Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and meta-analysis

Abstract

ObjectiveTo evaluate association between biomarkers and outcomes in COVID-19 hospitalised patients. COVID-19 pandemic has been a challenge. Biomarkers have always played an important role in clinical decision making in various infectious diseases. It is crucial to assess the role of biomarkers in evaluating severity of disease and appropriate allocation of resources.Design and settingSystematic review and meta-analysis. English full text observational studies describing the laboratory findings and outcomes of COVID-19 hospitalised patients were identified searching PubMed, Web of Science, Scopus, medRxiv using Medical Subject Headings (MeSH) terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from 1 December 2019 to 15 August 2020 following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines.ParticipantsStudies having biomarkers, including lymphocyte, platelets, D-dimer, lactate dehydrogenase (LDH), C reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT) and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers.Main outcome measuresComposite poor outcomes include intensive care unit admission, oxygen saturation <90%, invasive mechanical ventilation utilisation, severe disease, in-hospital admission and mortality. The OR and 95% CI were obtained and forest plots were created using random-effects models. Publication bias and heterogeneity were assessed by sensitivity analysis.Results32 studies with 10 491 confirmed COVID-19 patients were included. We found that lymphopenia (pooled-OR: 3.33 (95% CI: 2.51–4.41); p<0.00001), thrombocytopenia (2.36 (1.64–3.40); p<0.00001), elevated D-dimer (3.39 (2.66–4.33); p<0.00001), elevated CRP (4.37 (3.37–5.68); p<0.00001), elevated PCT (6.33 (4.24–9.45); p<0.00001), elevated CK (2.42 (1.35–4.32); p=0.003), elevated AST (2.75 (2.30–3.29); p<0.00001), elevated ALT (1.71 (1.32–2.20); p<0.00001), elevated creatinine (2.84 (1.80–4.46); p<0.00001) and LDH (5.48 (3.89–7.71); p<0.00001) were independently associated with higher risk of poor outcomes.ConclusionOur study found a significant association between lymphopenia, thrombocytopenia and elevated levels of CRP, PCT, LDH, D-dimer and COVID-19 severity. The results have the potential to be used as an early biomarker to improve the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic.

Risk factors for severe and critically ill COVID‐19 patients: A review

“…A CRP cutoff value of 34.67 mg/L (sensitivity 82.3%, specificity 73%) discriminates severe and nonsevere COVID‐19 pneumonia relative to D‐dimer 207 . Out of 32 studies, 20 have shown a nearly four‐fold higher risk of poor outcomes in COVID‐19 patients with elevated CRP 208 . Laboratory analysis of patients admitted to the ICU showed an overall increase of CRP levels in the first seven days, peaking between days two and three 48 …”

Calprotectin, an Emerging Biomarker of Interest in COVID-19: A Systematic Review and Meta-Analysis

“…Recent studies state that calprotectin level is raised in severe COVID-19 and thus could discriminate the various forms of COVID-19 as well as predict the outcome in terms of who ends up in the intensive care unit (ICU) or would die [ 12 , 14 ]. Recent studies suggest that several biomarkers including lymphopenia, and raised C-reactive protein (CRP), procalcitonin (PCT), D-dimer, creatine kinase (CK), aspartate aminotransferase (AST), alanine transaminase, creatinine and serum amyloid A are significantly associated with poor prognosis in COVID-19 patients [ 15 , 16 , 17 ]. However, there has been growing evidence that calprotectin is a better biomarker than the aforementioned markers [ 8 , 12 , 14 , 18 ].…”

COVID-19 pneumonia and the appropriate use of antibiotics

“… 4 , 5 From accumulating data and reports, there appears to be a clear association between elevated concentrations of procalcitonin and increasing COVID-19 disease severity, despite a variety of cutoffs chosen. 6 , 7 …”