# Neutralizing activity against Omicron subvariants BA.1, BA.2, and BA.4/5 following the third SARS-CoV-2 vaccination in cancer patients undergoing chemotherapy

## TL;DR

Cancer patients undergoing chemotherapy, especially those with blood cancers, have weak immune responses to the third SARS-CoV-2 vaccine, highlighting the need for stronger vaccination recommendations.

## Contribution

The study identifies hematologic cancer patients and those without prior Omicron infection as having significantly lower neutralizing antibody responses to the third SARS-CoV-2 vaccine.

## Key findings

- Hematologic cancer patients showed significantly lower neutralizing antibody responses to Omicron subvariants compared to solid tumor patients.
- Uninfected patients had much lower sVNT inhibition scores across all Omicron subvariants.
- Treatment delays due to infection occurred in 9 patients, averaging 17.75 days.

## Abstract

•COVID-19 bivalent vaccine uptake in Korea is low at 12.95 %.•Cancer patients with no history of Omicron infection exhibit low antibody titers.•Hematologic cancer patients exhibit the lowest immune response.•These high-risk patients need additional vaccinations.•Stronger recommendations are needed for these individuals.

COVID-19 bivalent vaccine uptake in Korea is low at 12.95 %.

Cancer patients with no history of Omicron infection exhibit low antibody titers.

Hematologic cancer patients exhibit the lowest immune response.

These high-risk patients need additional vaccinations.

Stronger recommendations are needed for these individuals.

Despite the availability of bivalent vaccines targeting both the ancestral SARS-CoV-2 strain and Omicron subvariants, vaccination rates remain low in South Korea. This study aims to evaluate the neutralizing activity against Omicron subvariants following the third SARS-CoV-2 vaccination in patients undergoing chemotherapy, as well as to assess the need for additional vaccinations.

Between April and November 2022, the authors assessed the neutralizing activity of the third SARS-CoV-2 vaccine dose in 63 patients undergoing chemotherapy using an ELISA-based surrogate Virus Neutralization Test (sVNT). The authors examined the influence of factors such as prior COVID-19 infection, cancer type (solid vs. hematologic malignancy), type of chemotherapy regimen (cytotoxic chemotherapy, targeted therapy, immune checkpoint inhibitors), and vaccine type (homologous vector, homologous mRNA, heterologous) on neutralizing activity.

Among the 57 patients included in the analysis, 26 (45.6 %) had a history of SARS-CoV-2 infection. Patients with hematologic cancers exhibited lower neutralizing antibody responses compared to those with solid tumors for Omicron subvariants BA.1 (24.44 % vs. 71.68 %, p = 0.020), BA.2 (48.22 % vs. 94.59 %, p = 0.006), and BA.4/5 (24.76 % vs. 78.06 %, p = 0.046). Among uninfected patients (n = 31), sVNT inhibition scores were significantly lower across all subvariants (e.g., 5.89 % for BA.1 vs. 58.11 % in infected, p = 0.0025). Treatment delays due to infection were observed in 9 patients (17.75 days on average). Although no deaths were directly attributed to infection, one patient died due to disease progression following a treatment delay caused by the infection.

Patients undergoing chemotherapy displayed weak neutralizing responses against Omicron subvariants, especially those with hematologic cancers or no prior infection. Consequently, it is crucial to actively recommend additional vaccinations with bivalent or newly developed vaccines for these vulnerable patients.