Serological SARS‐CoV‐2 antibody response, potential predictive markers and safety of BNT162b2 mRNA COVID‐19 vaccine in haematological and oncological patients

Abstract

Summary Haemato‐oncological patients are at risk in case of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection. Currently, vaccination is the best‐evaluated preventive strategy. In the present study, we aimed to assess serological response, predictive markers, and safety of BNT162b2 in haemato‐oncological patients. A total of 259 haemato‐oncological patients were vaccinated with two 30 µg doses of BNT162b2 administered 21 days apart. Serological response was assessed by ELECSYS® Anti‐SARS‐CoV‐2‐S immunoassay before vaccination, and at 3 and 7 weeks after the first dose (T1, T2). Safety assessment was performed. At T2 spike protein receptor binding domain (S/RBD) antibodies were detected in 71·4% of haematological and in 94·5% of oncological patients (P < 0·001). Haematological patients receiving systemic treatment had a 14·2‐fold increased risk of non‐responding (95% confidence interval 3·2–63·3, P = 0·001). Subgroups of patients with lymphoma or chronic lymphocytic leukaemia were at highest risk of serological non‐response. Low immunoglobulin G (IgG) level, lymphocyte‐ and natural killer (NK)‐cell counts were significantly associated with poor serological response (P < 0·05). Vaccination was well tolerated with only 2·7% of patients reporting severe side‐effects. Patients with side‐effects developed a higher S/RBD‐antibody titre compared to patients without side‐effects (P = 0·038). Haematological patients under treatment were at highest risk of serological non‐response. Low lymphocytes, NK cells and IgG levels were found to be associated with serological non‐response. Serological response in oncological patients was encouraging. The use of BNT162b2 is safe in haemato‐oncological patients.

Immunogenicity and risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection after Coronavirus Disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis

“…Following title and abstract review, 1,233 records were excluded given that they reported non-original findings, did not include cancer patients, or did not assess COVID-19 vaccines’ immunogenicity. Of the 54 articles that underwent full-text review, 35 articles[ [17] , [18] , [19] , [20] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] ] were considered eligible and were included in the meta-analysis ( Figure 1 ).

Figure 1 The PRISMA flowchart summarizing the process for the identification of eligible studies.

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“…of cancer patients No. of controls Patients’ age (years) Type of cancer Vaccine type Vaccine scheme Reported outcomes Addeo et al[ 17 ] Switzerland/USA Multicenter, prospective, cohort 244 NA 63 (IQR 55–69) Hematologic malignancy and solid tumor mRNA (BNT162b2/mRNA1273) Incomplete and complete Anti-S IgG Ab, adverse effects, SARS-CoV-2 infection Agha et al[ 41 ] USA Single-center, prospective, cohort 67 NA 71 (IQR 65-77) Hematologic malignancy mRNA (BNT162b2/mRNA1273) Complete Anti-S IgG Ab Barrière et al[ 42 ] France Single-center, prospective, cohort 122 29 69.5 (range 44-90) Solid tumor mRNA (BNT162b2) Incomplete and complete Anti-S IgG Ab, adverse effects Benda et al[ 37 ] Austria Single-center, prospective, cohort 259 NA 65.1 (SD 12.2) Hematologic malignancy and solid tumor mRNA (BNT162b2) Incomplete and complete Anti-S IgG Ab, adverse effects, SARS-CoV-2 infection Benjamini et al[ 53 ] Israel Multi-center, prospective, cohort 373 NA 70 (range 40-89) Hematologic malignancy mRNA (BNT162b2) Complete Anti-S IgG Ab, anti-N IgG Ab, adverse effects Bird et al[ 43 ] UK Single-center, retrospective, cohort 93 NA 67 (IQR 59-73) Hematologic malignancy mRNA (BNT162b2) and viral vector (AZD1222) Incomplete Anti-S IgG Ab Chowdhury et al[ …”

“…Of the included 35 studies, 20 reported the seroconversion rate in cancer patients after partial COVID-19 immunization (2574 patients)[ 17 , 20 , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , 37 , [42] , [43] , [44] , [47] , [48] , [49] , [50] , [51] , [52] ] and 24 after complete vaccination schemes (4708 patients). [ [17] , [18] , [19] , [20] , 27 , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , 45 , 46 , 48 , 49 , 53 , 54 ] A lower seroconversion rate was achieved by those with incomplete vaccination regimens (51%; 95%CI 41-62) compared to those with fully immunized patients (73%; 95%CI 64-81) ( P =0.0009) ( Figure 2 ).

Figure 2 Rates of seroconversion in patients with cancer according to vaccination regimen.

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“…In a pooled analysis of 14 studies including patients with hematologic or solid malignancies,[ 17 , 20 , 24 , [28] , [29] , [30] , [31] , 33 , 34 , 37 , 42 , 47 , 49 , 52 ] a subsequent SARS-CoV-2 infection was documented in 0.78% (95%CI 0.18-3.26; I 2 = 33%) of the 1444 patients with a partial COVID-19 vaccination regimen and in 0.41% (95%CI 0.09-1.89; I 2 = 51.5%) of the 3000 patients with a complete vaccination regimen ( P= 0.4976 ) . Overall, patients with cancer had a 0.55% (95%CI 0.20-1.5; I 2 = 59.5%) likelihood of SARS-CoV-2 infection after being immunized with at least 1 dose of COVID-19 vaccines.…”

SARS-COV2 Infection in Vaccinated Patients: Look for Clinical History and Test Humoral Immunity

“…As a matter of the fact circulating anti-S antibodies were detected at very low levels (16.7 UI/ml). This case shows that accurate clinical history and lab tests addressing humoral immunity are mandatory in patients who received anti-SARS-CoV2 vaccine and were however infected [ 1 , 2 ].…”