Globally as of October 2020, COVID-19 has claimed the lives of over 1.1 million people (1). Severe manifestations of COVID-19 include acute respiratory distress syndrome, sepsis, and potentially fatal multi-organ failure. Medical laboratories around the world have been critical in the pandemic response providing essential diagnostic testing for SARS-CoV-2 as well as biochemical testing necessary for the management of patients with COVID-19 and their comorbidities.
Biochemical laboratory testing in COVID-19 patients aids in staging their disease, prognostication, and monitoring of therapeutic interventions (2). Patients with COVID-19 requiring hospitalization may present with or develop derangements in inflammation (including cytokine storm) and coagulation reflected by alterations in cytokines and coagulation parameters. Systemic inflammation can occur resulting in elevated c-reactive protein (CRP) (2). Tumor necrosis factor alpha, interleukin-1 and interleukin 6 may also be increased (3). Elevations in IL-6 and CRP have been shown to have a high predictive value for severe COVID19 requiring mechanical ventilation (5). Neutrophilia, leukocytosis and elevations in procalcitonin can be observed in association with bacterial superinfection (2). A common finding associated with severe disease is lymphopenia and specific reductions in CD3+, CD4+ and CD8+ subpopulations of T-cells (7). Also, a meta-analysis of 22 studies on hospitalized COVID-19 patients found that lymphopenia and neutrophilia at admission were associated with poorer outcomes (4). Consistent with the reports above, a high neutrophil-to-lymphocyte ratio or low CRP-to-lymphocyte ratio are two of the proposed biomarkers for severe COVID-19 (6).
Abnormalities in coagulation leading to venous and thromboembolic complications are found in 10-25% of COVID-19 patients requiring hospital care. Patients with coagulopathies in COVID-19 most commonly show elevations in D-dimer. Higher risk of mortality (18-times) was observed with patients with D-dimer concentrations above 1 mg/L. Less dramatic changes include prolongation of the prothrombin time (PT) and a mild decrease in platelets (3). Fibrinogen concentrations may be either increased or decreased, depending on their stage in the progression of the disease.
In the setting of lung, liver and systemic tissue injury, elevations in lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may be observed, as well as increases in serum bilirubin and decreases in serum albumin with diminishing liver function. Patients with COVID-19 are at high risk for acute kidney injury. Serum creatinine and serum urea nitrogen are associated with high risk of mortality in COVID19 and thus warrant monitoring in these patients (7). Cardiac injury is another common complication in COVID-19 patients. Elevations in troponin are present in 7-17% of hospitalized COVID-19 patients (8).
Biochemical testing is one piece of the clinical investigation to aid in decisions on whether patients are admitted, transferred to ICU care, started on certain therapies, or discharged. It is important to consider the utility of published biochemical parameter alterations in COVID-19 and what they mean for our own patients. The setting and mode of data collection is unique from most other studies of diagnostic testing for other conditions. The majority of the current studies on COVID-19 patients are retrospective with their own representative patient populations. Studies also differ in how they separate patients into groups for statistical analysis (confirmed SARS-CoV-2 positive vs negative, ICU vs. non-ICU, hospitalized vs. non-hospitalized, hospitalized with COVID-19 vs. hospitalized with another illness, etc. Furthermore, the management of patients has changed drastically during the start of the pandemic to the present day and will continue to change as we continue to test promising interventions, detect SARS-CoV-2 infection earlier, and manage the long-term sequelae associated with COVID-19. These early studies were essential for preparing to care for COVID-19 patients and to begin to understand the pathophysiology of COVID-19. More research into the performance of emerging calculations, algorithms, nomograms, and medical decision limits will further our ability to effectively manage COVID-19 patients.
Our knowledge of COVID-19 pathophysiology is rapidly evolving, necessitating strong communication across the global medical community. It is clear that the ability for laboratories to provide valuable, timely, and accurate testing in the setting of COVID-19 is essential in the management of the pandemic.
More references on studies reporting on clinical laboratory results from COVID-19 patients can be found here: Clinical Laboratory Findings in COVID19
- Dong E, Du H, Gardner L. An interactive web-based dashboard to track COVID-19 in real time. Lancet Inf Dis. 20(5):533-534. doi: 10.1016/S1473-3099(20)30120-1
- Lippi, G., & Plebani, M. (2020). The critical role of laboratory medicine during coronavirus disease 2019 (COVID-19) and other viral outbreaks, Clinical Chemistry and Laboratory Medicine (CCLM), 58(7), 1063-1069. doi: https://doi.org/10.1515/cclm-2020-0240
- Marcel Levi, Jecko Thachil, Toshiaki Iba, Jerrold H Levy. Coagulation abnormalities and thrombosis in patients with COVID-19, The Lancet Haematology, Volume 7, Issue 6, 2020, Pages e438-e440, ISSN 2352-3026, https://doi.org/10.1016/S2352-3026(20)30145-9.
- Henry B, Cheruiyot I, Vikse J, Mutua V, Kipkorir V, Benoit J, Plebani M, Bragazzi N, Lippi G. Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis. Acta Biomed. 2020 Sep 7;91(3):e2020008. doi: 10.23750/abm.v91i3.10217. PMID: 32921706.
- Herold T, Jurinovic V, Arnreich C, Lipworth BJ, Hellmuth JC, von Bergwelt-Baildon M, Klein M, Weinberger T. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4. doi: 10.1016/j.jaci.2020.05.008. Epub 2020 May 18. PMID: 32425269; PMCID: PMC7233239.
- Lagunas‐Rangel, F.A. (2020), Neutrophil‐to‐lymphocyte ratio and lymphocyte‐to‐C‐reactive protein ratio in patients with severe coronavirus disease 2019 (COVID‐19): A meta‐analysis. J Med Virol. doi:10.1002/jmv.25819
- Weidmann, Maxwell D, et al. “Laboratory Biomarkers in the Management of Patients With COVID-19.” American Journal of Clinical Pathology, 2020, doi:10.1093/ajcp/aqaa205.
- Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;324(8):782–793. doi:10.1001/jama.2020.12839
- Christensen B, Favaloro EJ, Lippi G, Van Cott EM. Hematology Laboratory Abnormalities in Patients with Coronavirus Disease 2019 (COVID-19). Semin Thromb Hemost. 2020;46(7):845-849