Serial negative response after standard and third (Booster) dose of COVID-19 inactivated vaccine is associated with low vitamin D levels in patients with solid cancers

Yifei Ma; Pengfei Zhu; Guanqing Zhong; Dao Wang; Lu Cao; Shenrui Bai; Youlong Wang; Ao Zhang; Xinjia Wang

doi:10.3389/fmed.2022.898606

Serial negative response after standard and third (Booster) dose of COVID-19 inactivated vaccine is associated with low vitamin D levels in patients with solid cancers

Front Med (Lausanne). 2022 Jul 29:9:898606. doi: 10.3389/fmed.2022.898606. eCollection 2022.

Authors

Yifei Ma¹, Pengfei Zhu², Guanqing Zhong³, Dao Wang⁴, Lu Cao⁵, Shenrui Bai⁵, Youlong Wang⁶, Ao Zhang³, Xinjia Wang^{1

7}

Affiliations

¹ Department of Orthopedics and Spine Surgery, The Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
² Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
³ Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁴ Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁵ Department of Hematological Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁶ Department of General Surgery, Hainan Hospital of PLA General Hospital, Sanya, China.
⁷ Department of Orthopedics, Cancer Hospital of Shantou University Medical College, Shantou, China.

Abstract

Introduction: The response is poorly understood to the third dose in patients with cancer who failed the standard dose of inactivated SARS-CoV-2 vaccines (CoronaVac). We aim to assess the immune response to the third dose and identify whether vitamin D deficiency is associated with serial serologic failure in patients with cancer.

Methods: Solid cancer patients (SCP-N) and healthy controls (HCs) who were seronegative after the standard-dose vaccines in our previous study were prospectively recruited, from October 2021 to February 2022, to receive the third dose vaccines and anti-SARS-CoV-2S antibodies were measured. SCP-N who failed the third dose (serial seronegative group, SSG) were matched by propensity scores with the historical standard-dose positive cancer patient group (robust response group, RRG). An exploratory analysis was carried out to validate the role of vitamin D on the serology response.

Results: The multi-center study recruited 97 SCP-N with 279 positive controls as RRG and 82 negative controls as HC group. The seroconversion rate after third-dose vaccination was higher in SCP-N than in HC (70.6% vs. 29.4%, p < 0.01). The matched comparison showed that patients in SSG had a significantly lower level of vitamin D and consumption rate than RRG or RRG-B (RRG with third-dose positive) (all p < 0.01). None had serious (over grade II) adverse events after the third dose.

Conclusion: Solid cancer patients with second-dose vaccine failure may have a relatively poor humoral response to the third dose of COVID-19 vaccines as compared with the seronegative HC group. The consecutively poor humoral response could be associated with poor vitamin D levels and intake. Vitamin D status and cancer-related immune compromise may jointly affect the humoral response following booster vaccination.

Keywords: Vitamin D; nested case-control study; serial seronegative response; solid cancer patients; third-dose-inactivated COVID-19 vaccine.