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.

Keywords: COVID-19; SARS-CoV-2; biomarkers; inflammation; inflammatory markers; prognosis.

Figure 1

Systemic inflammation markers discussed in this study. NLR is illustrated in the middle as it was the most studied marker with strong prognosticating capabilities. However, some of the less studied markers reviewed in the study might have the potential to overtake the predictive value of NLR. NLR, neutrophil to lymphocyte ratio; d-NLR, derived NLR; PLR, platelet to lymphocyte ratio; LMR, lymphocyte to monocyte ratio; LCR, lymphocyte to C-reactive protein ratio; FPR, fibrinogen to prealbumin ratio; AFR, albumin to fibrinogen ratio; CAR, C-reactive protein to albumin ratio; CPAR, C-reactive protein to prealbumin ratio; GPS, Glasgow prognostic score; mGPS, modified GPS; hs-mGPS, high-sensitivity mGPS; PI, prognostic index; PNI, prognostic nutritional index; SII, systemic immune-inflammation index; IFI27, interferon-alpha inducible protein 27.