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

Abstract

IntroductionThe 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.MethodsSolid 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.ResultsThe 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.ConclusionSolid 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.

Can vitamin D status influence seroconversion to SARS-COV2 vaccines?

“…On the other hand, a 2022 Chinese multicenter study found that, when compared to seronegative healthy controls, patients with solid malignancies who failed the standard 2-dose inactivated COVID-19 vaccines had a relatively poor humoral response to the third dose of vaccines, which was associated with low vitamin D levels and intake ( 71 ).…”

Does native vitamin D, or active vitamin D modulate the neutralising antibody responses to COVID-19 vaccination in haemodialysis patients?

“…Previous studies have reported variable results, with some reporting that the vaccination response to COVID-19 was reduced by having lower levels of Vitamin D 3 , 13,14 and others observing no effect. 15,16 This study is the first to investigate whether Vitamin D 3 or the prescription of activated forms of Vitamin D have affect the response to COVID-19 vaccination.…”

“…Although several studies have reported an association between low levels of Vitamin D 3 and the response to COVID-19 vaccination, 13,14,22 particularly studies in pati-ents with cancer. 23 Haemodialysis patients are recognised to have lower responses to vaccination compared to the general population, 9 and although many haemodialysis patients have low levels of Vitamin D 3 , any potential effect of Vitamin D may have been obscured by the overall poor response rates to vaccination.…”

Vitamin D and COVID-19: Narrative Review after 3 Years of Pandemic

“…The development of anti-COVID-19 vaccines has turned the fight against SARS-CoV-2 and its variants in a positive way [96]. It has been hypothesized that vitamin D may positively influence the efficacy of vaccines, considering that low vitamin D serum concentrations were associated with an insufficient humoral response after a COVID-19 vaccinations in patients suffering from solid tumors [97,98]. However, a sub analysis of the recent aforementioned open-label CORONAVIT study found no efficacy from a supplementation of 800 or 3200 IU of cholecalciferol daily for 6 months in improving the immunogenicity of anti-COVID-19 vaccines ChAdOx1 nCoV-19 and BNT162b2 [99].…”