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

Bicheng Zhang; Xiaoyang Zhou; Chengliang Zhu; Fan Feng; Yanru Qiu; Jia Feng; Qingzhu Jia; Qibin Song; Bo Zhu; Jun Wang

The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03.12.20035048 doi: medRxiv preprint NLR lo IgG hi or NLR lo IgG lo phenotype. A third of patients with NLR lo IgG hi had critical illness, suggesting that IgG response alone could lead to disease deterioration. Furthermore, high Th1 cytokine IFN-γ, proinflammatory cytokines IL-6, TNF-α, and IL-10 were noted in NLR hi IgG hi or NLR hi IgG lo phenotypes. Accordingly, we speculated that anti-IgG humoral response directly contributed to tissue damage. In SARS-CoV/macaque models, Liu et al. found anti-spike IgG, the presence of high anti-spike IgG prior to viral clearance, abrogated wound-healing responses and promoted proinflammatory cytokines monocyte chemotactic protein 1 and IL-8 production and monocyte/macrophage recruitment and accumulation, eventually cause fatal acute lung injury during SARS-CoV infection. 13 Thus, we proposed potential mechanisms associated with different immune response phenotypes and presented specific treatment recommendations which would be helpful in guiding clinical decision ( figure 3 ). For example, in the NLR hi IgG lo group, both virus directly mediated tissue damage and CRS are responsible for disease development. In this scenario, anti-virus, tocilizumab, and serum from convalescent should be considered. However, serum from convalescent should only be used in patients with low IgG levels and should not be used in the patients with high IgG level since its use might aggravate the disease especially in the patients with NLR hi IgG hi phenotype. 14 Tocilizumab treatment might not be beneficial for patients with low NLR, because these patients are in the immunosuppression stage rather than in CRS stage. 15 Our retrospective investigation had some limitations. Firstly, virus titers were not monitored during SARS-CoV-2 infection and patient recovery. Higher IgG levels, however, were previously detected in patients who had negative pre-discharge fecal RT-PCR results and SARS-CoV-infected rhesus macaques that had markedly reducing virus titers. 7 Secondly, it is unknown whether the change or increase of IgM or IgA is related to disease severity. The mechanism responsible for the immunopathologic reaction of IgG remains elusive. Finally, the IgG response and its correlation to the severity of COVID-19 in patients without high-dose corticosteroid intervention have not been addressed. Nevertheless, our findings indicate that severe COVID-19 was associated with a more robust IgG response that can be developed as an acquired immunity-related marker to predictive disease severity, along with other innate immunity-relate makers such as NLR. Further study on the immunopathogenesis of SARS-CoV-2 infection is warranted.