Immune Phenotyping Based on the Neutrophil-to-Lymphocyte Ratio and IgG Level Predicts Disease Severity and Outcome for Patients With COVID-19

Abstract

Introduction: A recently emerging respiratory disease named coronavirus disease 2019 (COVID-19) has quickly spread across the world. This disease is initiated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and uncontrolled cytokine storm, but it remains unknown as to whether a robust antibody response is related to clinical deterioration and poor outcome in COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients at a single center in Wuhan. Median IgG and IgM levels in acute and convalescent-phase sera (within 35 days) for all included patients were calculated and compared between severe and non-severe patients. Immune response phenotyping based on the late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratified patients into different disease severities and outcomes. Results: A total of 222 patients were included in this study. IgG was first detected on day 4 of illness, and its peak levels occurred in the fourth week. Severe cases were more frequently found in patients with high IgG levels, compared to those with low IgG levels (51.8 vs. 32.3%; p = 0.008). Severity rates for patients with NLR hi IgG hi , NLR hi IgG lo , NLR lo IgG hi , and NLR lo IgG lo phenotype were 72.3, 48.5, 33.3, and 15.6%, respectively (p < 0.0001). Furthermore, severe patients with NLR hi IgG hi , NLR hi IgG lo had higher inflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLR lo IgG lo phenotype (p < 0.05). Recovery rates for severe patients with NLR hi IgG hi , NLR hi IgG lo , NLR lo IgG hi , and NLR lo IgG lo phenotype were 58.8% (20/34), 68.8% (11/16), 80.0% (4/5), and 100% (12/12), respectively (p = 0.0592). Dead cases only occurred in NLR hi IgG hi and NLR hi IgG lo phenotypes. Zhang et al. Immune Phenotyping for COVID-19 Patients Conclusions: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on the late IgG response and NLR could act as a simple complementary tool to discriminate between severe and non-severe COVID-19 patients, and further predict their clinical outcome.

Predicting clinical outcome with phenotypic clusters in COVID-19 pneumonia: an analysis of 12,066 hospitalized patients from the Spanish registry SEMI-COVID-19

“…Accordingly, it would be necessary to study each of the present clinical clusters genetically and to verify that each cluster has a differentiated genetic background. In the literature, some studies attempted to phenotype patients with COVID-19 as a function of the immune response, and others is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted September 15, 2020. ; https://doi.org/10.1101/2020.09.14.20193995 doi: medRxiv preprint suggested phenotyping as a function of pathophysiology [16,17]. It would be interesting to combine all methods of phenotyping.…”

Antibody seroconversion in asymptomatic and symptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)

“…Immunoglobulin G (IgG) and immunoglobulin M (IgM) are known antibodies for monitoring humoral immune responses to infections by viruses such as SARS-CoV-2. [18][19][20][21][22][23][24] Because of their convenience and cost-efficiency, new serological assays of IgG and IgM antibodies have been recognised as a promising diagnostic tool to complement viral nucleic acid screening in the atrisk populations. 25 Of note, IgG/IgM seroconversion can be observed in many patients after their infections with SARS-CoV-2, 4,18,20,23,26 and serological responses are associated with disease severity.…”

“…25 Of note, IgG/IgM seroconversion can be observed in many patients after their infections with SARS-CoV-2, 4,18,20,23,26 and serological responses are associated with disease severity. 19 For instance, an observational study of 32 critically ill and 141 noncritically ill patients reported IgM and IgG seroconversion rates of 82.7% and 64.7%, respectively. 18 Furthermore, IgG/IgM seroconversion could be detected along with a steady decline in viral loads in mildly ill patients, 4 though IgG seroconversion can be observed at the same time or earlier than IgM seroconversion in symptomatic patients.…”

Frequencies of CD33+CD11b+HLA-DR–CD14–CD66b+ and CD33+CD11b+HLA-DR–CD14+CD66b– Cells in Peripheral Blood as Severity Immune Biomarkers in COVID-19

“…Laboratory parameters such as neutrophil-to-lymphocyte ratio (2,3), C-reactive protein (CRP), interleukin (IL)-6 and dimer-D levels (4) are reported as indicators of COVID-19 severity when associated to clinical features of the infection. COVID-19 patients hospitalized at intensive care unit (ICU) exhibit augmented levels of inflammatory cytokines and infection biomarkers, such as interleukin (IL)-1B, IL-7, IL-8, IL-9, IL-10, interferon (IFN)-γ, interferon gamma-inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)1A, MIP1B, platelet-derived growth factor (PDGF), tumor necrosis factor-alpha (TNFα), and vascular endothelial growth factor (VEGF).…”