Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19

Abstract

Background: 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 laboratory-confirmed COVID-19 patients. Methods: Anti-SARS-CoV-2 IgG and IgM antibodies were determined by chemiluminescence analysis (CLIA) in COVID-19 patients from 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 among severe and nonsevere patients. Immune response phenotyping based on late IgG levels and neutrophil-to-lymphocyte ratio (NLR) was characterized to stratify patients with different disease severities and outcome. Laboratory parameters in patients with different immune response phenotypes and disease severities were analyzed. Findings: 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 who with low IgG levels (51.8% versus 32.3%; p=0.008). Severity rates for patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 72.3%, 48.5%, 33.3%, and 15.6%, respectively (p<0.0001). Furthermore, severe patients with NLRhiIgGhi, NLRhiIgGlo had higher proinflammatory cytokines levels including IL-2, IL-6 and IL-10, and decreased CD4+ T cell count compared to those with NLRloIgGlo phenotype (p<0.05). Recovery rate for severe patients with NLRhiIgGhi, NLRhiIgGlo, NLRloIgGhi, and NLRloIgGlo phenotype was 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 NLRhiIgGhi and NLRhiIgGlo phenotypes. Interpretation: COVID-19 severity is associated with increased IgG response, and an immune response phenotyping based on late IgG response and NLR could act as a simple complementary tool to discriminate between severe and nonsevere COVID-19 patients, and further predict their clinical outcome.

Neutralizing Antibodies Responses to SARS-CoV-2 in COVID-19 Inpatients and Convalescent Patients

“…The results of our study indicated that convalescent patients had a higher antibody level than inpatients, which highlight the positive correlation between recovery and days since onset (Spearman correlation coefficient=0.5426, P<0.0001). Besides, we also found that antibody levels in asymptomatic or mild patients were slightly lower than moderate or severe patients, which was in line with other previous studies [16][17] . Zhang [17] came to a similar conclusion that severe cases were more frequently found in COVID-19 patients with high IgG levels, compared to those who with low IgG levels.…”

“…Besides, we also found that antibody levels in asymptomatic or mild patients were slightly lower than moderate or severe patients, which was in line with other previous studies [16][17] . Zhang [17] came to a similar conclusion that severe cases were more frequently found in COVID-19 patients with high IgG levels, compared to those who with low IgG levels. Previous data showed that severe SARS-CoV was also associated more robust serological responses including early seroconversion and higher IgG levels [18][19] .…”

“…The effect of gender was also not statistically significant in both univariate (P=0.9426) and multivariate (P=0.8543) GEE analysis. A significant neutralizing antibody response was observed in older patients with a geometric mean titer of 1:220.1 (95% CI, 71.8 to 674.8) compared to patients at age of [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] (1:71.0, 95% CI, 27.7 to 181.8) and at age of 31-60 (1:200.6, 95% CI, 150.4 to 267.6) (P=0.0140).…”

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), March 2020

“…All sera collected 29 or more days after onset of illness were antibody-positive in all four serological tests, findings similar to another recent report [14]. The OD levels in the IgG ELISA were statistically significantly higher in severe/critical cases, a finding also reported by others [14,15] but as the investigated number of patients remains small, these findings need to be confirmed in a larger patient cohort.…”

IL-6 signalling pathway inactivation with siltuximab in patients with COVID-19 respiratory failure: an observational cohort study

“…This compassionate-use program was initiated to understand the feasibility of suppressing CRP production with siltuximab and improving the outcomes in patients with COVID-19 requiring CPAP or NIV for pneumonia/ARDS treatment. Initial evidence from China where the first cases of COVID-19 emerged, indicate that excessive production inflammatory markers, such as IL-6 and CRP, correlate with severity of disease (Chen X et al 2020;Conti P et al 2020;Diao B et al 2020;Gong J et al 2020;Liu et al 2020;Yang et al 2020), and many more studies report a significant increase in IL-6 or CRP levels in patients with severe or critical COVID-19 compared with those patients with mild disease (Cai et al 2020;Chen J et al 2020;Feng C et al 2020;Huang Y et al 2020;Liu J et al 2020;Qin C et al 2020;Ruan Q et al 2020;Shi Y et al 2020;Wang Y et al 2020;Wang Z et al 2020;Wu C et al2020;Xu W et al 2020;Xu X et al 2020;Zeng Q et al 2020;Zhao Z et al 2020;Zhang B et al 2020;Zhou F et al 2020;Zhou Y et al 2020).…”