Absolute Lymphocytes, Ferritin, C-Reactive Protein, and Lactate Dehydrogenase Predict Early Invasive Ventilation in Patients With COVID-19

Salvador Payán-Pernía, MD; Lucía Gómez Pérez, MD; Ángel F. Remacha Sevilla, MD, PhD; Jordi Sierra Gil, MD, PhD; Silvana Novelli Canales, MD, PhD

Disclosures

Lab Med. 2021;52(2):141-145. 

In This Article

Discussion

Our work provides an approximation for the prediction of early (first 48 hours) MIV in patients with COVID-19 by means of simple laboratory tests that can be easily collected in any hospital. Although our results are concordant with those published by other authors about risk factors for severe disease and death, they refer specifically to the risk of MIV, which is of particular interest in the context of the high pressure on ICUs. Therefore, our data can help prioritize patients quickly when healthcare resources are limited.

We found that LDH is the biomarker that better can predict early MIV; with a sensitivity of 100%, patients will not be intubated if LDH on admission is <219 U/L. Based on LDH, we developed a classification tree to estimate the risk of MIV quickly. Research has shown that LDH is an intracellular enzyme found in nearly all organ systems that catalyzes the interconversion of pyruvate and lactate, with concomitant interconversion of Reduced nicotinamide adenine dinucleotide and Nicotinamide adenine dinucleotide. Abnormal values can not only result from cardiac damage or hemolysis but also from multiple organ injury and decreased oxygenation with upregulation of the glycolytic pathway. Because LDH is present in lung tissue, elevated levels seen in COVID-19 and other viral respiratory infections, such as Middle East Respiratory Syndrome, may represent the extent of lung injury that influences clinical outcomes.[12]

In severe COVID-19 infection, a deviation of the protective immune response into a dysfunctional program occurs, leading to cytokine release syndrome with severe inflammation and, eventually, multisystemic failure. A better understanding of the mechanisms lying at the root of immune response failure is needed; serum levels of inflammatory markers, such as CRP, ferritin, IL-6, and other cytokines, are increased in COVID-19.[13] In the setting of ongoing inflammation, evidence supports a role for ferritin in modulating the immune response, via its induction of anti-inflammatory cytokines and limitation of free radical damage. Alternatively, emerging work suggests a potential causative role of ferritin in the inflammatory pathology of disease.[14] Transcriptional induction of the CRP gene mainly occurs in hepatocytes in the liver in response to increased levels of inflammatory cytokines, especially IL-6. Similar to ferritin, evidence suggests that CRP is an important regulator of inflammatory processes and not just a marker.[15]

Lymphopenia, the fourth marker to predict early MIV, is a common feature in patients with COVID-19 and is more pronounced in severe cases of infection. It affects mainly T cells, including CD4 Th1 and Tregs, but particularly CD8. Although circulating CD8 in patients with severe COVID-19 has exhibited phenotypes associated with abnormal functionality and exhaustion, CD4 cells have been shown to express activation markers. In addition, natural killer lymphocytes have decreased in patients with both moderate and severe cases of the disease.[9,16] Injured alveolar epithelial cells could lead to the infiltration of lymphocytes.[16]

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