Emerging key laboratory tests for patients with COVID-19.

Listed below are six key laboratory tests/areas that have an important role in monitoring patients with COVID-19 with specific tests/scores highlighted in Table 1 . Additional resources for laboratory related testing may be found at the International Federation of Clinical Chemistry and Laboratory Medicine website (IFCC Information Guide on COVID-19: https://www.ifcc.org/ifcc-news/2020–03-26-ifcc-information-guide-on-covid-19/).

Table 1

Emerging key laboratory tests for patients with COVID-19.

Laboratory Test	Role in COVID-19
Lymphocyte count	• At least 75% of patients have a count <1.5 × 109/L [1], [2], [3]. • Patients with persistently low counts during hospitalization have a poor prognosis [1].
C-reactive protein (CRP)	• CRP median concentrations differ between non-survivors (n = 113) versus survivors (n = 161) (113 mg/L vs. 26 mg/L) as does ferritin (1418 µg/L vs. 481 mg/L) and IL-6 (72 ng/L vs. 13 ng/L) [2]. • Before convalescent plasma transfusion the median CRP concentration in 5 COVID-19 patients was 163 mg/L and at 12-days post-transfusion with no virus detected the median CRP concentration was 6 mg/L [4]. Of note, CRP concentrations <10 mg/L typically indicate no appreciable acute phase response.
Alanine Aminotransferase (ALT)	• Using an overall cutoff of >40 U/L approximately 30% of COVID-19 patients had liver injury at admission [1], [3]. • The rate of liver injury could be higher in females as the upper limit of normal is typically lower in females as compared to males.
D-dimer	• At admission 50% of patients who survived had concentrations <0.6 µg/mL while the non-survivors at least 75% had concentrations >1.3 µg/mL [1], [2].
High-sensitivity cardiac troponin	• At admission, 50% of the survivors had a high-sensitivity cardiac troponin I concentration ≤3 ng/L (a low normal level) [1], [2].
Clinical Scores	• Creatinine, total bilirubin, pO2 and platelet count are used for the SOFA (sequential organ failure assessment) score; while urea is used for the CURB-65 (confusion, urea, respiratory rate, blood pressure and age ≥65 years) score [1]. Lactate levels are also used to identify septic shock.

Complete blood count (CBC) with differential

The three CBC findings of poor prognosis are: leukocytosis, thrombocytopenia, and lymphocytopenia [1], [2], [3]. Lymphocytopenia occurs across populations regardless of co-infection. Whether poor prognosis is associated with lymphocytopenia below the reference interval or absolute count is unclear.

Acute phase response and inflammatory biomarkers

COVID-19 patients have high concentrations of the acute phase response proteins (i.e., c-reactive protein [CRP] and ferritin) and inflammatory biomarkers (i.e., cytokines such as Interleukin-6; IL-6) at admission [1], [2]. CRP is more widely available, and is a sensitive biomarker of inflammation and tissue damage that is increased at admission and during hospitalization [2], [4].

Kidney, liver and cardiac injury

Kidney injury prevalence (via creatinine measurement) at admission is unknown but 11–15% of hospitalized COVID-19 patients may have acute kidney injury [1], [2]. Alanine aminotransferase (ALT) elevations at admission range from 22% to 32% and cardiac injury (via cardiac troponin measurement) has been reported to range from 15% to 44% [1], [2], [3]. Other liver biomarkers are reported to be increased; however, ALT is more specific for liver injury and is also less affected by pre-analytical factors such as hemolysis.

Tests which may indicate improvement

Following recovery and 7-days post-convalescent plasma transfusion, CRP levels decreased by >10-fold, which was more pronounced than IL-6 and procalcitonin (~2-fold difference) [4]. Procalcitonin is a useful indicator for bacterial infections, though not all patients with COVID-19 have bacterial co-infections [3], [4].

Prognostic biomarkers

D-dimer and high-sensitivity cardiac troponin can also identify COVID-19 patients who are at low- and high-risk for death [1], [2], [5]. D-dimer is used in decision making for disseminated intravascular coagulation, deep vein thrombosis or pulmonary embolism and is given a high priority of testing in patients with COVID-19 [5]. While for high-sensitivity cardiac troponin, normal or low concentrations (typically below 5 ng/L, but cutoffs are assay specific) identifies patients at low-risk for cardiovascular outcomes and death in many different populations, including COVID-19 patients [1], [2].

Clinical scores

Two clinical scores that may also identify patients with COVID-19 at low- and high-risk for death are the sequential organ failure assessment (SOFA) score used in sepsis and the confusion, urea, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score in the assessment of severity in patients with community acquired pneumonia. Both clinical scores require laboratory testing.

Conflict of Interest Disclosures: Dr. Kavsak has received grants/reagents/consultant/advisor/ honoraria from serval diagnostic companies, including Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Randox Laboratories, Roche Diagnostics and Siemens Healthcare Diagnostics. McMaster University has filed patents with Dr. Kavsak listed as an inventor in the acute cardiovascular biomarker field. Dr de Wit has received a research grant from Bayer.