Biomarkers of cytokine storm as red flags for severe and fatal COVID-19 cases: A living systematic review and meta-analysis

Objective To describe the laboratory parameters and biomarkers of the cytokine storm syndrome associated with severe and fatal COVID-19 cases. Methods A search with standardized descriptors and synonyms was performed on November 28th, 2020 of the MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, LILACS, and IBECS to identify studies of interest. Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations. Two review authors independently screened the retrieved titles and abstracts, selected eligible studies for inclusion, extracted data from the included studies, and then assessed the risk of bias using the Newcastle-Ottawa Scale. Eligible studies were those including laboratory parameters—including serum interleukin-6 levels—from mild, moderate, or severe COVID-19 cases. Laboratory parameters, such as interleukin-6, ferritin, hematology, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer, were extracted from the studies. Meta-analyses were conducted using the laboratory data to estimate mean differences with associated 95% confidence intervals. Data synthesis The database search yielded 9,620 records; 40 studies (containing a total of 9,542 patients) were included in the final analysis. Twenty-one studies (n = 4,313) assessed laboratory data related to severe COVID-19 cases, eighteen studies (n = 4,681) assessed predictors for fatal COVID-19 cases and one study (n = 548) assessed laboratory biomarkers related to severe and fatal COVID-19 cases. Lymphopenia, thrombocytopenia, and elevated levels of interleukin-6, ferritin, D-dimer, aspartate aminotransferase, C-Reactive-Protein, procalcitonin, creatinine, neutrophils and leucocytes were associated with severe and fatal COVID-19 cases. Conclusions This review points to interleukin-6, ferritin, leukocytes, neutrophils, lymphocytes, platelets, C-Reactive Protein, procalcitonin, lactate dehydrogenase, aspartate aminotransferase, creatinine, and D-dimer as important biomarkers of cytokine storm syndrome. Elevated levels of interleukin-6 and hyperferritinemia should be considered as red flags of systemic inflammation and poor prognosis in COVID-19.

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Potensi Pemberian Tocilizumab pada Pasien COVID-19 Di ICU RSUD Ulin Banjarmasin

JAI (Jurnal Anestesiologi Indonesia) ◽

10.14710/jai.v12i3.32905 ◽

2020 ◽

Vol 12 (3) ◽

pp. 17-33

Author(s):

Rohmantuah Trada Purba ◽

Mahendratama Purnama Adhi ◽

Erna Kusumawardhani ◽

Rapto Hardian ◽

Andri Lumban Tobing

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Lactate Dehydrogenase ◽

Interleukin 6 ◽

Virus Disease ◽

C Reactive Protein ◽

Reactive Protein ◽

Corona Virus ◽

D Dimer

Latar Belakang: Corona Virus Disease 2019 (COVID-19) adalah penyakit pandemi yang menjadi masalah global yang melanda seluruh dunia. Manifestasi klinis dan tingkat keparahan penyakit COVID-19 sangat bervariasi. Pada pasien COVID-19 derajat kritis yang memerlukan perawatan di intensive care unit (ICU) telah ditemukan adanya proses badai sitokin yang meningkatkan mortalitas dan morbiditas. Interleukin-6 (IL-6) berperan dalam terjadinya badai sitokin.Kasus: Berikut kami laporkan serial kasus 5 pasien COVID-19 terkonfirmasi positif derajat sedang-kritis yang diberikan tocilizumab (TCZ) sebagai suatu IL-6 inhibitor yang memiliki potensi terapi menurunkan mortalitas dan morbiditas pasien COVID-19 derajat berat-kritis.Pembahasan: Dari 5 pasien yang diberikan TCZ, didapatkan hasil 3 pasien bisa pulang dan 2 pasien meninggal. Terdapat potensi pemberian IL-6 inhibitor karena dari patofisiologi penyakit COVID-19 yang berkaitan dengan IL-6 dan badai sitokin. IL-6 inhibitor dapat menurunkan mortalitas dan morbiditas dengan mencegah terjadinya badai sitokin. Hal ini diukur menggunakan evaluasi onset penyakit, kadar biomarker inflamasi dan gangguan koagulasi yang sering diteliti pada pasien COVID-19 seperti c-reactive protein (CRP), lactate dehydrogenase (LDH), D-Dimer dan ferritin.Kesimpulan: Pemberian TCZ memiliki potensi efek terapeutik jika diberikan pada onset penyakit <10 hari. Perlu dilakukan penelitian lebih lanjut untuk menilai efek terapeutik dan timing pemberian yang tepat.

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Are SOFA score, PaO2/FiO2 ratio, lymphocytes levels, total bilirubin, lactate dehydrogenase, ferritin, C-reactive protein and interleukin-6 significantly normalized following TPE completion: Is this fact or fiction?

Journal of Critical Care ◽

10.1016/j.jcrc.2021.04.015 ◽

2021 ◽

Author(s):

Patrick M. Honore ◽

Sebastien Redant ◽

Thierry Preseau ◽

Keitiane Kaefer ◽

Leonel Barreto Gutierrez ◽

...

Keyword(s):

Lactate Dehydrogenase ◽

Sofa Score ◽

Interleukin 6 ◽

Total Bilirubin ◽

C Reactive Protein ◽

Reactive Protein

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Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome

Viruses ◽

10.3390/v13061067 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1067

Author(s):

Oleksandr Oliynyk ◽

Wojciech Barg ◽

Anna Slifirczyk ◽

Yanina Oliynyk ◽

Vitaliy Gurianov ◽

...

Keyword(s):

Macrophage Activation Syndrome ◽

Macrophage Activation ◽

Cytokine Storm ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

C Reactive Protein ◽

Treatment Results ◽

Reactive Protein ◽

Median Serum ◽

D Dimer

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, p < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p = 0.043), RR = 2.1 (95% CI 1.0–4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p = 0.013), RR = 0.50 (95% CI 0.25–0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.

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The role of IL-6 receptor inhibitor treatment in critical patient monitoring with COVID-19

10.22514/sv.2021.068 ◽

2021 ◽

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Lactate Dehydrogenase ◽

Critically Ill ◽

Critically Ill Patients ◽

C Reactive Protein ◽

Reactive Protein ◽

Group 2 ◽

D Dimer

Objectives: The COVID-19 disease can manifest itself with acute respiratory distress syndrome, renal failure, and septic shock in critically ill patients. There are opinions that there is a correlation between high IL-6 levels and disease severity. In our intensive care unit, we evaluated the changes in the laboratory data and radiological involvement severity of our patients who underwent tocilizumab treatment and examined the appropriate laboratory parameter in the treatment follow-up and its effect on survival. Methods: In the critical patient follow-up of COVID-19, 17 of the 23 patients treated with tocilizumab had a mortal course (Group 1) and the remaining 6 (Group 2) were. The C-reactive protein, lactate dehydrogenase, IL-6, D-dimer, procalcitonin, albumin, and ferritin values, which were routinely screened in our clinic on the day of tocilizumab treatment and the 5th day after, were recorded. Both the change between the two groups and the change between days 1 and 5 were analyzed. Results: A total of 23 patients (55.35 ± 13.31 years) were included in the study. The computed tomography severity score assessed at the intensive care unit admission was statistically significantly higher in Group 2. The procalcitonin and lactate dehydrogenase values measured on day 5 after tocilizumab were significantly lower in Group 2. On the 5th day after treatment, the levels of C-reactive protein, ferritin, chest X-rays, IL-6 and D-dimer statistically significantly changed compared to the first day of the treatment. In correlation with the decrease in PCT as of the 5th day after tocilizumab administration, an increasing tendency was observed in 28-day survival. Conclusion: This study demonstrated that tocilizumab treatment may positively contribute to the treatment by decreasing cytokine levels. PCT and LDH follow-up before and after treatment in critically ill patients who are receiving tocilizumab treatment can give an idea about survival.

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Inflammatory Biomarkers Do Not Differ Between Persistently Seronegative vs Seropositive People With HIV After Treatment in Early Acute HIV Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa383 ◽

2020 ◽

Vol 7 (9) ◽

Author(s):

Catherine W Cai ◽

Suteeraporn Pinyakorn ◽

Eugène Kroon ◽

Mark de Souza ◽

Donn J Colby ◽

...

Keyword(s):

Hiv Infection ◽

Chronic Inflammation ◽

Interleukin 6 ◽

Inflammatory Biomarkers ◽

C Reactive Protein ◽

Acute Hiv Infection ◽

Reactive Protein ◽

Acute Hiv ◽

Cluster Of Differentiation ◽

D Dimer

Abstract Persistent viral activity may cause enduring seropositivity and inflammation in treated people with HIV (PWH). We compared inflammatory biomarkers between early treated PWH who remained seronegative or seroconverted and found similar levels of D-dimer, soluble cluster of differentiation 14, C-reactive protein, and interleukin-6, indicating that seronegativity does not affect chronic inflammation in early treated PWH.

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446. Prognostic Value of Absolute Lymphocyte Count for Disease Severity and Clinical Outcomes in Adult COVID-19 Inpatients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.645 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S324-S324

Author(s):

Jianli Niu ◽

Candice Sareli ◽

Maria Deane ◽

Aharon E Sareli

Keyword(s):

Lactate Dehydrogenase ◽

Clinical Outcomes ◽

Disease Severity ◽

Interleukin 6 ◽

Lymphocyte Count ◽

Absolute Lymphocyte Count ◽

Serum Levels ◽

C Reactive Protein ◽

Icu Admission ◽

Reactive Protein

Abstract Background Lymphopenia has been reported as a relatively frequent finding in patients with coronavirus disease 2019 (COVID-19). This study aimed to assess the use of absolute lymphocyte count (ALC) as a prognostic biomarker for disease severity and clinical outcomes. Methods A cohort of adult patients with COVID-19 admitted to Memorial Healthcare System, Hollywood, Florida from March 7, 2020 to January 18, 2021 was retrospectively analyzed. An absolute lymphocyte count (ALC) < 1.1 × 109/L was used as cutoff point to define lymphopenia. Correlations of ALC upon admission with age and serum levels of C-reactive protein, interleukin-6, lactate dehydrogenase, and creatinine were analyzed. Univariate and multivariate regression models were developed to assess the association of lymphopenia with the risk of ICU admission and clinical outcomes. Results 4,485 hospitalized patients were included in the final analyses. Median age was 61 (interquartile range, 47-73) years and 2,311 (51.5%) were men. Lymphopenia was more frequent in patients admitted to the ICU compared to those that were not admitted to the ICU, with an odds ratio of 2.14 (95% conﬁdence interval [CI], 1.78-2.56, p < .0001) (Figure 1). The actual value of the ALC was negatively correlated with age and serum levels of C-reactive protein, interleukin-6, lactate dehydrogenase, and creatinine (all p < 0.005). Patients with lymphopenia (n=2,409) compared to those without lymphopenia (n=2,076) had multivariable-adjusted odds ratios of 1.85 (95% CI, 1.53-2.24) for ICU admission, 2.08 (95% CI, 1.67-2.58) for intubation, 1.98 (95% CI, 1.31-3.00) for development of acute kidney failure, and 2.23 (95% CI, 1.79-2.79) for in-hospital mortality (Table 1). Analyses were adjusted for age, gender, race, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, malignancy, obesity, and smoking. Conclusion Lymphopenia in adult COVID -19 hospitalized patients was associated with increased risk of disease severity (as evidenced by need for ICU admission) and poor clinical outcomes. Absolute lymphocyte count may help with prognostication in individuals hospitalized with COVID-19. Disclosures All Authors: No reported disclosures

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