Therapeutic Effect of Tocilizumab on Inhibiting Cytokine Release Syndrome in Severe Coronavirus Disease 2019 Patients

Background and Objectives: Older adults are more susceptible to coronavirus disease 2019 (COVID-19). Interleukin-6 (IL-6) is an important cytokine in the cytokine release syndrome (CRS), and tocilizumab blocks the IL-6 receptor. The objective is to analyze the effect of tocilizumab on CRS in older patients with severe COVID-19. Materials and Methods: Between February 10 and March 21, 2020, a total of 19 patients aged ≥60 years with severe or critical COVID-19 met the study inclusion criteria at the Tongji Hospital in Wuhan City, Hubei Province, China. The patients were divided into two groups: the tocilizumab group, with IL-6 levels, which exceeded the upper limit of normal by >10-fold and non-tocilizumab group. Results: Patients in the tocilizumab group were older (73.20 ± 4.44 vs. 66.21 ± 5.06 years, P = 0.014), had lower lymphocyte counts (0.71 ± 0.18 vs. 1.18 ± 0.59 × 109/L, P = 0.016), and higher high-sensitivity C-reactive protein (hsCRP) levels (94.04 ± 57.24 vs. 51.65 ± 45.37 mg/L, P = 0.035). Increases in ferritin (FER) and hsCRP levels in patients in the tocilizumab group were marked. Except for one patient who died, IL-6, FER, hsCRP levels, and the neutrophil/lymphocyte ratio in the remaining four patients decreased following treatment with tocilizumab. Tocilizumab did not cause any serious adverse reactions. There were no differences in mortality, days until lung computerized tomography improvement, or renal function between the two groups. The total mortality rate was 10.53%. Conclusions: Our results support the therapeutic efficacy and safety of tocilizumab in older patients with severe COVID-19.

Characteristics of peripheral white blood cells in COVID-19 patients revealed by a retrospective cohort study.

BACKGROUND: Peripheral hematological changes in severe COVID-19 patients may reflect the immune response during SARS-CoV-2 infection. Characteristics of peripheral white blood cells as early signals were needed to be investigated for clarifying its associations with the fatal outcomes in COVID-19 patients. METHODS: A retrospective cohort study was performed and the hospitalized COVID-19 patients were recruited in wards of Sino-French New City Branch of Tongji Hospital in Wuhan, Hubei province, China. Characteristics of peripheral white blood cells in survivors and non-survivors were analyzed. Comparison among patients with different level of eosinophils was performed. RESULTS: Of 198 patients included in this study, 185 were discharged and 13 died. Levels of eosinophils, lymphocytes and basophils in non-survivors were significantly lower than those in survivors. Death rate in low eosinophils group was higher and no patient died in normal eosinophils group (16.7% vs 0, P < 0.001). The proportion of patients in low eosinophils group who used glucocorticoids was higher than in normal eosinophils group, but glucocorticoids usage was not an indicator for death in subgroup analysis in low eosinophils patients. Moreover, positive correlation was found between the counts of lymphocytes and eosinophils in patients with glucocorticoids use but not in patients without the treatment. CONCLUSIONS: Hematological changes differed between survivors and non-survivors with COVID-19. Lymphopenia and eosinopenia could be predictors for poor prognosis of COVID-19 patients. Initial counts of eosinophils may guide us in usage of glucocorticoids for COVID-19 treatment.

The dynamic changes of serum IgM and IgG against SARS-CoV-2 in patients with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide pandemic since it emerged in December 2019. Previous studies have reported rapid antibody response to SARS-CoV-2 in the first 2 to 3 weeks after symptom onset. Here, we retrospectively described the dynamic changes of serum immunoglobulin M (IgM) and IgG specifically against SARS-CoV-2 in later weeks (mainly 4-10 weeks) in 97 hospitalized patients with COVID-19. We observed that serum IgM and IgG, especially in patients with moderate-to-high levels, declined significantly between week 4 to 10 after illness onset. Notably, IgG levels in high percentage of patients (77.5%, 31 of 40) rapidly declined by half, from 212.5 (range, 163.7-420.3) to 96.3 (range, 75.0-133.4) AU/mL, within 1 to 2 weeks in the second month and then sustained at around 100 AU/mL until discharge from hospital. Significant reduction of IgM was also observed as SARS-CoV-2 nucleic acid turned negative (P = .002). In the recovery stage, serum IgG declined significantly (early vs late recovery stage, n = 16, P = .003) with a median reduction of 50.0% (range, 3.7%-77.0%). Our results suggested that the decline of IgM may be an indicator of virus clearance and recovered patients may have a robust immunity against reinfection within at least 3 months after illness onset. Yet, the rapid reduction of IgG by half rises serious concerns on the robustness and sustainability of the humoral immune response in the period after discharge, which is crucial for immunity strategy and developing a vaccine.

Tocilizumab May Be a Key in Therapy for Cytokine Release Syndrome in Older Patients With Severe Symptoms of COVID-19 (preprint)

Background Older adults are more susceptible to the novel coronavirus disease 2019 (hereafter, COVID-19) and more likely to develop severe illness. Cytokine release syndrome (CRS) may be an important factor in the development of severe disease in patients with COVID-19. Interleukin-6 (IL-6) is an important cytokine in CRS, and tocilizumab can block the IL-6 receptor. In this study, we analyzed the therapeutic effects and safety of tocilizumab on CRS in older patients with severe COVID-19. Methods Between February 10 and March 21, 2020, a total of 19 patients with severe or critical COVID-19 aged ≥ 60 years met the study inclusion criteria at Tongji hospital in Wuhan city, Hubei Province, China. Patients were divided into two groups: 1. The tocilizumab group, whose IL-6 levels exceeded the upper limit of normal by > 10-fold; and 2. The no tocilizumab group, with 1L-6 levels < 10-fold the upper normal limit. Results Patients in the tocilizumab group were older (73.20 ± 4.44 vs. 66.21 ± 5.06 years, P = 0.014); had lower lymphocyte counts (0.71 ± 0.18 vs. 1.18 ± 0.59 × 109/L, P = 0.016); and higher high-sensitivity C-reactive protein (hsCRP) levels (94.04 ± 57.24 vs. 51.65 ± 45.37 mg/L, P = 0.035). The increases in ferritin (FER) and hsCRP levels in patients in the tocilizumab group were marked. Except in one patient who died, IL-6, FER, and hsCRP levels, and the neutrophil/lymphocyte ratio, in the remaining four patients decreased following treatment with tocilizumab. Further, patient computerized tomography scan results improved after 3–8 days of tocilizumab treatment. Tocilizumab did not cause any serious adverse reactions. There were no differences in mortality or days until lung computerized tomography improvement between the two groups. The total mortality rate was 10.53%. Conclusions Our results support the therapeutic efficacy and safety of tocilizumab on older patients with severe COVID-19.