and nonsevere infection. RESULTS: Of the 452 patients with COVID-19 recruited, 286 were diagnosed as having severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough, and myalgia. Severe cases tend to have lower lymphocyte counts, higher leukocyte counts and neutrophil-lymphocyte ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and were more impaired in severe cases. Both helper T (Th) cells and suppressor T cells in patients with COVID-19 were below normal levels, with lower levels of Th cells in the severe group. The percentage of naive Th cells increased and memory Th cells decreased in severe cases. Patients with COVID-19 also have lower levels of regulatory T cells, which are more obviously decreased in severe cases. CONCLUSIONS: The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis, and treatment of COVID-19.
3,532 citations
TL;DR: In this paper, the authors found that severe respiratory failure (SRF) in COVID-19 patients is driven by a unique pattern of immune dysfunction, characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.
1,580 citations
TL;DR: In this paper, the authors evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial, which used a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence or futility.
Abstract: BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).
1,235 citations