A Comprehensive Appraisal of Laboratory Biochemistry Tests as Major Predictors of COVID-19 Severity

Abstract

<jats:p> Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. </jats:p><jats:p> Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. </jats:p><jats:p> Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. </jats:p><jats:p> Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. </jats:p><jats:p> The best cut-offs for death prediction were &gt;731 U/L for lactate dehydrogenase and ≤18 g/L for albumin, while a lactate dehydrogenase activity &lt;425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. </jats:p><jats:p> Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use. </jats:p>

Ferritin in the coronavirus disease 2019 (COVID‐19): A systematic review and meta‐analysis

“…A total of 777 records were collected by the databases and manual searching. After the exclusion of the duplicates, review articles, case reports, pre‐printed versions without peer‐review, and irrelevant studies by title or abstract screening, 187 studies remained for full‐text review; 52 studies 6,17‐67 were finally included into the meta‐analysis, and 18 studies were included in the qualitative synthesis (Figure 1). A total of 52 records involving 10 614 COVID‐19 patients confirmed between December 25, 2019, and June 1, 2020, were included.…”

“…Most of the selected studies (29/52) were performed in China 6,17‐25,27‐32,35‐37,50,59‐67 . Ten studies were performed in multicenters 6,17,23,34,45,49,57,58,60,64 . Among the included studies, 17 compared the ferritin level between groups with different severity of COVID‐19 18‐22,34,35,37‐39,44,50,53,56,61,64,65 and 18 compared its level between non‐survivors and survivors 6,17,23,24,26‐29,40‐42,45,46,52,55,58,63,66 .…”

“…Ten studies were performed in multicenters 6,17,23,34,45,49,57,58,60,64 . Among the included studies, 17 compared the ferritin level between groups with different severity of COVID‐19 18‐22,34,35,37‐39,44,50,53,56,61,64,65 and 18 compared its level between non‐survivors and survivors 6,17,23,24,26‐29,40‐42,45,46,52,55,58,63,66 . The characteristics of all studies included in this meta‐analysis are listed in Table 1.…”

Hypoalbuminemia and elevated D-dimer in COVID-19 patients: a call for result harmonization

“…We recently performed a study on 427 COVID-19 patients deriving cut-off values for six biochemistry tests showing high sensitivity and negative predictive value for excluding the need of admission in intensive care unit (ICU) during hospital stay [2]. Particularly, the best cut-offs for serum albumin and plasma D-dimer, the latter expressed as fibrinogen-equivalent units (FEU), associated with the ability in detecting patients not at risk of ICU admission, were ≥29 g/L and <1704 μg/L FEU, respectively.…”

Linking lactate dehydrogenase to the severity of COVID-19 cannot ignore the employed methodology

“…In collaboration with the Clinical Pathology Unit of the ‘Luigi Sacco’ academic hospital, one of the two Italian reference centers for infectious diseases, the Research Centre for Metrological Traceability in Laboratory Medicine (CIRME) recently supervised studies on hospitalized COVID-19 patients performed to evaluate the role of laboratory tests as clinical predictors of disease severity, by selecting the worst results for each evaluated biomarker of the whole hospitalization period. Optimum biomarker cut-offs were specifically selected to have a high rule-in ability in detecting patients at risk of in-hospital death and a high rule-out ability in identifying patients at very low risk of intensive care unit (ICU) admission [ 8 ]. At the multivariate analysis, high LDH concentrations were significantly associated with both higher odds of death [odds ratio (OR), 161.5 (95% confidence interval (CI): 2.28–11,422.8; p = 0.019], and lower odds of ICU admission [OR, 0.06 (95% CI: 0.01–0.54); p = 0.011].…”