Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis

Abstract Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.

[1]  Yan Zhao,et al.  Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. , 2020, JAMA.

[2]  J. Low,et al.  Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. , 2020, JAMA.

[3]  Yixiao Lin,et al.  Clinical analysis of risk factors for severe patients with novel coronavirus pneumonia , 2020 .

[4]  G. B. Tan,et al.  Hematologic parameters in patients with COVID‐19 infection , 2020, American journal of hematology.

[5]  G -Q Qian,et al.  Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series , 2020, QJM : monthly journal of the Association of Physicians.

[6]  I. Hozo,et al.  Estimating the mean and variance from the median, range, and the size of a sample , 2005, BMC medical research methodology.

[7]  Rui-guang Zhang,et al.  Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  Qiurong Ruan,et al.  Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China , 2020, Intensive Care Medicine.

[9]  Jiang Gu,et al.  Pathology and Pathogenesis of Severe Acute Respiratory Syndrome , 2007, The American Journal of Pathology.

[10]  Mario Plebani,et al.  Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis , 2020, Clinica Chimica Acta.

[11]  Wei Liu,et al.  Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease , 2020, Chinese medical journal.

[12]  D. Dwyer,et al.  Effects of severe acute respiratory syndrome (SARS) coronavirus infection on peripheral blood lymphocytes and their subsets , 2005, International Journal of Infectious Diseases.

[13]  Xiao Chen,et al.  Platelet‐to‐lymphocyte ratio is associated with prognosis in patients with coronavirus disease‐19 , 2020, Journal of medical virology.

[14]  Y. Hu,et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China , 2020, The Lancet.

[15]  F. Stentz,et al.  Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1 beta and IL-6 levels are consistent and efficient predictors of outcome over time. , 1995, Chest.

[16]  C. Akdis,et al.  Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China , 2020, Allergy.

[17]  J. Xiang,et al.  Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study , 2020, The Lancet.

[18]  Jing Yuan,et al.  Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury , 2020, Science China Life Sciences.

[19]  Xin Zhou,et al.  Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China , 2020, The Journal of Emergency Medicine.

[20]  C Chen,et al.  [Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19]. , 2020, Zhonghua xin xue guan bing za zhi.

[21]  Chuan Qin,et al.  Dysregulation of immune response in patients with COVID-19 in Wuhan, China , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[22]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[23]  Brandon Michael Henry,et al.  COVID-19, ECMO, and lymphopenia: a word of caution , 2020, The Lancet Respiratory Medicine.

[24]  Mario Plebani,et al.  Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis , 2020, Clinica Chimica Acta.

[25]  L. Chen,et al.  [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. , 2020, Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases.

[26]  K. Yuen,et al.  Clinical Characteristics of Coronavirus Disease 2019 in China , 2020, The New England journal of medicine.

[27]  Ting Yu,et al.  Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study , 2020, The Lancet Respiratory Medicine.