ABSTRACT
Background: Vaccination is an essential strategy to prevent infection in the SARS-CoV-2 pandemic. However, there are concerns about vaccine efficacy and the impact of vaccination on cancer treatment. Additionally, the emergence of novel variants may affect vaccination efficacy. This multi-center, prospective, observational study investigated the efficacy and impact of vaccination against SARS-CoV-2 variants on treatment among breast cancer patients in Japan. Methods: Breast cancer patients scheduled to be vaccinated with the SARS-CoV-2 vaccine from May to November 2021 were included. They were stratified into five groups according to their cancer treatment: no treatment, endocrine therapy, CDK4/6 inhibitor, chemotherapy, anti-HER2 therapy. Serum samples were collected before the first vaccination and after the second vaccination. Immunoglobulin (Ig)G levels against the SARS-CoV-2 S protein and neutralizing antibody titers against wild-type (WT), alpha (α), delta (δ), kappa (κ), and omicron (o) variants were measured by ELISA assay. The effect of vaccination on cancer treatment was also investigated. Results: There were 85 eligible patients (no treatment, n = 5;endocrine therapy, n = 30;CDK4/6 inhibitor, n = 14;chemotherapy, n = 21;and anti-HER2 therapy, n = 15) with a median age of 65 years. The overall seroconversion rate of anti-SARS-CoV-2 IgG was 95.3%. The seroconversion rate of the chemotherapy group was 81.8%. The anti-SARS-CoV-2 IgG antibody concentration was positively correlated with the lymphocyte count before vaccination (r = 0.232, p = 0.039). Overall neutralizing antibody titers against each variant were significantly lower than for WT. Overall positive rates of neutralizing antibodies against WT, α, δ, γ, and o variants were 90.2%, 81.7%, 96.3%, 84.1%, and 8.5%, respectively. A downward trend of neutralizing antibody titers against each variant was seen in chemotherapy and CDK4/6 inhibitor groups compared with other groups. Significant decreases were detected in neutralizing antibody titers against WT, α, and κ variants in the chemotherapy group, and WT and α variants in the CDK4/6 inhibitor group compared with the no treatment group. Withdrawal or postponement of systemic therapy because of vaccination was only observed in one patient. Conclusions: Our data support SARS-CoV-2 vaccination for cancer patients being treated with systemic therapy. However, neutralizing antibody titers against the o variant were very low even after two vaccinations among patients with or without cancer treatment. Further, a decrease in neutralizing antibody titer was suggested during chemotherapy and CDK4/6 inhibitor, raising concerns about the impact on long-term infection prevention. For these patients, infection-preventive behaviors should be recommended even after vaccination. They will also be good candidates for booster vaccinations.
ABSTRACT
Rational: Corticosteroid therapy plays a key role in the treatment of COVID-19 patients with respiratory failure. However, a rebound phenomenon after steroid cessation rarely occurs. Here, we investigated the clinical features of patients with rebound after steroid therapy. Methods: In total, 84 patients with COVID-19 treated with corticosteroids were enrolled and analysed retrospectively. A rebound was defined as when a patient’s respiratory status deteriorated after the cessation of corticosteroid therapy, without secondary bacterial infection. Results: Subjects in the rebound group were more likely to having severe respiratory failure than those in the non-rebound group. While the duration of steroid therapy was longer in the rebound group (8 days vs 10 days, p=0.0009), the dosage of steroid and the timing of the start or termination of steroid therapy did not show any differences between the two groups (p=0.17 and 0.68, respectively). The values of soluble interleukin-2 receptor (sIL-2R) at the baseline and the values of C reactive protein (CRP) or lactate dehydrogenase (LDH) at the end of steroid therapy were significantly higher in the rebound group (937 vs 1336 U/mL;p=0.002, 0.63 vs 3.96 mg/dL;p=0.01 and 278 vs 451 IU/mL;p=0.01, respectively). No patient in the rebound group suffered from thromboses, and the causes of death were exacerbation of COVID-19, ventilator-associated pneumonia or sepsis. The prediction model using baseline features for the rebound phenomenon included four variables of age >68 years, required supplemental oxygen >5 L/min, lymphocyte counts <792 /µL and sIL-2R >1146 U/mL. The discrimination ability of this model was 0.906 (0.755–0.968). Conclusion: These findings suggest that severe respiratory failure has a higher risk for the rebound phenomenon after the cessation of corticosteroids, and the values of sIL-2R, LDH and CRP are useful to assess the probability of developing rebound. A multivariate model was developed to predict rebound risk, which showed acceptable discrimination ability.