Prognostic Role of Neutrophil to Lymphocyte Ratio in COVID-19 Patients: Still Valid in Patients That Had Started Therapy?

Abstract

COVID-19 may appear with a widely heterogeneous clinical expression. Thus, predictive markers of the outcome/progression are of paramount relevance. The neutrophil/lymphocyte ratio (NLR) has been suggested as a good predictive marker of disease severity and mortality. Accordingly, we found that NLR significantly increased in parallel with the WHO severity stage in COVID-19 patients during the Ist wave (March-May 2020; n = 49), due to the significant reduction of lymphocyte and the significant increase of neutrophil in severe COVID-19 patients. While, we did not observe significant differences of NLR between the WHO severity stage among COVID-19 patients of the IInd wave (September 2020-April 2021; n = 242). In these patients, the number of lymphocytes and neutrophils did not change significantly between patients of different severity subgroups. This difference likely depends on the steroids therapy that the patients of the IInd wave performed before hospitalization while most patients of the Ist wave were hospitalized soon after diagnosis. This is also confirmed by serum interleukin (IL)-6 and myeloperoxidase (MPO) that gradually increased with the disease stage in patients of the Ist wave, while such biomarkers (whose production is inhibited by steroids) did not show differences among patients of the IInd wave in different stages. Thus, the NLR could be tested at diagnosis in naïve patients before starting therapies.

A Transient Increase in the Serum ANCAs in Patients with SARS-CoV-2 Infection: A Signal of Subclinical Vasculitis or an Epiphenomenon with No Clinical Manifestations? A Pilot Study

“…In the patients of the second wave (hospitalized between September 2020 and May 2021), we observed again an increase in the serum ANCAs but the serum levels of both the MPO and PR3 antigens were normal. Our data agreed with the lower number of circulating neutrophils that we observed in patients with SARS-CoV-2 infection of the second wave compared with those of the first wave and then on the lower release of cytoplasmic antigens during inflammation [5]. Thus, the increase in the ANCAs in the patients of the second wave remains unexplained.…”

“…Necroscopies of COVID-19 patients revealed that endothelial cell inflammation with the accumulation of lymphocytes, Viruses 2021, 13, 1718 2 of 8 plasma cells and monocytes involved several organs [3], particularly the lung [4]. In addition, circulating neutrophils, which are increased in COVID-19 patients [5], contribute to the endothelial damage by releasing tumor necrosis factor-alpha, interleukin (IL)-1 and IL-8.…”

Further Findings Concerning Endothelial Damage in COVID-19 Patients

“…Necroscopies of COVID-19 patients revealed endothelial inflammation with the accumulation of lymphocytes and monocytes in the majority of important organs [ 6 , 7 ], particularly the lungs [ 8 ]. In addition, neutrophils, which are increased in the blood [ 9 ] and tissues [ 7 ] of COVID-19 patients, may contribute to the endothelial damage and thus the release of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-8.…”

The Inflammatory Cytokine Imbalance for Miscarriage, Pregnancy Loss and COVID-19 Pneumonia

“…Additionally, in comparison to the non-severe patients, pro-inflammatory cytokines and chemokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, Granulocyte-colony stimulating factor(GCSF), mono cytochemoattractant protein 1 (MCP1) and macrophage inflammatory protein 1-alpha (MIP1-alpha) are often reported to be elevated in serum levels of critically ill patients ( 66 , 73 ). The elevated neutrophil-lymphocytes ratio (NLR), which is a biomarker of systemic inflammatory response syndrome, points to the devastated inflammatory state of COVID-19 patients in intensive care units ( 74 ). This hyperactive immune response along with impaired adaptive immune response may trigger pulmonary injury, ARDS, viral sepsis and organ failure as complications, and eventually death in some cases ( 74 ).…”

“…The elevated neutrophil-lymphocytes ratio (NLR), which is a biomarker of systemic inflammatory response syndrome, points to the devastated inflammatory state of COVID-19 patients in intensive care units ( 74 ). This hyperactive immune response along with impaired adaptive immune response may trigger pulmonary injury, ARDS, viral sepsis and organ failure as complications, and eventually death in some cases ( 74 ).…”