scholarly journals Prognostic and predictive biomarkers in patients with COVID-19 treated with tocilizumab in a randomised controlled trial

2020 ◽  
Author(s):  
Jennifer Tom ◽  
Min Bao ◽  
Larry Tsai ◽  
Aditi Qamra ◽  
David Summers ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Outcomes ◽  
Hospital Discharge ◽  
Interleukin 6 ◽  
Clinical Status ◽  
Predictive Biomarkers ◽  
Ordinal Scale ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
D Dimer

SummaryBackgroundRetrospective observational studies suggest that interleukin-6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, lymphocytes, monocytes, neutrophils, D-dimer, and platelets are associated with disease progression, treatment outcomes, or both, in patients with COVID-19 pneumonia. We explored these candidate prognostic and predictive biomarkers with efficacy outcomes after treatment with tocilizumab, an anti–IL-6 receptor antibody using data from the COVACTA trial for patients hospitalised with severe COVID-19 pneumonia.MethodsCandidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomisation) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses.FindingsModelling in the placebo arm showed all candidate biomarkers except LDH and D-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modelling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction p=0.03), mechanical ventilation (predictive interaction p=0.01), and clinical status (predictive interaction p=0.02) compared with placebo.InterpretationMultiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28.RESEARCH IN CONTEXTEvidence before this studyThe efficacy and safety of the anti–interleukin-6 receptor antibody tocilizumab in the treatment of patients hospitalised with COVID-19 pneumonia was investigated in COVACTA, a double-blind, randomised, placebo-controlled trial. The primary endpoint of improved clinical status on a seven-category ordinal scale (1, discharged/ready for discharge; 7, death) at day 28 was not met in this trial. Among the secondary endpoints, no difference in mortality at day 28 was observed, but time to hospital discharge was shorter in the tocilizumab group. Subgroup analysis suggested there might be a treatment benefit in patients grouped according to their ordinal scale category at baseline.We searched PubMed on September 14, 2020, using the terms “tocilizumab AND (COVID-19 OR coronavirus) AND biomarker” with no language or date restrictions. The search retrieved 18 articles, four of which identified laboratory measures as potential biomarkers in patients who received tocilizumab for the treatment of COVID-19 pneumonia. The biomarkers reported in these studies include interleukin-6, C-reactive protein, ferritin, fibrinogen, liver transaminases, lymphocytes, platelets, and D-dimer. However, these previous studies were single-centre, retrospective, observational studies. Larger, prospective, controlled trials are needed to investigate potential prognostic and predictive biomarkers to assess the outcomes and response to treatments for COVID-19.Added value of this studyThis exploratory analysis of data from COVACTA demonstrated interleukin-6, C-reactive protein, ferritin, neutrophils (percentage and absolute count), neutrophil-to-lymphocyte ratio, lymphocytes (percentage and absolute count), monocytes (percentage), and platelets as strong prognostic biomarkers in patients hospitalised with severe COVID-19 pneumonia. More important, ferritin showed predictive value for tocilizumab treatment effects on day 28 clinical outcomes of mortality, mechanical ventilation (among the subgroup of patients not receiving mechanical ventilation at randomisation), and clinical status compared with placebo.Implications of all the available evidenceIn patients with elevated levels of ferritin at baseline, tocilizumab decreased the probability of death, mechanical ventilation, and worsening clinical status at day 28 compared with placebo, suggesting that ferritin might be useful as a predictive biomarker of efficacy outcomes for tocilizumab in patients with severe COVID-19 pneumonia.

scholarly journals The Plasmatic Aldosterone and C-Reactive Protein Levels, and the Severity of Covid-19: The Dyhor-19 Study

2020 ◽  
Vol 9 (7) ◽  
pp. 2315 ◽  
Author(s):  
Orianne Villard ◽  
David Morquin ◽  
Nicolas Molinari ◽  
Isabelle Raingeard ◽  
Nicolas Nagot ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Clinical Course ◽  
Clinical Status ◽  
Plasma Renin ◽  
Ordinal Scale ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein

Background. The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. Since the RAAS can induce and modulate pro-inflammatory responses, it could play a key role in the pathophysiology of Covid-19. Thus, we aimed to determine the levels of plasma renin and aldosterone as indicators of RAAS activation in a series of consecutively admitted patients for Covid-19 in our clinic. Methods. Plasma renin and aldosterone levels were measured, among the miscellaneous investigations needed for Covid-19 management, early after admission in our clinic. Disease severity was assessed using a seven-category ordinal scale. Primary outcome of interest was the severity of patients’ clinical courses. Results. Forty-four patients were included. At inclusion, 12 patients had mild clinical status, 25 moderate clinical status and 7 severe clinical status. In univariate analyses, aldosterone and C-reactive protein (CRP) levels at inclusion were significantly higher in patients with severe clinical course as compared to those with mild or moderate course (p < 0.01 and p = 0.03, respectively). In multivariate analyses, only aldosterone and CRP levels remained positively associated with severity. We also observed a positive significant correlation between aldosterone and CRP levels among patients with an aldosterone level greater than 102.5 pmol/L. Conclusions. Both plasmatic aldosterone and CRP levels at inclusion are associated with the clinical course of Covid-19. Our findings may open new perspectives in the understanding of the possible role of RAAS for Covid-19 outcome.

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

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.

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

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) &lt; 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 &lt; .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 &lt; 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

scholarly journals Risk factors for clinical progression in patients with COVID-19: a retrospective study of electronic health record data in the United Kingdom

2020 ◽  
Author(s):  
Robert A Fletcher ◽  
Thomas Matcham ◽  
Marta Tibúrcio ◽  
Arseni Anisimovich ◽  
Stojan Jovanović ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Logistic Regression ◽  
Body Temperature ◽  
Blood Cell ◽  
Severe Disease ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Multivariable Logistic Regression ◽  
D Dimer

Background: The novel coronavirus disease 2019 (COVID-19) outbreak presents a significant threat to global health. A better understanding of patient clinical profiles is essential to drive efficient and timely health service strategies. In this study, we aimed to identify risk factors for a higher susceptibility to symptomatic presentation with COVID-19 and a transition to severe disease. Methods: We analysed data on 2756 patients admitted to Chelsea & Westminster Hospital NHS Foundation Trust between 1st January and 23rd April 2020. We compared differences in characteristics between patients designated positive for COVID-19 and patients designated negative on hospitalisation and derived a multivariable logistic regression model to identify risk factors for predicting risk of symptomatic COVID-19. For patients with COVID-19, we used univariable and multivariable logistic regression to identify risk factors associated with progression to severe disease defined by: 1) admission to the hospital AICU, 2) the need for mechanical ventilation, 3) in-hospital mortality, and 4) at least one measurement of elevated D-dimer (equal or superior to 1,000 ug/L) indicative of increased risk of venous thromboembolism. Results: The patient population consisted of 1148 COVID-19 positive and 1608 COVID-19 negative patients. Age, sex, self-reported ethnicity, C-reactive protein, white blood cell count, respiratory rate, body temperature, and systolic blood pressure formed the most parsimonious model for predicting risk of symptomatic COVID-19 at hospital admission. Among 1148 patients with COVID-19, 116 (10.1%) were admitted to the AICU, 71 (6.2%) required mechanical ventilation, 368 (32.1%) had at least one record of D-dimer levels ≥1,000 μg/L, and 118 patients died. In the multivariable logistic regression, age (OR = 0.953 per 1 year, 95% CI: 0.937-0.968) C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.007), and white blood cell counts (OR = 1.059 per 109/L, 95% CI: 1.010-1.111) were found to be associated with admission to the AICU. Age (OR = 0.973 per 1 year, 95% CI: 0.955-0.990), C-reactive protein (OR = 1.003 per 1 mg/L, 95% CI: 1.000-1.006) and sodium (OR = 0.915 per 1 mmol/L, 0.868-0.962) were associated with mechanical ventilation. Age (OR = 1.023 per 1 year, 95% CI: 1.004-1.043), CRP (OR = 1.004 per 1 mg/L, 95% CI: 1.002-1.006), and body temperature (OR = 0.723 per 1oC, 95% CI: 0.541-0.958) were associated with elevated D-dimer. For mortality, we observed associations with age (OR = 1.060 per 1 year, 95% CI: 1.040-1.082), female sex (OR = 0.442, 95% CI: 0.442, 95% CI: 0.245-0.777), Asian ethnic background (OR = 2.237 vs White ethnic background, 95% CI: 1.111-4.510), C-reactive protein (OR = 1.004 per 1 mg/L, 95% CI: 1.001-1.006), sodium (OR = 1.038 per 1 mmol/L, 95% CI: 1.001-1.006), and respiratory rate (OR = 1.054 per 1 breath/min, 95% CI: 1.024-1.087). Conclusion: Our analysis suggests there are several demographic, clinical and laboratory findings associated with a symptomatic presentation of COVID-19. Moreover, significant associations between patient deterioration were found with age, sex and specific blood markers, chiefly C-reactive protein, and could help early identification of patients at risk of poorer prognosis. Further work is required to clarify the extent to which our observations are relevant beyond current settings.

scholarly journals Effect of Alzheimer Caregiving Stress and Age on Frailty Markers Interleukin-6, C-Reactive Protein, and D-Dimer

2006 ◽  
Vol 61 (9) ◽  
pp. 963-969 ◽  
Author(s):  
R. von Kanel ◽  
J. E. Dimsdale ◽  
P. J. Mills ◽  
S. Ancoli-Israel ◽  
T. L. Patterson ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Caregiving Stress ◽  
D Dimer

scholarly journals Extended Thromboprophylaxis in Patients with COVID-19

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1065-1065
Author(s):  
Wei Zhao ◽  
Pin Li ◽  
Scott Kaatz ◽  
Katie Latack ◽  
Lonni Schultz ◽  
...  
Keyword(s):  
High Risk ◽  
Hospital Discharge ◽  
Research Funding ◽  
C Reactive Protein ◽  
Post Discharge ◽  
Event Time ◽  
Reactive Protein ◽  
Short Course ◽  
History Of ◽  
D Dimer

Abstract Introduction Patients hospitalized with COVID-19 have an increased incidence of venous thromboembolism (VTE) and arterial thromboembolism (ATE) events. These thrombotic events increase readmission and mortality rate in COVID-19 survivors who are recently discharged from hospital. To lower the risk of VTE, a short course of post-discharge anticoagulation at either prophylactic or therapeutic dose has been variably prescribed among different facilities to COVID-19 patients. This practice, however, is challenged by less than 3% incidence of VTE in unselected patients. The net clinical benefit of extended thromboprophylaxis beyond hospitalization remains unclear. Methods We conducted a retrospective multicenter observational study of 5613 hospitalized COVID-19 patients. After applying the inclusion and exclusion criteria, 2838 patients were included in statistical analysis. Patients were excluded if they had negative SARS-CoV-2 PCR, remained hospitalized at the time of analysis, or were discharged to hospice service. The first symptomatic ATE and VTE events up to 90 days after patients' discharge from their index admission for COVID-19 were identified using ICD-10 codes, and subsequently validated by chart review. The predictors for post-discharge VTE were identified using multivariate logistic regression. The average protective effect of anticoagulation was assessed using inverse propensity score weighting. Results The mean age (SD) of our cohort was 63.4 (16.7) years old and 47.6% were male. Black, white and other races were 38.9%, 50.7% and 10.3%, respectively. Thirty-six (1.3%) patients developed post-discharge VTE events that require hospital visits (18 deep vein thromboses, 16 pulmonary embolisms and 2 portal vein thromboses). Fifteen (0.5%) patients developed post-discharge ATE events (14 acute coronary syndromes and 1 transient ischemic attack). The incidence of VTE decreased with time (p &lt;.001) with the median event time of 16 days (Figure 1). The incidence of ATE was unchanged with time (p =.369) with the median event time of 37 days (Figure 1). Patients who had a history of VTE (OR=3.24, 95% CI 1.34-7.86), peak D-dimer &gt;3 µg/mL (OR=3.76, 95% CI 1.86-7.57), and predischarge C-reactive protein &gt;10 mg/dL (OR=3.02, 95% CI 1.45-6.29) were at a high risk of developing VTE after hospital discharge (Figure 2). A short course of prophylactic or therapeutic anticoagulation after hospital discharge markedly reduced VTE (OR=0, 95% CI 0-0, p&lt;.001, and OR=0.176, 95% CI 0.04-0.75, p=.02, respectively). Conclusions Although extended thromboprophylaxis in unselected COVID-19 patients is not recommended, post-discharge anticoagulation may be considered in high-risk patients who have a history of VTE, peak D-dimer &gt;3 µg/mL and predischarge C-reactive protein &gt;10 mg/dL if their bleeding risk is low. Our study has provided the first evidence to guide the selection of hospitalized COVID-19 patients who may benefit from post-discharge anticoagulation. Figure 1 Figure 1. Disclosures Kaatz: Gilead: Consultancy; Novartis: Consultancy; CSL Behring: Consultancy; Bristol Myer Squibb: Consultancy, Research Funding; Alexion: Consultancy; Pfizer: Consultancy; Janssen: Consultancy, Research Funding; Osmosis Research: Research Funding.

scholarly journals Risk stratification of hospitalized COVID-19 patients through comparative studies of laboratory results with influenza

2020 ◽  
Author(s):  
Yang Mei ◽  
Samuel E Weinberg ◽  
Lihui Zhao ◽  
Chao Qi ◽  
Adam Frink ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Clinical Outcomes ◽  
Laboratory Data ◽  
Rapid Decline ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Laboratory Courses ◽  
Discharge Rates ◽  
Laboratory Results ◽  
D Dimer

Background The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 overlaps with the flu season. Methods We compared clinical and laboratory results from 719 influenza and 973 COVID-19 patients from January to April 2020. We compiled laboratory results from the first 14 days of the hospitalized patients using parameters that are most significantly different between COVID-19 and influenza and hierarchically clustered COVID-19 patients based on these data. The clinical outcomes were compared among different clusters. Results Temporal analyses of laboratory results revealed that compared to influenza, patients with COVID-19 exhibited a continued increase in the white blood cell count, rapid decline of hemoglobin, more rapid increase in blood urea nitrogen (BUN) and D-dimer, and higher level of alanine transaminase, C-reactive protein, ferritin, and fibrinogen. Using these results, we sub-classified the COVID-19 patients into 5 clusters through a hierarchical clustering analysis. We then reviewed the medical record of these patients and risk stratified them based on the clinical outcomes. The cluster with the highest risk showed 27.8% fatality, 94% ICU admission, 94% intubation, and 28% discharge rates compared to 0%, 38%, 22%, and 88% in the lowest risk cluster, respectively. Patients in the highest risk cluster had leukocytosis including neutrophilia and monocytosis, severe anemia, higher BUN, creatinine, D-dimer, alkaline phosphatase, bilirubin, and troponin. Conclusions There are significant differences in the clinical and laboratory courses between COVID-19 and influenza. Risk stratification in hospitalized COVID-19 patients using laboratory data could be useful to predict clinical outcomes and pathophysiology of these patients.

scholarly journals ASSOCIATION BETWEEN ELEVATED HIGH SENSITIVITY CARDIAC-TROPONIN I LEVELS AND INCREASE IN LEVELS OF C-REACTIVE PROTEIN, INTERLEUKIN-6, D-DIMER, AND CONSEQUENT CARDIAC INJURY AND MORTALITY FOR PATIENTS WITH CORONAVIRUS DISEASE 2019: A META-ANALYSIS

2021 ◽  
pp. 160-166
Author(s):  
DHEAA SHAMIH ZAGEER ◽  
SUNDUS FADHIL HANTOOSH ◽  
WATHIQ Q SH. ALI
Keyword(s):  
Interleukin 6 ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Meta Analysis ◽  
Cardiac Injury ◽  
High Sensitivity ◽  
Cardiac Troponin I ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
D Dimer

Objectives: This meta-analysis aims to investigate the role of high sensitivity-cardiac troponin I (hs-cTnI) as a prognostic factor for cardiac injury and as a risk factor of death for patients with coronavirus disease 2019 (COVID-19). This meta-analysis studies the impact of hs-cTnI elevated levels on C-reactive protein (C-RP) protein, interleukin-6 (IL-6), and D-dimer (DD) levels in COVID-19 affected individuals. Methods: Of 557 downloaded articles according to chosen criteria for this meta-analysis, 11 were finally chosen as they met the criteria. Results: Male and elderly individuals were noticeably prone to COVID-19 infection and considerably underwent death in comparison with female and young individuals. Levels of hs-cTn I, C-RP, IL-6, and DD were significantly higher among dead compare to survivors for COVID-19 affected individuals. Conclusions: Levels of C-RP, IL-6, and DD were considerably high and in linear relation with elevated hs-cTn I levels. Hs-cTn I can be considered a reliable marker for COVID-19 infection prognosis and potent predictor of decease.

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

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253894
Author(s):  
Ana Karla G. Melo ◽  
Keilla M. Milby ◽  
Ana Luiza M. A. Caparroz ◽  
Ana Carolina P. N. Pinto ◽  
Rodolfo R. P. Santos ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Interleukin 6 ◽  
Aspartate Aminotransferase ◽  
Laboratory Data ◽  
Cytokine Storm ◽  
Red Flags ◽  
C Reactive Protein ◽  
Laboratory Parameters ◽  
Reactive Protein ◽  
D Dimer

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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