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 28 th , 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 Grey literature searches and snowballing techniques were additionally utilized to identify yet-unpublished works and related citations.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.
【초록키워드】 COVID-19, Neutrophils, Biomarker, Biomarkers, Lymphocytes, severe COVID-19, neutrophil, interleukin-6, C-reactive protein, D-dimer, ferritin, procalcitonin, Platelets, cytokine, Cytokine storm syndrome, lactate dehydrogenase, database, Laboratory, lymphopenia, serum, interleukin, controlled trials, Aspartate aminotransferase, Laboratory parameters, Mild, laboratory biomarkers, systemic inflammation, thrombocytopenia, hematology, predictor, moderate, parameters, patients, leukocytes, Hyperferritinemia, Lactate, creatinine, Analysis, meta-analyses, leucocyte, final analysis, Grey literature, Confidence intervals, Newcastle-Ottawa Scale, laboratory data, syndrome, abstracts, aspartate, C-Reactive-Protein, IBECS, leucocytes, LILACS, mean differences, poor prognosis, serum interleukin-6 levels, severe and fatal COVID-19 cases, Final, mean difference, fatal COVID-19, objective, laboratory parameter, synonym, selected, identify, elevated, conducted, was performed, screened, Controlled, eligible, for inclusion, laboratory biomarker, retrieved, risk of bia, the cytokine storm, the MEDLINE, the Newcastle-Ottawa Scale, 【제목키워드】 Meta-analysis, Cytokine storm, systematic review, fatal COVID-19,