Clinical Laboratory Parameters Associated with Severe or Critical Novel Coronavirus Disease 2019 (COVID 19) A Systematic Review and Meta analysis
Background: To date, several clinical laboratory parameters associated with COVID 19 severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID 19 disease Methods: We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre print server. We included hospital based observational studies reporting clinical laboratory parameters of confirmed cases of COVID 19 and excluded studies having large proportions >10% of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta analyses were done using random effects model. Meta median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Results: Forty five studies in 6 countries were included. Compared to non severe COVID 19 cases, severe or critical COVID 19 disease was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] x109 cells/L) and lower lymphocyte and CD4 counts with MMD (95% CI) of 0.39 0.47, 0.31) x109 cells/L and 204.9 302.6, 107.1) cells/l, respectively. Other notable results were observed for C reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L) interleukin 6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml, Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml) and D dimer (MMD: 0.65 [0.45, 0.85] mg/ml) Conclusions and Relevance: Relative to non severe COVID 19, severe or critical COVID 19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID 19.
medRxiv