key: cord-0852629-f15bxcqc authors: Israni, Alisha; Goulden, Christopher J.; Harky, Amer title: Laboratory biomarkers and prognosis in Covid‐19, where do we stand? date: 2021-09-13 journal: Rev Med Virol DOI: 10.1002/rmv.2296 sha: 2fb245d01648ebda5efbf47a9f330a1e0e4af1d6 doc_id: 852629 cord_uid: f15bxcqc nan reviews and meta-analyses have identified increased levels of white blood cells (WBC), lymphopenia (especially CD8+ cells), thrombocytopaenia, increased lactate-dehydrogenase (LDH), creatine kinase (CK), C-reactive protein (CRP), D-dimer and levels of proinflammatory cytokines (such as IL-6) to be associated with more severe inflammatory responses and consequent lung damages, with a greater need for intensive care unit (ICU) support and increased mortality rates. [2] [3] [4] [5] However, a greater knowledge of the prognostic biomarkers for patients with Covid-19 could enhance the timing of interventions, and the better allocation of resources, since hospital and ICU capacity is stretched across healthcare systems during this pandemic. 2, 4 The systematic review and meta-analysis by Le Huu Nhat Minh and colleagues collated clinical information from 62,909 confirmed cases of Covid-19 across 148 studies; with an aim to identify the laboratory factors associated with Covid-19, and how they relate to the severity of infection. 6 Specific blood biomarkers associated with increased disease severity include reduced lymphocytes as they are the key to maintain adequate immune responses. 4 Specifically, to Covid-19, it has been hypothesised that lymphocytes express SARS-CoV-2 receptor ACE2, and hence are attacked and depleted by fellow lymphocytes. 4 Raised proinflammatory cytokines in severe Covid-19 illness, including TNFa and IL-6, are likely to result in lymphocyte-induced apoptosis, posing an additional mechanism for depleted lymphocyte levels. 4 There is evidence to suggest that increased levels of proinflammatory mediators, including CRP, CK and LDH, are associated with increased disease severity. 4 CRP is a non-specific acute phase protein, produced via IL-6 in the liver, and hence is associated with increased inflammation and more severe infection. 4, 5, 10 Raised CK is reflective of muscular damage, which is likely to be due to antigen-antibody deposition in muscle, and increased circulating viral toxins. 11 One study found an approximate fourfold increase in CK in patients who had a more severe disease course of Covid-19. 4 Additionally, rhabdomyolysis has been reported as a possible late complication of Covid-19 infection. 12 Proportion of asymptomatic coronavirus disease 2019: a systematic review and meta-analysis Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study Biomarkers and outcomes of COVID-19 hospitalisations: systematic review and meta-analysis Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19 Clinical and laboratory factors associated with coronavirus disease 2019 (Covid-19): a systematic review and meta-analysis Liver disease and outcomes among COVID-19 hospitalized patients -a systematic review and meta-analysis COVID-19) Dashboard D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19. J Thromb Haemostasis C-reactive protein levels in the early stage of COVID-19 D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19 COVID-19 and multiorgan response COVID-19: abnormal liver function tests The diagnostic and prognostic role of neutrophil-to-lymphocyte ratio in COVID-19: a systematic review and meta-analysis The role of biomarkers in diagnosis of COVID-19 -a systematic review Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage Laboratory biomarkers of COVID-19 disease severity and outcome: findings from a developing country