Neutralizing Antibody Responses in Patients with Hematological Malignancies after Omicron Infection: A Multicenter, Prospective Cohort Study in China

Abstract

BACKGROUND The mortality rate of hospitalized hematological malignancies (HM) patients with COVID-19 has significantly decreased from 40.7% in the pre-Omicron era (before December 2021) to 16.5% in the Omicron era (Blennow O, et al. AJH 2022; Pagano L, et al. JHO 2021). However, the mortality rate of Omicron infection in the general population is approximately 1%, which is comparable to influenza (Wang B, et al. J Infect 2023). Therefore, COVID-19 continues to pose a substantial threat to HM patients, even under the Omicron era. Neutralizing antibodies (NAbs) play a crucial role in preventing breakthrough infections and reinfections by blocking the entry of SARS-CoV-2 into the body (Nordstrom P, et al. Lancet Infect Dis 2022). However, little is known about neutralizing antibody (NAb) response development after natural Omicron infection and the risk factors for poor responders in HM patients. METHODS A registered multi-center, prospective, observational study was conducted during the latest Omicron wave in Chongqing, China (November 2022 to January 2023). NAb titers (measured by serum IgG anti-receptor binding domain of spike protein [anti-S-RBD]) were assessed 3-6 weeks after infection in the HM cohort (HMC), healthy control cohort (HCC), and solid cancer cohort (SCC). The primary outcomes compared the anti-S-RBD IgG titer and seroconversion rate between the HMC and HCC or SCC. The exploratory outcome investigated risk factors for poor responders, defined as patients with non-seroconversion or low anti-S-RBD IgG titer, in the HMC. RESULTS Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, P=0.0513) or SCC (100%, P=0.1363); the median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than HCC (46.9 ng/mL, P<0.0001) or SCC (46.2 ng/mL, P<0.0001). Risk factors associated with non-seroconversion included no COVID-19 vaccination history (OR=4.58, 95% CI: 1.75-12.00, P=0.002), clinical course of COVID-19 ≤ 7 days (OR=2.86, 95% CI: 1.31-6.25, P=0.008) and severe B-cell reduction (0-10/μL) (OR=3.22, 95% CI: 1.32-7.88, P=0.010); Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR=2.58, 95% CI: 1.59-4.18, P<0.001) and severe B-cell reduction (0-10/μL) (OR=2.87, 95% CI: 1.57-5.24, P<0.001). CONCLUSIONS This study reveals a poor NAb response in HM patients after Omicron (BA.5.2.48) infection and identifies risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection; and the post-infection vaccination strategies for these patients should be tailored.