Novel Systemic Inflammation Markers to Predict COVID-19 Prognosis

Abstract

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic, challenging both the medical and scientific community for the development of novel vaccines and a greater understanding of the effects of the SARS-CoV-2 virus. COVID-19 has been associated with a pronounced and out-of-control inflammatory response. Studies have sought to understand the effects of inflammatory response markers to prognosticate the disease. Herein, we aimed to review the evidence of 11 groups of systemic inflammatory markers for risk-stratifying patients and prognosticating outcomes related to COVID-19. Numerous studies have demonstrated the effectiveness of neutrophil to lymphocyte ratio (NLR) in prognosticating patient outcomes, including but not limited to severe disease, hospitalization, intensive care unit (ICU) admission, intubation, and death. A few markers outperformed NLR in predicting outcomes, including 1) systemic immune-inflammation index (SII), 2) prognostic nutritional index (PNI), 3) C-reactive protein (CRP) to albumin ratio (CAR) and high-sensitivity CAR (hsCAR), and 4) CRP to prealbumin ratio (CPAR) and high-sensitivity CPAR (hsCPAR). However, there are a limited number of studies comparing NLR with these markers, and such conclusions require larger validation studies. Overall, the evidence suggests that most of the studied markers are able to predict COVID-19 prognosis, however NLR seems to be the most robust marker.

A Prospective Study Evaluating Cumulative Incidence and a Specific Prediction Rule in Pulmonary Embolism in COVID-19

“…Moreover, other biomarkers, such as PDW and NLR, were significantly higher in patients with PE as compared to patients without PE. Interestingly, both PDW and NRL have also been described as severity markers in COVID-19 (33,34), with more increased NLR among PE cases (35). Higher PDW, a surrogate marker of platelet activation, has also been found in non-COVID-19 PE patients (36).…”

The Predictive Role of NLR, d-NLR, MLR, and SIRI in COVID-19 Mortality

“…Serum biochemical analysis and blood count analysis are commonly used blood tests, which could be faster, easier to use, and low-cost techniques that can facilitate the diagnosis and prognosis of this disease [ 11 ]. From these routine tests, inflammatory markers have been used for predicting the severity of COVID-19 such as neutrophil to lymphocyte ratio (NLR), derivate neutrophil to lymphocyte ratio (dNLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR) [ 11 , 12 ]. NLR and PLR are biomarkers reflecting systemic inflammation, neutrophil and platelet activation, and are associated with increased mortality in cardiovascular disease and poor prognosis in various cancers or in polycythemia vera [ 13 , 14 , 15 ].…”

“…The systemic inflammatory response index (SIRI) may also reflect the host’s immune and inflammatory balance [ 20 ]. In addition, systemic immune-inflammation index (SII), defined as platelet count × NLR, is effective in reflecting inflammatory status, being a basic biomarker for predicting the prognosis [ 12 ]. The current study assesses the utility of various inflammatory markers in predicting mortality among hospitalized patients with COVID-19.…”

Predictive role of blood eosinophils in adult varicella patients

“…The NLR is widely used across almost all medical disciplines as a reliable marker of the immune response to various infectious and non-infectious stimuli [24]. However, the application of the NLR in patients with viral infection is mostly limited to the prognostication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated patient outcomes [25][26][27]. Considering eosinophils attenuate viral infectivity through production of nitric oxide [9] and a high NLR is associated with excessive levels of reactive oxygen species [28], we speculated that eosinopenia and the increase of NLR were associated with a decrease in antioxidant defences, which can promote inflammation and oxidative damage during infection.…”